THE PRACTICING NEUROLOGIST - Global Issues... · World Federation of Neurology Seminars in Clinical Neurology Epilepsy: Global Issues for the Practicing Neurologist Jerome Engel,

World Federation of NeurologySeminars in Clinical Neurology

EPILEPSY: GLOBAL ISSUES FOR THE PRACTICING NEUROLOGIST

World Federation of NeurologySeminars in Clinical Neurology

Epilepsy: Global Issues for the Practicing Neurologist

Jerome Engel, Jr., MD, PhD, CHAIRJonathan Sinay Professor of Neurology and Neurobiology

Chief of Epilepsy and Clinical NeurophysiologyDirector, Seizure Disorder Center

David Geffen School of Medicine at UCLAReed Neurological Research Center

Los Angeles, CA

Gretchen L. Birbeck, MD, MPHAssistant Professor

Departments of Neurology & EpidemiologyMichigan State University

Core Faculty African Studies CenterEast Lansing, MI

DirectorChikanhata Epilepsy Care Center, Chikanhata Health Services

Mazabuka, Zambia

Amadou Gallo Diop, MD, PhDProfessor of Neurology, Epileptology, and Neurobiology

Clinique NeurologiqueC.H.U. Fann

Dakar, Senegal

Satish Jain, MD, DMProfessor

Head of Neurology—FORTIS HospitalsDirector, Indian Epilepsy CentreHauz Khas, New Delhi, India

André Palmini, MD, PhDAssociate Professor of Internal Medicine

Division of NeurologyFaculty of Medicine

Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS)Scientific Director

Porto Alegre Epilepsy Surgery ProgramHospital São Lucas—PUCRS

Porto Alegre, Brazil

Series EditorTheodore L. Munsat, MD

Professor of Neurology EmeritusTufts University School of Medicine

Boston, Massachusetts

New York

Demos Medical Publishing, LLC. 386 Park Avenue SouthNew York, NY 10016, USAVisit our website at www.demosmedpub.com

© 2005 by World Federation of Neurology. All rights reserved.

This work protected under copyright under the World Federation of Neurology and the fol-lowing terms and conditions apply to its use:

PhotocopyingSingle photocopies of single chapter, may be made for personal use as allowed by nationalcopyright laws. Multiple or systematic copying is permitted free of charge for educationalinstitutions that wish to make photocopies for non-profit educational classroom use, but notfor resale or commercial purposes.

Permission of the World Federation of Neurology is required for advertising or promotionalpurposes, resale and all forms of document delivery.

Permissions may be sought directly from the World Federation of Neurology, 12 ChandosStreet, London W1G 9DR, UK.

Derivative WorksTables of Contents may be reproduced for internal circulation but permission of the WorldFederation of Neurology is required for resale of such material.

Permission of the World Federation of Neurology is required for all other derivative works,including compilations and translations.

NoticeNo responsibility is assumed by the World Federation of Neurology for any injury and/ordamage to persons or property as a matter of products liability, negligence or otherwise, orfrom any use of operation of any methods, products, instructions, or ideas contained in thematerial herein. Because of the rapid advances in the medical sciences, in particular, inde-pendent verification of diagnoses and drugs dosages should be made.

First edition 2005

Library of Congress Cataloging-in-Publication Data

Epilepsy : global issues for the practicing neurologist / Jerome Engel ... [et al.].p. ; cm.

Includes bibliographical references and index.ISBN 1-888799-88-9 (pbk. : alk. paper)

1. Epilepsy. 2. Epilepsy—Developing countries.[DNLM: 1. Epilepsy—diagnosis. 2. Epilepsy—therapy. ] I. Engel, Jerome.RC372.E665 2005616.8'53—dc22

2004030996

Epilepsy is one of the most common serious primary brain disorders, affecting 40 millionpeople worldwide. According to the World Health Organization (WHO), epilepsy accountsfor 1% of the Global Burden of Disease, equivalent to lung cancer in men and to breast can-cer in women. It is not surprising, therefore, that 10 to 20 textbooks on epilepsy are pub-lished annually. These texts contain the very latest information on the diagnosis and treat-ment of various aspects of epilepsy; however, approximately 80% of people with epilepsyin the world live in developing countries, where modern diagnostic and treatment approach-es do not exist. Upwards of 90% of people with epilepsy in these areas receive no treatmentat all. It is surprising, therefore, that no textbook on epilepsy addresses the issues faced byneurologists who must deliver care with limited resources, often in a setting of tropical dis-eases and malnutrition that characterizes practice in developing countries. This text is specif-ically designed for this purpose.

The World Federation of Neurology has recognized the unmet need of neurologists who mustpractice medicine without many of the advantages that are often taken for granted in theindustrialized world, and has undertaken the task of creating a series of textbooks on neuro-logic subspecialty topics, in an effort to address issues important for neurologists in develop-ing countries, but which are not covered in standard textbooks. This is the first in the seriesspecifically intended to achieve this goal. At this point, the book is a work in progress,because the authors’ experience is limited to only a few areas of the extensive developingregions of the world, and undoubtedly, many important problems remain to be identified andaddressed. Consequently, we will appreciate feedback from our colleagues who use this textto help us make it more comprehensive in future editions.

Although I, as chief editor, practice at the University of California in Los Angeles, with all theadvantages available to neurologists in the industrialized world, my familiarity with the prob-lems of people with epilepsy in developing countries has increased since 1993, when I servedfirst as treasurer, then president, of the International League against Epilepsy (ILAE), and mostrecently as co-chair of the joint ILAE/International Bureau for Epilepsy (IBE)/WHO GlobalCampaign against Epilepsy. My personal lack of hands-on experience is complemented bythe coauthors of this book, all of whom are neurologists practicing in developing countries.Gretchen Birbeck is a neurologist in a general medical clinic in rural Zambia, and she haswritten a handbook on epilepsy for healthcare workers in similar environments. AmadouGallo Diop is a member of the neurology department at a medical college in Dakar, Senegal,and has been instrumental in organizing epilepsy programs for the WHO and the ILAE in Sub-Saharan Africa. Satish Jain heads an epilepsy center in New Delhi, India, and has been activein programs of the Southeast Asian region of the WHO. André Palmini is the scientific direc-tor of an epilepsy center at a university hospital in Porto Alegre, Brazil, and was chair of theILAE Commission on Latin American Affairs.

The authors are grateful to Martin Brodie from Glasgow, Scotland, an expert on the clinicalpharmacology of antiepileptic drugs, who chaired the ILAE Commission on European Affairs

v

Preface

and is currently a vice president of that organization; Olivier Dulac, a pediatric epileptologistin Paris, France, who has worked in various developing countries; J.A.W. Sander of London,who has organized epidemiologic studies throughout the developing world, and is currentlytreasurer of the ILAE, and C.T. Tan, a general neurologist in Kuala Lumpur, Malaysia, whochairs the ILAE Commission on Asian and Oceanian Affairs, for their review and critical com-ments on the manuscript.

Jerome Engel, Jr., MD, PhDLos Angeles, CaliforniaSeptember 2004

PREFACE

vi

The mission of the World Federation of Neurology (WFN, wfneurology.org) is to developinternational programs for the improvement of neurologic health, with an emphasis on devel-oping countries. A major strategic aim is to develop and promote affordable and effectivecontinuing neurologic education for neurologists and related health care providers. With thiscontinuing education series, the WFN launches a new effort in this direction. The WFNSeminars in Neurology uses an instructional format that has proven to be successful in con-trolled trials of educational techniques. Modeled after the American Academy of Neurology’shighly successful Continuum, we use proven pedagogical techniques to enhance the effec-tiveness of the course. These include case-oriented information, key points, multiple choicequestions, annotated references, and abundant use of graphic material.

In addition, the course content has a special goal and direction. We live in an economicenvironment in which even the wealthiest nations have to restrict health care in one form oranother. Especially hard pressed are countries where, of necessity, neurologic care is oftenreduced to the barest essentials or less. There is general agreement that much of this prob-lem is a result of increasing technology. With this in mind, we have asked the faculty to pres-ent the instructional material and patient care guidelines with minimal use of expensive tech-nology. Technology of unproven usefulness has not been recommended. However, at thesame time, advice on patient care is given without compromising a goal of achieving the verybest available care for the patient with neurologic disease. On occasion, details of certaininvestigative techniques are pulled out of the main text and presented separately for thoseinterested. This approach should be of particular benefit to health care systems that areattempting to provide the best in neurologic care but with limited resources.

These courses are provided to participants by a distribution process unusual for continu-ing education material. The WFN membership consists of 86 individual national neurologicsocieties. Societies that have expressed an interest in the program and agree to meet certainspecific reporting requirements are provided a limited number of courses without charge.Funding for the program is provided by unrestricted educational grants. Preference is givento neurologic societies with limited resources. Each society receiving material agrees to con-vene a discussion group of participants at a convenient location within a few months ofreceiving the material. This discussion group becomes an important component of the learn-ing experience and has proved to be highly successful.

Our second course addresses the important area of epilepsy management. The Chair ofthis course, Professor Jerome Engel, Jr. a recognized international authority, has selected anoutstanding faculty of experts. We very much welcome your comments and advice for futurecourses.

Theodore L. Munsat, M.D.Professor of Neurology EmeritusTufts University School of MedicineBoston, Massachusetts

vii

Editor’s Preface

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .v

Editor’s Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vii

1. What Is Epilepsy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

2. Differential Diagnosis and Classification of Seizures and Epilepsy . . . .11

3. Epidemiology and Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35

4. Diagnostic Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43

5. Practical Approaches to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . .61

6. Antiepileptic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .83

7. Alternative Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95

8. Psychosocial Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107

9. Public Health Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115

Appendix: Out of the Shadows . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135

ix

Contents

1

CHAPTER 1

WHAT IS EPILEPSY?

KEYPOINTS

n Eighty percent of theglobal health burden ofepilepsy is borne by thedeveloping world.

n Epileptic seizures provokedin an otherwise normalbrain, which will not recurafter the provocative insultis removed, does notwarrant a diagnosis ofepilepsy.The nervous system has a limited repertoire

of responses to insult; it can underact, caus-ing negative signs and symptoms such asparalysis and blindness, or it can overact,causing positive signs and symptoms such aspain, hallucinations, and epileptic seizures.This, of course, is an oversimplification,because most neurologic disorders producecomplex signs and symptoms with both neg-ative and positive features; for instance,paresis is often accompanied by spasticity,and epileptic seizures often are followed bypostictal functional impairment of some sort.Epileptic seizures represent the most com-mon positive signs and symptoms of braindisturbance, and an individual with a lifeexpectancy of age 70 has a one-in-tenchance of experiencing at least one epilepticseizure.

All epileptic seizures, however, are notepilepsy, which is defined as a conditionassociated with recurrent epileptic seizures.In the industrialized world, only about one-third of individuals who have a singleseizure will go on to have one or more addi-tional seizures and warrant a diagnosis ofepilepsy. Furthermore, epilepsy, consistingof recurrent seizures, is not always a fixedcondition, because many patients undergospontaneous remission of their epileptic dis-order. Thus, the prevalence of active epilep-sy worldwide is only about 5 to 10 per 1,000(see Chapter 3). Nevertheless, epilepsy isone of the most common primary brain dis-orders; it appears to be more prevalent indeveloping countries, where the risk of pre-disposing factors such as poor perinatalcare, head trauma, and intracranial infection,including parasitic infestations, is oftengreater than in industrialized countries(Chapter 9), and most patients in thesecountries receive poor treatment, or none at

all. Indeed, it has been estimated that 80% ofthe global health burden of epilepsy isborne by the developing world, where morethan 80% of people with epilepsy are notreceiving treatment, or are often not evenidentified. This disparity between the num-ber of people with active epilepsy and thenumber being adequately treated is referredto as the “treatment gap.” The information inthis text is designed to help narrow the treat-ment gap.

DEFINITIONSThe term epilepsy, or more correctly, theepilepsies, refers to a group of chronic neu-rologic conditions characterized by recurrentepileptic seizures. The diagnosis of anepileptic disorder implies that the neurolog-ic dysfunction responsible for generatingepileptic seizures continues to exist, evenwhen seizures are not occurring. It is impor-tant to recognize, therefore, that epilepticseizures provoked in an otherwise normalbrain, which do not recur after the provoca-tive insult is removed, do not warrant a diag-nosis of epilepsy. Such a diagnosis is onlywarranted when an enduring epileptogenicbrain abnormality is diagnosed, or suspect-ed, which has the potential to continue togenerate epileptic seizures.

Epileptic seizures are the clinical manifes-tations (signs and symptoms) of excessiveand/or hypersynchronous, usually self-limit-ed, abnormal activity of neurons in the brain.Although it was once believed that epilepticseizures reflect disturbances involving onlythe cerebral cortex, it has recently becomeclear that subcortical structures are often alsoinvolved, and some epileptic seizures maybe primarily generated at a subcortical level.Thus, the distinction between epilepticseizures and some subcortical positive symp-

toms, such as certain myoclonic phenomena,is not well-defined. The behavioral featuresof epileptic seizures reflect the functions ofthe brain areas involved, and may take theform of impaired higher mental function oraltered consciousness, involuntary move-ments or cessation of movement, sensory orpsychic experiences, or autonomic distur-bances, and often evolve with a combinationof these signs and symptoms. Specific epilep-tic seizure types are electroclinically defined,i.e., by their behavioral and electroen-cephalogram (EEG) features.

Ictal event refers to the epileptic seizure,whereas postictal refers to dysfunctionoccurring after the seizure is over, and inter-ictal refers to the period between seizures,when ictal and postictal disturbances nolonger exist. Although an aura is a simplepartial seizure, and therefore an ictal event,some patients experience poorly definedprodromal symptoms that occur minutes orhours prior to epileptic seizure onset, whichare not ictal events, and therefore can beconsidered pre-ictal phenomena.

Epileptogenesis refers to the developmentof an epileptic disorder, although the term isoccasionally used also to refer to the initia-tion of epileptic seizures.

Epileptic focus is defined electrophysio-logically as the brain area that appears togenerate the most prominent interictalepileptiform EEG discharges. From this EEGperspective, epileptic conditions may be dueto a single focus, bilateral independent foci,multiple foci, or there may be diffuse unilat-eral or generalized epileptiform abnormali-ties with no focal features. It is important tounderstand, however, that the actual epilep-togenic abnormality is rarely limited to a dis-crete focal area of the brain, even in apatient who has a single, well-defined EEGepileptic focus. The area of brain necessaryand sufficient for generating habitual epilep-tic seizures in patients with focal epilepsy ismore correctly referred to as the epilepto-genic region. The epileptogenic region is atheoretical concept, and its exact boundariescan only be implied from a variety of diag-nostic information, including ictal behavior,interictal and ictal EEG, and neuroimaging.

Epileptic encephalopathy is a term appliedto conditions, usually seen in infants and

children, in which the epileptogenic processitself is responsible for progressive interictalcerebral dysfunction. In this case, the patientloses previously acquired abilities.Exceptionally, the consequent motor, senso-ry, or cognitive disturbances are the onlyexpression of the epileptic disorder.

Control and cure are terms that are poor-ly defined with respect to epileptic seizures.Epileptic seizures can be considered well-controlled when their frequency and/orseverity is reduced by treatment to someacceptable level for some period of time, butno specific criteria have been established.Individuals with epilepsy are often referredto as seizure free when they no longer havedisabling epileptic seizures, even thoughsimple partial sensory seizures (auras) maypersist. Epidemiologically, an individual isconsidered to have active epilepsy untilseizure free and off medications for 5 years,so presumably after this point, it is appropri-ate to consider the individual cured.Complete elimination of the underlyingepileptic disturbance is most common inthose epileptic conditions that undergospontaneous remission, and following surgi-cal resection of the epileptogenic region. Inmost cases, pronouncement of a completecure can only be made retrospectively.

DIFFERENTIAL DIAGNOSIS OF EPILEPSYMany intermittent and paroxysmal signs andsymptoms can be mistaken for epilepsy, anddifferential diagnosis can be difficult, particu-larly in countries with limited resourceswhere EEG, including inpatient video/EEGmonitoring and sophisticated neuroimaging,are not available. Unfortunately, countrieswith limited resources, where it is difficult torule out a diagnosis of epilepsy, often areculturally predisposed to damaging miscon-ceptions that enhance the disability associat-ed with a diagnosis of epilepsy (Chapter 8).Consequently, when diagnosis is in doubt,even in the industrialized world, but particu-larly in developing countries, it is better tomake no diagnosis at all and wait until thecondition has clearly declared itself beforepronouncing a definitive verdict of an epilep-tic disorder. In this respect, it is of utmostimportance to understand what is not epilep-sy. In addition to nonepileptic events that


2

KEYPOINTS

n When diagnosis is in doubt,it is better to make nodiagnosis at all and waituntil the condition hasclearly declared itselfbefore pronouncing adefinitive verdict of anepileptic disorder.

mimic epilepsy, discussed in Chapter 2, thisincludes single seizures, discussed in Chapter5, and provoked seizures, which may berecurrent, but no longer occur when theunderlying cause is removed (Figure 1.1).

Although an epileptic seizure is always anabnormal event, it can be a natural responseof the normal brain to noxious insult anddoes not necessarily imply a persistent under-lying epileptogenic abnormality. It is possibleto provoke a seizure in anyone, but the sus-ceptibility or threshold for the induction ofsuch provoked ictal events varies consider-ably from one individual to another. Forinstance, someone with a low threshold toprovoked seizures may have a single general-ized tonic-clonic convulsion as a result of sev-eral nights of sleep deprivation, alcohol with-drawal, or use of a convulsant drug such ascocaine, and this should not be considered

epilepsy, although it is an indication that thespecific provocation should be avoided ifpossible. Seizures provoked by fever ininfants and young children (Chapter 5) con-stitute the most common provoked ictalevents that do not require a diagnosis ofepilepsy. In some cases, single or recurrentseizures result from treatable causes such asintracranial infections, mass lesions, or otherintracranial pathologies, which can be com-pletely cured or removed. In these patients, ifseizures do not continue after this treatment,a diagnosis of epilepsy is not warranted.

CAUSES OF EPILEPSYTreatment approaches usually depend onthe type of epilepsy (Chapter 2) and the eti-ology (Chapters 5, 6, and 7). The causes ofepilepsy are most often multifactorial, and itis useful to consider three general factors

(Figure 1.2). The first factor is thesusceptibility of individual brainsto generate seizures in responseto epileptogenic perturbations.Whether an individual has a highor low susceptibility, or threshold,for seizures to occur is largelydependent on genetic factors,although structural damage to thebrain can also alter threshold.Furthermore, threshold is not astatic condition, but changes overtime, so that most people have alower threshold during drowsi-ness and slow-wave sleep thanduring wakefulness and REMsleep, and many women havelower thresholds before menses,and sometimes during ovulation.Virtually all antiepileptic drugswork by raising the threshold.The second factor is the specificepileptogenic abnormality, whichcould be an acquired lesion of thebrain or a genetic disturbance(Chapter 3). Potentially epilepto-genic disturbances are more like-ly to produce epilepsy in individ-uals with a low threshold than inindividuals with a high threshold.Specific epileptogenic distur-bances may require specific treat-ment that can eliminate seizures,

What Is Epilepsy?

3

KEYPOINTS

n In some cases, single orrecurrent seizures resultfrom treatable causes suchas intracranial infections,mass lesions, or otherintracranial pathologies,which can be completelycured or removed. In thesepatients, if seizures do notcontinue after thistreatment, a diagnosis ofepilepsy is not warranted.

Steps in evaluation of paroxysmalevents.

From Engel J Jr. Seizures and Epilepsy. Philadelphia: F. A.Davis, 1989, with permission.

FIGURE 1.1

Is the eventepileptic? Diagnose and

treat systemicneurologic or

psychogenic disorders

Is thisa chroniccondition?

Diagnose andtreat (if necessary)cause of reactive

seizures

Patientdoes not

haveepilepsy

Is there atreatablecause?

Is specifictreatment for cause

successful incuring seizures?

Patient has epilepsy.

Diagnose seizure type, and if

possible, epileptic syndrome. Institutespecific treatment

for epilepsy.

Yes

Yes

No

No

No

No

Yes

Yes

and if they are localized, they can often besurgically removed. The third factor consistsof precipitating events that cause seizures tooccur at a given point in time (Chapter 3).These may be seizures without epilepsy, forinstance in children with febrile seizures oran individual who has an isolated seizuredue to alcohol withdrawal or sleep depriva-tion, or these may be recurrent seizures inpatients with epilepsy. Examples of the lat-

ter are most obvious in patientswith reflex epilepsies who haveseizures precipitated by specificsensory and cognitive experiences,but precipitating factors like sleepdeprivation or menses may also beidentified in patients with othertypes of epilepsy. The avoidance ofprecipitating factors when possible,and added protection when notpossible, can be an important partof treatment.

Epileptic disorders are consid-ered to be idiopathic or primarywhen they are just epilepsy andnot the result of some other brainabnormality, epilepsy sui generis.Idiopathic epilepsies are usuallybenign, age-related, genetic disor-ders unassociated with lesions inthe brain or other neurologic dis-turbances, and they often remitspontaneously. Epileptic disordersare considered to be symptomaticor secondary when they resultfrom lesions or other disturbancesof the brain that may produceother signs and symptoms besidesepilepsy. These abnormalities maybe acquired, or the result of agenetic disease such as tuberoussclerosis or phenylketonuria. Thus,genetic and acquired disturbancesinteract in a variety of ways thatcan result in epileptic seizures orepilepsies. With respect to inherit-able factors in epilepsy, these maynonspecifically affect threshold, orthey may be specific genetic distur-bances that cause idiopathicepileptic syndromes or diseasesassociated with brain lesionsresulting in symptomatic epilepticdisorders. Diagnostic strategies are

aimed at determining the type of seizuresand epilepsy in each patient and, if possi-ble, identifying a treatable underlying cause(Chapter 4). Epileptic disorders that areprobably symptomatic, but do not have anidentified cause, are sometimes called cryp-togenic. Further discussion of the classifica-tion of seizures and epilepsy can be foundin Chapter 2, and specific causes of epilep-


4

Schematic diagram illustrating inter-actions of the fluctuating threshold

for seizures determined by nonspecific predisposingfactors (A); independent fluctuations of a specificepileptogenic disturbance (B); and intermittent pre-cipitating factors (C). With a high threshold, epilep-togenic disturbances and precipitating factors alone(D1, D2) and combined (D3) fail to generateseizures. With an intermediate threshold, epilepto-genic disturbances and precipitating factors alone(D4, D5) fail to generate seizures, but seizures(arrows) occur when these factors are combined(D6). With a low threshold, epileptogenic distur-bances and precipitating factors alone (D7, D8) areeach capable of generating seizures, and combined(D9), generate even more seizures, perhaps consti-tuting intractable epilepsy or status epilepticus.From Engel J Jr. Seizures and Epilepsy. Philadelphia: F. A.Davis, 1989, with permission.

FIGURE 1.2

A

D1

4 5 6

7 8 9

2 3

B C

sy, including genetic causes, arepresented in Chapter 3.

Discussion of the fundamentalmechanisms of epilepsy arebeyond the scope of this text, but itis important to recognize that thereare many different types of epilep-sy, and they do not all share a com-mon pathophysiologic basis.Enhanced inhibition and disturbedfunction of certain low-thresholdcalcium channels in the thalamuscause the abnormal hypersynchro-nization underlying generalizedspike-and-wave discharges associ-ated with absence seizures, andantiabsence drugs work by block-ing these calcium currents. On theother hand, generalized tonic-clonic seizures may result fromenhanced excitation in brainstemand neocortical structures, andthese are successfully treated bydrugs that block sodium and calci-um channel–mediated excitation,suppress glutamatergic excitatoryactivity, and enhance gammaaminobutyric acid (GABA)-ergicinhibitory activity. The most com-mon form of epilepsy in adoles-cents and adults, at least in theindustrialized world, is mesial tem-poral lobe epilepsy (MTLE). Thiscondition is undoubtedly under-diagnosed in the developing worldbecause of limited neuroimaging.MTLE is usually associated withhippocampal sclerosis, whichappears to be epileptogenic as aresult of enhanced excitation andinhibition, resulting in hypersyn-chronization. It is likely that agenetic predisposition and earlycerebral insult combine to causethe characteristic pattern of cell lossand gliosis in the hippocampus.Such early insults, for example pro-longed febrile seizures, are com-mon in developing countries. Thesynaptic reorganization of survivingneurons is believed to increase sus-ceptibility for abnormal hypersyn-chronization, which then leads to

What Is Epilepsy?

5

KEYPOINTS

n The most common form ofepilepsy, at least in theindustrialized world, ismesial temporal lobeepilepsy (MTLE). Thiscondition is undoubtedlyunderdiagnosed in thedeveloping world becauseof limited neuroimaging.

Reciprocal innervation of a hypothet-ical neuronal system is shown

schematically (A). This is the typical synapticorganization of neocortex and hippocampus.Excitatory afferent input terminates on the den-drites of principal neurons (filled triangles). Axoncollaterals from these principal neurons terminateon inhibitory interneurons (empty circles), which inturn make hyperpolarizing synapses on the somaof the same, and adjacent (not shown), principalneurons. With cell loss, a number of synaptic reor-ganizations are likely to occur, as shown schemati-cally (B). Fewer afferent input fibers sprout toinnervate more principal neurons, predisposing tohypersynchronization. Because the dendrites ofprincipal neurons are shorter, these excitatoryinfluences are closer to the axon hillock and morelikely to induce neuronal firing. Neuronal excitabil-ity is further increased by the establishment ofmonosynaptic excitatory recurrent circuits. Someinhibitory interneurons also sprout new terminalsto produce more powerful, and/or more extensive,recurrent inhibitory influences, further enhancingthe potential for hypersyhchronization.From Engel J Jr. Functional explorations of the humanepileptic brain and their therapeutic implications.Electroenceph Clin Neurophysiol 1990;76:296-316, withpermission.

FIGURE 1.3

A

B

the manifestation of epileptic seizures(Figure 1.3). Understanding these epilepto-genic mechanisms has helped to design newantiepileptic drugs, and it is hoped that fur-ther insights will eventually lead to noveltherapeutic approaches; however, a detailedunderstanding of the pathophysiology ofepilepsy is only peripherally relevant toissues dealt with in this text on the diagno-sis and treatment of epileptic seizures andepilepsies in developing countries.

ADDRESSING THE BURDEN OF EPILEPSY IN THE DEVELOPING WORLDStudies by the World Health Organization(WHO) have determined that epilepsyaccounts for approximately 1% of the globalburden of disease. Among primary disordersof the brain, epilepsy is one of the four mostimportant causes of economic and personalloss, the other three being affective disor-ders, dementias, and alcohol abuse. Manyindustrialized countries have recognized thisfact and are improving the diagnosis andtreatment of epilepsy by setting aside addi-tional funding for research, the creation ofspecialized epilepsy centers, and training ofepilepsy specialists. This effort is greatlyaided by recent advances in diagnostic tech-nology, particularly neuroimaging, improvedtreatment approaches, which include theintroduction of seven new antiepilepticdrugs in the past decade (Chapter 6), andrapidly expanding use of alternative treat-ments, particularly surgery (Chapter 7). TheInternational League against Epilepsy (ILAE),the international organization of medicalprofessionals working in the field of epilep-sy, has increased the number of its nationalchapters from 40 to over 90 in the past eightyears, and increased attendance at its inter-national congresses from 2,000 to over5,000, indicating a tremendous redirection ofpersonnel and resources within the medicalcommunity toward the problems of thosewith epilepsy. The International Bureau forEpilepsy (IBE), the international lay organi-zation concerned with the myriad socialproblems that tragically add to the disabili-ties encountered by individuals with epilep-sy, has experienced a similar increase inchapter membership and activities. Most ofthese developments, however, have had lit-

tle impact in developing countries, wherethe majority of individuals with epilepsy live.

More information about the ILAE and IBE,and about their chapters, can be found ontheir websites www.ilae-epilepsy.org andwww.ibe-epilepsy.org. The objectives of thistext would be greatly enhanced by theestablishment of ILAE and IBE chapters inthose developing countries that do notalready have them. These websites also con-tain information about the procedures forbeginning new ILAE and IBE chapters. Thisis addressed in more detail in Chapter 9.

The Global Campaign against Epilepsy, ajoint program of the WHO, ILAE, and IBE,was launched in 1997 to “bring epilepsy outof the shadows,” in order to address discrim-ination against those with epilepsy and tonarrow the treatment gap in developingregions of the world. The objectives of theGlobal Campaign against Epilepsy are statedin Table 1.1. Not only have a majority of theILAE and IBE national chapters taken upaspects of the Global Campaign in their owncountries, but Regional Declarations, whichidentify problems and propose solutions forministries of health and other health careorganizations, have been created for Europe,


6

KEYPOINTS

n The Global Campaignagainst Epilepsy, a jointprogram of the WHO, ILAE, and IBE, was launchedin 1997 to “bring epilepsyout of the shadows,” in order to addressdiscrimination againstthose with epilepsy and tonarrow the treatment gapin developing regions ofthe world.

Objectives of theILAE/IBE/WHO GlobalCampaign against Epilepsy: Bringing Epilepsy Out ofthe Shadows

TABLE 1.1

• To increase public and professionalawareness of epilepsy as a universal,treatable brain disorder;

• To raise epilepsy to a new plane ofacceptability in the public domain;

• To promote public and professionaleducation about epilepsy;

• To identify the needs of people withepilepsy on a national and regionalbasis; and

• To encourage governments anddepartments of health to address the needs of people with epilepsy,including awareness, education, diagnosis, treatment, care, services,and prevention.

sub-Saharan Africa, Latin America, Asia andOceania, and North America, and one moreis planned in the near future for the easternMediterranean region (Middle East andNorth Africa). Demonstration projectsdesigned to identify people with epilepsyand bring them to treatment centers are nowongoing in China and Senegal, and areplanned for Argentina and Zimbabwe.

In 1999, the WHO raised the GlobalCampaign against Epilepsy to cabinet level,making it one of its highest priority projects.Every regional office of WHO has pledgedto commit personnel and resources to thiscampaign. Further information on the GlobalCampaign against Epilepsy can be obtainedfrom its website www.who.int/mental_hea l th /managemen t /g loba lep i l epsycampaign/en/, or by writing to: PO Box 21,2100 AA Heemstede, The Netherlands.

OBJECTIVESThis textbook is intended for neurologistsworking in developing countries. It assumessophisticated training in neurology andaccess to standard textbooks (although cur-rent journals may not always be available);therefore, it is not a comprehensive reviewof epileptology. Rather than present materi-al readily available in many excellent vol-umes (some of which are cited in the refer-ences to this chapter), this text is designed toaddress those aspects of epileptology rele-vant to neurologists practicing under condi-tions common in the developing worldwhich may not be adequately covered inavailable published material.

The difficulties encountered in develop-ing regions of the world derive from apoverty of resources and trained personnel,as well as an often inadequate and ineffi-cient administrative and political infrastruc-ture, usually compounded by tropical condi-tions. Risk factors for epilepsy in developingregions differ from those usually discussedin textbooks written for North American andEuropean consumption, as a consequence ofpublic health deficiencies, such as poor orabsent prenatal care and failure to controlinfectious diseases; and of a relatively highincidence of head trauma from traffic acci-dents, endemic social violence, and endur-ing political conflicts. This not only means

that neurologists should look for differentunderlying causes of epilepsy in theirpatients than they would in the industrial-ized world, but that there is much that canbe done to prevent epilepsy in these popu-lations. In addition, medical care in thedeveloping world may be severely compro-mised by several other factors. Large dis-tances between clinical facilities and poortransportation limit patient access to care; alow level of education not only complicatesthe instruction of individual patients andtheir families about diagnosis and treatment,but also presents obstacles to improvingknowledge, attitudes, and perceptions aboutepilepsy in the general population. Someprevalent cultural influences lead patientsand their families to seek alternative healthcare, foster concepts that stigmatize peoplewith epilepsy and increase the morbidityand mortality resulting from their seizures,and promote customs, such as consan-guineous marriage, which contribute to ahigher incidence of epilepsy.

The ratio of trained neurologists to peo-ple with epilepsy is extremely low in devel-oping nations compared with that in theindustrialized world. Consequently, neurolo-gists in these situations are likely to be moreeffective, for most patients, as educatorsthan primary caregivers. As such, healthadministrators in developing regions shouldconsider the benefits of allowing neurolo-gists to focus their professional activities onimproving the capability of general practi-tioners, nurses, and other health workers toprovide adequate care for people withepilepsy, leaving the neurologists to seeonly the most difficult patients themselves.Invariably, the paucity of well-trained neu-rologists, and in many cases the virtualabsence of epileptologists in developingcountries, is exacerbated by the “braindrain” when neurologists who seek furtherspecialized training abroad do not return totheir home country. However, the practiceof neurology, and particularly of epileptol-ogy, in the developing world can be intellec-tually challenging, and tremendous opportu-nities for creative and important researchexist. The U.S. National Institutes of Health,for instance, has shown increasing interest insupporting international collaborations for

What Is Epilepsy?

7

KEYPOINTS

n This text is designed toaddress those aspects ofepileptology relevant toneurologists practicingunder conditions commonin the developing worldwhich may not beadequately covered inavailable publishedmaterial.

n Neurologists in thesesituations are likely to bemore effective, for mostpatients, as educators thanprimary caregivers. As such,health administrators indeveloping regions shouldconsider the benefits ofallowing neurologists tofocus their professionalactivities on improving thecapability of generalpractitioners, nurses, andother health workers toprovide adequate care forpeople with epilepsy

capacity-building research in low and mid-dle income countries. The WHO has givenepilepsy the highest priority for researchsupport, and it is hoped that more neurolo-gists interested in improving care for peoplewith epilepsy in the developing world willremain in, or return to, their home countriesto pursue these research activities.

It is necessary to recognize that condi-tions differ markedly from one developingcountry to another. For some large countrieslike India, China, and Brazil, there are suffi-cient resources and trained personnel to cre-ate medical centers of excellence equal tothose in North America and Europe, butaccess to these centers is limited.Consequently, some people with epilepsyreceive a high standard of medical care,while many others do not. Solving the finan-cial and logistical problems that prevent theorganization of adequate health care provi-sion to all people with epilepsy in thesecountries is obviously quite different fromthose in countries, such as the majority insub-Saharan Africa, which have little or nomodern medical facilities or neurologists.Furthermore, obstacles to the adequate diag-nosis and treatment of people with epilepsyin rural settings of developing countries arequite different from those in urban settings,and countries differ in the degree to whichurban and rural problems contribute to thehealth care burden. Of course, the emergingcountries of the world do not have amonopoly on the financial, political, andcultural problems that contribute to inade-quate health care for people with epilepsyaddressed in this volume. Most industrial-ized countries also have pockets of under-privilege where similar conditions prevail, asexemplified in the United States by certainghetto neighborhoods in the large cities,some remote rural areas, and a few unique-ly isolated ethnic and cultural groups, suchas the Indian reservations and urban com-munities of recent immigrants from thedeveloping world. It is likely, therefore, thatefforts to resolve the problems that limitepilepsy prevention and health care deliveryin developing countries will also contributeimportantly to the resolution of similar prob-lems in the industrialized world. More infor-

mation about resources in every country canbe obtained from the WHO Atlas, WHOGeneva HQ, 2002, and about epilepsy inAfrica from WHO AFRO, 2004.

Although this text is divided into 10 chap-ters that deal with the traditional topics cov-ered by other epilepsy textbooks, eachchapter is specifically organized to recognizethe unique problems posed by epilepsy inthe developing world, to emphasizeapproaches to diagnosis and treatment thatare most applicable in areas with limitedresources, and to assist in promoting theacceptance of people with epilepsy bydefining and correcting the misinformationresponsible for discrimination, mistreatment,and inappropriate restrictions that contributegreatly to their disability in many developingcountries of the world.

CONCLUSIONSEpileptic seizures represent the most com-mon positive signs and symptoms of braindisturbance, and epilepsy is one of the mostcommon primary brain disorders. The greatmajority of people with epilepsy live in thedeveloping world, and most of them receiveno treatment at all. Although much has beenwritten documenting tremendous advances inthe diagnosis and treatment of epilepsy inrecent years, standard textbooks do notaddress the needs of neurologists who mustcare for patients with epilepsy in areas withlimited resources where modern approachesare not available and in circumstances, suchas tropical conditions, where different healthproblems exist. This text, designed to provideinformation of use to neurologists in develop-ing countries that is not available in standardtextbooks, begins with an introductoryoverview of definitions, basic concepts of dif-ferential diagnosis, a brief discussion of caus-es, and a description of the ILAE/IBE/WHOGlobal Campaign against Epilepsy designedpredominantly to address the burden ofepilepsy in the developing world. Subsequentchapters are concerned with differential diag-nosis and classification, epidemiology and eti-ology, diagnostic approaches, treatmentapproaches, antiepileptic drugs, alternativetherapy, psychosocial issues, and publichealth.


8

KEYPOINTS

n The emerging countries ofthe world do not have amonopoly on the financial,political, and culturalproblems that contribute toinadequate health care forpeople with epilepsy. Mostindustrialized countries alsohave pockets ofunderprivilege wheresimilar conditions prevail.

CITATIONS AND RECOMMENDED READINGCommission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised

clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22: 489–501.

This is a summary of the revised classification of epileptic seizures, as proposed by the ILAE Commission onClassification and Terminology in 1981. Epileptic seizures are defined based on semiology and EEG features.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revisedclassification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–399.

This is a summary of the revised classification for epilepsies and epileptic syndromes as proposed by the ILAECommission on Classification and Terminology in 1989. Epilepsies are defined based on the seizure types andtheir possible etiology.

Engel J Jr, Pedley TA, (eds.), Epilepsy: A Comprehensive Textbook. Vols. 1, 2, and 3. Philadelphia: Lippincott-RavenPublishers, 1997.

This is an extensive reference work on all aspects of epilepsy.

Engel J Jr. Functional explorations of the human epileptic brain and their therapeutic implications. Electroenceph ClinNeurophysiol 1990;76:296–316.

This review article summarizes concepts of basic mechanisms of epilepsy based on invasive studies in the humanbrain, suggesting that inhibition is not decreased, but increased, contributing to abnormal hypersynchrony. Thispaper is also the source of Figure 3.

Engel J Jr. Seizures and Epilepsy. Philadelphia: F. A. Davis, 1989.

This comprehensive but concise textbook is the source of Figures 1 and 2.

Hauser WA, Hesdorffer DC. Epilepsy: Frequency, Causes and Consequences. New York: Demos Press, 1990.

Although now somewhat out of date, this is the most comprehensive source for epidemiologic information onepilepsy.

Kale R. Editorial: Bringing epilepsy out of the shadows. B Med J 1997;315:2–3.

This editorial eloquently sets out the problems facing people with epilepsy who live in developing countries, andclarifies the need for the WHO/ILAE/IBE Global Campaign against Epilepsy.

Levy RH, Mattson RH, Meldrum BS, Perucca E. Antiepileptic Drugs, 5th ed. Philadelphia: Lippincott, Williams &Wilkins, 2002.

This is the most recent edition of the standard reference work for antiepileptic drugs, which is updated every fewyears.

Meinardi H, Scott RA, Reis R, Sander JWAS, on behalf of the ILAE Commission on the Developing World. The treat-ment gap in epilepsy: the current situation and ways forward. Epilepsia 2001;42:136–149.

This paper is a report of the proceedings of a meeting of the Commission on Developing Countries of theInternational League against Epilepsy held in Marrakech, Morocco, in May 1999, during which the treatment gapwas defined and approaches to reducing the treatment gap were discussed.

Murray CJL, Lopez AD, (eds.). Global Comparative Assessment in the Health Sector; Disease Burden, Expenditures,and Intervention Packages. Geneva: World Health Organization, 1994.

This work documents the global burden of disease, based on disability-adjusted life years (DALYs). According tothis study, epilepsy represents 1% of the global burden of disease, equivalent to breast cancer in women and lungcancer in men.

Pellock JM, Dodson WE, Bouregois BFD. Pediatric Epilepsy: Diagnosis and Therapy. New York: Demos MedicalPublishing, 2001.

This is a recent comprehensive textbook on pediatric epilepsy.

Reynolds EH. The ILAE/IBE/WHO Global Campaign against Epilepsy: bringing epilepsy “out of the shadows.”Epilepsy & Behavior 2000;1:S3–S8.

This paper discusses the creation of the ILAE/IBE/WHO Global Campaign against Epilepsy, and details its accom-plishments up until 2000, and plans for the future.

Reynolds EH, (ed.) Epilepsy in the World: Launch of the second phase of the ILAE/IBE/WHO Global Campaignagainst Epilepsy. Epilepsia 2002;43(suppl 6).

This supplement to Epilepsia contains a series of articles relevant to the Global Campaign against Epilepsy, derivedfrom presentations at the launch of the second phase of this campaign in Geneva, Switzerland, in February 2001.

Shorvon S. Handbook of Epilepsy Treatment. London: Blackwell Science, 2000.

This is a clear and concise reference on treatment of epilepsy.

Wyllie E, (ed.) The Treatment of Epilepsy: Principles and Practice, 3rd ed. Philadelphia: Lippincott, Williams &Wilkins, 2001.

This is the most recent edition of a comprehensive textbook on epilepsy.

What Is Epilepsy?

9

This Page Intentionally Left Blank

11

CHAPTER 2

DIFFERENTIAL DIAGNOSIS AND CLASSIFICATION OF SEIZURES AND EPILEPSY

KEYPOINTS

n Particularly in developingcountries, an unwarranteddiagnosis of epilepsyenhances disability as aresult of the stigma andsocial limitations associatedwith this disorder, as wellas an often burdensomecost of unnecessary AEDs.

n Most of the conditionsmimicking epileptic seizurescan be suspected on clinicalgrounds.

There are many nonepileptic conditions thatcan produce an abrupt loss or alteration ofconsciousness, generalized convulsivemovements, sudden falls to the ground, oreven localized abnormal movements, sensa-tions, or autonomic symptoms. Whenever aclinician encounters a patient with any ofthese manifestations, however, the first pos-sibility that should come to his or her mindis that of an epileptic seizure. The need fora correct diagnosis of the type of spell can-not be overemphasized: Nonepilepticseizures may be life-threatening, affectedpatients with nonepileptic seizures needspecific types of treatment, and the use ofantiepileptic drugs (AEDs) may even worsenthe condition. Furthermore, particularly indeveloping countries, an unwarranted diag-nosis of epilepsy enhances disability as aresult of the stigma and social limitationsassociated with this disorder, as well as anoften burdensome cost of unnecessaryAEDs. Conversely, the diagnosis of epilepsycan be missed if there is not a high degreeof suspicion, particularly in infants andyoung children with epilepticencephalopathies, where the major symp-toms are progressive neurologic or mentaldeterioration.

In this era of high technology applied tomedicine in general, and particularly to neu-rology, it is reassuring that the diagnosticarmamentarium needed for the differentialdiagnosis between epileptic and nonepilep-tic spells is usually simple. Most of the con-ditions mimicking epileptic seizures can besuspected on clinical grounds. Electro-encephalograms (EEGs), electrocardiograms(ECGs), and imaging studies may be occa-sionally required, but the correct diagnosis isusually reached by history and examination.The key issue is to always keep in mind the

possibility of alternative diagnoses inpatients who at first glance appear to haveepileptic seizures.

Once the diagnosis of epileptic seizures isestablished, therapeutic management, prog-nosis, and counseling are dependent uponthe identification of the underlying cause,the exact type of seizure, and epilepsy syn-drome (where possible). In developingcountries, this implies a thorough knowl-edge of the presentation of epilepsies relat-ed to infectious processes, trauma, congeni-tal disturbances, and other disorders com-monly encountered in these environments.A flow chart for the differential diagnosis ofepileptic seizures is shown in Figures 2.1through 2.4.

A CLINICAL APPROACH TO CONDITIONS OFTEN MISDIAGNOSED AS EPILEPSYAn extensive list of conditions that can bemisinterpreted as epilepsy is shown inTable 2.1. Because an unwarranted diagno-sis of epilepsy can have dire consequences,considerable space is devoted in this text todifferential diagnosis, particularly empha-sizing clinical points that help to distinguishepileptic seizures from other paroxysmalevents when availability of sophisticateddiagnostic technology is limited or absent.Most patients with nonepileptic spells whoare evaluated in developing countries havethe same conditions commonly seen indeveloped regions. However, a few condi-tions may be peculiar to developing coun-tries. This section emphasizes differentialdiagnoses between epilepsy and othercommon paroxysmal disorders, based onclinical features. More complete descrip-tions of the other conditions are availablein standard textbooks and will be dealt withonly briefly here.

12

Differential diagnosis of sudden alteration of consciousness.FIGURE 2.1

Sudden alteration orloss of consciousness

Preceded bylightheadedness,global weakness,

blurred vision

Not preceded bypresyncopal or

overt signsof anxiety

Orthostatic,emotional, ormildly painful

precipitant

Emotional context:

tachycardia,shortness of

breath

Recurrentepisodes in

psychologicallystressfulsituations

Exercise-related

Difficultyto focusattention

Repeated, briefepisodes of

disconnectionfrom

environment

Aura,motionless

stare, simpleautomatisms

Youngperson,

history ofmigraine

SyncopePanicattack

Psychogenic,nonconvulsive

seizures

Long QTsyndrome orother cardiacconditions

ADHD

Absenceattacks

Temporallobe complex

partialseizures

Basilarmigraine

Differential diagnosis of generalized convulsive movements.FIGURE 2.2

Generalizedconvulsivemovements

Inconsistent LOC,side-to-side head

movements,pelvic thrusting

Preceded bypresyncope or

syncope

Preceded by partialsensori-motor signs, or

unequivocal LOC,cyanosis, tongue biting,

or incontinence

Minimalpostictal

confusion

Nonepilepticpsychogenicconvulsiveseizures

Usually brief,generalized

tonic stiffening

Convulsivesyncope

Overtpostictal

somnolence,sore muscles

Generalizedepilepticseizures

Common Conditions Often Misdiagnosed as EpilepsyThe paroxysmal events most frequently mis-diagnosed as epileptic seizures are reviewedbelow, and summarized in Table 2.1 and inthe algorithms shown in Figures 2.1 through

2.4. Neurologists in developing countries areoften under pressure to examine too manypatients in a short period of time. Thus, apractical clinical approach to patients pre-senting with spells will narrow diagnosticpossibilities and optimize the use of more

Differential Diagnosis and Classification of Seizures and Epilepsy

13

Differential diagnosis of paroxysmal focal signs and symptoms.FIGURE 2.3

Complex sequence ofunilat/bilat movement;compulsive repetition;feasibility to control

Focalmotor orsensory

manifestations

Paroxysmal unilateraluncontrolled movements

precipation bymovement or

alcohol and fatigue

Scintillating scotomasblack/white irregular

lines, focal paresthesias,nausea, throbbing

headache

Migrainewithaura

Paroxysmalkinesiogenicdyskinesias

Complextics

Paroxysmalnonkinesiogenic

dyskinesias

Transientischemicattacks

Simplepartial

epilepticseizures

Recurrent focalsensori-motor signs;variable duration;

history of convulsion

Focal paresthesias,weakness or dysphasia;

risk factors for CVD;recovery within

24 hours

Differential diagnosis of drop attacks.FIGURE 2.4

History ofrecurrent vertigo,

hypoacusis

Suddendrop

attacks

Precipitated bysudden emotion,

laughing

Women > 50 yearsold, recurrent episodes,

sudden falls,immediate recovery

Cryptogenicdrop attacksin elderlywomen

Cataplexy(narcolepsy)

Otolitic crisis(Menère’s spectrum)

Hyperekplexia(other regionaldenominations)

Epilepticattacks

Sudden episodes, tonicatonic, or myoclonic;

diffuse encephalopathy,usually rapid recovery

Precipated by anykind of sensory startle; usually

neurologically normal


14

Disorders Associated with Nonepileptic Paroxysmal Signs and SymptomsThat Can Be Mistaken for Epilepsy

TABLE 2.1

Systemic Disturbances

• Syncope

– Vasovagal

– Cardiogenic

– Orthostatic hypotension (associatedwith Shy-Drager, familial dysautono-mia, hypovolemia, Parkinson’s disease,diabetes, porphyria, amyloidosis,vasoactive drugs)

• Breath-holding spells

• Hyperventilation

• Toxic and metabolic disturbances

– Alcoholic blackouts

– Delirium tremens

– Porphyria

– Hypoglycemia

– Pheochromocytoma

– Asterixis with hepatic and renal failure

– Tetanus

– Rabies

– Psychomimetic drugs

– Tonic spasm with camphor and strych-nine

– Jitteriness in newborns

Neurologic Disturbances

• Cerebrovascular disorders

– Transient ischemic attacks

– Vertebral basilar insufficiency

– Moya moya disease

– Migraine

– Transient global amnesia

• Sleep disorders

– Narcolepsy (cataplexy, sleep paralysis,hypnogogic or hypnopompic hallucina-tions)

– Neutral-state syndrome (micro-sleeps)

– Encephalitis lethargica

– Kleine-Levin syndrome

– Pickwickian syndrome

– Parasomnias

> Incubus

> Pavor nocturnas

> Somnambulism

> Sleep talking

> Bruxism

> Jactatio capitis nocturna (headbanging)

> Adult parasomnias (nocturnal wandering and night terrors)

• Motor disorders

– Myoclonus

– Dystonia

– Chorea

– Athetosis

– Hemiballismus

– Tremors

– Paroxysmal dyskinesias

> Familial paroxysmal kinesigenicchoreoathetosis

> Familial paroxysmal dystonicchoreoathetosis

> Acquired paroxysmal dyskinesias

> Nocturnal paroxysmal dystonias

– Startle disease (hyperekplexia)

– Gilles de la Tourette syndrome

– Alternating hemiplegia in childhood

– Hemifacial spasms

– Cerebellar fits

• Sensory disorders

– Paroxysmal vertigo

– Trigeminal neuralgia

– Peduncular hallucinosis

• Neonatal disorders

– Some neonatal seizures

– Intraventricular hemorrhage

Psychiatric disorders

• Nonepileptic psychogenic seizures

• Episodic dyscontrol

• Dissociative states (dissociative hystericalneuroses)

– Psychogenic fugue

– Multiple personality disorder

– Psychogenic amnesia

– Depersonalization disorder

• Daydreaming (vs. absence seizures)

• Obsessive-compulsive behavior

• Panic attacks

• Schizophrenia (hallucinations)

advanced resources when needed to estab-lish treatment strategies.

Many of the conditions to be reviewedbelow may be more prevalent in developingcountries. Although specific data on theregional prevalence of these conditions maynot be available, the profile of risk factorsassociated with them predicts a higherprevalence in poorer countries. Tropical dis-eases affecting the heart and insufficientcontrol of other cardiovascular disorders, aswell as the high occurrence of alcoholism,unemployment, depression, political insta-bility, and domestic and social violence, areexamples of risk factors associated withnonepileptic seizures.

SyncopeSyncopal attacks are most often misdiag-nosed as epileptic seizures when patientsnot only lose consciousness, but have tonicstiffening of the extremities (convulsive syn-cope). Vasovagal syncope often occurs infamilies and, interestingly, family memberscan also have migraine, benign rolandicepilepsy, or benign rolandic spikes.Vasovagal syncope occurs in physiologic sit-uations in which either venous return is

reduced, or there is a sudden increase inparasympathetic (vagal) tone. Generally, asensation of dizziness, weakness, and ‘cold’progresses to a faint on rising from a bed ora chair. Alternatively, the person may bestanding for a long time (as in a concert orchurch service), and then reach the pointwhen baroreceptor reflex mechanisms fail,and syncope ensues. Sudden stressful situa-tions, such as the sight of blood or badnews, can trigger a parasympatheticresponse and syncope. Often, the bradycar-dia and the progressively diminished brainperfusion is signaled by symptoms ofimpending loss of consciousness (presyn-cope): sounds in the environment becomedistant, legs weaken, and vision becomesblurred. When reported, these presyncopalsymptoms are very helpful in making thecorrect diagnosis, because they tend to bestereotyped and differ from the most com-mon forms of epileptic auras.

Primary cardiac disorders associated withsyncope usually have a poor prognosis, andthus should be promptly identified and treat-ed. The two main mechanisms leading tocardiogenic cerebral hypoperfusion and syn-cope are cardiac arrhythmias and pump fail-


15

CASE STUDY

Presentation: A 16-year-old student loved to surf on weekends. He was referred after a third episode of loss of consciousnessin the period of 1 year, which occurred while he was taking 1,200 mg/day of carbamazepine, because an interictal EEG showedrare right-sided centro-parietal spikes. His mother had a history of recurrent fainting during adolescence, in situations such asdrawing blood or standing up for long periods of time. The first of his episodes occurred while standing at a bus stop on asummer afternoon. He felt weak, dizzy, and the next thing he remembers was being on the ground with people around him.Two months later, when a door squeezed his fingers, he cried, became pale, and fainted. The third episode occurred in a restau-rant. He had had a large meal, and upon rising from his chair, he felt weak, dizzy, became pale, and fainted. This time, he hada few tonic convulsive movements, but quickly recovered. There was no past history of typical epileptic seizures.

Evaluation: Physical, cardiovascular, and neurologic examinations were normal. He had already been examined with a CT scan,which was normal. A ‘tilt’ test showed abnormal cardiovascular compensation of orthostatism, and was considered positive. Asimilar result was seen in his mother’s examination, and thus a diagnosis of predisposition to vasovagal syncope was made.

Treatment and outcome: The patient has been on amitriptyline 50 mg/day at bedtime, with no recurrence of symptoms formore than a year. Carbamazepine was discontinued. The nature of the boy’s diagnosis was fully discussed with the family,including the low risks of a syncopal episode while surfing.

Comment: Vasovagal syncope is a disorder with a familial predisposition. Genetic factors explain why several members of afamily can present with the same syncopal symptoms as well as others with migraine, perirolandic spikes, and serotonergicabnormalities, such as anxiety and depression. A key aspect is a good cardiovascular evaluation to exclude disorders that maylead to serious consequences (such as the long QT syndrome). A common misconception is that the tonic stiffening that mayoccur represents an ‘epileptic seizure.’ In the context of the rolandic spikes, this led to the inappropriate prescription of anantiepileptic drug to this patient. These syncopal fits have a mechanism purely dependent on energetic failure of brainstemnuclei and do not represent epileptic phenomena. Thus, the use of AEDs is not indicated.

ure. The type of arrhythmia is dependent onthe underlying cardiac disorder. Patients canhave syncope due to the long QT syndromeand conduction defects dependent on previ-ous ischemic events or chamber dilatationdue to protracted hypertension and cardiacfailure. The latter is likely to be common,even in young people in developing coun-tries, because the primary and secondaryprevention of cardiovascular conditions isoften suboptimal. In addition, some disor-ders of the heart are much more frequent indeveloping countries, such as cardiomyopa-thy, which may result from rheumatic heartdisease or Chagas’ disease.

Nonepileptic Psychogenic SeizuresIt may be difficult to reliably differentiate anonepileptic psychogenic from an epilepticseizure, although some aspects do help inthe differential diagnosis. Nonepileptic psy-chogenic seizures usually present as recur-rent generalized motor seizures. Non-noctur-nal generalized motor seizures are rarely theonly seizure type of a given patient and arealmost never refractory to AEDs. A history ofonly recurrent daytime motor convulsionsthat do not respond to AEDs should raise thesuspicion of psychogenic seizures. Unlikegeneralized tonic-clonic seizures, general-

ized nonepileptic psychogenic attacks canlast for more than 15 minutes, but with rapidpostictal recovery. Back and forth pelvicthrusts and side-to-side head movements arecommon in nonepileptic psychogenicseizures and inconsistent with epilepticseizures. Nonepileptic psychogenic seizuresthat mimic complex partial seizures are moredifficult to diagnose. Keep in mind that evenin industrialized countries, only rare selectedcases need to be referred for video-EEGtelemetry. These often are patients whohave both epileptic seizures and nonepilep-tic psychogenic seizures.

Breath-holding Spells (BHSs)The most typical scenario of BHSs involvesan infant or a child up to age 6 who startscrying following a minor injury or frustra-tion, and then stops breathing. Clinical histo-ry is usually all that is needed to make thediagnosis. The first episode is frightening toparents, because the prolonged cryingepisode is followed by cyanosis, limpness,and loss of consciousness. Less frequently, apallid form of BHS may occur. Both formscan present with tonic or clonic movementstoward the end of the episode, due to tran-sient brain hypoxia. BHSs are due to a com-bination of recurrent Valsalva maneuvers


16

CASE STUDY

Presentation: A 34-year-old married man, with no children, had been unemployed for the last 3 years. He usually carried a stackof emergency room admission reports, “to show how much I’ve been suffering lately” (sic). He was an adopted and abusedchild, and had only seven years of formal education. He started to work during adolescence, but never stayed on a job forlonger than a year or two. His wife provided the household with their basic needs. After losing one more job, about 3.5 yearsbefore presentation, the patient began with generalized convulsions. They could occur any time, but most commonly whenthere was some “tension in the air.” His wife described what appeared to be generalized tonic clonic seizures, except that theepisodes were very prolonged, lasting sometimes more than 20 minutes. He would be systematically taken to an emergencyroom, where he received IV diazepam and/or phenytoin and promptly recovered without postictal symptoms. The seizures didnot have partial components. He was tried on many AED combinations, but none brought any significant seizure alleviation.

Evaluation: General and physical exams were normal. Over 20 interictal EEGs, a CT scan, and a MRI were all normal.

Treatment and outcome: After several visits to the clinic, AEDs were slowly discontinued. He is currently engaged in psycho-logic and psychiatric treatment, and receives fluoxetine and low dosages of haloperidol. The frequency of his emergencyroom visits has been decreasing slowly.

Comment: The diagnosis of nonepileptic psychogenic seizures may be difficult. Understanding the patient’s background andcurrent psychosocial context is crucial in the overall appraisal of the situation, but when the level of suspicion is high, it isimportant to pay attention to details of the seizures themselves. The long duration of what appeared to be generalized con-vulsive seizures, the prompt recovery of consciousness after the attacks, and the fact that the episodes were never milder orshorter despite the use of AED in adequate dosages, all suggest that nonepileptic seizures should be considered. The diag-nosis is even more likely in the absence of EEG or structural imaging abnormalities.

and excessive parasympathetic (vagal) acti-vation, resulting from forceful crying. Theremay be some genetic contribution, and EEGabnormalities, unrelated to the BHS, may attimes be present. BHSs should not be con-fused with anoxia in young infants causedby tonic seizures. Benzodiazepines in thissituation can precipitate respiratory arrest.

Panic AttacksA growing sensation of anxiety, fear ofsomething vague, tachycardia, and effortfulbreathing that occurs during panic attacksmay lead to loss of consciousness. In theseepisodes, some patients may have aparasympathetic syncope and others mayhyperventilate and faint. Irrespective of thefinal mechanism, panic attacks are alwaysassociated with an initial sensation of anxi-ety. As with most neuropsychiatric condi-tions, panic attacks result from an interactionof genetic predisposition with environmentaldeterminants of anxiety states.

Hyperventilation SyndromeLoss of consciousness associated with thisentity is similar to that occurring during panicattacks. However, prolonged hyperventila-tion may be subtle and represent an unim-pressive, often unnoticed, manifestation ofanxiety. The final common pathway,nonetheless, may be the same, featuringgrowing alkalosis, hypocarbia, and cerebralhypoperfusion. In addition, the associated,

acute hypocalcemia often leads to dystoniccontractions of the fingers, hands, wrist, andface, which may be confused with motorseizures. Because the manifestations of anxi-ety are less intense, hyperventilation syn-drome may be more difficult to differentiatefrom epilepsy on clinical grounds alone.Nevertheless, a heightened level of suspicionusually allows the clinical diagnosis, which ishelped by a history of flexion of both wrists.

