Tal Gilboa MD Pediatric Neurology Epilepsy overview Tal Gilboa MD Pediatric Neurology

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

Illustrative case Physical exam – important clues

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

Illustrative case

Illustrative case

Illustrative case

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

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

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

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

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

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

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

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

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

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;353:623- 6.

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

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

Preventive medications 1990’s: Felbamate, Gabapentin, Lamotrigine, Topiramate; Fosphenytoin, Tiagabine, Levetiracetam. 2000 - today: Oxcarbazepine; Zonisamide, Stiripentol, Rufinamide, Lacosamide, Eslicarbazepine, Perampanel, Ezogabine / Retigabine…

Other medications ACTH IVIG Diuretics Lidocaine

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

Mechanisms of action

Ligand-gated chloride channel Phenobarbital Benzodiazepines

Ligand-gated cation channel – NMDA Lacosamide Felbamate

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

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

Response to AED Therapy Success 47% Success 46% Failure 54% Toxicity 16% Toxicity + 38% inadequate sz control Inadequate 0% sz control Failure 53% Toxicity 20% Toxicity + 30% 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.

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

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

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

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

Epilepsy surgery