Epilepsy Flashcards
What is epilepsy?
A neurological disorder representing a brain state supporting recurrent unprovoked seizures
What are seizures?
Abnormal, paroxysmal changes in electrical activity of the brain
- reflect large synchronous discharges of neuronal networks
What is elieptogenesis?
Where normal brain function generates abnormal electrical activity
What is a focal onset epileptic seizure?
Initially affects one hemisphere of the brain
What is a generalised onset epileptic seizure?
seizures affecting both sides of the brain
What are the features of a tonic-clonic seizure?
- premonition
- pre-tonic-clonic phase (myoclonic jerks)
- tonic phase
- clonic phase
- postictal period (lethargy, decreased muscle tone, headaches, muscle soreness)
What does the tonic phase consist of?
Tonic contraction of axial musculature
- upward eye deviation and pupillary diltation
- tonic limb contraction
- cyanosis
- respiratory muscle contraction
- epileptic cry (tonic contraction of jaw muscles)
What is clonic?
Arms and legs jerk rapidly and rhythmically followed by relaxation
What are myoclonic jerks?
Brief shock like jerks of a muscle group
person usually awake
What is atonic jerk?
Muscles suddenly become limp
How does a clinical history help you diagnose epilepsy?
- occurrence of 2 or more seizures
- account of witnesses is essential
What are the main structural changes in epilepsy?
- reorganisation of tissue in temporal lobe epilepsy
- sprouting of mossy fibres of granule cells (reverbant excitatory circuits)
- neurogenesis (new neuron formation changes circuits)
- loss of chandelier cells (increases abnormal excitatory activity)
How does reorganisation of tissue in temporal lobe epilepsy manifest?
- loss of CA2 and CA3 hippocampal areas
- sclerotic hippocampus
What are chandelier cells?
Special population of interneurons which are GABAergic cells
- control activity of cortical pyramidal cells by synapsing on axons
Which conditions have a high risk of developing epilepsy?
- craniotomy
- traumatic brain injury
- stroke
- aneurysm
- brain tumour
- CNS infection
Which cellular mechanisms are linked to epilepsy development?
- abnormal neuronal excitability (ion channels)
- decreased neuronal inhibition (GABA-dependent)
- increased neuronal excitation (glutamate dependent)
- glial abnormalities
What do glial cells do to glutamate?
Help transport/clear it through glutamate transporters -EAAT1 and 2
What is a channelopathy?
- genetic cause of epilepsy
- deficiency of sodium/potassium/calcium/GABA channels
- imbalance in influx/efflux = paroxysmal electrical activity
Which drugs work on the sodium channels?
- phenytoin
- carbamazepine
- sodium valproate
- lamotrigine
- topiramate
- lacrosamide
What is the mechanism of action of phenytoin?
- stabilises inactivated state of channels
- zero order: constant amount of drug eliminated per time units (saturation easy but toxicity risk)
- teratogenic
- liver enzyme induction
- DO NOT USE IN ABSENCE SEIZURES
What is the mechanism of carbamazepine?
- stabilises inactivated state of channels
- liver enzyme induction
- DO NOT USE IN ABSENCE SEIZURES
When is sodium valproate used?
In all types of seizures
How does lamotrigine work?
- presynaptic inhibition of glutamate release
How does topiramate work?
Increases GABA transmission and inhibits glutamate (AMPA)
How does lacrosamide work?
Binds to inactivated state of channels
Which drugs are benzodiazepines?
Clonazepam - sedation
What do benzodiazepines do?
- positive allosteric modulators
- enhance functioning of GABA receptors
Which drugs act on barbiturates? (GABA receptor)
Phenobarbitone - liver enzyme induction
Which drugs acts on calcium channels?
Zonisamide
Ethosuximide
Gabapentin (Pregabalin)
How does zonisamide work?
Blocks calcium channels
How does ethosuximide work?
- used in absence seizures
- blocks T-type calcium channels
How does gabapentin work?
Blocks alpha2delta2 subunit of calcium channels
- pregabalin increases GABA levels
Which drugs affect neurotransmitter release?
Levetiracetam - bonds to synaptic proteins SV2a which modulates neurotransmitter release
Which drugs affect neurotransmitter uptake?
Tiagabine - inhibits GAT-1 transporter for GABA (involved in removing GABA from synaptic cleft)
Which drugs affect neurotransmitter synthesis?
Vigabatrin - inhibits GABA transaminase, protects GABA
Which drugs affect neurotransmitter receptors?
Perampanel - selective non-competitive antagonist of AMPA receptors
Felbamate - NDMA receptors
What surgery options are there?
Love resection
Corpus callostomy
Functional hemispherectomy
What other treatment methods are there?
Vagal nerve stimulation
Deep brain stimulation
Ketogenic diet
What is status epilepticus?
medical emergency
- treatment of lorazepam and diazepam
