What is a syndrome?

An epileptic disorder characterised by a cluster of signs and

symptoms customarily occurring together

Consistency?Haw many syndromes can a patient have?

Disease? How many etiologies a syndrome could have?

Boundaries? Which are the limits of a syndrome?

�Generalized Seizures�

• Myoclonic jerks• Absence seizures (with few variants)• Generalized Tonic-Clonic Seizures

Idiopathic �Generalized Epilepsies�

• Myoclonic Epilepsy in Infancy• Generalized Epilepsies with Febrile Seizures Plus• Epilepsy with Myoclonic Astatic Seizures• Childhood Absence Epilepsy• Epilepsy with Myoclonic Absences• Idiopathic Generalized Epilepsies with Variable

PhenotypesJuvenile Absence EpilepsyJuvenile Myoclonic EpilepsyEpilepsy with Generalized Tonic-Clonic Seizures Only

(J. ENGEL, 2001)

üNatural course of epileptic syndromeüImpact of seizures on quality of lifeüPercentage of drug resistance in the different

syndromesüConsistency of EEG epileptic activity with cognitive/

behavioral profile

To treat?What to treat?How much treat?

Simple absence seizure

P.S. F. 12 years; Juvenile Absence Epilepsy

NeocortexP4 -O2

C4-P4

T4-T6

Fp1-F3

P3 -O1

F3 -C3

C3-P3

Fz-Cz

F8-T4

T6-O2

T3-T5

F7-T3

T5-O1

Cz-Pz

100 : V1 sec

F4 -C4

Fp2-F4

100 : V1 sec

Thalamus

Childhood Absence Epilepsy ( Petit Mal)

Age at onset . 2 - 8 yrsVariable frequency of seizures ( 3-4 to 40-50/ day)VPA, ESM, LTG: : effective in 50 - 90%

Childhood absence epilepsy prognosis

¡Drug refractoriness does not influence long-term prognosis

¡More than 90% of patients will remain seizure free after drug discontinuation

¡The vast majority of patients will achieve seizure freedom before the age of 20 years

Livingston et al, 1965; Headstrom & Olsson, 1991

Juvenile Myoclonic Epilepsy

¡ �Idiopathic� i.e. genetically determined epilepsy

¡ Polygenetic

¡ Age-related onset

¡ �Generalised� i.e. with a bilateral quasi-symmetric and synchronous ictogenesis

¡ Three possible seizure types¡ Myoclonic (100% per definition)¡ GTCS on awaking (most)¡ Absences (minority)

¡ Onset with any of these types

EPILESSIE FOCALI IDIOPATICHE

CARATTERISTICHE GENERALI

- 22% delle epilessie in età pediatrica- Sviluppo psicomotorio normale- RM encefalo nella norma- Epilessie età-dipendenti con

scomparsa delle crisi in etàadolescenziale nella maggior partedei casi

FORME

1. Epilessia benigna dell’Infanzia conparossismi centro-temporali (EpilessiaRolandica)

2. Epilessia occipitale con crisi con segniautonomici (Sindrome diPanayiotopoulos)

3. Epilessia focale occipitale idiopatica(Gastaut)

EPILESSIE FOCALI IDIOPATICHE

Benign childhood partial seizures with focal EEG sharp-slow wave

complexes may be a group of syndromes that are linked together

due to a common, genetically determined, mild and reversible,

functional derangement of the brain cortical maturational process

that is called “benign childhood seizure susceptibility syndrome”.

This is often clinically silent, manifested in more than 90 per cent with

EEG sharp and slow waves with an age related-localization. In the

remaining minority, there are infrequent partial seizures of which

their symptoms also are localization and age-related and

dependent.

Panayiotopoulos P., Epileptic Syndromes in infancy, childhood and adolescence, Chapter 15, 2002

CARATTERISTICHE delle CRISI

- Segni autonomici (pallore/rossore/cianosi, nausea,malessere, ipotonia)

q Con vomito 72/93 (77.4%)

- Segni motoriq Deviazione del capo e/o degli occhi 68/93 (73%)q Convulsione coinvolgente un emilato 11/93 (11.8%)q Segni opercolari 10/93 (9.2%)

- Compromissione della coscienza 83/93 (89%)

- Sonno 65/93 (69.9%)

- Durata

- Risoluzione della crisi

SINDROME DI PANAYIOTOPOULOS

SINDROME DI PANAYIOTOPOULOS

PROGNOSI

- Nonostante la durata e la ricorrenza delle crisi, i

pazienti non presentano sequele a lungo

termine

- Le anomalie EEG non hanno significato

prognostico

- Terapia: 59/93 pazienti in terapia AE, ma 34/59

continuavano a presentare crisi

- Remissione: 64/93 dopo un anno dalla prima crisi

Somministrazione di WISC-R dopo la prima crisi ( range 3-79 mesi)

- QI nella norma per età (QIT 103, QIV 102, QIP 104)

- Differenze significative in alcune sottoscaleq Ragionamento aritmetico (p 0.04)q Comprensione (p 0.04)q Picture arrangement (p 0.05)

