TheroleofEEGinthe diagnosisandclassiﬁcation ...eeg-emg.hu/textbox/media/The role of EEG part 2.pdfmTOR pathway (D’Gama et al., 2015). Beside the focal structural epilepsy with

Journal Identification = EPD Article Identification = 0952 Date: January 11, 2018 Time: 12:9 pm

do

i:10.

1684

/ep

d.2

017.

0952

E

F

CMSL<

Seminar in EpileptologyEpileptic Disord 2017; 19 (4): 385-437

The role of EEG in thediagnosis and classificationof the epilepsy syndromes:a tool for clinical practiceby the ILAE NeurophysiologyTask Force (Part 2)*

Michalis Koutroumanidis 1, Alexis Arzimanoglou 2,3,Roberto Caraballo 4, Sushma Goyal 5, Anna Kaminska 6,

8 9
7
pileptic Disord, Vol. 19, No. 4, December 2017 385

IGURES ONLINE

orrespondence:ichalis Koutroumanidis

t Thomas’ Hospital,ondon, [email protected]>

Pramote Laoprasert , Hirokazu Oguni , Guido Rubboli ,William Tatum 10, Pierre Thomas 11, Eugen Trinka 12,Luca Vignatelli 13, Solomon L. Moshé 141 St Thomas’ Hospital, London, UK2 University Hospitals of Lyon (HCL), Department of Paediatric Clinical Epileptology,Sleep Disorders and Functional Neurology, Member of the European Reference CentreEpiCARE, Lyon, France3 Epilepsy Unit, Department of Paediatric Neurology, San Juan de Deu Hospital, Memberof the European Reference Centre EpiCARE, Barcelona, Spain4 Hospital J P Garrahan, Neurology, Capital Federal, Buenos Aires, Argentina5 Evelina Hospital for Children, London, UK6 APHP, Hopital Necker-Enfants Malades, Department of Clinical Neurophysiology, Paris,France7 Children’s Hospital, Neurology, Aurora, Colorado, 80045, USA8 Tokyo Women’s Medical University, Department of Pediatrics, Shinjuku-ku, Tokyo,Japan9 Danish Epilepsy Centre, Department of Neurology, Dianalund, Denmark10 Mayo Clinic, Neurology, Jacksonville, Florida, USA11 Hopital Pasteur, Neurology, Hôpital Pasteur 24C, Nice, France12 Paracelsus Medizinische Privatuniversitat, Salzburg, Austria13 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy14 Albert Einstein College of Medicine, Neurology, Neuroscience, and Pediatrics, Bronx,New York, USA

*This report was written by experts selected by the International League Against Epilepsy(ILAE) and was approved for publication by the ILAE. Opinions expressed by the authors,however, do not necessarily represent the policy or position of the ILAE.

Part 1 was published in the September 2017 issue of Epileptic Disorders : KoutroumanidisM, Arzimanoglou A, Caraballo R, et al. The role of EEG in the diagnosis and classificationof the epilepsy syndromes: a tool for clinical practice by the ILAE Neurophysiology TaskForce (Part 1). Epileptic Disord 2017; 19(3): 233-98.

mailto:[email protected]


3

M. Koutroumanidis, et al.

ABSTRACT – The concept of epilepsy syndromes, introduced in 1989,was defined as “clusters of signs and symptoms customarily occurringtogether”. Definition of epilepsy syndromes based on electro-clinical fea-tures facilitated clinical practice and, whenever possible, clinical researchin homogeneous groups of patients with epilepsies. Progress in the fieldsof neuroimaging and genetics made it rapidly clear that, although crucial,the electro-clinical description of epilepsy syndromes was not sufficient toallow much needed development of targeted therapies and a better under-standing of the underlying pathophysiological mechanisms of seizures.The 2017 ILAE position paper on Classification of the Epilepsies recognizedthat “as a critical tool for the practicing clinician, epilepsy classification mustbe relevant and dynamic to changes in thinking”. The concept of “epilepsysyndromes” evolved, incorporating issues related to aetiologies and comor-bidities. A comprehensive update (and revision where necessary) of the EEGdiagnostic criteria in the light of the 2017 revised terminology and conceptswas deemed necessary. Part 2 covers the neonatal and paediatric syndromes

th thdiso

psy sEG A

1

PptAo(pA––es–is–em(–woTmpicIcsuE

ssbsktltbTcemtyfhtsoaftahes

in accordance wiat www.epileptic

Key words: epileEEG Telemetry, E

. Introduction

art 2 of this work includes the main neonatal andaediatric epilepsy syndromes, presented according

o age at onset (Scheffer et al., 2017). CAE (Childhoodbsence Epilepsy) and Eyelid Myoclonia with or with-ut Absences have already been discussed in Part 1

Koutroumanidis et al., 2017a) amidst the genetic (idio-athic) generalized epilepsies (GGE/IGE).s in Part 1, the structure of each chapter includes:(i) a brief overview of the presented syndrome;(ii) a description of the symptoms and semiology of

ach of the seizure types that are associated with theyndrome;

(iii) an EEG section with the pertinent background,nterictal and ictal characteristics in the awake state andleep;(iv) recording protocols developed according to the

vidence presented in the preceding EEG section toaximize diagnostic yield at two levels of complexity

see section 1.5 of Part 1);(v) levels of EEG diagnostic confidence in accordanceith the strength of the EEG findings (see section 1.3f Part 1).he importance of adequate pertinent clinical infor-ation for the use of the appropriate recording

rotocol and the correct interpretation of the EEG find-

86

ngs and clinically useful final EEG report across all agesannot be overemphasized (figure 1.01 of Part 1).n contrast to the important role of the EEG in thelinical diagnosis and the characterization of epilepsyyndromes, its contribution for the diagnosis of thenderlying aetiology is overall moderate. CertainEG patterns and combinations may strongly indicate

osia(iu

e age of onset. [Published with educational EEG platesrders.com].

yndromes, EEG and epilepsy diagnosis, EEG protocols,tlas

pecific genetic syndromes (such as GGE/IGE, progres-ive myoclonus epilepsy, or Dravet syndrome [DS]),ut others, such as the commonly encountered focalpikes in association or not with focal slowing, are ineeping with aetiologies as diverse as genetic, struc-ural, or unknown (see also section 1.6 of Part 1). In theatter case, the EEG may localize the focus, highlighthe high probability of a structural lesion, and guiderain imaging studies.here is a dominant maturational element in thelinical and EEG presentation of the structural focalpilepsies during childhood (Nordli et al., 2001), whichay render localization and even lateralization of

he responsible lesion very difficult, particularly inounger children. In children up to 2-3 years of age,or example, the repertoire of seizure manifestationsas been shown to be limited, with four seizure

ypes (epileptic spasms, tonic, clonic, and hypermotoreizures) constituting up to 80% of the total ictal semi-logies (Hamer et al., 1999). In addition, the interictalnd ictal EEG findings in infants and young children arerequently diffuse, even when the responsible struc-ural lesion is small (supplementary figures 1.01-1.03),phenomenon presumably related to age-dependentyperexcitability. Such bilateral or diffuse/generalizedpileptic discharges may not per se preclude epilepsyurgery (Wyllie et al., 2007; Arzimanoglou et al., 2016)

Epileptic Disord, Vol. 19, No. 4, December 2017

r, on the other hand, prompt unsuitably early inva-ive procedures. It is important to emphasize thatn this period of life, regional interictal backgroundbnormalities, such as polymorphic delta activity (PDA)supplementary figure 1.04), are much more importantndicators of the epileptic focus and the associatednderlying structural lesion (Noh et al., 2013). As in


E

The role of EEG in the diagnosis and classification of the epilepsies

AbbreviationsABFEC: atypical benign partial epilepsy of childhood IED: interictal epileptic dischargesBFIE: benign familial infantile epilepsy IPS: intermittent photic stimulationBFNE: benign familial neonatal epilepsy IS: infantile spasmsBFNIE: benign familial neonatal-infantile epilepsy LKS: Landau-Kleffner syndromeBFNIS: benign familial neonatal-infantile seizures LGS: Lennox-Gastaut syndromeBIE: benign infantile epilepsy MAE: myoclonic-atonic epilepsyBRE: benign rolandic epilepsy MAS: myoclonic absence seizuresCAE: childhood absence epilepsy MEI: myoclonic epilepsy in infancyCSWS: continuous spike-and-wave during slow sleep MS: myoclonic seizureCTS: centrotemporal spikes OE-G: occipital childhood epilepsy of GastautDS: Dravet syndrome OLE: occipital lobe epilepyED: epileptic discharge OS: Ohtahara syndromeEIMFS: epilepsy of infancy with migrating focal seizures PDA: polymorphic delta activityELMA: eyelid myoclonia with absences PKD: kinesigenic dyskinesiaEMA: epilepsy with myoclonic absences PPR: photoparoxysmal responsesEMAS: epilepsy with myoclonic-atonic seizures PS: Panayiotopoulos syndromeEME: early myoclonic encephalopathy RMEI: reflex myoclonic epilepsy in infancyESES: electrical status epilepticus during sleep S-B: suppression burstFOS: fixation-off sensitivity SES: status epilepticus during sleepFS: febrile seizure SSW: slow spike-waves

sis

tsdi(CtstiteNscmW[htdAiobte

2S

2

NwanncaompeMbtnc

GSPWD: generalized spike/polyspike-and-wave dischargesGSWD: generalized spike-and-wave dischargesGTCS: generalised toni-clonic seizureHV: hyperventilationICCA: infantile convulsions and paroxysmal choreoatheto

he adolescent and the adult patient, sleep recordingshould be pursued because they can activate epilepticischarges, which acquire higher lateralizing and local-

zing value during rapid eye movement (REM) sleepOchi et al., 2011).linical-EEG presentation changes with brain matura-

ion such that by the age of 6-7 years and in adolescents,eizure symptoms and semiology, as well as interic-al and ictal EEG findings, become similar to thosen adults, providing valuable information about theopography of the primary neural network that gen-rates focal seizures.eonatal structural focal epilepsies are comprehen-

ively discussed in Section 2 of this paper, while EEGhanges in specific paediatric epilepsy syndromes thatay also relate to structural brain lesions (such asest syndrome [WS] or Lennox Gastaut syndrome