Basilar MigraineThe usual sequence of events in patientswith basilar migraine leading to nonepilepticseizures is lightheadedness or vertigo fol-lowed by loss of consciousness and a throb-bing headache upon recovery. Paroxysmalnystagmus with vertigo in young children isa variant of this disorder. A history of recur-rent headaches is almost always present.While unconscious, the patient may stiffenhis or her extremities, a picture that resem-bles the nonepileptic tonic seizures dis-cussed above in regard to vasovagal syn-cope. The final common mechanism forboth is transient brainstem metabolic orischemic insult. Differentiating basilarmigraine from epilepsy is not always simple,and the main features are depicted in Figure2.1. Migraine auras can usually be distin-guished from epileptic auras because theformer progress much more slowly. Onemust keep in mind that EEG abnormalitiescan occur with migraine.


17

CASE STUDY

Presentation: A 40-year-old woman witnessed, while hidden somewhere in her house, the murder of her husband, four chil-dren, a sister and parents-in-law by a group of rebels in a troubled region of a developing country. Three to four monthslater, she presented with “jumping,” feelings of sudden death, and panic attacks. Every loud noise (door, voices, etc.) pro-voked these symptoms. She also began hearing bizarre voices.

Evaluation: On clinical evaluation, she stands up suddenly, hands on her head, and calls for help. This scenario could berepeated briefly very often during a day. EEG was normal.

Treatment: Anxiolytics and antidepressant drugs alone were insufficient to improve her status. She found more relief from aseries of baths with different vegetable materials, inhalation, amulets, and special mystical celebrations accompanied withreligious songs and dances. The themes of these evocations are generally dedicated to the patient’s family and ancestors.Sacrifices of a sheep and a chicken were also made “to satisfy evil powers and calm the devils.”

Outcome: She became free of psychogenic seizures, but continued to have persistent delirium with the same initial themesduring less severe panic attacks.

Comment: The conjunction of modern and traditional medicines provided the only solution to improve her mental and phys-ical health. This beneficial association of both approaches is reported for many regions of the developing world. Knowledgeof the cultural background of people with epilepsy or psychogenic seizures is necessary to optimize effective management.

Transient Ischemic Attacks (TIAs)Focal paresthesias, weakness, or dysphasia,which appear suddenly and disappear aftera few seconds or minutes may be partialseizures, but can also be due to TIAs.Differential diagnosis can rely solely on theclinical features and is not difficult in mostcases. Despite apparent similarities andsome clinical and epidemiologic intersec-tions, the two conditions differ in terms ofage of occurrence, type of motor manifesta-tions, clinical evolution, and duration of theepisodes. Although TIAs and strokes aremore likely to occur in young people indeveloping countries than elsewhere, TIAsusually affect older people with risk factorsfor cerebrovascular disorders. TIA-relatedneurologic deficits usually evolve over a fewminutes, the motor manifestations are almostalways negative (e.g., paresis), and althoughthe episodes may be short-lasting, they usu-ally last several minutes. Focal seizures, onthe other hand, occur in all age ranges; oftenproduce clonic, tonic, or dystonic move-ments; reach a maximum in a few seconds;and seldom last more than a minute or two.Only rarely is EEG or neuroimaging neces-sary, and both are often normal in eithercondition.

Paroxysmal Movement DisordersParoxysmal dyskinesias with variable dura-tion and precipitating factors can be con-fused with epilepsy because choreic, dyston-

ic, athetotic, or mixed movements can bebrief and recurrent, thus more suggestive ofepileptic phenomena. Sudden movement orexercise usually precipitates the kinesio-genic and exercise-induced dyskinesias,respectively, while other types may appearduring sleep, or are related to fatigue, ten-sion, or alcohol use (the paroxysmal, nonk-inesiogenic dyskinesias). Consciousness isretained during the episodes, and except forthe sleep-related form, the other types ofparoxysmal dyskinesias tend to disappearduring sleep.

Hyperekplexia is another form of parox-ysmal movement abnormality in which sud-den stimulus leads to massive myoclonus.The patient may fall to the ground, in whatresembles an epileptic drop attack. In thenewborn, hyperekplexia produces jerks andtonic attacks that can last for several min-utes. This can be life-threatening but isstopped by neck flexion, a maneuver thatcan be taught to parents. Low doses of clon-azepam usually control the tonic attacks.Hyperekplexia is a genetically determinedhyperexcitability of cortical sensori-motorloops. This condition and similar disordershave many different names in differentcountries: “jumping Frenchman of Maine” inCanada, “latah” in Malaysia, “jauns” inBurma, “bahtsche” in Thailand, “mali mali”in The Philippines, “ainu imu” in Japan,“ikota” in Siberia, and “panic” among theLapps of northern Scandinavia. The EEG is


18

CASE STUDY

Presentation: A 14-year-old girl began to have episodes of throbbing headaches and vomiting at age 11. At a 2- to 3-monthinterval, she would also feel dizzy and lose consciousness for several minutes, complaining of a throbbing headache uponrecovery. Just before presentation, she had had a similar but more prolonged episode, in which the loss of consciousness wasaccompanied by tonic stiffening of the extremities. Recovery was also accompanied by headaches. Her mother had a long his-tory of headaches followed by vomiting, and her younger sister had benign rolandic epilepsy and was taking a low dose ofoxcarbazepine.

Evaluation: General and neurologic examinations were unremarkable. Several EEGs showed infrequent bilateral rolandic andoccipital interictal spikes, but were otherwise normal. Imaging exams were not deemed necessary.

Treatment and outcome: She took amitriptyline for 8 months. Although a few mild headache attacks occurred, she did nothave any new episodes of loss of consciousness. After full discussion of the situation, the patient and her parents decided tostop the medication.

Comment: This girl probably had basilar migraine, in which episodes of dizziness and loss of consciousness in children or ado-lescents are followed by throbbing headaches. Tonic stiffening of the extremities can occur during the period of loss of con-sciousness. Many of these patients have some inconspicuous EEG abnormalities and also a family history of migraine orbenign rolandic epilepsy. The nonepileptic nature of the episodes should be made clear.

usually normal, and unexpected startle is thesine qua non to the occurrence of the mas-sive myoclonus. Hyperekplexia is not asso-ciated with other neurologic deficits, asopposed to startle-induced epilepsy, whichusually occurs in children with diffuse braindamage.

Alternating hemiplegia in infants is oftenclaimed to be related to migraine, although ithas a more severe course. The diagnosis ismade clinically. The first attacks in earlyinfancy consist of episodic dystonia of thetrunk and limbs that can be mistaken fortonic seizures. Later, the child exhibitsepisodes of unilateral paralysis alternatingfrom one side to the other, often mistaken forpostictal paralysis. Alternating hemiplegia,however, can coexist with epileptic disor-ders, including pharmacoresistant epilepsies.

Tremulousness or jitteriness is a benignnonepileptic condition of newborns. It canbe distinguished from epileptic seizures bythe characteristic rapid rhythmic movement,and by its abolition with passive flexion orrestraint of affected limbs.

MyoclonusMyoclonus may or may not be an epilepticmanifestation. Epilepsy is less likely whenthis condition occurs in the setting of anoth-er underlying medical condition. Non-epileptic myoclonus is usually one of sever-al signs and symptoms of neurologic disor-ders involving hyperexcitability of motorsystems, including cortical and subcorticaldementias and diffuse cortical dysfunctionassociated with metabolic disorders.Likewise, epileptic myoclonus usually is notan isolated phenomenon, and the occur-rence of other seizure types allows a defini-tive diagnosis of epilepsy. Subcortical(spinal) myoclonus can be clinically diag-nosed on the basis of the recognition of theassociated spinal cord disorder. Myoclonus-opsoclonus in infants and young children isrecognized by sudden, often unilateral eyemovements, and can be the presentingsymptom of neuroblastoma. Focal and mul-tifocal myoclonus is often seen in comatosepatients after hypoxic insults, and the ques-tion of epileptic seizures can arise. Whereasepileptic seizures typically involve muscleswell represented in the homunculus of the

motor cortex (e.g., face and fingers),nonepileptic focal and multifocal myoclonususually involves muscles that do not havelarge cortical representation, such as truncalmuscles.

ParasomniasParasomnias include a host of abnormalmotor and behavioral manifestations occur-ring during sleep. Some of these may mimicepileptic seizures, such as sleep terrors,somnambulism, or REM-related agitatedbehavior. The difficulties in formatting a dif-ferential diagnosis are compounded by thefact that partial seizures in many epilepticsyndromes can occur predominantly duringsleep. Furthermore, witnesses often miss theinitial elements of the episode. Clinical fea-tures that suggest epileptic seizures includethe occurrence of oroalimentary or gesturalautomatisms, focal motor phenomena,tongue biting, urinary incontinence, andoccasional attacks during wakefulness. Inthe absence of any of these features, a para-somnia is likely. When sleep EEG studies ormonitoring are not available, a therapeutictrial with a medication for treating the mostlikely entity should be performed. Such atrial usually allows a clinical diagnosis.

Attention Deficit-Hyperactivity Disorder (ADHD)The inattention and vacant look seen in anychild, particularly in children with ADHD,can be misinterpreted as absence seizures.However, absence seizures are almostalways characterized by brief episodes ofdisconnection with sudden onset and termi-nation, usually occurring many times a day.In contrast, the distractability associated withADHD depends on whether the child ismotivated by ongoing activities. Hyper-ventilation should precipitate an absenceattack and make the diagnosis obvious.

Abnormal EEGs in Nonepileptic Children and AdolescentsThere is a strong, but by no means absolute,correlation between the occurrence of inter-ictal EEG epileptiform discharges and thepredisposition for epileptic seizures.Therefore, the EEG may be useful in theworkup of patients presenting with paroxys-


19

mal clinical events that potentially representepileptic seizures. Availability, interpretation,and clinical necessity of the EEG are impor-tant considerations, particularly in develop-ing countries, where both expertise andtechnological resources are often scanty andunevenly distributed. Unless the EEG is per-formed correctly and interpreted by some-one formally trained in EEG, it can do moreharm than good.

The concept of brain dysrhythmia wasinherited from developed countries, whichchampioned the idea that deviations fromnormal distribution, symmetry, or synchronyof EEG rhythms had some clinical relevance.Nonspecific EEG disturbances provided anexplanation for myriad somatic behavioralor cognitive symptoms, leading to severaldecades of inappropriate prescriptions ofAEDs to treat the abnormal EEG rhythms.Unfortunately, as concepts of EEG interpre-tation have become more conservative, col-orful computerized brain mapping of EEGrhythms have appeared. The latter has rein-augurated the idea that if background EEGrhythms deviated from statistical normalcy,

then something was wrong, perhapsexplaining the symptoms for which the brainmapping was ordered. This circular reason-ing has been very difficult to eliminate indeveloping countries where such tests areavailable. It cannot be overemphasized thatthere is significant variability in the rate ofmaturation of EEG rhythms during wakeful-ness and sleep, and that clinically relevantinformation obtained from EEG or brainmapping in the absence of bona fide epilep-tiform discharges or unequivocally localizedslow wave activity is negligible.

Paradoxically, in developing countries,where EEG may be relatively difficult toobtain, the test is often inappropriatelyordered. Because the EEG is a relatively easytest to perform and sometimes is the onlyancillary neurodiagnostic method available,it is not uncommon to see EEG referrals fora large variety of conditions where epilepticseizures might be incorrectly invoked toexplain the signs and symptoms. For exam-ple, headaches, agitated behavior, schooldifficulties, dizziness, and sleep disorders donot usually warrant EEG investigations.


20

KEYPOINTS

n Unless the EEG isperformed correctly andinterpreted by someoneformally trained in EEG, itcan do more harm thangood.

n There is significantvariability in the rate ofmaturation of EEG rhythmsduring wakefulness andsleep. Clinically relevantinformation obtained fromEEG or brain mapping inthe absence of bona fideepileptiform discharges orunequivocally localizedslow wave activity isnegligible.

n Headaches, agitatedbehavior, school difficulties,dizziness, and sleepdisorders do not usuallywarrant EEG investigations.

CASE STUDY

Presentation: A 10-year-old girl failed the third grade at elementary school. Her parents were often summoned by schoolteachers and psychologists, who claimed the girl was not interested in school activities. She was easily distracted, her writingwas very slow, and she often did not finish her work. One year before referral, she had psychologic and neurologic evalua-tions. A primary learning disorder was ruled out, and there was nothing significantly wrong from a psychologic standpoint.Neurologic evaluation at that time disclosed left-sided centrotemporal spikes on the EEG, and for the last 9 months she wasprescribed oxcarbazepine, 600 mg a day. However, she was not clinically improving.

Evaluation: Physical and neurologic examinations were normal. A review of the teacher’s report made clear that the girl ful-filled criteria for ADHD. Another EEG confirmed bilateral centrotemporal spikes, increasing markedly in frequency duringsleep.

Treatment and outcome: The parents were told that although children with epileptiform EEG spikes have an increased riskof seizures, this finding does not constitute an indication to use an AED. In addition, they were told that the EEG abnormal-ities had nothing to do with the ADHD, and that oxcarbazepine was not a treatment for those symptoms. She was put onmethylphenidate in increasing dosages, up to 0.8 mg/kg/day, and has had remarkable improvement in her school perform-ance.

Comment: The management of this patient shows that the EEG should be interpreted in the context of the clinical picture.The epileptogenic significance of benign perirolandic spikes in a child without clinical seizures is minimal. Avoid treating theEEG instead of the patient’s clinical problem. Either the attentional problems of this girl were ignored, or the electrical abnor-malities were interpreted as possibly interfering with cognitive function. The latter was clearly not the case.

In addition to nonepileptiform, usuallynegligible EEG findings, individuals withoutepilepsy may exhibit true interictal epilepti-form EEG discharges. These are particularlylikely to occur in the nonepileptic relatives ofpatients with familial epileptic disorders. If acorrect differentiation between epilepsy andconditions mimicking epilepsy is to be made,then the physician must realize that patientswithout epilepsy can have epileptiform EEGdischarges. This is particularly true in childrenwith centrotemporal and occipital EEG spikes.In one study of people referred to an EEG lab-oratory for various reasons, including knownor suspected epilepsy, only about 40% ofthose with centrotemporal EEG spikes andabout 75% of those with frontal spikes had ahistory of epileptic seizures. Similarly, onlyabout 75% of children with irregular 4 to 6 Hzgeneralized spike and wave complexes had ahistory of epileptic seizures. Conversely, peo-ple with epilepsy can have a normal EEG.

Conditions Peculiar to Some Areas ofthe Developing World that May Be Misdiagnosed as Epileptic Spells

Parasitic DisordersThese usually present with diarrhea, malaise,vomiting, and abdominal distension. In addi-

tion, some children may have extremeweakness and even loss of consciousness,simply as another constitutional symptom.However, some parasitic disorders are soendemic in poorer regions of the globe, thatthe first clinical diagnosis of malnourishedchildren or adolescents who faint or developmotor or behavior disturbances is a parasiticdisorder. Actually, this is the usual diagnosisof influential nonmedical personnel in theseareas. Thus, in many instances, these chil-dren are treated through traditional medi-cine or even by primary care doctors whoprescribe standard medication for para-sitoses. The problem here is that trueseizures often pass undiagnosed, at leastuntil after several recurrences, when alterna-tive diagnoses may be entertained.

NeurocysticercosisNonepileptic spells with loss of conscious-ness can occur due to acute intracranialhypertension associated with intraventricularcysts. The much more common scenario,however, is misdiagnosis of epilepsy as aresult of different types of nonepilepticparoxysmal spells in patients in whom com-puted tomography (CT) shows single ormultiple residual calcified cysts. In endemicregions for neurocysticercosis, particularly


21

KEYPOINTS

n The physician must realizethat patients withoutepilepsy can haveepileptiform EEGdischarges.

CASE STUDY

Presentation: This 22-year-old woman with a history of recurrent throbbing headaches presented for evaluation because ofrecent episodes of loss of consciousness preceded by vertigo, diplopia, and paresthesias in both arms. After a similar episode2 months earlier, she was prescribed carbamazepine, 800 mg/day. Neither episode was accompanied by motor manifestationsor incontinence. Postictal symptoms lasted between 10 and 30 minutes. Previous medical history was otherwise unremark-able, but family history was positive for migraine and epilepsy.

Evaluation: General medical and neurologic examinations were normal, as were routine laboratory exams. Serum immuno-logic assays for cysticercosis were positive for IgG and negative for IgM. An EEG during wakefulness and sleep showed irreg-ular background activity and a few sharp waves during wakefulness over the right temporo-occipital regions. A contrast-enhanced CT scan showed three small calcified nodules (about .5 centimeter in diameter), in the right frontal, right anteriortemporal, and left parietal lobes.

Treatment: Carbamazepine was slowly discontinued, and verapamil (a calcium channel blocker) was started, at a single doseof 120 mg/day in the evening.

Outcome: A few instances of mild throbbing headache recurred in the ensuing year, but the patient did not report any otherepisode of loss of consciousness.

Comment: This patient most likely had basilar migraine, but an episode of loss of consciousness was misinterpreted as anepileptic seizure because of a mildly abnormal EEG and the presence of calcified lesions on CT scan. The latter are most like-ly related to a previous exposure to cysticercosis (as suggested by the serum immunologic findings) and do not representactive disease. Although calcified cysts may give rise to epileptic seizures, the possibility of alternative diagnoses for parox-ysmal phenomena must be entertained in endemic regions.

where CT is more easily available, it is acommon mistake to assume that paroxysmalsymptoms are epilepsy, when calcificationsare found on CT. This is certainly incorrectin many instances, and the indication for aCT scan in these regions should take intoaccount the most likely diagnosis on a clini-cal basis. In this regard, such indication issimilar to that previously discussed for therole of EEG.

Stomach CongestionIn some developing countries, episodes ofloss of consciousness are often attributed todigestive tract abnormalities. Some epilepticseizures by chance occur after meals, whichsupports the traditional hypothesis thatdiversion of blood to the digestive tract leadsto loss of consciousness. Similar to the dis-cussion on parasitic disorders, these beliefscan delay diagnosis of true epilepticseizures. On the other hand, infants withepileptic spasms can have spasms duringfeeding, which causes them to cry, a situa-tion that can be mistaken for colic.

Distinguishing Isolated Epileptic Seizures from EpilepsyEpilepsy is a disorder of recurrent seizures, soa single event, even if it is unequivocallyepileptic, does not make a diagnosis ofepilepsy. Even recurrent epileptic seizures, ifthey are clearly provoked, for example as aresult of alcohol withdrawal or use of procon-vulsant agents, do not warrant a diagnosis ofepilepsy. Treatment in these situations is notAEDs, but avoidance of the provocative insultwhere possible. More detailed discussions ofthe differential diagnosis between isolatedepileptic seizures and epilepsy are presentedin Chapters 1 and 4. Whether epilepticseizures are isolated or recurrent, however,the next step in providing care is to deter-mine whether there is an underlying treatablecause. If epileptic seizures are due, for exam-ple, to an intracranial infection or a braintumor, once this underlying cause is treatedand epileptic seizures stop, a diagnosis ofepilepsy is not warranted. Only if a treatableunderlying cause is not identified; is identi-fied, treated, and epileptic seizures persist; oris not treated at all, is it appropriate to makea diagnosis of epilepsy.

CLASSIFICATION OF SEIZURES AND EPILEPSIES

Classification of Epileptic SeizuresThe current International League againstEpilepsy (ILAE) classification recognizesmany types of epileptic seizures (Table 2.2).These are divided into generalized seizures,meaning that they appear to begin simulta-neously on both sides of the brain, and par-tial or focal, meaning that they appear tobegin in a part of one hemisphere. Partialseizures are further divided into simple, ifconsciousness is preserved, and complex, ifconsciousness is impaired.

There are at least two important reasonswhy epileptic seizures should be correctlyclassified. The first is that the selection ofAEDs is still heavily based on seizure type.The second is that the correct identificationof the epilepsy syndrome depends on thecorrect classification of the seizure type(s) ina given patient. The identification of a syn-drome is key to establishing the prognosis ofepileptic conditions and to selecting specificpharmacologic and surgical approaches totreatment.

Most Common Seizure TypesThe most common and important types ofepileptic seizures are described here, fol-lowed by a discussion on potential pitfalls inthis semiological diagnosis.

Simple partial seizures without motor fea-tures involve sensory, autonomic, and psy-chic symptoms. The latter can consist ofcomplicated multimodality sensory phenom-ena, emotional experiences, alterations inmemory such as déjà vu and jamais vu, andpsychiatric phenomena, such as depersonal-ization, forced thinking, and delusions.Unlike many psychiatric symptoms, howev-er, psychic epileptic events are stereotypedand relatively brief, interictal behavior isnormal, and patients are aware that theirexperiences are unreal. These simple partialseizures can occur in isolation or progress tocomplex partial or generalized tonic-clonicseizures, in which case they are calledauras. Autonomic or experiential phenome-na suggest temporal lobe involvement,whereas somatosensory and elementaryvisual auras point to ictal generation in the


22

KEYPOINTS

n In endemic regions forneurocysticercosis,particularly where CT ismore easily available, it is acommon mistake to assumethat paroxysmal symptomsare epilepsy, whencalcifications are found onCT.

posterior quadrant. Frontal lobe seizures, onthe other hand, are often ushered in by feel-ings of lightheadedness, ‘conscious confu-sion,’ or other cephalic sensations.Interestingly, the experiential or psychictemporal lobe auras may be misinterpretedas unnatural phenomena. Thus, déjà vu andmemory flashback experiences, sudden

unmotivated fear, or olfactory and gustatoryhallucinations may be attributed to the directaction or influence of spirits or other entitiesrelated to the religious folklore of differentcultures. Such misattributions are certainlyoverrepresented in less educated communi-ties of developing countries.

Simple partial motor seizures initiallyinvolve body parts well represented in thecortical motor strip humunculus, such as thehand or face, on one side of the body. Asthe seizure progresses, ictal involvement of awhole hemibody can occur. Both the type ofinitial motor phenomena and the character-istics of the propagated motor activity pro-vide valuable information as to the cerebrallocalization of seizure origin and spread.Partial motor seizures can be conceptualizedalong two main axes: 1) type: whether theinitial and sequential focal motor phenome-na are clonic, tonic, dystonic, myoclonic, oratonic; and 2) topography of initial and sec-ondary involvement of body parts.Paroxysmal motor movements involvingtruncal and other muscles not well repre-sented in the cortical motor strip are usuallymyoclonic and not epilepsy.

Complex partial seizures (CPSs) originatein or involve limbic structures, usuallymesial temporal, and often are preceded bysimple partial seizures with autonomic orpsychic symptoms. The most common ofthese are a sensation of epigastric rising andemotional experiences such as fear. Partialseizures are designated as complex whenconsciousness is impaired, although impair-ment of consciousness is not always easy todocument. Typically, seizures begin with anarrest of movement and stare, during whichpatients may not be responsive to the envi-ronment. Commonly, there are oroalimenta-ry automatisms such as chewing and lip-smacking, followed by more complexbehavioral automatisms that may be influ-enced by the environment. For example,simple automatisms may involve gestures ofupper or lower extremities or dystonic pos-turing, whereas more complicated automa-tisms may involve running or walking, orpatients may continue repetitive activitiessuch as washing dishes, or exhibit bizarrebehaviors. By definition, complex partialseizures are associated with amnesia for the


23

International Classificationof Epileptic Seizures

TABLE 2.2

I. Partial (focal, local) seizures

A. Simple partial seizures

1. With motor signs

2. With somatosensory or specialsensory symptoms

3. With autonomic symptoms orsigns

4. With psychic symptoms

B. Complex partial seizures

1. Simple partial onset followedby impairment of consciousness

2. With impairment of conscious-ness at onset

C. Partial seizures evolving to second-arily generalized seizures

1. Simple partial seizures evolvingto generalized seizures

2. Complex partial seizures evolv-ing to generalized seizures

3. Simple partial seizures evolvingto complex partial seizuresevolving to generalizedseizures

II. Generalized seizures (convulsive ornonconvulsive)

A. Absence seizures

1. Typical absences

2. Atypical absences

B. Myoclonic seizures

C. Clonic seizures

D. Tonic seizures

E. Tonic-clonic seizures

F. Atonic seizures (astatic seizures)

III. Unclassified epileptic seizures

From: Commission on Classification andTerminology of the International LeagueAgainst Epilepsy, 1981. Used with permission.

ictal event, and patients usually experiencepostical confusion for several minutes.

Typical absence seizures are brief (10 sec-onds or less) episodes of unresponsivenessto the environment; these seizures bothappear and disappear suddenly, withoutwarning or postictal confusion. Patients usu-ally display a blank, motionless stare for afew seconds, and episodes characteristicallyrecur several times a day. Typical absencescan often be precipitated by asking the childto hyperventilate during the examination.There can be subtle yet significant motoraccompaniments such as eyelid myoclonia,perioral myoclonia, upper limb myoclonia,and even simple reactive automatisms.Perioral and upper limb jerks are more like-ly to be pharmacoresistant, and the latter isassociated with a higher risk of mental delay.

Atypical absence seizures are distinct fromtypical absence episodes because they oftenlast longer, can be associated with markedtonic or atonic motor components, and areusually followed by postictal confusion.Their precise onset and offset are difficult todetermine. Whereas typical absence seizuresoccur in the benign idiopathic generalizedepilepsies unassociated with other neurolog-ic disturbances, atypical absences resultfrom generalized brain damage and usuallyoccur in patients who also have or developmental retardation, additional neurologicimpairment, and other types of epilepticseizures. These seizures are all usually phar-macoresistant.

Generalized tonic clonic seizures are thehallmark of the diffuse involvement of corti-cal and subcortical structures by ictal epilep-tic activity. They can be primarily general-ized, starting directly as a generalized tonicand then clonic seizure, or secondarily gen-eralized, evolving from any type of partialseizure, which then propagates through cor-tical and subcortical circuits and leads to thesame final common pathway of a general-ized tonic-clonic seizure. The intense, exces-sive, neuronal, and muscular activity usuallyleads to protracted postictal somnolence,confusion, and sore muscles. Patients canbite their tongues during the seizure and beincontinent of urine and feces. Generalizedmotor seizures can also be purely tonic,purely clonic, or clonic-tonic-clonic.

Drop attacks are seizures leading to sud-den falls to the ground. These can be gener-alized atonic, myoclonic, myoclonic-atonic,or brief tonic attacks. At times, there isprompt recovery of consciousness after thefall, which, however, does not diminish therisk of injury. Some partial seizures can alsolead to drop attacks, usually through veryfast access to interhemispheric propagationpathways, such as the corpus callosum.

Epileptic spasms occur mainly in infancy,but occasionally later in life. The axial con-traction, in flexion or tension, with upwarddeviation of the eyes, lasts longer than amyoclonic jerk (about 1 second) and usual-ly recurs in clusters in 10-second intervals.The jerk is often followed by a cry, leadingto misdiagnosis of colic.

Status EpilepticusStatus epilepticus (SE) is characterized byseizures that do not spontaneously stop.Formally, SE is defined as recurrent epilepticseizures without full recovery of conscious-ness between seizures or continuous clinicaland/or electrical seizure activity lasting morethan 30 minutes. Consciousness may or maynot be fully impaired, depending on thetype of SE. SE is classified into generalizedconvulsive SE (GCSE), absence SE, complexpartial SE, and simple partial SE (also calledepilepsia partialis continua). GCSE is themost common type and is a medical emer-gency. If untreated, these events are associ-ated with irreversible neuronal damage anddeath from both altered cerebral metabolismand secondary injury due to lactic acidosis,hypoxia, hypercarbia, hyperthermia, anddirect brain insult. Causes of SE include poorAED compliance (especially in countrieswhere drug distribution is unreliable), sud-den and recent change or withdrawal ofAEDs, acute illnesses such as meningoen-cephalitis, stroke, head injury, metabolic dis-orders, and alcohol or substance abuse.Rarely, GCSE may be the first manifestationof epilepsy. Ironically, patients in develop-ing areas whose seizure disorders begin withGCSE have the best chance to benefit frommedical treatment because the emergencyleads them directly to a health center.Outcome depends on the age of the patient,underlying conditions, and duration of SE


24

KEYPOINTS

n Ironically, patients indeveloping areas whoseseizure disorders beginwith GCSE have the bestchance to benefit frommedical treatment becausethe emergency leads themdirectly to a health center.

before treatment is initiated. If GCSE is leftuntreated or is inadequately treated, the clin-ically evident GTCS can fade into subtle con-vulsive motor activity, usually mildmyoclonus, making the diagnosis very diffi-cult. Subtle convulsive SE can be diagnosedwith the help of EEG monitoring, but a highlevel of suspicion may identify the subtlemanifestations and circumvent the need forEEG monitoring. Treatment must be urgent-ly instituted to prevent further damage.

Absence SE and complex partial SE areoften referred to as nonconvulsive SE, andsymptoms can overlap. Whereas the moststriking features of both types of status consistof confusional states with occasionalmyoclonic jerks and automatisms, absencestatus is more often continuous and seen mostcommonly in children, whereas complex par-tial status typically is associated with fluctuat-ing consciousness, often has more pro-nounced automatisms, and occurs more com-monly in older children and adults. Absencestatus, particularly in children with sympto-matic generalized epilepsy, can have verysubtle myoclonic and cognitive features andcontinue for days to weeks without severepostictal symptoms. Prolonged complex par-tial status, however, is followed by severememory impairment, and occasionally otherfocal neurologic deficits that may be enduringor permanent. Aggressive therapeutic inter-vention is justified to terminate complex par-tial status, but absence status in childrenshould also be considered an emergency.

Simple partial SE, or epilepsia partialis con-tinua (EPC), is a rare epileptic manifestationwith a narrow etiological differential diagno-sis. Most often, EPC presents as continuous orfrequently recurring clonic or myoclonic jerksinvolving parts of a limb up to a whole hemi-body, lasting from several hours to manydays. EPC indicates the presence of an acutefocal insult or of a structural lesion, which canbe diffuse. Most commonly, the latter repre-sents a tumor, cortical dysplasia, Rasmussen’sencephalitis, or, in infants and small children,an inborn error of metabolism.

Common Causes for Misdiagnosis ofSeizure TypeData leading to seizure diagnosis are usual-ly obtained indirectly and based on the

accounts of the patient and reliable witness-es. Even in developed countries, only asmall minority of patients with definite orsuspected epilepsy have their seizuresvideotaped and correlated with the EEG, tobe analyzed by a neurologist. Thus, thephysician must encourage a detaileddescription, while making every effort totranslate the patient’s or witness’ expressionsinto known and relevant semiological hall-marks of seizure types. People in developingcountries often have misconceptions aboutthe nature of an epileptic attack and tend tofocus their observations on the generalizedconvulsive part of the seizure. Tonic-clonicgeneralized convulsive movements, withtongue biting and incontinence are frighten-ing, and often eclipse the fact that theepisode was heralded by a few jerks in onehand or in the corner of the mouth.Similarly, periods of unresponsiveness andoroalimentary automatisms, either as recur-rent isolated episodes or preceding general-ized seizures are often not voluntarilyreported and require some direct question-ing by the neurologist. Two difficult differ-ential diagnoses are discussed next.

Absences versus complex partial seizures.Typical absence attacks as part of ideopath-ic generalized epilepsy syndromes (see nextsection) are usually fully responsive to med-ical treatment with specific AEDs (particular-ly valproic acid and ethosuximide), thusconstituting a fairly “benign” seizure pattern.In contrast, the environmental disconnection(often referred to by patients and relatives as“absences”) observed in complex partialseizures are actually localization-related phe-nomena, thus more prone to be controlledby drugs like carbamazepine and phenytoin.Indeed, these latter medications may evenworsen absence seizures. Therefore, correctdiagnosis of the seizure type in this contexthas an immediate impact on treatment effi-cacy. Typical absences are usually very brief(less than 10 seconds), not preceded byauras, and not followed by postictal confu-sion. Simple automatisms can be present.Complex partial seizures dominated by envi-ronmental disconnection are often precededby typical temporal lobe-type auras, tend tolast at least 20 to 40 seconds, are often


25

KEYPOINTS

n People in developingcountries often havemisconceptions about thenature of an epilepticattack and tend to focustheir observations on thegeneralized convulsive partof the seizure. Tonic-clonicgeneralized convulsivemovements, with tonguebiting and incontinence arefrightening, and ofteneclipse the fact that theepisode was heralded by afew jerks in one hand or inthe corner of the mouth.Similarly, periods ofunresponsiveness andoroalimentaryautomatisms, either asrecurrent isolated episodesor preceding generalizedseizures are often notvoluntarily reported andrequire some directquestioning by theneurologist.

accompanied or followed by oroalimentaryor gestural automatisms, and are followedby postictal confusion. The differentiationbetween these seizure types is usually possi-ble by clinical history, and only rarely areEEG or video-EEG needed.

Primarily versus secondarily generalizedseizures. Partial ictal phenomena preced-ing secondary generalization may be missedwhen subtle, occurring during sleep, or whenalmost immediately followed by generalizedconvulsive movements. Indeed, the latter aresuch impressive phenomena that they domi-nate the episode and their reporting bypatients and relatives. Missing a partial onsetcan lead to incorrect seizure and syndromeclassification (see next section), and negative-ly impact medical management and progno-

sis. Antiepileptic drugs that are effective forprimarily generalized seizures (particularlywhen part of ideopathic generalized epilep-sies; see next section) can be less prone tofully control partial seizures with rapid sec-ondary generalization. Careful history takingwith explicit questioning of the patient andwitnesses is often sufficient to distinguishbetween these conditions, although EEGsmay occasionally be necessary.

Classification of Epilepsy SyndromesSimilar to the approach to any other neuro-logic disorder, it is important for the clini-cian to arrive at a syndromic, topographic,and etiologic diagnosis in each patient withepilepsy. There are many different epilepticsyndromes, which are distinguished on thebasis of 1) type or types of epileptic


26

CASE STUDY

Presentation: For more than a year, a couple living in a poor country had been facing a significant socioeconomic dilemmarelated to the costs of treatment of their 11-year-old son, who had recurrent episodes of disconnection from the environ-ment. The episodes began 2 years earlier, and after sequential trials of phenobarbital, phenytoin, and carbamazepine, theboy was given newer and more costly antiepileptic drugs. These medications have also fallen short of controlling the attacks,but the boy was maintained on oxcarbazepine 1,500 mg/day. Since the beginning of his problem, school performance andbehavior have worsened. Despite the impact of the costs on the household budget, the parents have complied with all physi-cians’ prescriptions.

Seizures were initially noted at school and described as episodes lasting about 10 seconds, characterized by sudden arrestof activity, staring, and drooling. There was questionable confusion for a few seconds afterwards, although the boy couldeasily resume his activities. Two to four of these episodes occurred every day. About 1 year after the onset of seizures, he hada single nocturnal generalized tonic-clonic seizure. Previous medical history was remarkable for three brief febrile convul-sions between ages 1 and 3 years, and there was also a positive family history for febrile convulsions and epilepsy.

Evaluation: General medical and neurologic examinations were normal. Two EEGs during wakefulness and sleep showed nor-mal background activity and sharp waves over the centrotemporal regions, which increased markedly during sleep. Photicstimulation was not available at the EEG lab, and the boy did not cooperate with voluntary hyperventilation. A CT scan wasnormal, and the parents were informed that an MRI was needed—despite the fact that they would need to pay for the exam.The latter was also normal.

Treatment: Oxcarbamazepine was slowly discontinued, and ethosuximide begun, up to a dosage of 750 mg/day.

Outcome: Seizures were completely controlled, although interictal centrotemporal sharp waves persisted on the EEG.

Comment: This boy had a form of idiopathic generalized epilepsy, most likely juvenile absence epilepsy. A combination offacts led to misdiagnosis of both the epileptic seizures and the epileptic syndrome, and therefore, to inadequate seizure con-trol and increased costs of evaluation and treatment. A core aspect was the misinterpretation of absence seizures as complexpartial seizures. The history of febrile convulsions and the focal epileptiform activity on EEG probably added to the diagnos-tic confusion. However, both a personal and family history of febrile convulsions and centrotemporal (rolandic) sharp wavesare also observed in patients with idiopathic generalized epilepsy syndromes. Furthermore, generalized spike and wave com-plexes on the EEG may be missed in juvenile absence epilepsy, especially if photic stimulation is not available (a common sit-uation in EEG labs in developing countries) and voluntary hyperventilation is not adequately performed. The very favorableresponse to ethosuximide—an inexpensive AED specific for absence and myoclonic seizures—supports the hypothesis of anidiopathic generalized epilepsy syndrome.

seizures; 2) age of seizure onset; 3) etiolo-gy; 4) degree of associated neurologic andintellectual deficits; 5) clinical evolution ofthe epilepsy and any underlying condition;6) pattern of EEG abnormality; and 7)abnormalities on imaging exams.Identifying an epileptic syndrome implies aparticular therapeutic approach and prog-nosis; however, many patients have epilep-tic conditions that do not fit into a recog-nized syndromatic category.

The currently accepted ILAE classificationof epilepsies and epilepsy syndromes (Table2.3) divides these conditions into general-ized and localization-related. The former aredue to diffuse bilateral disturbances, where-as the latter are due to abnormalities relatedto a part of one hemisphere. In addition,syndromes are divided into idiopathic,which are benign, age-related genetic distur-bances manifesting only as epilepsy; symp-tomatic, which are secondary to lesions ofthe brain, either acquired or genetic; andcryptogenic, meaning probably sympto-matic, but the etiology is unknown. Theprognosis of symptomatic epilepsiesdepends on the prognosis of the underlyingsubstrate.

Most Common Epilepsy Syndromes

Symptomatic Partial EpilepsiesRecurrent partial seizures associated with alocalized lesion are the defining features ofsymptomatic partial epilepsies. Althoughdefinitive studies have not been done, themost common symptomatic partial epilepsiesfound in developing countries are most like-ly to be mesial temporal lobe epilepsy withhippocampal sclerosis, and neocorticalepilepsies due to neurocysticercosis, otherinfectious disorders, trauma, and malforma-tions of cortical development (MCD). Theidentification of the lesion often relies onneuroimaging, but clinical history and neuro-logic examination can suffice to raise a highlevel of suspicion of this group of entities. Attimes, this scenario is associated with normalneuroimaging, leading to a diagnosis of‘cryptogenic’ partial epilepsy—symptomaticepilepsy for which the cause is beyond theresolution of available neuroimaging.

Mesial temporal lobe epilepsy. Abouttwo-thirds of all symptomatic partial epilep-sy syndromes involve the temporal lobes,particularly their anteromesial structures,


27

CASE STUDY

Presentation: This 62-year-old noninsulin-dependent diabetic man experienced generalized tonic-clonic seizures exclusivelyduring sleep 3 years before presentation. His wife did not report focal components, describing instead generalized body stiff-ening preceded by a loud scream from the very onset of the attacks. Despite treatment with 2,250 mg/day of valproic acid,seizures recurred every month. There were no other vascular risk factors. Family history was positive for stroke, but negativefor epilepsy.

Evaluation: General medical and neurologic examinations showed only reduced pinprick and tactile sensation in both feet.Fasting glucose, creatinine, and LDL cholesterol levels were mildly elevated, but other laboratory tests were normal. Two EEGsduring wakefulness and sleep were normal. Neuroimaging exams were not available in the patient’s region.

Treatment: Phenytoin was started and titrated up to 350 mg/day. Valproic acid was slowly discontinued.

Outcome: Seizures have not recurred for 2 years.

Comment: In the context of generalized seizures occurring only during sleep, normal EEGs, and unavailable neuroimagingfacilities, the diagnosis of the type of epileptic seizure and syndrome may be difficult. The clinical key to the present case wasthat “de novo” idiopathic generalized epilepsy with tonic-clonic seizures is not common at this patient’s age. Thus, in the eventof inadequate seizure control with an antiepileptic medication best suited to control primarily generalized seizures, the pos-sibility of secondarily generalized seizures without obvious focal features should be considered. With no additional cost, thishypothesis can be tested by introducing or substituting an AED with a greater specificity for partial onset seizures.


28

International Classification of Epilepsies, Epileptic Syndromes, and RelatedSeizure Disorders

TABLE 2.3

1. Localization-related (focal, local, partial)

1.1 Idiopathic (primary)

• Benign childhood epilepsy withcentrotemporal spikes

• Childhood epilepsy with occipitalparoxysms

• Primary reading epilepsy

1.2 Symptomatic (secondary)

• Temporal lobe epilepsies

• Frontal lobe epilepsies

• Parietal lobe epilepsies

• Occipital lobe epilepsies

• Chronic progressive epilepsia partialis continua of childhoodsyndromes characterized byseizures with specific modes of precipitation

1.3 Cryptogenic, defined by:

• Seizure type

• Clinical features

• Etiology

• Anatomical localization

2. Generalized

2.1 Idiopathic (primary)

• Benign neonatal familial convulsions

• Benign neonatal convulsions

• Benign myoclonic epilepsy ininfancy

• Childhood absence epilepsy(pyknolepsy)

• Juvenile absence epilepsy

• Juvenile myoclonic epilepsy (impulsive petit mal)

• Epilepsies with generalized tonic-clonic seizures on awakening

• Other generalized idiopathicepilepsies

• Epilepsies with seizures precipitat-ed by specific modes of activation

2.2 Cryptogenic or symptomatic

• West syndrome (infantile spasms,Blitz-Nick-Salaam Krämpfe)

• Lennox-Gastaut syndrome

• Epilepsy with myoclonic-astaticseizures

• Epilepsy with myoclonic absences

2.3 Symptomatic (secondary)

2.3.1 Nonspecific etiology

• Early myoclonicencephalopathy

• Early infantile epilepticencephalopathy with sup-pression bursts

• Other symptomatic general-ized epilepsies

2.3.2 Specific syndromes

• Epileptic seizures may com-plicate many disease states.

3. Undetermined epilepsies

3.1 With both generalized and focalseizures

• Neonatal seizures

• Severe myoclonic epilepsy in infancy

• Epilepsy with continuous spike-waves during slow wave sleep

• Acquired epileptic aphasia(Landau-Kleffner syndrome)

• Other undetermined epilepsies

3.2 Without unequivocal generalized orfocal features

4. Special syndromes

4.1 Situation-related seizures(Gelegenheitsanfälle)

• Febrile convulsions

• Isolated seizures or isolated statusepilepticus

• Seizures occurring only when thereis an acute or toxic event due tofactors such as alcohol, drugs,eclampsia, nonketotic hyper-glycemia

From: Commission on Classification andTerminology of the International LeagueAgainst Epilepsy, 1989. Used with permission.

which have a low epileptogenic thresholdwhen confronted with a wide variety ofinsults. The most common associatedpathology is hippocampal sclerosis.Although MRI is needed to identify the scle-rotic hippocampus, the syndrome of mesialtemporal lobe epilepsy associated with hip-pocampal sclerosis may be suspected whentypical temporal auras and complex partialseizures are associated with an initial precip-itating insult during early childhood, usuallya febrile seizure.

Partial epilepsies due to neurocysticerco-sis. Cysticercosis is an endemic parasiticdisorder in many developing countries,where neurocysticercosis is a common causeof epileptic seizures. Seizures may occur asa manifestation of the acute cerebral infec-tion or as a sequelae of the calcified cysts. Inthe former scenario, other signs and symp-toms usually are present, suggestive either ofincreased intracranial pressure (e.g.,headache, malaise, nausea, and vomiting) orof localized cortical dysfunction, in the formof sensorimotor or cognitive deficits. Theattacks are usually partial, with occasionalsecondary generalization. Epilepsy associat-

ed with calcified cysts is usually an isolatedentity after resolution of the acute infection.Interestingly, seizure semiology may or maynot be functionally related to the site of sin-gle or multiple calcifications, and electroclin-ical features of mesial temporal lobe epilep-sy often are the presenting picture, irrespec-tive of the location of the calcifications. CTscanning and EEGs in an endemic region areusually sufficient for diagnosis and treat-ment. If CT is unavailable in endemic areas,cutaneous and muscle symptoms plus serol-ogy may suffice to make the diagnosis.

Disappearing CT lesions. This syndromeappears to be unique to India. The CT/MRIscans usually show a small, subcortical con-trast enhancing, hyperdense ring or disclesion surrounded by a variable area show-ing edema. Most of the CT/MRI lesions dis-appear completely or show a near completeresolution within a few weeks without anyspecific treatment except AEDs. The so-called “disappearing CT lesions” or “single,small enhancing lesions (SSELs)” are nowaccepted to be a common feature in a largenumber of patients with epilepsy from India,where such cases constitute about 10% of all


29

CASE STUDY

Presentation: A 15-year-old boy presented with a history of jerking of the right upper limb followed by a secondarily gener-alized tonic-clonic seizure lasting for a few minutes. He noticed weakness of the right upper limb after the seizure, and theweakness improved over the next 2 hours. The next day, he had another seizure similar to the previous one, but without anypostictal limb weakness. He had no previous history of seizures and none of his family members were affected with seizures.

Evaluation: His neurologic examination was normal. The CT scan of the head showed evidence of a single small ring-enhanc-ing lesion in the left posterior frontal cortical region with surrounding edema. The EEG was reported to be normal.

Treatment and Outcome: He was treated with phenytoin (250 mg per day) and subsequently remained seizure free. A repeatcontrast-enhanced CT scan of the head after 6 months of the first scan showed complete resolution of the lesion and wasinterpreted as normal. He was continued on phenytoin for the next year and the drug was then gradually stopped. He con-tinues to be seizure free when last seen about 4 years after the first seizure.

Comment: This is an example of a benign symptomatic epilepsy syndrome peculiar to the Indian subcontinent. This syndromeaccounts for about 10% of all epilepsy cases in large Indian centers and most patients are usually young and have a few sim-ple partial seizures with or without secondarily generalized seizures. Some of them may have evanescent postictal focal neu-rologic deficits. The syndrome is so benign that seizures among most of these patients remain under control irrespective of theAED used. The exact duration of AED therapy has not been defined, but most physicians would treat such patients with AEDsfor about 1 to 2 years.

epilepsy patients presenting at various cen-ters. These patients are usually young andhave a few simple partial seizures with orwithout secondarily generalized seizures.Some of them may have postictal focal neu-rologic deficits that disappear in a few days.The etiology of the SSELs is presumed to bediverse, but some have been proved to be ofcysticercal origin.

Partial epilepsies due to malformationsof cortical development (MCD). A com-bination of genetic and environmental fac-tors can lead to MCDs, which often presentwith epilepsy accompanied or not by vari-able degrees of mental retardation and othersigns of neurologic dysfunction. The exactnature of the associated epileptic picturedepends on the type and extent of the mal-formation. Early prenatal care is critical forthe prevention of some types of these disor-ders. MCD often leads to severe partialsymptomatic epilepsies refractory to medicaltreatment. In developing countries, MCDshould be suspected as the epilepsy etiologywhen there is no history of perinatal or post-natal distress, and a CT scan rules out neu-rocysticercosis. Early onset of partial seizuresor spasms is the usual presentation.

Symptomatic Generalized EpilepsiesThese relatively intractable epileptic disor-ders result from diffuse brain damage ofmoderate to severe intensity and are usuallyassociated with developmental delay, cogni-tive dysfunction, and behavioral abnormali-ties. Severe early infantile myoclonus orinfantile spasms is often the mode of onset.Seizures are polymorphic and include gener-alized tonic, tonic-clonic, atonic, myoclonic,and atypical absence spells. The most com-mon underlying etiology of symptomaticgeneralized epilepsies in developing coun-tries is hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy. Hypoxic-ischemic encephalopathy due to perinataldistress is a frequent cause of epilepsy indeveloping regions. A shortage of doctors,poorly trained midwives, and unexplaineddelays in making decisions about the mostadequate form and timing of delivery are alltoo common. If there is one group of epilep-

tic disorders that may be considered aspotentially preventable through improvededucation and professional commitment, it isthat related to perinatal hypoxic-ischemicencephalopathy. The extent of the ultimatebrain insult will determine the type andseverity of the epileptic disorder and associ-ated cognitive and motor dysfunction, but acombination of partial and severe general-ized seizures coupled with abnormal psy-chomotor development is the gloomy out-come for a significant percentage of thesechildren.

Idiopathic Generalized EpilepsiesAs a group, the idiopathic generalizedepilepsies deserve special emphasis,because their correct identification usuallyleads to effective medical treatment, thusdecreasing the burden of epilepsy forpatients and relatives. Several discrete age-related syndromes have been identified, butsome unifying features should be consid-ered: patients are developmentally and neu-rologically normal; seizures consist of eitherprimarily generalized tonic-clonic attacks,typical absences, bilateral myoclonus, or acombination of these; a positive family his-tory of epilepsy or febrile convulsions isoften present; EEGs have at least reasonablywell organized background activity and gen-eralized spike and wave or polyspike andwave discharges at 3 Hz or faster; andseizures are usually fully responsive to med-ication. Seizures commonly remit sponta-neously when onset is before puberty, butlifelong treatment is usually necessary forthe juvenile onset forms.

Idiopathic Partial EpilepsiesThese benign conditions typically begin inchildhood, remit spontaneously in adoles-cence, and seizures can be so mild andinfrequent that no treatment is required. Themost common syndrome is benign child-hood epilepsy with centrotemporal spikes.Most children with this disorder are develop-mentally normal and neurologically intactand have fairly stereotypical focal sensori-motor seizures of the face, which may beaccompanied by head turning or motorinvolvement of the ipsilateral hemibody. TheEEG reveals unilateral or bilateral centrotem-


30

KEYPOINTS

n If there is one group ofepileptic disorders that maybe considered aspotentially preventablethrough improvededucation and professionalcommitment, it is thatrelated to perinatalhypoxic-ischemicencephalopathy.

poral spikes with a characteristic transversedipole. This is one of the few epilepsy syn-dromes for which anticipation of remissionby adolescence truly applies. The combina-tion of typical ictal semiology and EEG in anormal child allows the correct diagnosis. Avariant is associated with occipital spikes,vomiting, and asymmetrical tonic activitylasting up to 2 hours.

Plans for a New Classification Schemefor Seizures and EpilepsiesA major criticism of the ILAE classification ofepileptic seizures, which was intended to bepurely phenomenological because of lack ofinformation on pathophysiologic andanatomic substrates in 1981, when it wasadapted, has been the need for a prioriassumptions about etiology and detailedEEG data before a diagnosis could be made.This makes the classification difficult toapply in developing countries, where EEGrecordings and other diagnostic tests are noteasily obtained. This problem negativelyimpacted epidemiologic studies in develop-ing regions of the world, as well as in clini-cal practice. Consequently, the ILAE hasnow proposed two approaches to the classi-fication of epileptic seizures. The first ofthese consists of a purely semiologicaldescription of the ictal signs and symptoms,which requires no a priori assumptions andno laboratory information. This purely phe-nomenological descriptive approach, there-fore, would be easy to apply everywhere inthe world, regardless of available diagnosticresources. The second approach would treatepileptic seizures as diagnostic entities, sim-ilar to epileptic syndromes. Seizure types arecurrently considered based on modern con-cepts regarding specific pathophysiologicand anatomic substrates. Diagnosis of a spe-cific seizure type, therefore, will have etio-logic, therapeutic, and prognostic implica-tions. A diagnosis of seizure type, or types,in an individual patient can supplement thesyndromic diagnosis and, in the not uncom-mon situation where a syndromic diagnosiscannot be made, further diagnostic evalua-tion and treatment can be determined by thediagnoses of seizure types.

The list of accepted epileptic syndromes isalso being updated based on the latest infor-

mation, which now includes extensive genet-ic studies. Despite great conceptual advancesin our understanding of the fundamentalmechanisms of the epilepsies since the cur-rent ILAE Classification of the Epilepsies wasadopted in 1989, many, if not most, patientspresenting with one or more epilepticseizures have a constellation of signs andsymptoms that still do not fit neatly into anaccepted syndromic diagnosis. This is partic-ularly true in areas with limited resources,where modern diagnostic facilities are notreadily available. For these patients, phe-nomenological description of ictal semiologyand diagnosis of a seizure type will beimportant for guiding management.

The ILAE has also proposed a diagnosticscheme consisting of five axes, which can beused to fully characterize the epileptic condi-tion in each individual patient (Table 2.4).The first four axes, ictal phenomenology,seizure type, syndrome, and etiology, arearranged in order of increasing diagnosticcomplexity, and details may not be availableto definitively assign a diagnosis for the latteraxes, particularly in developing countries;however, assumptions can be made based ondiagnoses assigned in the earlier axes to planmanagement. The optional fifth axis, impair-ment, is based on a proposed WHO classifi-cation of impairment in neurologic disordersand can be useful for advising patients andothers regarding functional prognosis, includ-ing compensation for disability.

The ILAE is now debating how to organ-ize and categorize the lists of epilepticseizures and epileptic syndromes into usefulclassifications. Any new classifications ofepileptic seizures and epilepsies cannot straytoo far from the current classifications,because the tremendous advantages gainedfrom the universal application of certainbasic taxonomic concepts should not be lost.Some changes in terminology, however,have already been proposed (Table 2.5).These classifications will be designed to takeinto account the fact that they will be used indiverse ways, each with its own inherent tax-ological requirements. Some will demandsimplicity, e.g., for teaching, use by primarycare physicians, and in developing countrieswhere detailed diagnostic evaluations are notpossible. Others will require unique special-


31

ized details, e.g., for various types of epi-demiologic purposes, experimental drug tri-als, epilepsy surgery, and basic research. Forthese reasons, a flexible group of classifica-tions is envisioned, perhaps in a modular for-mat, which can be reorganized for specificpurposes and easily changed as experiencewith application dictates and as new infor-mation becomes available. Participation inthis process by epileptologists working indeveloping countries is as important as par-ticipation by epileptologists working in fieldsof epidemiology, clinical pharmacology,epilepsy surgery, and basic research.Similarly, experience gained from the exten-sive use of any new classifications in devel-oping countries will be as important as expe-rience from use in other areas for decidingon subsequent revisions and refinements.

CONCLUSIONSA differential diagnosis between epilepsyand other conditions is of primary impor-tance in the care of individuals presentingwith suspected events. An unwarranteddiagnosis of epilepsy is to be avoided in anycase, but is of particular concern in develop-ing countries, where patients who receivethis diagnosis may be victims of stigma andsocial exclusion, and where the cost of AEDscan cause extreme financial hardship.Accurate differential diagnosis can beachieved in most cases on clinical groundsbut requires familiarity not only with the typ-ical presentation of epileptic seizures andepilepsy syndromes, but with a variety ofconditions such as breath-holding spells,panic attacks, hyperventilation syndrome,basilar migraine, psychogenic seizures, syn-copy, transient ischemic attacks, movementdisorders, myoclonus, parasomnias, andattention deficit-hyperactivity disorder,which are commonly mistaken for epilepsy.

Furthermore, it is important to recognizethat paroxysmal events in association withevidence of conditions common in develop-ing countries, such as neurocysticercosis, donot mean that the events are epileptic, or ifthey are, that they are in fact due to the mostobvious disease process. A single epilepticseizure also is not epilepsy; it may be a pro-voked or acute symptomatic event that doesnot indicate the presence of a chronic epilep-


32

Proposed Diagnostic Scheme forPeople with Epileptic Seizures, andwith Epilepsy

TABLE 2.4

Epileptic seizures and epilepsy syndromes are to bedescribed and categorized according to a system thatutilizes standardized terminology and that is suffi-ciently flexible to take into account the followingpractical and dynamic aspects of epilepsy diagnosis:

1. Some patients cannot be given a recognized syn-dromic diagnosis.

2. Seizure types and syndromes change as newinformation is obtained.

3. Complete and detailed descriptions of ictal phe-nomenology are not always necessary.

4. Multiple classification schemes can, and should,be designed for specific purposes (e.g., communi-cation and teaching; therapeutic trials; epidemio-logic investigations; selection of surgical candi-dates; basic research; genetic characterizations).

This diagnostic scheme is divided into five parts, oraxes, organized to facilitate a logical clinicalapproach to the development of hypotheses neces-sary to determine the diagnostic studies and thera-peutic strategies to be undertaken in individualpatients:

Axis 1: Ictal phenomenology—from the Glossary ofDescriptive Ictal Terminology, can be used to describeictal events with any degree of detail needed.

Axis 2: Seizure type—from the List of EpilepticSeizures. Localization within the brain and precipitat-ing stimuli for reflex seizures should be specifiedwhen appropriate.

Axis 3: Syndrome—from the List of EpilepsySyndromes, with the understanding that a syndromicdiagnosis may not always be possible.

Axis 4: Etiology—from a Classification of DiseasesFrequently Associated with Epileptic Seizures orEpilepsy Syndromes when possible, genetic defects,or specific pathologic substrates for symptomaticfocal epilepsies.

Axis 5: Impairment—this optional, but often useful,additional diagnostic parameter can be derived froman impairment classification adapted from the WHOICID.

From Engel J Jr. A proposed diagnostic scheme forpeople with epileptic seizures and with epilepsy:Report of the ILAE Task Force on Classification andTerminology. Epilepsia 2001;42:796–803 with permission.

togenic disturbance. A diagnosis of epilepsyrequires the presence of an enduring brainabnormality capable of generating recurrentspontaneous seizures. Understanding theclassification of epileptic seizures, and ofepilepsy syndromes, is essential to making a

correct diagnosis that in turn will determinewhether additional diagnostic evaluation isnecessary to search for an underlying treat-able cause, as well as to infer specific treat-ment and provide prognostic information.


33

Definitions of Key TermsTABLE 2.5

Epileptic Seizure Type: An ictal event believed to represent a unique pathophysiologic mechanism and anatomic substrate. This is adiagnostic entity with etiologic, therapeutic, and prognostic implications. (New concept)

Epilepsy Syndrome: A complex of signs and symptoms that define a unique epilepsy condition with different etiologies. This mustinvolve more than just the seizure type; thus, frontal lobe seizures per se, for instance, do not constitute a syndrome. (Changed con-cept)

Epilepsy Disease: A pathologic condition with a single specific, well-defined etiology. Thus, progressive myoclonus epilepsy is a syn-drome, but Unverricht-Lundborg is a disease. (New concept)

Epileptic encephalopathy: A condition in which the epileptiform abnormalities themselves are believed to contribute to the progres-sive disturbance in cerebral function. (New concept)

Benign epilepsy syndrome: A syndrome characterized by epileptic seizures that are easily treated, or require no treatment, andremit without sequelae. (Clarified concept)

Reflex epilepsy syndrome: A syndrome in which all epileptic seizures are precipitated by sensory stimuli. Reflex seizures that occurin focal and generalized epilepsy syndromes that are also associated with spontaneous seizures, are listed as seizure types. Isolatedreflex seizures can also occur in situations that do not necessarily require a diagnosis of epilepsy. Seizures precipitated by other spe-cial circumstances, such as fever or alcohol withdrawal, are not reflex seizures. (Changed concept)

Focal seizures and syndromes: Replaces the terms partial seizures and localization-related syndromes. (Changed terms)

Simple and complex partial epileptic seizures: These terms are no longer recommended, nor will they be replaced. Ictal impairmentof consciousness will be described when appropriate for individual seizures, but will not be used to classify specific seizure types.(New concept)

Idiopathic epilepsy syndromes: A syndrome that is only epilepsy, with no underlying structural brain lesion or other neurologic signsor symptoms. These are presumed to be genetic and are usually age-dependent. (Unchanged term)

Symptomatic epilepsy syndrome: A syndrome in which the epileptic seizures are the result of one or more identifiable structurallesions of the brain. (Unchanged term)

Probably symptomatic epilepsy syndrome: Synonymous with, but preferred to, the term cryptogenic, used to define syndromes thatare believed to be symptomatic, but no etiology has been identified. (New term)

From Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force onClassification and Terminology. Epilepsia 2001;42:796–803, with permission.

