epilepsy

Question 1

what are seizures?

Answer 1

abnormal paroxysmal changes in electrical activity of the brain causing large scale synchronous discharge or neuronal networks

Question 2

wha tis the incidence of epilepsy in the Uk and worldwide?

Answer 2

1% of UK population; 65 million individuals worldwide

Question 3

how is epilepsy classified?

Answer 3

1. partial seizures
   - simple partial
   - complex partial
   - partial to secondary generalised
2. generalised
   - tonic clonic
   - tonic
   - clonic
   - myoclonic
   - absence

Question 4

describe the phases of tonic clonic seizures

Answer 4

premonition/aura before seizures
10-40 seconds of tonic phase; contraction of all muscles, rigid, epileptic cry, cyanotic,
2-3 minutes of clonic phase; rapid jerking movements, tongue biting and froth at mouth, tachycardia, urinary and faecal incontinence,
post-ictal phase: confusion and exhaustion

Question 5

what is status epilepticus? how is it treated?

Answer 5

5 or more minutes of continuous seizures or repetitive seizures without recovery - medical emergency
- treated with benzodiazepines (lorazepam)

Question 6

how is epilepsy diagnosed?

Answer 6

2 or more seizures and account of witness

Question 7

what structural changes take place in epilepsy?

Answer 7

hippocampal sclerosis: CA2 and CA3 regions
- sprouting of mossy fibres —> reverberant excitatory circuits
- abnormal neurogenesis - aberrant circuits
loss of chandelier cells - gabaergic neurons that inhibit pyramids cells

Question 8

describe the cellular mechanisms of epilepsy

Answer 8

imbalance of excitatory and inhibitory systems
- increased glutamatergic neurons
- decreased GABAergic signalling
channelopathy- altered excitability of neurones

Question 9

how can glial cells contribute to epilepsy?

Answer 9

glial cells are involved in clearance of glutamate by EAAT1 and EAAT2 channels
-gliosis can lead to increase extracellular glutamate and increased excitation of neurones

Question 10

what is the mechanism of action of phenytoin and carbamazepine?

Answer 10

bind to inner pore of sodium channels in their inactive state - prolong refactory period and reduce sustained and repetitive firing of neurones
- not used in absence seizures

Question 11

what is the mechanism of action of lamotrigine?

Answer 11

decrease sodium conductance, inhibit ca2+ channels and reduce calcium entry - reduced neurotransmitter release

Question 12

what is the mechanism of action of topiramate?

Answer 12

blocks sodiumchannels, inhibits AMPA/kainate glutamate receptors

Question 13

what are the mechanism of action of lacosamide and zonisamide?

Answer 13

sodium channel blockage

Question 14

what is the mechanism of action of ethosuximide?

Answer 14

blocks T-type CA2+ channels - absence seizures

Question 15

what are the mechanism of action of gabapentin and pregabalin?

Answer 15

bind to alpha-2-delta subunit of N-type calcium channels, reduced ca2+ influx, reduced neurotransmitter release

Question 16

what is the mechanism of action of levetiracetam?

Answer 16

binds to synaptic protein SV2A and modulate neurotransmitter release

Question 17

name some benzodiazepines and what is the mechanism of action?

Answer 17

clonazepam, diazepam, lorazepam
positive allosteric modulator of GABAa receptor (increases frequency of channel opening)–> CL- influx leads to hyper polarisation of neurones

Question 18

what is the mechanism of action of barbiturates? name some

Answer 18

positive allosteric modulator of GABAa receptor (prolongs channel opening and directly activates channel at high concentrations)
phenobarbitone
stiripentol

Question 19

which drug inhibits GAT-1?

Answer 19

tiagabine

Question 20

what is the mechanism of action of vigabatrin?

Answer 20

inhibits GABA trans amine to reduce GABA breakdown and increase its levels

Question 21

what is the mechanism of action of peramparel?

Answer 21

glutamte AMPA receptor antagonist

Question 22

what other non-pharmacological treatment options are available?

Answer 22

corpus callostomy
vagal nerve or deep brain stimulation
ketogenic diet

Question 23

quantify the risks of major congenital malformations due to anti epileptic drugs in pregnancy

Answer 23

2.2% - carbamazepine
3.2 % - lamotrigine
6.2% - sodium valproate
and 3.5% in untreated pregnant women