LGS]) are fully covered in the relevant chaptersere. Structural epilepsies in adults (also applicable

o adolescents and older children) have already beenescribed in Part 1 under specific lobar syndromes.

pileptic Disord, Vol. 19, No. 4, December 2017

specific chapter on structural focal epilepsies innfancy and early and late childhood across the vari-us aetiologies is not included in this paper, but wille the topic of a later publication. Readers are referred

o the relevant chapters of excellent textbooks (Bureaut al., 2012; Arzimanoglou et al., 2016).

dDtnKM

SWI: spike-wave indexTA: typical absencesTLE: temporal lobe epilepsyWS: West syndrome

. NEONATAL SEIZURES ANDYNDROMES

.1 Overview of neonatal seizures and epilepsies

eonatal seizures require rapid diagnosis, aetiologicalorkup, and therapy, as delayed recognition of a treat-

ble cause can have a significant impact on the child’seurodeveloment. In conjunction with advances ineuroimaging, metabolic, and genetic testing, electro-linical characterization with video-EEG recordingllows more rapid determination of seizure aetiol-gy and implementation of targeted treatment (e.g. inetabolic disorders with treatable conditions such as

yridoxine- and pyridoxal 5 ′ -phosphate dependentpilepsy) (for review see Pearl, 2016).ajor aetiologies of neonatal seizures are acute cere-

ral injury including hypoxic-ischaemic encephalopa-hy, intracranial haemorrhage and infarctions, centralervous system infection, metabolic disturbances,ongenital structural brain lesions, and drug with-

387

rawal (Kang and Kadam, 2015; Arzimanoglou anduchowny, 2018). Epilepsies beginning in the neona-

al period represent, therefore, an uncommon butot rare cause of neonatal seizures (Mizrahi andellaway, 1998; Co et al., 2007; Volpe, 2008; Sands andcDonough, 2016).


3

M

SpbfsatAdaCrmBotAistwEem

IsrKA(MocIiodosfra

2Esa

OEstsEt

eAcfkpcaa(Afa2mASEffoas(pa

SIbaIt(owsoOIttceljbi

. Koutroumanidis, et al.

tereotyped focal seizures beginning in the neonataleriod in the absence of metabolic or infectious distur-ances may reveal an underlying structural anomaly, as

ocal cortical dysplasia or cortical tubers in tuberousclerosis complex (TSC), or more diffuse anomaliesssociated with major congenital brain malforma-ions, such as hemimegalencephaly or lissencephaly.dvances in identification of genetic causes of cerebralysgenesis in recent years include somatic mutationssociated with hemimegalencephaly, type IIb Focalortical Dysplasia, and Tuberous Sclerosis Complex

esulting from mutations in various components of theTOR pathway (D’Gama et al., 2015).

eside the focal structural epilepsy with neonatalnset, three electroclinical syndromes with neona-

al onset are recognized by the International Leaguegainst Epilepsy (ILAE). One of these, Benign Famil-

al Neonatal Epilepsy, is characterized by transienteizures and good neurodevelopmental outcome. Thewo other syndromes belong to the encephalopathiesith epilepsy, are associated with a burst suppression

EG pattern, and their prognosis is in most patientsxtremely poor with high mortality during the firstonths of life and severe development impairment.

n neonatal-onset epilepsies without metabolic ortructural alteration, at least three groups withelated functions were identified: ion channels (i.e.CNQ2), regulators of forebrain development (e.g.RX), and regulators of synaptic function (e.g. STXBP1)

Weckhuysen and Korff, 2014). Epilepsy with Infantileigrating Focal Seizures (EIMFS) (with de novo gain-

f-function mutation of KCNT1 as the most commonause) can present near the end of the neonatal period.n addition to anamnestic, clinical, and imaging data,ctal and interictal EEG can direct to a possible aeti-logy, which helps determine the degree of cerebralysfunction and prognosis, but also in the evaluationf treatment response. The neonatal EEG recordinghould be at least 60 minutes long (to include wake-ulness and sleep) with elementary polygraphy (ECG,espiration) and bilateral EMG if abnormal movementsre suspected (Beal et al., 2017).

.2 Neonatal epileptic encephalopathies:arly-Infantile Epileptic Encephalopathy withuppression-burst pattern (Ohtahara syndrome)nd Early Myoclonic Encephalopathy (EME)

88

verviewarly Myoclonic Encephalopathy (EME) and Ohtaharayndrome (OS) are severe neonatal or early infan-ile epileptic/developmental encephalopathies. Theyhare some types of seizure and also a pertinentEG feature, namely the suppression-burst (S-B) pat-ern. The strategy for diagnostic EEG recording is

sNtcdFc

ssentially the same (Ohtahara and Yamatogi, 2003;icardi and Ohtahara, 2005). EME is typically asso-iated with metabolic disorders and a degree ofamilial occurrence (i.e. pyridoxine-dependency, non-etotic hyperglycinaemia, methylmalonic academia,roprionic acidaemia, molybdenum co-factor defi-iency, sulphite oxidase deficiency, Menkes disease,nd Zellweger syndrome), while in OS, congenital orcquired structural brain lesions are more frequenthemimegalencephaly, lissencephaly, polymicrogyria,icardi syndrome, dentato-olivaro dysplasia, and dif-

use cerebral migration disorders) (Schlumberger etl., 1992; Miller et al., 1998; Ohtahara and Yamatogi,006; Arzimanoglou and Duchowny, 2018). Numerousutations have been associated with OS, includingRX, mitochondrial glutamate transporter, SLC25A22,TXBP1, and SCN2A (Weckhuysen and Korff, 2014).volution to WS or multifocal epilepsy occurs morerequently in OS. Both syndromes, EME and OS, areairly similar in terms of age at onset, EEG aspectf suppression-burst, and overlapping seizure types,nd therefore their distinction is often difficult andometimes impossible in the beginning of the diseaseSchlumberger et al., 1992). Moreover, some childrenresent motor manifestations during the bursts ofctivity that may be impossible to classify.

eizures: symptoms and semiologyn the two syndromes, seizures begin very soon afterirth, usually within the first month of life (Yamatogind Ohtahara, 2002).n OS, the most characteristic seizures are epilep-ic spasms and tonic seizures, in clusters or isolatedOhtahara and Yamatogi, 2006). They can be lateralized,r generalized but asymmetric particularly in neonatesith lateralized structural lesions. Other seizure types

uch as focal motor seizures and hemiconvulsionsccur in about a third of patients (Yamatogi andhtahara, 2002).

n contrast, myoclonic seizures (MS) (axial, segmen-ary, or erratic) are typical in EME and rare in OS. In EME,he frequency of seizures is variable but can be almostontinuous. Erratic and segmentary myoclonus occurarly on, often within the first few days or month of

ife (Guerrini and Aicardi, 2003). In erratic myoclonus,erks appear to shift randomly from one area of theody to another, mainly involving the face or extrem-

ties. Axial myoclonus is less common. Focal clonic or


ubtle seizures may follow myoclonus.ot infrequently, however, complex ictal movements

hat are usually stereotyped in the given child and asso-iated with EEG bursts of paroxysmal activity can beifficult to classify as either spasms or myoclonias.ocal seizures occur more or less equally in bothonditions and are very common. These may be


E

The

mhn(

E

BIasc(boiime

IIco(6opOt(uccolcfitAAeiTsb(piaiOabmb

tl

IEprvfevfinawfiCccpctFotsuoaiu

RBStiEitALiEa

L(

otor with deviation of the eyes, tonic posturing, oremiconvulsions. Subtle seizure with autonomic phe-omena, such as flushing or apnoea, can also occur

Yamatogi and Ohtahara, 2002; Beal et al., 2017).

EG section

ackgroundn EME, EEG can be normal at the onset of the seizures,nd repetitive EEGs may be necessary for the diagno-is (Ozyurek et al., 2005). When the presentation isomplete, there is no spatial or temporal organizationbackground rhythms are not different between cere-ral areas and do not cycle/change with time and statef vigilance), and there are no physiological features

n either wakefulness or sleep. S-B is the prevailingnterictal pattern, however, clinical seizures conco-

itant with the bursts have been reported (Fuscot al., 2001).

nterictal abnormalitiesn EME and OS, the suppression-burst (S-B) patternonsists of bursts of high-voltage asynchronous deltar theta waves, mixed with spikes and polyspikes

from 150 up to 350 �V) that last from 1 toseconds and alternate with inter-burst intervals

f low-voltage (


3

M

BTsgcpfCNrReam

D–situ–tto

Ir––eNic

AireLapePi

2

OBktsS

o4conhnse

Ndiieba(biaitctdistas

SSdfctBnaSoakf(

E


. High diagnostic certainty (probable)he EEG shows stable/invariant S-B pattern withouteizures. This also applies to basic level recordingiven the specificity of S-B in the absence of otheronditions that can show a similar/reminiscent EEGicture (hypoxia, phenobarbital, fentanyl, etc.-see dif-

erential diagnosis below).. Low diagnostic certainty (possible)o S-B is registered on the EEG, which may have been

ecorded too early during the course of the disease.epeat basic or advanced recordings once seizures arestablished to register the typical S-B pattern/seizuresnd move diagnostic certainty to probable or confir-atory level.

ifferential diagnosis(1) A discontinuous EEG pattern that may have some

imilarities to S-B can be seen in neonatal hypoxicschaemic encephalopathy. However, in this condition,he pattern is usually transient and can be reactive ornstable in character.(2) A pattern reminiscent of S-B may be secondary to

reatment for neonatal status epilepticus with medica-ion, such as midazolam infusion and sometimes withpioids such as sufentanyl and fentanyl.

ndications for repeating advanced video-EEGecording level

(1) Failure to record seizures.(2) Clinical suspicion of other types of seizure and/or

pileptic syndrome (focal structural epilepsy).ote. Repeat video-EEG basic level recording to mon-

tor response to treatment for possible metabolicauses.

typical EEG/video-EEG features to be highlightedn the EEG report, which may cast doubts on (orefute) the diagnosis of a neonatal epilepticncephalopathyow amplitude of bursts, rare or absent spikes,nd moderate flattening during the hypoactivityeriod would suggest other causes of neonatalncephalopathy.ersistence of physiological background features dur-ng wakefulness and sleep.

