epilepsy Flashcards
classification of epilepsy, epileptogenesis and treatment of epilepsy (23 cards)
what are seizures?
abnormal paroxysmal changes in electrical activity of the brain causing large scale synchronous discharge or neuronal networks
wha tis the incidence of epilepsy in the Uk and worldwide?
1% of UK population; 65 million individuals worldwide
how is epilepsy classified?
- partial seizures
- simple partial
- complex partial
- partial to secondary generalised - generalised
- tonic clonic
- tonic
- clonic
- myoclonic
- absence
describe the phases of tonic clonic seizures
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
what is status epilepticus? how is it treated?
5 or more minutes of continuous seizures or repetitive seizures without recovery - medical emergency
- treated with benzodiazepines (lorazepam)
how is epilepsy diagnosed?
2 or more seizures and account of witness
what structural changes take place in epilepsy?
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
describe the cellular mechanisms of epilepsy
imbalance of excitatory and inhibitory systems
- increased glutamatergic neurons
- decreased GABAergic signalling
channelopathy- altered excitability of neurones
how can glial cells contribute to epilepsy?
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
what is the mechanism of action of phenytoin and carbamazepine?
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
what is the mechanism of action of lamotrigine?
decrease sodium conductance, inhibit ca2+ channels and reduce calcium entry - reduced neurotransmitter release
what is the mechanism of action of topiramate?
blocks sodiumchannels, inhibits AMPA/kainate glutamate receptors
what are the mechanism of action of lacosamide and zonisamide?
sodium channel blockage
what is the mechanism of action of ethosuximide?
blocks T-type CA2+ channels - absence seizures
what are the mechanism of action of gabapentin and pregabalin?
bind to alpha-2-delta subunit of N-type calcium channels, reduced ca2+ influx, reduced neurotransmitter release
what is the mechanism of action of levetiracetam?
binds to synaptic protein SV2A and modulate neurotransmitter release
name some benzodiazepines and what is the mechanism of action?
clonazepam, diazepam, lorazepam
positive allosteric modulator of GABAa receptor (increases frequency of channel opening)–> CL- influx leads to hyper polarisation of neurones
what is the mechanism of action of barbiturates? name some
positive allosteric modulator of GABAa receptor (prolongs channel opening and directly activates channel at high concentrations)
phenobarbitone
stiripentol
which drug inhibits GAT-1?
tiagabine
what is the mechanism of action of vigabatrin?
inhibits GABA trans amine to reduce GABA breakdown and increase its levels
what is the mechanism of action of peramparel?
glutamte AMPA receptor antagonist
what other non-pharmacological treatment options are available?
corpus callostomy
vagal nerve or deep brain stimulation
ketogenic diet
quantify the risks of major congenital malformations due to anti epileptic drugs in pregnancy
2.2% - carbamazepine
3.2 % - lamotrigine
6.2% - sodium valproate
and 3.5% in untreated pregnant women
