Epilepsy Flashcards
Define seizures.
abnormal, paroxysmal changes in electrical activity of the brain –> reflect large scale synchronous discharges of neuronal networks
Define epileptogenesis.
Process by which normal brain function progresses towards generation of abnormal electrical activity
How many people have epilepsy worldwide? What fraction of these are resistant to treatment?
65 million
1/3 are resistant to treatment
What is status epilpeticus? How is it treated?
form of epilepsy which is life-threatening (medical emergency)
Seizures last longer than 5 minutes, or have multiple seizures within 5 minutes without regain of consciousness
treated with IV lorazepam or diazepam
Describe the different stages of a tonic-clonic seizure.
- Premonition: vague sense that a seizure is imminent
- Pre-tonic-clonic phase: few myoclonic jerks/brief clonic seizures
- Tonic phase: tonic contraction of axial musculature (upward eye deviation, pupillary dilatation, tonic contraction of limbs, cyanosis, resp muscle contract + contraction of jaw)
- Clonic phase: jerks of increasing amplitude followed by relaxation
- Postictal phase: generalised lethargy, reduced muscle tone, headaches, muscle soreness
What structural changes of the brain occur in temporal lobe epilepsy?
Reorganisation of tissue (loss of cells in CA2/CA3 hippocampal areas) Hippocampal sclerosis (loss of neurones, distortion + compression of layers, gliosis, different tract orientation)
Why is the loss of chandelier cells associated with epilepsy?
Chandelier cells are GABAergic interneurones
loss of these cells increases the risk of abnormal excitatory activity
List some secondary causes of epilepsy.
Craniotomy TBI Stroke Aneurysm Brain tumour CNS infections
Give examples of cellular mechanisms linked to the development of epilepsy.
Abnormal neuronal excitability (ion channels)
Reduced neuronal inhibition (GABA-dependent)
Increased neuronal excitation (glutamate-dependent)
Which major signalling pathways have been associated with the mechanism of epileptogenesis?
mTOR pathway
REST pathway
What mutations (in ion channels) have been associated with epilepsy?
SCN1B - increased in-flow of Na+, same outflow of K+
KCNQ2, KCNQ3 - normal Na+ inflow, more K+ outflow (benign familial neonatal convulsions)
Perampanel is an antagonist of which receptor?
(selective non-competitive antagonist) AMPA
Which drugs can be used to treat focal seizures?
Carbamazepine
Lamotrigine
Sodium valproate
Which drugs can be used to treat myoclonic seizures?
Sodium valproate
Clonazepam
Levetiracetam
Which drugs can be used to treat tonic-clonic seizures?
Carbamazepine
Lamotrigine
Sodium valproate
Which drugs can be used to treat absence seizures?
Ethosuximide
Sodium valproate
Which anti-epileptic drug has zero order kinetics?
Phenytoin
What ion channel does phenytoin act on?
Na+ channels
What ion channel(s) does carbamazepine act on?
Na+ channels
What ion channel(s) does sodium valproate act on?
Na+ channels
What ion channel(s) does lamotrigine act on?
Na+ and Ca2+ channels
- also inhibits release of glutamate
What is the MOA of topiramate?
- Acts on Na+ channels
- Augments GABAa
- Inhibits glutamate AMPA/Kainate signalling
What ion channel(s) does lacosamide act on?
Na+ channels
What ion channel(s) does zonisamide act on?
Na+ and Ca2+ channels
What is the MOA of ethosuximide?
Targets T-type Ca2+ channels
What is the MOA of gabapentin?
Acts on alpha2delta subunit of Ca2+ channels
What type of drug is clonazepam?
Benzodiazepine
What type of drugs are phenobarbitone and stiripentol?
Barbiturate
What is the MOA of levotiracetam?
Binds to synaptic protein SV2A
What is the MOA of tiagabine?
Targets GAT-1 transporter (inhibits GABA reuptake)
What is the MOA of vigabatrin?
Inhibits GABA transaminase and therefore inhibits the breakdown of GABA
What receptor does felbamate act on?
NMDA receptor