.3 Benign familial neonatal epilepsy (BFNE)

90

verviewenign Familial Neonatal Epilepsy (BFNE), previouslynown as Benign Familial Neonatal Seizures, belongso a group of autosomal dominant benign epilepticyndromes with onset during the first year of life.eizures typically start on the second or third day

BN

IIe

f life (in neonates born at full-term) or at around0 post-menstrual weeks in premature neonates; rareases with seizure onset after the first four weeksf life have also been described. Prenatal and peri-atal history is unremarkable and there is familyistory of neonatal seizures. Two autosomal domi-ant epilepsy syndromes may present with neonataleizures: BFNE and benign familial neonatal-infantilepilepsy/seizures (BFNIE/BFNIS) (Zara et al., 2013).

ote. BFNE was the first proper genetic epilepsyescribed, hence some more information on its genet-

cs was deemed appropriate. Genetic mutation in BFNEs found in around 90% of cases, with the KCNQ2ncoding the voltage dependent K+ channel subuniteing the most common gene; occasionally KCNQ3nd SCN2A mutation were found in BNFE familiesGrinton et al., 2015). KCNQ2 mutations have alsoeen found in families, in which one or more fam-

ly members had more severe outcome, includingvariable degree of intellectual disability, suggest-

ng that the clinical disease severity may be relatedo the extent of the mutation-induced functional K+hannel impairment. Recently, de novo KCNQ2 muta-ions were found in patients with neonatal-onsetrug-resistant seizures, psychomotor retardation, and

mportant interictal abnormalities including “suppres-ion burst” and abnormal neuroradiological features,hus defining a so-called “KCNQ2 encephalopathy”nd the variable phenotype of KCNQ2-related epilep-ies (Weckhuysen et al., 2012; Kato et al., 2013).

eizures: symptoms and semiologyeizures usually start with tonic posture, head or eyeeviation or staring, apnoea, and other autonomic

eatures, and often progress to unilateral or bilaterallonic movements. The postictal state is brief, interic-al examination is unremarkable and feeding is normal.iochemical examinations and cerebral imaging areormal (Hirsh et al., 1993; Ronen et al., 1993; Grinton etl., 2015).eizure remission in BFNE occurs at around 4-6 monthsf age, irrespective of treatment. Development is usu-lly normal and febrile or afebrile seizures are widelynown to occur later in life after a prolonged seizure-ree period in approximately 15-25% of BFNE casesGrinton et al., 2015).

EG section


ackgroundormal or subnormal.

nterictal abnormalitiesnterictal recordings are normal or show minorpileptiform or non-epileptiform focal or multifocal


E

The

a“wimsiofe

IFowrcbcawrittOeates(ottoaa

RBApeshtAPtb

LAr

(RB(NC(Sms

Ir––oib(

Aie––––––

2

OAtataowtbm(mfe

bnormalities (Grinton et al., 2015). A pattern calledtheta pointu alternant” can rarely occur in childrenith BFNE. It is defined as a dominant theta activ-

ty that is non-reactive, alternating or discontinuous,ay be intermixed with sharp waves, and frequently

hows inter-hemispheric asynchrony. It is present dur-ng active and quiet sleep, impeding precise definitionf maturational age. “Theta pointu alternant” can be

ound in other conditions and therefore is not consid-red as specific for BFNE.

ctal EEGocal seizures with initial tonic phase. When recordedn video-EEG, semiology is typical and stereotypedith initial diffuse hypertonia (symmetric or asymmet-

ic), associated with apnoea/cyanosis and followed bylonic movements, unilateral or involving the wholeody, symmetric or not. The semiology may alsoonsist of “staring” with the arrest of activity beingssociated with autonomic or oculo-facial featuresithout clonic movements. Pure clonic seizures are

are. Generalized seizures have never been reportedn this syndrome. Seizures are brief and last for lesshan two minutes and may be very frequent, with upo 30 seizures per day.

n the EEG, seizures begin with diffuse bilateral,ventually asymmetric, flattening of the backgroundctivity for 5-20 seconds (which corresponds to theonic and/or apnoeic phase), followed by focal or bilat-ral rhythmic, high-amplitude slow waves, and then byharp waves over the frontal, temporal or central areascorresponding to vocalizations, chewing, or unilateralr bilateral clonic movements). The preponderance of

he ictal EEG changes and associated motor manifes-ations may vary between the left and right side, fromne seizure to the next, in the same child (Ronen etl., 1993; Hirsch et al., 1993) (supplementary figure 2.10nd 2.11).

ecording protocolsasic levelttempt to record during wakefulness and sleep, ifossible with polygraphy (ECG, respiration, and bilat-ral deltoid EMG to record autonomic and other ictaligns). Seizures are expected to occur within a fewours, as they are very frequent at onset and before

reatment, sometimes amounting to status epilepticus.dvanced level


erform long video-EEG recordings for up to 24 hourso recover seizures. Polygraphy, as described in theasic level, is mandatory.

evels of EEG diagnosis) Confirmatory of suspected BFNE in neonates with

elevant family history

aomoota

role of EEG in the diagnosis and classification of the epilepsies

For both basic and advanced recording levels)ecording of typical ictal and interictal patterns.) High diagnostic certainty (probable)

For both basic and advanced recording levels)ormal background activity but no seizures recorded.) Low diagnostic certainty (possible)

For both basic and advanced recording levels)lightly abnormal background activity with few focal,ostly multifocal, spikes or sharp waves), or atypical

eizures recorded

ndications for repeating advanced level video-EEGecording

(1) Failure to record seizures.(2) Clinical suspicion of other types of seizures

r of acute underlying pathologies, such as hypoxia-schaemia, infectious processes, metabolic distur-ances, or diseases or other epileptic syndromes

structural focal epilepsies).

typical EEG/video-EEG features to be highlightedn the EEG report, which may cast doubts on orliminate a diagnosis of BFNEAbnormal background activityAbundant focal or multifocal interictal abnormalitiesSuppression-burst patternFocal seizures without typical features of BFNEEpileptic spasmsMyoclonias

.4 Focal structural epilepsy of neonatal onset

verviewmong neonatal epilepsy syndromes, focal struc-

ural epilepsies are rare and may overlap with OS,s both can share similar electroclinical presen-ation. Indeed, studies focusing on electroclinicalspects of focal structural epilepsies with neonatalnset other than those on epileptic encephalopathiesith suppression-burst (S-B; see relevant chap-

er) are scarce. Among 38 infants with seizureseginning within the first two months (mean: 0onths), not related to acute symptomatic causes

anoxic-ischaemic encephalopathies, neonatal stroke,etabolic, or infectious), the main seizure types were

ocal (76%) and epileptic spasms (24%) (Akiyamat al., 2010); 34 of those (89%) had focal seizures

391

nd epileptic spasms in combination, with the sec-nd seizure type appearing after a median of threeonths. Multiple correspondence analysis, performed

n electroclinical features, showed that the presencer absence of S-B pattern and of an asymmetry in

he EEG background were the most meaningful vari-bles to separate these very-early-onset epilepsies into


3

M

sps2aacpAYTsfcieAci[olirS

SItesiK2F(mmFacdsdMiopEenomMs

coApbstd(i

E

BTaopp(

ITtatfiohsfpat

IFeastnmaoaTflo


ubgroups, thus confirming the relevance of the S-Battern in the classification of neonatal-onset epilepsyyndromes (Akiyama et al., 2010; Yamamoto et al.,011). While the asymmetry in interictal EEG was oftenssociated with the presence of a structural brainbnormality, the S-B pattern was also associated witherebral lesions in around half of the patients, asreviously reported for OS (see relevant section andicardi and Ohtahara [2005], Akiyama et al. [2010], andamamoto et al. [2011]).ypically, the presence of a focal lesion is suggested bytereotyped focal seizures, electrographically arisingrom the same region (but potentially multifocal in thease of tuberous sclerosis complex), or by asymmetriesn voltage or frequency of background activities (Bealt al., 2017), however, interictal EEG can also be normal.lthough EEG findings can sometimes be fairlyharacteristic (for instance periodic focal abnormal-ties in focal cortical dysplasia or cortical tubersDomańska-Pakieła et al., 2014; Kotulska et al., 2014]),r high-voltage monomorphic theta or delta activity in

issencephaly), precise diagnosis relies on neuroimag-ng. Typically, treatment relies on epilepsy surgery, butesponse to medical treatment may be good (Kröll-eger et al., 2007).

eizures: symptoms and semiologyctal semiology relates to the topography of the epilep-ic discharge. Seizures may be tonic or clonic, orxhibit only subtle motor manifestations or autonomicymptoms, or be sub-clinical, especially when aris-ng from temporal regions (Volpe, 1989; Mizrahi andellaway, 1987; Mizrahi and Kellaway, 1998; Beal et al.,017).ocal clonic. These seizures consist of rhythmicusually one to three jerks per second), repetitive

ovements of the face, proximal or distal limb, or axialuscles.

ocal tonic. Sustained posturing of a limb or later-lized axial flexion characterizes these seizures thatan also be accompanied by sustained conjugate eyeeviation to one side. Like focal clonic seizures, toniceizures are usually associated with synchronized EEGischarges.yoclonic. These seizures manifest as sudden brief

rregular, single or multiple contractions of musclesr muscle groups in the face, the proximal and distalarts of the limbs, or the trunk.

92

pileptic spasms. Spasms manifest as sudden flexion,xtension or mixed flexion and extension of limbs,eck, and body, which can be bilateral symmetricr asymmetric, or focal. A spasm is longer than ayoclonic jerk, but less sustained than a tonic seizure.otor automatisms. Also called “subtle”, these

eizures occur frequently in the new-born and

tvoFota

onsist of minimal motor manifestations, with or with-ut autonomic signs.utonomic. These seizures manifest with a variety ofaroxysmal autonomic changes such as alterations inreathing, heart rate or blood pressure, salivation,weating, and colour changes. Autonomic manifesta-ions are often encountered in association with seizureischarges that originate from the temporal areas

Watanabe et al., 1982), and have also been describedn subtle seizures.

