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Tal Gilboa MD Pediatric Neurology

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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

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