Seizure & Epilepsy.pdf

DEFINITIONS AND EPIDEMIOLOGY A general simplified definition of a seizure is a suddentemporary change in brain function caused by anabnormal rhythmic electrical discharge. Epilepsy is,simply put, a state of recurrent seizure activity. Themechanism whereby a seizure turns into epilepsy, aprocess known as epileptogenesis, is controversial.

Seizures are common in humans, with an inci-dence of approximately 80/100,000 per year and anoverall risk of epilepsy of 1% to 3%.1 Status epilepticusis a less common form of severe prolonged seizure activ-ity with a high morbidity and mortality.

PATHOGENESIS Seizures arise secondary to a number of etiologies. Idio-pathic seizures, or “cryptogenic” seizures, are fairly com-mon. Contrary to what many patients and familiesmight think, the inability to find a cause for the seizureis not necessary “bad.” In fact, this may portend a some-what better prognosis for long-term seizure control.Febrile seizures are common in children and are coveredin detail in Chapter 4.

Trauma contributes to the risk of seizures in twofairly distinct fashions. Early posttraumatic seizures aretypically associated with intracranial hemorrhage, focalneurological deficits, posttraumatic amnesia exceeding24 hours, and linear skull fractures. Late posttraumaticseizures are also associated with intracranial hemor-rhage and posttraumatic amnesia exceeding 24 hours,but are usually seen in patients with depressed skullfractures and with the injury after age 16 years.2–4

A number of congenital malformations increasethe risk for epilepsy. Disorders associated with migrational

disorders and structural anomalies often increase therisk of subsequent seizures. The genetic diseases listed inTable 3-1 also increase the risk of epilepsy whether or notthey are associated with structural malformations.5–7

Infections are also common causes of seizureactivity in the pediatric population. Meningitis andencephalitis can result in seizures either related to thefever or to the direct effects of the infection. These arecovered in detail in the chapters on infectious disease.Bacterial infections can result in meningitis, encephalitis,and abscess formation. Herpes simplex virus (HSV) is awell known cause of seizures and can be catastrophic.8

Other viral infections including cytomegalovirus (CMV)infection and various viral encephalitides can result inseizures. Fungal infections and toxoplasmosis also raisethe risk of developing seizures.

A wide array of toxic and metabolic disorders canresult in seizures. These derangements can causeseizures to occur de novo but can also worsen a pre-existing epilepsy. The common metabolic and toxiccauses of seizures are listed in Table 3-2.

Seizures and EpilepsyPaul R. Carney and James D. Geyer

CHAPTER 3

Table 3-1.

Genetic Causes of Epilepsy

Amino aciduriasChannelopathiesLysosomal storage diseasesPhakomatoses—tuberous sclerosis, von Hippel–Lindau

disease, neurofibromatosisPhenylketonuria (PKU)Sturge–Weber syndrome

Carney_Ch03.qxd 9/18/09 8:16 PM Page 30

Cerebral ischemia is a common cause of seizuresin the neonate and in the older adult but is relativelyuncommon in the older pediatric population.

Seizures usually occur in the more slowly growingtumors. Tumors located in the supratentorial regioncause seizures more frequently than do cerebellar orbrainstem tumors.

CLINICAL PRESENTATIONEpilepsy is divided into several categories with signifi-cant differences in the characteristics of the electrical dis-charges as well as the clinical manifestations. Localization-related epilepsy or partial epilepsy has a primary focusfrom which the electrical discharges arise. Complex par-tial seizures occur with alteration of awareness whilesimple partial seizures have no alteration of awareness.Jacksonian motor seizures, Rolandic epilepsy, temporallobe epilepsy, and frontal lobe epilepsy are all examplesof partial epilepsy.

The Revised International Classification of Epilep-sies, Epileptic Syndromes and Related Seizure Disordersdivides the localization-related epilepsies as follows:10

Idiopathic localization-related epilepsySymptomatic or secondary localization-related

epilepsyCryptogenic localization-related epilepsy

Generalized seizures are the other major seizuretype. In this category of epilepsy, the seizure affects theentire cortex electrically. Several subtypes of generalizedseizures have also been identified, including absenceepilepsy with 3-Hz spike and wave activity, generalizedtonic-clonic seizures, juvenile myoclonic epilepsy, andprogressive myoclonic epilepsy.