EPILESSIA BENIGNA CON PAROSSISMI CENTRO-TEMPORALI o EPILESSIA ROLANDICA

CARATTERISTICHE GENERALI

- Età all’esordio: 75% tra i 4 ed i 10 anni

- Genere: prevalentemente maschi

- Prevalenza: 15% in assenza di febbre

SEMEIOLOGIA delle CRISI

q Sintomi unilaterali facciali senso-motori

(30%)

q Sintomi oro-faringo-laringei (53%)

q Afasia (40%)

q Ipersalivazione (30%)

Attenzione!!Non abbiamo la sintomatologia tipicadelle crisi del lobo temporale

- Si manifestano nel sonno NREM

(addormentamento/risveglio)

- Durata: breve! (1-3 minuti)

EPILESSIA BENIGNA CON PAROSSISMI CENTRO-TEMPORALI o EPILESSIA ROLANDICA

EPILESSIA BENIGNA CON PAROSSISMI CENTRO-TEMPORALI o EPILESSIA ROLANDICA

PROGNOSI

- 10-20% dei pazienti presenta una singola crisi

- La maggior parte dei pazienti avrà meno di 10 crisi totali

- Remissione entro 2-4 anni dall’esordio ed entro l’età di 16 anni

Antiepileptic drug treatment of rolandic epilepsyand Panayiotopoulos syndrome: clinical practicesurvey and clinical trial feasibilityLouise C Mellish,1 Colin Dunkley,2 Colin D Ferrie,3 Deb K Pal1

▸ Additional material ispublished online only. To viewplease visit the journal online(http://dx.doi.org/10.1136/archdischild-2013-304211).1King’s College London,London, UK2Sherwood Forest Hospitals,Notts, UK3Department of PaediatricNeurology, Leeds GeneralInfirmary, Leeds, UK

Correspondence toProfessor Deb K Pal,Department of Basic andClinical Neuroscience, King’sCollege London, Institute ofPsychiatry, Psychology &Neuroscience, LondonSE5 8AF, UK;deb.pal@kcl.ac.uk

Received 26 February 2014Revised 1 August 2014Accepted 4 August 2014Published Online First8 September 2014

To cite: Mellish LC,Dunkley C, Ferrie CD, et al.Arch Dis Child2015;100:62–67.

ABSTRACTBackground The evidence base for management ofchildhood epilepsy is poor, especially for the mostcommon specific syndromes such as rolandic epilepsy (RE)and Panayiotopoulos syndrome (PS). Considerableinternational variation in management and controversyabout non-treatment indicate the need for high qualityrandomised controlled trials (RCT). The aim of this studyis, therefore, to describe current UK practice and explorethe feasibility of different RCT designs for RE and PS.Methods We conducted an online survey of 590 UKpaediatricians who treat epilepsy. Thirty-two questionscovered annual caseload, investigation and managementpractice, factors influencing treatment, antiepileptic drugpreferences and hypothetical trial design preferences.Results 132 responded (22%): 81% werepaediatricians and 95% at consultant seniority. Weestimated, annually, 751 new RE cases and 233 PS cases.Electroencephalography (EEG) is requested at least halfthe time in approximately 70% of cases; MRI brain atleast half the time in 40%–65% cases andneuropsychological evaluation in 7%–8%. Cliniciansreported non-treatment in 40%: main reasons were lowfrequency of seizures and parent/child preferences.Carbamazepine is the preferred older, and levetiracetamthe preferred newer, RCT arm. Approximately one-halfconsidered active and placebo designs acceptable,choosing seizures as primary and cognitive/behaviouralmeasures as secondary outcomes.Conclusions Management among respondents isbroadly in line with national guidance, although withpossible overuse of brain imaging and underuse of EEGand neuropsychological assessments. A large proportionof patients in the UK remains untreated, and cliniciansseem amenable to a range of RCT designs, withcarbamazepine and levetiracetam the preferred active drugs.

INTRODUCTIONEpilepsy affects 63 400 young people under18 years of age in the UK.1 Seizures represent oneof the top five avoidable reasons for admission ofchildren to emergency departments in the UK.2

Aside from seizures, cognitive and behaviouralcomorbidities cause a substantial impact affectingabout two-thirds of children with epilepsy.3 Indeed,the comorbidity-associated burden may outweighthat of the seizures themselves4 and in some epilep-sies, comorbidities are stronger predictors ofquality-of-life than seizures.5 Hence, the compre-hensive management of epilepsy necessitates therecognition and management of individual epilepsysyndromes and their specific comorbidities.

