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)
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Introduction32
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Basal Ganglia46
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Pharmacology of Movement28
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Motor Systems72
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Anatomy Practical 197
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Cerebellum35
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Anatomy Practical 222
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Anatomy & Physiology of Pain55
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Headache and Migraine26
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Blood Supply to the Brain46
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Head Injury24
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Vestibular System38
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Anatomy Practical 348
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Epilepsy39
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Pharmacology of Pain53
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Antidepressants33
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Addiction18
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Drug Dependency66
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Deep Brain Stimulation27
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Structure & Function of the Limbic System55
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Dementia31
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Memory & Amnesia22
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Schizophrenia33
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Persistent Vegetative State45
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Anxiety & Sleep47
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Sleep and consciousness40
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DRUGS18
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Stroke22
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CAL24
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TRACTS27
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Multiple Sclerosis21