The Revised International Classification ofEpilepsies, Epileptic Syndromes and Related SeizureDisorders divides the generalized epilepsies as follows10:

Primary generalized epilepsySymptomatic generalized epilepsyCryptogenic epilepsy

A number of seizures and epilepsies may be verydifficult to categorize. The Revised International Classi-fication of Epilepsies, Epileptic Syndromes and RelatedSeizure Disorders groups these disorders in the “unde-termined” category. These seizures may be divided asfollows10:

Both focal and generalizedSituation-related epilepsyFebrile convulsionsIsolated seizureIsolated status epilepticusToxic/metabolic

In each of these cases, the electroencephalo-graphic (EEG) findings may be different. The EEGserves as a vitally important tool in the correct diagno-sis of the various epilepsy subtypes and syndromes.

DIAGNOSIS

Seizure TypesGeneralized tonic-clonic seizuresGeneralized tonic-clonic seizures typically have no pre-ceding aura but may have a prodrome of apathy or irri-tability. During the tonic phase, the jaw snaps shut fol-lowed by 10 to 15 seconds or longer of tonic spasms,apnea, and cyanosis. The clonic phase usually consists of1 to 2 minutes of rhythmic generalized muscle contrac-tions and increased blood pressure. The postictal phaselasts for minutes to hours, with confusion, somnolence,and possibly agitation.

The ictal EEG usually consists of generalized spikeand wave or polyspike activity. The interictal EEG ishighly variable with a normal background in somepatients and slowing present in others.

Generalized seizures are rare in newborns. Gener-alized seizures occur most frequently in children sec-ondary to fevers and metabolic derangements.

CHAPTER 3 Seizures and Epilepsy ■ 31

Table 3-2.

Toxic/Metabolic Causes of Seizures

Drug IntoxicationAmphetaminesCocaineLidocaineTheophyllineTricyclic antidepressants

Drug withdrawalAntiepileptic drugs (AEDs)BarbituratesBenzodiazepinesEthanol

Electrolyte—hypo/hypernatremia, hypo/hyperglycemia,hypocalcemia, hypomagnesemia

Heavy metals—lead, mercuryHyperosmolarityHypoxiaLiver failurePorphyriaPyridoxine deficiencyThyroid stormUremia (usually following 3 days of anuria)


Absence seizuresAbsence seizures typically have no preceding aura orprodrome. An absence seizure usually lasts for only sev-eral seconds to minutes. There is a sudden interruptionof consciousness, staring, 3-Hz blinking, and less fre-quently automatisms. There is no postictal confusion.11

The ictal EEG usually consists of 3-Hz generalizedspike and wave activity with some slowing of the dis-charge frequency during the seizure. The interictal EEGusually has a normal background. Atypical absenceseizures have generalized spike and wave activity butusually have a frequency less than 3 Hz.12

Absence seizures typically start between ages 4and 10 years and resolve by age 20 years. Atypicalabsence epilepsy usually occurs in children who are neu-rologically or developmentally abnormal.13

Febrile seizuresFebrile seizures occur with a prodromal fever. A simplefebrile seizure occurs as a brief generalized tonic clonicseizure occurring after the onset of fever. A complicatedfebrile seizure has prolonged seizure activity or focalseizure activity. Febrile seizures are covered in detail inChapter 4.

Juvenile myoclonic epilepsyThe seizures associated with juvenile myoclonic epilepsytypically have no preceding aura but may have a pro-drome of morning myoclonus. The seizures may consistof generalized tonic-clonic activity; however, absenceseizures may also occur. The postictal phase is variabledepending on the seizure type.11

The ictal EEG usually consists of generalized poly-spike and slow wave activity. The interictal EEG is typi-cally unremarkable.12

The age of onset of juvenile myoclonic epilepsy istypically 10 to 20 years. Patients are usually develop-mentally and neurologically normal.13

Progressive myoclonic epilepsyThe family of disorders known as the progressivemyoclonic epilepsies (Table 3-3) consists of a number ofloosely related disorders. These epilepsy subtypes are quiterare and have complex presentations and diagnostic find-ings. Most of these disorders have a genetic basis, thoughsporadic cases have occurred in some cases (Table 3-4). TheEEG associated with these disorders is variable. The back-ground is often slow.The seizures are typically generalized.11

