Epilepsy overview

Tal Gilboa MDPediatric 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

A = activation gateI = inactivation gate

Na+ Na+

CarbamazepinePhenytoin

Topiramate

LamotrigineValproateNa+ Na+

I

A

I

A

Open Inactivated

Voltage-gated calcium channel

SubtypesL-typeT-typeN-typeP-type

Ca2+ Ca2+

Ca2+ Ca2+Valproate Dimethadione

Ethosuximide

Response to AED Therapy

Initial AED

(N = 421)

Success 47%

Failure 53%

• Toxicity 20%

• Toxicity + 30%inadequate sz control

• Inadequate 3%sz control

Success 46%

Failure 54%

• Toxicity 16%

• Toxicity + 38%inadequatesz control

• Inadequate 0%sz control

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