EG section

ackgroundhe background is usually normal on the non-ffected hemisphere, but shows variable alterationsn the affected side that range from mild to com-lete absence of physiological features and containaroxysmal abnormalities, or hemi-suppression-burst

supplementary figure 2.12 and 2.13).

nterictal abnormalitieshe interictal paroxysmal patterns depend on theype and the extent of the lesion. Spikes, polyspikesnd sharp waves, but also slow delta waves, some-imes of pseudo periodic occurrence (supplementarygure 2.14), and focal rapid rhythms may be foundver the affected side. Abnormalities may also includeemi-suppression bursts concerning the whole hemi-phere, in which case they are highly suggestive ofocal cortical dysplasia or hemimegalencephaly (sup-lementary figure 2.15A). Nevertheless, absence of EEGbnormalities does not exclude the diagnosis of struc-ural focal epilepsy.

ctal EEGocal seizures may or may not be associated withpileptic spasms in the given patient. Focal seizureslways begin in the same side or area of the brain andhow stereotyped electroclinical course that relateso the topography of the lesion, however, those ineonates with tuberous sclerosis complex may beultifocal. Coexistent epileptic spasms are usually

symmetric and may precede, follow a focal seizure, orccur during its evolution (supplementary figure 2.15Bnd C).he ictal EEG depends on the seizure type with focalattening in focal tonic seizures, rhythmic, periodicr irregular spiking in clonic seizures (supplemen-


ary figure 2.15C and 2.16), and rhythmic or periodicery-low-amplitude slow-wave discharges in “subtle”r subclinical seizures (supplementary figure 2.17).ocal myoclonic jerks, unilateral or predominating onne side, may be present in cortical malformations

hat involve central areas (supplementary figure 2.18nd 2.19).


E

The

RBss

LCuqw(tA(RB(TrtlC(Bmt(

Ir––a

AidMn

3

3

OWqcosmtaa

bs“ctoiIwtinaihe

SEatbi(mstcmTetbaafe(bSsiFbtt

E

ecording protocolsasic and advanced level recordings are exactly theame as for neonatal epileptic encephalopathies withuppression-burst (see relevant chapter).

evels of EEG diagnosislinical suspicion of focal structural epilepsy inntreated neonates after exclusion of the most fre-uent causes of acute symptomatic neonatal seizures,hich are mostly focal (such as in stroke) or multifocal

such as in neonatal hypoxic ischaemic encephalopa-hy).. Confirmatory of diagnosis

For both basic and advanced recording levels)ecording of typical ictal and interictal features.. High diagnostic certainty (probable)

For both basic and advanced recording levels)ypical focal interictal abnormalities, but no seizuresecorded. Proceed with, or repeat advanced level EEGo register seizures and move diagnostic certainty toevel A.. Low diagnostic certainty (possible)

For both basic and advanced recording levels)ilaterally abnormal background activity with focal,ultifocal or diffuse interictal epileptiform abnormali-

ies, or non-stereotyped seizures with multifocal onsetsee below).

ndications for repeating advanced level video-EEGecording

(1) Failure to record seizures.(2) Clinical suspicion of other types of seizure or of

cute underlying pathologies (as cited above).

typical EEG/video-EEG features to be highlightedn the EEG report, which may cast doubts on aiagnosis of focal structural epilepsyultifocal interictal abnormalities and multifocal and

on-stereotyped seizures.

. INFANCY/EARLY CHILDHOOD

.1 Infantile Spasms (IS) and West Syndrome (WS)

verviewS is a unique, age-dependent epilepsy that fre-

uently presents in the first year of life, most


ommonly between the first three to nine monthsf life. Traditionally, the triad of clusters of epilepticpasms, developmental regression, and hypsarrhyth-ia on the EEG is termed as WS. It is now recognized

hat infantile spasms (IS) may not always be associ-ted with the prototypical hypsarrythmic EEG patternnd can also affect children later in life, though rarely

BC

IHid


eyond the age of two years. The term “infantilepasms”, particularly when used synonymously toWest syndrome” should be reserved to very younghildren. The recent ILAE classification included theerm “epileptic spasms” when this seizure type isbserved at other ages. Hypsarryhthmia can also be

ncidentally recorded in the absence of spasms.n the vast majority of cases, IS are associatedith structural brain abnormalities, including perina-

al ischaemia/hypoxia, congenital or early acquirednfections, abnormalities of cortical development,eurocutaneous conditions, etc., while familial casesre rare. Prognosis depends on aetiology and is bettern children without apparent structural cause. In nearlyalf of the patients, WS evolves into LGS or multifocalpilepsies.

eizures: symptoms and semiologypileptic spasms (ES) are the defining seizure type,lthough they are not exclusive for WS (see also sec-ion on neonatal epileptic encephalopathies). ES arerief muscle contractions that predominate in prox-

mal and truncal muscles and cause sudden flexionalso known as “salaam spasms”), extension, or mixed

ovements. EEG-EMG polygraphy recordings havehown that a spasm reaches the maximum contrac-ion more slowly compared to myoclonia, but fasterompared to a tonic seizure (Vigevano et al., 2001). ESay be isolated but most frequently occur in clusters.

he intensity and frequency of the sequential ES inach cluster often increase gradually to a peak, andhen progressively decrease until they stop. ES cane “subtle”, limited to only grimacing, eye deviation,nd head nodding, or even be subclinical. ES may besymmetric, or asynchronous, associated with variousocal components that may involve the limbs, head, oryes, or show compartmental and vegetative featuresWatanabe et al., 2001). ES may be preceded or followedy, or intermixed with, focal seizures (Gaily et al., 1995).tereotyped focal seizures preceding epileptic spasmsuggest a focal lesion and polygraphic video recordings required for detailed analysis.ocal seizures. Occur mainly in infants with overt cere-ral lesions and can be multifocal. A focal seizure may

rigger a cluster of spasms, or occur independently ofhem.

EG section

393

ackgroundontinuously abnormal during wakefulness and sleep.

nterictal abnormalitiesypsarrhythmia, a term coined by Gibbs and Gibbs

n their atlas of electroencephalography in 1952,escribes a high-voltage (hypsos=height), completely


3

M

dn(imbWrrftdatdlModyS1a2wat(aAhthcafiam(pAwiottpmcfm

II–

––iTtdmeoarblamcw

RBTiaAaapPtATrptaP

LCAIsRtatps


isorganized and chaotic (without any discernibleormal background rhythm=arrhythmia) EEG pattern

supplementary figure 3.01), which is the characteristicnterictal presentation in WS. At onset, hypsarrhythmia

ay be present only during drowsiness and light sleep,ut it soon becomes abundant during wakefulness.akefulness. The main (typical) pattern of hypsar-

hythmia occurs during wakefulness: it consists ofandom high-amplitude slow wave and spikes that varyrom moment to moment, both in duration and loca-ion (supplementary figure 3.01). Occasionally, spikeischarges appear to be focal, or multifocal, but nevers a rhythmically repetitive and highly organized pat-ern. The abnormality is almost continuous, but earlyuring the clinical course, the age-dependent physio-

ogical background may be intermittently preserved.ost frequently, hypsarrhythmia may predominate

ver the posterior head regions, while anterior pre-ominance is rare and only seen after the firstear of age.leep. Hypsarrhythmia remains maximal in sleep Stage, but becomes less continuous during sleep Stages 2nd 3, and disappears during REM sleep. During Stagesand 3, a tendency of the multifocal spike and sharpave discharges to group results in a quasi-periodic

ppearance of the paroxysmal activity (supplemen-ary figure 3.02). Physiological graphoelements of sleepvertex sharp transients, spindles, and K-complexes)re usually absent.

number of different variants of hypsarrhythmiaave been reported beyond its typical presen-

ation (Hrachovy and Frost, 2003). These includeypsarrhythmia with increased inter-hemispheric syn-hronization (examples in supplementary figure 3.02nd 3.03), asymmetric hypsarrhythmia (supplementarygure 3.04), hypsarrhythmia with episodes of voltagettenuation (supplementary figure 3.05), hypsarrhyth-ia with a consistent focus of epileptic discharges

supplementary figure 3.06) or focal slowing, and otheratterns.n underlying structural origin can be suspectedhen the EEG reveals atypical hypsarrhythmia: for

nstance, predominating focal spikes or spike-wavesr slow complexes may indicate a focal lesion, addi-

ional abnormal rhythms (i.e. diffuse high-voltageheta-alpha activity) may indicate lissencephaly orachygyria, and persistent asymmetry or asynchronyay indicate a focal lesion or agenesis of the corpus

allosum; asymmetric ictal patterns or interspersing

94

ocal seizures (supplementary figure 3.07A to 3.07B)ay be of similar significance (see ictal EEG below).

ctal EEGctal discharges associated with ES include:

(i) a diffuse high-amplitude triphasic slow wave;

m(B(Noi

(ii) a low-amplitude brief fast discharge;(iii) a short-lasting diffuse flattening of ongoing activ-

ty (supplementary figure 3.08 and 3.09).he frequency of occurrence of these three pat-erns and their terminology has varied according toifferent authors, but the first pattern may be theost frequent (Fusco and Vigevano, 1993; Vigevano

t al., 2001). A transient disappearance or reductionf the hypsarrhythmic pattern is usually seen duringcluster of ES (supplementary figure 3.08). Symmet-

ic epileptic spasms (supplementary figure 3.10) maye idiopathic or of structural origin. Infants with brain

esions may show an asymmetry of the ictal high-mplitude slow wave, reflecting the pathologicallyore involved hemisphere. Focal or unilateral fast dis-

harges immediately preceding the high-voltage slowave are highly suggestive of focal cortical lesion.