Infantile spasmsWest syndrome typically begins between 3 months and3 years of age.14–16 The seizures associated with Westsyndrome consist of a jack-knifing movement andmyoclonus. The EEG consists of a hypsarrhythmia pat-tern with bursts of asynchronous slow waves; spikes and

sharp waves alternate with a suppressed EEG.17 The clin-ical features of West syndrome include infantile spasmsand mental retardation, which varies according to theetiology of the spasms.

Aicardi syndrome is an X-linked disorder presentfrom birth that is associated with infantile spasms. Theseizures are described as infantile spasms, but alternat-ing hemiconvulsions may also be seen. The clinical fea-tures of Aicardi syndrome include coloboma, chori-oretinal lacunae, agenesis of the corpus callosum,vertebral anomalies, and seizures.18

Lennox–Gastaut syndromeLennox–Gastaut syndrome typically begins between 1and 10 years of age. There are multiple seizure types,associated with variable degrees of mental retardation.

The EEG reveals a slow spike wave complex witha frequency of 1 to 2.5 Hz, multifocal spikes, and gener-alized paroxysmal fast activity (GPFA).19

Partial seizures: localization-related epilepsyJacksonian motor seizures are simple partial seizureswith no alteration of consciousness. These seizuresbegin with tonic contractions of the face, fingers, or feetand transform into clonic movements that march toother muscle groups on the ipsilateral hemibody. Thereis no alteration in consciousness, but postictal aphasiamay occur if the primary epileptogenic zone involvesthe dominant hemisphere. Simple partial seizures mayinvolve autonomic (Table 3-5), sensory, motor, or psy-chic functions.

Complex partial seizuresBenign Rolandic epilepsy. Benign Rolandic epilepsyusually begins between ages 5 and 10 years and is trans-mitted in an autosomal dominant pattern with variablepenetrance. It is fairly common, with an incidence of

32 ■ Section 2: Common Pediatric Neurologic Problems

Table 3-3.

Progressive Myoclonic Epilepsies

Dentorubral-pallidoluysian atrophyJuvenile neuroaxonal atrophyLafora diseaseLate infantile and juvenile GM2 gangliosidosisMyoclonic epilepsy and ragged red fibers (MERRF)Neuronal ceroid lipofuscinosis (NCL) (also known as Batten

disease)Noninfantile Gaucher diseaseSialidosisUnverricht–Lundborg disease (Baltic myoclonus)


21/100,000 children.20 The clinical features include a singlenocturnal seizure with clonic movement of the mouthand gurgling. Secondary generalization is common.Alteration in consciousness, aura, and postictal confusionare rare. The seizures resolve by age 16 years.21, 22

The interictal EEG consists of central and mid-temporal high-amplitude spike and wave with a charac-teristic dipole. The ictal EEG usually consists of a focalcentral or mid-temporal ictal onset, with the possibilityof secondary generalization.23,24

Temporal lobe epilepsy. Temporal lobe epilepsyaccounts for approximately 70% of partial seizures.Many patients have a prior history of febrile seizuresor head trauma. A prodrome consisting of lethargy iscommon. Auras are also common but not universaland include an array of findings such as déjà vu. Theictal findings or semiology include oral or motorautomatisms, alteration of consciousness, head andeye deviation, contralateral twitching or tonic–clonicmovements, and posturing. Right temporal lobeseizures are often hypermobile. Left temporal lobeseizures often result in behavior arrest. Versive headmovements are relatively common, and 90% ofpatients with versive head movements had a primaryepileptogenic zone in the contralateral hemisphere.Ipsiversive movements are less common but occurmost commonly in patients with temporal foci. Thepostictal phase consists of minutes to hours of confu-sion and somnolence.24–30

Frontal lobe epilepsy. Frontal lobe epilepsy accountsfor approximately 20% of partial seizures. A prodromeis rare. Auras are unusual. The seizures typically consistof combinations of behavior alteration and automa-tisms of very brief duration. Frontal seizures often haveatypical presentations and vary widely depending onthe region of the frontal lobe from which the seizuresarise (Table 3-6). Postictal confusion is rare.31–36


Table 3-5.