CITATIONS AND RECOMMENDED READINGAndermann F. Overview: Disorders that can be confused with epilepsy. In: Engel J Jr, Pedley TA, (eds.) Epilepsy: A

Comprehensive Textbook, Philadelphia: Lippincott Raven, 1997;2645–2648.

This chapter provides an overview of the entities to be considered in the differential diagnosis of epileptic seizures.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revisedclinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22: 489–501.

This is a summary of the revised Classification of Epileptic Seizures, as proposed by the ILAE Commission onClassification and Terminology in 1981. Epileptic seizures are defined based on semiology and EEG features.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revisedclassification of epilepsy and epileptic syndromes. Epilepsia 1989;30:389–399.


Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAETask Force on Classification and Terminology. Epilepsia 2001;42:796–803.

This report discusses the need for revision of the current international classifications of epileptic seizures andepilepsy syndromes and presents the ILAE diagnostic scheme for describing individual patients.

Grubb BP, Gerard G, Roush K, et al. Differentiation of convulsive syncope and epilepsy with head-up tilt testing.Ann Intern Med 1991;115:871–876.

This study of clinical and EEG features that distinguish convulsive syncope from epileptic seizures emphasizes thevalue of tilt testing and unresponsiveness to AEDs.

Linzer M, Yang EH, Estes NA 3rd, Wang P, Vorperian VR, Kapoor WN. Diagnosing syncope. Part 1: Value of history,physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College ofPhysicians. Ann Intern Med 1997;126:989–996.

This work concludes that the combination of a comprehensive history, physical examination, and ECG identifiesthe etiology of syncope in the majority of patients in whom an etiology is ever found, and that the yield of addi-tional sophisticated evaluative procedures is low.

Martin R, Burneo JG, Prasad A, et al. Frequency of epilepsy in patients with psychogenic seizures monitored byvideo-EEG. Neurology 2003;61:1791–1792.

This study provides evidence that the coexistence of epileptic and nonepileptic psychogenic seizures is much lessfrequent than previously believed.

Panayiotopoulos CP. Visual phenomena and headache in occipital epilepsy: a review, a systematic study and differ-entiation from migraine. Epileptic Disord 1999;1:205–216.

This detailed study shows that the clinical differential diagnosis between visual seizures and migraine auras iseasy if duration, color, shape, size, location, movement, speed of development, and progress of the aura are iden-tified, although visual seizures often trigger migrainous headache.

Thompson SA, Duncan JS, Smith SJM. Partial seizures presenting as panic attacks BMJ. 2000;321:1002–1003.

This study describes a few patients in whom the differential diagnosis between panic attacks and complex partialseizures was challenging. The most important features differentiating the two entities are discussed.


34

35

CHAPTER 3

EPIDEMIOLOGY AND ETIOLOGY

KEYPOINTS

n The neurologists and otherphysicians practicing in thedeveloping world need tobe aware that a substantialproportion of the epilepsythey encounter results fromtreatable or preventablecauses.

n Available population-baseddata from developedcountries cannot beextrapolated to developingnations.

The epidemiology of epilepsy in the devel-oping world is poorly documented and theprevalence and etiology of epileptic disor-ders in these areas often differ from those inpublished textbooks, which report informa-tion largely derived from studies in theindustrialized and developed world.Poverty, illiteracy, poor sanitation, and pooraccess to health care are probably directly orindirectly responsible for the large burden ofepilepsy found in developing countries.

Birth injuries and parasitic diseases arecommon and account for a considerableproportion of epilepsy in developing coun-tries. Tropical conditions, societal violence,accidents, war, and consanguinity may alsocontribute to the burden of epilepsy in theseregions. A disproportionately young popula-tion also results in differential causes forepilepsy relative to developed countries.The neurologists and other physicians prac-ticing in the developing world need to beaware that a substantial proportion of theepilepsy they encounter results from treat-able or preventable causes.

EPIDEMIOLOGYEpilepsy contributes substantially to theburden of noncommunicable diseases inthe developing world. For example, recentwork in South Africa indicates that epilep-sy accounts for ~16% of all noncommuni-cable disorders. Within India, epilepsycosts consume ~0.5% of the gross nationalproduct. Despite these indicators of theimportance of epilepsy in such environ-ments, epidemiologic data from the devel-oping world are limited. Available popula-tion-based data from developed countriescannot be extrapolated to developingnations because of problems associatedwith diagnosis, ignorance regarding the

disorder, sociocultural milieu, and differentcausative factors.

IncidenceUndoubtedly, to fully understand the epi-demiology of epilepsy, one should haveinformation regarding the incidence ofepilepsy—meaning new cases of the diseaseoccurring in the population over some spec-ified time period. Unfortunately, the stigmaof the disorder and lack of readily availablemedical resources result in delayed presen-tation for care. An accurate assessment ofnew cases of epilepsy remains extremely dif-ficult to obtain in the developing world, soestimates from cross-sectional data are oftenutilized for this purpose.

Data from the United States indicates anepilepsy incidence of 40/100,000 person-years, whereas incidence reports from thedeveloping world seem somewhat higher.For example, the incidence is 49.3/100,000in rural southern India, 122–190/100,000 inEcuador, and 64/100,000 in Ethiopia.Incident cases occur most often in the veryyoung and the very old. The incidence inthe United States is 82/100,000 person-yearsamong children under 1 year and 77/100,000person-years in people over 60 years of age.Males appear to have a slightly higher inci-dence of epilepsy than females. This genderdifferential probably results from a dispro-portionately high rate of traumatic braininjuries in males relative to females.

Cumulative incidence (CI) refers to thelikelihood of having developed epilepsy bysome specified age and, therefore, CIincreases throughout the life span. Data onthe CI of epilepsy are even more difficult toobtain than incidence data, and no CI datafor epilepsy in the developing world areavailable. In developed countries, the CI is

estimated to be 1% at 15 years of age,increasing to 3% at 74 years and 4.4% at 85years. Note that the CI of epilepsy is signifi-cantly less than the CI of any seizure, whichis 10% by 85 years of age.

PrevalenceEpilepsy prevalence is substantially easier toassess than incidence. As per the WorldHealth Organization, epilepsy is considered“active” among those people with epilepsywho have experienced at least one seizureand/or have been on antiepileptic drugs(AEDs) for seizures in the preceding 2 years.However, most epidemiologic studies definesomeone with “active” epilepsy as anyonewith a history of epilepsy who has experi-enced a seizure and/or been on AEDs forseizures in the past 5 years.

In many regions of the developing world,the prevalence of epilepsy appears to be sig-nificantly higher than the prevalence of 5 to7/1,000 seen in devel-oped countries (Table3.1). A review of morethan 100 epidemiologicstudies indicates anunequal distribution ofepilepsy with a higherprevalence in develop-ing countries. The greatvariability in this table,however, also reflectsdifferences in method-ology.

The prevalence ofepilepsy varies widelywithin regions of devel-oping countries, andnot all developingregions report ratesabove those seen in thedeveloped world. Thishigh variance is seeneven when cases areevaluated by the samemethods and the sameresearchers, suggestingthat environmentalexposures or otherlocal factors contributesubstantially to the bur-den of disease in these

areas. If epilepsy in some developingregions is associated with substantiallyincreased mortality, then prevalence ratesmay underestimate the disorder’s impact onthe population. Some studies have reportedregions of high incidence, but not highprevalence, suggesting either high remissionor high mortality rates.

Epilepsy subtypes also differ betweendeveloped and developing regions.Comparative studies have found rates of focalepilepsies (epilepsies due to an epileptogenicregion in a part of one hemisphere) to be sub-stantially higher in developing countries. Focalepilepsies comprise only 62% of seizure disor-ders in France compared to 80% in India, 77%in Nigeria, and 74% in Sri Lanka. Insults relat-ed to tropical location and economic disadvan-tage, which result in focal brain injury, couldpotentially explain higher rates of epilepsy andtherefore a predominance of focal epilepsiesin low-income, tropical countries.


36

KEYPOINTS

n In many regions of thedeveloping world, theprevalence of epilepsyappears to be significantlyhigher than the prevalenceof 5 to 7/1,000 seen indeveloped countries.

Results of Some Published Door-to-Door Surveysof Prevalence Rates in a Variety of DevelopingCountries

TABLE 3.1

Prev Ratio Location Pub Date Population # of Cases (/1,000)

Urban Nigeria 1987 18,654 101 5.0 *

Rural Kashmir 1988 63,645 157 2.5

Bombay 1988 14,010 50 3.7 *

Rural Ethiopia 1990 60,820 316 10.0 *

Ecuador 1992 72,121 575 8.0

Rural Tanzania 1992 18,183 185 12.6 *

Rural Guanajuato 1992 7,187 179 20.8

Urban Tunisia 1993 35,370 141 3.5 *

Pakistan 1994 24,130 241 9.9 *

Turkey 1997 11,497 81 6.7 *

Rural Bolivia 1999 9,955 112 14.0 *

Kerala, India 2000 238,102 1,175 4.7 *

Riyadh, Saudi Arabia 2001 23,700 155 6.5

Urban Brazil 2002 982 20 5.1

China 2003 55,616 257 4.6

Contributed by Allen Hauser, MD, Columbia University (note thatcitations for individual studies cannot be included here, but can beobtained from Dr. Hauser.)

* age-adjusted

When reviewing epidemiologic data fromdeveloping countries, one should recognizethat most study limitations lead to an under-estimation of seizure disorders. People arereluctant to admit to suffering from a stigma-tizing condition, especially if few medicalservices are available to them once the disor-der is recognized. Absence and focal seizuresthat fail to generalize will likely be underrec-ognized. Decreased epilepsy-associated stig-ma, improved health care services, andincreased research infrastructure are neededto optimally evaluate epilepsy epidemiologyand etiology in developing countries.

Natural HistorySpontaneous remissions do occur even inuntreated people with epilepsy, and con-cerns that “seizures beget seizures” have notbeen substantiated in longitudinal, popula-tion-based studies in developed countries.Neither the duration of epilepsy nor thenumber of seizures appears to reliably reflectthe response a patient will have to AEDs, butsymptomatic seizures associated with anunderlying brain lesion are much less likelyto spontaneously remit. Some epileptic syn-dromes have a good prognosis and are like-ly to remit. These include neonatal epilepsy,childhood absence epilepsy, and benignrolandic epilepsy. Juvenile myoclonic epilep-sy and mesial temporal lobe epilepsy are lesslikely to spontaneously remit.

Morbidity and MortalityEpilepsy substantially increases mortality risk,particularly in environments that generallylack medical resources, including basic anti-convulsants, and have health care providerspoorly trained to diagnose and treat neuro-logic disorders. The extreme social stigmaassociated with seizures in some cultures isparticularly detrimental. Untreated individualswho have frequent seizures and live whereopen fires are used for cooking and heatingoften experience severe burns. Patients withepilepsy in some regions often exhibit scarsfrom significant burns or fractures thatoccurred during seizure activity. In hospital-based observations in sub-Saharan Africa,such scars are evident in ~30% of patients.Where water is collected from rivers orstreams and fishing provides a significant

source of food, drowning among people withepilepsy is also common.

Many commonly held beliefs contributeto the morbidity and mortality of epilepsy.For example, where epilepsy is thought tobe contagious, bystanders and perhaps evenfamily members may be reluctant to assistsomeone during a seizure. Under such cir-cumstances, people with epilepsy candrown while onlookers do nothing. Peoplewho have fallen into a fire may suffer full-thickness burns rather than the superficialwound that would have occurred if some-one had simply pulled them from the fire.Substantial seizure-related injury can poten-tially be averted with public health educa-tion to discourage such beliefs.

In the United States, even among peoplewith severe epilepsy, only 20% of deaths aredirectly attributable to the seizure disorder,and the standardized mortality ratio (risk ofdeath among people with epilepsy/risk ofdeath in the general population) is 2:3.Unfortunately, within developing countries,the morbidity and mortality of epilepsyappear to be substantially greater. Death andinjury occur primarily due to status epilepti-cus (especially in the setting of abrupt med-ication withdrawal), burns, and drowning.Standardized mortality ratios for people withepilepsy in developing regions, meaning theratio of the number of deaths observedamong people with epilepsy relative to thenumber of deaths expected in the generalpopulation, are not available. However, one30-year follow-up study in Tanzania found a67% mortality rate among people withepilepsy, and most deaths were seizure-related.

Socioeconomic ImpactThe magnitude of the negative socioeco-nomic impact of epilepsy varies dependingon the environment. Within many devel-oped countries, laws make it illegal to dis-criminate in employment against peoplewith disabilities, assisting in protecting therights of people with epilepsy.Unfortunately, few developing countrieshave laws offering such protection. In fact,some countries may even have legislationthat contributes to discrimination againstpeople with epilepsy. Data from Africa, Asia,

Epidemiology and Etiology

37

KEYPOINTS

n Epilepsy substantiallyincreases mortality risk.

n Many commonly heldbeliefs contribute to themorbidity and mortality ofepilepsy.

and Latin America indicate that people withepilepsy have less access to education,employment, and marriage than their unaf-fected counterparts. Some countries even listepilepsy as lawful grounds for divorce.

Febrile SeizuresFebrile seizures (FSs) are seizures that occurin association with fever in childrenbetween 6 months and 5 years of age. Mostoften, FSs occur during the second year oflife. To diagnose FS, the fever should not bedue to any intracranial infection, includingmeningitis or encephalitis. In malaria-endemic regions, malarial fevers are themost common cause of fever-relatedseizures, although some argue that seizuresoccurring in this setting are symptoms ofprimary central nervous system (CNS)involvement rather than a FS. FSs have beenclassified as “simple” or “complex.”Complex FSs include seizures with focalonset, a single FS lasting for more than 15minutes, or recurrent FS within 24 hours.Important risk factors predicting recurrenceof FS are: a) young age of onset, b) evi-dence of developmental delay, c) family his-tory of FS among first-degree relatives, andd) low grade fever for a short durationbefore the febrile seizure occurred.

Data from developed countries indicatethat FSs occur in about 3% to 4% of all chil-dren. Most FSs are benign events, as onlyabout 5% of all children with FS developepilepsy. The risk of epilepsy is estimated tobe 2.4% following a simple FS compared to8% to 15% after a complex FS. Risk factorsassociated with the development of epilepsyafter FS include: a) evidence of developmen-tal delay and, b) family history of epilepsy.Fever-associated seizures may be more com-mon in developing countries, especially inregions with endemic P. falciparum malaria.Furthermore, in developed countries com-plex FS represent only ~15% of FSs whereasreports from developing regions indicatethat complex FS comprise >50% of febrileseizures and that multiple complex featuresare common. High rates of complex FS indeveloping countries may be due to a selec-tion bias, with only significantly ill childrenpresenting for care. Alternatively, such com-plex FSs may be due to the underlying fever-

inducing illness (i.e., malaria) or may be themanifestation of previous CNS insults.

RISK FACTORS FOR SEIZURES AND EPILEPSYRisk factors for epilepsy vary depending onthe age of the individual. Children, and par-ticularly infants, appear to have a lowerseizure threshold than adults (including theFS phenomena exclusively seen in children),but may be more resistant than adults to thedevelopment of recurrent, unprovokedseizures. For example, children are morelikely to have a seizure after head injury, butare less likely than adults to develop epilep-sy after head injury. Epilepsy in adults occursmost often in the elderly and reflects thehigher incidence of CNS injury in this popu-lation due to stroke, dementia, and otherneurodegenerative processes. The locationof CNS injuries also impacts the risk of recur-rent seizures, with the temporal and frontalregions appearing to be most epileptogenicand the occipital and subcortical regions lessso. Recognizing that in at least 30% of peo-ple with epilepsy, no underlying cause canbe identified even with state-of-the-art imag-ing and technology, several clear risk factorsdo exist. Table 3.2 indicates the commoncauses of epilepsy in sub-Saharan Africa.

It is important to remember that the riskfactors for seizures may not always be thesame as the risk factors for epilepsy.Unprovoked seizures can either be second-ary to a known enduring disturbance of thebrain or due to unknown causes. On theother hand, provoked seizure(s) are thosethat occur in the setting of an acute transientinsult to the brain. Usually such acute symp-tomatic seizures occur as isolated events, butthe insult can also be associated with perma-nent brain injury and lead to the develop-ment of epilepsy later. For example, acutehead injury or stroke can produce acutesymptomatic seizures and/or chronic seizuredisorders.

Acquired Risk Factors

Infections and InfestationsIn Latin America and parts of Asia, neurocys-ticercosis is the commonest cause of epilep-sy. Studies in the 1960s in Africa, found


38

KEYPOINTS

n In malaria-endemic regions,malarial fevers are the mostcommon cause of fever-related seizures, althoughsome argue that seizuresoccurring in this setting aresymptoms of primarycentral nervous systeminvolvement rather than afebrile seizure.

neurocysticercosis evident in only 10% ofepilepsy cases. More recent work suggestsgreater prevalence, but high rates of asymp-tomatic cerebral cysticerci, high rates of pos-itive serologies for T. solium in the generalpopulation, and the lack of brain imagingfacilities make interpretation of these find-ings difficult. Seizures secondary to CNStuberculosis are also common in many devel-oping countries. Today, many cases of CNStuberculosis are associated with HIV infec-tion. Nearly 50% of patients with TB menin-gitis experience seizures sometime duringthe course of their illness, and a high inci-dence of focal seizures has been reported.

Tropical infectious diseases thought tocontribute substantially to the epilepsy bur-den in developing countries include malaria,neurocysticercosis, and onchocerciasis. Inregions with endemic P. falciparum, highrates of complex fever-associated seizureshave been reported in children with malari-al fevers. If these seizures are indicative ofmalaria-induced CNS injury, such eventsmight predispose to later epilepsy.Additional factors such as poor perinatalmanagement and delivery, as well as bacte-rial and viral CNS infections, undoubtedlyplay a role. The relationship betweenHIV/AIDS and chronic seizure disorders indeveloping countries has not been welldescribed. HIV-related CNS infections, suchas toxoplasmosis, can certainly causeseizures, but without aggressive treatment ofthe underlying infection, few of thesepatients will survive. Children with HIVencephalopathy, who often present withdevelopmental delay, are at increased risk ofseizure disorders. Relapsing Nipah virus is acause of recurrent seizures in Malaysia andother areas of southeast Asia.

Head Trauma, Stroke, and Degenerative Brain Disorders High rates of head trauma in developingcountries occur through a wide variety ofmechanisms. Poor enforcement of motorvehicle safety, including roads frequented byovercrowded vehicles without seat belts,brakes, and/or headlights is particularlyproblematic. Riding motor bikes without ahelmet is a common cause of brain injury.Societal violence and war contribute sub-stantially to traumatic brain injury in devel-oping regions. Prolonged unconsciousnessafter head trauma, post-traumatic amnesiafor more than 30 minutes, intracranial bleed-ing, penetration of the brain by a missile,and depressed skull fractures are complica-tions associated with a greater likelihood ofdeveloping epilepsy after head injury. Therisk for epilepsy is greatest in the first fewyears after the trauma, but can persist for atleast 15 years, depending on the nature ofthe injury.

The incidence and prevalence of strokeand degenerative brain disorders werethought to be lower among developing coun-


39

Reported Causes ofSeizures and EpilepsyRegarding the Age ofOnset in Sub-SaharanAfrica

TABLE 3.2

0 to 4 months: Neonatal asphyxia; perinatal trauma; infections; cerebralmalformation; subdural hematoma;hypoglycemia; hypocalcemia; inbornerrors of metabolism.

4 months to 2 years: Sequalae of previ-ous causes; infections; vascular causes;inborn errors of metabolism.

2 to 10 years: Sequalae of previous caus-es; idiopathic generalized epilepsy; infections; post-traumatic epilepsy; intoxication; inborn errors of metabolism: primary tumors.

10 to 20 years: Sequalae of previouscauses; idiopathic generalized epilepsy;post-traumatic epilepsy; intoxicationincluding alcohol and other drugs; infec-tions; inborn errors of metabolism, mal-formations, neurodegenerative disorders.

20 to 40 years: Sequalae of previouscauses; trauma; brain tumors; alcohol;infections; vascular diseases, tumors andabscesses, neurodegenerative disorders.

40 to 60 years: Tumors; Alcohol; headtrauma; infections; vascular causes; metabolic disorders.

>60 years: Vascular causes and metabolicdisorders primary and secondary tumors;neurodegenerative disorders; infections.

From “Epilepsy in Africa: Bridging theGap”, Report, WHO/AFRO, 2004

tries, mainly due to the relatively younger ageof the population. However, an increase inthe average life span in some developingcountries, coupled with “Westernized diets”and increased tobacco use, have resulted inan increase in cerebrovascular accidents anddementia in these areas.

Seizures have been reported to occur in~8% of patients with acute stroke. Amongacute stroke survivors with occlusive cere-brovascular disease, up to 20% developepilepsy, most of them within the first 2years following stroke, although the risk forpost-stroke epilepsy remains for a muchlonger period. Patients with cortical infarctsare at a greater risk. As in post-traumaticepilepsy, early post-stroke seizures (in thefirst week following stroke) are associatedwith an increased risk for epilepsy com-pared to stroke patients who do not haveseizures at the time of the infarct.

Roughly 15% of patients with Alzheimer’sdisease (AD) experience unprovokedseizures in the course of their illness. Inindustrialized countries, AD accounts foralmost 15% of all newly diagnosed cases ofepilepsy in the elderly (after the age of 65).There is an urgent need to have reliable dataon the occurrence of epilepsy after headinjury, stroke, and degenerative brain disor-ders among populations living in developingcountries. Such information would assistwith public health interventions to preventepilepsy and health services planning.

Toxic ExposuresToxic exposures specific to developingregions may predispose to sporadic seizures.Organophosphate poisoning, a commonevent among children in rural regions, fre-quently presents with status epilepticus.Pesticides are often used and stored inap-propriately, and public education couldpotentially avert many of these events.Traditional medicines, such as an Africanmedicine containing a combination of cowurine and nicotine, may also precipitateseizures. Whether such toxic exposures pre-dispose to later epilepsy is unknown.

Hereditary Risk FactorsGenetic factors also contribute to the causa-tion of epilepsy, but the extent to which her-

itable traits contribute varies according to thetypes of epilepsy. Hereditary epilepsies withsimple Mendelian inheritance are not com-mon, but gene mutations for some of thesesyndromes have been identified and havecontributed to our understanding of themechanisms involved in the genesis ofseizures. Epilepsies and other episodic disor-ders, such as benign familial neonatal convul-sions and generalized epilepsy with febrileseizures plus (GEFS+), result from mutationsin ion channels and are referred to as chan-nelopathies. However, most of the commonidiopathic epilepsy syndromes are suspectedto reflect complex inheritance, either second-ary to the added effect of multiple mutantgenes (“polygenic”) or examples of “multifac-torial inheritance” (disorders resulting froman interaction of an inherited predispositionwith an environmental insult). Hereditary fac-tors could play a different role in the causa-tion of epilepsy in some developing countriesdue to the practice of consanguineous mar-riage, especially among first cousins.

Hereditary Epilepsies with Complex InheritanceThe most common forms of idiopathic gen-eralized epilepsies are childhood absenceepilepsy, juvenile absence epilepsy, juvenilemyoclonic epilepsy, and epilepsy with gen-eralized tonic-clonic seizures on awakening.These four syndromes account for 30% of allepilepsies in the developed world and arethe most common genetic epilepsies. Manyclinical features of these epilepsies overlap,but significant differences among the syn-dromes are the age of seizure onset andprognosis for complete remission. An impor-tant distinguishing feature is that most ofthese syndromes present with at least twotypes of seizures, but the temporal order inwhich different seizure types manifest in dif-ferent patients is not fixed.

Hereditary focal epilepsies with complexinheritance also occur, the most common ofwhich is benign childhood epilepsy withcentrotemporal spikes. There are idiopathicfocal childhood seizures from occipital andother locations as well. Most respond well tomedications, or may be so benign as not torequire any medications, and remit sponta-neously in adolescence.


40

For a variety of reasons, these epilepsysyndromes are often not recognized byphysicians practicing in developing coun-tries. The importance of a syndromicapproach among patients with epilepsy liesnot in arriving at a correct diagnosis per se,but in using this diagnosis to counsel thefamily regarding prognosis, select the mostappropriate drug treatment, and determinethe duration of treatment warranted.

Other Rare Epilepsies Associated withSimple Mendelian InheritanceSeveral other less common epilepsies resultfrom simple Mendelian inheritance, such asthe progressive myoclonus epilepsies.However, these disorders are exceedinglyrare and generally require diagnostic tech-nologies not available in developing worldsettings. Mitochondrial disorders includemyoclonic epilepsy with ragged red fibers(MERRF) and mitochondrial encephalomy-opathy with lactic acidosis and stroke-likeepisodes (MELAS). The overlapping featuresof mitochondrial disorders include seizures,dementia, progressive external ophthalmo-plegia, sensory neural hearing loss, cardiacabnormalities, and elevated levels of lactateand pyruvate.

Phakomatoses include a group of devel-opmental disorders characterized by a vari-ety of skin lesions evident in childhood andtherefore potentially identifiable clinically.These disorders are often followed later inlife by the development of tumors in otherorgans, including the CNS. Tuberous sclero-sis (TS) and neurofibromatosis 1 are two rel-atively common autosomal dominant phako-matoses. TS patients present with the classi-cal triad of seizures, mental subnormality,and skin lesions (hypopigmented macules,adenoma sebaceum, shagreen patches, andsubungual fibromas). TS-associated tumorsmay undergo malignant transformation. TScommonly presents with infantile spasmsand the subsequent development of general-ized tonic-clonic seizures, myoclonic jerks,and even partial seizures.

Despite the theoretical possibility ofinheriting epilepsy, the overall risk of inher-iting epilepsy from a parent is close to zerofor most types of epilepsy and very small forothers. However, the common occurrence of

consanguinity in developing countries cancontribute to an increased incidence of cer-tain hereditary epilepsies; therefore, thispractice should be avoided. While it is wellknown that epilepsy itself and theantiepileptic drugs used during pregnancydo result in complications among a verysmall number of children born to womenwith epilepsy, there is no justification forbarring marriage or childbearing.

CONCLUSIONSModifiable risk factors for seizures andepilepsy need to be identified to facilitatethe prevention of seizures and epilepsy inthe population. Potentially preventable casesof epilepsy substantially add to the societalburden of this chronic disorder. Simplemeasures such as improved antenatal care,adequate sanitation, and basic road safetycould prevent many cases of brain injury.People residing in developing countries areat greater risk of experiencing CNS insults,for example through perinatal injuries, CNSinfections (including cerebral malaria andneurocysticercosis), or head trauma relativeto people in developed countries. This sug-gests that people presenting with a singleseizure in developing countries are at high-er risk of harboring an underlying CNSinjury and may therefore have a higher riskof developing epilepsy than the “singleseizure” patient from the developed world.No systematic evaluation of this has beencompleted. Public health measures institutedto decrease brain insults and injury wouldultimately result in decreased epilepsy and abetter prognosis for all those affected bysporadic seizures. Although hereditary fac-tors contribute to the risk of epilepsy andconsanguinity increases this risk, the overallrisk from hereditary factors is small and peo-ple with epilepsy should not be advisedagainst childbearing, though consanguinityshould be discouraged.


41

KEYPOINTS

n While it is well known thatepilepsy itself and theantiepileptic drugs usedduring pregnancy do resultin complications among avery small number ofchildren born to womenwith epilepsy, there is nojustification for barringmarriage or childbearing.

n Although hereditary factorscontribute to the risk ofepilepsy and consanguinityincreases this risk, theoverall risk from hereditaryfactors is small and peoplewith epilepsy should not beadvised againstchildbearing, thoughconsanguinity should bediscouraged.

CITATIONS AND RECOMMENDED READINGBerkovic SF, Scheffer IE. Genetics of the epilepsies. Curr Opin Neurol 1999;12:177–182.

This is a review of the principles of molecular approaches to epilepsies and highlights the recent progress in thegenetics of the idiopathic epilepsies.

Carpio A, Escobar A, Hauser WA. Cysticercosis and epilepsy: a critical review. Epilepsia 1998;39:1025–1040.

This is an exhaustive review of the different aspects of neurocysticercosis and epilepsy.

Clark GD. Cerebral gyral dysplasias: molecular genetics and cell biology. Curr Opin Neurol 2001;14:157–162.

An extensive review of the pathogenesis of cerebral gyral dysplasias and processes involved in neuronal migration.The author has used the lissencephalies as a model for explaining the contributions of genetics toward our under-standing of the human brain development.

Commission on Classification and Terminology of the International League Against Epilepsy: proposal for revisedclassification of epilepsy and epileptic syndromes. Epilepsia 1989;30:389–399.


Daoud A. Febrile convulsion: review and update. J Pediatric Neurol 2004;2:9–14.

This is an excellent and a very recent review article on various aspects of febrile convulsions.

Epilepsy in Africa: Bridging the Gap. Report, WHO/AFRO, 2004.

The first in a series of regional reports on epilepsy.

Jain S, Padma MV, Puri A, Jyoti, Maheshwari MC. Occurrence of epilepsies in family members of Indian probandswith different epileptic syndromes. Epilepsia 1997;38:237–244.

A study reporting on the occurrence and pattern of epilepsies among relatives of epilepsy patients seen in a largetertiary care hospital in India.

Janz D. The idiopathic generalized epilepsies of adolescence with childhood and juvenile age of onset. Epilepsia1997;38:4–11.

An excellent article on the relation between the syndromes included under idiopathic generalized epilepsies inregard to the age at onset, nosology, overlap, trigger factors, pathological features, and genetics.

MacCollin M, Kwiatkowski D. Molecular genetic aspects of the phakomatoses: tuberous sclerosis complex and neu-rofibromatosis 1. Curr Opin Neurol 2001;14:163–169.

A detailed review of different aspects of the pathogenesis of tuberous sclerosis and neurofibromatosis 1, particu-larly in regard to the molecular advances that have been made possible by the cloning of genes for these disorders.

McNamara JO. Genetics of epilepsy. In: Martin JB, (ed.) Molecular Neurology. New York City: Scientific AmericanPress, 1999:75–93.

An exhaustive review that provides a framework for understanding genetic studies, the terminology and classifi-cation of the epilepsies, and implications of the recent discoveries of mutations underlying several epilepsy syn-dromes.

Shorvon SD, Farmer PJ. Epilepsy in developing countries: a review of epidemiological, sociocultural, and treatmentaspects. Epilepsia 1988;29(suppl 1):S36–54.

A review of various medical and social aspects of epilepsy in developing countries.

Tandon PN. Neurotuberculosis: Clinical Aspects. In: Chopra JS, Sawhney IMS, (eds.) Neurology in Tropics. New Delhi:B.I. Churchill Livingstone Pvt. Ltd, 1999:358–369.

A review of the various forms of CNS tuberculosis and their treatment.


42

43

CHAPTER 4

DIAGNOSTIC APPROACHES

Limited diagnostic resources indeveloping countries demand acost-effective approach to evaluat-ing patients with spells. Such anapproach is heavily dependent onthe clinical skills of the neurologist.Data obtained through history andphysical examination, complement-ed by epidemiologic knowledge,should direct the diagnosticworkup. Three questions are para-mount when approaching a patientwith a spell. The first is whether it isan acute episode occurring for thefirst time in the patient’s life, or if itis a recurrence of a given type ofspell for which help already mayhave been sought. The second con-cerns the nature of the episode: Arethe events truly epileptic? If theepileptic nature of the spells isestablished, then the seizure type(s)should be classified. Finally, thesyndromic diagnosis and the etiolo-gy of the brain disorder leading toseizures should be established. Analgorithm for evaluation of patientswith events that might be epilepticseizures is shown in Figure 4.1.

First Seizure, Single Seizure, andRecurrent Spells: The Boundariesof the Definition of EpilepsyThe physician faced with a patientexperiencing a single seizure mustfirst determine whether this is a pre-senting symptom of a life-threaten-ing disorder that should be prompt-ly identified and treated, or the pre-senting symptom of a benign idio-pathic form of epilepsy, which doesnot necessarily require extensive

Algorithm for diagnosis and treatment of seizures.

FIGURE 4.1

Is event epileptic?

Seizure Dx

Acute symptomatic? Dx and Rx conditionnot epilepsy

Rx, seizures stopnot epilepsy

Maintenance,social, psych,quality of life

Syndrome Dx

Underlying treatablecause?

Pharmacotherapy

Surgery?

Dx and Rx conditionnot epilepsy

No

Yes

Yes

Effective

Yes

No

Ineffective

No orseizurescontinue

Idiopathic Symptomatic

Description

Description

?EEG, ?CT, ?MRI?LP

Hx

?EEG, ?CT, ?MRI

Hx

neurodiagnostic evaluation, or a provokedevent that is unlikely to recur. The approachto a patient with a new onset acute seizureis completely different from the approach toa patient who has been having seizures forsome time, particularly because a seizure inthe latter is less likely to reflect some poten-tially life-threatening substrate (see alsoChapter 1).

A history and examination consistent withdrug or alcohol abuse, decompensation of ametabolic disorder, intracranial infection,increased intracranial pressure, or strokerequires extensive further evaluation to ruleout an underlying cause that requires imme-diate attention. The patient’s relatives shouldbe asked about any underlying metabolic orcardiovascular diseases, such as diabetes orarterial hypertension, and also for the occur-rence of fever, headache, somnolence, vom-iting, acute behavioral changes, and acutemotor deficits in the hours or days surround-ing the episode. This should be comple-mented by a thorough physical and neuro-logic examination, including elucidation ofhigh blood pressure, the presence ofmeningeal signs, papilledema, and focalneurologic deficits. Focal features of the ictalevent also increase the likelihood that this isa symptomatic, rather than idiopathic or pro-voked, condition. In most circumstances,ancillary laboratory tests will be needed,including at least a complete blood count,electrolytes, and serum glucose, as well as acomputed tomography (CT) scan (or an MRIif available). In selected circumstances, alumbar puncture to rule out meningitis orencephalitis and blood levels of illicit drugsor alcohol will be needed.

AdultsA history of a generalized tonic-clonic con-vulsion following sleep deprivation, alcoholor sedative drug withdrawal, or other well-known precipitating factors in an otherwisehealthy person with a normal history, phys-ical, or neurologic examination, and routinelaboratory findings suggests a provokedevent which is not likely to recur as long asprecipitating stimuli are avoided. An elec-troencephalogram (EEG) and CT (or MRI)scan are still indicated to look for some pre-disposing abnormality, but where resources

are limited, these tests are less necessarywhen clear precipitating factors are present.An EEG performed within 24 to 48 hours ofthe seizure can show nonspecific diffuseabnormalities, which are expected postictalchanges and do not rule out a diagnosis ofa provoked seizure. To avoid unnecessaryfurther evaluation and antiepileptic drugs, itis better to wait a week before performingthe EEG.

Febrile Seizures in Infants and ChildrenIn infants and children, fever is a precipitat-ing factor, but identification of intracranialinfection is difficult. Focal seizures are themost characteristic feature of herpesencephalitis in infancy and childhood.Lumbar puncture and CT scan may be nor-mal. It is urgent to treat before status epilep-ticus leads to brain damage. The occurrenceof a febrile seizure before the age of 12months requires that the child be referred toa hospital for lumbar puncture to rule outmeningitis. A third cause of seizures withfever, particularly in developing countries, ismalaria (see Chapter 5). A febrile seizure ininfants with or without any identifiableunderlying condition, which is focal andprolonged, can cause hippocampal atrophyand later mesial temporal lobe epilepsy. Inthe middle of the first year of life, the sameseizure type can be the expression of Dravetsyndrome, and the occurrence of recurrentbilateral independent seizures suggests thisdiagnosis. In the context of severe dehydra-tion, whether febrile or nonfebrile, duralsinus thrombosis could occur, and the diag-nosis relies on CT scan or the discovery ofhemorrhagic cerebrospinal fluid on lumbarpuncture.

Nonfebrile Seizures in Infants and ChildrenIn neonates and infants, nonfebrile seizurescan be due to hypoglycemia or hypocal-cemia. In the latter case at the age of 2 to 3months, other signs of rickets contribute tothe diagnosis. It may seem paradoxical tosee rickets in tropical countries, but infantsare usually kept in the shadow of the houseto prevent the risks related to excess of sun.Acute trauma is another common cause.Macrocephaly is rarely present when trau-


44

KEYPOINTS

n The occurrence of a febrileseizure before the age of12 months requires that thechild be referred to ahospital for lumbarpuncture to rule outmeningitis.

matic encephalopathy produces seizures.Fundiscopic examination showing hemor-rhage is useful. Only lumbar puncture andCT scan permit the diagnosis. Ischemicencephalopathy begins several hours afterbirth. Seizures are usually tonic and repeat-ed for several hours in a comatose neonate.Very early onset of convulsions during thefirst hours of life would suggest pyridoxineor pyridoxal phosphate dependency, even ifthere is evidence of prenatal distress (prema-ture birth or dysmaturity). Seizures are poly-morphic, unilateral, and generalized, includ-ing tonic, clonic, myoclonic, and spasms.The child is usually agitated and cryingstrongly. Repeat focal seizures involving agiven part of the body indicate eitherischemia, in which case the seizures willcease after a few hours, or a malformation,including hemimegancephaly. In this disor-der, asymmetrical spasms would soon add tothe pattern.

Between 2 and 4 months of age, statusepilepticus without evidence of a triggeringfactor can result from the same disturbancethat causes sudden infant death syndrome(near miss), the apnea often being over-looked because it occurred during sleep.

In infants and children, exogenous intox-ication with chemical or pharmaceuticalcompounds can produce severe convulsion.Reflex epileptic seizures are rare in infants.One example is hot water epilepsy in whichbefore the age of 5 years in previously nor-mal children, a bath in hot water triggersarrest of activity, hypotonia, pallor, orcyanosis, then evidence of loss of conscious-ness. No seizures occur without this trigger-ing factor.

A single seizure in children can also bethe first manifestation of a benign age-relat-ed idiopathic epilepsy, which often can bediagnosed by a detailed description of theictal event by a reliable observer. A historyof similar seizure types in other family mem-bers is helpful, but very rarely present.Often, the patient presents because of a sin-gle generalized tonic-clonic seizure, butprior absences or myoclonic jerks, whichhelp to make a specific diagnosis, have notbeen recognized as epileptic events and canonly be elicited by careful questioning.Diagnosis of an age-related idiopathic

epilepsy syndrome is further supported byabsence of a history of risk factors forepilepsy, a normal physical and neurologicexam, and unremarkable laboratory find-ings. In these cases, further expensive diag-nostic evaluation is not necessary. WhereEEG is available, a characteristic pattern ofinterictal spikes on a normal backgroundoften helps to make a diagnosis of a specif-ic idiopathic syndrome.

It is common in developing countries forgeneralized tonic-clonic seizures to be theonly ictal event of particular concern to indi-viduals and their families. Consequently, apatient presenting with a single generalizedtonic-clonic seizure does not necessarilyhave an acute condition. A careful historymay reveal simple or complex partialseizures occurring for many years prior tothe seizure that precipitated the clinic visit,or nocturnal seizures may have been missedbut can be elicited by asking if the patientawakens occasionally with severe musclesoreness, a bitten tongue, or a wet bed.When there is such a history of prior unrec-ognized seizures, this is a chronic condition,a diagnosis of epilepsy is appropriate, andtreatment is necessary. Depending on theseizure types, history, physical, and neuro-logic examination, further diagnostic evalua-tion is indicated, as discussed subsequently.

Epileptic versus Nonepileptic SeizuresMisdiagnosis of other entities as epilepsyleads to social stigma, a failure to recognizeand treat the true underlying pathology, andthe unwarranted risk and expense ofantiepileptic drugs. Because epilepsy is achronic condition requiring continuoustreatment for a substantial time, misdiagno-sis can result in unnecessary long-term phar-macologic treatment. Paradoxically, inunderdeveloped communities where neuro-logic care is substandard relative to devel-oped regions, the misdiagnosis of epilepsy isfrequent and the patient may be at a lesserrisk of iatrogenic harm when managed by“traditional healers.” Of course, neither situ-ation is acceptable, and the remainder of thischapter will discuss ways to improve neuro-logic care through an appropriate diagnosisof epilepsy. Refer to Chapter 2 for a detaileddiscussion of the differential diagnosis of

Diagnostic Approaches

45

KEYPOINTS

n It is common in developingcountries for generalizedtonic-clonic seizures to bethe only ictal event ofparticular concern toindividuals and theirfamilies. Consequently, apatient presenting with asingle generalized tonic-clonic seizure does notnecessarily have an acutecondition. Partial seizuresmay have occurred butwere not recognized assuch.

epilepsy and nonepileptic entities, particu-larly those that are common in developingcountries.

Seizures versus EpilepsyAs described in Chapter 1, not all seizuresindicate the presence of epilepsy. “Epilepsy”is the chronic persistence of a brain dysfunc-tion, which leads to recurrent epilepticseizures. Some individuals may have a singleepileptic seizure, while others may have afew recurrent seizures during life, alwaysrelated to a specific transient provoking fac-tor. These people do not have epilepsy.Examples include generalized seizures insusceptible individuals under conditions ofalcohol withdrawal or prolonged sleep dep-rivation, or excessive use of illegal stimulantdrugs such as cocaine or amphetamines. Stillothers may harbor specific lesions, such ascortical tumors or parasitic cysts, which mayclinically present with a few seizures, butwhose tendency to further episodes is elim-inated by resection or medical treatment ofthe lesion.

Underlying Treatable CausesThe possibility that epileptic seizures may besecondary to some acute or subacute, yettreatable, cerebral insult must be kept inmind by physicians practicing in developingcountries (see also Chapter 3). In theseregions, the prevalence of symptomaticseizures and epilepsies is higher than thatfound in developed countries. Thus, anunderlying treatable cause for new onsetseizures should be sought and the conditionmanaged as early as possible, reducing therisk of permanent injury and epilepsy.

In developing countries, febrile illnessessuch as malaria and pneumonia are associat-ed with febrile convulsions and should bediagnosed and treated early. Mass lesionsassociated with tuberculosis or neurocys-ticercosis should always be considered as apossible etiology of new onset seizures bothin adults and children in regions wherethese conditions occur frequently. Indeed,cysticercosis remains a major public healthproblem in many Latin American, Asian, andAfrican regions. Other potentially preventa-ble etiologies with a major representation indeveloping countries include head injuries,

infections, and perinatal trauma. Finally,congenital CNS abnormalities, tumors, vas-cular lesions, and metabolic disorders areresponsible for variable proportions ofsymptomatic seizures. While the etiologicdiagnosis of the epilepsies may be more dif-ficult in developing countries, due to limitedinvestigative resources, many can be diag-nosed on the basis of simple clinical andepidemiologic knowledge, complementedby nonsophisticated serologic studies.

Seizure Types/Epilepsy SyndromesOne of the major difficulties in the optimaltreatment of epileptic seizures and epilepsysyndromes in developing countries is thatthe classification framework proposed byILAE (see Chapter 2) is often not taken intoconsideration by medical personnel. Thisleads to underdiagnosis of potentially treat-able conditions and to undesirable therapeu-tic short cuts, such as the use of similarantiepileptic drug regimens, in similardosages, irrespective of the seizure type orthe underlying disorder giving rise to theseizures. Adequate seizure and syndromediagnosis can simplify the diagnosticworkup, provide prognostic information,and direct treatment decisions.

HISTORY-TAKING AND THE DIAGNOSIS OF EPILEPTIC EVENTSTo understand the nature of a potentiallyepileptogenic event and to have an approx-imate idea of the seizure type, one mustunderstand the circumstances surrounding aseizure. Seizures that do not have general-ized tonic-clonic components are often notrecognized as epileptic. Thus, it is importantfor the physician to know the semiologicevolution of the most common seizure typesand to actively interact with the patient andwitnesses during history-taking. Specific,direct questioning of key semiologic featuresis often the only possible way to elicit a reli-able history. The diagnosis of epilepsy anddetermination of seizure type should bemade on the basis of history and examina-tion with technological studies used to sup-port diagnosis, particularly when the resultsof such studies will influence managementdecisions. Open and interactive discussionduring the consultation is also important as


46

KEYPOINTS

n The possibility thatepileptic seizures may besecondary to some acute orsubacute, yet treatable,cerebral insult must be keptin mind by physicianspracticing in developingcountries.

n Seizures that do not havegeneralized tonic-cloniccomponents are often notrecognized as epileptic.

n Open and interactivediscussion during theconsultation is alsoimportant as a teachingtool for both the patientand relatives. It is essentialthat the patient and familymembers have a simplifiedunderstanding of thespecific behaviors that thedoctor considers to be aseizure, for purposes ofclinical follow-up.

a teaching tool for both the patient and rel-atives. It is essential that the patient and fam-ily members have a simplified understandingof the specific behaviors that the doctor con-siders to be a seizure, for purposes of clini-cal follow-up.

About the Seizure

The CircumstancesAn epileptic seizure can occur anywhere,anytime. A description of the circumstancesshould first determine whether the seizure isa new acute event, or whether it is a typicalseizure for someone with long-standingepilepsy. If it is a single event, it is para-mount to identify and then treat acute symp-tomatic seizures that reflect a potentially life-threatening underlying condition. It is alsonecessary to distinguish between provokedseizures that are not likely to recur, and thosethat might indicate the initial symptom of achronic epileptic disorder. The physicianshould collect data on seizure evolution andalso on the usual circumstances surroundingseizure occurrence. This also allows theapplication of measures to prevent both theattacks and their potential harmful conse-quences. The physician should elucidate pre-cipitating events such as menses, sleep dep-rivation, alcohol intake, emotional changes,

delay in taking medication, or excessivephysical exercise. Furthermore, becauseseizures occurring only during sleep areassociated with smaller risks than thoseoccurring when the patient is awake, therelation to sleep-wake cycle is an importantpiece of information. Finally, the possibilityof seizures occurring in situations where thepatient may be particularly at risk should beanticipated to prevent tragic events such asburns or drowning.

Questioning the PatientPeri-ictal information obtained from thepatient is frequently incomplete or equivo-cal. However, any symptoms precedingseizure onset for minutes to hours shouldbe noted, including tiredness, sleepiness,dizziness, malaise, headache, or nervous-ness. When consistent, symptoms such asthese can reflect preictal prodromal statesand can warn the patient that a seizure isapproaching. Even though this informationis often volunteered, its potential meaningmay not be realized and should be empha-sized. It is important to differentiate theseprodromal symptoms from the aura. It ishelpful to explain from the start the sever-al possible “phases” in the evolution of aseizure, and then guide the patient throughthat.


47

KEYPOINTS

n Recurrent, unexplainedinjuries, particularly burns,should raise the suspicionof seizures. If a history ofseizure is not offeredvoluntarily, a directquestion about seizures,using local (not medical)terminology, should beaddressed to the patientand care providers. Thisquestion must be asked ina private setting. In openwards with other patientsand families nearby, thediscussion should takeplace outside of the ward.

CASE STUDY

Presentation: A 6-year-old female was seen on the Burn Unit for a brief, generalized seizure. She had been admitted 4 daysprior with full-thickness burns over >30% of her body, primarily on her upper trunk. Initially, the consultant suspected thiswas an acute, symptomatic seizure related to metabolic derangements associated with such a severe injury.

The child was surprisingly awake, alert, and oriented. Her neurologic examination was unremarkable.Review of the medical record indicated multiple admissions and visits for injuries including facial lacerations from a fall, a

clavicle fracture, and an earlier burn to her right foot. The family had been unable to adequately explain the circumstancesof these injuries and child abuse was suspected.

On direct questioning, the grandmother admitted reluctantly that the child had had “fits” almost weekly for the past 3years. The injuries were all seizure-related. The family clearly felt ashamed about the child’s condition and were fearful thatthey would be ostracized if it was known that someone in the family suffered from epilepsy. They were surprised wheninformed that medications might stop or at least decrease the number of seizures experienced.

Treatment/Outcome: Oral phenobarbital was initiated and no further seizures occurred. Unfortunately, the child’s woundsbecame infected and failed to respond to available treatments. She died of sepsis 2 weeks later.

Comment: Fear of stigma and lack of knowledge about epilepsy treatments may result in concealment of epilepsy and trag-ic, avoidable deaths undoubtedly occur. Recurrent, unexplained injuries, particularly burns, should raise the suspicion ofseizures. If a history of seizure is not offered voluntarily, a direct question about seizures, using local (not medical) terminol-ogy, should be addressed to the patient and care providers. This question must be asked in a private setting. In open wardswith other patients and families nearby, the discussion should take place outside of the ward.

In addition, one should attempt to identifyany pattern of recurring, potentially seizure-provoking factors. The latter most often willinclude sleep deprivation, excessive tension(preoccupation), alcohol abuse or withdraw-al, missed dosages of antiepileptic medica-tions, and hormonal changes occurring in thecatamenial period. Some of these factors arerelated to poverty or low levels of educationand can be difficult to prevent.

The patient should be asked explicitlyabout the presence of an aura, and the mostcommon types of auras should be describedas examples. If unusual symptoms appearjust before loss of contact with the environ-ment or loss of consciousness, these symp-toms should be characterized in detail. Thepossibility that such symptoms do representauras is increased by their occasional occur-rence as the sole “ictal” manifestation.Events following the aura may or may notbe perceived by the patient. Loss of aware-ness is characteristic of complex partialseizures, which propagate predominantlythrough limbic/subcortical pathways. Inpartial motor seizures that secondarily gen-eralize, on the other hand, the patient canoften relate the sequence of body partsinvolved before loss of consciousness.Specific questioning on the clonic or tonic(sustained) nature of head turning or limbcontractions can provide important clues tolateralization and localization of the corticalgenerators. Likewise, the occurrence ofrecurrent, brief episodes of loss of aware-ness or of early morning myoclonus areimportant clues to the presence of an ideo-pathic generalized epilepsy syndrome, evenin the absence of tonic-clonic generalizedseizures.

The functional impact of the seizures canbe inferred from frequency and severity, aswell as postictal dysfunction and symptomssuch as headache, somnolence, malaise,depression, and lack of initiative. Even mildcomplex partial seizures can have a dis-abling effect for hours following the attack,attesting to the broad neurochemicalchanges that can be produced by a seizure.

Physical ConsequencesCulturally, epilepsy is equated with gener-alized tonic-clonic seizures and their phys-

ical consequences. The spectacle of a gen-eralized event associated with frothing,tongue biting, and urinary incontinencehas a tremendous impact on bystandersand relatives. The idea that someone maybe suddenly “seized” by such a horrendousattack contributes to the stigma of epilep-sy. Patients and relatives can be offeredsome assurance that such generalizedattacks are often the easiest to bring undercontrol with adequate antiepileptic drugmanagement, provided compliance is alsoadequate. Furthermore, it should beemphasized during history taking that mostseizures do not reach the stage of second-ary generalization, and thus, minor featuresshould also be identified and reported. Thedread of a generalized tonic-clonic seizureis so culturally ingrained that minor ictalphenomena (for instance, the staring andautomatisms of complex partial seizures)are often neglected or entirely missed.Because complex partial seizures may alsoresult in injuries, their identification isimportant, and specific questions regardingwhat happens before generalization super-venes should be posed.

Taken in isolation, loss of consciousness,frothing at the mouth, and urinary inconti-nence could be associated with other typesof (nonepileptic) spells (see also Chapter 2).Prolonged vasovagal or cardiogenic syn-cope, for instance, can be associated withurination, and even with tonic stiffening andfrothing at the mouth. However, the wholepicture of sequential tonic and then clonicviolent movements associated with tonguebiting, frothing, and urination is very charac-teristic of a generalized epileptic seizure. Asdiscussed in Chapter 8, relatives and col-leagues should be instructed on ways to pro-tect the patient against injuries during aseizure and when urgent medical assistanceis required.

Questions to Accompanying PersonsBecause the patient is at least partiallyunaware of his or her environment duringthe majority of seizures, reliable informationon the circumstances and details of theattack need to be obtained from accompany-ing persons. The educational level and thepossible biases of the informant should be


48

KEYPOINTS

n The dread of a generalizedtonic-clonic seizure is soculturally ingrained thatminor ictal phenomena (forinstance, the staring andautomatisms of complexpartial seizures) are oftenneglected or entirelymissed.

taken into account. Important data includeclues to localization of the ictal generators(e.g., patient’s mention of a sudden feeling,a partial motor onset, staring followed byoroalimentary automatisms), as well as evi-dence that might help confirm the episodeas epileptic (or raise the suspicion of anonepileptic fit). In this regard, some fea-tures that could more likely pertain to syn-copal or psychogenic seizures should bespecifically questioned (see Chapter 2).

Asking what kind of help has been pro-vided to the patient during seizures, particu-larly during complex partial or generalizedtonic-clonic attacks, also offers the opportu-nity to provide instructions on the mostappropriate measures to be taken in futureepisodes. These include the description ofmeasures to protect the patient againstunnecessary injury, the correction of mis-conceptions regarding the safety of handlingthe patient’s secretions (i.e., the fact that sali-va and urine do not transmit epilepsy andthat objects should not be forced into themouth), and the need to avoid interferencewith the patient’s movements which couldcause combative behavior during the imme-diate postictal period. In addition, a descrip-tion of any treatment applied at the time ofa seizure should be elicited. Education aboutthese points can then be provided.

Because seizures may be precipitated byexcessive alcohol use or withdrawal, as well

as by consumption of central nervous sys-tem–active drugs, any information regardingsuch treatments is of value. A history of sim-ilar episodes in the past, in the same con-text, can give a clue to a harmful behavioralpattern that should be specifically modifiedthrough treatment.

Family Perceptions about the SeizuresDifferent attitudes can be observed from thefamily of a patient with epilepsy. In a fewisolated societies of the developing world,epilepsy is sometimes seen as a manifesta-tion of supernatural powers, thus leading toa “positive” appraisal of the recurringseizures. However, in most instances, fami-lies of persons with epilepsy “overprotect”the patient, and directly or indirectly supporta kind of marginalization from the main-stream of society. Close relatives at times areashamed of a seizure occurring in publicplaces and tend to isolate the patient fromsuch environments. Globalization of theaccess to information is changing this pic-ture to the benefit of the people with epilep-sy. A more positive attitude of the family isnow seen in some societies. Common preju-dices, such as the belief that an epilepticwoman should not get married, are declin-ing in regions where social marketing hassuccessfully provided epilepsy education tothe public.


49

KEYPOINTS

n Close relatives at times areashamed of a seizureoccurring in public placesand tend to isolate thepatient from suchenvironments.

CASE STUDY

Presentation: This woman is now 40 years old. She has suffered from generalized tonic-clonic seizures since the age of 9, andwas not treated with modern antiepileptic drugs until she was 27. Since age 19, her seizures very often occurred while cook-ing meals over a wood fire in her family’s kitchen. She experienced many falls into the fire with severe burns.

Evaluation: She did not see a physician until age 27 because in her African cultural context, a person falling into the fire dur-ing a fit is considered to be “an untreatable patient.” Healers had convinced her family not to go to a health center, despitethe opinion of one of her brothers, who later became an MD. He eventually succeeded in convincing their mother to “secret-ly” try a modern approach at the University hospital. On clinical examination, this lady presented with several burns in vari-ous parts of her forearms, trunk, back, and legs. Several EEGs were abnormal.

Treatment: The best results were obtained with a combination of phenobarbital, sodium valproate, and lorazepam. Her MDbrother is supplying the drugs.

Outcome: This woman now has one to three seizures a month, rather than the 10-a-day she had prior to treatment. Her skinlesions are still apparent, and some have developed cheloid patterns, which continue to embarrass her.

Comment: This case illustrates a dramatic reality in some developing countries. In certain cultural contexts, it is believed that“when a person seizes and falls into a fire, that means that it is a resistant case and that there is nothing the traditional heal-er can do.” This can lead to death or to severe injuries, as in this case. Only very progressive educational programs can reducethe incidence of such disabling consequences.

About Remote HistoryIn addition to the elicitation of aspects thatwill bear on the etiology of the epilepsy andon precipitating or protective factors thatincrease or decrease the chances of seizurerecurrence, the medical history must deter-mine whether a given seizure was an acute,unexpected, event in a person without a his-tory of recurrent seizures or simply anotherseizure in a patient with chronic epilepsy.This is of particular importance in areaswhere resources are limited, because theneed for more costly evaluations is greater inthose presenting with a single seizure thatcould indicate an acute life-threatening con-dition, than in those with known chronicepilepsy.

The Medical Past of the Patient: Birth,Development, Immunization, andMedical AntecedentsIt is important to collect information on thepatient’s past medical history, includingconditions of gestation (duration, intercur-rent illnesses, and use of prescription, over-the-counter, or illicit drugs), delivery(including where and by whom, whetherthe baby cried immediately, and the needfor resuscitation), and early postnatal peri-od. In addition, age of acquisition of devel-opmental milestones should be assessed. Indeveloping countries, one of the most pre-ventable etiologies of epilepsy and epilep-tic encephalopathies is poor prenatal andperinatal care. Mismanagement due to lackof facilities or personnel is vexingly fre-quent, and the circumstances of pregnancyand delivery should be specifically ques-tioned. Furthermore, events such asepisodes of high fever due to systemicinfections or a past history of meningitis,cerebral malaria, febrile convulsions, headtrauma, or other cerebral injury, should besought.

Frequency and Provoking FactorsAs mentioned in other parts of this volume,close attention should be paid to the possi-ble relationship between seizure occurrenceand seizure-provoking factors. Developingcountry environments increase the likeli-hood of several factors that can precipitateseizures. Foremost is suboptimal compli-

ance with the intake of antiepileptic drugs.Such noncompliance may be driven by cul-tural factors (such as the perception by rel-atives that the patient is taking too muchmedication, or that the medication willprove harmful in the future), by the incon-sistent availability of antiepileptic medica-tions in public pharmacies, and/or by inad-equate personal resources to access thesemedications. The temporal relationshipbetween seizure occurrence and missedmedication, as well as with other knownprovoking factors (such as excessive alco-hol intake and sleep deprivation) shouldalways be considered.

Illicit Drug Abuse and Other HabitsIllicit use of central nervous system–activedrugs is a universal phenomenon. Drug pro-ducing and poorly enforced drug-restrictingregulations lead to major drug-related casu-alties in developing countries. Large-scaledrug availability leads to high rates of druguse and abuse, which in turn may produceboth seizures related to overdose and sec-ondary brain lesions, causing subsequentepilepsy. Furthermore, persons who alreadyhave epilepsy may experience periods ofseizure recurrence or increase in frequencywhen using illicit drugs. Alcohol use, abuse,and withdrawal can cause similar problems.History should clarify whether drug-relatedseizures in a given individual represent theoveruse of a stimulant drug or the suddenwithdrawal of a sedative drug in someonewho is known to have epilepsy, or if theseizures are an acute reaction of a normalbrain. In the latter case, a diagnosis ofepilepsy is unwarranted, but in either situa-tion, counseling should be instituted to pre-vent further seizures.

Family HistoryGenetic factors can play a significant role inthe occurrence of epilepsy in a given indi-vidual. There are several levels of geneticpredisposition to seizures, which rangefrom the presence of sporadic seizures orepilepsy in other family members, to thepresence of electro-clinically definedepilepsy syndromes with a proven orstrongly suspected genetic etiology. Thus,the clinical history should include data on


50

the occurrence of seizures in other familymembers, ideally complemented by detailson the types of seizures and specific diag-noses given for those affected. A soundgenetic history concerning such details isvery difficult in developing countries anddata in patients’ files are often insufficient.However, a detailed family history, includ-ing information on febrile convulsions,should be obtained. Although syndrome-specific details may not be available foraffected family members, the simple factthat several members of a given family haveexperienced seizures may be of diagnosticand therapeutic value.

