multidisciplinaire aanpak van het kind met epilepsie

Kinderepilepsie:
multidisciplinaire benadering
Lieven Lagae
Kinderneurologie
Universitaire Ziekenhuizen KULeuven
Kinderepilepsie : totaal-concept
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Diagnostiek : Epilepsie als een symptoom
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Herhaalde anamnese en klinisch onderzoek
Video-EEG studies
Anatomische en functionele beeldvorming
Genetische studies
Neurometabole studies
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Invloed op Cognitie en Gedrag: neuropsychologie
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Aanbieden van alle behandelingsmodaliteiten
Behandeling
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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
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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
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Valproic acid
Lamotrigine
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Levetiracetam
Topiramate
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Carbamazepine / Oxcarbazepine
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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
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Amygdalo-hippocampectomie
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Hemisferotomie
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mesiaal temporaal sclerose
Cerebro vascular accident
Rasmussen encefalitis
Hemimegalencefalie
Polymicrogyrie unilateraal
Lesionectomies
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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
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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
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Epilepsy syndrome
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Underlying aetiology
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Effects on specific processes
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Seizure frequency and severity
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EEG abnormalities
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Treatment – antiepileptic drugs (AEDs)
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Effects on cognitive instruments
Psychosocial environment
Toekomst
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Individueel bioprofiel
Genetica / moleculaire biologie
Voorbeeld : multidrug-resistentie (MRD genen)
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Anti-epileptogene medicatie
voorbeeld : posttrauma-epilepsie (vb HIE)
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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