Possible Autonomic Seizure Clinical Features

Abdominal sensationsApneaArrhythmiaChest painCyanosisErythemaFlushingGenital sensationsHyperventilationIncontinenceMiosisPerspirationVomiting

Table 3-4.

Distinguishing Characteristics of the Progressive

Myoclonic Epilepsies

Clinical Features

CChhoorreeaaDentorubral-pallidoluysian atrophyJuvenile neuroaxonal dystrophyJuvenile Gaucher diseaseDDeeaaffnneessssBiotin-responsive encephalopathyMERRFSialidosis type IIFFooccaall OOcccciippiittaall SSppiikkeessMERRFUnverricht–Lundborg diseaseLLiittttllee oorr NNoo DDeemmeennttiiaaBiotin-responsive encephalopathyNoninfantile Gaucher diseaseMyoclonus—nal failureSialidosis type IUnverricht–Lundborg diseaseSSeevveerree DDeemmeennttiiaaGM2 gangliosidosisJuvenile neuroaxonal dystrophyLafora diseaseLate infantile NCLSSeevveerree MMyyoocclloonnuussLafora’s diseaseMERRFSialidosis

Genetics

AAuuttoossoommaall DDoommiinnaannttDentatorubral-pallidoluysian atrophyKuf disease

Geography

CCaannaaddaaMyoclonus—renal failureFFiinnllaannddSantavori diseaseUnverricht–Lundborg diseaseJJaappaannDentatorubral pallidoluysian atrophySialidosis type IISSwweeddeennGaucher disease

Maternal InheritanceMERRF



Occipital lobe epilepsy. Occipital lobe epilepsy is rare,accounting for less than 10% of partial seizures. Pro-dromes are rare with occipital lobe seizures and aurasare unusual. As with the frontal lobe seizures, the seizurecharacteristics are dependent on the area of the occipi-tal lobe involved. When the striate cortex is involved,there are typically elemental visual hallucinations.Involvement of the lateral occipital lobe results intwinkling, pulsing lights. Seizures arising from thetemporo-occipital are usually associated with formedvisual hallucinations.37-39

Parietal lobe epilepsy. Parietal lobe seizures are alsorelatively uncommon. The may be seen as simple partialseizures but they will often propagate. The initial fea-tures can include contralateral paresthesias, contralateralpain, idiomotor apraxia, and limb movement sensations.As the seizure progresses and propagates, asymmetrictonic posturing and automatisms may develop.40-42

Landau–Kleffner syndrome. Landau–Kleffner syndromeis a rare, invariably progressive, idiopathic acquired apha-sia related to a focal epileptic disturbance in the area of thebrain responsible for verbal processing.43 The syndromebegins between ages 3 and 10 in a child with normallyacquired language abilities. The child then develops averbal auditory agnosia and infrequent nocturnal partialor secondarily generalized seizures. The syndrome has apathognomonic EEG pattern consisting of high-voltagemultifocal spikes, predominating in the temporal lobes.44

Treatment is usually with valproic acid and benzodi-azepines.45 Sometimes corticosteroids and IV Ig or evensurgery with subpial transection46 are used in refractory

cases. The outcome for overall language and cognitivefunction depends in part on how early the syndrome isrecognized and treated, but over 2/3 of children are leftwith significant language or behavioral deficits.47

Rasmussen encephalitis. Rasmussen encephalitis is asyndrome of diffuse lymphocytic infiltration of the brainassociated with partial seizures and progressive neurolog-ical deterioration with hemiparesis. This disorder typicallyaffects children 1 to 14 years old. The syndrome is associ-ated with perivascular cuffing on pathologic sections, andantibodies to the glutamate subunit GluR3 are commonlyidentified. The disorder is usually unilateral. Rasmussenencephalitis is very difficult to treat and frequentlyrequires surgical management with hemispherectomy.

EVALUATION As with many facets of neurology, the history is themost important diagnostic tool and should includeinformation on each of the items in Table 3-7. Thehistory should be obtained from family and eyewit-nesses, if possible. Many patients are unable to provideaccurate descriptions of the seizure and the postictalperiod.