A thorough family history may be difficultto obtain. In many developing countries,family members may attempt to concealfrom other relatives that a particular child oradolescent has or had seizures. Finally, theissue of consanguineous marriages shouldbe considered. Such unions are frequent insome ethnic groups and may lead to epilep-sy, usually as part of a more severe neuro-logic syndrome.

Previous Events That Might Have Been SeizuresOnce a firm suspicion of epilepsy or of asingle epileptic seizure is raised, the occur-rence of previous events that might havebeen seizures but were not recognized assuch should be explored. This common sit-uation within the context of developingcountries has already been mentionedabove, namely, the ignorance that partialseizures with minor manifestations are alsomanifestations of epilepsy. Thus, one has toask the patient and relatives about previousrecurrent episodes of staring, minorautomatisms, periods of confusion follow-ing some type of strange behavior, focalmotor seizures without secondary general-ization, and tongue-biting or incontinenceduring sleep. In addition, the patientsshould be asked about recurrent visual,auditory, somatosensory, olfactory and gus-tatory sensations, as well as about psychicphenomena that could represent auras.Patients and relatives often miss these minorepisodes, and not uncommonly, a diagnosisof epilepsy can be traced back to severalyears.

Cultural Resistance to Providing anAccurate History, And Cultural CluesThat Aid DiagnosisA family may attempt to hide people withepilepsy from society. Such efforts make itmore difficult to obtain a reliable historyabout the actual nature of the seizures, thedegree of control with medication, and thepresence of epilepsy in other family mem-bers. Only education can overcome theseattitudes. Campaigns such as the ILAE/IBE/WHO global campaign to bring epilepsy“Out of the Shadows” appropriately targetthis problem.

In some societies, scarifications of epilep-tic patients are used to designate aspects oftheir disorder. For example, scarifications inTogo, West Africa, are done at the frontalroot of the hairline for subtle or simplecases. When seizures become severe, thescarifications are more visible on the fore-head and the cheeks. In Zambia, tattoos orscarifications are also common on the regionof the body where focal seizures begin, i.e.,the hand with Jacksonian seizures.

Physical Examination

General Physical ExaminationA complete physical examination should beconducted during the evaluation of patientswith possible epilepsy. The examination cangive clues to the presence of heart or anyother systemic disease that could be impli-cated either in the generation of acuteseizures or in secondary brain injury leadingto chronic epilepsy. A detailed discussion ofthese entities is beyond the scope of thistext, and only a few entities will be high-lighted. The general appearance of thepatient can suggest a state of dehydration orshow diffuse edema, suggesting the pres-ence of electrolyte abnormalities. This isimportant in poorer regions of the globe,where malnutrition can lead to severe elec-trolyte imbalance. A history of diabetes mel-litus should prompt a search for additionalsigns of dehydration that can accompanysevere hyperglycemia. Arrhythmias, valvulardisorders, or cardiac failure can all besources of cardiac emboli that can lead tobrain infarcts. Infarcts can occur withoutclinical deficits and may manifest only with


51

KEYPOINTS

n A thorough family historymay be difficult to obtain.In many developingcountries, family membersmay attempt to concealfrom other relatives that aparticular child oradolescent has or hadseizures. Finally, the issueof consanguineousmarriages should beconsidered. Such unions arefrequent in some ethnicgroups and may lead toepilepsy, usually as part ofa more severe neurologicsyndrome.

n The examination can giveclues to the presence ofheart or any other systemicdisease that could beimplicated either in thegeneration of acuteseizures or in secondarybrain injury leading tochronic epilepsy.

seizures. Chagas’ disease, which is endemicin many developing countries, is a commonetiology of cardiac problems that can causeseizures. Patients with severe, chronicobstructive pulmonary disease can haveperiods of hypoxia or hypercapnia that canlower the seizure threshold. In addition, stig-mata of chronic liver and kidney disease inthe skin, extremities, or abdomen shouldraise suspicion of seizures in the context ofliver or renal failure. Of course, an objectivephysical examination is much facilitated by acomplete history.

Examination under Special ConditionsThe patient’s age can focus the physicalexamination. For instance, children present-ing with seizures should have their bodytemperature checked and receive a thor-ough evaluation for infections, includingexamination for the presence of meningealsigns. In developing countries, particularlyin regions with endemic parasitosis or mal-nutrition, physical signs related to chronicdiarrhea, malnutrition, skin lesions, andother related abnormalities often provide aclue to the etiology of the seizures or epilep-sy, without the need for costly laboratorytests. Similarly, the physical examination ofelderly patients should focus on evidence ofactual or impending organ failure, and onphysical signs that can detect risk factors forspecific diseases common in older people(e.g., hypertension, chronic obstructive pul-monary disease).

When a patient is suspected of havingneurocysticercosis, one should carefullylook for tiny subcutaneous nodules. If facili-ties are available, a nodule can even bebiopsied to look for evidence of cysticercalgranuloma. Occasionally, simple X-rays canbe used to show the presence of calcifiedcysts, especially when the thigh regions areX-rayed. Rarely, muscle enlargement hasalso been documented secondary to cys-ticercal cysts in the affected muscles.

After head trauma, it is crucial to examinethe patient for physical clues of acuteintracranial hemorrhage or skull fracturesthat can lead to cerebrospinal fluid fistulaeand predispose to infections. The presenceof hemorrhage through the ears or bruisesaround the orbits suggests skull base frac-

ture, while lacerations around the templesshould raise the suspicion of middlemeningeal artery rupture, with a risk ofextradural or subdural hematomas. Ofcourse, the presence of pupillary abnormal-ities as well as the level of consciousnessshould be continuously checked.

Examining the Patient after a SeizureWhen possible, a physical examinationshould be performed immediately after anattack, aimed at identifying signs of injury,cyanosis, cardiac rhythm abnormalities,acute motor deficits, and the level of con-sciousness. The presence of bruises, tongueor other oral lesions, as well as of prolongedstupor or obtundation suggests that theseizure was indeed epileptic and general-ized. Vital signs and cardiac rhythm shouldbe checked. Any focal motor or sensorydeficits or aphasia should be noted, becausethese may represent acute postictal phenom-ena with significant localizing value (seebelow).

Seizure SequelaeSeizure sequelae can represent either neuro-logic deficits provoked by acute neuronalexhaustion and other neurochemicalchanges depressing neuronal function, orinjuries sustained during the actual or previ-ous seizures. Scars may offer evidence ofprevious seizure-related injuries. The pres-ence of scars probably indicates the need toimprove seizure control. Scar identificationoffers an opportunity to educate the patientand his or her relatives about measures toavoid further similar injuries. For example,the patient should be instructed to stay awayfrom open fires, at least until seizures arereliably controlled. Other preventive meas-ures are dealt with in Chapter 8. Somepatients may experience protracted post-ictal behavior abnormalities, includingaggressiveness, irritability, or overt depres-sion. The identification of these motor andcognitive abnormalities assists relatives inunderstanding the nature of these abnormal-ities, may decrease the tendency of family toblame the patient, and provides the physi-cian with an opportunity to discuss the bestway to manage seizures.


52

KEYPOINTS

n When a patient issuspected of havingneurocysticercosis, oneshould carefully look fortiny subcutaneous nodules.A nodule can even bebiopsied. Simple X-rays canbe used to show thepresence of calcified cysts.

NEUROLOGIC EXAMINATIONThe neurologic examination is differentdepending on whether the patient presentswith a single seizure or is known to haveepilepsy with chronically recurrent seizures.In the former scenario, an active searchshould be made for the presence ofmeningeal signs, papilledema, and focalmotor deficits that would indicate an acutebrain insult that should be promptly diag-nosed and treated. On the other hand, inpatients known to have epilepsy, the physi-cal examination will primarily be directed atsigns of chronic brain lesions. The rationaluse of scarce investigative resources indeveloping countries requires prioritizingneuroimaging studies to those patientswhose physical and neurologic examinationpresent abnormalities suggestive of acute orprogressive intracranial localized lesions.The presence of hemiparesis and hemiatro-phy usually attests to remote hemisphericinsult, usually during the pre- or perinatalperiod. In contrast, hemiparesis withouthemiatrophy suggests a more recent lesionthat should be fully evaluated. Several inves-tigators have identified a mild “emotional”facial palsy, contralateral to the side of onsetof temporal lobe seizures. The presence ofclinically identifiable mental retardation isalso a useful sign, suggesting either a diffuseencephalopathy or a unilateral (usuallyhemispheric) disease with severe secondaryimpact on overall brain function. Childrenand adolescents with mental retardation areat an increased risk for seizures. The cogni-tive status, an important part of the initialphysical examination, should be assessedduring each outpatient visit. A carefulappraisal of the age of acquisition of psy-chomotor milestones, taken in conjunctionwith the rate of progress the patient is mak-ing at school or when in contact with peers,can give a fairly reliable idea of the presenceand severity of mental retardation.Furthermore, skin lesions can give clues asto the underlying nature of an epileptic dis-ease. Café-au-lait spots, hypochromic orhypomelanotic lesions, facial hemangiomas,and linear nevus sebaceum are all associat-ed with intracranial lesions that give rise toepilepsy. Finally, fundoscopic examinationcan reveal lesions associated with diseases

that cause epilepsy. Such examination candisclose abnormalities suggestive either of aphacomatosis (e.g., neurofibromatosis,tuberous sclerosis), a storage disorder (e.g.,sialidosis, with a marked cherry red spot inthe fundi), a metabolic disease (e.g., theretinitis pigmentosa associated with mito-chondrial diseases), or can show signs ofintracranial hypertension, indicative of amass lesion, that should be aggressivelydiagnosed and treated.

COMPLEMENTARY DIAGNOSTIC PROCEDURES

Electroencephalogram (EEG)One problem with EEG studies in develop-ing countries is that the quality of therecordings and of the interpretation is oftensubstandard. In many regions, recordingsare performed by poorly trained technicians,and interpretation is done in a hurry.Unfortunately, as in the industrialized world,EEG is too often overused as a way ofincreasing medical income without demand-ing much time and effort. In addition, theEEG is erroneously perceived by patientsand relatives as a reliable measure of theevolution of the epileptic disorder, and thisperception is encouraged by some physi-cians. Conversely, the EEG tends to beunderused (or less available) for some pur-poses due to restrictions that have little to dowith unquestionable medical need. Thesesituations must be taken into account whendiscussing indications and cost-effectivenessof the EEG in developing countries.

EEG in the Diagnosis of EpilepsyAn abnormal EEG is not essential for a diag-nosis of epilepsy, and it should never sub-stitute for careful history-taking. In mostinstances, the diagnosis of epilepsy is clini-cally not challenging, and EEG has a limitedrole for this purpose. On the other hand,there are situations in which the physicianfaces a difficult differential diagnosisbetween epilepsy and other disorders thatmay mimic epilepsy (see Chapter 2), andthe EEG can, at times, be helpful to confirmthat recurrent spells are most likely epilep-tic seizures. Nevertheless, EEG findings canbe misleading in two ways: They can be


53

KEYPOINTS

n The rational use of scarceinvestigative resources indeveloping countriesrequires prioritizingneuroimaging studies tothose patients whosephysical and neurologicexamination presentabnormalities suggestive of acute or progressiveintracranial localizedlesions.

n An abnormal EEG is notessential for a diagnosis ofepilepsy, and it shouldnever substitute for carefulhistory-taking.

n A clear diagnostichypothesis should be in thephysician’s mind before theEEG is ordered, to avoidthe simplistic and oftenmistaken approach ofprescribing antiepilepticmedications for peoplewith epileptiformabnormalities on the EEG,without regard for theclinical picture.

normal in a significant percentage ofpatients with epileptic seizures, or epilepti-form discharges may be present in personswho do not have epilepsy. Therefore, aclear diagnostic hypothesis should be in thephysician’s mind before the EEG is ordered,to avoid the simplistic and often mistakenapproach of prescribing antiepileptic med-ications for people with epileptiform abnor-malities on the EEG, without regard for theclinical picture.

EEG in the Diagnosis of Seizure Type and SyndromeIn contrast to its limited role in the diagnosisof epilepsy, the EEG can be very importantfor a correct delineation of the seizure typeand/or the epileptic syndrome. In some situ-ations, EEG findings are the key to diagnosisof the type of seizure and have a significantimpact on the choice of antiepileptic medica-tion. Thus, interictal EEG patterns can deter-mine whether episodes of loss of awarenessor brief automatisms are due to complex par-tial seizures or to generalized absences. Inaddition, in patients presenting with general-ized motor seizures, the finding of a focalregion of electrical abnormality on the inter-ictal EEG can help differentiate a partialepilepsy leading to secondarily generalizedseizures from a generalized epilepsy syn-drome. This is often difficult from clinical his-tory alone, particularly in those patients whohave a genetic or acquired tendency to fast

seizure generalization, and in those in whomthese seizures occur during sleep.

The diagnosis of the specific epilepsysyndrome is, sometimes, dependent on theEEG findings. Cost-effective use of EEGrequires an understanding of the importanceof syndromic diagnosis to patient manage-ment. For instance, a diagnosis of juvenilemyoclonic epilepsy or of temporal lobeepilepsy due to mesial temporal sclerosisleads to specific actions in terms of furtherevaluation and treatment, and the identifica-tion of the epileptiform and backgroundabnormalities related to the symptomaticgeneralized epilepsies has significant prog-nostic impact. In contrast, subdividing spe-cific subsyndromes according to absenceseizures in ideopathic generalized epilepsieshas much less practical value, and scarceresources for long-term EEG are betterdirected at other clinical situations.

Laboratory Investigations

What Is Useful and What Is NotIn most cases, epilepsy is unassociated withlaboratory abnormalities. Thus, the physi-cian practicing in developing countries mustunderstand those situations in which labora-tory investigations are needed: 1) to diag-nose specific diseases that may cause epilep-sy or isolated epileptic seizures, 2) to detectabnormalities that require adjustments inantiepileptic treatment, 3) to monitor bio-


54

KEYPOINTS

n An understanding of thelocal epidemiology ofepilepsy is of great help instreamlining anyevaluation.

CASE STUDY

Presentation: An 18-year-old woman suffers from headaches, which are often diffuse, but from time to time lateralized toeither the right or the left side. The types of pain are variably tension or pulsatile. These symptoms are accompanied by afeeling of drowsiness, blurred vision, and chest pressure. The headaches usually are brief and transient. She has seen severaldoctors over 3 years, and was diagnosed as “epileptic” without evidence.

Evaluation: ECG and blood investigation were normal, except for a moderate anemia. EEG demonstrated nonspecific abnormal-ities with slow waves and some rapid rhythms. Since the first one, seven more EEGs have been performed: four on the demandof the patient; three from general practitioners. The results were approximately the same, leading to no change in treatment.

Treatment: Several types of analgesics and tranquilizers were prescribed. On the basis of the first EEG, a general practition-er prescribed lorazepam once a day.

Outcome: Every attempt to stop lorazepam was “unsuccessful” by EEG criteria, despite the fact that the patient was clinical-ly fine with very few headaches.

Comment: This case demonstrates EEG abuse, leading to misdiagnosis and maintenance of a nonindicated treatment. It empha-sizes the importance of treating the patient and not the EEG.

chemical and hematologic side effects ofantiepileptic drugs, and, occasionally, 4) tomonitor serum levels of antiepileptic med-ications.

There are a number of situations in devel-oping countries where the etiology of symp-tomatic seizures or epilepsies will be diag-nosed through laboratory tests. An under-standing of the local epidemiology ofepilepsy is of great help in streamlining anyevaluation. Substandard prenatal care canpose a greater risk for congenital or neona-tal hypothyroidism, syphilis, cytomegalo-virus, and other infectious diseases, as wellas metabolic derangements such as hypo-glycemia, and hypocalcemia. Thus, childrenwith seizures in the neonatal period shouldbe at least evaluated for these more com-mon disorders. Poor hygienic conditions atdelivery increase the risk for acute bacterialinfections, including sepsis or meningitis inthe first days or months of life. Hence,seizures in a baby without obvious metabol-ic derangement should be evaluated with acomplete blood cell count (CBC) and a lum-bar puncture (LP). Irrespective of age, thepossibility of infectious diseases endemic inspecific areas should be kept in mind. Theseinclude cysticercosis, malaria, and others,which should be diagnosed through specificblood and cerebrospinal fluid (CSF) tests.The need for LP in children presenting withfebrile convulsions is specifically discussedbelow. Cost-efficiency dictates that moresophisticated exams should be used onlysparingly when such studies will diagnoserare diseases with a uniformly gloomy prog-nosis (e.g., the causes of progressivemyoclonus epilepsies).

Hematologic and biochemical panels,when available, are indicated prior to theintroduction of antiepileptic drugs forpatients with known or suspected pre-exist-ing systemic diseases or who start theirepilepsy at an older age. Thus, patients withor at risk for hepatic or kidney diseases,abnormalities of the cardiac rhythm, andother systemic illnesses, which can be wors-ened by specific antiepileptic drugs orwhose metabolic impact can interfere withthe pharmacokinetics of the antiepilepticmedications, should be evaluated beforetreatment is introduced.

The use of tests to monitor potential bio-chemical and hematologic side effects ofantiepileptic drugs and to monitor serumdrug levels requires balancing responsiblepractice based on clinical experience—withthe risk of potential negligence. The majori-ty of patients using antiepileptic drugs donot develop significant hematologic or bio-chemical abnormalities. Except in circum-stances of a previous history of drug-induced abnormalities, very young or veryold age, or comedication with other poten-tially harmful drugs, these “monitoring” testsshould be used sparingly, no more oftenthan once a year, unless clinical side effectsoccur. An example is a patient complainingof easy fatigability, who has ankle edemaand uses carbamazepine; he/she should bechecked for the presence of hyponatremia.Periodic clinical evaluation for adverse sideeffects is much more important than labora-tory evaluations, and severe idiopathic sideeffects such as hepatotoxicity and blooddyscrasias usually appear clinically beforethey are detected by “routine” blood tests.

Routinely repeated, systematic monitoringof antiepileptic drug serum levels is expen-sive and unnecessary. With a few excep-tions, discussed in Chapter 5, adjusting thetherapeutic regimen on the basis of drug lev-els can do more harm than good. A commonsituation encountered in developing coun-tries is the inappropriate addition of a sec-ond or a third antiepileptic drug whenseizures persist despite “therapeutic” levelsof a first drug, rather than increase of thefirst drug to effect or toxicity. Another com-mon situation is the reduction of a well tol-erated dosage of an antiepileptic drug that iscontrolling the seizures, because the serumlevel is above the “therapeutic” laboratoryvalues. Dose adjustments of antiepilepticdrugs should be made on the basis of clini-cal parameters of seizure control and sideeffects obtained by physical examinationand consultation with the patient and rela-tives. If seizures are well controlled withminimal side effects, there is no need tomodify the treatment, irrespective of theserum levels (which should not be evenordered in this situation). If a patient is hav-ing seizures and not complaining of sideeffects, the dosage should be slowly but


55

KEYPOINTS

n Poor hygienic conditions atdelivery increase the riskfor acute bacterialinfections, including sepsisor meningitis in the firstdays or months of life.Hence, seizures in a babywithout obvious metabolicderangement should beevaluated with a completeblood cell count and alumbar puncture.

n Dose adjustments ofantiepileptic drugs shouldbe made on the basis ofclinical parameters ofseizure control and sideeffects obtained by physicalexamination andconsultation with thepatient and relatives.

steadily increased, irrespective of the actualserum levels. Adding a second drug becausethe level of the first is “within therapeuticrange” risks worsening seizure control orprovoking side effects, depending onwhether the new drug is enzyme inducingor inhibiting (see Chapter 5).

When to Do a Lumbar Puncture (LP)When to do an LP for a febrile illness associ-ated with a seizure is of particular interest.LP should be performed without delay on apatient with a febrile illness and signs andsymptoms of central nervous systeminvolvement unrelated to the seizure, whichraises the suspicion of meningitis orencephalitis, unless there is evidence ofincreased intracranial pressure and a risk ofherniation. In contrast, when there are nosigns of central nervous system involvementin a child who has a febrile illness due tosome other (usually mild) infection, theoccurrence of a seizure will most likely rep-resent a typical febrile convulsion, and an LPis usually not necessary.

The indications for LP are less clear inchildren with prolonged febrile convulsionsor febrile status epilepticus, in whom theprobability of a central nervous system infec-tion is higher than with single seizures. Thesafest approach, especially in childrenyounger than a year in whom meningialsigns and symptoms can be absent, would beto perform an LP. LPs can also be performedmore often in patients who live in endemicareas for specific infectious diseases with apotential to cause meningitis or encephalitis.In developing countries, this would apply,for example, to people presenting withfebrile seizures in areas endemic for malaria.Although the presence of a meningo-encephalitis due to these disorders will usu-ally be signaled by other clinical signs andsymptoms such as meningeal irritation,behavioral changes, or abnormal level ofconsciousness and physical illness, this isoften not true in very young infants. Otherstudies, such as immunologic tests, are notusually performed, and examination of thecerebrospinal fluid will be needed later onlyfor confirmation of the diagnosis, rather thanacutely after the seizure. Brain abscesses andthe edema surrounding cysts and other

lesions due to infectious disorders can beassociated with fever, seizures, and focalsigns of neurologic dysfunction. The possi-bility of meningitis or encephalitis accompa-nied by focal signs indicates a risk of cerebralherniation, and the decision when and if toperform an LP must be taken on an individ-ual basis. A detailed fundoscopic examina-tion often indicates the presence of increasedintracranial pressure that would contraindi-cate a lumbar puncture, at least until imagingis available. Ideally, patients such as theseshould have at least a CT scan; however, invery young children, the risk of herniation isless than the risk of missing an intracranialinfection, and LP should be performed whenCT is not available.

NeuroimagingCost-effective indications for neuroimagingin epileptic patients living in developingcountries depend on balancing several clini-cal and epidemiologic aspects. One is that athird of all epilepsies are ideopathic general-ized syndromes, most likely with a geneticbasis, and usually unassociated with struc-tural abnormalities detectable in neuroimag-ing studies. These patients can be identifiedby a careful history, physical examination,and EEG. In addition, many chronic epilep-sies are due to lesions whose nature can beanticipated by clinical history and neurolog-ic examination. These occur in children,adolescents, and even adults who had welldocumented pre-, peri-, or postnatal insults,leading to epilepsy and hemiparesis or otherfocal neurologic deficits, accompanied ornot by mental retardation. For these patients,an exact anatomical diagnosis is less rele-vant, unless seizures are refractory toantiepileptic drugs and surgery is contem-plated (see Chapter 7). Conversely, everyeffort should be made to make an anatomi-cal diagnosis in patients with focal seizuresof recent onset, or in those whose seizuresbecome medically refractory over the years.

Cranial X-rayCranial X-ray is of limited value in the eval-uation of epilepsy and should be performedonly when CT is not available and there is asuspicion of a calcified lesion associatedwith the seizures, such as in areas endemic


56

KEYPOINTS

n In very young children, therisk of herniation is lessthan the risk of missing anintracranial infection, andLP should be performedwhen CT is not available.

for cysticercosis. Additionally, other condi-tions can be associated with intracranial cal-cifications, including Sturge-Weber disease,tuberous sclerosis, and celiac disease.Although diagnosis of these conditions isusually apparent from general examination,when there is doubt, X-ray can show typicalpatterns of calcified lesions that render thesediagnoses more likely. Finally, the detectionof skull fractures following epileptic dropattacks is another potential indication forcranial X-ray.

CT ScanningCT scanning detects much more intracranialabnormalities than a skull X-ray, but muchless than MRI. CT scans can detect acutebleeding as the cause of acute onset seizuresand also calcified lesions associated withinfections or phacomatoses. In such situa-tions, plain CT can be better than MRI, atleast outside major academic centers. CT can

be used to rule out focal mass lesions inpatients with fever, convulsions, and focalsigns, reducing the risk of a LP. CT is impor-tant to evaluate patients in whom an MRIwould be ideal, but is not available for anyreason. These are patients with partialepilepsies of recent onset with no obviousetiology, who may harbor a potentially cur-able progressive lesion. CT scan is almost asuseful as an MRI scan to document cysticer-cal cysts in the brain, although many timeswhen CT scan is equivocal, an MRI scan canstill show the presence of cysticercal cysts.Occasionally, when CT shows a single cyst,an MRI can show more than one lesion. MRIis a much better imaging technique for intra-ventricular cysts. MRI is a superior investiga-tion as compared to CT scan, but is not nec-essary to diagnose cerebral cysticercosis.Finally, CT has been a great adjunct in thedetection of central nervous system disor-ders related to HIV-AIDS. Toxoplasmosis,


57

KEYPOINTS

n CT has been a greatadjunct in the detection ofcentral nervous systemdisorders related to HIV-AIDS. Toxoplasmosis,lymphomas, and othercerebral lesions related toopportunistic infections cancause seizures and aredetected or stronglysuspected on the basis of aCT scan. Thus, indeveloping countries,where AIDS is a majorpublic health problem, CT isstill useful in the evaluationof acute seizures, allowingprompt introduction ofspecific treatment relatedto an array of HIV/AIDS-related brain lesions

CASE STUDY

Presentation: A 43-year-old woman was seen in the ER for repeated seizures occurring with fever, which started that morn-ing. For 2 days, she had been suffering from headache, vomiting, and drowsiness. She had been having right partial motorthen secondarily generalized seizures for two years. There was a history of blood transfusion prescribed for an operation 7years ago. HIV2, HTLV-1, and syphilis seropositivity had been detected and confirmed 8 months before. She presented at thattime with acute transitory meningitis, which resolved after 5 days of antibiotic therapy.

Evaluation: Three different EEGs showed diffuse slow waves and inconstant spikes. There were no MRIs in her country, andshe could not afford a CT scan. A cranial X-ray showed small calcifications in the right hemisphere.

Treatment: She was treated with phenobarbital, then, when seizures continued, carbamazepine 400 mg twice a day. She wasplaced on a ward, because there was no room in the intensive care unit. She received diazepam IV, phenobarbital IM, andtrimethoprim and sulfamethoxazole associated with antipyretic medications.

Outcome: Her situation worsened and she was transferred after 2 days to the intensive care unit and placed on oxygenbecause of aspiration. Due to her advanced clinical status, it was too late for her to benefit from the new drugs. She finallyreceived a free CT scan, which demonstrated multiple associated hyperdense and heterogeneous lesions predominantly inthe left hemisphere, strongly suggestive of toxoplasmosis. Her condition deteriorated with continued right partial secondar-ily generalized seizures, then status epilepticus, and she died before she could benefit from anti-toxoplasmosis therapy.

Comment: This case illustrates an increasing reality in many developing countries and poses the problem of neuro-AIDS andits associated epileptic seizures. What is due to HIV itself and what is due to opportunistic infections? Transient meningitisand progressive encephalopathy are often suspected and reported, but in many developing countries, a high incidence ofsecondary infectious diseases can colonize the brain and present as an epilepsy syndrome. The appropriate approach for thispatient would have been to strongly suspect opportunistic infection by Toxoplasma gondii at an early stage, and to begin atherapeutic trial of pyrimethamine and sulfadiazine (or clindamycin if the patient is allergic to sulfadiazine). It was appropri-ate to avoid doing lumbar puncture without evidence that there was no brain mass, which only a CT scan could demonstrate.If obtained, the cerebrospinal fluid would have shown a mild to moderate pleocytosis and elevated protein content. Brainbiopsy can also be diagnostic. With early use of CT scan to support the hypothesis of brain toxoplasmosis, early anti-toxoplas-mosis treatment (and sustained lifelong prophylaxis with trimethoprim/sulfamethoxazole or clindamycin/ pyrimethamine),continued antiepileptic therapy, and government-subsidized antiretroviral drugs, the prognosis would have been much bet-ter because recurrence of such treatable opportunistic epileptogenic brain lesions can be prevented.

lymphomas, and other cerebral lesions relat-ed to opportunistic infections can causeseizures and are detected or strongly sus-pected on the basis of a CT scan. Thus, indeveloping countries, where AIDS is a majorpublic health problem, CT is still useful inthe evaluation of acute seizures, allowingprompt introduction of specific treatmentrelated to an array of HIV/AIDS-related brainlesions.

MRIMRI is the ideal neuroimaging modality toevaluate patients with epilepsy. From a cost-effective perspective, however, the role ofMRI in this evaluation should be placed inthe context of the previous discussionregarding the place of neuroimaging inepilepsy in general, the applications of CTscanning, and the difficulties in obtaining anMRI in developing countries.

MRI is very important in two situations.One is when a progressive lesion not detect-ed by CT is suspected in patients with par-tial seizures of recent onset accompanied byfocal neurologic deficits. The other concernspatients with refractory epilepsies in whomsurgical treatment is contemplated. A signif-icant number of nonprogressive epilepto-genic lesions is detected by MRI and oftenmissed by CT, the malformations of corticaldevelopment being the most notable exam-ple. In these patients, MRI is irreplaceablefor identifying surgically treatable epilepsysyndromes and diseases, to help determinethe epileptogenic zone, and to delineate theamount of tissue to be resected. The issue ofsurgical treatment of the epilepsies is dealtwith in Chapter 7.

Functional ImagingThere is little or no indication for functionalimaging studies in the evaluation of epilep-sy outside tertiary centers involved in theworkup of surgical candidates (see Chapter7). Most instances in which single photonemission computed tomography (SPECT) isused to study patients with epilepsy outsidethe context of presurgical evaluation repre-sent inadequate utilization of resources,which should be discouraged, even more soin developing countries.

HOW TO PROCEED WHEN YOU DO NOTHAVE ACCESS TO COMPLEMENTARYTESTINGHistory, physical, and neurologic examina-tions alone often suffice for a diagnosis ofthe seizure type and the most likely epilep-sy syndrome, thus allowing a successfultreatment in patients with epilepsy. Themajority of patients presenting with seizuresto an outpatient clinic or doctor’s office (asopposed to a hospital emergency depart-ment) do not have any major acute disorderand, even when this is suspected, knowl-edge of the epidemiology of the regionwhere the physician is practicing is helpfulin streamlining the clinical approach. Thus,in endemic areas, patients should probablyreceive antiparasitic medication if they pres-ent acutely with seizures and complementa-ry testing is not available. These clinical andempirical measures are important from apublic health perspective, and also to singleout those patients in whom all efforts shouldbe undertaken to transfer to a larger centerand perform complementary testing.

CONCLUSIONSThe diagnostic approach to the epilepsies isa good example of how much history-takingand clinical examination can still be of prac-tical and pragmatic use in neurology. Theapproach, however, differs depending onwhether the seizure is an acute single eventor a chronic condition that has just come tothe attention of the medical practitioner. Alarge number of diagnostic and therapeuticsteps can be taken effectively on clinicalgrounds alone, and this has been the unify-ing theme of this chapter. Neurologists prac-ticing in developing countries should excelin the clinical approach to persons withseizures and epilepsy, because this is theonly way to rationalize the use of the scarcetechnological resources that should bereserved for patients posing specific diag-nostic and treatment challenges.


58

KEYPOINTS

n The majority of patientspresenting with seizures toan outpatient clinic ordoctor’s office (as opposedto a hospital emergencydepartment) do not haveany major acute disorderand, even when this issuspected, knowledge ofthe epidemiology of theregion where the physicianis practicing is helpful instreamlining the clinicalapproach.

CITATIONS AND RECOMMENDED READINGDekker PA. Epilepsy: A Manual for Medical and Clinical Officers in Kenya. Leiden: Epicadec, 1998.

This is a revised and up-to-date version of a book written by PA Dekker from an extensive experience as a doctorin rural Kenya.

Engel J, Pedley TA, (eds.) Epilepsy: A Comprehensive Textbook. Vols. 1, 2 and 3. Philadelphia: Lippincott-RavenPublishers, 1997.

This is a worldwide reference for anyone interested in all detailed aspects of epilepsy.

Genton P, Epilepsies. Paris: Masson, 1992.

A book written in French summarizes the essentials about seizures and epilepsy, and their treatment.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revisedclinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489–501.

This is a summary of the revised Classification of Epileptic Seizures, as proposed by the ILAE Commission onClassification and Terminology in 1981. Epileptic seizures are defined based on semiology and EEG features.

Commission on Classification and Terminology of the International League against Epilepsy: proposal for revisedclassification of epilepsy and epileptic syndromes. Epilepsia 1989;30:389–399.



59


61

CHAPTER 5

PRACTICAL APPROACHES TO TREATMENT

KEYPOINTS

n Physicians in thedeveloping world shouldhave a higher threshold forinitiating pharmacotherapyafter a single unprovokedseizure, and a lowerthreshold for withdrawingpharmacotherapy after agiven period of seizurefreedom.

n The need to balance thecost of antiepilepticmedication and thepotential stigmatizingeffect of a diagnosis ofepilepsy against the impactof one or more additionalseizures must be addressedfor each patientindividually when making atherapeutic decision.

The ultimate objective in the management ofpeople with epilepsy, in all regions of theworld, is treatment to prevent recurrence ofattacks, reverse cognitive and motor impair-ment, and improve quality of life. Decisionsregarding treatment include when to start andwhen to stop treatment, how to select theappropriate antiepileptic drugs (AEDs), andhow to monitor efficacy and adverse eventsthat require changes in therapy. In developingareas of the world, negative perceptions relat-ed to a diagnosis of epilepsy and to the chron-ic use of medication are more common thanin the industrialized world, as are problemsposed by reduced AED availability, the impactof AED cost, unreliable supplies of AEDs, anddifficulties in complying with periodic outpa-tient visits. Consequently, in general, physi-cians in the developing world should have ahigher threshold for initiating pharmacothera-py after a single unprovoked seizure, and alower threshold for withdrawing pharma-cotherapy after a given period of seizure free-dom. These decisions are often complicatedin developing countries by the limitation ofdiagnostic resources, such as neuroimagingand EEG, which makes it more difficult todetermine whether events in question areepileptic seizures warranting treatment withAEDs. This chapter considers these issues inthe management of patients with differenttypes of epileptic disorders in the context ofthe various treatment options that may beavailable in countries with limited resources.

WHEN AND HOW TO START TREATMENT

Differential Diagnosis, Risk of SeizureRecurrence, and Psychosocial MorbidityEpilepsy, by definition, presents the threat ofrecurrent seizures, often in an unpredictableway. AED treatment helps decrease the risk

of such recurrences. However, becausepatients will often present after a singleevent, and not everyone with a singleseizure goes on to experience further events,the decision on “when to start” AED treat-ment requires much consideration. In manypoor regions of developing countries, ancil-lary technology that might directly or indi-rectly help establish the nature of dubiousspells (e.g., EEG, imaging studies) will oftennot be available. Such resource-poor regionsmay also have limited health care resourceswith difficult drug accessibility and limitedAED options (e.g., only phenobarbital). Inthese circumstances, when doubts remainon the nature of the first spell, treatmentshould be withheld until it becomes clearthat the episodes are recurrent and theirepileptic nature becomes clinically estab-lished. As discussed in Chapter 4, the latteris dependent on a detailed, dynamic history.

The need to balance the cost ofantiepileptic medication and the potentialstigmatizing effect of a diagnosis of epilepsyagainst the impact of one or more addition-al seizures must be addressed for eachpatient individually when making a thera-peutic decision. Here, issues peculiar todeveloping countries come into play, suchas the negative attitudes associated with adiagnosis of epilepsy on the one hand, andon the other, the prospect of losing a jobshould a seizure recur at work (and the dif-ficulty of getting another one later), or thefact that children are usually rejected fromnurseries and school if they have seizures.Also, people are often under professional orpersonal pressure to drive, and tend not tocomply with doctors’ requests to not drivewhile the clinical situation gets clarified.Thus, the overall psychosocial environmentof developing countries must be taken into

account in the decision on when to starttreatment.

How to Start TreatmentOnce it is decided that AED treatmentshould be started, cost-effectiveness isimportant and should guide drug choice.Ideally, an equation based on seizure type,need for prompt achievement of therapeuticlevels, side effect profile, and drug availabil-ity should dictate the decision on what drugto use. Unfortunately, in developing coun-tries, drug availability often takes prece-dence over the other factors (see Chapter 6).

A practical way to follow the generalprinciples mentioned above, for most typesof epilepsy, is to start treatment with a sin-gle, traditional (older) AED of proven effica-cy for the seizure type/epilepsy syndrome inquestion. This monotherapy approach witha traditional AED suits the economic limita-tions of developing countries, and is usuallyat least as effective as any other regimen,including the newer and more expensivedrugs. Furthermore, among the older AEDs,some like phenobarbital and phenytoin canbe given with a loading dose when neces-sary, or at least with a full dose. This con-trasts with most other drugs, including thenew drugs, which usually require that thera-py be initiated over a considerable time(“start low, go slow”). A loading dose, how-ever, is rarely necessary for routine initiationof AED therapy, and is usually reserved foracute life-threatening situations such as gen-eralized tonic-clonic status epilepticus.

Some specific epilepsy syndromes in chil-dren benefit from the newer drugs wherethey are available. Infantile spasms respondto vigabatrin, given orally, in over 60% of thecases. Tonic-clonic seizures starting between2 and 5 years of age, and either repeated orcombined with drop attacks, are most likelyto result from myoclonic-astatic epilepsy,and require valproate combined with lamot-rigine. The same applies for the occurrenceof drop attacks with hyperkinesias occurringbetween 5 and 8 years of age that are likelyto indicate Lennox-Gastaut syndrome.

TRIAGE OF EPILEPTIC CONDITIONSMost people with epilepsy have seizures thatare easy to treat, respond to relatively low

doses of all appropriate AEDs, and can usu-ally be managed by primary care physicians.The majority of patients with these types ofepilepsy will experience no disability if treat-ment is initiated appropriately, and forsome, seizures will eventually remit andmedication will no longer be necessary. Inreality, ~40% of patients with epilepsy haveepileptic seizures that are difficult to control,but for many of these, more intensive phar-macotherapy, or alternative treatments, par-ticularly surgery, will result in seizure free-dom. In developed countries, these patientsusually require referral to a tertiary epilepsycenter to accurately diagnose the epilepto-genic abnormality and to initiate effectivemedical or surgical treatment. Truly refracto-ry epilepsy requires supportive care, at timesinvolving institutionalization where suchfacilities are available. For these patients,specialized pharmacotherapeutic, and insome cases surgical or other alternativetreatments, as well as psychosocial servicesoffered by a tertiary epilepsy center, cangreatly reduce the disability associated withresidual seizures and maximize quality oflife. It is essential that primary care physi-cians and general neurologists distinguishbetween these three types of epileptic con-ditions and effect timely referrals when spe-cialized expertise is necessary and available.Where these services are absent, familycounseling to provide a safe environment,and the establishment of local supportgroups, can be extremely beneficial.

Easy-to-Control EpilepsiesAbout half the people with epilepsy mani-fest with only a few seizures that are easy tocontrol with low to moderate dosages of tra-ditional AEDs. They consist largely of inher-ited disorders, which are corroborated by afamily history of single seizures or epilepsy.Patients with easy-to-control epilepsies usu-ally present after a first or a few partial orgeneralized seizures, which may or may nothave had convulsive movements. In devel-oping countries, the number of availableAEDs may be limited. It is not uncommonthat public services provide only one, or atbest two, AED(s), which, however, are usu-ally effective in easy-to-control epilepsies.More costly AEDs are also available in many


62

KEYPOINTS

n Start treatment with asingle, traditional (older)AED of proven efficacy forthe seizure type/epilepsysyndrome in question. Thismonotherapy approachsuits the economiclimitations of developingcountries, and is usually atleast as effective as anyother regimen, includingthe newer and moreexpensive drugs.

n Most people with epilepsyhave seizures that are easyto treat, respond torelatively low doses of allappropriate AEDs, and canusually be managed byprimary care physicians.

developing countries, and it is not uncom-mon that physicians indirectly add anunnecessary significant financial burden topatients and families by prescribing highcost AEDs as first options, even in these mildcases. Education is the key to limiting suchpracticing and achieving rational AED pre-scription, particularly in patients with easy-to-treat epilepsy. Inexpensive drugs inmonotherapy, often at low doses, will suf-fice for many patients.

Hard-to-Control EpilepsiesSuccessful seizure control in patients withcryptogenic or symptomatic epilepsies is acontinuous challenge, and can only be metthrough 1) adequate clinical diagnosis of thetype of seizure and epilepsy syndrome; 2)practical use of the concepts of maximumtolerated AED dosages and serum levels; 3)reasonable anticipation of the level ofdosage of the selected AED(s) that will mostlikely be needed to increase chances ofseizure control; and 4) adequate knowledgeof AED pharmacokinetics, including theputative favorable and unfavorable interac-tions with other AEDs.

A correct characterization of the seizuretype(s) should take into account the fact that

many people in developing countriesbelieve that epilepsy or an epileptic seizureis present only when there are convulsive,tonic-clonic generalized movements. Thus,people tend to limit their report to thesetypes of seizures. This can be potentiallymisleading, stressing the need to specificallyask about focal features that might precedegeneralization. Historical or clinical evidencefor a major brain insult, particularly focalmotor signs or developmental delay, strong-ly suggests a symptomatic epilepsy syn-drome and anticipates difficulties in achiev-ing complete seizure control with AEDs. Inhard-to-control epilepsies, familiarity withthe pharmacokinetic properties of AEDsallows prescription of adequate dosages,which are often close to the maximum toler-ated ranges, and rational polytherapy whenmore than one drug is necessary.

If new AEDs have a place in developingcountries, it is for these hard-to-controlepilepsies. Thus, before assuming medicalrefractoriness (see below), at least somepatients should be tried on the new AEDs.This is contingent on drug availability andthe epilepsy syndrome. In practice, newAEDs should be considered for thosepatients whose epilepsies are both refractory

Practical Approaches to Treatment

63

KEYPOINTS

n More costly AEDs are alsoavailable in manydeveloping countries, andit is not uncommon thatphysicians indirectly add anunnecessary significantfinancial burden to patientsand families by prescribinghigh cost AEDs as firstoptions, even in these mildcases. Inexpensive drugs inmonotherapy, often at lowdoses, will suffice for manypatients.

n A correct characterizationof the seizure type(s)should take into accountthe fact that many peoplein developing countriesbelieve that epilepsy or anepileptic seizure is presentonly when there areconvulsive, tonic-clonicgeneralized movements.

n If new AEDs have a place in developing countries, itis for hard-to-controlepilepsies.

CASE STUDY

Presentation: A 48-year-old man has had generalized tonic-clonic seizures since the age of 9, treated with phenobarbital.During the first 10 years, he received 100 mg of phenobarbital with five to seven fits per month. The dose was increased to150 mg, then to 200 mg, leading to a reduction in seizure frequency to one or two per month. He progressively improvedand became totally seizure free. The dose was gradually reduced to 150, 100, and 50 mg per day, then 25 mg every other day.

Evaluation: The first EEGs were abnormal, but the latest were normal. No drug level facility was available.

Treatment and outcome: The patient is still taking 25 mg of phenobarbital every other day. His weight is 65 Kg. He has beentaking this dose for 3 years and is seizure free. His doctor, judging that this dose is very low, decided to stop the medication.The patient disagreed but respected this medical decision. Three weeks later, he came back to his doctor because he had asevere generalized tonic-clonic seizure for the first time in 7 years. The medication was restarted and he has done well since.

Comment: This situation is very often encountered in developing countries. Many patients receive low doses of AEDs, farbelow the doses used in the industrialized world, with a good outcome. When patients are taking very low doses ofantiepileptic medications, it does not necessarily mean that they do not need them. This does not, however, countermandthe overriding recommendation to discontinue medication when possible.

to traditional AEDs and not surgically reme-diable. Even with an adequate approach todrug selection and prescription, about aquarter to a third of all patients with epilep-sy will fall short of complete seizure control.

Early identification of patients withseizures that are unresponsive to medicaltherapy, but that may be responsive to alter-native treatments, can improve the efficacyof these interventions, particularly surgery.In many cases, neurologists can predictmedical unresponsiveness after two or threeappropriate drug trials have failed due toinefficacy, as opposed to intolerance. Ofcourse, close questioning, tablet counting,and careful examination to verify adherenceto the prescribed AED regimen is needed toassure the “refractory” seizures are not sim-ply due to medical noncompliance. In thefew developing countries where surgery isan option, it is then important to determinewhether the patient has a surgically remedi-able epilepsy syndrome. This is usually thetask of a tertiary epilepsy center. However,one cannot overemphasize the role of thecommunity neurologist in identifyingpatients who may be helped by epilepsysurgery early enough to avoid irreversibleadverse social and psychological conse-quences of disabling seizures.

Refractory EpilepsiesA subset of patients have truly refractoryepilepsies, and their early identification isoften possible. Of course, in most of thedeveloping world, where surgery and othertertiary facilities are unavailable, manypatients with hard-to-control epilepsies are,for practicable purposes, refractory.Nevertheless, in those developing countrieswhere resources for surgical treatment existbut are scarce, it is important to identify trulyrefractory patients, because surgery is usual-ly palliative at best and is not a cost-effectiveintervention. These patients typically havediffuse cortical dysfunction resulting frommalformations, hypoxic-ischemic encephalo-pathies, or neonatal meningitis, and theirepilepsy is usually associated with develop-mental delay, as well as with cognitive,motor, and behavioral dysfunction. Seizuresare usually frequent and polymorphic, andcharacteristically include generalized tonic,

atonic, and tonic-clonic seizures, as well asatypical absences and myoclonic jerks.Several age-related medically refractoryepilepsy syndromes are recognized, includ-ing the severe myoclonic epilepsies of infan-cy (Dravet’s syndrome), Ohtahara, West, andLennox-Gastaut syndromes. Emphasisshould be placed on the potential for pre-vention in many patients in whom insultsresult from substandard pre-, peri-, and post-natal care, affecting the management ofpregnancy, labor, delivery, or the neonatalperiod. AED management of these complexcases is difficult and aims at the best possi-ble balance between seizure control andside effects.

BASIC PRINCIPLES AND PHARMACOKINETICS OF ANTIEPILEPTIC DRUGS

Absorption to Clearance, and the Concept of Half-LifeThe biological availability of AEDs is deter-mined by a dynamic process, which beginsthrough absorption, proceeds with distribu-tion in the various body compartments, andconcludes with the metabolic and excretorymechanisms related to their elimination. Thetemporal sequence of these processes with-in the context of chronic treatment is betterconceptualized as a continuum, and absorp-tion, distribution, and elimination actuallycoexist at different levels. For practical pur-poses, all these processes should be viewedas potential limiting factors to the achieve-ment of the best possible therapeutic effectfrom a given AED, that is, the ratio betweenantiepileptic efficacy and side effects. Keyvariables related to individual AED pharma-cokinetics are given in Chapter 6.

The rate of absorption determines theinterval between the ingestion of the pill andthe attainment of its peak serum levels (peaklevel). This, in turn, determines the onset oftherapeutic action as well as the temporalpattern of occurrence of side effects. Onceabsorbed, the drug is distributed within thedifferent body tissues. The percentage of thedrug within the various body tissues is spe-cific for each drug.

Finally, AEDs are metabolized and excret-ed. This step is responsible for the clearance


64

KEYPOINTS

n The percentage of the drugwithin the various bodytissues is specific for eachdrug.

of the drug and its gradual elimination fromthe body. Most AEDs in current use aremetabolized through the liver, and thuspeculiarities of hepatic metabolism are piv-otal to both dosage planning and to theanticipation of type and degree of interactionwith other drugs (including other AEDs).This leads us to the concept of biologicalhalf-life, the time it takes for the serum con-centration of a given drug to decrease by50% after absorption and distribution havebeen completed. Thus, AEDs with fastermetabolism will have shorter half-lives andwill need to be administered more frequent-ly. Half-life is very long in prematures, equalto the adult at term, then decreases dramati-cally until the second month of life.Therefore, dose per body weight should bedouble that of the adult in infants, and 1.5times that of the adult in children.

Enzyme Induction, Enzyme Inhibition, and the Pharmacokinetic Counterparts of AED Mono- versus PolytherapyMost, but not all drugs are detoxified in theliver. Hepatic metabolism occurs through aconcerted action of enzymatic systems,which are influenced by a variety of factors,including hepatic dysfunction and the inter-ference of a variety of drugs (includingAEDs). The interaction among differentAEDs at the level of hepatic enzymatic sys-tems is the main reason why polytherapy(that is, combination of two or more drugs)often leads to an increased incidence oftoxic side effects and may even interferewith the efficacy of one or all of the drugsbeing used. This is related to the fact thatsome drugs are enzyme inducers, while oth-ers are enzyme inhibitors, respectively accel-erating or slowing down the metabolism ofother drugs used concurrently, with a directimpact in the latters’ half-life. Thus, polyther-apy with enzyme inducers leads to reducedantiepileptic efficacy in comparison withthat achieved with correctly appliedmonotherapy, while polytherapy withenzyme inhibitors can result in enhancedadverse dose-related toxicity. Polytherapymay be necessary, however, in difficult-to-control epilepsy. In these situations, poten-tial metabolic interactions must be consid-ered in the choice of drugs.

Planning the Adequate Dosage for Each PatientThe goal of AED dosages for individualpatients is maintenance of serum levels thatare adequate to prevent seizure recurrence,while at the same time below those causingundesirable side effects (the therapeuticrange). Once a maintenance dose of an AEDis instituted, steady-state serum levels areachieved within five half-lives of the drug,but actual levels fluctuate between doses(Figure 5.1). To avoid wide swings in peak(highest) and trough (lowest) levels, dosageinterval should correspond to 50% of thehalf-life of the drug. This strategy also canprotect the patient against a seizure whenmedication intake is occasionally delayed ormissed.

DEALING WITH ADVERSE EFFECTSAdverse effects are almost inevitable withhigh-dose AED use. The aim is to useamounts appropriate to each individual sothat any side effects are deemed acceptable.Tolerance to adverse effects usually occursand should be anticipated as an encourage-ment to patient compliance at treatment out-set. Nevertheless, some degree of compro-mise is usually needed, its most obviousrationale being that adequate seizure controlsignificantly reduces the limitations imposedby the epileptic condition and permits, asmuch as possible, a normal life.

The need to reach a satisfactory balancebetween beneficial and adverse effects ofAED treatment should be discussed with thepatient and his or her relatives, and the neu-rologist should always be willing to revisethe AED regimen. Unfortunately, there canbe a limitation to this process, which is evenmore marked in developing countries,where economic factors reduce the choiceof AEDs available to most patients.

Clearly, there are situations in which com-promise is appropriate, and others when it isnot. For instance, the more difficult to con-trol the seizures, the more reasonable it is toaccept some degree of side effects, provid-ing adequate control is a realistic goal. Thisis the typical scenario of the hard-to-controlbut (medically) controllable epilepsies.Conversely, epilepsy syndromes toward thetwo ends of the spectrum of controllability


65

KEYPOINTS

n Dose per body weightshould be double that ofthe adult in infants, and 1.5times that of the adult inchildren.

n To avoid wide swings inpeak (highest) and trough(lowest) levels, dosageinterval should correspondto 50% of the half-life ofthe drug. This strategy alsocan protect the patientagainst a seizure whenmedication intake isoccasionally delayed ormissed.

may not invite too much compromise. Thus,in most easy-to-control epilepsies, completeseizure control can be achieved with mostAEDs, and more than minimal side effectsshould prompt consideration of an alterna-

tive drug. For entirely different reasons,compromise may be inadequate in the trulymedically refractory epilepsies. In thesemost severe conditions, suboptimal seizurecontrol is often inevitable, and morbidity


66

KEYPOINTS

n In these most severeconditions, suboptimalseizure control is ofteninevitable. Adjust the AEDregimen to a morecomfortable level, withlower dosages and/or fewerdrugs, which may lead to asimilar degree of seizurecontrol as compared tomore toxic regimens, but abetter overall quality oflife.

A. Repeated doses of a drug at intervals of one half-life or less result in asteady state serum drug level after five half-lives. The objective of dose

planning is to maintain the serum drug level within the therapeutic range so that thepeak level does not cause toxic side effects and the trough level is sufficient to maintainprotection against seizures.B. If a drug dose is repeated at intervals of one half-life, it is usually possible to maintainthe serum drug level within the therapeutic range, although a single missed dose resultsin a fall in serum drug level into the unprotected range. With a dose interval of 0.5 half-life, fluctuation of serum drug level is decreased, and a missed dose is less likely to causeinadequate protection.From Engel J. Jr.. Seizures and Epilepsy. Philadelphia: F.A. Davis, 1989, with permission.

FIGURE 5.1

Steady State

Toxic Side Effects

Therapeutic Range

Unprotected

Trough Level

Peak Level

Time in Half-Lives

1 2 3 4 5 6 7Se

rum

Dru

gLe

vel

Dose Schedule

1 Half-Life

0.5 Half-Life

Time in Half-Lives

1 2 3 4 5 6

Seru

mD

rug

Leve

l

Dose Missed

Dose Missed

A

B

should not be increased by severe adverseeffects. A more reasonable approach, there-fore, is to adjust the AED regimen to a morecomfortable level, with lower dosagesand/or fewer drugs, which may lead to asimilar degree of seizure control as com-pared to more toxic regimens, but a betteroverall quality of life.

The management of adverse effects beginsby attempting to minimize or prevent theiroccurrence. The principle of “start low andgo slow” should be usually applied, with thefew exceptions related to the introduction ofphenytoin and phenobarbital and the acute-ness of the clinical situation. When dose-related adverse effects occur during thecourse of chronic treatment, a number ofstrategies can be used. First, the total dailydose can be further subdivided, circumvent-ing the need for dose reduction. This is a use-ful strategy with drugs like carbamazepine,for which a QID regimen with smaller indi-vidual dosages can often eliminate dose-relat-ed side effects observed with BID or TID reg-imens. Second, dosage can be reduced whensymptoms of toxicity are reported. This mayor may not be safe, however. For instance,performed in isolation, this may be a danger-ous move in patients with hard-to-control-but-controllable epilepsies, in whom ade-quate seizure control was achieved onlywhen maximally tolerated dosages of a drugused in monotherapy were reached. Thus,should one consider dosage reduction, a sec-ond drug with low potential for interactionshould be added as a measure of compensa-tion. Third, in patients who are alreadyreceiving more than one AED, the potentialfor interaction should be checked and takeninto consideration as an explanation for thedose-related adverse effects. In this context,reduction of the dosage of an enzymeinhibitor drug could accelerate the metabo-lism of the other AED, reducing the adverseeffects. Finally, for medications for which acontrolled-release formulation is available, itssubstitution may reduce side effects related topeak serum levels resulting from rapid drugabsorption. This latter strategy, however, is oflimited use in developing countries, becausecontrolled-release preparations are moreexpensive and usually not made availablethrough public health systems.

Whereas dose-related side effects canoften be avoided by increasing the doseslowly, often dissipate after a week or two,and invariably reverse when medication isdiscontinued, idiosyncratic side effects aremuch more serious and can be life-threaten-ing. Reactions such as Stevens-Johnson syn-drome, aplastic anemia, and liver failure arefortunately rare, but can occur with mostAEDs. Usually they cannot be predicted bylaboratory studies, so the absence of the abil-ity to carefully monitor blood chemistriesand hematology does not present a particu-lar handicap. Rather, patients must bewarned about symptoms of these disorders,such as rashes, recurrent infections, bleeding,and jaundice, and advised to contact theirphysician immediately if these should occur.When appropriate emergency laboratoryevaluations fail to rule out a serious adverseevent, or if laboratory facilities are not avail-able, the AED should be discontinued.

Long-term side effects of AEDs, such asneuropathies, connective tissue disorders,and cerebellar degeneration, can also occur,particularly with chronic use of phenytoinand phenobarbital. In most cases, theseeffects are not symptomatic, but phenytoincan produce gingival hyperplasia and cos-metic changes that are disturbing, and phe-nobarbital can produce Depuytren’s contrac-tures. In some people, valproate causesweight gain and alopecia, which can be aproblem, particularly for young women.

MONITORING ANTIEPILEPTIC DRUG SERUM LEVELSFacilities for monitoring serum levels areoften not available in developing countries,but where they are, it is important that theynot be overused. Even in the industrializedworld, adjustments in AED regimens are pri-marily based on clinical grounds, irrespec-tive of the serum levels. Dosage adjustmentsshould always be made on an individualbasis and dictated by the performance of agiven AED regimen in terms of seizure con-trol on the one hand and side effect profileon the other.

Serum levels above or below the pub-lished therapeutic range have little meaning,unless the patient is having seizures or com-plaining of toxic side effects. Published ther-


67

KEYPOINTS

n Idiosyncratic side effects areserious and can be life-threatening. Usually theycannot be predicted bylaboratory studies. Patientsmust be warned aboutsymptoms of thesedisorders.

n When appropriateemergency laboratoryevaluations fail to rule outa serious adverse event, orif laboratory facilities arenot available, the AEDshould be discontinued.

n Facilities for monitoringserum levels are often notavailable in developingcountries, but where theyare, it is important thatthey not be overused.

apeutic ranges for AEDs are populationaverages, and individual patients vary great-ly in response to drugs. A common mistakeis to precipitously change the AED regimensolely because of specific serum level deter-minations, disregarding both efficacy andside effects in the individual patient. It isinadequate to simply replace an AED (oradd a second, a third, or a fourth AED)because seizures persist despite “adequateserum levels,” even when there are no sideeffects. A key concept here is that of themaximum tolerated dosage—irrespective ofserum level determinations—that can beachieved in an individual patient by gradual-ly increasing the dose until either seizurecontrol or intolerable side effects ensue.Furthermore, most literature on AED serumlevels has been generated in industrializedcountries. Therefore, the appropriateness ofextrapolating “adequate” or “inadequate”serum levels for genetically different individ-ual patients or populations in developingcountries can be challenged. Validation stud-ies in these populations are needed.

There are some situations in which deter-mination of serum levels is useful. Theseinclude the need: 1) to determine, for futurereference in the event of clinical changes(seizure breakthrough or toxic side effects),the individual therapeutic range of a drugonce an effective dose has been reached; 2)to rule out poor compliance as a possiblecause for otherwise unexplainable seizurerecurrence; 3) to decide whether seizurerecurrence may be due to some pharmaco-kinetic peculiarity leading to low serum lev-els, including rapid drug clearance or druginteraction; 4) to determine which AEDshould be held responsible for unexpected,undesirable side effects when the patient ison polytherapy, and 5) to identify changesin levels due to physical factors such asweight change (especially in children), preg-nancy, diseases that affect absorption, pro-tein binding and elimination, and addition ofmedications that can cause pharmacokineticinteractions. Serum levels are particularlyuseful with larger doses of phenytoinbecause of its unique saturation kinetics.

When serum levels are difficult to obtainor not available, the questions posed by thesituations just mentioned should be

approached through judicious environmen-tal and pharmacologic manipulation.Compliance can be increased by askingsomeone to help in the administration of thepills for a certain period of time. If subopti-mal levels are suspected, the dosage of themain AED should be progressively and care-fully increased to the maximum tolerateddosages. This will rule out low serum levelsas the reason for seizure recurrence, evenwithout the actual determination of the lat-ter. Finally, to solve the issue of side effectsin the context of polytherapy, the dosage ofthe AED less likely to be the cause of sideeffects should be increased, with the subse-quent reduction or discontinuation of theother drug(s).

STOPPING TREATMENT

When to ConsiderBecause a diagnosis of epilepsy and thechronic use of AEDs are attended by psy-chological, social, and physical disadvan-tages, the need to maintain patients on med-ication after a period of seizure freedommust be carefully reevaluated. This is evenmore so for patients in developing countries,for whom the psychosocial consequences ofepilepsy have a greater impact and the costand availability of AEDs are of significantconcern.