There are almost 40 electroclinical epilepsy syn-dromes defined by constellations of seizure type(s),age of onset, electroencephalography (EEG) andclinical features, each requiring individual assess-ment and management. The evidence base for man-agement of childhood epilepsies in the UK isdetailed in the National Institute of Health andCare Excellence (NICE) Guidelines6 and by itsScottish equivalent, the Scottish IntercollegiateGuidelines Network (SIGN).7 This guidance pro-vides a care standard framework against which arecent national ‘Epilepsy12’ audit of childhood epi-lepsy care was conducted.8 However, the evidencebase for antiepileptic drug treatment in these guide-lines remains poor for many common childhoodepilepsies, consisting of only a few high-quality ran-domised controlled trials (RCT).9 Much of the evi-dence available to NICE is extrapolated fromheterogeneous studies of seizures mixing epilepsytypes and age groups,10 with uncertain applicabilityto well-defined childhood epilepsy syndromes.11

Furthermore, while there is now an emerging ideaof how childhood epilepsy as a whole is managedin the UK,8 there is little detail about the variationin management of specific epilepsy syndromes andpaediatricians’ familiarity with them. Hence, amore detailed survey of practice is justified.

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What is already known on this topic?

▸ UK management of rolandic epilepsy andPanayiotopoulos syndrome are not well knownand there is limited scientific basis for drugtreatment or non-treatment.

▸ Paediatric opinion towards clinical trial designsis also unknown and important to assess priorto further planning.

What this study adds?

▸ There are suggested patterns of underuse ofEEG and neuropsychological assessment andoveruse of brain MRI; 40% of patients areroutinely untreated.

▸ Half the respondents would be open tohead-to-head or active versus non-active designor placebo-controlled clinical trials withcarbamazepine and levetiracetam as thepreferred active treatments.

Review

62 Mellish LC, et al. Arch Dis Child 2015;100:62–67. doi:10.1136/archdischild-2013-304211

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Association between November 2012 and December 2012.Respondents could only reply once and this was checked bynames and internet protocol addresses. We sent weekly emailreminders before closing the weblink after 4 weeks. This profes-sional survey was deemed exempt from ethics approval.

AnalysisResults were available both as summary data and as rawresponse files. We edited out inconsistent responses using theraw data. We summarised and visualised results using a spread-sheet tool.

RESULTSCharacteristics of respondentsThere was a total of 132 respondents from the 590 individualscontacted with valid email addresses, a response rate of 39%from Epilepsy-12 audit leads and 22% overall. With weeklyemail prompts, 74 responded in the first week, another 34 inthe second week and the remainder responded over the follow-ing fortnight. Fifty-three percent of respondents were generalpaediatricians with special expertise in epilepsy; 17% weregeneral, community or neurodisability paediatricians; 19% werepaediatric neurologists. In terms of seniority, 95% were consul-tants; 5% associate specialists. Fifty-three percent of respon-dents were men. Age-wise, 11% of respondents were under40 years; 54% were 41–50 years; 35% over 50 years.

CaseloadThe majority (90%) of clinicians reported diagnosing six orfewer new RE and six or fewer PS cases annually; by summatingmonthly individual case loads, we estimated an annual total of751 new RE cases and 233 new PS cases from the 132 UKrespondents.

InvestigationEEG is the most often requested investigation (figure 1). Mostclinicians only infrequently request CT or MRI brain scans.Only 7%–8% of clinicians request neuropsychological assess-ments in RE or PS.

TreatmentForty percent of RE and PS cases are never treated with regularAEDs. Both seizure frequency/severity and parental/child prefer-ence were judged important factors influencing the decision notto prescribe AED (figure 2).

AED preference in RCTsAED preferences were almost identical for RE and PS (figure 3).Carbamazepine was overwhelmingly rated as the most preferredactive comparator for an RCT and also the preferred ‘older’AED; sodium valproate was the second most preferred AED; noother AEDs were indicated as first choice by >10% of respon-dents. Among the newer AEDs, respondents indicated a slightpreference for levetiracetam over lamotrigine as active compara-tor, with no other popular first-line choices >10%. About 10%of respondents would object to ethosuximide, benzodiazepines,phenobarbital or phenytoin as an active treatment arm.

Attitudes to clinical trial designIn RE, just over one-half of respondents (55%) would recruit toan RCT comparing either two active treatments, 48%–49% toactive versus no active treatment design and 41% to activeversus placebo, regardless of the preceding number of seizures(<3 or ≥3 in 6 months). In PS, there was a greater preference

for a two active drug design (59%) than a trial with no activetreatment (44%) or placebo (38%). The great majority (82%for RE and 79% for PS) chose seizure remission as the preferredprimary outcome in a RE trial, with close to two-thirds (73%for RE and 60% for PS) choosing cognitive or broad quality oflife measures as a secondary outcome.

DISCUSSIONThis is the first physician survey regarding the common epilepsysyndromes of childhood RE and PS. The results indicate first,that the pattern of investigations requested for patients withthese syndromes appears broadly appropriate and in line withNICE guidance, although with a few unexplained observations.

Figure 2 Factors rated as quite or very important influencing ano-treatment decision in rolandic epilepsy, expressed as percentage ofrespondents (data for Panayiotopoulos Syndrome very similar).

Figure 1 Use of investigations in rolandic epilepsy (RE) andPanayiotopoulos Syndrome (PS) expressed as percentage ofrespondents: electroencephalography (EEG); brain MRI;neuropsychological assessment (NP).

Review

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