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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