Before analyzing the risks of seizurerecurrence for individual patients upon dis-continuation of AEDs, one should define theepilepsy syndrome and the amount of timethe patient has been seizure free on medica-tion. A good approach is to explain thatwhen the time comes, the decision will betaken in conjunction with the patient and hisor her family. The prerequisite for discussingthe discontinuation of AED treatment is theattainment of a prolonged period of seizurefreedom, particularly in the context of non-lesional epilepsies.

Several factors increase or decrease thechances of successful discontinuation ofAEDs in a given patient (Table 5.1). In theindustrialized world, almost half of patientswith epilepsy will be able to discontinuemedication; however, the number may besmaller in developing countries, where riskfactors for symptomatic epilepsies are much


68

KEYPOINTS

n Most literature on AEDserum levels has beengenerated in industrializedcountries. Therefore, theappropriateness ofextrapolating “adequate”or “inadequate” serumlevels for geneticallydifferent individualpatients or populations indeveloping countries canbe challenged.

more common than for idiopathic epilepsies.Patients whose seizures are most likely toremit over time are those in whom a genet-ic predisposition is the predominant or sin-gle pathogenetic mechanism, and the contri-bution of any major remote lesional compo-nent is minimal or nonexistent. Syndromicdiagnosis provides the best predictor of thechances that a given patient will eventuallydiscontinue medication.

An important issue for neurologists prac-ticing in developing countries is that thedecision to discontinue AEDs, as in the deci-sion to begin AEDs, transcends the simplefact that seizures may recur. It must balance

what is at stake should a seizure returnagainst the cost and possible side effects ofAEDs, as well as the stigma of continuing tobe viewed as epileptic. If the epileptic con-dition is already known to the employer,arrangements can be made to protect thepatient against physical harm during at leasta 2-year period of dosage reduction andeventual AED discontinuation. For instance,this might include asking a farmer or a plantmanager to remove the patient from operat-ing machines, or asking the manager of abank to arrange for the patient to avoiddirect public contact as a cashier. If theemployer is not aware of the epileptic con-dition, the patient may either try to raise thisissue at work or take the risks. For women,other relatives might be asked to assumepotentially dangerous tasks such as cookingover an open fire or drawing water fromopen sources. In developing countries, thedecision to take such risks usually is not leftonly to the patient, but involves otherresponsible relatives. Commonly, patientswith low educational levels are unable tofully appreciate what is at stake shouldseizures recur. When patients work forthemselves, in activities that are incompati-ble with recurrent seizures, such as taxi driv-ing or other professional driving, AED dis-continuation may not be practical.

Discontinuation of AEDs is less likely toresult in seizure recurrence if it is carried outslowly, tapering dosages at 1- to 2- to 3-month intervals, in a process that may last ayear. When the patient is on polytherapy,this process could last even longer, becauseonly one drug should be discontinued at atime. The majority of seizure recurrenceswill take place during taper, but protectivemeasures, such as not driving, should con-tinue for 3 to 6 months after the drug is com-pletely discontinued. Thus, in adolescentswith apparently easy-to-control epilepsies, itis better to attempt AED discontinuationbefore the patient begins to drive, because itis always better to postpone than to suspenda driver’s license.

In developing countries, many issues maybe more important for patients and theircaregivers than driving. In children, onecommon problem is that teachers very oftendon’t want a child with epilepsy in their


69

KEYPOINTS

n An important issue forneurologists practicing indeveloping countries is thatthe decision to continueAEDs must balance what isat stake should a seizurereturn against the cost ofAEDs, as well as the stigmaof continuing to be viewedas epileptic.

n In adolescents withapparently easy-to-controlepilepsies, it is better toattempt AEDdiscontinuation before thepatient begins to drive,because it is always betterto postpone than tosuspend a driver’s license.

n In developing countries,many issues may be moreimportant for patients andtheir caregivers thandriving.

Risk Factors for Recurrenceafter Discontinuation ofAntiepileptic Drugs inPatients Who Are SeizureFree for 1 To 4 Years*†

TABLE 5.1

Factors most commonly found in themost relevant studies

• Defined etiology (remote sympto-matic epilepsies, abnormal imaging)

• First seizure after 10 years of age

• Partial seizures

• Mental retardation and other abnor-malities in neurologic examination

• EEG spikes at time of tapering

Factors found in single or smaller number of studies

• Epilepsy onset after age 5

• Interval between seizures of less than1 month at onset of illness

• Longer duration of active disease(took longer to control seizures)

• Start withdrawing AEDs after age 6

• Abnormal (epileptogenic) EEG duringwithdrawal

• Less than three years of remission

• Psychiatric diagnosis

* Some factors apply to specific subpopu-lations, such as children/adolescents,adults, or only patients with cryptogenicepilepsies.

† Some factors were not confirmed in allstudies.

classroom even if the seizures are well con-trolled. Many students after finishing schooljoin educational courses at places away fromhome and very often they live alone. Theparents of children with epilepsy whoseAEDs are being withdrawn have great anxi-ety in such situations. Marriage at or aroundthe time of discontinuation of AEDs is anoth-er problem, especially for young womenwith epilepsy. The fear of seizure recurrenceduring the wedding ceremony (that veryoften may be long affairs requiring girls tobe awake for two to three nights in countrieson the Indian subcontinent) is anotherimportant aspect of the problem.

DEALING WITH SEIZURESMost seizures occur at home, school, or theworkplace. Learning how to approach andprotect the person with epilepsy during aseizure is thus important for relatives, teach-ers, and colleagues who will confront thissituation on repeated occasions. Only asmall fraction of epileptic seizures are pro-longed to a point where transference to anemergency room is warranted. Mostepisodes simply need an organizedapproach by the witnesses to prevent harmfrom fire, water, excessive bruises, and inter-ference with respiration.

Patients whose seizures are not fully con-trolled should refrain from cooking, becauseall too often, burns from boiling water, oil, orby simply placing the hands on the stoveoccur during seizures. The best preventivemeasure against burns is not to be exposed tofire. This is not an easy undertaking forwomen in developing countries, who oftenhave to cook for several children, with no fur-ther help. Occasionally, a patient may wanderaround in an automatic, semi-purposeful fash-ion and potentially approach a stove or a fire-place during a complex partial seizure. A highlevel of vigilance is required from relatives toprevent the confused patient from doing so,and ideally, patients with these seizure typesshould not be in environments where there isfire. In practical terms, this means that personswith epilepsy should not be in a kitchen whilefood is being cooked or in an area near a fire-place or bonfire.

Harm from water may be even more seri-ous than that from fire, because persons

with epilepsy may drown while bathing orswimming. Epileptic patients should bestrongly advised against bathing in bathtubs,and those with suboptimal seizure controlshould not go on boats alone. Advice onswimming is more difficult and should beconstrued on an individual basis. Patientsmust not swim alone, but swimming accom-panied by vigilant relatives or friends underprotected situations may be feasible as longas the accompanying individual is capable ofpulling the person with epilepsy to safety ifa seizure occurs.

Partial motor and generalized seizurescan lead to bruises or fractures, and thepatient’s head and arms should be held orprotected with a cushion to avoid repeatedtrauma against the floor or other surface.The potential for injuries should be antici-pated and prevented. For instance, by relo-cating the patient’s bed in relation to thewall, recurrent injuries due to clonic move-ments or dystonic posturing against the wallin sleep-related seizures can be prevented.In addition, objects that could harm thepatient should be taken away. A more chal-lenging situation is that posed by suddendrop attacks, which often accompany severeepilepsies and lead to injury. Some of themeasures that could be helpful in these situ-ations are difficult to implement in house-holds of developing countries, such as con-stant supervision and modification of thetype of floor to reduce the impact of injury.One helpful measure is the use of a protec-tion helmet, although compliance with thisis variable.

During generalized tonic-clonic seizures,there is a need to assure ventilation and pre-vent aspiration. Tight clothes should beloosened and glasses removed. The patientshould be turned to his or her side and thehead gently held. A supine position must beavoided so that saliva and mucus can runout of the mouth. Excess salivation may bewiped with a tissue. The family should beclearly informed that fingers or objectsshould not be introduced into the patient’smouth during the attack. Someone shouldstay with the patient until consciousness isregained.

Prolonged seizures, particularly whengeneralized, need to be stopped through


70

KEYPOINTS

n The best preventivemeasure against burns isnot to be exposed to fire.This is not an easyundertaking for women indeveloping countries, whooften have to cook forseveral children, with nofurther help.

n The family should be clearlyinformed that fingers orobjects should not beintroduced into thepatient’s mouth during theattack.

n Harm from water may beeven more serious thanthat from fire, becausepersons with epilepsy maydrown while bathing orswimming.

emergency medical intervention with IVdrugs and other supporting measures. Thus,if a seizure does not stop in a matter of afew minutes, or if generalized tonic-clonicseizures recur without return of conscious-ness in-between, transfer to an emergencyroom should be organized, to prevent theharmful consequences of status epilepticus.Patients should also be taken to an emer-gency room if they have experienced theirfirst seizure, they have injured themselvesduring the seizure, or they are pregnant.Otherwise, the loss of time and cost associ-ated with an emergency room visit furtheradds to the disability associated with anepileptic seizure.

SPECIAL ISSUES IN PHARMACOTHERAPY

When to Treat a Single Seizure or Infrequent SeizuresEstimates of seizure recurrence after a firstunprovoked seizure vary from 20% to 70%within the next two to five years, althoughmost patients will have their second seizurewithin a year of the first. The lower recur-rence figures apply to patients who havehad a generalized (as opposed to focal)attack with no past history of febrileseizures, and who present with a normalneurologic development and examination,no family history of seizures, and normalEEG and brain imaging after the firstseizure. The presence of one or more ofthese predisposing factors progressivelyincreases the likelihood of recurrence.Thus, consideration of AED initiation isentertained after a single seizure only if oneor more of the known predictors of subse-quent seizures can be documented in agiven individual (Table 5.2). It is useful forpatients to understand that if AED therapyis instituted and they remain seizure freefor several years, they face the choice oftapering or discontinuing the drug. Thus,unless the intention is to treat the patientfor a lifetime, instituting treatment after asingle unprovoked seizure to prevent recur-rence of another does not resolve the prob-lem, but merely postpones it. Coupled withthe fact that patients in the developingworld face significantly more difficulties

related to cost and availability of AEDs,these considerations should stronglyencourage a high threshold for initiatingtreatment after a single seizure in thesecountries.

One situation to be singled out is the riskof recurrence after a first seizure related toacute or transitional phases of neurocysticer-cosis. It has been shown that while activeinfection persists, the risk of seizure recur-rence is high, and an AED should be main-tained during this period. After resolution,usually in 6 months to a year, the risk ofseizure recurrence is low, and discontinua-tion of the AED should be considered.

Some patients with chronic epilepsy havevery infrequent seizures, a condition some-times referred to as oligoepilepsy. Whenseizures occur many years apart, the risksposed by a subsequent ictal event may notwarrant the cost, inconvenience, and possi-ble adverse side effects of continuous AEDtreatment. Often in industrialized countries,patients and their physicians choose not toundergo treatment for seizures that occurmany years apart, and there would seem tobe even more justification for foregoingtreatment in such patients in developingcountries.


71

KEYPOINTS

n Coupled with the fact thatpatients in the developingworld face significantlymore difficulties related tocost and availability ofAEDs, these considerationsshould strongly encouragea high threshold forinitiating treatment after asingle seizure in thesecountries.

n When seizures occur manyyears apart, the risks posedby a subsequent ictal eventmay not warrant the cost,inconvenience, and possibleadverse side effects ofcontinuous AED treatment.

Risk Factors for Recurrenceafter a First UnprovokedSeizure*

TABLE 5.2

Factors most commonly found in themost relevant studies

• History of prior febrile convulsions

• Defined etiology (abnormal imaging,remote symptomatic etiology)

• Todd’s paresis

• Seizure during sleep

• Abnormal EEG

Factors found in single or smaller number of studies

• Family history of epilepsy

* Some factors apply to specific subpopu-lations, such as children/adolescents,adults, or only patients with cryptogenicepilepsies.


72

CASE STUDY

Presentation: The patient is a 35-year-old man in good health. At the age of 26, after a day spent swimming, playing foot-ball, and other physical activities under the sun, on the beach, he experienced a sudden massive generalized tonic-clonicseizure. There was no medical or surgical event in his early past and no complaints on this day. He had been successfully treat-ed for malaria with new drugs 2 months ago. There is a history of absence epilepsy in a cousin.

Evaluation: He was transported by friends to the hospital 35 km away, in a state of drowsiness and generalized pain. Bloodand urine examinations were performed, including Plasmodium falciparum parasitology, without any abnormality. The dayafter, an X-ray and EEG were performed and were normal. Because there was no contraindication, a lumbar puncture wasperformed and was also normal.

Treatment: IV glucose with 10 mg of diazepam was given the first night, but not repeated. He was given paracetamol for hisgeneralized pain.

Outcome: Since this seizure, no other events have occurred. He is performing very well at work.

Comment: This case illustrates the need for a high threshold before instituting a long-term treatment for an uncertain condi-tion. In such cases, it is important to carry out a full evaluation, to be sure that there is no underlying treatable disorder (e.g.,infections, metabolic, hemorrhagic, traumatic). Even if modern diagnostic tests are not available, careful surveillance can leadto a good outcome. A symptomatic neuromalaria seizure could be considered, but is unlikely for someone of his age in anendemic area, even if he had experienced a recent episode of malaria 2 months ago. A history of absence epilepsy in a rela-tive is also not sufficient to conclude that he has chronic epilepsy. Such people in developing countries could be better off treat-ed by traditional healers than by the modern medical system, where an inexperienced MD might prescribe lifelong AED ther-apy for a single seizure that would never recur.

CASE STUDY

Presentation: A 17-year-old man presented with a history of recent onset of recurrent seizures. He would have jerking of hisright arm and leg, occasionally evolving into secondarily generalized seizures. The seizures occurred every few days. Therewas no family history of seizures or other risk factors for epilepsy.

Evaluation: The patient’s examination was unremarkable. He had no subcutaneous nodules. A contrast enhanced CT scan ofthe brain revealed multiple, bilateral small rounded calcified lesions in the brain parenchyma without surrounding edema.

Treatment and Outcome: Seizures no longer occurred after he began taking phenytoin, 300 mg/day.

Comment: This patient’s seizures could readily be ascribed to acute neurocysticercosis; however, the calcified lesions couldalso be an incidental finding, given their common occurrence in developing countries. Further imaging, such as MRI if avail-able, is recommended to exclude other, more serious or treatable etiologies. The AEDs in acute cases of neurocysticercosis areprescribed to prevent seizure recurrence, and can be stopped after about 6 months if the patient remains seizure free, evenif the CT lesions persist.

Febrile Seizures and Fever-RelatedSeizuresFebrile seizures are common and illustratethe interactions between maturational andgenetic vulnerability to seizures during thefirst years of life. Episodes occur between 6months and 7 years of age, with a peakbetween ages 1 and 3. Differentiation fromepilepsy and intracranial infection (seeChapter 4) is not always easy, and rests bothon typical clinical features and clinical evo-lution. Febrile seizures occur in childrenwith normal development, usually during acommon viral illness, when the temperatureis rising. Most episodes are single, general-ized, and short-lasting, features that charac-terize simple febrile convulsions.Infrequently, they are focal, last more than20 minutes, recur within 24 hours, or are fol-lowed by a postictal abnormality in the neu-rologic examination. The latter complexfebrile convulsions are accompanied by ahigher risk of epilepsy in the future. Seizuresin the context of fever in children with pre-vious brain damage or the association offebrile and nonfebrile seizures suggest thepresence of epilepsy. A first episode withouta clear cause must be thoroughly evaluated,particularly to rule out meningitis.

Parental counseling and indication ofmeasures to actively treat the rising temper-

ature (paracetamol and tepid bath) is all thatis needed in most circumstances to preventrecurrence of simple febrile seizures.However, in the event of recurrent episodes,or if the first episode is complex, additionalprophylactic treatment might be considered.This may be effected either through rectaldiazepam at the time of fever, or throughchronic administration of phenobarbital orvalproic acid until age 5. The risks and ben-efits of initiating prophylactic anticonvul-sants for complex fever-associated seizuresthat occur in the setting of malaria remainunclear. When trying to determine whetherto initiate treatment in this setting, oneshould consider the magnitude of the risk ofa prolonged, untreated seizure recurring inthe patient’s environment, the likelihood ofparental adherence to treatment, and theimpact of any drug-related side effects.

Some considerations apply to the man-agement of febrile seizures in developingcountries. First, in regions where malaria isendemic, this infection should always beruled out. Second, preventive measures formalaria and for other childhood infections,such as measles vaccination, should beenforced. Third, the indications for chronicprophylaxis are much wider for practical,epidemiologic, and psychosocial reasons. Inpractice, diazepam for rectal use is not avail-


73

KEYPOINTS

n The risks and benefits ofinitiating prophylacticanticonvulsants for complexfever-associated seizuresthat occur in the setting ofmalaria remain unclear.When trying to determinewhether to initiatetreatment in this setting,one should consider themagnitude of the risk of aprolonged, untreatedseizure recurring in thepatient’s environment, thelikelihood of parentaladherence to treatment,and the impact of anydrug-related side effects.

CASE STUDY

Presentation: A 34-year-old male accountant was brought for assessment after what was initially thought to be a singleseizure. Although he had no memory for the event, eye-witness accounts reported a versive right head turn followed by gen-eralized tonic-clonic activity and postictal confusion. Closer history-taking revealed that he had experienced complex febrileseizures as a child that also began with the head turning and had gone on to experience approximately one seizure every 2years since then for at least the past 6 years. He had previously been treated with phenobarbital, but reported severe cogni-tive side effects that resulted in job losses. The only other reasonably available AED, carbamazepine, caused him to developa severe rash.

Evaluation: His examination was unremarkable. EEG and CT were not available in his community. His general health had notchanged in the past 5 years, and he denied any headaches or interim neurologic symptoms.

Treatment/Outcome: After some discussion, the patient opted to forego treatment, given the limited options available to himand the adverse effects these agents had previously caused. He did not own a vehicle or drive. He was counseled regarding therisks of open fires and bodies of water, exposure to heights, etc. Over the subsequent 8 years, he continued to be seen annual-ly by the neurologist to assure no progressive problems developed. He continues to have a seizure approximately every 24months, but with no significant sequalae, given the precautions he takes, and he has been able to remain gainfully employed.

Comment: Under the circumstances, this patient was best served by counseling and reassessments. Treatment might have pre-vented his rare seizures, but would almost certainly have had a more negative impact on his quality of life.

able in many developing countries. Also, theoccurrence of childhood infections is higher,increasing the risk of recurrence. Finally,febrile convulsions in nurseries or maternalschools may be a significant issue both forattending professionals and working moth-ers, with potentially harmful psychosocialimpact.

NeurocysticercosisNeurocysticercosis, the most common causeof seizures in many parts of the developingworld, presents unique therapeutic chal-lenges, not only for antiepileptic treatment,but for antiparasitic treatment. When larval

cysts located in the brain parenchyma orsubarachnoid space degenerate, they releaseexcretory products that are highly epilepto-genic. Recurrent acute seizures usuallyresolve spontaneously within months, unlessthe formation of a surrounding granulomaserves as a chronic epileptogenic lesion.Consequently, antiepileptic treatment forpatients presenting with acute seizures dueto neurocysticercosis should not be long-term. Attempts to taper and discontinuemedication after 3 or 4 months are usuallysuccessful and, in this case, indicate that achronic epileptic condition does not exist.Where computed tomography (CT) or mag-


74

KEYPOINTS

n Antiepileptic treatment forpatients presenting withacute seizures due toneurocysticercosis shouldnot be long-term.

CASE STUDY

Presentation: A 4-year-old boy from a region with endemic P. falciparum malaria presented in status epilepticus with a feverof 40.2 degrees Celsius. The rains had recently commenced and a great deal of malaria was being seen at the hospital. Heresponded to 10 mg of IV diazepam initially and was also given rectal acetaminophen. He regained consciousness briefly, butseizures recurred 2 hours later.

Evaluation: A thick blood smear confirmed 4+ parasites and a lumbar puncture was entirely normal. A review of his medicalrecords revealed that the child had experienced three previous episodes of status epilepticus—all occurring in the setting ofacute malaria with high fevers during the rainy season. He had experienced other fever-associated seizures also, but his moth-er denied any history of seizures occurring without “body hotness,” and all seizures documented in the child’s medical recordhad occurred with fevers. His older brother had also experienced seizures with fever as a child.

Treatment and Outcome: He was given IV 50% dextrose at 1 ml/kg and a 15 mg/kg load of phenobarbital. IV quinine in 5%dextrose was initiated. He regained consciousness over the next 12 hours. His hospital course was otherwise unremarkable, andhis examination on day 3 was remarkable only for decreased hearing attributed to the cinchonism secondary to quinine.

Comments: Does this child have epilepsy? Should he receive some prophylactic treatment to prevent further episodes of sta-tus? If yes, should he receive antimalarial agents for preventive therapy? Or anticonvulsants? And how long should thesemedications be continued?

This child likely suffered from recurrent provoked seizures related to repeated malaria infection, not epilepsy. In malaria-endemic regions, children may experience 3 to 5 infections annually from age 1 to 6. It is encouraging that his brother, whohad similar events as a child, had not continued to experience these after age 7. One might consider treating this child withprophylactic chloroquine, but most of the malaria in the region in question was recognized to be resistant to chloroquine,and partial treatment could cause false negative test results. More effective agents for prophylaxis, such as mefloquin, weretoo expensive for the family to purchase.

After discussion with the mother, the child was discharged on phenobarbital, to be continued until the season whenmalaria risks decline. The mother was instructed to bring the child back for review when the rains started the following year,so the medication could be reinitiated for the 3 months of peak seasonal malaria. She was also provided with a treated bednet and acetaminophen to be used if the child developed fevers. She was told very explicitly that the medicine to treat thefever would not treat malaria and she must seek care for the child if fevers recurred.

netic resonance imaging (MRI) are available,it can be used to assist antiepileptic treat-ment. Resolution of epileptogenicity is oftenaccompanied by disappearance of the activecyst. Less than one-quarter of patients expe-rience seizure recurrence on drug withdraw-al when active cysts are no longer presenton imaging. After the acute stage, dead cystscan appear on CT as small calcifications.Therefore, the finding of such calcificationson CT at the time of seizure onset suggestsa chronic condition, and prognosis for drugwithdrawal is poorer than when active cystsare seen. If seizures recur with drug with-drawal, chronic pharmacotherapy is neces-sary. When pharmacotherapy fails to controlseizures, and an epilepsy surgery center isavailable, surgical excision of the epilepto-genic granuloma is indicated.

A more controversial issue is whether andwhen to treat neurocysticercosis withantiparasitic medication. The argumentagainst antiparasitic treatment is that acutecysts resolve without this intervention, whileantiparasitic agents, such as albendazole,accelerate the release of toxic substances,increasing the risk for more severe seizuresand increased intracranial pressure.Furthermore, this response could result inthe formation of a more vigorous granulo-matous reaction, which could be more like-ly to cause chronic epilepsy. Deaths associ-ated with antiparasitic treatment are rare,however, especially in patients with low cystburden and absence of increased intracranialpressure or hydrocephalus. A recent clinicaltrial (Garcia et al., 2004) found that albenda-zole was well tolerated, and no deathsoccurred in 60 patients treated. Althoughacute seizures were initially more frequentin the albendazole-treated patients, theywere controlled by antiepileptic medication,and the later occurrence of generalizedtonic-clonic seizures (but not partialseizures) in treated patients was less fre-quent than in patients given placebo. A larg-er, multicenter trial is necessary to betterresolve the safety and efficacy of antipara-sitic treatment before it can be recommend-ed in this situation.

As noted in Chapter 2, diagnosis of cys-ticercosis is most appropriately made by MRI,CT, or X-ray, but where neither CT nor X-ray

are available, serology and evaluation of skinand muscle can be helpful. For the majorityof patients with seizures due to neurocysticer-cosis, CT is not available, and other tests areeither negative or not possible to perform.Therefore, the decision to treat with antipara-sitic drugs may be moot, and relatively little islost by opting not to introduce the risk andcost of another drug regimen. As also notedin Chapter 2, however, another importantissue is that in endemic areas, calcified cere-bral cysts on CT may be a fortuitous finding.

Furthermore, on the Indian subcontinentat least, single small enhancing lesions maynot indicate cysticercosis and often disappearspontaneously (see Chapter 4).Consequently, the diagnosis of neurocysticer-cosis or findings of small calcifications inpatients presenting with acute seizures doesnot necessarily mean that the seizures are dueto this disturbance. Because viable (nonde-generating) cysts are commonly asympto-matic, antiparasitic administration in suchpatients with epilepsy due to another causecould unnecessarily create a second epilepto-genic lesion that would complicate diagnosisand treatment. An argument for antiparasitictreatment of viable cysts is that these willeventually die, with a risk of consequentseizures, and that treatment can permit theseizures to appear under more controlledconditions. Recent studies do not address thisissue, but most specialists recommend nottreating viable asymptomatic cysts. Cautionshould be exercised in patients presentingwith headaches or signs of increased intracra-nial pressure, where antiparasitic therapy canincrease morbidity and mortality.

Epilepsy in PregnancyThe physiological changes that occur duringpregnancy result in altered distribution andelimination of AEDs. This may interfere withseizure control, particularly in women whowere already poorly controlled before con-ception. Increased plasma estrogens, waterand sodium retention, vomiting, poor com-pliance with AEDs, anxiety, and sleep irreg-ularities are some of the factors that mayaffect seizure frequency during pregnancy.

There are several aspects to considerwhen planning AED therapy during preg-nancy. These include preconceptional coun-


75

KEYPOINTS

n CT or MRI can be used toassist antiepileptictreatment. Resolution ofepileptogenicity is oftenaccompanied bydisappearance of the activecyst.

n The finding of calcificationson CT at the time of seizureonset suggests a chroniccondition, and prognosisfor drug withdrawal ispoorer than when activecysts are seen.

n The argument againstantiparasitic treatment isthat acute cysts resolvewithout this intervention,while antiparasitic agents,such as albendazole,accelerate the release oftoxic substances, increasingthe risk for more severeseizures and increasedintracranial pressure.

n Where neither CT nor X-rayare available and othertests are either negative ornot possible to perform,relatively little is lost byopting not to introduce therisk and cost of anotherdrug regimen.

n The diagnosis ofneurocysticercosis orfindings of smallcalcifications in patientspresenting with acuteseizures does notnecessarily mean that theseizures are due to thisdisturbance.

n Most specialists recommendnot treating viableasymptomatic cysts.

seling, choice of drug, adjustment of theAED regimen throughout gestation, anddelivery planning. When it is possible toadjust the AED regimen before conception,attempts should be made to ensure the bestpossible control with monotherapy at theminimum effective dosages, and folate sup-plementation should be started. In develop-ing countries, limited access to public healthsystems may reduce the chances of precon-ceptional counseling, although public cam-paigns in this regard should be instituted.Although no AED is yet proven to beabsolutely free of teratogenic effects, someof the newer drugs may have a relativelylower risk than commonly used older ones.If possible, valproic acid should be avoidedbecause of an apparently greater risk ofcausing neural tube defects, especially in thepresence of a positive family history of ter-atogenic drug effects.

The increase in the volume of distributionof most AEDs in the third trimester may leadto seizure recurrence due to reduced serumlevels. The latter should be checked anddosage adjusted accordingly, particularly inpatients who experienced difficulties inseizure control before conception and inthose who already had seizures during preg-nancy. Pregnancy also is associated withreduced serum protein and a resultantincrease in the free fraction of protein-bound AEDs. This, in turn, causes increasedrenal clearance and lower total serum levels,but the amount of unbound drug availableto the brain remains the same. If serum druglevels fall during pregnancy as a result ofdecreased protein binding, increasing thedrug dosage may not be necessary and,indeed, may increase the risk of toxicity.Vitamin K1 (10 mg/day by mouth) duringthe last few weeks of pregnancy reduces thechances of neonatal intracerebral hemor-rhage when mothers are on enzyme-induc-ing AEDs. All these measures highlight thepivotal role of good quality prenatal care inthe outcome of pregnancies of women withepilepsy, and no specific managementguidelines substitute for that. Neurologistsfrom developing countries should work inconcert with gynecologists and policy-mak-ers to improve the quality of prenatal carefor pregnant women with epilepsy.

There is a two- to threefold increase inthe incidence of major malformations andminor anomalies among babies born tomothers with epilepsy. The use of AEDs dur-ing pregnancy plays a major role in theincreased risk of abnormalities like cleft lip,cleft palate, congenital heart disease, andneural tube defects. The risk increases withthe number of AEDs used during pregnancy,which makes a strong case for monotherapy.However, more than 90% of women withepilepsy treated during pregnancy can beexpected to have an uneventful pregnancyand a normal healthy baby.

Although women with epilepsy who aretaking AEDs excrete these drugs in theirmilk, this is not a contraindication to nurs-ing. Nursing babies should be watched,however, to make sure that there is no seda-tive effect that suppresses the nursing reflex.

Eclampsia is the occurrence of seizures inwomen (with no prior history of epilepsy)during pregnancy in a setting of pre-eclamp-sia (proteinurea, edema, and high bloodpressure after the 20th week of gestation).The causes of eclampsia and seizures duringthat period are poorly understood and arebelieved to be multifactorial. If seizures dur-ing eclampsia are not controlled quickly,there is significant maternal as well as fetalmortality. Eclampsia is a common cause ofmaternal and fetal mortality in developingcountries because most of the pregnanciesand subsequent deliveries are still not con-ducted under the supervision of trained per-sonnel. The diagnosis of eclamptic seizures ismainly established by the clinical setting.When evaluating a patient thought to haveeclampsia, it is important to ask explicitquestions privately of the family members toconfirm that indeed the patient does nothave a history of prior epileptic seizures,because a history of epilepsy may not havebeen disclosed to those delivering obstetricalcare, especially among women recently wedwho have not revealed their seizure disorderto their husband’s family. Magnesium sulfatehas been the standard treatment for both pre-eclampsia and eclampsia. Magnesium sulfateacts by various mechanisms, but is not effec-tive in seizures due to epilepsy. Magnesiumsulfate can cause sedation in the mother, andhypotonia and lethargy in the newborn.


76

KEYPOINTS

n When evaluating a patientthought to have eclampsia,it is important to askspecific questions about ahistory of prior epilepticseizures, because a historyof epilepsy may not havebeen disclosed to thosedelivering obstetrical care,especially among womenrecently wed who have notrevealed their seizuredisorder to their husban’sfamily.

n Vitamin K1 (10 mg/day bymouth) during the last fewweeks of pregnancyreduces the chances ofneonatal intracerebralhemorrhage when mothersare on enzyme-inducingAEDs.

Other drugs that have been used in eclamp-sia include phenytoin and diazepam.Phenytoin can be used for status epilepticus(15 mg per kg loading dose followed bymaintenance dose). The best treatment foreclampsia, however, is delivery of the baby.

Sexually active women who do not wishto become pregnant should know that manyenzyme-inducing AEDs (carbamazepine,oxcarbazepine, phenytoin, primidone, andphenobarbital) can decrease the efficacy oforal contraceptives taken by women withepilepsy. This problem can partially be over-come by taking a contraceptive pill withhigher estrogen content. Barrier methods areparticularly useful adjuncts to oral contra-ception. Benzodiazepines, gabapentin, lam-otrigine, levetiracetam, tiagabine, and val-proate do not influence the efficacy of oralcontraceptives.

Status EpilepticusStatus epilepticus (SE) was defined and clas-sified in Chapter 2. Generalized convulsiveSE is one of the most life-threatening neuro-logic emergencies. Rapidly recurring or con-tinuous generalized convulsive seizureswithout return of consciousness betweenictal events are associated with irreversibleneuronal damage leading to substantial mor-bidity and mortality. As a common neurolog-ic emergency requiring rapid response fromthe frontline care provider, one importantfunction of neurologists in developing coun-tries is to work with the primary careproviders serving hospitals, clinics, andcasuality departments to establish appropri-ate algorithms of care to be followed whenpatients present in SE. An ideal algorithm isshown in Table 5.3, along with algorithmsfor treatment of nonconvulsive (complexpartial and absence) status, refractory status,and unilateral status. These algorithms willneed to be considerably modified from loca-tion to location depending on resourceavailability. Serial convulsive seizures, whichare frequent events with return of conscious-ness, are also a medical emergency and cansignify impending status, but treatment withIV phosphenytoin or phenytoin is preferredin order to preserve consciousness.

Standard texts typically describe the man-agement of SE to include ventilation, if

needed. Because ventilators are not general-ly available in developing regions outside ofacademic centers, the reality for most careproviders in these settings is the need tomanage SE without recourse to ventilation.This means treading a fine line betweenundertreating seizures (and therefore expos-ing the patient to long-term neurologicsequelae from SE-medicated brain damage)and extinction of seizures utilizing variousmedications that produce significant respira-tory depression (and, therefore, placing thepatient at risk of acute respiratory failureand/or aspiration).

When working with the primary health-care providers in your countries to developappropriate protocols for the managementof SE, keep in mind that healthcare person-nel will respond most effectively to emer-gencies when they have a few simpleinstructions on how to proceed.

Some general considerations when devel-oping algorithms for SE evaluation and treat-ment are listed below.

Initial Assessment and TreatmentEnsure patent airway and adequate ventila-tion; assess vital signs and complete a rapidphysical examination assessment for grosstrauma, pregnancy, and comorbidity. If thepatient is being treated for epilepsy, contin-ue the previous treatment, by gastric tube ifnecessary, unless there is evidence that themedications caused an increase in seizurefrequency.

If the patient is pregnant, eclampsiashould be considered. Special attentionshould be given to looking for other evi-dence of eclampsia (e.g., hypertension).Magnesium sulfate may be used as the long-acting antiseizure medication; 2 g given IM,then continuous administration of 2 g perhour in 5% dextrose. Because magnesiumsulfate is also a muscle relaxant, it can maskcontinuing status when EEG is not available;thus, deep tendon reflexes should be moni-tored and the rate decreased if reflexes can-not be elicited. Maximum of 40 g per 24hours. Rapid delivery of the infant should beconsidered.

Establish an IV line with normal saline. Ifthis cannot be achieved rapidly, treat thepatient with one of the rapid acting anti-


77

KEYPOINTS

n One important function ofneurologists in developingcountries is to work withthe primary care providersserving hospitals, clinics,and casuality departmentsto establish appropriatealgorithms of care to befollowed when patientspresent in SE.

n Because ventilators are notgenerally available indeveloping regions outsideof academic centers, thereality for most careproviders in these settingsis the need to manage SEwithout recourse toventilation.

n Healthcare personnel willrespond most effectively toemergencies when theyhave a few simpleinstructions on how toproceed.

n Because magnesium sulfateis also a muscle relaxant, itcan mask continuing statuswhen EEG is not available;thus, deep tendon reflexesshould be monitored.


78

Ideal Therapeutic Algorithms for Status EpilepticusTABLE 5.3

Generalized Convulsive SE

Indications: 5 minutes of continuous generalized convulsive seizures OR: 15 minutes of intermittent generalized convulsive seizureswithout full recovery of consciousness between seizures.

Treatment: First maintain airway and blood pressure, start an IV line, draw blood, and inject 50 ml of 50% DW and 100 mg thiamine. Take Hx of allergy if possible, then inject anticonvulsants:

IV fosphenytoin 20 mg/kg PE and IV midazolam 0.2 mg/kg bolus followed by 10 µg/kg/hr for 1 hr.

Unless: Hx of drug intolerance (e.g., allergy to phenytoin or benzodiazepine): replace by IV phenobarbital 20 mg/kg.

Unless: Acute intermittent porphyria: avoid P450 inducers, replace by NG gabapentin (if possible) or by IV valproate.

Unless: Hx of PME or JME: phenytoin/fosphenytoin harmful in PME, ineffective in JME. Replace by IV phenobarbital 20 mg/kg, or byIV valproate.

Unless: Tonic SE with Lennox-Gastaut syndrome: avoid benzodiazepines, replace by IV phenobarbital 20 mg/kg.

Unless: Focal SE without impairment of consciousness: IV treatment not indicated. Stop seizures by loading anticonvulsants PO orrectally (diastatic 15–20 mg).

Generalized Nonconvulsive SE

Indications: 15 minutes of continuous clinical or electrographic nonconvulsive seizures OR: two complex partial seizures withoutrecovery of function between seizures.

Treatment:

Complex partial SE: IV fosphenytoin 20 mg/kg and IV midazolam 0.2 mg/kg bolus followed by 10 µg/kg/hr for 1 hr. If SE is refractoryto those agents, bring fosphenytoin to 30 mg/kg and proceed with treatment as in CGSE.

Unless: Hx of drug intolerance: avoid specific antigen.

Unless: CPSE associated with PME or JME: IV midazolam and phenobarbital 20 mg/kg or IV valproate. Avoid hydantoins.

Unless: Acute intermittent porphyria: avoid all P450 inducers. If mild, NG gabapentin, otherwise IV valproate.

Absence SE: IV midazolam followed if necessary by IV valproate for childhood, juvenile, or atypical absence epilepsy, or epilepsywith myoclonic absences.

Unless: Hx of intolerance to those drugs: avoid specific antigen.

Unless: Lennox-Gastaut with tonic SE: omit benzodiazepines, go directly to IV valproate.

Unless: Associated with PME or JME: IV midazolam and IV phenobarbital 20 mg/kg or IV valproate. Avoid hydantoins.

Unless: Acute intermittent porphyria: avoid all P450 inducers. If mild, NG gabapentin, if severe IV valproate.

Electrical SE with impaired consciousness: IV fosphenytoin and midazolam.

Electrical SE without impairment of consciousness: no need for IV treatment. Load PO or rectally.

Electrical SE during sleep: No need for IV treatment.

Refractory SE

Convulsive or complex partial seizures persist at end of infusion:

First maximize anticonvulsant dosage: Intubate, use low dose pressors to maintain BP >90 if necessary.

Bring IV fosphenytoin up to 30 mg/kg PE. If still seizing 30 minutes after the end of the infusion:

Option 1: Depakote IV 30 mg/kg IV at 20 mg/min.

Option 2: Propofol 1.5 mg/kg followed by IV drip at 5-10 mg/kg/hr. If still seizing after 1 hr: CT scan to rule out structural sources ofincreased intracranial pressure and if none is found switch to

Option 3: Ketamine 1–1.5 mg/kg/hr (usually 100 mg). R/O increased ICP. If still seizing after 1 hr:

Option 4: Pentobarbital anesthesia: 15 mg/kg loading dose, maintenance ≥1.5 mg/kg/hr, adjust to obtain burst suppression pattern,stop IV every morning and monitor seizures, if they recur, commit to another 24 hours of anesthesia.

Unilateral SE

15 minutes of continuous clinical and/or EEG seizures: No need for IV treatment unless seizures spread.

Load PO, aim for high therapeutic/low toxic levels of multiple anticonvulsants.

Simple partial hemiconvulsions: The risk of generalization indicates treatment similar to generalized convulsive SE.

From Wasterlain C, and Treiman D (eds.). Status Epilepticus: Mechanisms and Management. Boston: MIT Press, 2004, with permission.

seizure medications listed below via rectal orintramuscular route.

Treat with a rapidly acting antiseizureagent. Two coadministered agents are rec-ommended in the ideal situation: IV fos-phenytoin because it is easier to give anddoes not cause tissue damage if the IV infil-trates, and midazolam because it has a short-er half-life than lorazepam or diazepam andallows more flexibility when used togetherwith fosphenytoin. These drugs are expen-sive, however, and not likely to be availablein developing world situations.Consequently, a more standard approach isto choose:

lorazepam 0.05 mg/kg IV or PR

OR

diazepam 0.2 mg/kg IV or 0.4 mg/kg PR

OR

paraldehyde 0.1 mg/kg IM (do not leavesolution in plastic syringe. Draw up onlywhat is needed and discard the syringeafter each dose.)

With an established IV, deliver 1 cc/kg ofIV glucose push. If available, consider IVadministration of 100 mg of thiamine. This isespecially critical during times of famineand/or if heavy, chronic alcohol use is sus-pected.

Send laboratory assessments for bloodsmear (in malarial regions), glucose, hemo-globin (if severe anemia is suspected), andany other available metabolic assessmentsthat seem reasonable.

If the patient continues to convulse 5 to 10minutes after initial treatment, repeat a doseof the rapidly acting antiseizure agent usedabove.

Initiate oxygen therapy if available, posi-tion patient to allow oral secretions to clearwithout aspiration, suction airway, and placebite block if needed.

If the patient continues to convulse 5 to 10minutes after the second dose of rapidly act-ing antiseizure medication.

Assess respiratory rate for a full minute.Count respirations. Do not estimate. If therespiratory rate is at least 8 breaths perminute for adults or 10 breaths per minutefor children, give the third dose of the rap-

idly acting antiseizure agent and prepare toadminister a long-acting agent. If the respira-tory rate is less than 8 breaths per minute inadults or 10 breaths per minute for children,proceed directly to the use of the long-act-ing agent without giving a third dose of theshort-acting agent. If the respiratory rate isseverely depressed (<4 breaths per minute),delay delivery of the long-acting agent for 30minutes and provide supplementary oxygenand respiratory support by manual baggingduring this time. If a ventilator is availableand status is refractory, general anesthesia isindicated, as in Table 5.3.

Long-acting antiseizure medications for SE:

phenytoin 15 mg/kg IV over four hours

It is critical to have a well-functioningperipheral IV site when utilizing thisagent.

If the IV site infiltrates tissues duringphenytoin administration, severenecrosis may result. Phenytoin shouldnever be administered IM.

OR

phenobarbital 15 mg/kg IV over fourhours

This may also be given IM in fourdivided doses simultaneously if IVaccess is problematic.

OR

If IV formulations for phenobarbital orphenytoin are not available, give a thirddose of the rapidly acting agent, place anasogastric tube, and administer a half ofthe loading dose of phenobarbital orphenytoin orally. Deliver the second halfthree hours later.

When the seizures are under controland/or maximally tolerated, therapy hasbeen initiated.

Conduct a more thorough history andexamination to attempt to discern the possi-ble cause of SE. Common causes of SE to beassessed include cerebral malaria, meningi-tis, alcohol withdrawal, abrupt discontinua-tion of antiseizure medications in a personknown to have epilepsy, and poisonings,especially with organophosphates. Status in


79

a febrile child poses a common diagnosticdilemma, particularly in malaria-endemicareas, as noted in the earlier section onfebrile seizures. In this situation, convulsivestatus must be regarded as a medical emer-gency and treated as discussed above.

If EEG is available and the patientremains unconscious, consider using EEG toassure the seizures have been controlled.

For infants and children, the administra-tion of rectal diazepam should first be con-sidered (0.5 mg/kg as a total dose, given in15 to 30 seconds) if no IV is available, par-ticularly outside the hospital facility. Thisdose may be repeated within 30 minutes ifnot effective. If IV is available, diazepam canbe given (0.5 mg/30 sec, until the seizurestops, not exceeding 0.5 mg/kg).Clonazepam is then administered (0.05mg/kg IV, followed by a slow infusion of 0.5mg/kg/6 hours). Repeat seizures requirephenytoin IV, 15 mg/kg. Blood level moni-toring is necessary to determine if furtheracute administration is appropriate.

For newborns, pyridoxine dependencyfirst needs to be ruled out by administeringpyridoxine 50 mg IV very slowly. Then, phe-nobarbital (0.5 mg/kg) is the best option.Phenytoin is indicated if repeat seizures arenot responding to phenobarbital.

The indication for artificial ventilation isvery restricted, both in infants and in chil-dren: In practice it is indicated in cases ofrespiratory failure due to the underlyingbrain damage, not in order to administer res-piratory-depressing compounds such as gen-eral anesthesia.

Aggravation of Seizures by AEDsCertain AEDs may worsen seizures whosephysiopathogenesis is negatively affected bythe action of the drug. Absence, myoclonic,and atonic generalized seizures may worsenwith AEDs that interfere with inward sodiumcurrents, usually prescribed for treatment ofpartial seizures, including carbamazepine,oxcarbazepine, phenytoin, and phenobarbi-tal, and also with GABAergic compoundssuch as vigabatrin and gabapentin.Furthermore, myoclonic seizures may beprovoked “de novo” by some of these drugs,even in patients with partial epilepsies. Thishas been already documented for carba-

mazepine and oxcarbazepine. Toxic dosesof these drugs can also exacerbate partialand secondarily generalized seizures. Spike-and-wave activity during sleep and somemyoclonus can be worsened by lamotrigine,and infantile spasms are accentuated by car-bamazepine, phenytoin, and phenobarbital.

AED-related seizure worsening is not acommon occurrence, but should be consid-ered when seizure frequency actuallyincreases following the introduction of agiven AED. This problem assumes a greaterrelevance in developing countries wheremost patients depend on AED dispensationthrough the public health system. Notuncommonly, a shortage of one type of AEDwill lead to substitution by another drug,which may occasionally worsen the clinicalpicture by aggravating or leading to de novoseizures.

Pharmacokinetic Considerations in Pediatric and Geriatric Age GroupEpilepsy management at extremes of ageneeds special attention. Drug trials usuallyhave excluded these groups. Some AEDsaffect children and adults differently. Forexample, phenobarbital can cause youngerchildren to become hyperactive, but causesedation in older patients. The increasedhalf-life of most AEDs in the immature brainwas discussed earlier in this chapter. Withthe onset of puberty, the drug-metabolizingpatterns resemble that of adults. AED treat-ment in children must be followed moreclosely than in adults, with estimation ofserum levels when indicated and available.

The general principles of AED treatmentfor the elderly are similar to those for otheradults, but some differences in the pharma-cokinetics need to be remembered whentreating the elderly. Older patients are at riskof having toxic AED levels because ofreduced hepatic metabolism and reducedrenal clearance of certain AEDs. This popu-lation is also at greater susceptibility to cog-nitive and other neurotoxic side effects dueto concurrent illnesses like Alzheimer’s dis-ease. Reduced protein binding and hypoal-buminemia can lead to increased free frac-tion of highly bound drugs. Most of the eld-erly population will be on other medicationsfor various medical problems, and drug


80

KEYPOINTS

n Status in a febrile childposes a common diagnosticdilemma, particularly inmalaria-endemic areas. Inthis situation, convulsivestatus must be regarded asa medical emergency andtreated as discussed above.

interactions along with the basic medicalconditions become a very important man-agement issue.

AED ProphylaxisSevere head trauma, particularly associatedwith a depressed skull fracture, cerebral con-tusion, or intracerebral bleeding, as well asbrain surgery, particularly involving vascularmalformations and bleeding, are associatedwith a high risk of epileptic seizures andAED prophylaxis, particularly with pheny-toin, has been recommended. However,although this drug has been shown to beeffective against early post-traumatic/postop-erative seizures, it does not prevent the lateseizure development of post-traumaticepilepsy. Consequently, in such patients whoare at high risk for early epileptic seizures,phenytoin can be given for a few weeks toreduce the chance of ictal events that mightcompromise convalescence, but there is nojustification for prolonged prophylaxis over 1or 2 years to prevent the development of anepileptic condition.

CONCLUSIONSThe principal treatment of epilepsy is AEDs,and approaches to pharmacotherapy in thedeveloping world are largely dependent oncost and availability. The threshold for

beginning treatment after a single seizureshould be high, in order to avoid unneces-sary financial burden. When treatment isnecessary, the older, less expensive drugs, inmonotherapy, are generally as effective asthe newer ones, and both phenobarbital andphenytoin can be initiated with a loadingdose if necessary. Most people with epilep-sy have seizures that will be easy to treat,and very low doses of a single AED may suf-fice. For difficult-to-control seizures, sophis-ticated diagnostic and therapeutic approach-es available only at major medical centersmay be necessary. Where such facilities areabsent, or when seizures persist despite thebest available treatment, management con-sists of balancing seizure control with sideeffects and supportive care. This requires anunderstanding of the pharmacokinetics ofAEDs and recognition of their adverseeffects. When seizures are controlled bypharmacotherapy for several years, it is par-ticularly advantageous for people in devel-oping countries to determine whether it ispossible to discontinue treatment, again toavoid unnecessary financial burden. Febrileseizures, particularly in malaria-endemicregions, pregnancy, SE, and pharmacokinet-ic variations at the extremes of age requirespecialized approaches to treatment.


81

KEYPOINTS

n After head trauma, there isno justification forprolonged prophylaxis over1 or 2 years to prevent thedevelopment of anepileptic condition.

CITATIONS AND RECOMMENDED READINGBerg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology

1994;44:601–608.

This literature review found the risk of seizure relapse to be 0.25 at 1 year and 0.29 at 2 years after AED with-drawal. Adult and adolescent onset, remote symptomatic seizures, and an abnormal EEG increased recurrencerisk.

Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis.Neurology 2002;59:1730–1734.

This study of people in Ecuador with acute seizures due to neurocysticercosis found a low rate of late seizurerecurrence when cysts resolved on CT, but slightly greater than 50% recurrence with persistence of active cysts. Theuse of antihelminthics did not influence seizure recurrence.

Engel J Jr. Seizures and epilepsy. Philadelphia: F. A. Davis, 1989.

This comprehensive but concise textbook is the source of Figure 1.

Garcia HH, Pretell EJ, Gilman RH, et al. A trial of antiparasitic treatment to reduce the rate of seizures due to cere-bral cysticercosis. N Engl J Med 2004;350:249–258.

A recent study found that antiparasitic treatment reduced the late occurrence of generalized seizures, but not par-tial seizures.

Hauser WA, Rich SS, Lee JRJ, Annegers JF, Andreson VE. Risk of recurrent seizures after two unprovoked seizures.N Engl J Med 1998;338:429–434.

This study reports that the risk of recurrence after two unprovoked seizures is over twice the risk after a singleunprovoked seizure, increasing the justification for treatment after a second seizure.

Hirtz D, Berg A, Bettis D, et al. Practice Parameter: Treatment of the child with a first unprovoked seizure.

Report of the Quality Standards Subcommittee of the American Academy of Neurology and the PracticeCommittee of the Child Neurology Society. Neurology 2003;60:166–175.

These guidelines of the American Academy of Neurology conclude that the risk of significant trauma or death fol-lowing a recurrent seizure is low, side effects of AED are relatively common, and the use of chronic medicationin children is often attended by psychosocial morbidity.

Maguire JH. Tapeworms and seizures—Treatment and prevention. N Engl J Med 2004;350:215–217.

This review discusses the pathophysiology of neurocycticercosis and ways to manage it from a public health per-spective.

Sirven JI, Sperling M, Wingerchuk DM. Early versus late antiepileptic drug withdrawal for people with epilepsy inremission. Cochrane Database Syst Rev 2001;(3):CD001902.

This recent literature review found a greater risk of seizure recurrence in children with AED withdrawal earlierthan 2 seizure free years if seizures were partial and the EEG was abnormal.

Tennison M, Greenwood R, Lewis D, Thorn M. Discontinuing antiepileptic drugs in children with epilepsy: a com-parison of a 6-week and a 9-month taper period. N Engl J Med 1994; 330:1407–1410.

In this study, seizures recurred in 40% of children. Risk of seizure recurrence was unrelated to the length of thetapering and the length of seizure freedom, but was increased by the presence of mental retardation and persist-ence of epileptiform spikes.

Wasterlain C, Treiman D, (eds.) Status Epilepticus: Mechanisms and Management. Boston: MIT Press, 2004.

This recent textbook on status epilepticus is the source of the ideal protocol for treatment of status presented here.


82

83

CHAPTER 6

ANTIEPILEPTIC DRUGS

KEYPOINTS

n While planning treatmentprograms for people withepilepsy in developingcountries, it is important toensure that these aresimple, cost-effective, andalso take into account thetraditional views andattitudes toward epilepsy.

n PB can be used for allseizure types exceptabsence seizures andspasms, as it is known toworsen absences. Inaddition to its beingeffective in most seizuretypes, it is still the cheapestAED and is available almostuniversally.

Most people with newly diagnosed andchronic epilepsy in the developed countrieswill be treated with one or anotherantiepileptic drug (AED) and followed up atregular intervals. AEDs are the mainstay inthe long-term management of people withepilepsy. The usual practice of initiating treat-ment with AEDs in the developed countriesdoes not necessarily apply in the developingnations, especially among the people withepilepsy living in rural and far-flung areas.

The neurologists responsible for treatingpeople with epilepsy in developing coun-tries certainly need to know about the state-of-the-art approaches to the management ofindividual cases of epilepsy. On the otherhand, it is equally important for them to beable to modify the ideal treatment schedulesto suit their own socioeconomic milieu.While planning treatment programs for peo-ple with epilepsy in developing countries, itis important to ensure that these are simple,cost-effective, and also take into account thetraditional views and attitudes towardepilepsy. Further, the treatment programsneed to be tailored as per the regulationsand resources of an individual country sothat the AEDs recommended are actuallyavailable to the population with provisionsthat allow facilities for long-term follow-up,counseling, and education about the role ofearly treatment of people with epilepsy.

This chapter reviews the important aspectsof currently available conventional and newAEDs, and the basic principles of choosingAEDs, the most suitable AED for a specificcondition with contingency solutions, andexamples of a few typical situations.

MECHANISMS OF ACTION OF AEDsMost AEDs work through different, multiplemechanisms while the exact mechanism of

action of a few of the drugs is not known.Some AEDs act on sodium channels, otherspotentiate the effect of g-aminobutiric acid(GABA—a naturally occurring inhibitoryneurotransmitter), while AEDs that are effec-tive against absence seizures act by inhibit-ing calcium channels. A few other AEDs actby antagonizing the effect of the excitatoryamino acid glutamate on one or more of itsreceptors.

CURRENTLY AVAILABLE AEDs

Drugs Commonly Used in DevelopingCountries (Conventional or First-LineDrugs)

Phenobarbital (PB)PB is the oldest of the currently availableAEDs (it was first used in 1912) and eventoday remains the most commonly pre-scribed AED in terms of volume. It is aremarkable and effective drug for partial andgeneralized tonic-clonic seizures. PB can beused for all seizure types except absenceseizures and spasms, as it is known to wors-en absences. In addition to its being effec-tive in most seizure types, it is still thecheapest AED and is available almost uni-versally.

Because PB is still a commonly used AEDand very often the first AED to be used inmany developing countries, knowledgeabout its actions and interactions is neces-sary for the neurologists and other physi-cians using this drug. PB acts not only bylimiting the spread of seizure activity, butalso raises the seizure threshold. It has beenshown to have actions on the sodium, potas-sium, and calcium channels, GABA recep-tors, and even modify the glutamateexcitability. It has the longest half-life com-

pared to any of the available AEDs exceptzonisamide, and has the advantage of beingavailable as oral preparation for routine use(tablet and elixir) and intramuscular andintravenous injection for use in emergencysituations. When used orally, it can be con-veniently given once daily, usually at bedtime, since that can, to some extent, reducethe impact of its sedative side effect.

PB has a number of drug interactions thatare of particular importance in developingcountries. Phenytoin, valproate, and felba-mate inhibit metabolism of PB, causing anincrease in its levels. Rifampin, a commonlyused antitubercular drug, is a powerfulenzyme inducer and lowers the PB levels. Indeveloping countries, many patients haveepilepsy secondary to tuberculosis of thebrain or may have concomitant extra–centralnervous system tuberculosis and suchpatients receive treatment with rifampicin.PB is also a potent hepatic enzyme inducerand can increase the metabolism of manycommonly used drugs like estrogen-contain-ing oral contraceptives, steroids, and amino-phylline. The metabolism of the other com-monly used AEDs like carbamazepine, val-proate, diazepam, and clonazepam can alsobe enhanced by the concomitant use of PB.Theoretically, there are many possibilities,but in clinical practice, the drug interactionsof PB in a given individual are perhaps notthat severe and, in the general population,not that commonly seen because these areoften a result of a combined effect of manyinhibitory and excitatory actions.

Although PB has been extensively used inclinical practice, few studies compare its effi-cacy and side effects with the other com-monly used AEDs. In a multicenter double-blind trial, the overall efficacy for the controlof partial and secondarily generalizedseizures with PB was equal to that withphenytoin and carbamazepine. Although PBhas been out of favor in many developedcountries, mainly due to its reported sideeffects, the trial interestingly found PB to beassociated with the lowest incidence ofmotor and gastrointestinal side effects andidiosyncratic reactions. A few other open-label studies have reported comparable effi-cacy and side effects of PB with valproateand carbamazepine. In developing coun-

tries, phenobarbital should still be seriouslyconsidered as a first-line AED due to its lowcost and efficacy.

The most common side effects of PB areimpairment of cognition and alteration ofbehavior, particularly in children. It should beused with caution in children because of itspotential for paradoxical excitement andhyperactivity. Being a barbiturate, PB cancause physical dependence, and abrupt cessa-tion of the drug can result in withdrawalseizures. Occasionally, children born to moth-ers receiving PB during pregnancy can alsosuffer from withdrawal seizures during theneonatal period. Chronic intake of PB hasbeen associated with coarsening of features,Dupuytren’s contracture, osteomalacia andrickets, folate deficiency, and rarely a mega-loblastic anemia. PB has a relatively good safe-ty profile with regard to idiosyncratic reactions.Generalized hypersensitivity is rare, but mayinclude exfoliative dermatitis. Occasionally,hepatitis that is believed to be immunological-ly mediated has also been reported.

Carbamazepine (CBZ)CBZ is widely preferred for generalizedtonic-clonic and partial (with or without sec-ondarily generalized) seizures. It is ineffec-tive against, and may worsen, absence andmyoclonic seizures. Its efficacy in partial andtonic-clonic seizures is equal to that of othercommonly used AEDs like phenytoin (PHT)and phenobarbital (PB), but it is less likelyto cause sedation than PB and does notcause cosmetic side effects like PHT. CBZ isuseful in children and adults and needs tobe given in divided doses. It is known toworsen absences and myoclonic jerks insome patients, and a higher incidence ofspina bifida has been reported among chil-dren born to mothers taking CBZ duringpregnancy. CBZ is available as tablets of var-ious strengths and as syrup in most coun-tries. Sustained-release preparations are alsoavailable in many countries, but no parenter-al preparations are currently available.

Phenytoin (PHT)PHT is still commonly used for all seizuretypes except generalized absence andmyoclonic seizures and spasms and is aneffective AED for all ages. Oral preparations


84

KEYPOINTS

n In developing countries,phenobarbital should stillbe seriously considered as afirst-line AED due to its lowcost and efficacy.

are of limited value during the first fewmonths of life when bioavailability is verypoor. It is best avoided among youngwomen because of its cosmetic side effects.There is no definite evidence that PHT is anymore teratogenic than other AEDs. It is not avery easy drug to use because of its nonlin-ear dose and serum level relationship and anarrow therapeutic range. PHT is availableas tablets and capsules of various strengths,as syrup, and as intravenous injection. Itshould not be given as intramuscular injec-tion because of its local toxicity, but a moreexpensive preparation, fosphenytoin, can begiven intramuscularly.

Sodium Valproate (VPA)VPA is most frequently used for generalizedabsences, myoclonic jerks, and also general-ized tonic-clonic seizures. Since this drug iseffective in controlling all seizure types seenin the idiopathic generalized epilepsies(IGEs), it has emerged as the first-line drugfor most of the IGEs. It is also effective inother seizure types, but needs to be usedwith caution among very young childrendue its hepatic toxicity. Hepatotoxicity maybe as much as 100 times greater in infants asin adults. Among the conventional AEDs,VPA has been reported to have the most ter-atogenic potential. It is usually available astablets of various strengths, as elixir, and asintravenous injections and microgranules insome countries.