ecording protocolsasic levelime: any time of the day, but preferentially dur-

ng spontaneous sleep and after feeding (planningrrangements with parents are essential).ctivation: sleep is strongly recommended, and ifchieved, further recording of at least 10 minutes afterwakening is required, as ES occur very often in thateriod.olygraphy: bilateral deltoid EMG is desirable, even athe expense of complete 10-20 EEG cover.dvanced levelime: anytime of the day, but lengthy recordings areecommended to include spontaneous sleep and aeriod after feeding; if necessary induce sleep. Allow

he patient to reach Stage 2 for at least 10-15 minutesnd record for at least 30 minutes after awakening.olygraphy: bilateral deltoid EMG is mandatory.

evels of EEG diagnosislinical suspicion of IS/WS in untreated infants. Confirmatory of IS/WS

ctal recording of epileptic spasms with interictal EEGhowing typical hypsarrhythmia or any of its variants.ecording of hypsarrhythmia and history of ES in clus-

ers upon awakening are sufficient for diagnosis of WSt level 1 (if video-EEG is not available or if epilep-ic spasms do not occur during the recording; askingarents to bring along video recordings of the typicalpasms on portable phones will allow clinical confir-


ation; there is no need for SD recording level 2however, see clinical indications below).. High diagnostic certainty

Probable IS/WS, for both recording levels 1 and 2).o hypsarrhythmia or spasms recorded, but presencef multifocal spike discharges during sleep record-

ng and history of epileptic spasms in clusters upon


E

The

atC(Ndsnaais

Ir–c–a

I––

3

ODdapiaicpftcftap(attnniavwma

srteDSomrtoSefsTlEb

SSheotioOss(MtA–cnso–I–Tcdst

wakening: repeat recordings level 1 and 2 (if possible)o record epileptic spasms or hypsarrhythmia.. Low diagnostic certainty

Possible IS/WS, for both recording levels 1 and 2).o hypsarrhythmia, but presence of multifocal spikeischarges during sleep recording and history of pos-ible (subtle) epileptic spasms (for instance, headodding or eye deviation): Repeat recordings level 1nd 2 (if possible) to record the ictal EEG of the attacksnd confirm the diagnosis of IS by showing that thectal EEG pattern is compatible with that of epilepticpasms.

ndications for repeating advanced level SDecording(1) First EEG (recording level 1 or 2) normal or incon-

lusive.(2) Resistance to appropriate AED (vigabatrin,

drenocorticotropine, predonine).

ndications for video telemetry(1) Clinical suspicion of additional seizure type.(2) Confirm the treatment response.

.2 Dravet syndrome (DS)

verviewravet Syndrome is an infantile-onset epilepsy syn-rome, first described in 1978 by Charlotte Dravets “severe myoclonic epilepsy in infancy”. Estimatedrevalence is around 1% of epilepsy syndromes in

nfancy and childhood with males being more oftenffected. The natural course of DS during childhoods traditionally divided into an early phase (roughlyorresponding to the first year of life) and a steadyhase within the next 2-5 years, during which the

ull electroclinical picture becomes established. Inhe early phase, prolonged hemi- or generalizedonvulsive seizures occur, typically associated withever, while some children show generalized pho-oparoxysmal responses (PPR) to photic stimulation,n unusual finding for this age. During the steadyhase, MS, atypical absences, complex partial seizures

CPS), and episodes of non-convulsive status may alsoppear, while cognitive development slows leadingo moderate/severe intellectual disability usually afterhe age of 4-5 years; some children may also showon-progressive ataxia, pyramidal signs, or hypoto-


ia. Seizure evolution may vary in some children; fornstance, clear association with fever may be lackingnd myoclonic or CPS may start early. Such courseariability and the overall seizure polymorphism, asell as the largely non-specific interictal EEG findings,ay delay diagnosis. Long-term outcome is invari-

bly unfavourable. DS is highly pharmaco-resistant and

agobsjo


eizure freedom remains an exception, while patientsemain cognitively impaired, often severely. Early mor-ality, sometimes due to sudden unexpected death inpilepsy (SUDEP), occurs in about 10% of patients.S is a channelopathy due to mutation in theCN1A gene which encodes the alpha 1 subunitf the voltage-gated sodium channel. SCN1A abnor-alities (mostly mutations and deletions) in DS are

eported in 80% of patients. Identifying SCN1A muta-ions might be helpful in some patients as a meansf supporting an early diagnosis of DS. However,CN1A aberrations can be associated with severalpilepsy syndromes, ranging from mild phenotypesound in families with genetic epilepsy with febrileeizures plus (GEFS+) to the severe infant-onset DS.hus, diagnosis of DS is still based on the constel-

ation of the many different seizure types and theirEG characteristics, and their evolution, as describedy Dravet.

eizures: symptoms and semiologyeizures start in the first year of life in previouslyealthy children. Initial seizures are unilateral or gen-ralized convulsive, mainly clonic or tonic-clonic andften prolonged (>10 min), evolving into status epilep-

icus. They are typically triggered by fever (givingnitially the impression of atypical febrile convulsions),r occur after immunization, but may also be afebrile.ther types of seizure, mostly afebrile, occur in the

econd or third year of life in addition to the convul-ive seizures that are present throughout the evolutionBureau and Dalla Bernardina, 2011; Dravet et al., 2012).

yoclonic seizures may be absent at the first stages ofhe syndrome (Guerrini and Aicardi, 2003).. Convulsive seizures are traditionally classified into:

(i) “Unilateral” with clear hemi-clonic or toniconvulsions that, on different occasions, may alter-ate sides in the same child; such alternating unilateraleizures can offer a significant clue to early diagnosisf DS. These seizures become rarer with age.

(ii) “Generalized tonic-clonic” seizures as inGE/GGE, although of somewhat shorter duration.

(iii) “Falsely generalized” and “unstable” seizures.hese are bilateral convulsive but with asymmetriclonic or tonic movements and postures, at times pre-ominating on one side, or switching sides during theeizure. For falsely generalized seizures, the descrip-ion reported by the family appears to correspond to

395

generalized tonic-clonic seizure (GTCS), but poly-raphic video-EEG recordings have shown that thenset of the bilateral motor manifestations may lagehind a brief period of eye opening and unrespon-iveness, associated or not with eye deviation and facialerking. The EEG onset is bilateral synchronous butften asymmetric in the falsely generalized seizure


3

M

aBsBttdttuCmgmDaEkosremasaFSupp4Sblalm

EAEmmrp

BWdoaitf

SAoac(nu

II((mpfomIso4atissTwptswfbs2ds

IA–tracr


nd focal in the unstable seizure (see EEG section).oth these types tend to mainly occur during non-REMleep.. Focal seizures, usually of the complex partial

ype, are frequently associated with autonomic symp-omatology (pallor, cyanosis, respiratory changes, androoling), oral automatisms and hypotonia, and some-

imes with eyelid or distal jerks. They last from oneo a few minutes; when longer they can evolve into anilateral motor or secondary generalized seizure.. Myoclonic seizures can be either massive axialovements leading to falls or mild (isolated or

rouped) manifesting as a few jerks. Erratic myocloniasay also occur.. Atypical absences may be at times associated withmyoclonic component.

. Non-convulsive status epilepticus (NCSE), alsonown as obtuntation status: NCSE episodes consistf prolonged (hours or days) impairment of con-ciousness with loss of contact or variably reducedesponsiveness, hypotonia and somnolence, andrratic or segmental myoclonus. Obtundation statusay be initiated, punctuated or terminated by gener-

lized tonic-clonic seizures, or be combined with othereizure types, such as axial myoclonic, myoclonic-tonic or clonic.. Tonic seizures are exceptional.eizures may be triggered by intermittent photic stim-lation (IPS), visual patterns, hot water immersion, andhysical effort (Dravet et al., 2012), and sensitivity tohotic or pattern stimulation is noted in approximately0% of patients, particularly in younger children.tatus epilepticus or at least worsening of seizures maye provoked by inappropriate AEDs (carbamazepine,

amotrigine, and vigabatrin). In adults, MS, atypicalbsences, and focal seizures tend to remit, but long-asting clonic seizures or short tonic-clonic seizures

ay persist, particularly during sleep (Ohki et al., 1997).

EG sectionlthough abnormalities are non-specific, interictalEG is helpful for differential diagnosis and patientanagement. Moreover, sequential EEG recordingsay demonstrate the evolution of DS, while ictal

ecordings with EMG polygraphy document seizureolymorphism, which is diagnostically very important.

ackground

96

akefulness. Background activity is normal at onsetespite the frequent seizures; rhythmic theta activitiesf 4-5 Hz may be present over the central-parietal areasnd vertex. Diffuse or asymmetric slowing may be seenf EEG is performed immediately after a seizure; some-imes, focal postictal abnormalities may linger on for aew days (supplementary figure 3.11).

Ibcafoc

leep. Normal patterns, at least initially.fter the first year, there is usually a gradual slowingf the background activity, more marked if seizuresre frequent. Theta band waves predominate over theentral areas with persistence of physiological patternssupplementary figure 3.12). Physiological sleep phe-omena and organization generally remain preserved,nless frequent nocturnal seizures occur.

nterictal abnormalitiesnterictal abnormalities may be present at onset22% of patients) and increase during evolution77%) (Specchio et al., 2012). Generalized, focal and

ultifocal abnormalities, spikes, and spike-wave orolyspike-wave discharges, symmetric or not, are more

requent over the frontal and central areas, but alsoccur over the temporal and occipital areas (supple-entary figure 3.13).

nterictal abnormalities are usually enhanced duringleep (supplementary figure 3.14). Generalized PPRccur in 9% of patients at onset, increasing to 22-4% during evolution (Specchio et al., 2012; Caraballond Fejerman, 2006). Slow waves occur mainly overhe central regions at onset and tend to diffuse dur-ng evolution. Both generalized and focal spikes andpike-wave discharges and slow waves are enhanced ifeizures are more numerous.here is no homogeneous evolution of the EEG aspectsith age, with the overall pattern in the individualatient being dependent on the number and dura-

ion of seizures. A distinctive EEG pattern of frontallow bi- or triphasic spikes, followed or not by slowaves when awake and activated by sleep with dif-

use 5-10-second discharges of 8-9-Hz polyspikes, haseen noted in a minority of adolescents with DS,ome of whom had tonic seizures (Nabbout et al.,008); despite some similarities with LGS, this patternoes not indicate transition of DS to LGS (see alsoection on LGS).

ctal EEG. Convulsive seizures(i) Unilateral. These are frequent at the onset of

he disease. The ictal discharge is characterized byhythmic (2-3/second) bilateral slow waves of highermplitude over the hemisphere contralateral to thelinical manifestations and intermixed with 10/secondecruiting rhythms.


n other focal unilateral seizures, the EEG pattern cane variable with onset over the frontal or frontal-entral regions of one hemisphere, or with bilateralsymmetric onset, but always predominant over therontal areas (supplementary figure 3.15A, B). The EEGnset consists of “pseudo-rhythmic” spikes and waves,ontralateral to the clinical manifestations, and may be


E

The

pt–I–IisuTjfUgsthTtItecseBIploo(fiCTpsaDTuss(EEsaafoFTda

RBPpwrAL(HcoSrfppRat

LAcfdsufBofsIEio–if––iC(MmD

eriodically interrupted by a 1-2-second flattening ofhe EEG.

