1. Tal Gilboa MD Pediatric Neurology
Epilepsy overview
Tal Gilboa MD
Pediatric Neurology

2. Illustrative case 8 months old baby girl
Normal pregnancy except for hyperechogenic spot in the heart
Normal delivery – normal echo
Development - crawls, sits unsupported, laugh, playful. Last 2 weeks - regressed
2nd child, healthy non-consanguineous parents
Last 2 weeks having episodes when waking up of eye rolling and arm opening

3. Illustrative case
Physical exam – important clues

4. Illustrative case Parents video – if possible Video EEG – overnight
Imaging – MRI

5. Illustrative case

6. Illustrative case

7. Illustrative case

8. Illustrative case Diagnosis – IS due to TSC Treatment – Vigabatrin
Further investigation needed – abdominal US, eye exam
Course – IS stopped, AED d/c – 6m, development slow
Genetic counseling

9. Illustrative case
Age 2y – multiple SZ types, walks, says few word, hyperactive, repetitive play
Treatment – multiple AEDs failed
Other treatment options?

10. Epilepsy Unprovoked seizures Comorbidities – ADHD, LD, depression
Specific syndromes
“benign” / transient
EEG – ictal, interictal
Imaging – MRI
Other tests – neuropsychological, devlopmental

11. Must know Epilepsy syndromes
Early epileptic encephalopathies
West syndrome / IS
Rolandic / BCECT
Childhood absence
ESES / CSWS / LKF
Juvenile absence
Juvenile myoclonic epilepsy

12. Treatment goals Prevent seizures Reduce seizure frequency
Abort generalization
Minimize side effects
Good general health
Quality of life

13. When to treat? 2nd unprovoked seizure
1st unprovoked seizure and high risk of recurrence
Special circumstances – head trauma / surgery, infantile spasms, increased risk of serious injury, language regression, febrile seizures

14. How to treat? Preventive measures Abortive medication
Preventive medications
Ketogenic diet
VNS – vagal nerve stimulator
Epilepsy surgery

15. Preventive measures Avoid sleep deprivation
Avoid flashing lights or other known triggers (ETOH, drugs, medications)
Dot not miss medication dose

16. Abortive medication Lorazepam IV Diazepam PR Midazolam IN or buccal
IV lorazepam is as effective as IV diazepam in the treatment of acute tonic clonic convulsions, 19/27 (70%) versus 22/34 (65%), RR 1.09 (95% CI 0.77 to 1.54) and has fewer adverse events.
Appleton R, Macleod S, Martland T. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database of Systematic Reviews. 2008, Issue 3

17. Abortive medication
Oral transmucosal midazolam was effective in 75% of cases (30 of 40 seizures), whereas rectal diazepam was effective in 59% (23/39) ( P = non significant). There were no adverse cardiorespiratory effects in either group.
Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet 1999;353:

18. Abortive medication
The rate of respiratory depression or circulatory complications was lower in the two BDZ groups (10 to 11%) compared with the placebo group (22.5%). This (and other studies) confirm that not giving BDZs is more risky than giving them for prolonged convulsive seizures.
Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001;345:631– 637

19. Preventive medications
1857: Bromides.
1912: Phenobarbital.
1937: Phenytoin.
1940’s : Trimethadione; Mephenytoin.
1950’s: Ethosuximide; Primidone.
1968: Diazepam.
1970’s: Carbamazepine, Clonazepam, Valproic acid, Clobazam

20. Preventive medications
1990’s: Felbamate, Gabapentin, Lamotrigine, Topiramate; Fosphenytoin, Tiagabine, Levetiracetam.
today: Oxcarbazepine; Zonisamide, Stiripentol, Rufinamide, Lacosamide, Eslicarbazepine, Perampanel, Ezogabine / Retigabine…

21. Other medications
ACTH
IVIG
Diuretics
Lidocaine

22. Mechanisms of action
Post synaptic ligand gated ion channels – blocks post synaptic depolarization
Pre synaptic voltage gated ion channels – blocks pre synaptic depolarization and prevents neurotransmitter release
Neurotransmitter analogs

23. Mechanisms of action

24. Ligand-gated chloride channel
Phenobarbital
Benzodiazepines

25. Ligand-gated cation channel – NMDA
Lacosamide
Felbamate

26. Voltage-gated sodium channel
Open
Inactivated
Na+
Na+ A A I I
Carbamazepine Phenytoin Topiramate
Lamotrigine Valproate
Na+
Na+
A = activation gate
I = inactivation gate

27. Voltage-gated calcium channel
Subtypes
L-type
T-type
N-type
P-type
Ca2+
Valproate
Dimethadione Ethosuximide

28. Response to AED Therapy
Success 47%
Success 46%
Failure %
Toxicity %
Toxicity % inadequate sz control
Inadequate 0% sz control
Failure %
Toxicity %
Toxicity % inadequate sz control
Inadequate 3% sz control
Initial AED
(N = 421)
Other AED
(N = 89)
Mattson RH, et al. N Engl J Med. 1985;313:145.
Mattson RH, et al. Epilepsia. 1986;27:645.

29. Ketogenic diet
3 to 4 grams of fat for every 1 gram of carbohydrate and protein
50% have at least a 50% reduction in the number of their seizures.
10-15%, become seizure-free
Mechanism of action - unknown

30. Ketogenic diet
Side effects – constipation, vitamin def, high TG & cholesterol
Close monitoring

31. Vagal nerve stimulator
prevent seizures by sending regular, mild pulses of electrical energy to the brain via the vagus nerve.
Abort SZs
Improve QOL

32. Epilepsy surgery
Lobectomy or cortical resection is the most common form of epilepsy surgery
Hemispherectomy - to remove all or almost all of one side of the brain
Corpus Callosotomy - sectioning, or separating, the corpus callosum
Multiple Sub-pial Transection

33. Epilepsy surgery