MRI of the head with temporal lobe protocol (thincoronal slices through hippocampi) is the preferred imag-ing modality for most patients. The MRI sequences aremuch more sensitive to the causes of epilepsy than is CTimaging. CT can, however, be of help in the emergencydepartment setting. EEG is a vital component of the eval-uation to categorize the seizure type and assist with plan-ning of the treatment strategy. The need for laboratorytesting is highly variable depending on the history. Initialevaluation with fluid balance profile (FBP), Ca++,

Table 3-6.

Frequency of Aura Types by Location

Temporal Frontal Occipital

Aura Type (%) (%) (%)

Auditory 10 0 0Cephalic 5 15 5Epigastric 50 15 5General 10 15 5Gustatory 10 0 10None 15 40 5Olfactory 10 0 10Psychical 15 5 15Somatosensory 5 15 0Visual 10 5 50Vertiginous 10 2 0

Table 3-7.

Aura Types

Psychical Auras Illusion Hallucination

Memory Déjà vu, jamais Flashbacksvu, strangeness

Sound Advancing, receding, Voices, musiclouder, softer, clearer

Self-image Depersonalization, Autoscopyremoteness

Time Stand-still, rushing,slowing

Vision Macropsia, micropsia, Objects, faces,near, far, blurred scenes



Mg++, and liver function tests (LFTs) is important forboth the search for a potential cause of the seizures andfor medication selection. Urine drug screening should beobtained for patients with new-onset seizures.

TREATMENT Physicians and families often agonize over the decisionabout whether to initiate therapy after a single seizure.In the absence of a structural cause for the seizures or atypical syndrome of epilepsy, most patients do notrequire long-term treatment with an antiepileptic med-ication. The patient selection criteria for treatment aftera single seizure are listed in Table 3-8.48,49

Stopping the antiepileptic medication can alsobe a challenge. The prognostic factors used for makingthe decision regarding discontinuation are listed inTable 3-9.49 The selection of a particular antiepileptic medica-

tion for a given subtype of epilepsy has long been thesubject of controversy. When selecting a given drug,the concomitant medical disorders such as headache,bone marrow dysfunction, and liver insufficiencyshould be considered. Guidelines for the selection ofantiepileptic drugs, the pharmacology of the commonantiepileptic drugs, and potential interactions arereviewed in Tables 3-10 to 3-13.50-53

Surgery for epilepsy is an important but oftenunderutilized treatment option. The surgical optionprovides an opportunity for some patients to becomeseizure free. However, this is a complex discussion andbeyond the scope of this book.

Table 3-9.

Components of a Seizure History

AuraBirth and developmental historyCNS infectionsExacerbating factors (sleep, emotion, stress, menstrual cycle,

substance abuse)Family history of epilepsyHead traumaPostictal stateSeizure description by an eyewitness

Table 3-8.

Characteristics of Frontal Lobe Seizures by Region of Onset

Anteromedial Frontal

Contralateral eye and head versionFrequent generalizationSomatosensory auraTonic posture

Cingular

AmnesiaFacial expressions of fear and anger“Psychotic” appearance

Dorsolateral frontal

Simple partialTonic eye and head contraversion

Frontopolar

Loss of toneRapid generalization

Opercular/Insular

Complex seizures include gagging, swallowing, chewing,amnesia, genital manipulation

Seizures include gustatory sensation, salivation, gagging

Orbitofrontal

Blinking or staringComplex automatisms

Supplementary Motor Area

Contralateral tonic postureSimple motor seizureSomatosensory auraTonic eye and head contraversionVocalizes

Table 3-10.

Patient Selection Criteria for Treatment After a Single

Seizure

Probably

AVMBrain tumorCNS infectionImmediate family history of epilepsy

Probably Not

Acute febrile illnessDrug withdrawal or intoxicationElectrolye imbalanceEtOH withdrawalHyper/hypoglycemiaImmediate posttraumatic seizureSevere sleep deprivation–related seizure


Non-epileptic EventsNon-epileptic events are unusual in the pediatric popu-lation, especially in the younger child. Several categoriesof non-epileptic events (thrashing, staring, etc.) havedifferent natural histories and variable prognosis. Eti-ologies include conversion disorder, malingering, andmedical conditions, especially cardiac disorders. Symp-toms suggesting non-epileptic events include closedeyes, resisted eyelid opening, non-physiologic progres-sion, pelvic thrusting, lack of cyanosis, lack of tonguebiting, variable semiology, crying, and rapid reorienta-tion following the event.54-56

Neonatal SeizuresNeonatal seizures are poorly classified, under-recognized,especially in sick neonates, and often difficult to treat.

