week 5- Epilepsy Pathophysiology

Question 1

what are seizures? different types? symptoms of seizure affects what?

Answer 1

• Seizures are due to an unregulated neuronal discharge in the brain• Can remain in one place
– Focal seizures
– Localised structural abnormality (lesion)
• Waves of activity spread from the focal centre
– Generalised seizures
– Chain reaction of depolarizations and synaptic activity
• Manifestation of the seizure is dependant on the area of the brain
affected
– Eg. motor cortex; somatosensory cortex; hypothalamus; reticular system– Focal v generalised
– Aura

Question 2

what causes epilepsy?

Answer 2

• The precise underlying neuronal abnormality or neurochemical basis is
not well understood
• Arises as a result of imbalance of inhibitory (mainly via GABA) and
excitatory (mainly via glutamate) activity.
– Decreased inhibitory activity
• GABAA
antagonists cause convulsions
– Increased excitatory activity
• Can cause excitotoxicity

Question 3

how does a seizure in epilepsy actually start?

Answer 3

• Neurons in the focal area have been shown to display sudden
depolarizations (30mV for few second)
– Paroxysmal depolarization shift (PDS)
– Burst of action potentials
– NMDA receptors?
• Synchronous activity in networks of neurons
• Hyperexcitability in regions surrounding the focal area
• Absence seizures
– Oscillatory feedback between cortical and thalamic neurons
– Involve activity of T-type voltage-gated Ca2+ channels

Question 4

what are the genetics of epilepsy?

Answer 4

• Genetic component
• Family history
• ̴ 2% of cases due to specific mutations
• Many mutations identified
– ion channels
– GPCRs
– enzymes
– neurotransmitters
• >150 spontaneous mutations to the voltage-gated Na+
 channel have
been associated with epilepsy