(ii) Generalized tonic-clonic seizures (See section onGE/GGE).

(iii) “Falsely generalized” and “unstable” seizures.n the falsely generalized seizures, the EEG discharges of bilateral symmetric or asymmetric onset with alow spike or SW, sometimes followed by a brief atten-ation, and fast activities intermixed with slow waves.hese seizures can be preceded by isolated massive

erks for several minutes, increasing progressively inrequency and amplitude.nstable seizures are characterized by varying topo-raphic changes of the ictal discharge. The seizure cantart over one area of one hemisphere and then spreado another area of the same hemisphere or to the entireemisphere, or asymmetrically to both hemispheres.he pattern of propagation is variable from one seizureo another in the same patient.n general, polygraphic video-EEG recordings of bothhese seizure types have documented complex ictalvolution and a degree of discrepancy betweenlinical and EEG manifestations (for further detailsee Bureau and Dalla Bernardina [2011] and Dravett al., 2012).. Focal (complex partial) seizures

ctal EEG consists of a rhythmic sequence of fastolyspikes intermixed with theta activity during the

ast part of the seizure, involving, for the durationf the seizure, the temporal-parietal-occipital regionf one hemisphere or more rarely a frontal region

Bureau and Dalla Bernardina, 2011) (supplementarygure 3.16).. Myoclonic seizureshese are accompanied by generalized spike- orolyspike-wave discharges at 3Hz or more, lasting 1-3econds and of higher voltage over the central-parietalreas (supplementary figure 3.17 and 3.18).. Atypical absenceshese are associated with generalized regular or irreg-lar spike-wave discharges at 2-3.5 Hz, lasting 3-10econds, and are accompanied by impaired con-ciousness and sometimes a myoclonic componentsupplementary figure 3.19).. NCSE (obtuntation status)EG background activity is replaced by diffuse deltalow waves, superimposed with multifocal spikesnd spike-waves, sharp waves, and generalised spike-nd-wave discharges (GSWD) predominating over


rontal-central areas, associated with myoclonic jerksr without a clinical correlate (atypical absence status).. Tonic seizureshese occur only exceptionally and are associated withiffuse discharges of polyspikes at 8-9 Hz (Nabbout etl., 2008).

I–t–a


ecording protocolsasic levellanned recording during wakefulness and sleep witholygraphy (ECG, respiration, bilateral deltoid EMG)ith hyperventilation (HV) and IPS. IPS is important to

ecord early photoparoxysmal responses.dvanced levelong-duration video-EEG with polygraphy, as abovewith at least bilateral deltoid EMG). Include IPS andV, as in level 1. Hospitalization of the child during a

luster of febrile or afebrile seizures provides a goodpportunity.leep is important to enhance the probability ofecording interictal discharges and unstable andalsely generalized seizures. More extensive EMGolygraphy will better demonstrate the ictal polymor-hism of these seizure types.epeat sleep EEGs when clinically indicated (i.e.ppearance of a new seizure type) to better documenthe evolution of the syndrome.

evels of EEG diagnosiss already discussed, diagnosis of DS relies on thelinical evolution and is supported by serial (and asrequent as possible) video-EEG evidence that willocument seizure polymorphism. Early EEG photo-ensitivity and video-recorded falsely generalized ornstable seizures provide pertinent diagnostic clues. It

ollows that confirmatory (level A) and probable (level) levels are not applicable here, as for most of thether syndromes; in DS, there are no specific interictal

eatures, and seizure polymorphism is unlikely to behown by even an ictal EEG.n the untreated child with suspected DS, the firstEG (both basic and advanced recording levels) canncrease diagnostic certainty if it shows a combinationf the following:

(1) Background showing focal or diffuse slowingn postictal recordings, following repeated admissionsor atypical febrile seizures (FS) or status epilepticus.

(2) Early-onset photosensitivity.(3) Myoclonic and either unstable or falsely general-

zed seizures.) Low diagnostic certainty (possible)

For both basic and advanced recording levels)onomorphic epilepsy syndrome with onlyyoclonus.evelopment remains unaffected.

397

ndications for video-EEG telemetry(1) Worsening with suspicion of minor status epilep-

icus.(2) Clinical suspicion of other types of seizures

nd/or epilepsy syndrome.


3

M

AidPcfFo

3

OMbawthGouarAfha2asa(1aMprnOswaNdDscehNcfildc

SM1asciMdAbTaTrLribosAaa

E

BNamb

IGatmWaaGtacGpM


typical EEG/video-EEG features to be highlightedn the EEG report, which may cast doubts on aiagnosis of DSersistent focal slowing of background activity asso-iated with spike or polyspike-wave focus, suggestingocal structural epilepsy.requent tonic seizures associated with diffuse burstsf polyspikes (however, see also Nabbout et al. [2008]).

.3 Myoclonic Epilepsy in Infancy (MEI)

verviewyoclonic Epilepsy in Infancy (MEI) is characterized

y brief generalized myoclonic seizures (MS) that aressociated with brief generalized spike/polyspike-and-ave discharges (GSWD/GSPWD) and occur between

hree months and four years of life in previouslyealthy children (Auvin et al., 2006; Darra et al., 2006;uerrini et al., 2012; Caraballo et al., 2013). There are nother seizure types. A history of earlier FS is noted inp to 18% of children, while a family history of epilepsynd FS has been described in 29% and 16% of children,espectively.lthough these children usually have good prognosis

or seizures, cognitive and behavioural disturbancesave been reported in around 40% of patients (Zuberind O’Regan, 2006; Guerrini et al., 2012; Auvin et al.,013). Some children have mainly reflex myoclonusctivated by unexpected auditory, tactile, and photictimulation. This presentation has been considered asvariant, termed “reflex myoclonic epilepsy in infancy

RMEI)”, with some differentiating features (Ricci et al.,995; Verrotti et al., 2013) that include: earlier meange at onset (10 months, compared to 20 months forEI), shorter duration of the MS, most of which are

rovoked by sudden and unexpected stimuli, betteresponse to antiepileptic medication, and better cog-itive outcome.n rare occasions, other genetic generalized epilep-

ies may develop after MEI remits, including epilepsyith myoclonic-atonic seizures, JME, childhood

bsence epilepsy, and eyelid myoclonia with absences.ote. Recognizing MEI is not difficult in chil-ren with the typical clinical/EEG presentation.ifferential diagnosis should include some other

yndromes and conditions in infancy and earlyhildhood, such as Glut-1 deficiency, non-epilepticvents including benign non-epileptic myoclonus and

98

ead atonic attacks, and IS without hypsarrhythmia.eurometabolic conditions, such as mitochondrial

ytopathies (myoclonic epilepsy with red raggedbres; MERRF), storage disorders, neuronal ceroid

ipofuscinosis, hexoamidase deficiency, and biopterineficiency, may all present with MS and need to beonsidered in the differential diagnosis.

IM(Gp1

eizures: symptoms and semiologyyoclonic seizures (MS) typically start between 16 and

8 months of age and are often subtle at onset (Zuberind O’Regan, 2006; Caraballo et al., 2013). They occureveral times daily, usually in isolation, but also inlusters, and are easily controlled by antiepileptic med-cation, especially valproic acid.

S are commonly brief and isolated, and can occururing wakefulness and the first two stages of sleep.variant with predominantly nocturnal MS has also

een described (Prabhu et al., 2014). Intensity varies.hey predominantly involve the upper limbs with briefrm abduction and the head, appearing as head drops.hey involve the lower limbs less commonly, but mayarely cause sudden drop attacks when strong.onger MS can occur as a sequence of arrhythmic orhythmic jerks lasting 3-7seconds. When the durations >4 seconds, alertness may be affected. MS may alsoe subtle, with eye blinking, rolling-up of the eyeballs,r a brief head movement. Reflex myoclonus can beeen along with spontaneous MS.

rare coexistence of MS with absences during thective course of MEI has been described (Caraballo etl., 2013).