Neonatal seizures are often the presenting clinicalmanifestation of underlying neurological conditionssuch as hypoxic-ischemic encephalopathy, stroke,intraventricular or intraparenchymal hemorrhages,meningitis, sepsis, or metabolic disorders. Of these,hypoxic ischemic encephalopathy is the most commonetiology, accounting for 50% to 60% of patients withneonatal seizures.57

The neonatal brain is particularly vulnerable toseizure activity as a result of an imbalance of excitatoryto inhibitory circuitry. The imbalance favors excitation,and does so to facilitate important developmentalprocesses that occur during the neonatal period (synap-togenesis, apoptosis, progressive integration of circuitry,synaptic pruning). The imbalance occurs anatomicallyand physiologically by an overexpression of NMDAreceptor in the hippocampus and neocortical regions ofthe neonatal brain, a delay in the maturation of theinhibitory system, and neurons in such regions as thehippocampus are excited rather than inhibited by theneurotransmitter GABA (normally the primaryinhibitory neurotransmitter in the brain).

Clinical presentationSubtle. Subtle seizures are more common in prema-ture infants. As the name suggests, the seizures may bedifficult to identify with only tonic horizontal eye move-ments, sustained eye opening, chewing, or apnea. Insome cases there may be “boxing” movements. Theseseizures may have limited EEG changes correlating withthe seizure activity. 58-61

Clonic. Clonic seizures typically present as rhythmic,slow movements. The movements have a frequency of1 to 3 Hz. Focal clonic seizures involve one side of thebody, and the infant is not clearly unconscious.


Table 3-11.

Prognostic Factors for Stopping AEDs

Favorable Unfavorable

Primary generalized epilepsy Partial epilepsyIdiopathic epilepsy Identifiable lesionsChildhood onset Adult onsetEasy to control Difficult to controlNormal neurological examination Abnormal neurologic

examinationNormal intelligence Mental retardationMore than 2–3 years seizure-free Less than 3 years seizure-

freeNormal EEG Epileptiform EEG

From Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed.Philadelphia: Lippincott Williams & Wilkins; 2006.

Table 3-12.

Antiepileptic Drug Selectiona

Seizure Type VPA LTG TPM LVT ETX ACTH GBP CBZ PHT PHB

Infantile spasms 1 2Absence 2 2 1Tonic-clonic 1 2 2 2 3 2 4, 1bb

Myoclonic 1 2Atypical absence 1 2Simple partial 3 2 2 2 1 2 1bb

Complex partial 2 2 2 2 2 1 2 1bb

aNumbers refer to order of preference for use in specific seizure types.bbInfants.From Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006.


upper limbs and tonic extension of lower limbs (mim-icking decerebrate posturing). There are no EEGchanges in 85% of cases.58–61

Myoclonic. Focal myoclonic seizures usually involveflexor muscles of an upper extremity. Often, there are noEEG changes. Conversely, generalized myoclonicseizures exhibit bilateral jerks of both upper and lowerlimbs, and may resemble infantile spasms. These gener-alized seizures are more likely to have EEG changes.58–61


Table 3-13.

Drug–Drug Interactions: Effects on Serum Concentration of Adding a Second Antiepileptic Drug to First

Antiepileptic Drug

Effects of Added Drug on Serum

Original Drug Added Drug Concentration of Original Drug

Carbamazepine Clonazepam No changePhenobarbital DecreasePhenytoin DecreasePrimidone Decrease

Clonazepam Phenobarbital DecreasePhenytoin DecreaseValproate No change

Ethosuximide Carbamazepine DecreaseMethylphenobarbital IncreasePhenobarbital No changePhenytoin No changePrimidone No changeValproate Increase or no change

