Epilepsy - Masalha

Question 1

What are the characteristics of Lennox-Gastaut syndrome?

Answer 1

Seizure disorder, onset in childhood

Tonic, atonic, myoclonic, generalized tonic-cloinc, absence types

Associated with mental retardation

Slow EEG spike-and-wave

Treated with Valproid acid, lamotrigine, felbamate

Question 2

What are the main characteristics of Benign rolandic epilepsy?

Answer 2

Childhood onset

Simpal partial seizure types involving mouth and face, generalized tonic-clonic

Associated with nocturnal preponderance of seizures

Centrotemporal spikes found on EEG

Treated with Carbamazepine (or none)

Question 3

What are the main characteristics of Absence epilspsy?

Answer 3

Onset in childhood and adolescence

Absent, generalized tonic-clonic seizure types

Associated with hyperventilation as a trigger

3 Hz spike-and-wave found on EEG

Treated with Ethosuximide and valproic acid

Question 4

What are the characteristics of Juvenile myoclonic epilepsy?

Answer 4

Onset in adolescence and young adulthood (usually 13-14 up to 21)

Myoclonic, ansence, can transform into generalized tonic-clonic types

Associated with early morning preponderance of seizures (myoclonic jerks often while brushing teeth or coffee)

4-6 Hz polyspike-and-wave found on EEG

Treated with Valproic acid and lamotrigine (carbamazapine and phenytoin often exacerbate seizures)

Autosomal domnant

Question 5

What are the neurotransmitters responsible for seizures (most likely) and the target of many drugs?

Answer 5

Glutamate (excitatory, increases neuronal activity) - antagonists prevent seizures (along with antagonists of Na+ and Ca+ channels)

GABA (inhibitory, decreases neuronal activity) - agonists prevent seizures (along with K+ channel agonists)

Question 6

When are the epidemiological peaks of epilepsy?

Answer 6

1 year (from congenital causes)

18 months (from febrile causes)

Adolescence (from psychomotor/temporal lobe epilepsy)

65 years old (from ischemia)

Question 7

What are the uses of Valproic acid?

What are its side effects?

Answer 7

First line for all generalizes or partial seizures.

Na+ channel blocker and may increase GABA levels

Side effects:
Amenorrhea, alopecia, weight gain, ovarian cysts, teratogenic

(90% protein body and small percentage crosses BBB)

Question 8

What are the uses and side effects of lamotregine?

Answer 8

Wide spectrum

• Glutamate release inhibitor (neuro-protector in rodent models).
• 50-60% protein bound.
• Hepatic metabolism
• effective for all types of epilepsy (add-on or monotherapy)
• 39% seizure free- as mono therapy ( PCS, GTC)
• 50% seizures reduction in 25% refractory epi
• Rash (3-5%), nausea , vomiting and visual abnormality

Question 9

What are the effects, uses, and side effects of carbamazepine (tegretol) and Oxcarbazepine?

Answer 9

Blockade/Slowing of Na+ channels
Metabolized in lever by: cytochrome P450- causes hepatic toxicity

35 – 50% diplopia, blurred vision, headache, dizziness, nausea.
Reversible mild leucopenia:No need to stop treatment if WBS above 2500/ml.

Can also cause hyponatremia (SIADH)

Oxcarbazepine: same mechanism with potassium and L-type calcium channels. No drug interaction. Less side effects.

Question 10

What are the effects, uses and side effects of phenytoin (dantoin)?

Answer 10

Blockade/Slowing of Na+ channels

Reversible gingival hypertrophy (20%) (childhood), peripheral neuropathy (30%), Nystagmus, Ataxia, Mental slowing, Drowsiness, nausea, toxic hepatitis, systemic lupus, Hersutism, anemia, decreased vitamin K

Question 11

What are the effects, uses, and side effects of Gabapentin?

Answer 11

Increase GABA levels in human brains (indirectly)
Not protein bound and not hepatic metabolized, short half life

50% decrease seizure frequency, 23% respond but None seizure free

Mild CNS side effects

Question 12

What are the effects, uses, and side effects of Levetiracetam (Keppra)?

Answer 12

Newest drug, wide spectrum, good for refractory epilepsy

Inhibits presynaptic glutamate release or stimulates postsynaptic GABA absorption

5% psych side effects

Low drug interactions

Question 13

What are the effects, uses, and side effects of Toperamate?

Answer 13

Wide spectrum, also for tremor and chronic migraine.

NMDA, Kainate receptor inhibitor and GABA receptor
desensitization, Carbonic anhydrase inhibitor, primarily excreted by the kidney- contraindicated for renal stone patients.

No drug interaction.

Long half life.

CNS side effects (abnormal thinking, fatigue, dizziness, memory loss, confusion). Can cause weight loss.