EG section

ackgroundormal in wakefulness and sleep with preserved sleep

rchitecture (supplementary figure 3.20). Occasionally,onomorphic synchronous 4-6-Hz theta activity can

e seen in the central regions.

nterictal abnormalitiesPSWD/GSWD are rare during wakefulness, but are

ctivated by drowsiness and slow sleep (supplemen-ary figure 3.21 and 3.22). However, a given sleep EEG

ay be normal.hen present, interictal GSWD/GPSWD are brief

nd can be asymmetric. Photoparoxysmal responsesre rarely seen, though IPS-triggered fast (3-4-Hz)SWD/GPSWD with concomitant MS may occur at

he onset. Focal interictal epileptic discharges (suchs low-voltage fronto-central spike or spike-wave dis-harges) are rarely seen.PSWD/GSWD and photoparoxysmal responses mayersist for many years after the clinical remission ofEI (Caraballo et al., 2013).


ctal EEGS are associated with fast (3-4-Hz) GSWD/GPSWD

supplementary figure 3.23-3.26). These GSWD/PSWD complexes are often preceded by anteriorredominant spike-and-wave discharges (Ricci et al.,995). Eye blinking can be the mildest form of a MS


E

The

(sA

RBRiEcoonTAvaAAEdc

LAaRpbsNesBN(NsPrCNPrd

IWmf–pm

–c–atL

3

OBiooletiudBstesgi1leAdi(pqIcDwegibfim

Darra et al., 2006). Some children exhibit photosen-itive MS associated with GPSWD (Ricci et al., 1995;uvin et al., 2006).

ecording protocolsasic levelecord during wakefulness and, at least, drowsiness;

nclude sleep if possible.mploy EMG polygraphy (at the expense of two EEGhannels if not enough channels are available) tobtain a definite diagnosis of MS. Technologists shouldbserve closely and annotate, particularly if video isot available.ime: anytime of the day.ctivation: IPS/HV (blowing a windmill); specific acti-ation should include unexpected tactile stimulationnd noises (supplementary figure 3.26).dvanced levels in basic level, but perform prolonged video-EG-EMG polygraphy to include sleep (for instance,ay telemetry), to recover interictal GSWD andapture MS.

evels of EEG diagnosis. Confirmatory of suspected MEI (in the absence ofbnormal neuroimaging)ecording of MS with the typical EEG-EMG polygra-hy features and typical interictal presentation (normalackground, with or without interictal GSWD), astated above.o atypical features or other types of seizure includingpileptic spasms, myoclonic-atonic, tonic, or absenceeizures.. High diagnostic certainty (probable)o MS recorded, but typical interictal presentation

normal background with interictal GSWD), as stated.o atypical background or interictal features; no other

eizure types.roceed with prolonged advanced level recording toegister MS and move diagnostic certainty to level A.. Low diagnostic certainty (possible)ormal EEG without MS or any other seizure type.roceed with (or repeat) prolonged advanced levelecording to register MS or interictal GSWD and moveiagnostic certainty to level A or B.


ndications for long video telemetry/ambulatory EEGhen basic or advanced EEG of limited length is nor-al (as in level C above), or when they show atypical

eatures. The latter include:(i) Background activity: persistent diffuse slowing,

ersistent focal/lateralized PDA, or distortion of nor-al sleep architecture.

OBapico


(ii) Florid interictal epileptiform discharges: multifo-al spikes, frequent GSWD or hypsarrythmic features.(iii) Other types of seizure beyond MS: for instance

tonic, myoclonic-atonic, tonic, spasms, etc. (see chap-ers on epilepsy with myoclonic-atonic seizures, WS,GS, etc.).

.4 Benign Infantile Epilepsy (BIE)

verviewIE, or benign infantile seizures (BIS), is character-

zed by focal seizures that often occur frequentlyr in clusters, and appear resistant to treatment atnset, but spontaneously resolve weeks or months

ater. Pregnancy and perinatal history, neurologicalxamination, and developmental milestones beforehe onset of seizures are normal. Diagnostic workups,ncluding metabolic and neuroimaging studies, arenremarkable. The patients ultimately achieve normalevelopment milestones.IE can be sporadic (Watanabe et al., 1993) or familial,howing autosomal dominant (AD) mode of inheri-ance; the latter is known as “benign familial infantilepilepsy/seizures” (BFIE) (Vigevano et al., 1992). BFIEhows incomplete penetrance and genetic hetero-eneity. Four susceptibility loci for BIFE have been

dentified so far: chromosome 19q (BFIE1), 2q24 (BFIE3),p36.12-p35.1 (BFIE4), and 16p12-q12 (BFIE2), with theatter being by far the most frequently mapped (Strianot al., 2006).

combination of BFIE with paroxysmal kinesigenicyskinesia (PKD), occurring in 17% of BFIE, is called

nfantile convulsions and paroxysmal choreoathetosisICCA). Mutation in the proline-rich transmembranerotein 2 gene (PPRT2) located on chromosome 16p12-12 has been identified as the major cause of PKD,

CCA and BFIE and may be present in 80-90% of familialases (Heron et al., 2012).e novo PRRT2 mutations have been found in casesith non-familial benign infantile seizures (Specchiot al., 2013), but the majority of sporadic cases remainenetically unexplained. The phenotypic spectrum of

nfantile epilepsy with PPRT2-related pathology haseen further expanded. PPRT2 mutation was also

ound in BFIE and heterogeneous phenotypes includ-ng FS and SUDEP (Labate et al., 2013) and benign

yoclonus of early infancy (Maini et al., 2016).

399

ther conditions that may be related to BIE include:enign focal epilepsy in infancy with midline spikesnd waves during sleep (Capovilla et al., 2006). Patientsresented with focal seizures and typical midline

nterictal spikes solely during sleep with a benign out-ome. Seizures were characterized by brief episodesf cyanosis, staring, and rare lateralizing signs.


4

M

CrhwntrB(Btm

STsaadtistofaoBaf2bswtdbsatbmcfbC

E

BNNced

Ftaa

IWSvdNst(

ISdTtfico

RBRrTAAPltc

LAopRfBNAI


onvulsions with mild gastroenteritis caused by eitherotavirus or norovirus (Imai et al., 1999). The patientsad mild gastroenteritis associated with focal seizuresith secondary generalization. Seizure foci wereoted in occipital, parietal, and frontal, but not in the

emporal areas. Clinical manifestations were similaregardless of the site of origin (Maruyama et al., 2007).enign familial neonatal-infantile epilepsy or seizures

BFNIE or BFNIS), shares many clinical features withFIE (Vigevano, 2005). The typical hallmark of BFNIE is

he occurrence of seizures by age four months. SCN2Autation has been identified (Berkovic et al., 2004).

eizures: symptoms & semiologyhe typical characteristic of BIE is clustering of briefeizures lasting between one and three days. Seizuresre usually longer at the onset and became shorterfter treatment. Isolated seizures can occur 10 to 15ays prior to the cluster. The onset of seizures is in

he first or second year of life in the absence of def-nite causes. The patients are normal between theeizures and subsequently have normal developmen-al milestones (Vigevano et al., 2012). Clinical featuresf BIE are not diagnostic, although the presence of

amily history of seizures, PKD, and choreoathetosisre very helpful. However, a lack of family historyf these conditions in small families cannot excludeFIE. Sporadic forms are more difficult to diagnosend early diagnosis is possible only in the familialorms (Okumura et al., 2000; Specchio and Vigevano,006). Although the recognition of BIE is possible at theeginning of epilepsy (Espeche, 2010), a recent studyhowed that around 30% of patients initially diagnosedith BIE did not have a benign clinical course, and

heir clinical features during the acute phase did notistinguish individuals with BIE from those with non-enign infantile seizures (Kikuchi et al., 2015). Seizureemiology includes behavioural arrest, slow headnd eye version with shifting predominance, bilateralonic posturing, cyanosis, and unilateral followed byilateral clonic limb jerking (Vigevano, 2005). Treat-ent is practically required during the initial seizure

lustering, as there are no diagnostic electroclinicaleatures of BIE. There are no electroclinical differencesetween BFIE and BNFIE (Lispi and Vigevano, 2001;araballo et al., 2003).

EG section

00

ackgroundormal in wakefulness and sleepote. Mildly diffuse background slowing may be

aused by sedative medications. Consider otherpilepsy syndromes if EEG background is consistentlyiffusely slow.

sp

Np––

ocal slowing may occur but should not be persis-ent in a single area. Persistent focal slowing in onerea should prompt search for a structural brainbnormality.

nterictal abnormalitiesakefulness. Typically absent.

leep. typically absent although a variant with low-oltage midline spikes during slow sleep has beenescribed (Capovilla et al., 2006).ote that interictal EEG performed during a cluster of

eizures may show lateralized slow waves and spikes inhe occipital-parietal areas (supplementary figure 3.27)Specchio and Vigevano, 2006).

ctal EEGeizures are accompanied by focal ictal epileptiformischarges, which may spread to both hemispheres.he ictal discharge often ends in the hemisphere con-ralateral to the ictal onset. The ictal onset may varyrom lobe to lobe or from hemisphere to hemispheren different seizures in the same patient. In familialases, the seizures originate mostly in the parieto-ccipital, but not the temporal areas (Vigevano, 2005).

ecording protocolsasic leveloutine EEG during wakefulness and sleep: Sleepecording may activate low-voltage midline spikes.ime: any time of the day.ctivation: photic stimulation and sleep.dvanced levelrolonged video-EEG, up to 24 hours, to evaluate

onger portions of sleep and recover interictal epilep-iform discharges (IED) and record seizures during aluster.

evels of EEG diagnosis. Confirmatory of suspected BIE (in the presencef normal development, positive family history [ifresent] and negative neuroimaging)ecording a typical seizure or a cluster of characteristic

ocal seizures, as described above (ictal EEG).. High diagnostic certainty (probable)ormal EEG background.bsence of IED, except low-voltage midline spikes.

nterictal EEG performed during a cluster of seizures


howing lateralized PDA and spikes in the occipital-arietal areas.

ote. The diagnosis of BIE is unlikely in theresence of:persistent diffuse background EEG;persistent focal/lateralized PDA;


E

The

–s–si–po

ITnCs

3S

OEste(1islmbpPsiwnoswpRn52rt(

STd(toa

mtflaIbfosteamcimridstTroaom

E

BTdaedf

IUqMsgwgric

IEDs beyond low-voltage midline spikes duringleep;

focal spikes shifting from one region to another inequential EEGs, as in epilepsy of infancy with migrat-ng focal seizures (see relevant chapter);

atypical clinical seizures and ictal EEG, especially withersistent localization/lateralization of seizure semiol-gy and ictal EEG suggesting structural epilepsy.

ndications for video telemetry/ambulatory EEGo capture seizures during a cluster and confirm diag-osis.linical and EEG suspicion of other types of epileptic

yndromes.

