Challenges in idiopathic/ genetic epilepsy syndromes
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1 Herlev and Gentofte Hospital Department of Pediatrics Indsæt h af objekt 1. Højrek vælg Gitt 2. Sæt kr tegnehjæ 3. Vælg O Challenges in idiopathic/ genetic epilepsy syndromes g Navn menuen Sidefod tår Navn der står krivelse Anvend kel slide Maria J. Miranda, MD Ph.D., Department of Pediatrics, Herlev University hospital NNPS, Copenhagen 2018 Herlev and Gentofte Hospital, University of Copenhagen 1
2 Which challenges do we face when treating and following children with Childhood absence epilepsy (CAE) and Epilepsy with Centro-Temporal Spikes (ECTS)? 2
3 Childhood Absence Epilepsy (CAE) Evidence Epilepsy with CentroTemporal Spikes (ECTS) 3
4 Questions Treat or not to treat Which antiepileptic drug (AED)? Consequences? Risks? School? Future? 4
5 5.5 million inhabitants ~ 1,3% have epilepsy by age 15 ~ children have epilepsy in DK 15-25% = ECTS ~ 10% = CAE
6 New ILAE epilepsy classification: V. Etiology CAE Absences Self-limited idiopathic/ genetic generalised epilepsy syndrome 6
7 Case S, 3,5 years old Girl S, born as twin A, GA 36+1, Apgar score 8/1 10/5 Normal development Febrile seizures from 17 month old, x 7-8, last 2½ years old, uncomplicated Since the age of 3 y. 4 mo. many daily episodes lasting 5-10 seconds where she suddenly stares, stops activity, non-reacting, sometimes chewing loud 7
8 EEG EEG: Spike-wave 3 Hz paroxysms 8
9 Cont. case S EEG: 3 Hz generalised spike-wave paroxysms and several absences Starts Valproic acid (VPA), on 30 mg/ kg Starts ethosuximide (ETX) 5 weeks later, 25 mg/kg, VPA unchanged 2 nd EEG ½ year later: normalised 2 year later (2016): medicine-free, absence-free and normal EEG Normal development, starts school 9
10 CAE history First described in 1705 by Poupart and Tissot in : hyperventilation and absences 1930: EEG 10
11 New ILAE epilepsy classification: V. Etiology CAE 4-10 y (5-7) > 3 / 1 Self-limited idiopathic/ genetic generalised epilepsy syndrome 11
12 CAE EEG EEG: Spike-wave 3 Hz paroxysms 12
13 Challenges Treatment Developmental consequences 13
14 Treatment of CAE VPA Valproic acid ETX Ethosuximide LTG Lamotrigine 14
15 CAE treatment study A double-blind RCT comparing efficacy, tolerability and neuropsychological effects of ETX, VPA and LTG in children with CAE. 15
16 CAE study ETX and VPA were similar in efficacy LTG less efficacy ETX better cognitive profile ETX less relapse Patients with no response to ETX: Higher risk of GTCs and progression to JME ETX: disease-modifying effect? 16
17 Treatment protocol ETX: Start 10 mg/ kg, increase every 5th day to mg/kg Side effects: gastrointestinal, tiredness Ethosuximide: Zarondan syrup or Petnidan capsules (in DK requires special application to Danish Medicines Agency) 17
18 Developmental consequences CAE 36% have attention deficits before treatment start (x 4 background population) IQ: normal Attention deficits similar in seizure-free and nonseizure free Important to pay attention to school achievements and children's well-being 18
19 CAE-prognosis 12% had GTCS throughout 7 years 19
20 CAE-prognosis Bad prognosis: Lack of response to 1 st choice treatment Good prognosis: Response to ETX 20
21 ECTS- Epilepsy with Centro-temporal spikes or Rolandic Epilepsy Self-limited idiopathic/ genetic focal epilepsy syndrome 25% of epilepsies in children under 16 years 2/3 of self-limited focal epilepsy syndromes Peak of onset 5-8 years (2-14 years) 21
22 New ILAE epilepsy classification: V. Etiology ECTS Syndrome: self-limited idiopathic/ genetic focal epilepsy syndrome 22
23 Seizures in ECTS Only 20% have frequent seizures Brief seizures, 1-2 min. 70% in sleep (may occur during wakefulness, far lees common) 23
24 ECTS- EEG awake 24
25 ECTS- EEG sleep 25
26 Prognosis ECTS For seizure remission good Self-limited in most children by years And usually within 2-4 years of onset 26
27 ECTS-comorbidity Neuro-cognitive and behavioural: increasing evidence of significant difficulties 27
28 ECTS- comorbidity 12-30% difficulties in: Language Memory Behaviour Attention Anxiety Depression Cognition... 28
29 ECTS- evolution ECTS CSWS/ ESES (electric status epilepticus in slow sleep) Landau-Kleffners syndrome (acquired aphasia) ECTS with frequent refractory seizures 29
30 ECTS- treatment challenges Treat or not to treat individual decision seizure frequency parents/ child Cost/ benefit Which AED? No clear scientific evidence Levetiracetam Others: Valproic acid, Sulthiam 30
31 Questions and challenges regarding ECTS AED reduces seizures: YES EEG SW activity in sleep correlates with comorbidities?? AED ameliorates EEG SW activity in sleep?? AED reduces comorbidity?? AED may prevent (or worsen) development to atypical evolution of ECTS? 31
32 Treatment with AED- challenges (cont.) Will AED reduce SW-frequency under sleep? Some evidence Reducing SW in sleep by treating with AED, will we ameliorate cognitive and behavioural issues? No clear scientific evidence 32
33 Take home messages TREATMENT: CAE: 1. choice ETX ECTS: Individual (start LEV?) DEVELOPMENTAL CHALLENGES: CAE: YES ECTS: YES FUTURE: SELF-LIMITED CAE: YES ECTS: YES BUT. 33
34 Take home messages Treat right from the beginning Be aware of children s school difficulties, behaviour and psychiatric symptoms Be aware of changes 34
35 35
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