Primidone (PRM)After oral consumption, PRM is rapidly bro-ken into its two metabolites, phenobarbital(PB) and phenylethylmalonamide (PEMA)—both have antiepileptic activity in addition tothat of PRM. Since the predominant effect isdue to PB, both the antiepileptic and sideeffects of PRM are similar to those of PB.PRM is not the first choice drug for anyseizure type. It is associated with a high inci-dence of toxicity at the time of initiation,causing significant sedation, ataxia, dizzi-ness, and depression. Chronic therapy isassociated with impaired cognition and psy-chiatric problems in many patients; the latteris not seen with PB. It is available as tabletsand has been used for all seizure typesexcept absence seizures.

Ethosuximide (ESM)ESM has very limited use because it is effec-tive only for typical absence seizures. It isavailable as a capsule and as a suspension.This drug does not have any serious sideeffects. ESM is not available in many coun-tries.

Drugs Less Commonly Used inDeveloping Countries (New AEDs)

Clobazam (CLB)This drug is related to diazepam and is usedmainly as add-on therapy for partial as wellas generalized seizures. It is rarely usedalone and tolerance to the antiepilepticeffect has been reported, but many patientsdo continue to have benefit with long-termtherapy. It is available as tablets of differentstrengths.

Clonazepam (CZP)This drug is mostly used as add-on therapyfor atypical absence, atonic, and myoclonicseizures. It is also effective in typicalabsence seizures, but is rarely used alonebecause of its sedative and cognitive sideeffects and development of tolerance to theantiepileptic effect. It is available as tabletsof different strengths.

Felbamate (FBM)Felbamate is effective in the treatment ofpartial and secondarily generalized tonic-clonic seizures and is also useful for theLennox-Gastaut syndrome. Felbamate hasbeen associated with a high risk of potential-ly fatal bone marrow and liver failure,restricting its use to patients in whom thebenefit is expected to be greater than therisk, particularly those with frequent dropattacks. It is available as tablets and as anelixir for children.

Gabapentin (GBP)GBP is chemically related to GABA, but itsmechanism of action remains controversial.It is effective for partial and secondarily gen-eralized seizures, but is not as effective forprimary generalized seizures. GBP has mini-mal side effects and no significant druginteractions. These properties make it usefulamong patients on multiple other drugs, par-

Antiepileptic Drugs

85

ticularly the elderly. Because GBP is notmetabolized in the liver and depends on thekidneys for elimination, it will accumulate inpatients with chronic renal failure. It is avail-able as capsules of different strengths.

Lamotrigine (LTG)Lamotrigine is commonly used in adults forpartial and secondarily generalized seizures.It has also been approved for use in childrenwith Lennox-Gastaut syndrome. LTG alsoappears to be effective for generalizedseizures including absence and atonicseizures and juvenile myoclonic epilepsy.LTG can cause skin rash, especially inpatients concurrently taking VPA. Very slowtitration, particularly when used with VPA,reduces the risk of rash. Occasionally, therash may be life-threatening (Stevens-Johnson syndrome). It is available as tabletsof various strengths.

Levetiracetam (LEV)LEV, a piracetam analogue, is unique amongthe newer AEDs because it is effective start-ing with the initial dose. Its mechanism ofaction appears to be different from that ofother AEDs and, like GBP, its tolerability andpharmacokinetics are very attractive, withminimum drug interactions. Sedation andbehavioral problems are the most commonside effects. It has mostly been used as add-on therapy for partial and secondarily gener-alized seizures and photosensitive epilepsy.

Oxcarbazepine (OXC)OXC is chemically related to CBZ and isequally effective in controlling partial andgeneralized tonic-clonic seizures. Its sideeffect profile is better than CBZ and it is bet-ter tolerated. It has recently become avail-able in the form of tablets in many countries.

Tiagabine (TGB)TGB is a safe and well tolerated drug that isuseful for treating partial and secondarilygeneralized seizures. The experience withthis drug is limited. There are anecdotalreports of precipitating absence status inidiopathic generalized epilepsy.

Topiramate (TPM)TPM is used as add-on therapy for the treat-

ment of adults with partial onset seizures,children with partial seizures, Lennox-Gastaut syndrome, and both adults and chil-dren with primary generalized tonic-clonicseizures. Side effects include sedation, word-finding difficulties, weight loss, parasthesias,and renal stones. TPM is available as tabletsof various strengths. It has a bitter taste, sothe tablets should not be broken.

Vigabatrin (VGB)VGB has mainly been used to treat complexpartial and secondarily generalized tonic-clonic seizures that do not respond to thefirst-line drugs. It has also been recommend-ed as a first-line drug for the treatment ofinfantile spasms. Because it is effective ininfants and can be rapidly titrated, VGB isuseful in partial seizures in infancy. Recentreports of visual field deficits in 40% ofpatients taking VGB have limited its use forchronic treatment.

Zonisamide (ZNS)ZNS has been used to treat all seizure typesincluding atonic seizures and certain typesof progressive myoclonic epilepsy. Commonside effects include anorexia, dizziness, som-nolence, confusion, poor concentration, andrenal stones.

The most commonly accepted mecha-nism(s) of action and some important fea-tures of AEDs are summarized in Table 6.1.

BASIC PRINCIPLES FOR CHOOSING AEDsThe decision to initiate treatment with AEDsis a unique one because of the impact it canhave with regard to self confidence of theaffected individual, education, employment,marriage, and other societal responsibilitiesand obligations. The benefits of therapy areobvious and include the reduced risk forfuture seizures and potential injury and evendeath, besides the psychosocial benefits tothe individual and family members of theperson not having seizures. Treatment withAEDs has potential shortcomings in the formof side effects of drugs, cost, inconvenience,and the societal stigma. Further, the sideeffects of chronic long-term therapy areobvious only after many years of treatmentand many times are unfortunately irre-versible. The decision to treat should always


86

Antiepileptic Drugs

87

Important Pharmaco-Kinetic Features of the First Line and Second Line AEDsTABLE 6.1

Daily maintenance

Mechanism(s) dose range Dosage interval Drug of action in adults (mg) (times per day) Important side effects

Carbamazepine 1 400–2400 3–4 Dizziness, ataxia, water retention, skin rash, seizure increasein infants and children

Clobazam 1,2 10–40 1–2 Tiredness, unsteadiness, irritability, tolerance (reduction of itsantiepileptic activity)

Clonazepam 1,2 2–8 1–3 Drowsiness, ataxia, skin rash

Ethosuximide 3 500–2000 1–2 Nausea, vomiting, loss of appetite, weight loss, bone marrowdepression

Felbamate 5 1800–4800 3–4 Decreased appetite, weight loss, insomnia, potentially fatal bone marrow or liver failure

Gabapentin 8 1200–4800 3–4 Tiredness, dizziness, weight gain, irritability

Lamotrigine 1,4 100–800* 1–2 Dizziness, unsteadiness, rash (occasionally Stevens-Johnson syndrome)

Levetiracetam 8 1000–4000 2–3 Somnolence, asthenia, dizziness, psychosis

Oxcarbazepine 1 900–2700 3–4 Tiredness, dizziness, headache, unsteadiness, rash, water retention

Phenobarbital 1,2 60–240 1 Tiredness, depression, memory problems, impotence, hyperactivity (in children), skin rash

Phenytoin 1 100–700 1–2 Tiredness, dizziness, memory problems, gum hypertrophy, hirsutism, acne, facial coarsening, skin rash, decreased bonedensity, cerebellar atrophy

Primidone 1,2 250–2500 3–4 Tiredness, depression, memory problems, psychosis,impotence, hyperactivity (in children), skin rash

Tiagabine 1,6 20–60 2–4 Dizziness, light-headedness, slow response

Topiramate 1,2,4,7 100–1000 2 Drowsiness, dizziness, impaired memory, weight loss, renalstones, seizure worsening, word–finding difficulty

Valproate 1,2 500–3000 3–4 Anorexia, nausea, liver damage, weight gain, hair loss, polycystic ovarian disease, thrombocytopenia

Vigabatrin 6 2000–7000 1–2 Drowsiness, fatigue, dizziness, weight gain, hyperactivity, visual field deficits

Zonisamide 1,3 400–600 1–2 Dizziness, anorexia, memory problems, weight loss, renalstones, skin rash

1: Sodium currents

2: g-aminobutyric acid-A (GABA-A) receptor currents

3: T-calcium currents

4: Glutamate and/or AMPA/kainate receptor antagonist

5: Interaction at N-methyl-D-aspartate (NMDA) receptor

6: Inhibitor of GABA transaminase (GABA-T)/blocking the reuptake of GABA

7: Calcium current inhibitor

8: Unknown

*300-800 without valproate, 100–400 with valproate

be individualized, keeping in mind the totalpicture of an individual’s problem. The ben-efits of therapy should be weighed againstthe potential harmful effects.

It is most useful to formulate a treatmentplan at the time of each patient’s initial eval-uation. In order to be successful, the treat-ment plan should allow for flexibility in viewof either a change in the clinical situation orthe availability of the first choice AED. Theclinicians need to be fully conversant withthe ideal drug for a condition and should beready with contingency or alternative plans,if the ideal drugs are not available.

Symptomatic Focal EpilepsiesIdeal situation: Carbamazepine is generallythe drug of choice for symptomatic focalepilepsies in the industrialized world, andthe extended release form is preferredbecause twice-a-day dosing is possible.Although phenytoin is as effective and canbe given once a day, it is less often pre-scribed because of the cosmetic side effectsand saturation kinetics. Oxcarbazepine issimilar to carbamazepine and is beingincreasingly used as a first-line drug. Otherdrugs that are commonly tried if the first-choice drug fails, in no particular order,include valproate, lamotrigine, topiramate,levetiracetam, and zonisamide. Because effi-cacies are similar, decisions are based moreon side effect profiles and dosage regimensacceptable to each individual patient.Tiagabine is less commonly used, and drugsthat are sedating, such as phenobarbital,primidone, and the benzodiazepines, areusually avoided. Felbamate and vigabatrinare extremely effective antiepileptic drugswith serious toxicity, so they are generallyconsidered a last resort, to be used with fullpatient disclosure. Not all of these drugs areavailable in every country, and regulationsvary with respect to use as monotherapy, oras adjunctive medications for some of thenewer drugs.

Contingency situation: Very often, idealtreatment schedules cannot be practiced indeveloping countries due to the poor avail-ability of drugs and the costs involved.Therefore, flexibility on the part of the treat-ing physician is important for planning con-

tingency alternatives. In developing coun-tries with limited resources, an alternativecontingency strategy (though not ideal)could be to begin with phenobarbital, and ifthat fails, go on to use phenytoin, carba-mazepine, or valproate. While commonlyused AEDs (PHT, PB, CBZ, and VPA) havebeen shown to have differential efficacy incomparative studies, there is no conclusiveevidence that these and other AEDs havedifferential efficacy against partial seizuresarising from different parts of the brain.

PB is no longer used as a first-line drugby most people in developed countries dueto its adverse cognitive and behavioraleffects, but may be the drug of choice fordeveloping countries, especially for patientswho are struggling for subsistence. Thereare real-life situations in developing coun-tries where the cost of AEDs becomes themost important adverse effect. Very often theissue at stake is whether to treat epilepsy orprovide food and clean water. Clinicians indeveloping countries could follow the sim-ple strategy to initiate treatment with PB andbe ready to change to other AEDs in case ofdisabling adverse effects with PB.

Idiopathic Generalized EpilepsiesIdeal situation: Valproate is commonly pre-ferred as the drug of choice for patients withprimary generalized epilepsies that do, orcan, manifest with multiple seizure types,because it is effective against generalizedtonic-clonic seizures, absences, andmyoclonic jerks. Other wide-spectrumantiepileptic drugs that can be used to con-trol all seizure types with a single medicationinclude lamotrigine, levetiracetam, zon-isamide, and topiramate. When these drugsfail, polytherapy is necessary for patientswho have generalized tonic-clonic seizuresand either absences or myoclonic jerks.Absences can be treated with ethosuximide,and myoclonic jerks with clonazepam and,rarely, primidone. Care must be taken whencombining medications to avoid pharmacoki-netic and pharmacodynamic interactions thatincrease the likelihood of adverse events.

Contingency situation: Even while treatingIGEs, PB could have an important role as thealternative drug for treatment of different


88

KEYPOINTS

n Very often, ideal treatmentschedules cannot bepracticed in developingcountries due to the pooravailability of drugs andthe costs involved.Therefore, flexibility on thepart of the treatingphysician is important forplanning contingencyalternatives.

n There are real-lifesituations in developingcountries where the cost ofAEDs becomes the mostimportant adverse effect.

seizures associated with IGEs in developingcountries, since this may be the only avail-able AED. Additionally, while CBZ is wellknown to worsen myoclonic jerks, the useof PHT as a first-line AED in IGEs (as in par-tial epilepsies) is associated with problemsof its adverse effects. Further, both CBZ andPHT are not effective against absenceseizures.

Idiopathic Focal EpilepsiesIdeal situation: These conditions, typified bybenign childhood epilepsy with centrotem-poral spikes, are often so mild that no treat-ment is necessary. When seizures are recur-rent, particularly during the day, theapproach to treatment is essentially the sameas that for symptomatic focal epilepsies.Here the clinicians need to be aware of thepossibility of seizure worsening due to CBZamong patients with benign childhoodepilepsy with centrotemporal spikes.Because CBZ can precipitate continuousspike-and-wave during slow sleep, it can bea problem in situations where EEG is notavailable. Under ideal conditions, VPA ispossibly the drug of choice even for treatingseizures seen in most of the benign focalepilepsies, but the other AEDs are also aseffective. Very often, AEDs in low dose areeffective for the treatment of idiopathicchildhood focal epilepsies.

Contingency situation: The treatment ofidiopathic focal epilepsies in developingcountries also has to be tailored on the pat-tern described above. When a decision totreat is arrived at, most such epilepsieswould respond to any of the commonlyused AEDs. The AED used in developingcountries would largely depend on its avail-ability and affordability.

Symptomatic Generalized EpilepsiesIdeal situation: Patients with diffuse braindamage and epileptic seizures usually expe-rience multiple seizure types, including gen-eralized tonic-clonic seizures, atypicalabsences, myoclonic jerks, and drop attacks.The Lennox-Gastaut syndrome typifies thisgroup of conditions. When multiple seizuretypes occur, valproate is often the drug ofchoice, but commonly polytherapy is neces-

sary, and often seizures cannot be complete-ly controlled. Drop attacks are particularlyrefractory to pharmacotherapy, although fel-bamate, lamotrigine, topiramate, and zon-isamide may be of some benefit. Becausethese patients are almost always intellectual-ly compromised, drugs that further impaircognitive function, like the barbiturates andbenzodiazepines, should be avoided.

Contingency situation: As pointed out earli-er, these syndromes constitute the difficult-to-treat epilepsies even under optimal situa-tions. While treating such patients, theefforts of the clinicians in developing coun-tries are hampered not only by the refracto-ry nature of the seizures but also by the lim-ited availability of AEDs. The choice of AEDswhile treating such patients in developingcountries will be limited to those drugs thatare available, and many times, the drugsused are not necessarily the ideal ones.Rectal diazepam (if available) could prove tobe a very handy drug in case of recurrentand breakthrough seizures and even manag-ing status epilepticus before the patient canbe shifted to a hospital or even at a hospitalwith limited facilities.

Special SyndromesIdeal situation: Management of febrileseizures is a topic by itself and is discussedelsewhere (Chapter 5). The treatment ofneonatal seizures is usually directed primari-ly at the cause, and that usually requiresextensive investigations. Hypoglycemia,hypocalcemia, hypomagnesemia, and pyri-doxine deficiency need to be treated ener-getically with specific replacements. Whenthe decision to use AEDs is arrived at, PB isgenerally the drug of choice, with PHTbeing the second-line drug. A loading doseis usually given, followed by a maintenancedose for variable periods. The treatment ofchoice for infantile spasms in the industrial-ized world is ACTH or vigabatrin, althoughsome success has also been achieved withVPA. Lennox-Gastaut syndrome is anothercondition with seizures that are usually notresponsive to treatment. VPA and benzodi-azepines (clobazam and clonazepam) arethe commonly used AEDs that are effectiveagainst different seizure types. ACTH and

Antiepileptic Drugs

89

corticosteroids have also been used withlimited success. Trials with lamotrigine, fel-bamate, and topiramate have all shown areduction in seizure frequency. Ketogenicdiet has also been shown to be effective,especially in young children.

Contingency situation: In developing coun-tries, the management of epilepsy syn-dromes mentioned above largely dependson the availability of AEDs. While managingpatients with resistant seizures, there is atendency to increase the dose of an individ-ual drug and also to increase the number ofdrugs. Such high-dose polytherapy withAEDs can often result in worsening ofseizures, especially absences and tonicseizures. PB and other benzodiazepines canadditionally worsen the overactivity andaggressive behavior that is commonly asso-ciated with many of these syndromes, partic-ularly those secondary to a brain insult.Rectal diazepam, when available, can bevery helpful in emergency situations.

ANTIEPILEPTIC DRUG CHOICE FOR SPECIFIC CONDITIONSThe guidelines for choosing AEDs and initi-ating treatment are summarized in Tables 6.2and 6.3, while Table 6.4 lists the commonlyused first- and second-line AEDs for differ-ent seizure types. The details of practicalapproaches to treatment of seizures andepilepsy are listed in Chapter 5.

DRUG INTERACTIONS AND OTHER ASPECTS OF PARTICULAR CONCERN IN DEVELOPING COUNTRIESMany developing countries are still endemicareas for malaria, HIV infection, tuberculo-sis, and parasites. They have, at the sametime, the highest rates of incidence andprevalence epilepsy rates, mainly due tomany of the secondary (and often preventa-ble) causes of epilepsy. Many situations inthe management of these disorders candirectly or indirectly either precipitateseizures for the first time or result in theworsening of pre-existing seizures.

The increase of the incidence of tubercu-losis has led to the increased use of isoniazid(INH). Acute intoxication by isoniazid isknown to cause seizures, especially in

infants, accompanied by lactic acidosis,coma, and even death. This antituberculardrug raises the steady-state serum levels ofprimidone and phenytoin. Isoniazid-inducedvalproic-acid toxicity, or vice versa, has alsobeen reported. For the same reasons, one


90

KEYPOINTS

n In developing countries,the management ofepilepsy syndromesmentioned above largelydepends on the availabilityof AEDs. While managingpatients with resistantseizures, there is atendency to increase thedose of an individual drugand also to increase thenumber of drugs. Suchhigh-dose polytherapy withAEDs can often result inworsening of seizures,especially absences andtonic seizures.

Guidelines for Choosingand Initiating Treatmentwith AEDs among Patientswith Newly DiagnosedEpilepsy

TABLE 6.2

1. Establish the seizure type(s) and,when possible, syndrome and etiologywith the help of a good clinical evalu-ation and relevant investigations.

2. Start treatment with the first-choicesingle AED (Table 6.4). Start with alow dose and increase gradually tothe acceptable maintenance dose.

3. If seizures are not controlled, increasethe dose and check serum levels ofthe drug (if facility is available).

4. If seizures are controlled, continuethe AED in the minimum effectivedose. Almost two-thirds of patientswill have good seizure control with asingle appropriate AED.

5. In case of poor seizure control, tryanother drug (alternative monothera-py). First introduce the second drugwith gradual dose increments until atherapeutic dose is reached, and thenslowly taper off the first drug thathad failed to control the seizures.

6. Refer the patient to a specialized cen-ter if seizures are not controlled withthe second drug regimen. Infants andsmall children should also be referredif there is pre-existing developmentaldelay, abnormal neurologic examina-tion, or the patient does not exhibitfeatures of a recognizable syndrome.

The common reasons for poor seizurecontrol among patients with newly diag-nosed epilepsy are: incorrect diagnosis(either missing an epilepsy syndrome orpatient has nonepileptic seizures), poordrug compliance, poor bioavailability ofcheaper ‘generic drugs’, failure toincrease dose to the recommended levelin the absence of side effects, and failureto introduce drug slowly, resulting inside effects and poor AED compliance.

needs to be careful when using isoniazidwith carbamazepine and do a regular clini-cal and biological surveillance. Pyridoxinegiven early is the only effective antidote, ina dose equivalent to the amount of INHingested. Rifampicin interacts with pheny-toin and decreases the serum level of pheny-toin by increasing its hepatic metabolism.Pyrazinamide is hepatotoxic and requiresbiological surveillance before and duringtreatment with AEDs.

New-onset seizures are a frequent mani-festation of central nervous system disorderamong patients infected with humanimmunodeficiency virus (HIV). Seizures aremore common in advanced stages of the dis-

ease, although they may occur early in thecourse of illness. The majority of patientshave generalized seizures, and status epilep-ticus is not uncommon because the associat-ed metabolic abnormalities increase the riskfor status epilepticus. Opportunistic infec-tious and/or tumor-like cerebral lesions canalso lead to partial and/or generalizedseizures in HIV-infected patients. Severalnew anti-retroviral drugs have been pro-duced during the last 10 years. Some havebeen shown to have a clear-cut neurotoxici-ty including peripheral effects. Some are toonew to prove their eventual undesirableeffects, while others may have pharmacolog-ic interactions with AEDs. For these reasons,one needs to be very cautious when facingsituations necessitating a long-term use ofAEDs and anti-retroviral drugs.

Malaria is a common problem in manydeveloping countries. The high fever inmalaria can itself cause seizures, and chloro-quine used commonly for the treatment ofmalaria can also rarely cause seizures.Among the new antimalarial drugs, meflo-quine has been reported to increase seizurefrequency in epileptic patients and shouldnot be administered to patients with a histo-ry of convulsions, those with history ofepilepsy in first-degree relatives, or thosehaving serious psychiatric disorders. On thewhole, the risk of mortality due to malaria ismuch more than the risk of single or recur-rent seizures due to malaria except whileusing mefloquine.

Although PB has been in clinical use foralmost a century, its efficacy and side effectsamong people living in developing countrieshave never been determined. Genetic,dietary, or other environmental factors couldgreatly alter pharmacokinetic and pharmaco-dynamic activities in these populations, andaffect the efficacy and side effects of this andother drugs. It is not an uncommon clinicalexperience that PB used in smaller doses isan effective and safe AED among peoplewith epilepsy in developing countries. Thereis a strong case to study the efficacy andsafety profile of this cheap AED among pop-ulations in developing countries. Backed bysupportive data, PB could be a very goodcandidate for the first-line single AED for useat the community level in developing coun-

Antiepileptic Drugs

91

KEYPOINTS

n It is not an uncommonclinical experience that PBused in smaller doses is aneffective and safe AEDamong people withepilepsy in developingcountries.

Guidelines for theTreatment in Patients withChronic Epilepsy in anEpilepsy Center

TABLE 6.3

1. Carefully review the history (if possi-ble try to speak with a person whohas seen the seizures), EEGs, CT/MRIscans, and other relevant investiga-tions.

2. Try to classify the ‘epilepsy syndrome’and also the seizure type(s). Rule outnonepileptic seizures by recording afew seizures with EEG (long-termvideo-EEG). Many times, epilepticseizures may coexist with nonepilepticseizures.

3. Ensure AED compliance (determineserum levels of AEDs) and construct atable of all the AEDs previously usedwith their maximum doses (ensuringthat maximum doses have been used),beneficial effects, and side effects.

4. Find out about any other drugs thatthe patient may be taking that couldcause drug interactions.

5. Try the second-line (new) AEDs asadd-on therapy.

6. Evaluate the patient for epilepsy sur-gery, especially if patient hasintractable partial seizures.

Remember that a small percentage ofpatients with seizures have trulyintractable seizures and current AEDtherapy has a limited role in such situations.

tries. Similar studies are required for othercommonly used AEDs also so that their cor-rect place in clinical usage could be ascer-tained.

Irregular supply and the availability ofspurious drugs in many of the developingcountries are important issues especiallywhile using drugs like PB. Many genericbrands are available in most of the develop-ing countries that are usually much cheapercompared to the brand name drugs.Bioavailability of the generic drugs can bevariable and not reliable, resulting in break-through seizures or sudden appearance ofadverse side effects.

It should also be remembered that manypeople with epilepsy in developing coun-tries use traditional medicines even while onmodern AEDs. These traditional medicinescould contain substances with potentialantiepileptic effects, and this is anotheraspect that needs to be investigated veryseriously. As neurologists, we should notnecessarily discourage the use of traditionalmedicines, particularly when the seizuresare controlled and these medicines are not

causing any side effects. The use of yoga,different forms of meditation, and other suchphysical measures have been shown to beeffective in reducing the seizures in isolatedstudies and this issue also needs to beaddressed in a more organized and scientif-ic manner.

CONCLUSIONSNeurologists practicing in developing coun-tries, even more than in the industrializedworld, need to be aware of the importantpharmacokinetic properties that permitavailable AEDs to be used most effectively,with minimum side effects and drug interac-tions, in order to make the best use of limit-ed resources. Irregular supply of the avail-able AEDs resulting in breakthroughseizures is also a major problem in manydeveloping countries. Besides the effective-ness of a particular drug, its cost becomes animportant issue in developing countrieswhen selecting AEDs. In this context, PBcould still be used as the first-line AEDdespite its reported adverse effects.Clinicians in developing countries would still


92

Recommended AEDs for Different Seizure TypesTABLE 6.4

Seizure Type First-line Second-line Third-line

Generalized Seizures

Absence Valproate Ethosuximide Levetiracetam (typical and atypical) Lamotrigine Zonisamide

Myoclonic Valproate Topiramate Clobazam Levetiracetam Clonazepam Lamotrigine PhenobarbitalZonisamide

Tonic-clonic Phenobarbital Lamotrigine Topiramate Phenytoin Oxcarbazepine Levetiracetam Carbamazepine ZonisamideValproate

Atonic Valproate Lamotrigine FelbamateTopiramate

Partial Seizures

Simple and complex Phenobarbital Valproate Gabapentin partial with or Phenytoin Oxcarbazepine Tiagabine without secondary Carbamazepine Lamotrigine Vigabatrin generalization Topiramate Felbamate

Levetiracetam Zonisamide

have the option of switching over to otherfirst-choice AEDs in case of problems withPB. Interestingly, the efficacy as well as theadverse drug reactions of the AEDs amongpeople with epilepsy in developing coun-tries could be significantly different com-pared to that among those in the industrial-ized world due to genetic, dietary, or envi-ronmental factors. Hardly any trials on theusefulness and safety of conventional and

new AEDs have been conducted amongpopulations in developing countries despitethe fact that most of the people with epilep-sy today live in developing countries. Thepharmaceutical industry needs to correctlyestimate the marketing potential of AEDs inthe developing countries, and should investmore in developing nations when planningfuture trials with AEDs.

Antiepileptic Drugs

93

CITATIONS AND RECOMMENDED READINGBourgeois BF. Pharmacokinetic properties of current antiepileptic drugs: what improvements are needed? Neurology

2000;55(suppl 3):S11–S16.

A very well written review article on the pharmacokinetic properties of current antiepileptic drugs. It has nice tableson the pharmacokinetic interactions among AEDs, pharmacokinetic parameters of AEDs, and the pharmacoki-netic properties of conventional and newer AEDs.

Brown TR, Holmes GL. Antiepileptic Drugs. In: Handbook of Epilepsy. Philadelphia: Lippincott Williams & Wilkins, 2000.

A very handy and compact volume that has reviewed the mechanism of action, indications, pharmacokinetics,and clinical use of common AEDs.

de Silva M, MacArdle B, McGowan M. Randomised comparative monotherapy trial of phenobarbitone, phenytoin,carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy. Lancet 1996;347:709–713.

This article reports the comparative efficacy of the four main first-line antiepileptic drugs in children with newlydiagnosed epilepsy. The drugs evaluated are the most commonly used drugs for treating epilepsy all over the world.

French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs I: Treatment of newonset epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality StandardsSubcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology2004;62:1252–1260.

French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refrac-tory epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality StandardsSubcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology2004;62:1252–1260.

Two recent guidelines for the use of antiepileptic drugs in new onset and chronic epilepsy.

Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: A critical review. Epilepsia2004;45:1141–1149.

A comprehensive meta-analysis of the use of phenobarbital for epilepsy, prepared specifically to facilitate the useof the drug in developing countries.

Levy RH, Mattson RH, Meldrum BS, Perucca E. Antiepileptic Drugs. 5th ed. Philadelphia: Lippincott, Williams &Wilkins, 2002.

This is the most recent edition of the standard reference work for antiepileptic drugs, which is updated every fewyears.

Marson AG, Kadir ZA, Hutton JL, Chadwick DW. The new antiepileptic drugs: a systematic review of their efficacyand tolerability. Epilepsia 1997;38:859–880.

A very informative review article on the efficacy and usefulness of some of the new antiepileptic drugs in manag-ing patients with epilepsy.

Mattson RH. Current challenges in the treatment of epilepsy. Neurology 1994;44(suppl 5):S4–S9.

A good review article that includes historical perspective on AED evaluation, efficacy of AEDs, desirable propertiesof an AED, and the selection criteria for AEDs.

Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone inpartial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985;313:145–151.

Very important reading material that compares the efficacy of four of the first-line antiepileptic drugs in the man-agement of the more common type of seizures. Unfortunately, this report does not include sodium valproate sincethis drug was not used frequently during the study period.

Patsalos PN, Fröscher W, Pisani F, Van Rijn CM. The importance of drug interactions in epilepsy therapy. Epilepsia2002;43:365–385.

A recent review of drug-drug interactions.

Shorvon SD, Hart YM, Sander JWA, van Andel F. The management of epilepsy in developing countries: an ‘ICEBERG’manual. International Congress and Symposium Series, Royal Society of Medicine Services Limited, London: 1991.

A consensus report of the workshop convened by the International Community Based Epilepsy Research Group (ICE-BERG), held in Delhi, October, 1989. It covers various aspects of epilepsy management in developing countries.


94

95

CHAPTER 7

ALTERNATIVE TREATMENTS

KEYPOINTS

n About 20% to 30% ofepileptic patients haveseizures that are notcompletely controlled withmedication, and this figurehas remained stable overthe last 20 years, despitethe introduction of manynew and expensiveantiepileptic drugs.

n Alternative treatments,particularly those that donot require sophisticatedand expensive technology,are more important in thedeveloping world than inthe industrialized world,where refractory epilepsy ismore common becauseeffective AEDs areunavailable, or the supply isunreliable. In thesesituations, avoidance ofprecipitating factors andappropriate use oftraditional healers cangreatly improve chancesthat seizures will bereduced or eliminated.

n The fairly recent concept ofsurgically remediableepilepsy syndromes is keyto the view that surgicalintervention can be apractical alternativetherapy in manydeveloping countries.

About 20% to 30% of epileptic patients haveseizures that are not completely controlledwith medication, and this figure hasremained stable over the last 20 years,despite the introduction of many new andexpensive antiepileptic drugs (AEDs).Current research suggests that seizures notcontrolled with adequate trials of two first-line drugs in monotherapy, nor with one ortwo rational drug combinations, should beconsidered medically refractory. There is nofixed time frame for the sequential trials ofmedications because this depends on ageand seizure frequency.

The proportion of refractory patientsvaries significantly among the variousepilepsy syndromes. For instance, the pro-portion of medically refractory patients withpost-traumatic or post-stroke epilepsies issmaller than with temporal lobe epilepsydue to hippocampal sclerosis or with focalcortical dysplasia. Syndromic and etiologicdiagnoses, therefore, are helpful in deter-mining which patients are likely to continueto have seizures despite adequate pharma-cotherapy. For these patients, timely andsuccessful use of alternative treatments, par-ticularly epilepsy surgery, can spare themyears of suboptimal quality of life and pre-vent irreversible cognitive, psychosocial, andoccupational disability. Thus, early recogni-tion of pharmacoresistance and applicationof available alternative treatments is crucialto a good outcome.

Alternative treatments, particularly thosethat do not require sophisticated and expen-sive technology, are more important in thedeveloping world than in the industrializedworld, where refractory epilepsy is morecommon because effective AEDs areunavailable, or the supply is unreliable. Inthese situations, avoidance of precipitating

factors and appropriate use of traditionalhealers can greatly improve chances thatseizures will be reduced or eliminated.

RESECTIVE SURGICAL TREATMENT OF EPILEPSYThe second half of the 19th century wit-nessed the first modern neurosurgical proce-dures to alleviate pharmacoresistantseizures. However, epilepsy surgery pro-gressed in a stepwise fashion rather than ata steady pace, because concerns with effica-cy and safety, as well as the development ofAEDs during the 20th century, have oftenchallenged the procedure. The attainment ofthe current situation, where epilepsy surgeryhas a firm place in the neurological thera-peutic armamentarium, depended on a num-ber of advances in functional neuroanatomy,neurophysiology, and neuroimaging. Theintroduction of high-resolution MRI in thepast decade has now simplified presurgicalevaluation sufficiently for some patients tomake surgical treatment for epilepsy a reali-ty in the developing world.

Approaches to Resective Surgical Treatment in the Developing WorldThe fairly recent concept of surgically reme-diable epilepsy syndromes is key to the viewthat surgical intervention can be a practicalalternative therapy in many developingcountries. Surgically remediable syndromesare conditions with known pathophysiologyand natural history, characterized by dis-abling seizures that are highly likely to bepharmacoresistant if the first few trials ofAEDs fail, but have a 70% to 90% chance ofbeing eliminated by an appropriate surgicalresection. Surgery for these conditions iscost-effective because the epileptogenicregion to be resected can be localized nonin-

vasively, usually by identification of a struc-tural abnormality with high-resolution mag-netic resonance imaging (MRI), which is con-firmed to be epileptogenic by electroen-cephalogram (EEG). Patients with surgicallyremediable epilepsy syndromes commonlyhave normal, or near-normal, functionalcapacity at the outset, apart from theirepileptic seizures, but progressive psycho-logical and social problems, or developmen-tal delay in children, ensue if seizures are notcompletely controlled. Consequently, earlysurgical intervention can rescue a patientfrom a lifetime of disability and dependenceon family and society for support.

The prototype of a surgically remediableepilepsy syndrome is mesial temporal lobeepilepsy, the most common form of epilep-sy, and one of the most resistant to AEDs.Patients with focal seizures due to easilyaccessible discrete neocortical lesions, aswell as infants and young children with cat-astrophic epilepsy due to diffuse lesions lim-ited to one hemisphere, such as extensiveSturge-Weber malformations andhemimegencephaly, also have surgicallyremediable syndromes. All of these condi-tions can be easily diagnosed by appropri-ately trained personnel using MRI and EEG.If epilepsy surgery practice is limited to thisfairly significant portion of the populationwith medically refractory epilepsy, theresults will be excellent and the cost will besignificantly less than that of long-term med-ical care and welfare support.

MRI is the single most important tool inthe identification of surgically remediablesyndromes. In patients with medically refrac-tory epilepsies, the convergence of clinicaland EEG abnormalities to a cortical regionharboring a resectable structural lesionshould immediately lead to consideration ofsurgical candidacy. In regions where MRI isnot available, a suspicion of a surgicallyremediable syndrome is the first step towardreferral to more specialized centers. Patientswith recurrent partial seizures unresponsiveto medication should be considered aspotential surgical candidates until provenotherwise. In particular, a clinical historycompatible with complex partial seizures oftemporal lobe origin (see Chapter 2) associ-ated with epileptiform EEG abnormalities in

one or both temporal lobes should promptreferral to a center where MRI is available, todetermine the presence of the single mostcommon surgically remediable syndrome,namely temporal lobe epilepsy due to hip-pocampal sclerosis. In most developingcountries, the identification of the surgicallyremediable syndrome and the determinationof surgical candidacy will both be performedat the referral center where MRI is available.The crucial role of the neurologist workingin the community is the timely identificationof pharmacoresistance and suspicion of asurgically remediable syndrome.

Technological advances in long-termvideo-EEG monitoring, intracranial electroderecordings, functional imaging, and intraop-erative monitoring as part of the surgicalarmamentarium are the rule in industrializedcountries. Epilepsy surgery in this context isa highly sophisticated procedure; saferresections of epileptogenic regions close toeloquent cortex are now possible throughneuronavigation and intraoperative MRI.These procedures, however, are necessaryfor only a small fraction of the patients whoare potential surgical candidates. For mostwho have surgically remediable syndromes,sophisticated technology is not needed forevaluation and surgery, provided adequatelytrained and experienced personnel can opti-mize the use of the available resources.

Surgical candidacy is determined by iden-tification of an epileptogenic region that canbe safely resected with a high probability ofseizure control and a low probability ofintroducing new, unacceptable neurologicdeficits. History and careful description ofthe ictal semiology provides important cluesregarding the site of seizure generation. Forpatients with surgically remediable syn-dromes, it is then necessary to demonstratethe presence of a structural lesion in the sus-pected brain area, usually by MRI. Finally,the epileptogenic nature of this lesion mustbe confirmed by EEG, preferably by long-term video-EEG monitoring of ictal onsets.Where such facilities are available, however,a single, well-localized interictal EEG spikefocus will suffice for many patients. Interictalfocal functional deficits further help to iden-tify the brain area that is persistently abnor-mal, and provides confidence that it can be


96

KEYPOINTS

n The prototype of asurgically remediableepilepsy syndrome is mesialtemporal lobe epilepsy, themost common form ofepilepsy, and one of themost resistant to AEDs.

n MRI is the single mostimportant tool in theidentification of surgicallyremediable syndromes.

n In most developingcountries, the identificationof the surgically remediablesyndrome and thedetermination of surgicalcandidacy will both beperformed at the referralcenter where MRI isavailable. The crucial roleof the neurologist workingin the community is thetimely identification ofpharmacoresistance andsuspicion of a surgicallyremediable syndrome.

n For most who havesurgically remediablesyndromes, sophisticatedtechnology is not neededfor evaluation and surgery,provided adequatelytrained and experiencedpersonnel can optimize theuse of the availableresources.

removed without producing additional neu-rologic disturbances. The neurologic examcan be used for this purpose when theepileptogenic region is in primary corticalareas. For the more common mesial tempo-ral lobe epilepsies, careful neuropsycholog-ic evaluation is necessary to document ver-bal learning and memory problems withlesions in the language-dominant hemi-sphere, and visual-spatial problems whenthe lesion is in the nondominant hemi-sphere. Given the results of this presurgicalevaluation, an experienced epilepsy surgeryteam, with specialized expertise in epileptol-ogy, clinical neurophysiology, neuroradiolo-gy, neuropsychology, and neurosurgery canprovide the patient with a realistic surgical

prognosis with respect to seizure outcome,subsequent quality of life, and risk of addi-tional deficits. In the industrialized world,when results of this noninvasive presurgicalevaluation are equivocal, more detailedstudies can be carried out using intracranialdepth or grid electrodes to record ictalevents; however, the development of facili-ties for this purpose is not likely to be cost-effective for most developing countries.Intraoperative interictal electrocorticography(ECoG), however, can still be used toanswer residual questions in some patients.

A reasonable first step for centers indeveloping countries is to focus on the surgi-cal treatment of mesial temporal lobe epilep-sy and of certain types of neocortical lesion-

Alternative Treatments

97

KEYPOINTS

n A reasonable first step forcenters in developingcountries is to focus on thesurgical treatment ofmesial temporal lobeepilepsy and of certaintypes of neocortical lesionalepilepsies. Besidesconstituting the largestproportion of surgicallyremediable epilepsies,these syndromes have theadditional advantage ofnot being too demandingin terms of technologicalrequirements.

CASE STUDY

Presentation: A 27-year-old woman complained of difficulties maintaining jobs, being repeatedly fired due to “inadequatebehavior at work.” She had been working as a secretary, and often became “spaced out” during phone calls, did not regis-ter important appointments, and failed to deliver messages to her colleagues and chiefs. In addition, her colleagues wouldmention strange behaviors during which she would stare fixedly ahead and purposelessly remove all objects from her table-top, or else lick her lips repeatedly, producing a strange sound. After a minute or so, movements would stop, and she wouldslowly recover, without recollection of what had happened, except that she probably had had a seizure. She had a diagno-sis of epilepsy, which she omitted in job interviews. She had been treated with many different combinations of AEDs, formore than 10 years, but seizures were not controlled. She had had two prolonged febrile convulsions during a benign viralmeningitis at age 2 and was kept on AEDs for about a year after that. She then remained free of seizures up to mid-adoles-cence. At present, she was taking carbamazepine 1,200 mg/day and clonazepam 6 mg/day.

Evaluation: General medical and neurologic examinations were normal. She had a stack of EEGs performed over the years,and they all showed epileptiform and slow-wave abnormalities over the right temporal lobe, only occasionally being inde-pendently recorded on the left side. A CT scan was normal, and doctors had told her that her epilepsy probably was causedby some abnormality during delivery. She was sent to an epilepsy center in her region, where an MRI showed atrophy andincreased signal in the right hippocampus. The diagnosis of hippocampal sclerosis in a woman with medically refractoryseizures and significantly negative psychosocial impact, led to the discussion of the possibility of epilepsy surgery. She wasthen referred to a tertiary center to undergo preoperative evaluation. The latter could be streamlined due to a consistentclinical, interictal EEG, and imaging picture. A 24-hour prolonged 16-channel EEG showed an abundance of spikes and irreg-ular slow waves over the right anterior and basal temporal lobes. Neuropsychology showed preservation of most cognitiveabilities, except for visual memory.

Treatment and outcome: The patient underwent an anterior temporal lobectomy. She has been maintained with carba-mazepine 1,200 mg/day, and is now seizure free for 2.5 years.

Comment: This woman suffered from delayed diagnosis of a common and surgically remediable epilepsy syndrome, namelymesial temporal lobe epilepsy due to hippocampal sclerosis. The delay in diagnosis allowed this often curable disorder to neg-atively impact her professional life. Important points illustrated by this case are the occurrence of a prolonged febrile con-vulsion with several years of a “latent period,” followed by the appearance of complex partial seizures, which eventuallybecome difficult to control and prone to interfere with personal and professional activities. A common scenario, also illus-trated by this woman, is the use of many different combinations of AEDs, until a point is reached where no doubts remainthat the disorder will not be controlled by medication alone. Unfortunately for this woman, such realization occurred in herlate 20s, although the clinical picture was fully established a decade earlier. Current evidence suggests that a period of 1 to2 years may be enough to determine medical refractoriness. Surgical treatment for this disorder is now available in manydeveloping countries. When indicated, it can help control seizures in more than 80% of patients.

al epilepsies. Besides constituting the largestproportion of surgically remediable epilep-sies, these syndromes have the additionaladvantage of not being too demanding interms of technological requirements. Manycandidates for temporal lobe surgery canundergo surgery with excellent results on thebasis of interictal EEG epileptiform abnor-malities, neuropsychologic assessment, andMRI. When evidence of hippocampal sclero-sis is present and the other data are concor-dant for the same anterobasal temporal loberegion, surgery is usually successful, irre-spective of the data provided by scalp ictalEEG. Presurgical evaluation without ictalEEG recordings, however, will demand evengreater experience on the part of the diag-nostic team, which is why “skilled personnel”are the most essential component of anepilepsy surgery center where resources arelimited. A 16-channel EEG machine with avideo recorder plus a 1.5T MRI and verygood neuropsychology is all that is requiredto operate on many surgical candidates withmesial temporal lobe epilepsy (as well as

certain types of neocortical lesional epilep-sies and surgically remediable catastrophicepilepsies of infancy and early childhood).Thus, the challenge for specialized epileptol-ogists in these countries is to develop realis-tic protocols, and to continuously re-evaluatesurgical results in order to improve presurgi-cal and operative approaches.

A valid question in this era of ever-increasing, high-technology approaches todiagnosis and treatment is whether mini-mum requirements for epilepsy surgery arechanging. The answer is: probably not.Technological progress allows patients withmore complex epilepsy to be adequatelyevaluated and occasionally operated on inepilepsy surgery centers in the industrializedworld, but is not contributing much to man-agement of the “easy” surgical candidates.The ability to operate on additional patientsin these high-tech centers is, of course,important, but their numbers are small incomparison with the number of patientswho have mesial temporal lobe epilepsy andother surgically remediable epilepsy syn-


98

KEYPOINTS

n Thus, the challenge forspecialized epileptologistsin these countries is todevelop realistic protocols,and to continuously re-evaluate surgical results inorder to improvepresurgical and operativeapproaches.

CASE STUDY

Presentation: An 11-year-old girl had left school 2 years before presentation because of multiple epileptic seizures duringsleep. She was a good student until seizures began 3 years earlier, when she had a dramatic decrease in school performance.She would have between 10 and 30 seizures per night, all stereotyped: the left arm would extend, her head would rotate tothe left, and the right arm would flex at the elbow. She would then have difficulties breathing, awaken, and after a few min-utes would again fall asleep. During the day she would be somnolent and irritable, and her concentration was poor.Behavioral abnormalities and low grades led her to drop out of school. Multiple AEDs, in mono- and polytherapy, failed tocontrol or even reduce the frequency of the nightly attacks. When evaluated, she was taking carbamazepine 1,000 mg/day,valproic acid 1,500 mg/day, and clobazam 20 mg/day. History disclosed no presumed etiology for the epilepsy.

Evaluation: General medical and neurologic examinations were normal. EEGs showed frequent bilateral synchronous frontalspikes, without lateralization. A CT scan was normal. She was referred to an epilepsy center, where an MRI revealed an areaof increased cortical thickness and abnormal signal in the right superior frontal gyrus, about 4 cm in front of the precentralgyrus. One night-time prolonged video-EEG recording sufficed to record 14 seizures, all starting in the right anterior quad-rant, with fast generalization. After additional testing, she was referred to epilepsy surgery.

Treatment and outcome: The patient underwent resection of the lateral and medial surfaces of the right superior frontalgyrus, under ECoG guidance. The lesion appeared to be completely resected. Focal cortical dysplasia was confirmed on patho-logic examination. There were no complications. She has been maintained on carbamazepine 1,200 mg/day and clobazam 20mg/day. Despite this, she continues to have one to three sleep-related seizures per month. However, because she now can gofor weeks without any seizures, she has been able to successfully resume school activities.

Comment: This girl illustrates the severe partial epilepsies that can be associated with malformations of cortical development,and particularly with focal cortical dysplasia. The frontal lobe seizures occurred so often that they caused prolonged sleepdeprivation, with a negative impact on cognition and behavior. Malformation of cortical development should be suspectedin patients with such severe epilepsies, even when cognition is uncompromised. Even though surgical outcome for this disor-der is not as universally beneficial as it is for mesial temporal lobe epilepsy, a surgical approach can still be cost-effective indeveloping countries where epilepsy surgery centers exist.

dromes. Furthermore, satisfactory surgicalresults are much more dependent on theclinical skills of relevant specialists than oncutting-edge advances in neuroimaging orclinical neurophysiology. In addition, thereis the obvious need to optimize the alloca-tion of limited technological resources. Inpractice, this means that potential candidatesfor epilepsy surgery must have access to MRIand video-EEG monitoring in countrieswhere inequalities of medical care restrictavailability of costly procedures to thosewho need them most.

Justification for Resective Epilepsy Surgery in the Developing WorldApproximately 80% of persons with epilep-sy live in developing countries. Thus, 80%

of patients who could potentially benefitfrom surgical treatment live in theseregions. It is hardly acceptable that themajority of individuals who could benefitfrom any particular form of treatment can-not receive it. The challenge is to reconcilethe need for careful presurgical evaluationwith the need to make epilepsy surgerywidely available. Developed countries, withall their technology and experience, shouldhelp developing countries design simpler,but effective strategies to evaluate patientsfor surgery. Efforts in the industrializedworld to support and disseminate advancesthat make epilepsy surgery more cost-effec-tive will aid millions of people in develop-ing countries who need not suffer the con-sequences of medically refractory seizures.


99

KEYPOINTS

n Approximately 80% ofpersons with epilepsy livein developing countries.Thus, 80% of patients whocould potentially benefitfrom surgical treatment livein these regions. It is hardlyacceptable that themajority of individuals whocould benefit from anyparticular form oftreatment cannot receive it.The challenge is toreconcile the need forcareful presurgicalevaluation with the needto make epilepsy surgerywidely available.

CASE STUDY

Presentation: This 34-year-old woman, with recurrent seizures since age 8, presented to the epilepsy clinic after having failedepilepsy surgery 2 years earlier. Her history was remarkable for a prolonged febrile convulsion at 6 months of age. Her cur-rent attacks began with nonspecific dizziness, progressing to disconnection from the environment and dystonia of the lefthand. Secondary generalization was uncommon, and the partial seizures recurred at least twice a week. Neither semiologi-cal features nor seizure frequency were modified by operation, which consisted of a right anterior temporal lobectomy,including resection of the mesial structures.

Review of the notes of the preoperative evaluation showed that abundant interictal spikes were recorded from the right sphe-noidal, anterior, and mid-temporal electrodes, and that ictal recordings consistently showed seizure onset over the entire righttemporal lobe. Computed tomography (CT) disclosed three small calcifications, respectively, in the right posterior temporal, rightparietal, and left occipital regions. MRI hinted at these small lesions, but was remarkable for a reduced volume of the right hip-pocampus, without abnormal signal intensity. Neuropsychologic evaluation had shown abnormal visual memory. Postoperativehistopathology was not available. Presently, she was taking carbamazepine 1,600 mg/day and clobazam 30 mg/day.

Evaluation: IgG, but not IgM, immunoassays for cysticercosis were positive. Repeat video-EEG monitoring disclosed spikes andictal onsets from the right mid and posterior temporal regions. MRI showed the extent of previous resection and the voidsignal related to the calcifications shown on CT.

Treatment: After discussing with the patient and relatives the risks inherent in reoperations and the potential for a visualfield defect, a right mid- and posterior temporal lobectomy was performed under electrocorticographic monitoring. Very fre-quent spikes were recorded from the cortex surrounding the posterior temporal calcified cyst.

Outcome: Seizures were completely controlled, and have not recurred after 30 months of follow-up. A left superior quadran-tanopia can be detected by clinical examination. The patient is currently taking carbamazepine 1,200 mg/day and clobazam20 mg/day.

Comment: This woman had seizures related to a calcified cysticercotic temporal lobe cyst and surrounding epileptogenic cor-tex, whose role in seizure generation was initially neglected. The presence of an atrophic ipsilateral hippocampus and a his-tory of prolonged febrile convulsions directed the attention to the anteromesial temporal lobe structures. Although bothinterictal spikes and ictal onsets also involved the anterior temporal regions, they were much more widespread over the righttemporal lobe. These EEG findings, the nonspecific semiological features, and the lack of an abnormal signal intensity of theatrophic hippocampus should have raised a red flag in regard to an anteromesial localization of the ictal generators.

Some patients with calcified cysts and refractory epilepsy may also have hippocampal sclerosis. The hippocampus was notlikely to have been epileptogenic in this woman, because improvement after the first operation—directed at the mesial tem-poral structures—was virtually nil. An important issue to be clarified through further studies is why some calcified cysticer-cotic cysts are epileptogenic and others are not—such as the right parietal and the left occipital cysts in this patient.

The best model will involve a creative part-nership between specialists trained abroadand their local colleagues to developregional or national epilepsy surgery pro-grams. The next step will be to train peoplelocally and legitimize the concept ofregionally relevant approaches.

The economic feasibility of surgical treat-ment in countries with limited resources isreadily apparent. Data from Colombia showthat epilepsy surgery can be performed atone-tenth the cost of that in developedcountries, and countries like Brazil, India,and Turkey have reported a similar experi-ence. In contrast, AEDs are often unavail-able, unaffordable, or irregularly distributedin the developing world. Eighty percent ofthe pharmaceutical market is focused on the20% of persons with epilepsy living in indus-trialized countries. For patients with pharma-coresistant seizures, who are the greatestconsumers of AEDs and are in the mostneed of other health care resources, elimina-tion of disabling seizures by surgery couldhave an enormous beneficial impact on thecost of their care. The realistic goal to reduceor eliminate the need of AEDs in manypatients should be considered in both theethical and economic arguments for epilep-sy surgery in developing countries.

Because opportunities for education andwork are considerably more limited indeveloping countries, the handicap imposedby uncontrolled epilepsy is almost certainlygreater than in areas where schooling andemployment are easier to obtain. About halfthe people unemployed before epilepsy sur-gery can find a job after operation, providedthe patient is not mentally retarded andseizures are satisfactorily controlled by theprocedure. Psychological and social rehabil-itation, however, is dependent on the preop-erative educational and vocational status ofthe patient, indicating the need for an earli-er and more aggressive approach to surgicalintervention. For nonwelfare states, losing ajob, or not obtaining one in the first place,can be catastrophic for the lifetime of theindividual (see Chapter 5). Reintegration intosociety, not only of patients, but also of theircaregivers, also justifies the costs of imple-menting epilepsy surgery.

PALLIATIVE PROCEDURESA sizable proportion of patients with med-ically refractory seizures have epilepsy syn-dromes that are not surgically remediable.They do not have a single, resectable epilep-togenic zone, and often have a diffuseepileptic encephalopathy, in which disablingseizures coexist with generalized or multifo-cal EEG abnormalities and intellectual dis-ability. A number of palliative procedureshave been developed to alleviate the condi-tion in these patients, including corpus cal-losotomy, vagal nerve stimulation, and keto-genic diet. All these procedures target corti-cal epileptogenicity in a nonspecific fashion,do not involve resection of cortical tissue,and act through mechanisms that are notfully understood.

Corpus CallosotomyA section of the corpus callosum interfereswith interhemispheric synchronization ofepileptic activity, thus reducing the probabil-ity of occurrence of generalized seizuresdependent on such synchronization. Assuch, the procedure aims at reducing tonic,atonic, and myoclonic drop attacks, as wellas generalized tonic-clonic seizures. Partialseizures are often unaffected or evenincreased by the procedure. Preoperativeevaluation must exclude a resectable epilep-togenic zone, but is usually straightforward.Long-term outcome after corpus callosotomyis variable. Because there is a risk of motorand cognitive complications, the pros andcons of corpus callosotomy should be bal-anced on an individual basis. However,because an expensive presurgical evaluationis not required, corpus callosotomy could beoffered cost-effectively in developing coun-tries with neurosurgical facilities.

Ketogenic DietThe increase in ketone bodies associatedwith a diet rich in lipids and low in carbohy-drates decreases seizure frequency in a sig-nificant percentage of patients with pharma-coresistant epilepsy. The mechanismsthrough which the ketogenic diet exerts itsantiepileptic effect are not fully understood.Open studies report that some patients maybecome seizure free and that more than 50%achieve a significant reduction in seizure fre-


100

KEYPOINTS

n For patients withpharmacoresistant seizures,who are the greatestconsumers of AEDs and arein the most need of otherhealth care resources,elimination of disablingseizures by surgery couldhave an enormousbeneficial impact on thecost of their care.

n Reintegration into society,not only of patients, butalso of their caregivers, alsojustifies the costs ofimplementing epilepsysurgery.

n Because an expensivepresurgical evaluation isnot required, corpuscallosotomy could beoffered cost-effectively indeveloping countries withneurosurgical facilities.

quency. The need for absolute compliancewith the diet and gastrointestinal side effectsare the main deterrents to its use. Although amultidisciplinary support team of diet spe-cialists, clinicians, and psychologists is usual-ly considered necessary for effective imple-mentation of the ketogenic diet in the indus-trialized world, this alternative therapy hasbeen successfully and cost-effectively used indeveloping countries without such support.

Vagus Nerve StimulationEvidence that subcortical structures maymodulate cortical epileptogenicity and path-ways of seizure propagation led to thedevelopment of vagal nerve stimulation.This technique involves implantation ofelectrodes on the cervical portion of thevagus nerve and of a subcutaneous stimula-tor, which costs several thousands of dollars.Stimuli are delivered at a given frequency,travel through the nerve toward relay nucleiin the medulla and pons, and from there,interfere diffusely with cortical and subcorti-cal excitability. A reduction of about 50% ofthe seizure frequency in 50% of patientsseems to be the uniform result in mostseries. Thus, vagal nerve stimulation is not acost-effective alternative treatment for coun-tries with limited resources.

DEALING WITH PRECIPITATING FACTORSThe management of seizure-precipitatingfactors usually does not include AEDs, and itmay be appropriate to discuss this issue inthe context of alternative treatments (seealso Chapter 5). Many of these factors canlead to seizures even in patients withoutepilepsy, and all can precipitate seizures inepileptic patients. With a few exceptions,change of habit is key to dealing with thesefactors, but this may prove difficult toachieve. Patients often come to accept thatepilepsy demands the use of pills, but aremuch less prone to accept that the conditionmay require the change of habits or attitudesthat are perceived as part of their lives. Thus,the first step is to provide a simplified expla-nation to the patient and relatives about themechanisms through which these precipitat-ing factors can lead to seizures, making itclear that avoiding them (whenever possi-ble) is the logical thing to do.

MensesSeizure precipitation by menses is commonin women with partial epilepsies and is relat-ed to reduced progesterone levels duringthis period. There are different ways to dealwith the increase in seizures just before andduring menses, and individualizedapproaches are the rule. A rather nonspecif-ic approach is to simply augment the dailydosage of AEDs, thus increasing protectionduring the whole month. Another way is toincrease AED dosages or add rapidly actingdrugs such as benzodiazepines only in theweek around menses, provided regular peri-ods are the rule. Finally, for more severeepileptic disorders, hormonal therapiesbased on restoring progesterone levels canbe administered.

Sleep-Wake CyclesFor the purpose of dealing with personswith increased seizure susceptibility, thesleep wake cycles can be divided into fourstates: full wakefulness, deep sleep, the tran-sition between sleep and wakefulness, andthat between wakefulness and sleep.Different epilepsy syndromes tend to gener-ate seizures in specific states of the sleep-wake cycles, and this should be recognizedand managed accordingly. Approaches varyfrom adjusting the schedule of AED dosagesto promote higher serum levels during themore vulnerable states, to the anticipation ofan increased risk of seizures in specific situ-ations related to the sleep-wake cycle, thusleading to the implementation of protectivemeasures to avoid injuries during seizures.For instance, patients with some primarygeneralized epilepsy syndromes whoseseizures tend to occur upon awakeningshould be advised to avoid driving in thefirst 2 or 3 hours of the day if they had fewhours of sleep the night before. The role ofsleep deprivation in seizure occurrence is animportant issue for discussion with patients,particularly adolescents. Managementoptions include encouraging a small napbefore going out in the evening or theadministration of an extra dosage of theusual AED before going into sleep. The rel-evance of sleep-wake cycles for seizure pre-cipitation is illustrated in the following casereport.


101

KEYPOINTS

n Although amultidisciplinary supportteam of diet specialists,clinicians, and psychologistsis usually considerednecessary for effectiveimplementation of theketogenic diet in theindustrialized world, thisalternative therapy hasbeen successfully and cost-effectively used indeveloping countrieswithout such support.

n Thus, the first step is toprovide a simplifiedexplanation to the patientand relatives about themechanisms through whichthese precipitating factorscan lead to seizures,making it clear thatavoiding them (wheneverpossible) is the logical thingto do.

n The role of sleepdeprivation in seizureoccurrence is an importantissue for discussion withpatients, particularlyadolescents.

Alcohol and Sedative Drug WithdrawalSeizures can occur upon sudden alcoholand sedative drug withdrawal, particularlywhen these drugs have been used for pro-longed periods. Although this is much morecommon in people with epilepsy, seizuresin this context can also occur in peoplewithout epilepsy. When planned inadvance, the period of alcohol withdrawalshould be accompanied by the temporaryadministration of benzodiazepines, whichwill control not only the anxiety stateinduced by alcohol discontinuation, but willalso increase seizure threshold. Theapproach to the safe discontinuation ofsedative drugs is different, and requiresdecrease of dosages over a long period oftime. In people with epilepsy, rapid with-drawal of barbiturates or benzodizepinesare well known seizure precipitants, and thediscontinuation of these drugs should bedone over weeks or months. When epilep-sy is more severe, there is a definite risk ofan increase in seizures even with slow dis-continuation of barbiturates, and thus smalldosages of a benzodiazepine can be admin-

istered temporarily. People who do nothave a history of epilepsy, but present withseizures clearly related to alcohol or seda-tive drug withdrawal, need not be managedchronically with AEDs, although these maybe prescribed for a short period of time.