Phenobarbital Carbamazepine No changeClonazepam Data conflictingMethsuximide IncreasePhenytoin IncreaseValproate Increase

Phenytoin Carbamazepine Increase or decreaseClonazepam Data conflictingEthosuximide No changeMethsuximide IncreasePhenobarbital Decrease, increase, or no changePrimidone No changeValproate Decrease

Primidone Carbamazepine Increased concentration of derived phenobarbitalClonazepam No changeEthosuximide No changePhenytoin Increased concentration of derived phenobarbitalValproate Increase

Valproate Carbamazepine Decrease, increase, or no changeClonazepam No changeEthosuximide No changePhenobarbital DecreasePhenytoin DecreasePrimidone Decrease

From Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006.

Multifocal clonic seizures involve several body parts,often in a migrating pattern. Generalized clonic seizuresare rarely observed in newborn because of the incom-plete myelination of the brain.58–61

Tonic. Focal tonic seizures result in sustained postur-ing of a limb, the trunk, or the neck. These seizures areusually accompanied by EEG changes. Generalizedtonic seizures exhibit tonic extension of all limbs(mimicking decorticate posturing) or tonic flexion of


occur with intravenous infusion of the highly alkalinephenytoin. The drug of choice for neonates in status islorazepam. This agent has several properties that makeit ideal—a long half-life and a small volume of distribu-tion, which prolongs its retention at high levels in thebrain.

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3. Statler KD. Pediatric posttraumatic seizures: epidemiol-ogy, putative mechanisms of epileptogenesis and prom-ising investigational progress. Dev Neurosci. 2006;28:354-363.

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SyndromesBenign familial neonatal seizuresBenign familial neonatal seizures occur as a geneticdisorder with an autosomal dominant inheritance pat-tern associated with chromosome 20q. The seizurestypically start on day of life 2 or 3. The neonate mayhave as many as 10 to 20 seizures per day. The syn-drome is usually self-limited and benign, but approxi-mately 10% of cases progress to an antiepilepticdrug-requiring seizure disorder. Neurological develop-ment is normal.58–61

Fifth-day fitsFifth-day fits usually begin on day of life 4 to 6. Theseizures are typically multifocal clonic seizures and arefrequently associated with apnea. The seizures usuallylast for less than 24 hours. Fifth-day fits progress to sta-tus epilepticus in 80% of cases.58–61

Benign neonatal sleep myoclonusBenign neonatal sleep myoclonus begins during the firstweek of life. The seizures are usually bilateral myoclonicjerks that last for several minutes and occur only duringNREM sleep. The EEG is normal or slow. The seizuresworsen with the administration of benzodiazepines. Theseizures usually resolve within 2 months and neurolog-ical outcome is normal.58–61

Benign myoclonus of early infancyBenign myoclonus of early infancy has an onset at age 3to 9 months but it can be much earlier. The seizuresresemble infantile spasms but the EEG is normal. Theseizures usually occur while the patient is awake. Theseizures disorder may continue for 1 to 2 years but neu-rological outcome is normal.58–61

TreatmentThe clinician should first search for underlying etiolo-gies producing the seizures and treat (hypoglycemia,hypocalcemia, sepsis). If the clinician cannot find areadily identifiable and treatable etiology, the frontlineagent of choice for treating seizures is phenobarbital(see Table 3-14 for dosing suggestions).62 Phenobarbi-tal as a single agent will stop seizure activity in 42% ofpatients. When the seizure does not respond to a singleagent, phenytoin is added with an increase in efficacy to65%. Currently, fosphenytoin, the salt ester of pheny-toin, is preferred in the neonate because it is an aqueoussolution that is soluble in glucose-containing solutions,can be administered more quickly than phenytoin, andwill not cause “purple glove syndrome.”62 Purple glovesyndrome is necrosis or injury of the soft tissue that can

Table 3-14.

Neonatal AED Dosing Suggestions

Phenobarbital—20 mg/kg load over 10 to 15 min.If necessary add more phenobarbital in 5-mg/kg bolusesFosphenytoin—20 mg/kg at 1 mg/kg/minAtivan—0.1 mg/kg

From Rennie J, Boylan G. Treatment of neonatal seizures. Arch Dis Child FetalNeonatal 2007;92:F148–F150.


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