. 5 Epilepsy of Infancy with Migrating Focaleizures (EIMFS)

verviewIMFS, previously called malignant migrating partialeizures of infancy, is a rare and severe conditionhat belongs to the group of early-onset epilepticncephalopathies. EIMFS was first described in 1995Coppola et al., 1995), and to date, approximately25 patients have been reported. EIMFS is character-zed by drug-resistant focal “migrating” or “random”eizures beginning within the first six months ofife, severe global developmental delay, and acquired

icrocephaly. Brain MRI is usually normal at onset,ut it later shows delayed myelination with thin cor-us callosum and cerebral atrophy (Barcia et al., 2012).atients whose seizures are brought under control mayhow steady neurological improvement. Those withntractable seizures show progressive deterioration

ith development of major axial and limb hypoto-ia, loss of visual contact, and a complete loss ofther motor and social skills; some children mayhow pyramidal and/or extrapyramidal manifestationsith athetotic movements; 18% of the so far reportedatients died (McTague et al., 2013).ecently, de novo KCNT1 mutations with KCNT1 chan-el gain of function have been reported in around0% of patients with sporadic EIMFS (Barcia et al.,012; McTague et al., 2013). Other mutations have beeneported in familial cases with recessive autosomalransmission (in SLC12A5, TBC1D24, and SLC25A22)Ohba et al., 2015).


eizures: symptoms and semiologyhe natural history of EIMFS is recognised by threeistinct phases, as described in the first report in 1995

Coppola et al., 1995). A first phase, generally starting inhe first six months after birth and lasting a few weeksr months, is characterized by sporadic seizures, usu-lly recurring every few weeks or months. Seizures are

c

IMSdo


ainly focal motor with rapid secondary generaliza-ion or with autonomic manifestations such as apnoea,ushing or cyanosis (Coppola et al., 1995; Caraballo etl., 2008a).n the second “stormy phase”, which can occuretween one and 12 months, seizures become very

requent, occurring in clusters several times a dayr being almost continuous for several days. Seizureemiology more often includes lateral deviation ofhe head and eyes, twitches of the eyelids, unilat-ral clonic or tonic jerks of one or both limbs,pnoea, flushing and/or cyanosis of the face, chewingovements, mastication, and secondary tonic-clonic

onvulsions. Milder clinical manifestations may be eas-ly overlooked and full detection of the frequent ictal

anifestations is possible only by long-term video-EEGecordings (Coppola, 2009). Furthermore, clinical man-festations may be “subtle” or absent despite the longuration of seizures. Prolonged video-EEG recordingshow a clear correlation between the topography ofhe ictal discharges and the clinical features.he age at onset of the third phase may vary widely,anging from the end of the first year to the fifth yearf age and over. This phase is relatively seizure-free,lthough interspersing illnesses can trigger clustersf seizures or occasionally status epilepticus. Later, ISay occur (Coppola et al., 1995; McTague et al., 2013).

EG section

ackgroundhis is usually normal during the first months of theisease with the exception of slowing for many hoursfter long-lasting seizures (see below). As the diseasevolves, background activities become progressivelyiffusely slower with reduction of physiological

eatures.

nterictal abnormalitiessually absent at onset, spikes rapidly increase in fre-uency and become multifocal within a few months.ultifocal spike-and-wave foci do not show any

pecific pattern and are not activated in sleep. Back-round activity may show alternating asymmetries,ith one hemisphere exhibiting slower activity on aiven trace and the other hemisphere showing slowerhythms on another trace (Coppola et al., 1995). Dur-ng seizure-free periods, sleep and wakefulness arelearly differentiated, but sleep spindles are rare, asyn-

401

hronous, and asymmetric.

ctal EEGigrating focal seizures

eizures occur typically in clusters that last for a feways and are then followed by a few weeks or monthsf recovery. Within a cluster, seizures are very frequent


4

M

amCytcitiwooqaIa1Wroaoceiltctfd–rr–o–pta(Amitb“

RBEfiUEa

APdftc

LAd(RB(NsircC(Na

Il––o–ts

Aiem–lr–t–

4

4


nd may even amount to status epilepticus (supple-entary figure 3.28).lusters increase in frequency within the first twoears of life. It is important for the diagnosis to recordhe typical ictal EEG pattern during such a cluster. Typi-ally, ictal discharges sequentially involve various areasn apparently migrating random fashion. The ictal pat-ern consists of mainly rhythmic monomorphic activityn the alpha-theta frequency range, although deltaaves and rhythmic spikes and spike-waves may alsoccur. Usually, seizure activity remains restricted tone region for some time before it slows down in fre-uency and stops, as it appears to progressively involven adjacent area (supplementary figure 3.28 and 3.29).ctal discharges are followed by postictal slow wavectivity without prolonged attenuation (Coppola et al.,995; Coppola, 2009).

hen seizures are frequent, ictal onsets shift from oneegion to another and from one hemisphere to thether. Consecutive focal ictal discharges overlap, withnew one beginning before the end of the previousne, resulting in continuous, but shifting, multifo-al ictal activity and a very complex pattern of statuspilepticus (supplementary figure 3.29). Simultaneous

ndependent discharges occur frequently without fol-owing usual propagation patterns or a stereotypedopographic course. Seizure activity may involve allerebral regions with a clear correlation between theopography of the ictal discharge and the clinicaleatures. Caraballo et al. (2008b) distinguished threeifferent clinical patterns:

(i) recurrence of ample rhythmic focal spikes orhythmic sharp theta or alpha activity over the rolandicegion;

(ii) polymorphic theta-delta activity over a temporo-ccipital region;(iii) initial flattening or small discharge of ample fast

olyspikes in one hemisphere. With increasing age,he amplitude of the ictal discharges tends to increase,nd frontal areas are more frequently affectedDulac, 2005).t the onset of the disease, focal seizures may beonofocal or multifocal without the typical “migrat-

ng” aspect. When the clinical picture is suggestive ofhe diagnosis, few long-duration EEG recordings maye required to convincingly show the multifocal andmigrating” nature of the seizures.

ecording protocols

02

asic levelEG should be recorded during wakefulness and sleepor as long as possible to recover seizures. Record dur-ng a cluster of seizures, if possible.se polygraphy (ECG, respiration, bilateral deltoid

MG), if possible, to detect ictal autonomic changesnd subtle movements.

F

OTabt

dvanced levelerform long-duration video-EEG with polygraphy, asescribed for basic level. Attempt to record from a

ew to 24-48 hours during a cluster of seizures to cap-ure multiple seizures and document their “migrating”haracter.

evels of EEG diagnosis) Confirmatory of suspected EIMFS in untreated chil-ren

For both basic and advanced recording levels)ecording of typical “migrating” ictal presentation.) High diagnostic certainty (probable)

For both basic and advanced recording levels)o atypical interictal presentation; focal or multifocal

eizures are recorded, but without the typical “migrat-ng” expression. A second 24-48-hour recording isequired to record the typical migrating seizures andonfirm the diagnosis.) Low diagnostic certainty (possible)

For both basic and advanced recording levels)o atypical interictal features (see below), but without

ny seizures recorded.

ndications for repeating video-EEG recordingevel 2

(1) Failure to record seizures.(2) Focal seizures are recorded, but are monofocal

r multifocal without a typical “migrating” aspect.(3) New clinical features suggesting another seizure

ype or epileptic syndrome or degenerative, chromo-omal, and/or metabolic disease.

typical EEG/video-EEG features to be highlightedn the EEG report, which may cast doubts orliminate the diagnosis of epilepsy of infancy withigrating focal seizures(1) Interictal abnormalities suggestive of a focal

esion, such as constant focus of spikes, polyspikes,apid rhythms, or slowing.(2) Monofocal seizures associated or not with epilep-

ic spasms.(3) Myoclonic seizures.

. CHILDHOOD

. 1 Febrile seizures (FS) and Genetic Epilepsy with


ebrile Seizures plus (GEFS+)

verviewhe term “Febrile Seizures” defines any seizureccompanied by fever (temperature >100.4◦F or 38◦Cy any method), without central nervous system infec-

ion occurring in children between six months and


E

The

fiATp“isemsaG(cgsst-bFoaAi–a––––––

FTamabatTpiuneto1((aa

sidteAa(iiboFswd

SM(umpsmfim

E

NcpfreHswwssnansrCetiming in complex FS in neurologically normal children

ve years of age (Subcommittee on Febrile Seizures;merican Academy of Paediatrics, 2011).he term “generalised epilepsy with febrile seizurelus” (Scheffer and Berkovic, 1997) has been renamedgenetic epilepsy with febrile seizure plus” because its now recognised that some of the associated epilep-ies may be focal (Camfield and Camfield, 2015; Zhangt al., 2017). The diagnosis of GEFS plus can only beade at a familial level (individuals may have “febrile

eizures plus”, a term reserved to febrile seizureslone persisting above the age of 5 years old).EFS+ is an important familial epilepsy disease state

rather than a homogenous epilepsy syndrome) withomplex inheritance and clinical and genetic hetero-eneity. Mutations are most frequently reported inodium channel and GABA (A) receptor subunit genes,egregating in large autosomal dominant families. Thewo main phenotypes in these families include: (i) FSgeneralised tonic-clonic seizures occurring with feveretween two months and five years of life, and (ii)S+ -generalised tonic-clonic seizures that occur afterr extend beyond six years of age. In some children,febrile seizures occur in addition to FS.dditional phenotypes within the affected GEFS+ fam-

lies include:FS/FS+ with other generalised seizures such as

bsences, and myoclonic and atonic seizuresAfebrile generalised tonic-clonic seizuresClassic genetic generalised epilepsiesFS/FS+ with focal seizuresFocal epilepsies aloneEpilepsy with myoclonic-atonic seizuresDravet syndrome

ebrile seizureshe lower age at onset of febrile seizures (FS) is debat-ble and for practical purposes a lower cut off of twoonths is considered useful. The peak incidence is

t 18 months with about 80% of seizures occurring atetween one and three years of age. Febrile seizuresre the most common phenotype in the GEFS+ familiesested (Zhang et al., 2017).he classic clinical distinction into “simple” and “com-lex” or “complicated” FS is based on prognostic

mplications: the majority of FS are simple, i.e. brief,sually generalized in their clinical expression, doot repeat in the same clinical illness, and havexcellent prognosis and therefore do not require fur-her diagnostic tests, including EEG (Subcommittee


n Febrile

Documents

TheroleofEEGinthe diagnosisandclassiﬁcation ...eeg-emg.hu/textbox/media/The role of EEG part 2.pdfmTOR pathway (D’Gama et al., 2015). Beside the focal structural epilepsy with