Stimulant DrugsStimulant drugs can facilitate seizure occur-rence in people both with and withoutepilepsy. Even small doses of cocaine orcrack, and drugs such as amphetamines,methylphenidate, or sympathomimetic drugsfor asthma can decrease seizure thresholdsufficiently to cause seizures in susceptibleindividuals. Should an increase in seizurefrequency occur in these contexts, preven-tive measures, including discontinuation ofthe precipitating drug or increase of AEDdosages, should be taken. In some highlysensitive patients, even the use of caffeineshould be discouraged. There are someregions of developing countries in which theingestion of stimulants is a routine, includingchewing or brewing coca leaves in theAndes and drinking mate (a stimulant herb)


102

KEYPOINTS

n People who do not have ahistory of epilepsy, butpresent with seizuresclearly related to alcohol orsedative drug withdrawal,need not be managedchronically with AEDs,although these may beprescribed for a shortperiod of time.

CASE STUDY

Presentation: A 15-year-old girl was noted to be convulsing during sleep at about 7 a.m. She had tonic-clonic jerking of allfour limbs with blood-tinged frothing from the mouth. She had passed urine in her clothes and vomited once after a fewminutes. She then slept for the next 2 hours and complained of headache and body aches on awakening. She also noticedthat she had bitten her tongue. The previous two nights, she was awake till 3 a.m. and 5 a.m. in a cousin’s wedding.

Evaluation: Her neurologic evaluation revealed a normal examination. She had no previous history of seizures or any neuro-logic insult. There was no family history of seizures. An EEG and CT scan of the head were performed and were normal.

Treatment and outcome: The issue of her risk for seizure recurrence was discussed with her and the family members. It wassuspected that sleep deprivation for two consecutive nights could have provoked the seizure. It was thought safe to keep herunder observation, and she was not prescribed any treatment. She was advised to change her lifestyle and observe regularhabits and was seizure free when last seen about 2 years after her first seizure.

Comment: The management of patients presenting with a single seizure will continue to be a dilemma for clinicians. It is esti-mated that 5% to 10% of the population will have a single seizure during their lifetime. Sleep deprivation, hypoglycemia,alcohol withdrawal, high fever, and many other acute metabolic insults are some of the factors known to provoke seizures.This girl had a single provoked seizure and should not be classified as having epilepsy (by definition, a diagnosis of epilepsyrequires two or more unprovoked seizures). People with a single provoked seizure need not be treated with AEDs exceptwhen there are associated factors that increase the risk for seizure recurrence, or a history of previous events that were unrec-ognized seizures (see Chapter 3 for details).

in the South American Pampa. These habitsmay need modification in some personswith epilepsy in these regions.

Toxic Metabolic InsultsElectrolyte imbalance, hypo- or hyper-glycemia, and other toxic metabolic insultsmay lead to or facilitate the occurrence ofseizures. Correction of the underlying sys-temic insult is the most important therapeu-tic measure, and AEDs are usually not indi-cated in those without a history of unpro-voked seizures. Prolonged periods of exces-sively hot temperatures as well as endemicparasitic disorders in developing countriesfrequently lead to dehydration, vomiting,and diarrhea. In these situations, the possi-bility of electrolyte imbalance should beconsidered in epileptic patients with an oth-erwise unexplainable increase in seizurefrequency.

Sensory StimulationSeizures may be precipitated by a variety ofsensory stimuli, particularly in certain specif-ic epilepsy syndromes. Most common arepatients with primary (idiopathic) general-ized epilepsies who display photosensitivity.Intermittent photic stimulation from videogames, stroboscopic lights, or a variety ofalternating dark/light patterns may inducemyoclonic jerks or generalized convulsionsin these patients. Photosensitive-relatedseizures are at times self-induced by intellec-tually disabled patients. Rare reflex epilep-sies are associated with seizures precipitatedby a variety of complex stimuli such as eat-ing, reading, music, and water baths.Somatosensory- or movement-inducedseizures can occur in patients with epilepto-genic zones in perirolandic regions, whileictal episodes associated with any modalityof startle can occur with epilepsies due toextensive brain damage.

The vast majority of these patients alsohave spontaneous seizures, but the possibil-ity that some episodes may be due to specif-ic types of sensory stimulation should beactively pursued through clinical history,because avoidance of offending stimulioffers a nonpharmacologic means to reduceseizure frequency.

THE PLACE OF TRADITIONAL MEDICAL TREATMENTSLong-held cultural views about epilepsy andthe failure of public health systems in devel-oping countries to systematically identify andadequately treat recurrent seizures leavesroom for traditional medical treatments.Educational campaigns led by governmentsand the World Health Organization (WHO),and non-governmental organizations (suchas International League Against Epilepsy andIBE), continuously attempt to promote anunderstanding of epilepsy as a brain disorderwith recognized causes and specific modesof treatment. Still, there is a long way to goas far as education is concerned.

Perhaps a bigger problem than the failureof people in developing countries to under-stand modern medical concepts of epilepsyis the failure of the allopathic medical estab-lishment to understand and respect tradition-al beliefs of their patient population. Even indeveloping countries, it is the rule ratherthan the exception that allopathic physiciansand healthcare workers are either not of thesame ethnic group as the majority of theirpatients, or are so far removed from the tra-ditional culture that they are no longer ableto empathize with patients’ and their fami-lies’ concerns about specific diagnoses andrecommended treatment plans. The per-ceived arrogance of allopathic medical prac-titioners and cross-cultural mismatchesundoubtedly account for a considerable per-centage of treatment failures in developingcountries, as well as avoidable disasters, aswas movingly documented by AnneFadiman in her book, The Spirit Catches Youand You Fall Down, about the tragic out-come of treatment offered to a Hmong childat a modern hospital in California. Both thephysicians and healthcare workers on theone hand, and the Hmong community onthe other, did their best to help this child,but failed to communicate adequately witheach other, not only because they did notshare a common language, but because theydid not share a common culture. Interpretersare necessary who will not only translatewords, but philosophies, and who willensure that both parties to the discussion aretreated with equal respect and understand-ing. The most common strategy used to


103

KEYPOINTS

n Perhaps a bigger problemthan the failure of peoplein developing countries tounderstand modernmedical concepts ofepilepsy is the failure ofthe medical establishmentto understand and respecttraditional beliefs of theirpatient population.

n The perceived arrogance ofmedical practitioners andcross-cultural mismatchesundoubtedly account for aconsiderable percentage oftreatment failures indeveloping countries.

n Interpreters are necessarywho will not only translatewords, but philosophies,and who will ensure thatboth parties to thediscussion are treated withequal respect andunderstanding.

overcome cross-cultural obstacles to optimalpatient care employs eight questions,designed by Arthur Kleinman, to elicit anexplanatory model of the patient and thepatient’s family. These are:

1. What do you call the problem?2. What do you think has caused the prob-

lem?3. Why do you think it started when it did?4. What do you think the sickness does?

How does it work?5. How severe is the sickness? Will it have

a short- or long-term course?6. What kind of treatment do you think the

patient should receive? What are themost important results you hope toreceive from this treatment?

7. What are the chief problems the sick-ness has caused?

8. What do you fear most about the sick-ness?

Although these questions might seemsimpleminded and obvious at first, they set atone that prevents the allopathic physicianfrom blindly and dogmatically assertingopinions and making requests that are total-ly incompatible with the patient’s and thepatient’s family’s cultural context. Cross-cul-tural discrepancies can then be easily identi-fied, and compromises can be reachedbased on informative discussions that arepredicated on mutual respect and under-standing.

Most traditional medical treatments forpeople with epilepsy are scientificallyunproven, but at least provide some comfortto patients and relatives, with a favorablepsychological impact that can be beneficial.Although these treatments can be harmful ifthey delay, or interfere with, standard med-ical attention that could provide more ade-quate diagnosis and treatment, or if tradi-tional healers advise against allopathic med-icine, they cannot be dismissed out of hand.A collaborative relationship should be devel-oped between traditional and allopathicapproaches to treatment.

Traditional medical approaches are dis-cussed in more detail in Chapter 8; howev-er, it is useful to provide some overviewhere. Most traditional healers utilize a holis-

tic approach, beginning with a diagnosticevaluation, for instance using cowries, sand,stones, animal sacrifices, interpretation ofdreams, and dialogue with supernatural per-sons and forces. Next, treatment often rec-ommends, transforms, or forbids the use ofvarious animal, vegetable, mineral, and liq-uid substances, depending on their pre-sumed benefit or potential harm to thepatient. Their utilization can take the form ofamulets, eating or drinking, inhalation, orbathing. In some societies, scarifications arepracticed. During mystical celebrations,supernatural forces are “invited” by the heal-er to visit the patient if they are protective,or to withdraw from the body and soul ifthey are negative. The blood from sacrificedanimals may be offered to the patient’s fam-ily and ancestors, as well as to supernaturalforces. Often the family is asked to make aspecific donation, perhaps to the children, areligious group, or people in need. Whilethese interventions can be highly effective asan adjunct to appropriate allopathic medicaltherapy, it is important to understand the tra-ditional practices in their area, and gentlydiscourage those that might have a detri-mental effect because of known toxicities orother unhealthful consequences, such asmalnutrition. On the other hand, it is notunlikely that some substances used by tradi-tional healers could, in fact, have antiepilep-tic properties, and further scientific investi-gation would be appropriate.

CONCLUSIONSAEDs are not always effective in controllingepileptic seizures. Alternative forms of treat-ment, however, can often be useful to con-trol seizures or reduce their frequency.While the identification and removal of pre-cipitating factors is an effective nonpharma-cologic intervention for some patients, manywill have truly medically refractory seizures.Where epilepsy surgery facilities exist, it iscrucial to suspect a surgically remediableepilepsy syndrome and refer promptly forfurther evaluation and surgical treatment.Epilepsy surgery as an alternative treatmentin developing countries has been shown tobe both feasible and cost-effective. Morethan technological sophistication, a positiveattitude of skilled personnel is the basis of a


104

successful epilepsy surgery program in thedeveloping world. Other alternative treat-ments, such as the ketogenic diet, can beeffectively used, but vagus nerve stimulation

is less practical for developing countries.There are potential benefits from collabora-tion with traditional healers.


105

CITATIONS AND RECOMMENDED READINGAdotévi F, Stéphany J. Représentations culturelles de l’épilepsie au Sénégal. Med Trop 1981;1:283–288.

This very instructive article is one of the first published by African professionals on the cultural context of epilep-sy in a francophone African country.

Arborio S, Jaffre Y, Farnarier G, Doumbo O, Dozon JP. Kirikirimasien (epilepsy) in Mali: etiologic and nosologicdimensions. Med Trop 1999;59:176–180.

A unique in-the-field study conducted by a multidisciplinary international team in Mali (West Africa) emphasiz-ing local traditional knowledge on some seizure types.

Engel J Jr. Surgery for seizures. N Engl J Med 1996;334:647–652.

This position paper emphasizes that surgical treatment for epilepsy is safe, cost-effective, and greatly underutilized,particularly in developing countries.

Engel J Jr, (ed.) Surgical Treatment of the Epilepsies, 2nd ed. New York: Raven Press, 1993.

This comprehensive textbook on surgical treatments for epilepsy is slightly out of date, but appropriate for practicewith limited resources.

Engel J Jr, Wiebe S, French J, et al. Practice parameter: Temporal lobe and localized neocortical resections for epilep-sy. Neurology 2003;60:538–547.

A recent guideline recommending surgery for temporal lobe epilepsy.

Fadiman A. The Spirit Catches You and You Fall Down. New York: Farrar, Straus and Giroux, 1997.

A true story of a Laotian child with epilepsy whose medical treatment in California was severely compromisedbecause of cultural impediments to communication. This book is required reading for anyone practicing medi-cine in a cross-cultural environment.

Jilek-Aall L. Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures. Epilepsia1999;40:382–386.

This Canadian author has tremendous experience as a “bush doctor” in East Africa. Here she describes the impactof religion on the cultural interpretation of epilepsy in this region.

Kleinman A. Patients and Healers in the Context of Culture. Berkeley: University of California Press, 1980.

This is a classic text on cross-cultural issues in medical practice and how they can be addressed.

Lüders HO, Comair YG. Epilepsy Surgery, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001.

The most recent comprehensive textbook on surgical treatment of epilepsy.

Palmini A. Medical and surgical strategies for epilepsy care in developing countries. Epilepsia 2000;41(suppl4):S10–S17.

This review discusses stepwise approaches to patient selection for epilepsy surgery, based on several different levelsof sophistication that are likely to be available in developing countries.

Shorvon SD, Farmer PJ. Epilepsy in developing countries: a review of epidemiological, sociocultural, and treatmentaspects. Epilepsia 1988;29(suppl 1):S36–S54.

This review emphasizes issues relevant to the diagnosis and management of epilepsy in developing countries.

Sperling M, O’Connor M, Saykin A, et al. A non-invasive protocol for anterior temporal lobectomy. Neurology1992;42:416–422.

This study shows the favorable results that can be obtained in the surgical treatment of temporal lobe epilepsybased on patient selection using a noninvasive presurgical evaluation protocol.


107

CHAPTER 8

PSYCHOSOCIAL ISSUES

KEYPOINTS

n The problems for a personwith epilepsy can beginwhile still at school andvery often continuethroughout life, limitingopportunities foreducation, employment,marriage, and children.

n For health workers andneurologists toappropriately care for theperson with epilepsy, it isnecessary to fullyunderstand all of the issuesthat contribute to thepatient’s predicament,which include the need toconsider traditionalremedies, the stigmacaused in part by beliefs ina supernatural power, andthe adverse consequencesof such misconceptions.

n Collaboration betweenmodern physicians andtraditional healers oftenprovides the bestopportunity for effectivetreatment.

Epilepsy has been associated with centuries-old stigma that is so deeply rooted in socie-ty that modern diagnostic and therapeuticadvances have not been able to nullify thepsychosocial burden of the disorder, partic-ularly in developing countries. The majorityof people with epilepsy have their firstseizure when they are still young. The prob-lems for a person with epilepsy can beginwhile still at school and very often continuethroughout life, limiting opportunities foreducation, employment, marriage, and chil-dren. The situation is complicated by thefact that in the majority of developing coun-tries, the sociocultural environment ofchronic disorders often leads to the dual uti-lization of modern and traditional medicinesby most people. This duality exists due tothe belief that chronic illness is “necessarily”the primary result of supernatural forces.Fostered by the family and local society,such a supernatural concept of disease has adramatic negative impact on the epilepticpatient’s life in terms of consultation, treat-ment compliance, follow-up, and burden.Efforts of nongovernmental organizations(NGOs), like the Global Campaign againstEpilepsy, are expected to play a vital role inreducing the peculiar psychosocial burdenposed by epilepsy.

THE EPILEPTIC PATIENT

The PredicamentPeople with epilepsy most often come to theattention of health workers, whether mod-ern or traditional, not because they haveseizures, but because the seizures are inter-fering with their lives. If their seizures didnot interfere with their lives, they would per-haps not seek help. It is, therefore, thehealth worker’s responsibility not only to

stop or reduce the seizures, but to under-stand how and why the seizures interferewith the patients’ lives and help them dealwith this. The disability caused by theseizures constitutes the predicament. Forhealth workers and neurologists to appropri-ately care for the person with epilepsy, it isnecessary to fully understand all of theissues that contribute to the patient’spredicament, which include the need toconsider traditional remedies, the stigmacaused in part by beliefs in a supernaturalpower, and the adverse consequences ofsuch misconceptions.

Traditional HealingUnfortunately, modern allopathic medicineis too often in conflict with traditional prac-tices. In such circumstances, traditional heal-ers can interfere with timely and appropriatemedical interventions, causing unnecessarydisability.

On the other hand, the unpredictablenature of epilepsy causes a psychologicaltension borne by the individual, the family,and the group, and this stress is often bettermanaged by the traditional healers than themodern doctors. The time and quality of lis-tening to the patient and relatives is general-ly better in the mysterious traditional heal-ers’ huts than at the crowded modern hospi-tals. Modern treatment, even when wellapplied, may not seem to be sufficient forthe patient. Consequently, collaborationbetween modern physicians and traditionalhealers often provides the best opportunityfor effective treatment.

The traditional treatment of epilepsy isstill widely used in many developing coun-tries and needs to be placed into its socio-cultural context utilizing a holistic approach.The diagnosis is based on the history of the

illness, “complementary exploration” viasearch with cowries, sand, stones, animalsacrifices, interpretation of dreams, contact,and dialogue with supernatural personages

and forces. The treatment usually utilizes thedifferent life elements: animal, vegetable,mineral, and liquid. Following indications,these natural means will be utilized, trans-


108

CASE STUDY

Presentation: A 29-year-old man has been experiencing sudden bursts of laughing since the age of 9, which can occur any-time or anywhere. Some laughing episodes are followed by loss of consciousness for less than 2 minutes and then full recov-ery. He has never been seen in a modern health center, but rather cared for by traditional healers who “diagnosed” him as“possessed by the devil.” Prescriptions of sacrifices, ritual baths, and amulets to wear have been respected, but the episodescontinued. When he was 29, his mother heard on TV a documentary produced by the National League against Epilepsy stress-ing that these spells might be gelastic seizures.

Evaluation: The next morning, his mother, who used to ask prayers to help him ‘’become more serious and attentive, ratherthan laughing and not listening to people who talked to him,’’ went to the only neurology service in the country anddescribed what her son had been experiencing for 20 years, which was very similar to what she had learned the day beforeon TV. An electroencephalogram (EEG) revealed spikes and slow waves predominant over the left frontotemporal area.

Treatment: A prescription of carbamazepine was given.

Outcome: Two months later, only two events had occurred, compared to more than eight per month during the last 20 years.

Comment: This case illustrates the long delay before modern management is sought due to misconceptions of epilepticseizures in some cultural environments. It also demonstrates the effectiveness of public education about epilepsy.

CASE STUDY

Presentation: Since the age of 8, this 37-year-old man experienced bizarre symptoms, which led his mother to consult a tra-ditional healer. Eleven years later, the healer recommended that she take him to a modern medical center. He has a sisterwith “seizures” who never consulted a medical doctor, but recovered 6 years after, without any specific treatment. Thepatient’s symptoms started at age 8, with complex absence seizures associated with brief jerks of both arms. Because theyoften occurred in the classroom, the teacher asked his parents to keep him at home to avoid “contaminating” the other chil-dren with the devil’s manifestations. He was cared for by a traditional healer who tried several techniques to “wash his spir-it and body from the supernatural forces.” He improved, but was not allowed to attend school. At the age of 16, when hisfather died, the symptoms became worse, with delirium and aggressive behaviors, in addition to myoclonic absences andsome tonic seizures with prolonged loss of consciousness. After the healer treated him with ritual baths, inhalation, amulets,long talks, and mystical incantations, his “psychiatric” symptoms improved, but the jerks and prolonged absences continued.At the age of 28, the healer recommended that his mother consult a neurologist. Antidepressant drugs were prescribed, butdid not improve his status.

Evaluation: All investigations performed after his first consultations with the neurologist were normal. A diagnosis of epilep-tic and nonepileptic seizures was made.

Treatment and outcome: Despite a normal EEG, the neurologist tried carbamazepine and clonazepam. The jerks and pro-longed absence improved, but when he does not consult the healer regularly, the psychiatric symptoms re-emerge.

Comment: This case is a rare one because there are very few traditional healers who are informed enough to accept thatsome symptoms and diseases are out of their area of expertise. In this case, the patient suffered from comorbidity, a reactivepsychopathologic condition aggravated by his father’s death (responding to a traditional approach) and a clear-cut epilepticpattern responding to carbamazepine (which also probably had an effect on his mood) and clonazepam. The collaborationof modern and traditional approaches provided excellent care for his mental and physical problems.

formed, or forbidden, depending on theirsupposed benefit or their disadvantages forthe patient. If they are diagnosed as positiveforces for the patient, they will be worn indifferent forms such as amulets for example,eaten, utilized for bath, drink, or breathed.Supernatural forces will be “invited” duringspecial mystical celebrations, to visit thepatient if they are protective, or withdrawnfrom his or her body and soul, if they arenegative. These rituals are often public andcrowded, accompanied with religious songsand dances. The themes of these evocationsgenerally focus on the patient’s family andancestors. Blood from sacrificed animalsmay be used to satisfy evil forces or to calmdevils.

Just as for allopathic medicine, traditionalhealers can be specialized in a domain ofaction or treatment. Specific means for diag-nosis and treatment can be strictly derivedfrom pure traditional culture or from holyreligious texts. Honest healers are able todirect their patient to medical doctors at anearly stage, if they are convinced that theproblem is not amenable to their abilities.Some traditional healers are reticent to man-age epileptic patients, because they areafraid of transmitting “contagious epilepsy”to their own family or descendants. Others,for financial reasons and very often for thesake of prestige, persist in telling the familyto follow their prescription only and not tomix it with antiepileptic drugs (AEDs). Thefamily expenses in the traditional networkare often higher than the annual cost ofmodern AEDs. Patients who have not beendirected to allopathic medicine often adoptresignation and consequently accept thedecision of God. On the other hand, patientswith provoked seizures or benign syn-dromes can at times be spared inappropriatelong-term pharmacotherapy by consulting ahealer rather than a physician who wouldmisdiagnose their condition. Some countriesare attempting to maximize the beneficialservices of honest traditional healers bydeveloping standards for certification that, inturn, permit government reimbursement.

Very often, the methods and practicesused in traditional healing leave a long-last-ing impact not only on the minds of thepatient and family members but, more

importantly, observers are impressed andoverly influenced by such rituals. When neg-ative, the message then spreads by word ofmouth, worsening the predicament for peo-ple with epilepsy and for society. The prac-tice of using traditional healing methods forthe treatment of epilepsy is so rampant anddeep rooted in society, especially among therural and uneducated living in the far flungareas of developing countries, that anyattempt to oppose these directly and aggres-sively could prove counterproductive.Epilepsy caregivers and health planners indeveloping countries need to understand thisaspect of societal behavior and first aim toimprove the public awareness and availabili-ty of modern treatment for people withepilepsy. Once seizures become controlledwith modern medicines, the belief in anddependence on, faith healers may decline,while the role of modern medicine in epilep-sy treatment gains acceptance by society.

StigmaIn addition to the burden of the diseaseitself, epileptic patients must cope with thestigma attached to this disorder. Epilepsy isstill classified with mental illnesses in thehealth care structure of many countries. Thisleads to further discriminative attitudesagainst people with epilepsy. Consideredcontagious in many cultural contexts, theepileptic patient is kept away from severalfamily and social activities and functions. Inmany regions of the developing world, neg-ative supernatural powers are considered tobe the cause of seizures, resulting in fearand repulsion toward those afflicted withepilepsy. In some rare contexts, the positiveaspects of these supernatural powers areevoked, leading also to fear, but also a cer-tain degree of respect. Neurologists indeveloping countries must be aware ofthese real-life situations when managingpatients with epilepsy because they con-tribute significantly to the societal stigmaattached to this disorder.

Safety Issues Relevant to Developing CountriesSome rituals practiced by faith healers indeveloping countries, such as scarificationand tattooing, are associated with risks.

Psychosocial Issues

109

KEYPOINTS

n Some countries areattempting to maximizethe beneficial services ofhonest traditional healersby developing standardsfor certification that, inturn, permit governmentreimbursement

n The practice of usingtraditional healing methodsfor the treatment ofepilepsy is so rampant anddeep rooted in society,especially among the ruraland uneducated living inthe far flung areas ofdeveloping countries, thatany attempt to opposethese directly andaggressively could provecounterproductive.

n Neurologists in developingcountries must be aware ofthese real-life situationswhen managing patientswith epilepsy because theycontribute significantly tothe societal stigmaattached to this disorder.

Ridiculing the traditional beliefs of patientsand their families is not the solution becauseit can offend their cultural and/or religioussensitivity and develop defensive behaviorleading to nonacceptance of modern treat-ment. Rather, the health professional shouldspend time and explain, with simple andunderstandable words, the epileptic disor-der, its determinants, its management, andwhy the advantages and safety of moderntreatment requires it to be continued for along period. It may be helpful for the neu-rologist to accept some of the proposed tra-ditional treatments, such as ritual baths,amulets, animal sacrifices, and prayers;methods that are less dangerous than theuse of oral preparations and certain physicalmeasures.

The use of generic drugs that have vari-able bioavailability compared to brand namemedications, the irregular supply of com-monly used AEDs, and improperly preparedor out-of-date drugs are common problemsin developing countries that pose risks notonly for an occasional breakthrough seizure,but also for grave emergencies like statusepilepticus.

In most developing countries, women stillcook around open fires and fetch drinkingwater from deep wells and fast-movingstreams. Similarly, men who are fishermengo out into the seas and rivers each day insearch of their livelihood. Whether or notsuch people with epilepsy are taking AEDs,they are always at risk for injury or evendeath, due to burns or drowning, as a resultof a seizure. Even those who are on treat-ment with modern medicines are not with-out risk.

Some rituals in developing countries lastthroughout the night (e.g., marriages, reli-gious congregations, political rallies), whichincreases the likelihood of seizure occur-rence because of sleep deprivation and thefact that many patients forget their medicinesduring such events.

In most developing countries, there areno uniform rules concerning driving andepilepsy. As a result, most people withepilepsy hide their condition and continueto drive their own private and even publictransport vehicles. Although it is safe forpeople with epilepsy whose seizures are

controlled to drive, those with epilepsy whocontinue to drive when their seizures are notcontrolled, or even treated, pose a risk tothemselves and society. Similarly, peopleemployed in high risk jobs like constructionwork and railway track maintenance whoare not on effective treatment can experi-ence severe injuries and death as a result ofseizures at work.

THE FAMILYIn developing countries, management ofepilepsy is not limited to the patient. Theindividual is part of a large group of people,including the family circle and the commu-nity. Individuals are not isolated in tradition-al societies. Members of the family arealways involved in the patient’s managementprocess. Any treatment plan must take thisfact into account and incorporate the entirefamily, social group, or community, ratherthan the individual.

Families of patients with chronic disor-ders such as epilepsy often move from onehealer to another before becoming suffi-ciently dissatisfied to visit a modern medicalcenter to try modern medicines. Thisprocess can take many years. When thedecision to seek modern medical care ismade and this happens, the health person-nel must avoid making the families feelguilty about their delay because such feel-ings may dissuade them from continuingwith modern medicines.

In consultations, it is common toencounter caregivers who do all the talkingand answer every question posed to thepatient, even if the patient is mentally ableto do so. It is important to identify these sit-uations because they reflect excessive, andconsequently harmful, overprotection. Thisbehavior, although well-intended, progres-sively becomes an obstacle to any initiativeon the part of the patient. Some patientsreact by purposely forgetting to take theirdrug and inducing seizures. Others developpsychogenic seizures when they want to puttheir parents or the family under stress.When confronted with such families, thetreating physician should set aside some pri-vate time during the consultation with justthe patient. It is also necessary to have a ses-sion with the parents only, to encourage


110

KEYPOINTS

n Ridiculing the traditionalbeliefs of patients and theirfamilies is not the solutionbecause it can offend theircultural and/or religioussensitivity and developdefensive behavior leadingto nonacceptance ofmodern treatment.

n In most developingcountries, there are nouniform rules concerningdriving and epilepsy. As aresult, most people withepilepsy hide theircondition and continue todrive their own private andeven public transportvehicles.

n When the decision to seekmodern medical care ismade and this happens, thehealth personnel mustavoid making the familiesfeel guilty about theirdelay because such feelingsmay dissuade them fromcontinuing with modernmedicines.

them to have more confidence in thepatient.

Epilepsy in a child profoundly affects theparents. Having a child with seizures canlead to a feeling of guilt for many parents.Their expressed or unexpressed questionsare: “Did I do something wrong to deservethis punishment from God? Am I paying forprevious misbehavior? Did I take adequatecare of this child? Were we right to have himor her? Do we harbor a bad gene that wehave given to our child?” Every seizure isstressful, especially generalized tonic-clonicevents that can evoke fear of death due tothe loss of consciousness. This fear leads tooverprotection. Outpatient consultationsprovide opportunities to discuss these issueswith parents. The support of a psychologistcan be useful to develop positive and moreconstructive attitudes on the part of the par-ents as well as the patient. On the otherhand, the sociocultural milieu in most devel-oping countries results in parents keepingchildren with poorly controlled seizures athome and not in institutions. As a result, thelife of at least one parent (usually the moth-er) is devastated, but he or she will contin-ue to sacrifice anything to be able to lookafter the ill child. Additionally, families oftenmust make severe compromises to be ableto afford the cost of AEDs prescribed to theirchildren.

Siblings suffer when a child with epilepsyis given undue attention by parents, whetheror not seizures are controlled. Furthermore,the needs of unaffected siblings are oftenunmet when parents spend limitedresources on AEDs.

PUBLIC KNOWLEDGE, ATTITUDES, AND PERCEPTIONSNegative attitudes toward people withepilepsy are the result of misconceptionsabout the nature of epilepsy. Although gov-ernments in most developing nations recog-nize the importance of epilepsy as a healthcare problem, they remain preoccupied withthe struggle to provide clean drinking water,immunizations, and other such basic healthneeds to their people. Poverty, illiteracy, andimproper use of limited resources continueto hamper efforts to educate the generalpublic about conditions such as epilepsy.

Belief in ContagionIn many parts of Africa and Asia, epilepsy isconsidered to be contagious. Consequently,epileptic patients may not be attended toduring or after seizures, because people areafraid of being contaminated by their sweat,urine, saliva, flatus, and even breath. Air isoften evoked as a way of entry of the devilinto the body, especially for pregnantwomen whose newborn could be affectedby this presumed epileptogenic influence.Very often, family members of persons withepilepsy ask if they should share food withothers in the house. Elimination of this sin-gle misconception would not only reduceanxiety and unnecessary complication, butprevent a considerable percentage of mor-bidity and mortality associated with epilepsyin developing countries. The authority of thechief of the village may be necessary to con-firm that epilepsy is not contagious and thata patient can be cared for without any dan-ger to the caregivers.

Belief in PossessionEpilepsy is often perceived as a supernaturalailment, caused by ancestral spirits or attrib-uted to possession by evil spirits. It is alsothought to be due to witchcraft and “poison-ing.” Under Christian missionary teaching,epilepsy may have come to be considereddemoniac possession or divine punishmentfor sins, in accordance with biblical exam-ples. Amalgamation of indigenous traditionswith Judeo-Christian or Islamic doctrinesinfluence popular attitudes toward epilepsy.Low levels of literacy and limited possibili-ties for people to acquire medical informa-tion contribute to the persistence of thesenegative cultural beliefs and resultant harm-ful behaviors.

Fear of InheritanceIn some countries, like the Indian subconti-nent, there may be no problem with mar-riage if the boy has epilepsy, but a girl withepilepsy usually finds it impossible to getmarried after disclosing her disorder. As aresult, parents of most girls with epilepsywill not reveal this information to a potentialmarriage prospect (most marriages are stillarranged in this region). Very often, thesewomen have a seizure soon after the mar-

Psychosocial Issues

111

KEYPOINTS

n Every seizure is stressful,especially generalizedtonic-clonic events that canevoke fear of death due tothe loss of consciousness.This fear leads tooverprotection.

n In many parts of Africa andAsia, epilepsy is consideredto be contagious.Consequently, epilepticpatients may not beattended to during or afterseizures, because peopleare afraid of beingcontaminated by theirsweat, urine, saliva, flatus,and even breath.

n Epilepsy is often perceivedas a supernatural ailment,caused by ancestral spiritsor attributed to possessionby evil spirits. It is alsothought to be due towitchcraft and “poisoning.”

n Low levels of literacy andlimited possibilities forpeople to acquire medicalinformation contribute tothe persistence of thesenegative cultural beliefsand resultant harmfulbehaviors.

riage (due to missed medicines, the stress ofmarriage, and sleep deprivation since mostmarriages are all night affairs), with drasticconsequences. Clear information about thegenetic risks of epilepsy should help allevi-ate this problem.

Restrictions on Activities of Daily LifeDue to stigma, misconceptions, and over-protection, many activities are forbidden forthe epileptic patient. These include familytasks, schooling, employment, and leisureactivities, even simple sports. Young personswith epilepsy are often excluded from nor-mal childhood activities because their play-mates believe they suffer from a contagiousillness or a psychiatric disturbance. Mosthealth care givers do not understand thatsports can be an excellent means to inte-grate children with epilepsy into their peergroup.

People with epilepsy are discriminatedagainst when seeking employment, for wantof any rules and regulations pertaining toepilepsy and unemployment in most devel-

oping countries. As a result, most peoplehide their epilepsy while applying for jobsor selecting careers. On the other hand,many persons with epilepsy have jobs thatpresent a risk of injury because of theirseizures. A vigorous effort is needed at thegovernment and local community levels tointegrate people with epilepsy into society,to make them feel as useful and productiveas possible.

There are no universal driving regulationsfor people with epilepsy. Every country hasits own laws. Many developing countriesthat have driving laws consider epilepsy,whether or not seizures are controlled, to beincompatible with ever obtaining a driver’slicense.

In many developing countries, there is ahigh rate of school dropout due to poorseizure control or ongoing subclinicalseizure activity, leading to poor scholasticperformance. Also, parents can be ashamedto send their child with seizures to school, todisturb the class, or reveal that they havesomeone with epilepsy in their family.


112

KEYPOINTS

n People with epilepsy arediscriminated against whenseeking employment, forwant of any rules andregulations pertaining toepilepsy andunemployment in mostdeveloping countries.

CASE STUDY

Presentation: A 25-year-old girl had a history of three generalized tonic-clonic seizures at age 15, 17, and 20 years. Oneseizure occurred in sleep while the remaining two occurred while she was awake during the day. She had no previous histo-ry of seizures, myoclonic jerks, or absences. No family member was affected with seizures.

Evaluation: Her neurologic examination was normal. The EEG done after the third seizure showed brief generalized spike-wave discharges “at a few places” and CT scan of the head was reported to be normal.

Treatment and outcome: She was treated with carbamazepine (600 mg per day) and subsequently remained seizure free. Itwas decided to taper off the carbamazepine after a seizure-free interval of 3 years, and finally, the medicine was stopped.She then became engaged to a boy chosen by her parents. While waiting for the marriage to take place, she experiencedanother seizure about 2 months after stopping carbamazepine. The girl’s family disclosed her seizure history to the boy’s fam-ily, and the boy’s parents canceled her engagement. The girl was restarted on carbamazepine, but became depressed. Withproper counseling, she returned to a normal life.

Comment: Even today, epilepsy carries a heavy stigma both in developing and developed countries. In many countries like inthe Indian subcontinent, a girl with epilepsy suffers greater discrimination than a boy with epilepsy. On the one hand, manygirls are declared not suitable for marriage due to epilepsy, while on the other, paradoxically, young girls with epilepsy maybe forced into marriage due to the belief that epilepsy will be cured by marriage. While managing such cases, it should beemphasized that the majority (>90%) of women with epilepsy can lead a normal married life and can have normal childrenwhile on AEDs. Additionally, people can develop seizures at any time—even after marriage. Epilepsy can neither be cured bymarriage nor is it a bar to marriage.

Often, teachers ask parents to keep theirchild at home because they are not willingto take responsibility for seizures that mightoccur in class. These factors contribute tothe education gap between people withepilepsy and the general population, whichaggravates the burden of epilepsy and neg-atively impacts the integration of peoplewith epilepsy into society.

FAILURE TO SEEK HELPEven where there are adequate means fortreatment of epilepsy, the majority of peoplesuffering from this disorder in many devel-oping countries are not treated. Large partsof the population who can, geographicallyand financially, reach modern medical facil-ities are treated intermittently. Eitherbecause their poverty does not allow themto afford the cheapest drugs, or they havenot been well health-educated about thenecessity of a long-term treatment, it is nowestimated that the treatment gap (related tomodern medications) is 80% of the popula-tion suffering from epilepsy in developingcountries. In Ethiopia, a prospective studyidentifying 139 people with previously diag-nosed epilepsy reported that 39% werereceiving AED treatment (phenobarbital);19% were using only traditional treatment;and 42% did not receive any—modern ortraditional—treatment.

PSYCHIATRIC COMORBIDITY IN DEVELOPING COUNTRIESTwo main situations occur in developingcountries regarding eventual neuropsychi-atric comorbidity. The first is the associationof epileptic seizures with a psychiatric con-dition. The main examples of this are epilep-tic encephalopathies. In this context, con-sanguineous marriages are responsible for afamilial distribution of such conditions. Thefamily then is considered to be “possessed”and becomes feared and discriminatedagainst. The second situation results from

the fact that people with epilepsy are moreoften referred to psychiatrists than neurolo-gists, because there are fewer of the latterand because a large part of the populationconsiders the clinical manifestations of manyseizure types as “psychic.” The result can behelpful when the epilepsy is intractable andthe behavioral problems are more easilymanaged; however, the prognosis is usuallynot good. In most developing countries,there are no centers or programs for dealingwith such cases. Better cooperation betweenrelevant specialists, such as neurologists,neurosurgeons, psychiatrists, psychologists,and social workers, is needed to providehelp in these very difficult situations.

CONCLUSIONSIn many developing countries, epilepsy isnot considered to be a medical disorder.People with epilepsy are subjected tostigmatization, rejection, discrimination, andrestrictions in social functions. A very heavyburden is borne in medical, social, and eco-nomic spheres. The major causes of thepatient’s predicament could be amelioratedby improving general knowledge and creat-ing a bridge between traditional and modernworlds. There are many cultural obstacles tothe application of modern medical practice.Patients can spend more than 20 years in tra-ditional therapies before seeking consulta-tion in a medical facility. However, it is notin the interest of the patient to consider thetwo practices mutually exclusive. In additionto modern pharmacological treatment, tradi-tional healers can help patients use theirown cultural background to deal with relat-ed psychological stress. These cultural fac-tors, which not only contribute to disability,but can also exacerbate seizures, includestigma, issues of safety, concerns of a largefamily circle, knowledge, attitudes, and per-ceptions of the community and the public ingeneral, failure to seek help, and the impactof psychiatric comorbidity.

Psychosocial Issues

113

KEYPOINTS

n Often, teachers ask parentsto keep their child at homebecause they are notwilling to takeresponsibility for seizuresthat might occur in class.

n Better cooperationbetween relevantspecialists, such asneurologists,neurosurgeons,psychiatrists, psychologists,and social workers, isneeded to provide help inthese very difficultsituations.

CITATIONS AND RECOMMENDED READINGAdotévi F., Stéphany J. Représentations culturelles de l’épilepsie au Sénégal. Med Trop 1981;(1)3:283–288.

This very instructive article is one of the first published by African professionals on the cultural context of epilep-sy in a francophone African country.

Gouro K. Épilepsie et culture. Synapse, 1995;149:23–24.

A concise but excellent discussion on the relationship between cultural background and the interpretation of epilepsy.

Jilek-Aall L. Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures. Epilepsia1999;40:382–386.

This Canadian author has tremendous experience as a “bush doctor” in East Africa. Here she describes the impactof religion on the cultural interpretation of epilepsy in this region.

Martino P, Bert J, Collomb H. Épilepsie et possession (à propos d’un cas privilégié). Bull Soc Med Afr Noire Lang Fr1964;(9)1:45–48.

The founder of modern neuropsychiatry in West African countries reports a case of epilepsy which was wronglyattributed to subnatural causes.

Milleto G. Vues traditionnelles sur l’épilepsie chez les Dogons. Méd Trop 1981;41:291–296.

This paper describes views on epileptic seizures held by the Dogon people, an ethnic group in West Africa basedmainly in Mali.

Pilard M, Brosset C, Jumod A. Les représentations sociales et culturelles de l’épilepsie. Med Afr N1992;(32)10:652–657.

An excellent paper by French physicians on their experience practicing medicine in Africa and their observationson the perceptions and cultural interpretations of seizures and epilepsy in the local populations.

Radhakrishnan K, Pandian JD, Santhoshkumar T, et al. Prevalence, knowledge, attitude and practice of epilepsy inKerala, South India. Epilepsia 2000;41:1027–1035.

This is an excellent article on attitudes about epilepsy in South India, where traditional culture is very strong.

Uchôa E, Corin E, Bibeau G, Koumaré B. Représentations culturelles et disqualification sociale. L’épilepsie dans troisgroupes ethniques du Mali. Epilepsia 1992;(33)6:1057–1064.

This paper compares the cultural impact and interpretation of epilepsy in three different ethnic groups in Mali.

Watts AE. The natural history of untreated epilepsy in a rural community in Africa. Epilepsia 1992;33:464–468.

In developing countries, chronic diseases are usually considered to have supernatural rather than natural caus-es. Chronic, untreated epileptic seizures are a dramatic example of this, as reported here.

Wig NM, Suleiman R, Routledge R, et al. Community reaction to mental disorders. A key informant study in threedeveloping countries. Acta Psychiat Scand 1980;61:111–126.

It is interesting to learn, from this article, that fear, discrimination, and stigmatization of epilepsy are commonthemes across traditional cultures.


114

115

CHAPTER 9

PUBLIC HEALTH ISSUES

KEYPOINTS

n Regions with limitedneurologic expertise areunfortunately also areas inwhich the burden ofneurologic disorders isheaviest and most medicalcare is provided bynonphysician practitioners.In such an environment,the neurologist needs tofunction as a medicaleducator and patientadvocate rather thansimply a clinician.

n The role of the neurologistin developing countries as apublic health advocatecannot be overstated.

The appropriate role for the neurologistworking in developing countries differssomewhat from that of most other medicalcare providers. Regions with limited neuro-logic expertise are unfortunately also areasin which the burden of neurologic disordersis heaviest and most medical care is provid-ed by nonphysician practitioners. In such anenvironment, the neurologist needs to func-tion as a medical educator and patient advo-cate rather than simply a clinician. Throughmedical education of general physicians,clinical officers, nurses, midwives, and othernonphysician care providers, the neurologistin developing countries will be able toimprove quality of care for a much greaterpopulation of patients—a populationextending far beyond the number of peoplewho could effectively be managed by a sin-gle physician or clinic. By active patientadvocacy through interactions with policymakers and hospital administrators, the neu-rologist can impact the very healthcare sys-tem people with epilepsy must access andutilize for effective treatment. The role of theneurologist in developing countries as apublic health advocate cannot be overstated.

The World Health Organization (WHO)defines a “public health issue” as a problem,which occurs frequently, carries a substantialrisk of death or disability, and places burdenupon the individual, family, community,and/or society. Certainly epilepsy meets thesecriteria. As discussed in Chapter 3, epilepsyrepresents a prevalent condition, particularlyin developing regions. For many individuals,especially those suffering from uncontrolledseizures, the burden of epilepsy includes sub-stantial physical disability. Even among peo-ple with fairly infrequent seizures, health-related quality of life is substantiallydecreased. The cost of the disease includes

the direct costs of utilizing medical care andeven greater expense associated with losthuman resource potential and decreasedwork productivity. The psychosocial and eco-nomic effects of epilepsy impact the personwith epilepsy, their family, and their commu-nity. And much of the global burden ofepilepsy results from preventable causes. Assuch, epilepsy from a public health perspec-tive deserves some consideration.

EPILEPSY AND SEIZURE PREVENTION

Primary PreventionEpilepsy represents the most commonchronic neurologic disorder in the develop-ing world, and preventable causes of epilep-sy abound there. Limited medical servicesand unstable drug supplies, as well asepilepsy-associated stigma, further increasethe urgency of epilepsy prevention. Focusedpublic health interventions and improvedaccess to and quality of specific medicalservices could substantially decrease theburden of epilepsy in most developingcountries.

In poverty-ridden regions, chronic malnu-trition and limited access to prenatal andantenatal medical services negatively impactmaternal health and substantially increasethe risk of birth injury and neonatal infec-tions. Improved nutrition for women ofchildbearing years and increased access toprenatal clinics would assist in decreasingthese early central nervous system (CNS)injuries. Perinatal care should be optimizedwith the use of trained traditional birth atten-dants (TBAs) and TBAs must have access toa secondary referral source that can providesurgical intervention, if needed. A greaternumber of TBAs are needed, especially inrural regions, to support the evaluation and

monitoring of pregnant women well beforetheir delivery. This will facilitate the timelyidentification of problems so preemptivemeasures can be taken before birth traumaor perinatal infections occur. Optimal prena-tal care will also identify potentially devastat-ing infectious disorders, such as syphilis andgonorrhea, averting damage to the child, themother, and her partner. Actions taken toimprove birth outcomes would not onlydecrease the burden of epilepsy and cerebralpalsy, but also would improve women’shealth and decrease infant mortality.

Children who escape early CNS injuriesremain at risk due to high rates of childhoodCNS infections, such as bacterial meningitisand cerebral malaria that undoubtedly con-tribute to epilepsy development. Appropriatevaccination measures, bed net usage, malar-ia prophylaxis when indicated, and readyaccess to adequately trained and equippedhealthcare providers who can offer expedi-ent treatment for these life-threatening eventsare all critical for averting such epilepsy-inducing injuries. When common childhoodillnesses go untreated, complications, such asbronchopneumonia with hypoxia andmeasles encephalitis, may ensue. Chronicotitis media or tonsillitis may progress withmeningeal seeding to secondary meningitis.Failure to manage less severe infections canallow prolonged fevers with recurrent com-plex febrile seizures. Adequate, affordablehealth services for children are of paramountimportance, since these services can avertmany of the epilepsy-inducing events.Parents and community leaders need educa-tion regarding the signs of serious CNS infec-tions, and feasible care options must beavailable to them. Health care providers mustbe made aware of opportunities for preven-tion and should have a heightened apprecia-tion for the earliest signs of CNS involvementwhen otherwise routine pediatric conditionspresent.

Among adults and children alike, traumat-ic brain injury predisposes to epilepsy indeveloping regions. The circumstances asso-ciated with head injury, including domesticand societal violence, wars, and motor vehi-cle accidents, all can be decreased if amplepublic and governmental support exists. Thestate of public roads and the vehicles travel-

ing these roads are especially appalling inmany low-income countries. Motor vehicleoccupants, as well as thousands of pedestri-ans and bicyclists, are injured every year bycars and trucks lacking such basic features asbrakes and headlights. The health implica-tions of poor roads and road safety must bemade clear to public officials. The use of seatbelts should be encouraged, possiblyrequired. Public education and ancillary fund-ing is needed to increase helmet usage bybicyclists and motorcyclists. Much can begained through public education, social mar-keting, and lobbying of government agencies.

Cerebrovascular disease, a key cause ofepilepsy in the older population of devel-oped countries, may soon become a signifi-cant contributor to the burden of epilepsy inthe developing world. In urban regions, thearrival of fast food, high in fat and salt, ispromoting an epidemic of malnourishedobesity accompanied by hypertension anddiabetes. Tobacco companies are increasing-ly marketing their wares in low-incomeregions where nicotine abuse and addictionare on the rise even among the poorestmembers of society. Public officials must bemade aware of the long-term health implica-tions of these market forces. Health centersstruggling to provide urgent medical servic-es must be encouraged and rewarded forsupplying preventive services through thescreening and treatment of hypertension anddiabetes. Rapid action is necessary to quellthe inevitable epidemic of cerebrovasculardisease that will undoubtedly be followedby increasing rates of stroke-associatedepilepsy.

Neurocysticercosis (NCC), the numberone cause of epilepsy in Latin America andthe likely culprit for much epilepsy in otherregions, can potentially be prevented withimproved sanitation measures and higherstandards of food preparation. Regions withendemic cysticercosis have a populationprevalence of 6% to 10% for systemic expo-sure to T. solium and an estimated 400,000people suffer from epilepsy due to NCC.Expensive, complicated immunizations arenot needed; simple provision and usage oflatrines that limit animal (primarily pig)access to human waste could break thecycle of cysticercosis. Improved personal


116

KEYPOINTS

n Healthcare providers mustbe made aware ofopportunities forprevention and shouldhave a heightenedappreciation for theearliest signs of CNSinvolvement whenotherwise routine pediatricconditions present.

n Neurocysticercosis (NCC),the number one cause ofepilepsy in Latin Americaand the likely culprit formuch epilepsy in otherregions, can potentially beprevented with improvedsanitation measures andhigher standards of foodpreparation.

hygiene and safer sources of drinking waterwould decrease the human fecal-oral spreadof infective ova that result in CNS infection.To date, immunization and mass chemother-apeutic measures have not shown long-termeffectiveness for cysticercosis control, butsince NCC-induced epilepsy often presentsyears after infestation, intervention studiesusing human and porcine chemotherapy willnot show improvements in epilepsy rates forseveral years, even if effective.

The necessary public health interventionsare not trivial—less than half of the develop-ing world’s inhabitants have access to safewater and sanitation. But decreasing thetransmission of cysticercosis would beaccompanied by decreases in other water-borne illnesses. The potential health benefitsof improved water and sanitation extend farbeyond the prevention of epilepsy.

Potentially Heritable Causes: Marriage and Childbearing for People with EpilepsyDespite much evidence to the contrary,common beliefs regarding the hereditabilityof epilepsy remain a source of stigma inmany developing countries. These concernsand beliefs should be addressed in an openforum with public education. As discussedin Chapter 3, genetic epilepsies are rare andepilepsy should not be considered a reasonfor preventing marriage and/or childbearing.In Egypt, 22% of people with epilepsy had afamily history of epilepsy, but parental con-sanguinity was found in 65% of the totalsample, and mental subnormality also result-ed from such intrafamilial unions. Althoughepilepsy is certainly not grounds for the pro-hibition of marriage and/or childbearing,consanguineous marriages should be dis-couraged regardless of the presence orabsence of epilepsies within families.

Seizure and Injury PreventionAlthough antiepileptic drugs (AEDs) com-prise a critical component of epilepsy care,AEDs will not “cure” epilepsy. However,some lifestyle interventions can assist withseizure control and injury prevention. Inaddition to encouraging patient compliancewith medications, healthcare providers car-ing for people with epilepsy should recom-

mend maintenance of a regular, adequatesleep schedule. People with epilepsy shouldalso be cautioned against excessive intake ofalcoholic beverages or stimulants, as thesecan precipitate seizure activity. Candidadvice regarding safety issues should begiven. People with active seizures should becautioned against driving or operating heavyor dangerous equipment, and in general,these individuals should not be placed invulnerable positions that could result ininjury if a seizure occurs.

People with epilepsy and their familiesmust be counseled regarding the risk ofexposure to bodies of water through fishing,fetching water, or swimming alone. Theseactivities must also be avoided in the pres-ence of people unlikely to assist if a seizureoccurs. Working over or around open firesor kerosene heaters should be discouraged.Often, household chores can be reallocatedto other members of the family to sparewomen with active epilepsy prolonged peri-ods of standing over open flames. Peoplewith epilepsy should also be cautionedagainst climbing heights and traveling intounpopulated regions alone. These instruc-tions may seem very obvious to trained neu-rologists, but other medical care providerswill almost certainly fail to offer such adviceunless explicitly trained to do so. All of theseissues should be considered when a patientis initially diagnosed with epilepsy. Asseizure control is gained, restrictions may begradually lifted.

THE ECONOMIC IMPACT OF EPILEPSYThe direct costs associated with epilepsyinclude medical expenses associated withmedications, hospitalization, and outpatientclinic fees. Costs not typically considered instudies of developed countries include med-ical services rendered for seizure-relatedinjuries (e.g., burns) and the high cost ofsimply reaching a clinic equipped to dealwith seizure disorders. Such expensesshould be included when assessing thedirect cost of epilepsy in developing regions.In Italy, the direct costs of epilepsy resultprimarily from hospital admissions in peoplewith severe epilepsy and AEDs in the gener-al population of people with epilepsy. In theUS, new cases of epilepsy are associated

Public Health Issues

117

KEYPOINTS

n People with epilepsy andtheir families must becounseled regarding therisk of exposure to bodiesof water through fishing,fetching water, orswimming alone.

n Working over or aroundopen fires or keroseneheaters should bediscouraged.

with a cost of ~$5,400/case in the initial yearafter diagnosis. Studies in India indicate thatamong patients in a tertiary care center,direct costs alone could consume up to 0.5%of the gross domestic product, if the expen-ditures from these individuals were repre-sentative of the general population of peo-ple with epilepsy. Where recently developedAEDs are available and highly technologicaldiagnostic services are accessible, these tendto drive the overall direct cost of epilepsycare.

Although novel AEDs have been devel-oped, the high cost of these new agents dic-tates that older AEDs will figure prominent-ly in the epilepsy care regimens of develop-ing countries. The AEDs most commonlyused in sub-Saharan Africa are: phenobarbi-tal (prescribed in 65%–90%); carbamazepine(5%–25%); phenytoin (2%–25%); and val-proate (2%–8%). Estimated annual costs forthese medications in sub-Saharan Africa are:phenobarbitone $25–50; carbamazepine$200–300; and valproate $300–500. Wherethe average laborer earns less than $1 a day,drug costs may present a significant barrierto care.

According to the World Bank, in 2001, thetotal annual healthcare expenditures (includ-ing public and private funding) for develop-ing countries ranged from $21–74 per capi-ta. Sources of epilepsy care funding includegovernmental budgets, donations from inter-national agencies and nongovernmentalorganizations, social or compulsory healthinsurance funds, private insurance, out-of-pocket spending, charitable donations, anddirect payments by private corporations. Todate, few studies have been published thatformally evaluate the economic aspects ofepilepsy in the developing world, and nosuch work has been undertaken in Africa.Specifically, studies to estimate the cost ofepilepsy care, cost-effectiveness of AEDsand epilepsy surgery, and lost economicopportunities are needed.

Chronic, disabling, stigmatizing disorderssuch as epilepsy are characterized by incur-ring much higher indirect than direct costs,and many of the indirect costs cannot beaccurately captured by simple economic fig-ures. Indirect costs should encompass lostwages and decreased productivity of the

people with epilepsy and their careproviders. No validated measures exist toassess lost opportunities for education,social advancement, and employment,although such lost human resource potentialcertainly occurs in regions where epilepsy isheavily stigmatized.

Given the limited number of physiciansand specialists in rural regions, manypatients require referral to more urban areasfor assessment. The difficulties these refer-rals pose for families and patients should notbe underestimated. User fees, the cost oftransport, and the costs of supporting familymembers who accompany the patients whilein the city require substantial resources fromrural dwellers, who may utilize a noncurren-cy, bartering system for most of their needs.Most traditional cultures require the dead tobe buried in or near their home villages.Therefore, for acutely ill patients, the fami-lies may also need to consider the exorbitantcost associated with transporting a deceasedfamily member from the city back to the vil-lage. Under such circumstances, localhealthcare workers are often reluctant tosuggest such distant referrals. This reluc-tance can be exacerbated by consultingphysicians who fail to give proper feedbackto the referring healthcare providers. Keepin mind that the referring healthcare worker,whether a physician, nurse, or clinical offi-cer, will ultimately be the person caring forthe patient. They need detailed instructionsabout management, prognosis, when to re-refer, and medication adjustments.

DELIVERY OF CARE IN COUNTRIES WITH LIMITED RESOURCESEighty-five percent of the world’s populationof people with epilepsy resides in develop-ing regions. Unfortunately, this great burdenof disease is accompanied by an 80% to 85%treatment gap—meaning less than 20% ofpeople requiring treatment for epilepsy arereceiving treatment. Several problems con-tribute to the treatment gap, including cul-tural interpretations of the seizures, insuffi-cient anticonvulsant drug supplies, poordrug distribution systems, and a lack ofphysician and paramedical personnel.Ironically, developed countries, especiallythe US and UK, solve their medical staff


118

KEYPOINTS

n Although novel AEDs havebeen developed, the highcost of these new agentsdictates that older AEDswill figure prominently inthe epilepsy care regimensof developing countries.

n Given the limited numberof physicians and specialistsin rural regions, manypatients require referral tomore urban areas forassessment. The difficultiesthese referrals pose forfamilies and patientsshould not beunderestimated.

n Several problemscontribute to the treatmentgap, including culturalinterpretations of theseizures, insufficientanticonvulsant drugsupplies, poor drugdistribution systems, and alack of physician andparamedical personnel.Ironically, developedcountries, especially the USand UK, solve their medicalstaff shortage by hiringphysicians and nurses fromdeveloping regions. Thispractice results indeveloping countriesbearing the financialburden of medicaleducation for developedones.

shortage by hiring physicians and nursesfrom developing regions. The medical per-sonnel rarely return to practice in theirnative country. Understandably, profession-als in resource-poor regions seek better cir-cumstances for themselves and their fami-lies. But it must be recognized that, inessence, this practice results in developingcountries bearing the financial burden ofmedical education for developed ones.

Strong traditional belief systems com-bined with limited access to formal health-care lead many people with epilepsy to seekcare through traditional healers. People withepilepsy admitted to a medical facility forseizure-associated burns or injuries oftennever bring their underlying disorder to theattention of medical staff. Neurologists mustprovide strong advocacy support to placeepilepsy care on the healthcare agenda fordeveloping countries. This will be particular-ly challenging where health systemresources already strain under the impact ofHIV.

Models of Epilepsy CareClearly, the model for epilepsy care deliveryused in developed countries where patientsare managed by physicians, often epileptol-ogists in tertiary care centers, is neither fea-sible nor desirable in resource-poor settings.Even in those developing regions where ter-tiary care centers are available, these epilep-sy services will be limited to the minority ofpatients. No single model for epilepsy caredelivery can be applied to all developingcountries, but a few general principles mayhelp formulate appropriate local and nation-al health policies.

Epilepsy care should be included in thebasic health services offered in most devel-oping countries. Medical care providers,regardless of their level of expertise, must befamiliar with epilepsy symptoms and presen-tations, since only through their diagnosticsuspicion will people with epilepsy come tothe attention of more sophisticated practi-tioners. Nurses and clinical officers staffingrural and primary care centers should beeducated to recognize possible cases of


119

KEYPOINTS

n Medical care providers,regardless of their level ofexpertise, must be familiarwith epilepsy symptomsand presentations, sinceonly through theirdiagnostic suspicion willpeople with epilepsy cometo the attention of moresophisticated practitioners.

CASE STUDY

Presentation: A 23-year-old male with well-characterized focal seizures and secondary generalization presented with an ocu-lar injury resulting in loss of the right eye. He had experienced a generalized seizure while setting barbed-wire fencing andhad fallen forward onto the roll of fencing, with subsequent eye and facial injuries. The ward nurses felt somewhat unsym-pathetic toward the patient. His outpatient records reported good seizure control when he was taking phenobarbital, buthe only came for medical review and medications intermittently. This seizure-related injury had occurred off medications.

Evaluation: The physician and social worker met with the patient together to discuss issues of treatment adherence given thedire consequences of his recent seizure. The patient pointed out that he lives 20 km from the hospital and there is no regu-lar transport available to the hospital. When he came for his medications, he was typically given only a 30-day supply (a gen-eral hospital policy that could be overridden if the physician writes a letter explaining why). To come to the hospital requireda day’s travel in each direction. Although there was a rural clinic nearer to his village, the supplies box provided included onlyvery basic drugs and did not include phenobarbital. One reason phenobarbital was not included in the basic drug box wasthat the clinical officer staffing the rural health clinic had never been trained in how to use this drug.

Treatment: The patient was restarted on phenobarbital and discharged with a 3-month supply. Later discussions with theRural Health Clinic staff throughout the district revealed that this was a common problem. Many of them had people withepilepsy come to their clinics seeking phenobarbital.

