Kinderepilepsie: multidisciplinaire benadering Lieven Lagae Kinderneurologie Universitaire Ziekenhuizen KULeuven
Kinderepilepsie : totaal-concept
Diagnostiek : Epilepsie als een symptoom
Herhaalde anamnese en klinisch onderzoek Video-EEG studies Anatomische en functionele beeldvorming Genetische studies Neurometabole studies
Invloed op Cognitie en Gedrag: neuropsychologie
Aanbieden van alle behandelingsmodaliteiten
Behandeling
Informatie- Begeleiding- Orientatie Medicatie: anti-epileptica Epilepsie-chirurgie Nervus Vagus stimulatie Ketogeen dieet Immunotherapie
Anti-epileptische medicatie
Idealiter Goede efficaciteit Breed spectrum Monotherapie Geen / weinig bijwerkingen Geen effect op cognitieve ontwikkeling en op gedrag Gemakkelijk toedienbaar Voorspelbare farmacokinetiek en dynamiek
Anti-epileptica
Oudere AED :
phenobarbital, fenytoine, primidone
Klassieke AED : carbamazepine, valproic acid, ethosuximide, sulthiame, benzodiazepines Nieuwe AED :
vigabatrine, lamotrigine, oxcarbazepine, topiramate, tiagabine, gabapentin, levetiracetam, felbamate, zonisamide, feneturide, stiripentol
Responder Rates (≥ 50% Seizure Reduction) in AED Adjunctive Paediatric Studies vs Placebo*
% of patients
50
44.6
42
39
40 30 20 10 0
41
22
21.2
19.6
20
*
*
*
*
*
LEV
TPM1
LTG2
OXC3
GBP4
16
17.5
1. Elterman RD. Neurology 1999: 2. Duchowny M. Neurology 1999: 3. Glauser TA. Neurology 2000: 4. Appleton R. Epilepsia 1999.
AED Results in Paediatric Partial Seizures Drug – placebo difference
LEV1
TPM2
LTG3
OXC4
GBP5
Median % reduction in partial seizures from baseline
27%
22.6%
29.4%
26%
10.5%
Responders (≥ 50% seizure reduction)
25%
19%
26%
19%
3.7%
% Seizure-free
6%
5%
No data
3%
2%
Discontinuations due to AEs
-4%
-2%
-1%
+7%
+3%
1. Glauser TA Epilepsia, Lagae EJPN, 2004: 2. Elterman RD. Neurology 1999: 3. Duchowny M. Neurology 1999: 4. Glauser TA. Neurology 2000: 5. Appleton R. Epilepsia 1999.
First choice anti-epileptic drugs 2005
Valproic acid Lamotrigine
Levetiracetam Topiramate
Carbamazepine / Oxcarbazepine
Epilepsie chirurgie
Epilepsie Chirurgie Screening bij refractaire epilepsie Video EEG (5dagen) NMR 1.5T en 3T Ictale en Interictale SPECT: SISCOM analyse Pet scan functionele MRI Neuropsychologie
Type Chirurgie
Amygdalo-hippocampectomie
Hemisferotomie
mesiaal temporaal sclerose
Cerebro vascular accident Rasmussen encefalitis Hemimegalencefalie Polymicrogyrie unilateraal
Lesionectomies
Cortical malformations Tuberous sclerosis
Rasmussen Encephalitis
Mesial Temporal sclerosis
Corticale dysplasie
Nervus vagus stimulatie
Effect Nervus vagus stimulatie
Ketogeen dieet
16 /0 2/ 1 6 2 00 4 /0 4/ 20 16 04 /0 6/ 1 6 2 00 4 /0 8/ 20 16 04 /1 0/ 1 6 2 00 4 /1 2/ 2 1 6 00 4 /0 2/ 2 1 6 00 5 /0 4/ 2 1 6 00 5 /0 6/ 20 16 05 /0 8/ 1 6 2 00 5 /1 0/ 20 16 05 /1 2/ 2 1 6 00 5 /0 2/ 2 1 6 00 /0 6 4/ 20 16 06 /0 6/ 20 06
16 /0 2/ 2 1 6 00 4 /0 4/ 1 6 2 00 4 /0 6/ 20 16 04 /0 8/ 2 1 6 00 4 /1 0/ 20 16 04 /1 2/ 2 1 6 00 4 /0 2/ 2 1 6 00 5 /0 4/ 1 6 2 00 5 /0 6/ 20 16 05 /0 8/ 2 1 6 00 5 /1 0/ 2 1 6 00 5 /1 2/ 20 16 05 /0 2/ 1 6 2 00 6 /0 4/ 2 1 6 00 6 /0 6/ 20 06
Decrease anticonvulsants (%)
Seizures
5 4
3 2
300 250 200 150 100 50 0
2,0
1 0 1,0
0,0
Ketogenic diet Tom [February 2004 - August 2006]
Seizures
RIVOTRIL
Ratio
DEPAKINE SABRIL
Ratio
Tom, 4 jaar, Tubereuze sclerose Ketogenic diet Tom [February 2004 - August 2006] 4,0
3,0
Outcome of 453 children with newly diagnosed epilepsy at 5 years of follow-up 150
n
100
27% 14%
24% 14% 9%
50
0
5 yr
4–5 yr
3–4 yr
2–3 yr
Duration of terminal remission
12%
1–2 yr
<1 yr
Pharmacoresistant Epilepsy Previously Untreated Epilepsy Patients (n=470)
Seizure-free with 1st drug
36% 47%
Seizure-free with 2nd drug Seizure-free with 3rd or multiple drugs Pharmacoresistant epilepsy
4% 13%
Kwan P, Brodie MJ. N Engl J Med. 2000;342:314-319.
I-5
Invloed op cognitie en gedrag
Brain dysfunction at specific age
Epilepsy Cognition
Behaviour
Medication
Neuropsychology: Cognitive Domains
Sensory processing / perception Attention / concentration Speed of processing Working memory Psychomotor speed Visuospatial abilities Problem-solving Non-verbal memory Verbal memory Motor control / performance Verbal reasoning Imagery General intelligence , IQ
cognitive instruments
‘specific’ processes
‘overall cognitive ability’ Lagae L, Seizure 2006
Cognition and Behaviour: Contributing Factors
Epilepsy syndrome
Underlying aetiology
Effects on specific processes
Seizure frequency and severity
EEG abnormalities
Treatment – antiepileptic drugs (AEDs)
Effects on cognitive instruments
Psychosocial environment
Toekomst
Individueel bioprofiel
Genetica / moleculaire biologie Voorbeeld : multidrug-resistentie (MRD genen)
Anti-epileptogene medicatie
voorbeeld : posttrauma-epilepsie (vb HIE)
Therapy-on-demand
closed-loop on line systeem: - continue EEG meting (subduraal) - anticipatie van aanvallen - locale, tijdelijke toediening medicatie of/en hesenstimulatie
Continue meting EEG: draadloos miniatuur eigen energiebron
Target:
V < 1cm3 or 5 cm2 P < 100µW