Clinical officers were asked to provide a list of the people with epilepsy in their catchment areas, and estimates were madefor the quantity of phenobarbital that each would need. Training sessions were held so clinical officers could maintain treat-ment for people already determined by local physicians to have epilepsy. They were also trained in how to recognize possi-ble cases of epilepsy for referral to the hospital. The number of people with active epilepsy receiving treatment increasedsubstantially after the local healthcare workers were provided with the training and medications needed.

Comments: Access to medications can be blocked by geographic barriers as well as simple economic barriers. Neurologists indeveloping regions can implement simple programs that may have a major impact on the population of people with epilep-sy in their countries. The role of the neurologist as a medical educator and patient advocate in such environments cannot beoverstated!

epilepsy and be provided with appropriatereferral options when potential cases cometo their attention. In countries such as India,specialized expertise in epilepsy is availablein major cities, either through trained neurol-ogists or generalists with particular interestin epilepsy. In these countries, more effi-cient use of limited specialty skills can bemade if a clear referral system is developedthat utilizes a screening system wherebypeople with possible epilepsy are first seenby their local physician before seeking high-er-level diagnostic services. If limited neuro-logic services are available without such afiltration system, more vulnerable personswho require such expertise will be less like-ly to access needed care. Of course, such asystem will only function properly if the pri-mary care physicians screening referrals areadequately educated regarding neurologicassessment and triage.

In regions such as sub-Saharan Africa,where neurology-specific training is sparseand neurologists are extremely rare, person-nel in rural and primary care clinics shouldhave recourse to physician-level referralwhenever possible. Physicians can then pro-vide confirmatory diagnosis (including anyindicated and available diagnostic services);assess patients to assure there is no omi-nous, treatable underlying etiology for newseizure disorders; initiate treatment; and pro-vide local medical personnel with a treat-ment maintenance plan that can be easilyfollowed by the healthcare providers towhom patients have ready access.

Distance from health care facilities isoften a problem, especially for ruraldwellers. Nonphysician primary healthcareworkers, when properly trained, can pro-vide appropriate care for people withepilepsy. Adherence to treatment improvessubstantially for patients when care is pro-vided closer to home. If resources are avail-able to establish local specialty clinics ded-icated to epilepsy care, patients may bene-fit substantially from the dedicated servicesof nonphysician providers who havereceived additional neurologic training.Nurse-led noncommunicable disease serv-ices have been established in South Africaand allow district hospitals to transferpatients with chronic disorders to these

nurses for long-term management.Otherwise, epilepsy care may be verticallyintegrated into the existing primary health-care programs. Ample experience indicatesthat without additional training and publicsupport, primary healthcare workers will bereluctant, possibly even resistant, to provid-ing care for people with such a misunder-stood and stigmatized condition.

Even physicians need to be better educat-ed in the cost-effective treatment of epilep-sy. In environments with limited resources,epilepsy can be diagnosed clinically.Extensive testing is not required unless diag-nostic uncertainty prevails. Less expensivemedications that are more likely to be avail-able and much more affordable for thepatients should be first-line therapies.Polypharmacy is not necessary in manycases, and with more drugs comes greaterexpense, more side effects, and decreasedcompliance. These basic principles shouldbe reiterated to primary care physicians andfrequently reinforced. In India, one tertiarycare center found that proper treatmentallowed up to one-third of patients onpolypharmacy to be maintained onmonotherapy, with considerable savings.

Health-Seeking StrategiesAn intact and efficient referral and health-care delivery system for epilepsy will onlybe effective if people with epilepsy accessthe formal healthcare system. Because tradi-tional beliefs dub epilepsy a supernaturalaffliction in many regions of the developingworld, the majority of the patients will ini-tially or exclusively consult an indigenous ortraditional healer. This care-seeking choiceoften results in long delays before consulta-tion with the modern medical system. Byworking in collaboration with traditionalhealers, physicians might be better able toaccess people with epilepsy early, and couldpotentially offer opportunities to modify cer-tain harmful practices. Developing such col-laborative associations may be very difficult,particularly where the physician-indigenoushealer relationship has historically been oneof competition and animosity. But to bestserve people with epilepsy in many devel-oping countries, efforts must be made toresolve this conflict. The possibility that


120

KEYPOINTS

n Adherence to treatmentimproves substantially forpatients when care isprovided closer to home.

n In environments withlimited resources, epilepsycan be diagnosed clinically.Extensive testing is notrequired unless diagnosticuncertainty prevails. Lessexpensive medications thatare more likely to beavailable and much moreaffordable for the patientsshould be first-linetherapies.

n By working in collaborationwith traditional healers,physicians might be betterable to access people withepilepsy early, and couldpotentially offeropportunities to modifycertain harmful practices.

locally available plants may possess anticon-vulsant properties certainly should also beconsidered.

Utilization of other members of the com-munity as assistants in the distribution ofdrugs and active community participationwill optimize local support for people withepilepsy and their families. The key to suc-cess for any national epilepsy care programis education—of the individual, the family,and the community, as well as healthcareprofessionals at all levels of training andexpertise. Since the estimated treatment gapfor epilepsy care in most developing coun-tries is >80%, we have much room forimprovement. Today, new opportunities forsocial marketing exist through mass media(newspaper, radio), and medical personnelcan benefit from medical education throughnew telemedicine technologies and theInternet.

Funding Epilepsy Care ServicesFiscal resources for funding even basichealth services are frequently insufficient tomeet the needs of people in the developingworld. Regardless, efforts must be made tomake public policy makers aware of the bur-den of this treatable disease. Even the poor-est countries may offer lower clinic fees andmedications to people with certain chronicconditions (e.g., hypertension, diabetes).Epilepsy should be included among theserecognized and subsidized disorders.Incorporating epilepsy care into the primaryclinics will best suit those countries orregions with the least resources available,since marginal costs will be least under thissystem. Optimal health policy planning forepilepsy care requires reviewing the health-care system’s resources and recognizing thepopulation’s geographic, social, and finan-cial barriers to accessing these services.

Cost-sharing, especially by individualswith the resources to seek more technologi-cally advanced care, may be an importantmeans of financial sustainability for anepilepsy care program. But many peoplewith epilepsy experience economic hard-ships related to their disorder, and everyeffort should be made to ensure that finan-cial barriers do not prevent patients fromseeking care and maintaining compliance.

INFORMATION AND EDUCATIONEducating the public can be difficult, giventhe high rates of illiteracy in many regions,which range from 29% to 60%, with femalesdisproportionately affected. These limita-tions make it especially important to utilizeavenues such as radio (available for 160 per1,000 in Africa) and television (60 sets per1,000 people). Local languages and dialectsshould be used whenever possible. As sev-eral studies have confirmed grave miscon-ceptions regarding epilepsy even amongeducated persons in developing countries,newspapers are also worthwhile avenues forpublic advocacy.

The Global Campaign against Epilepsy isa prominent movement that aims to increasepublic awareness and education regardingepilepsy, identify the needs of people withepilepsy, and encourage governments toaddress these needs. Such patient-orientedsocial interventions can substantially benefitpeople with epilepsy through improvedcompliance and quality of life.

Professional DevelopmentEvery neurologist and most physicians in

developing regions will at times feel over-whelmed by the burden of disease theyencounter and the limited resources avail-able for care provision. Furthermore, out-side of academic centers, intellectualendeavors may be difficult to identify thatwill help ongoing professional develop-ment. All of these issues undoubtedly con-tribute to the “brain drain,” whereby healthprofessionals from developing regionsmigrate to developed countries. It should berecognizesd that professor exchanges, localcontinuing medical education programs,and research opportunities do exist to helpovercome some of these academic lapses.Such opportunities can be found throughthe World Federation of Neurology(www.wfneurology.org), the U.S. FulbrightProgram (http://www.cies.org/), and theU.S. National Institutes of Health(www.nih.gov), among others.

CONCLUSIONSAs highly trained physicians, neurologists indeveloping countries carry substantial“social capital.” Because there are too few


121

KEYPOINTS

n Many people with epilepsyexperience economichardships related to theirdisorder, and every effortshould be made to ensurethat financial barriers donot prevent patients formseeking care andmaintaining compliance.

neurologists in most developing regions topersonally deliver services directly to theentire population of people with epilepsy,neurologic specialists should direct a sub-stantial proportion of their efforts towardpublic policy, patient advocacy, and medicaleducation. Given the many preventablecauses of epilepsy in the developing world,opportunities abound to educate and impacthealth policy. Higher quality maternal andchild health services, better road conditions,improved water safety, and latrines coulddecrease the burden of epilepsy while pro-viding multiple other positive health benefitsto the public. Patient advocacy that eluci-dates the economic and psychosocial bur-den placed on the entire society by epilepsymay gain governmental support more effec-tively than the humanitarian appeals andeducation that are often effective in social

marketing. Neurologists in the developingworld face a difficult but rewarding chal-lenge if they choose to tackle these criticalpublic health issues.

CONTACT INFORMATIONGlobal Campaign against EpilepsyHanneke M. de BoerStichting Epilepsie InstellingenNederlandAchterweg 52103 SW HeemstedeThe NetherlandsFax: 31-23-5-470-119www.ilae-epilepsy.orgwww.ibe-epilepsy.orgwww.who.int/mental_health/management/globalepilepsycampaign/en/


122

CITATIONS AND RECOMMENDED READINGBegley CE, Famulari M, Annegers JF, et al. The cost of epilepsy in the United States: an estimate from population-

based clinical and survey data. Epilepsia 2000;41(3):342–351.

This is a recent analysis of the cost of epilepsy in an industrialized country, where 80% is attributed to those whoseseizures are not controlled by antiepileptic drugs.

Bern C, Garcia HH, Evans C, et al. Magnitude of the disease burden from neurocysticercosis in a developing coun-try. Clin Infect Dis 1999;29(5):1203–1209.

An excellent overview of the contribution of neurocycticercosis toward the burden of epilepsy.

Coleman R, Gill G, Wilkinson D. Noncommunicable disease management in resource-poor settings: a primary caremodel from rural South Africa. Bull World Health Organ 1998;76(6):633–640.

Provides an overview of health systems design for epilepsy care in resource-poor settings.

Janca A, Prilipko L, Saraceno B. A World Health Organization perspective on neurology and neuroscience. ArchNeurol 2000;57 (12):1786–1788.

Report on the WHO Perspectives and Policy for Neurosciences in general and neurological disorders for the pres-ent and future.

Jilek-Aall L, Rwiza HT. Prognosis of epilepsy in a rural African community: a 30-year follow-up of 164 patients in anoutpatient clinic in rural Tanzania. Epilepsia 1992; 33:645–650.

We revisit the Tanzanian population of people with epilepsy in the Mahenge Mountains after political unrestrequired the epilepsy care team in the region to exit suddenly. The study clearly described the personal devasta-tion among people with epilepsy that abrupt withdrawal of care can produce.

Kaiser C, Asaba G, Mugisa C, et al. Antiepileptic drug treatment in rural Africa: involving the community. Trop Doct1998;28(2):73–77.

Describes the important aspects of community participation when initiating community-based care programs aswell as programs requiring community support of the individual affected.

Mani KS, Rangan G, Srinivas HV, Srindharan VS, Subbakrishna DK. Epilepsy control with phenobarbital or pheny-toin in rural south India: the Yelandur study. Lancet 2001;357:1316–1320.

An excellent study reporting on the comparative usefulness of phenobarbitone and phenytoin in the treatment ofseizures at the community level in southern India.

Neuman RJ, Kwon JM, Jilek-Aall L, Rwiza HT, Rice JP, Goodfellow PJ. Genetic analysis of kifafa, a complex familialseizure disorder. Am J Hum Genet 1995;57(4):902–910.

A genetic analysis of a well-described Tanzanian population with very high rates of epilepsy. This population iswell-described in almost 25 years of publications.

Rwiza HT. The Muhimbili epilepsy project, a three-pronged approach. Assessment of the size of the problem, organ-ization of an epilepsy care system and research on risk factors. Trop Geogr Med 1994;46(3):S22–S24.

A multifaceted approach to epilepsy care involving all stakeholders. A must-read for anyone contemplating theorganization of a community-based epilepsy care program.

Scott RA, Lhatoo SD, Sander JW. The treatment of epilepsy in developing countries: where do we go from here? BullWorld Health Organ 2001;79(4):344–351.

This review concerns existing treatment possibilities in several developing countries, the impact of the sociocultu-ral environment, and a realistic public health approach.

Thomas SV, Sarma PS, Alexander M, et al. Economic burden of epilepsy in India. Epilepsia 2001;42(8):1052–1060.

A good study of the economic aspects of epilepsy care in a tertiary care hospital in southern India.

Tieffenberg JA, Wood EI, Alonso A, Tossutti MS, Vicente MF. A randomized field trial of ACINDES: a child-centeredtraining model for children with chronic illnesses (asthma and epilepsy). J Urban Health 2000;77(2):280–297.

Wagner AK, Bungay KM, Kosinski M, Bromfield EB, Ehrenberg BL. The health status of adults with epilepsy com-pared with that of people without chronic conditions. Pharmacotherapy 1996;16(1): 1–9.

Watts AE. The natural history of untreated epilepsy in a rural community in Africa. Epilepsia 1992, 33, 464–468.

In developing countries, chronic diseases are usually considered to have supernatural rather than natural caus-es. Chronic, untreated epileptic seizures are a dramatic example of this, as reported here.


123


125

APPENDIX

“OUT OF THE SHADOWS”ILAE/IBE/WHO

GLOBAL CAMPAIGN AGAINST EPILEPSY

THE CAMPAIGN AT A GLANCEA Global Campaign Against Epilepsy ismuch needed—the burden of epilepsy isunderestimated and the means available toreduce it are underutilized.

The problem is too complex to be solvedby individual organizations.

The three leading international organiza-tions working in epilepsy have thereforejoined forces to bring epilepsy “out of theshadows.”

The Campaign will assist governmentsworldwide to make sure that diagnosis,treatment, prevention, and social acceptabil-ity of epilepsy are improved.

The Campaign StrategyWorking along two parallel tracks, theCampaign will:

• Raise general awareness and understand-ing of epilepsy;

• Support Departments of Health in identi-fying needs and promoting education,training, treatment, services, research, andprevention in their countries.

The Campaign Tactics• To generate Regional Declarations on

Epilepsy, produce information on epilep-sy for policy-makers, incorporate epilepsycare into National Health Plans, and facil-itate the establishment of national organi-zations of professionals and lay personswho are dedicated to promoting the well-being of people with epilepsy.

• To help organize Demonstration Projectsthat illustrate good practice in the provi-sion of epilepsy care.

The Global Campaign is managed by aSecretariat consisting of representatives ofthe three responsible organizations:

• World Health Organization (WHO)• International League Against Epilepsy

(ILAE), professionals• International Bureau for Epilepsy (IBE),

lay persons

WHY HAVE A GLOBAL CAMPAIGN AGAINST EPILEPSY?A Global Campaign Against Epilepsy is nec-essary because the burden of epilepsy onindividuals and communities is far greaterthan previously realized. The problem is toocomplex to be solved by individual organi-zations. The three leading internationalorganizations working in epilepsy havetherefore joined forces to bring epilepsy “outof the shadows.”

The Campaign is conducted by the WorldHealth Organization (WHO) in partnershipwith the International League AgainstEpilepsy (ILAE) and the International Bureaufor Epilepsy (IBE). The aims of theCampaign are to provide better informationabout epilepsy and its consequences and toassist governments and those concernedwith epilepsy to reduce the burden of thedisorder.

What Is the Global Campaign?

Campaign Strategy and TacticsThe mission statement of the Campaign is:“To improve acceptability, treatment, servic-es, and prevention of epilepsy worldwide.”

Major goals are to ensure that epilepsycare is incorporated into National HealthPlans and to facilitate the existence in every

Reprinted with the permission of the GlobalCampaign Against Epilepsy, 2003.

country of organizations of professionalsand lay people who are dedicated to pro-moting the well-being of people withepilepsy.

In order to increase awareness of theproblems caused by epilepsy and the meansavailable to deal with them, conferenceshave been organized between key persons inhealth care administration and governmentand experts in the field of epilepsy. Theseconferences were held in the six WHOregions (Africa, the Americas, the EasternMediterranean, Europe, South-East Asia, andthe Western Pacific) and have resulted inRegional Declarations on Epilepsy, WhitePapers, and regional reports.

In order to assist Departments of Health,which are looking for tools applicable intheir country to realize the objectives of theCampaign, Demonstration Projects areorganized in a number of countries in differ-ent regions. These Demonstration Projectsoffer models of how to identify needs; howto educate and train staff involved in diagno-sis, treatment, services, prevention, andresearch; and how to promote education ofthe general public.

Management of the CampaignThree organizations collaborate in theGlobal Campaign Against Epilepsy: WHO(specialized agency of the United Nations,with 192 Member States), ILAE (with mem-ber organizations in more than 90 countries),and IBE (with member organizations inmore than 60 countries). ILAE memberorganizations consist of professionals con-cerned with medical and scientific aspects ofepilepsy, while those of IBE are concernedwith social aspects and the quality of life ofpeople with epilepsy.

In June 1997, these three partnerslaunched the Global Campaign AgainstEpilepsy simultaneously from Geneva,Switzerland, and Dublin, Ireland, during the22nd World Congress on Epilepsy. ASecretariat was established consisting of arepresentative from each of the three organ-izations, which oversees the day-to-day run-ning of the Campaign. The Secretariat isaccountable to an Advisory Board composedof two representatives of each of the threebodies. Both the Secretariat and the Advisory

Board members are accountable to theirrespective organizations. WHO worksthrough its regional offices and country rep-resentatives. IBE and ILAE work throughtheir regional commissions, their resource-oriented and problem-oriented commissions,and their national member organizations.

The Campaign structure and activities areoutlined in Figure 1.

General Activities of the GlobalCampaign

Collaboration to Increase Awareness about EpilepsySince WHO Cabinet approval in December1999, collaboration with and support for theCampaign have been strengthened throughthe involvement of the Regional Offices ofWHO. Regular contacts are maintained withvarious interested clusters and departmentswithin WHO.

Support has been provided by the GlobalHealth Forum for Health Research for areview of the evidence base for priority set-ting in epilepsy research. Furthermore, theapplicability to epilepsy of the common for-mat for priority setting was determined.

A number of IBE/ILAE Commissions areengaged in various developmental activitiesfor the Campaign, for example, regarding adefinition of the treatment gap and outcomemeasures for the Demonstration Projects.

Regional Conferences and DeclarationsAs part of general awareness-raising, region-al conferences on public health aspects ofepilepsy were organized in the six WHOregions (Africa, the Americas, EasternMediterranean, Europe, South-East Asia, andthe Western Pacific).

At these regional conferences, delegatesof epilepsy organizations of national andinternational lay persons (IBE) and profes-sionals (ILAE) met with public health expertsfrom governments and universities and rep-resentatives from WHO headquarters andregions. As the result of intensive discussionand examination of data presented by dele-gates, a Regional Declaration on Epilepsywas adopted after each conference, summa-rizing perceived needs and proposingactions to be taken. These declarations call


126

on governments and all health careproviders to join in taking strong and deci-sive action to meet the objectives of theGlobal Campaign Against Epilepsy.

Following the European Conference, theWHO Regional Office for Europe, together

with all European member organizations ofIBE and ILAE, strongly supported by WHOheadquarters, agreed to submit theEuropean Declaration on Epilepsy with anaccompanying White Paper to the EuropeanParliament and European Governments. This

Out of the Shadows

127

FIGURE 1

ILAEMedical and scientific

professionals

WHOMember States

IBEPatients, families,

nonmedical professionals

How? What?

Global Campaign Against Epilepsy

Where?

Advisory Board(Representative of

IBE, ILAE, and WHO)

Awareness-raising Assistinggovernments tobuild national

epilepsy programs

Global events

Secretariat(One representative ofIBE, ILA, and WHO)

Conferences forregional experts

Regional events

Officers with specialresponsibilities

(Scientific project leader,regional facilitators,national or regional

officers, etc.)

Declarations,regional reports

National activities

Assessment of countryresources on epilepsy

Demonstrationprojects

Educational andsocial intervention,

epidemiologicalassessment, service

delivery and intervention,outcome measurement

event took place in March 2001, and was fol-lowed 8 months later by the establishmentof a group of Parliamentary Advocates forEpilepsy, whose role is to place epilepsy onthe health agenda of the European Union.

In other regions, the follow-up of theregional declarations will be tailored accord-ing to prevailing conditions.

Regional Reports and Country ResourcesA questionnaire on country resources hasbeen developed by a group of experts, inorder to map the resources for epilepsyworldwide. All IBE and ILAE member organ-izations and all WHO Member States havebeen invited to complete the questionnaire.

Reports on the implementation of theGCAE are being prepared in a number ofWHO regions, which will include the data col-lected through the questionnaires. These doc-uments are intended to be tools for advocacyand instruments for dialogue with govern-ments, health care providers, donors, andother partners. These reports are workingpapers and provide basic knowledge onepilepsy and basic facts about the epidemio-logic burden, as well as propose the next stepsto be taken.

National ActivitiesOn a national level, the elements of theGlobal Campaign are adapted by the nation-al member organizations to the needs specif-ic to each country. The national organiza-tions strive to implement the strategy of theCampaign through active engagement withtheir governments and local WHO offices.They also participate in planning theCampaign at an international level.

Technical Consultative Meetings Technical consultative meetings were organ-ized in a number of WHO regions by WHORegional Offices in collaboration with theCampaign Secretariat. The main objectiveswere:

• To review the present state of epilepsy inthe regions;

• To discuss regional reports on epilepsy;• To review the implementation of the

GCAE in the region, including theprogress of Demonstration Projects;

• To develop a framework of action forcountries.

The meetings brought together clinicianswith expertise in the field of epilepsy, lead-ers of the Global Campaign AgainstEpilepsy, and senior staff from WHO. Inaddition, a number of technical consultativemeetings were organized at WHO headquar-ters on the progress and prospects of theCampaign, at which, for example, it wasagreed that epilepsy interventions should besustainable and provide long-term care andthat the outcomes should be measured.

Specific Activities of the Global CampaignIn April 1999, representatives of the threepartners in the Campaign met in Genevawith epilepsy experts from industrializedand developing countries, to discuss thedevelopment and implementation ofDemonstration Projects, which theCampaign encourages to be set up in anumber of selected countries in differentregions.

The counterparts of these projects at acountry level will be the member organiza-tions of IBE and ILAE, working in close col-laboration with WHO country representa-tives. These local counterparts will beinvolved in raising awareness of the needsof people with epilepsy, as well as encour-aging and supporting the provision of goodtreatment and services.

The Demonstration Projects will illustrategood practice in providing services to peo-ple with epilepsy and will be used as mod-els of what can be achieved. When provento be effective, similar projects will be imple-mented in the whole of the country in whichthey are situated, in neighboring countriesand, finally, globally.

Demonstration Projects start in a repre-sentative region of limited size. This is theresearch phase: The aim is to investigate theimpact of local conditions on general strate-gies to improve epilepsy care. Results of theresearch phase are used by National HealthAuthorities to plan and implement servicesand awareness-raising about epilepsy allover the country. Results of the subsequentimplementation phase are assessed in order


128

to develop a National Program on Epilepsy.The components of these two phases areshown in Figure 2.

Demonstration Projects

Selection of location. Criteria for countryselection are:

• The likelihood that results of the Demon-stration Project can be utilized by othercountries;

• Availability of political and personal contacts;

• Willingness to participate;• Availability of a WHO collaborative center

or country representative;• Presence of an IBE and an ILAE member

organization, or groups that have thepotential to form a member organization;

• A regular supply of basic antiepilepticdrugs (AEDs);

• Facility of communications.

Management structure of demonstrationprojects. The Global Campaign partnerscoordinate the projects, working closely withthe national IBE and ILAE member organiza-tions, other nongovernmental organizationson neurology and neuroscience, WHO

Regional Offices, and countryoffices and local ministries.

The Demonstration Projects arethe responsibility of the Campaign’sSecretariat, which oversees the day-to-day running of the Campaign,providing governments and otherpartners with sufficient, clear infor-mation and ensuring adequatefunding. External funds will be usedto initiate Demonstration Projects;however, such funds will not beused to pay for services or drugs,because the provision of anythingexcept minimal outside funding forthese components would be likelyto indicate that the project couldnot be locally sustainable.

Scientific supervision of the proj-ects is delegated to a ScientificProject Leader, who liaises directlywith local Principal Investigators andRegional Facilitators in helping to setup and monitor the projects. TheScientific Project Leader also liaises

with local ILAE and IBE member organiza-tions in order to foster local ownership andcommunity participation and with the relevantWHO offices and Departments of Health.

The Scientific Project Leader is responsi-ble for helping to design and evaluate theproject protocols. An important aspect of theevaluation is ensuring that eachDemonstration Project has sustainabilitybuilt into its design and that outcomes aremeasurable. They are also responsible formonitoring the projects to see how they areperforming, and for writing up this perform-ance for scientific journals.

Principal Investigators have responsibilityfor the Demonstration Project in the countrywhere it is held. They are responsible forconstructing the project’s protocol accordingto the guidelines of the Scientific ProjectLeader and local circumstances. PrincipalInvestigators ensure that the protocol imple-mentation keeps to its budget andtimescales. The Principal Investigators arethe focal points of the Campaign’s relation-ship with the project and the people throughwhom information will flow. Ensuring thatthe project meets its outcome measures iscentral to their work.

Out of the Shadows

129

FIGURE 2

Demonstration Project: Research Phase(in selected country regions)

1. Assessment of knowledge and attitudes followed by education2. Epidemiologic assessment3. Service delivery including social and educational intervention4. Analysis of outcome and recommendations

Demonstration Project: Implementation Phase(on a national level)

1. Educational and social intervention2. Service delivery and intervention3. Development of a National Program on Epilepsy

Regional Facilitators, working in closerelationship with the relevant WHO RegionalAdvisers, will support the PrincipalInvestigators in the implementation of theirprojects.

An outline of the management structureof the Demonstration Projects is given inFigure 3.

Design and activities of the demonstra-tion projects. In general terms, eachDemonstration Project has four aspects:

1. Assessing whether knowledge and attitudesof the population are adequate, correctingmisinformation and increasing awareness ofepilepsy and how it can be treated (educa-tional and social intervention)

2. Assessing the number of people withepilepsy and estimating how many ofthem are appropriately treated (epidemi-ologic assessment and case-finding)

3. Ensuring that people with epilepsy areproperly served by health personnelequipped for their task (service deliveryand intervention)

4. Analyzing the outcome and preparingrecommendations for those who wish toapply the findings to the improvement of

epilepsy care in their own and in othercountries (outcome measurement)

Step 1: Educational and SocialInterventionIncorrect perceptions about epilepsy are oftenthe reason why people with epilepsy are stig-matized; this can be an incentive to hide thefact of having epilepsy. Symptoms from whichcertain persons suffer may not be recognizedas a sign of epilepsy, which is a disorder forwhich medication is available. Both these fac-tors are a source of underestimation whenassessing the prevalence of epilepsy.

The educational and social interventionwill prepare the population for the epidemi-ologic study, but will also promote a changeof attitude in the community, through thefollowing activities.

• A representative sample of the populationin the area will be surveyed to assesspublic awareness and understanding ofepilepsy and attitudes toward peoplewho suffer from the condition.

• An educational program to decreasesocial stigma, improve social relationsand leisure activities, and open up realis-tic job opportunities will be targeted on


130

FIGURE 3

Secretariat of GCAE(one representative of ILAE, IBE, and WHO)

Prinicipal Investigators

Scientific Project Leader

Regional Facilitators

Ministries of Health

Representatives of WHORegional Offices and

Country Offices

groups of key people in the communities,such as teachers at local primary and sec-ondary schools.

• People will be informed about epilepsythrough:– public address systems and the media;– distribution of materials on epilepsy;– posters.

• People will be informed about interna-tional and national professional and layorganizations concerned with epilepsy.

Step 2: Epidemiologic Assessment and Case-FindingCorrectly identifying people with epilepsyis crucial to establishing the extent of acountry’s treatment gap and to ensuringthat appropriate treatment is offered tothose who need it. It is essential that staffinvolved in a survey—and also health per-sonnel who care for patients with hithertounrecognized epilepsy—have sufficientknowledge of epilepsy, so that conflict isnot created when epilepsy is diagnosed ina survey while the person is receivingtreatment for another, wrongly diagnosedcondition.

• At the onset of the Demonstration Project,questionnaires to assess knowledge, atti-tudes, and practice regarding epilepsy aredistributed to all health personnel in thestudy area; the questionnaires are self-administered.

• All physicians and a number of the pri-mary health care personnel (village doc-tors) receive basic epilepsy training tocorrect deficiencies that were revealed bythe questionnaires.

• Participation in the professional epilepsysociety and support of the lay associationare encouraged.

• A door-to-door survey is carried out in arepresentative part of the area:– a screening questionnaire is applied,

designed to identify cases of epilepsywith convulsive seizures;

– a village doctor then applies a diagnos-tic questionnaire to those patients pre-liminarily identified as possible casesof epilepsy with generalized tonic-clonic seizures, with or without occur-rence of other seizure types;

– senior primary health care physiciansthen confirm the diagnosis; if there aredoubts, local neurologists will beresponsible for a final decision.

Step 3: Service Delivery and InterventionThis stage covers quality of diagnosis, treat-ment, follow-up, and referral networks. Inorder to provide appropriate treatment,activities that ensure the supply ofantiepileptic drugs and facilitate their use intreatment are necessary and will be put inplace if not available.

• People with epilepsy who are under thecare of the team involved in theDemonstration Project will be offered thepossibility of participation in the study. Iftheir epilepsy is not active, their previoustreatment will be continued; if they stillhave seizures, their treatment will beadjusted according to the treatment proto-col of the Demonstration Project. Peoplewho are diagnosed with epilepsy and arenot receiving regular treatment will beoffered treatment, provided they havehad at least two convulsive seizures in theprevious 12 months and if they and/ortheir guardian are able and willing to giveinformed consent.

• All people who follow the protocol willbe assessed separately. For each patientincluded in the study, a standard entryform and a follow-up form will be pre-pared. The protocol is based on:– treatment with available first-line

drugs;– provision of education that facilitates

compliance with treatment and, if nec-essary, adaptation of lifestyle;

– if seizures persist, referral to a localneurologist for reassessment and pre-scription of antiepileptic medicationaccording to the findings.

• The staff involved in the DemonstrationProject will receive:– a treatment protocol;– a chart to assist physicians in dealing

with side effects;– written instructions on evaluation and

how to boost compliance.• Patients and their families will be educat-

ed about:

Out of the Shadows

131

– the nature of epilepsy and its charac-teristics, causes, and prognosis;

– the nature and objectives of treatment,the way to use the drugs, possible sideeffects and how to deal with them, theduration of treatment, and the impor-tance of compliance.

– general health measures, emergencytreatment of seizures, and how to livewith epilepsy.

• Patients and their families will be encour-aged to join the local epilepsy organiza-tion for lay people.

Step 4: Outcome MeasurementWhether the Demonstration Projects are suc-cessful and provide suitable approaches forother countries to adopt will have to be con-firmed by evidence. Their success or other-wise will be seen in terms of the decrease ofthe treatment gap and its consequences inthe demonstration region.

In order to discern whether a project isachieving the desired results, its perform-ance will be specifically measured by com-paring the following before onset and aftercompletion of the project:

• The number of people with epilepsy whoreceived a correct diagnosis;

• The number of people successfully treated;• The social situation of people of various

age groups with epilepsy;• Knowledge, attitudes, and practice of

those interviewed at the onset.

Step 5: The Ultimate GoalThe ultimate goal of the DemonstrationProjects is the development of a successfulmodel of epilepsy control that will be inte-grated into the health care systems of theparticipating countries and regions and,finally, applied on a global level.

Furthermore it is hoped that the lessonslearned from the Demonstration Projects willsupport the development of preventativemeasure strategies globally.

Anyone interested in following the progressof the Global Campaign and its DemonstrationProjects will be able to do so from the regularupdates on the relevant websites:

who.int/mental_heal th/management/globalepilepsycampaign/en/

www.ibe-epilepsy.orgwww.ilae-epilepsy.org

Further information on the GlobalCampaign Against Epilepsy and how to helpachieve the goals of the campaign in specif-ic countries can be obtained from theaddresses shown below.

International Bureau for Epilepsy (IBE)Key Contact: Hanneke M. de BoerStichting Epilepsie Instellingen NederlandAchterweg 52103 SW HeemstedeThe Netherlandstel: + 31 23 5 237 418fax: + 31 23 5 470 119email: [email protected]

International League Against Epilepsy(ILAE)Key contact: Jerome Engel Jr.Reed Neurological Research CenterDavid Geffen School of Medicine at UCLA710 Westwood PlazaLos Angeles, CA 90095-1769, USAtel: + 1 310 825 5745fax: + 1 310 206 8461email: [email protected]

World Health Organization (WHO)Key Contact: Dr. Leonid L. PrilipkoDepartment of Mental Health andSubstance Dependence20 Avenue Appia1211 Geneva 27Switzerlandtel: + 41 22 791 3621fax: + 41 22 791 4160email: [email protected]

WHO Regional Offices

WHO Regional Office for AfricaCité du DjouéP.O. Box 06Brazzaville, Congotel: + 1 321 95 39498fax: + 1 321 95 39501/2email: [email protected]

WHO Regional Office for the Americas525 23rd Street N.W.Washington, DC 20037, USA


132

tel: + 1 202 974 3000fax: + 1 202 974 3663email: [email protected]

WHO Regional Office for the EasternMediterraneanWHO Post OfficeAbdul Razzak Al Sanhouri StreetNasr City, Cairo 11371, Egypttel: + 202 670 25 35fax: + 202 670 24 92/94email: [email protected]

WHO Regional Office for Europe8 Scherfigswej2100 Copenhagen Ø, Denmarktel: + 45 39 17 17 17fax: + 45 39 17 18 18email: [email protected] and [email protected]

WHO Regional Office for South-EastAsiaWorld Health House, Indraprastha EstateMahatma Gandhi RoadNew Delhi 110002, Indiatel: + 91 11 331 7804/7823fax: + 91 11 332 7972email: [email protected]

WHO Regional Office for the WesternPacificP.O. Box 29321099 Manilla, Philippinestel: + 632 52 88 001fax: + 632 52 11 036email: [email protected]

Out of the Shadows

133


135

INDEX

NOTE: Boldface numbers indicate illustrations or code listing; t indicates a table.

absence SE, 24absence seizures, 24

antiepileptic drugs (AEDs) and, 80complex partial seizures vs.,

25–26absorption to clearance properties of

AEDs, 64–65age at onset, 35ainu imu, 18alcohol abuse, withdrawal

seizures/symptoms in, 102alternative treatment for epilepsy. See

also traditional medicineapproaches to, in developing world,

95–98corpus callosotomy in, 100ketogenic diet in, 100–101psychiatric comorbidity in develop-

ing countries and, 113traditional medicine and, 107–109vagus nerve stimulation in, 101

Alzheimer’s disease (AD) and epilepsy,40

amphetamines, 102antiepileptic drugs (AEDs), 36, 61,

64–70, 83–94. See also particulardrugs listed by name

absorption to clearance propertiesof, 64–65

aggravation of seizures by, 80alternative treatments to, 95–105availability of, 92, 110birth control efficacy and, 77blood level testing for, 55–56compliance with, 92controlled-release formulations of, 67cost vs. benefit of, 61–62, 117–118differential diagnosis and, 61discontinuation of, 61, 68–70dosage calculations for, 65, 66easy-to-control epilepsies and, 62–63enzyme induction/inhibition in, 65febrile/fever-related seizures and,

73–74, 89gamma aminobutyric acid (GABA)

action of, 83

antiepileptic drugs (AEDs) (continued)geriatric dose considerations in,

80–81half-life of, 64–65hard-to-control epilepsies and, 63–64HIV/AIDS medications and, 91idiopathic focal epilepsies and, 89idiopathic generalized epilepsies

and, 88infant/neonatal seizures and, 89initiation of treatment using, 61interactions with other drugs/sub-

stances by, 90–92isoniazid interaction with, 90–92loading doses in, 62malaria and, 91mechanisms of action in, 83monotherapy regimes in, 62, 65nonepileptic seizures and, 11pediatric dose considerations in,

80–81pharmacokinetics of, 64–65polytherapy regimes in, 65pregnancy and,75–77prophylactic use of, in head trauma,

81psychosocial morbidity related to, 61recurrence risk of seizures vs., 71refractory seizures and, surgical

intervention warranted by, 64risk of seizure recurrence and, 61selection of appropriate, 86–87serum level monitoring in, 67–68side effects of, 65–67, 86–87, 90–92single or infrequent seizures and, 71sodium channel action of, 83special syndromes and, 88–89status epilepticus (SE) and, 77–80,

78tsymptomatic focal epilepsies and, 88symptomatic generalized epilepsies

and, 89teratogenicity of, 75–77titration of, 62

asthma medications, 102atheosis, 18

atonic generalized seizures, anti-epileptic drugs (AEDs) and worsening of, 80

attention deficit hyperactivity disorder(ADHD), 19

atypical absence seizures, 24auras, 22–23awareness of epilepsy, 126

bahtsche, 18barbiturates, 102basilar migraine, 17behavioral features of epilepsy, 2benign epilepsy syndrome, 33benign familial neonatal convulsions,

40birth injuries and epilepsySee

infant/neonatal seizuresblood tests, 55

drug serum level monitoring in,67–68

brain/CNS injury, 3, 4, 39–40, 41, 46prevention of epilepsy and seizures

in, 116prophylactic use of AEDs in, 81

breath-holding spells (BHSs), 16–17

caffeine, 102calcium-channel disruption, 5carbamazepine, 77, 87t, 92tcardiac disorders and syncope, 15–16causes of epilepsy, 3–6

treatable underlying causes ofepilepsy, 46

cerebrospinal fluid (CSF) testingSeelumbar puncture, 55

cerebrovascular diseases, preventionof epilepsy and seizures in, 116

Chagas disease, 16channelopathies, 40childhood absence epilepsy, 40chorea, 18classification of seizures and epilepsy,

22–32, 23t, 46triage for, 62–64, 62

clobazam, 85–92, 87t

clonazepam, 80, 85–92, 87tcoca, 102cocaine, 102complex partial SE, 24complex partial seizures (CPS), 23–24,

33absence seizures vs., 25–26

computed tomography (CT), 44, 57–58disappearing lesions/ single small

enhancing lesions (SSELs) on,29–30

neurocysticercosis, 74–75conferences and declarations spon-

sored under GCAE, 126–128contagion of epilepsy, beliefs in, 111control of epilepsy, 2controlled-release AED formulations,

67corpus callosotomy, 100crack cocaine, 102cryptogenic epilepsy, 4, 27cultural perceptions of epilepsy. See

also psychosocial issuescontagion of epilepsy, beliefs in, 111cultural clues (tattoos, scarification)

to, 51, 109–110dealing with seizure occurrences in,

70–71economic impact of epilepsy in,

117–118failure of epilepsy patients and fami-

ly to seek help and, 113, 120–121family perception of seizures and,

49, 110–111inheritance of epilepsy, beliefs in,

111–112marriage and childbearing in epilep-

sy patients, 117possession and epilepsy, beliefs in,

111prevention of epilepsy and seizures

in, 115–117psychosocial morbidity related to,

61, 107–114public knowledge, attitudes, percep-

tions of epilepsy in, 111resistance to diagnosis of epilepsy, 51restrictions on activities of epilepsy

patients and, 112–113safety issues of epileptic patients

and, 109–110, 117stigma of epilepsy in, 109traditional medicine in treatment of

epilepsy, 103–104, 107–109cultural clues (tattoos, scarification) to

epilepsy, 51, 109–110cumulative incidence (CI) for epilepsy,

35–36

cure of epilepsy, 2cysticercosisSee neurocysticercosis

degenerative brain disorders, 39–40deja vu, 22delivery of care in developing nations,

118–120demonstration projects, GCAE,

129–130, 129, 130diagnosis of epilepsy, 43–59

in adults, 44algorithmic flowchart for, 43birth trauma and, 50blood tests in, 55boundaries of definition of epilepsy

in, 43computed tomography (CT) and

magnetic resonance imaging(MRI) in, 44, 57–58

cultural clues (tattoos, scarification)to, 51, 109–110

cultural resistance to, 51electroencephalogram (EEG) in,

53–54first seizures and, 43functional imaging/functional MRI

(fMRI) in, 58history taking in, 44, 46–47

circumstances of seizure onset in,47

family history of seizures and,50–51

family perception of seizures and,49

frequency and provoking factors ofseizures in, 50

illicit substance use and, 50physical consequences described

in, 48previous events as possible

seizures in, 51questioning the patient in, 47–48questioning witnesses/accompany-

ing person in, 48–49remote history and medical past in,

50imaging studies in, 56–57in infant/neonate seizures, 44–45laboratory investigation in, 54–55lumbar puncture in, 44, 45, 55, 56magnetic resonance imaging (MRI)

in, 57, 58neurologic examination in, 53no access to complementary testing

and, 58nonepileptic seizures and, 45–46physical examination in, 51–52

post-seizure examination in, 52

diagnosis of epilepsy (continued)sequelae of seizures and, 52special conditions for, 52

psychosocial morbidity related to, 61recurrent seizures and, 43seizures vs. epilepsy in, 46single photon emission CT (SPECT)

in, 58single seizures and, 43X-rays (cranial) in, 56–57

diazepam, 77, 79, 80diet, ketogenic, 100–101differential diagnosis of epilepsy, 2–3,

11–34, 12, 14tabnormal EEG and, 19–21antiepileptic drugs (AEDs) and, 61attention deficit hyperactivity disor-

der (ADHD), 19basilar migraine as, 17breath-holding spells (BHSs) as,

16–17causes of misdiagnosis in, 25classification of seizures and epilep-

sy in, 22, 23tdrop attacks, 13generalized convulsive movements

in, 12hyperekplexia as, 18–19hyperventilation syndrome as, 17isolated seizures vs. epilepsy in, 22misdiagnosis of epilepsy, clinical

approach to, 11myoclonus as, 19neurocysticercosis as, 21–22nonepileptic psychogenic seizures

as, 16panic attacks as, 17parasitic disorders as, 21parasomnias as, 19paroxysmal focal signs and symptoms

in, 13paroxysmal movement disorders as,

18–19stomach congestion as, 22sudden alteration of consciousness

in, 12syncope as, 15–16transient ischemic attacks (TIAs) as, 18video-EEG in, 16

Diop, Amadou Gallo, viidisappearing CT lesions, 29–30discontinuation of AEDs, 68–70dosage calculations for AEDs, 65, 66Dravet’s syndrome, 64drop attacks, 24

differential diagnosis flowchart for,13

treatment of, 62


136

drug abuse, 50stimulant drug use as seizure trigger

in, 102–103withdrawal seizures/symptoms in, 102

drug-induced seizures, 3, 4dystonia, 18

eclampsia and pre-eclampsia, 76–77.See also pregnancy and epilepsy

economic impact of epilepsy, 37,117–118

educational and social interventionsunder GCAE, 130–131

electroencephalogram (EEG), 2, 53–54abnormal, in absence of epilepsy,

19–21overuse of, 19–21type of seizures and syndromes

diagnosed by, 54electrolyte imbalance, 103emerging countries and epilepsy, 7–8enzyme induction/inhibition in AEDs,

65epidemiologic assessment and case-

finding under GCAE, 131epidemiology and etiology of epilepsy,

35–42epilepsia partialis continua (EPC), 24,

25epilepsy, 1–11

active diagnosis of, 2behavioral features of, 2brain or intercranial lesions as cause

of seizures and, 3, 4calcium-channel disruption and, 5causes of, 3–6control of, 2cryptogenic, 4cure of, 2definition of, 1–2differential diagnosis of, 2–3, 11–34,

12, 14tdrug-induced seizures and, 3, 4electroencephalogram (EEG) studies

in, 2emerging countries and, 7–8epileptic encephalopathy in, 2epileptic focus (epileptogenic

region) in, 2epileptogenesis in, 2evaluation of paroxysm events in, 3,

3febrile/fever-induced seizures in, 3,

4, 38, 44gamma aminobutyric acid (GABA)

and, 5glutamatergic excitation and, 5ictal events in, 2

epilepsy (continued)idiopathic or primary, 4infectious causes of seizures and, 3, 4interictal events in, 2neuronal system and, 5, 5postictal events in, 2seizure-free periods and, 2seizures in, 1–2, 43, 46signs and symptoms of, 1–2sleep deprivation and, 4symptomatic or secondary, 4threshold and susceptibility of indi-

viduals to, 3–4, 4epilepsy disease, 33epilepsy syndrome, 33epilepsy with generalized tonic-clonic

seizures upon awakening, 40epileptic encephalopathy, 33epileptic encephalopathy, 2epileptic focus (epileptogenic region), 2epileptic seizures, 1–2, 22, 33epileptic spasms, 24epileptogenesis, 2ethosuximide, 85–92, 87t, 92tetiology of epilepsySee epidemiology

and etiology of epilepsyevaluation of paroxysm events, 3, 3

Fadiman, Anne, 103failure of epilepsy patients and family

to seek help, 113, 120–121family history of seizuresSee genetics

and epilepsyfamily perception of seizures and

epilepsy, 49, 110–111. See alsocultural perceptions of epilepsy

febrile/fever-induced seizures, 3, 4,38, 44

AEDs and, 89treatment of, 73–74

felbamate, 85–92, 87tfever-induced seizures See

febrile/fever-induced seizures focal seizures and syndromes, 33, 88frequency and provoking factors of

seizures, 50Fulbright Program, professional devel-

opment programs, 121functional imaging/functional MRI

(fMRI) in, 58funding for epilepsy care services in

developing countries, 121fundoscopic examination, 53

gabapentin, 85–92, 87tgamma aminobutyric acid (GABA), 5,

80AEDs and, 83

gender differences, 35generalized convulsive movements,

differential diagnosis flowchartfor, 12

generalized convulsive SE (GCSE), 24generalized epilepsy with febrile

seizures plus (GEFS+), 40generalized seizures

AEDs and, 89primarily vs. secondarily, 26–33, 28t

generalized tonic-clonic seizures, 24,45, 64

genetics and epilepsy, 40–41, 50–51hereditary risk factors for epilepsy,

40–41inheritance of epilepsy, beliefs in,

111–112marriage and childbearing, 117

geriatric groups and AED use, 80–81Global Burden of Disease, epilepsy

and, vii, 6–8Global Campaign Against Epilepsy

(GCAE), vii, 6–8, 107, 121,125–133

awareness of epilepsy and, 126contact information for, 122demonstration projects under,

129–130, 129, 130educational and social interventions

under, 130–131epidemiologic assessment and case-

finding under, 131general activities of, 126–133global activities of, 128–129goals of, 125management and structure of, 126,

127national level activities of, 128outcome measurements under, 132regional conferences and declara-

tions sponsored under, 126–128regional reports and country

resources under, 128service delivery and intervention

under, 131–132strategy and tactics of, 125–126technical consultative meetings of,

128glutamatergic excitation, 5

hakomatoses, 41half-life of AEDs, 64–65head traumaSee brain/CNS injury health-seeking strategies in developing

countries, 120–121hemiplegia in infants, 19hereditary risk factorsSee genetics and

epilepsy

Index

137

hippocampus, 5history taking in diagnosis of epilepsy,

44, 46–47circumstances of seizure onset in, 47family history of seizures and, 50–51family perception of seizures and, 49frequency and provoking factors of

seizures in, 50illicit substance use, 50physical consequences described in,

48previous events as possible seizures

in, 51questioning the patient in, 47–48questioning witnesses/accompanying

person in, 48–49remote history and medical past in,

50HIV/AIDS, 39, 57

antiepileptic drugs (AEDs) vs. antivi-ral medications for, 91

Hmong people, 103hyperactivity disorder (HD), 19hyperekplexia, 18–19hyperventilation syndrome, 17hypoxic-ischemic encephalopathies,

30, 64

ictal events, 2idiopathic epilepsy syndromes, 4, 27,

33, 40idiopathic focal epilepsies, AEDs and,

89idiopathic generalized epilepsies, 30

AEDs and, 88idiopathic partial epilepsies, 30–31ikota, 18illicit substance use, 50

stimulant drug use as seizure triggerin, 102–103

withdrawal seizures/symptoms in,102

imaging studies, 53, 56–57incidence of epilepsy, 35–36infant/neonatal seizures, 35, 44–45, 50

AEDs and, 89birth trauma in, 35, 50prevention of epilepsy and seizures

in, 115–117traditional birth attendants (TBA) in,

115–116infectious causes of seizures, 3, 4,

38–39, 46prevention of epilepsy and seizures

in, 116inheritance of epilepsy, beliefs in,

111–112. See also genetics andepilepsy

interictal events, 2International Bureau for Epilepsy

(IBE), vii, 6–8contact information, 132Global Campaign Against Epilepsy

(GCAE), 125–133International League Against Epilepsy

(ILAE), vii, 6–8classification of epilepsy under,

22–32, 23tGlobal Campaign Against Epilepsy

(GCAE), 125–133isoniazid and AEDs, 90–92

Jain, Satish, viijamais vu, 22janus, 18jumping Frenchmen of Maine, 18juvenile absence epilepsy, 40juvenile myoclonic epilepsy, 40

ketogenic diet, 100–101

laboratory investigation, 54–55lactic acidosis, 41lamotrigine, 62, 86–92, 87t, 92tlatah, 18Lennox-Gastaut syndrome, 64

AEDs and, 89treatment of, 62

levetiracetam, 86–92, 87t, 92tloading doses of antiepileptic drugs

(AEDs), 62lorazepam, 79lumbar puncture, 44, 45, 55, 56

macrocephaly, 44–45magnesium sulfate, in eclamptic

seizures, 76magnetic resonance imaging (MRI),

29, 44, 57, 58neurocysticercosis, 74–75

malaria, 38, 39, 46, 55, 116AEDs and, 91

malformations of cortical development(MCD), 27, 30, 64

mali mali, 18marriage and childbearing, 117mate (herb), 102meningitis, 64, 116menses as trigger for seizures,

101mesial temporal lobe epilepsy (MTLE),

5, 27, 29, 44methylphenidate, 102migraine, 17misdiagnosis of epilepsy, clinical

approach to, 11

mitochondrial encephalomyopathywith lactic acidosis and stroke-like episodies (MELAS), 41

monotherapySee antiepileptic drugs(AEDs), monotherapy regimes in

morbidity and mortality, 37movement disorders, 18–19myoclonic epilepsy with ragged red

fibers (MERRF), 41myoclonic seizures, 64

antiepileptic drugs (AEDs) and wors-ening of, 80

myoclonic-astatic epilepsy, treatmentof, 62

myoclonus, 19

National Institutes of Health (NIH/US),7–8

professional development programsof, 121

natural history of epilepsy, 37neurocysticercosis, 21–22, 29, 38–39,

46, 55, 74–75prevention of epilepsy and seizures

in, 116–117treatment of, 74–75

neurofibromatosis 1, 41neurologic examination in diagnosis

of epilepsy, 53neuronal system and epilepsy, 5, 5nonepileptic psychogenic seizures, 16,

45–46antiepileptic drugs and, 11

@idx1:Ohtahara syndrome, 64onchocerciasis, 39organophosphate poisoning, 40outcome measurements under GCAE,

132oxcarbazepine, 77, 86–92, 87t, 92t

Palmini, Andre, viipanic attacks, 17panic in Lapps, 18paraldehyde, 79parasitic diseases and epilepsy, 21, 35parasomnias, 19paroxysmal focal signs and symptoms,


paroxysmal movement disorders, 18–19pediatric patients and AED use, 80–81pesticide exposures, 40phenobarbital, 62, 77, 79, 83–92, 87t,

92tphenylketonuria, 4phenytoin, 62, 77, 79, 80, 84–92, 87t,

92t


138

physical examination in diagnosis ofepilepsy, 51–52

post-seizure examination in, 52sequelae of seizures and, 52special conditions for, 52

pneumonia, 46polytherapySee antiepileptic drugs

(AEDs), polytherapy regimes inpostictal events, 2pregnancy and epilepsy, 75–77, 117

AED use during, 75–77birth control vs. antiepileptic drugs

(AEDs), 77eclampsia and pre-eclampsia in,

76–77treatment of, 75–77

prevalence of epilepsy, 36–37, 36tprimarily generalized seizures, 26primary epilepsy, 4primidone, 77, 85–92, 87tprobably symptomatic epilepsy syn-

drome, 33professional development programs in

developing countries, 121progressive myoclonus epilepsies, 41psychiatric comorbidity in developing

countries, 113psychiatric phenomena, 22psychogenic seizures, 16psychosocial issues, 107–114. See also

cultural impact of epilepsycontagion of epilepsy, beliefs in, 111failure of epilepsy patients and

family to seek help and, 113,120–121

family perception of seizures and,110–111

inheritance of epilepsy, beliefs in,111–112

possession and epilepsy, beliefs in,111

psychiatric comorbidity in develop-ing countries and, 113

public knowledge, attitudes, percep-tions of epilepsy in, 111

restrictions on activities of epilepsypatients and, 112–113

safety issues of epileptic patientsand, 109–110, 117

stigma of epilepsy in, 109traditional medicine and, 107–109

psychosocial morbidity related toepilepsy diagnosis, 61

public health issues, 115–123delivery of care in developing

nations in, 118–120economic impact of epilepsy in,

117–118

public health issues (continued)funding for epilepsy care services in,

121health-seeking strategies in, 120–121prevention of epilepsy and seizures

in, 115–117professional development programs

in, 121safety issues of epileptic patients

and, 117pyridoxine/pyridoxal phosphate

dependency, 45, 80

reflex epilepsy, 33, 45refractory seizures, 64regional conferences and declarations

sponsored under GCAE, 126–128resistance to diagnosis of epilepsy, 51restrictions on activities of epilepsy

patients, 112–113rheumatic heart disease, 16rickets, 44risk factors for seizures and epilepsy,

38risk of seizure recurrence, antiepilep-

tic drugs (AEDs) and, 61

safety issues of epilepsy patients, 117scarification of epilepsy patients, 51,

109–110secondarily generalized seizures, 26secondary epilepsy, 4seizure-free periods, 2seizures, 1–2, 43, 46

dealing with occurences of, 70–71eclampsia and pre-eclampsia in, 76illicit substance abuse, withdrawal

seizures/symptoms in, 102isolated seizures vs. epilepsy in, 22recurrence risk of seizures vs., 71triggers forSee triggers for seizures

sensory stimulation as seizure trigger,103

sequelae of seizures, 52service delivery and intervention

under GCAE, 131–132side effects of AEDs, 65–67, 86–87,

90–92pregnancy and teratogenicity of, 75–77

signs and symptoms, 1–2simple partial epileptic siezures, 33simple partial motor seizures, 23simple partial SE, 24, 25simple partial seizures without motor

features, 22single or infrequent seizures,

antiepileptic drugs (AEDs) treat-ment for, 71

single photon emission CT (SPECT), 58single small enhancing lesions

(SSELs), 29–30sleep deprivation and seizures, 4, 19,

101. See also parasomniassmoking and prevention of epilepsy

and seizures in, 116social interventions under GCAE,

130–131socioeconomic impact of epilepsy, 37sodium channel action of AEDs, 83sodium valproate, 85–92spasms, epileptic, 24Spirit Catches You and You Fall Down,

The, 103status epilepticus (SE), 24–25, 40

infants and neonates, 45initial assessment and treatment of,

77–78treatment of, 77–80, 78t

stigma of epilepsy, 109stimulant drug use as seizure trigger,

102–103stomach congestion, 22stroke, 39–40

prevention of epilepsy and seizuresin, 116

subtypes of epilepsy, 36–37sudden alteration of consciousness,


surgical intervention, 64, 95–100symptomatic epilepsy, 4, 27, 33symptomatic focal epilepsies, AEDs

and, 88symptomatic generalized epilepsies, 30

AEDs and, 89symptomatic partial epilepsies, 27syncope, 15–16syndromes of epilepsy, classification

of, 26–33, 26–33, 28t, 33, 46

tattoos and scarification of epilepsypatients, 51, 109–110

threshold and susceptibility of individ-uals to epilepsy, 3–4, 4. See alsotriggers of seizures

tiagabine, 86–92, 87ttitration of antiepileptic drugs (AEDs),

62tobacco use, prevention of epilepsy

and seizures in, 116tonic-clonic seizures, 24, 64

treatment of, 62topiramate, 86–92, 87t, 92ttoxic exposure and epilepsy, 40, 103

in infants and neonates, 45toxoplasmosis, 57–58

Index

139

traditional birth attendants (TBA),115–116

traditional medicine in treatment ofepilepsy, 103–104, 107–109

contagion of epilepsy, beliefs in, 111inheritance of epilepsy, beliefs in,

111–112possession and epilepsy, beliefs in,

111prevention of epilepsy and seizures

in, 115–117restrictions on activities of epilepsy

patients and, 112–113traditional birth attendants (TBA) in,

115–116transient ischemic attacks (TIAs), 18treatable underlying causes of epilepsy,

46treatment of epilepsy, 61–82, 95–105

antiepileptic drugs (AEDs) in, 64–70.See also antiepileptic drugs(AEDs)

aggravation of seizures by AEDs in, 80alternatives to, 95–105antiepileptic drugs (AEDs) in, 61considerations pertaining to, 61corpus callosotomy in, 100cost vs. benefit analysis in, 62dealing with seizure occurences in,

70–71discontinuation of, 68–70drug serum level monitoring in,

67–68easy-to-control epilepsies and, 62–63febrile/fever-related seizures and,

73–74

treatment of epilepsy (continued)geriatric groups and AED use in,

80–81hard-to-control epilepsies and, 63–64initiation of AED treatment in, 61–62monotherapy regimes in, 62, 65neurocysticercosis, 74–75pediatric groups and AED use in,

80–81pharmacokinetics of AEDs inSee

antiepileptic drugs (AEDs), 64polytherapy regimes in, 65pregnancy and epilepsy, 75–77prophylactic use of AEDS in, 81psychiatric comorbidity in develop-

ing countries and, 113recurrence risk of seizures vs., 71refractory seizures and, 64side effects of, 65–67, 86–87, 90–92single or infrequent seizures and, 71status epilepticus (SE) and, 77–80,

78tsurgical intervention in, 64, 95–100traditional medicine in, 103–104,

107–109triage in, 62–64

tremulousness or jitters in infants, 19triage of epilepsy conditions, 62–64triggers for seizures, 50, 101–103

electrolyte imbalance and, 103menses and, as trigger for seizures,

101sensory stimulation as, 103sleep-wake cycles and, 101stimulant drug use as, 102–103toxic exposures and, 103

triggers for seizures (continued)withdrawal of drugs/alcohol and,

102tuberculosis, 46tuberous sclerosis (TS), 4, 41typical absence seizures, 24

vagus nerve stimulation, 101valproate, 62, 85–92, 87t, 92tvalproic acid, 76vasovagal syncope, 15–16video-EEG, differential diagnosis of

epilepsy and, 16vigabatrin, 62, 86–92, 87t

West syndrome, 64withdrawal seizures/symptoms, alco-

hol/drug abuse, 102World Federation of Neurology, vii

professional development programsand, 121

World Health Organization (WHO),vii, 6–8

classification of epilepsy under,31–32, 32t

contact information, 132–133Global Burden of Disease, epilepsy

and, vii, 6–8Global Campaign Against Epilepsy

(GCAE) and, 125–133public health issues and, 115

X-rays, cranial, 56–57

zonisamide, 86–92, 87t, 92t


140

Documents

THE PRACTICING NEUROLOGIST - Global Issues... · World Federation of Neurology Seminars in Clinical Neurology Epilepsy: Global Issues for the Practicing Neurologist Jerome Engel,