Mechanism of epilepsy generation

Question 1

Epilepsy and epileptic seizures

Answer 1

Epilepsy - tendency to have recurrent epileptic seizures
Epileptic seizures - abnormal synchronous firing of a large no of cortical neurons => symptoms

1% of population affected
Important cause of injury, mortality, unplanned hospital admissions
Linked to poor outcomes for education, employment, MH and stigma

Question 2

Why do they happen

Answer 2

Brain needs to be very close to hyperexitable state because brain needs to change dynamics very quickly

Normally:
Feedforward/feedback inhibition
Neurons tend not to fire repeatedly for long times
Patterns of long range connections

Question 3

Hyperexcitable neuronal firing

Answer 3

Paroxysmal burst firing of neurons at seizure focus at a neuronal level
-multiple firing of neuronal activity => repeated AP firing

Question 4

TYpes of epilepsy

Answer 4

Generalised
-absence - mainly in small children (issue starts in focal region and spread to thalamus and cortex

Focal
-temporal lobe epilepsy - abnormal hippocampus (issue starts in hippocampus and affect many brain regions

Question 5

Etiology

Answer 5

Genetic variation - many genes implicated

Environmental exposure

• traumatic brain injury
• brain infection
• alcohol/drug misuse

Gene-environment interaction

Unknown

Question 6

Management

Answer 6

Antiepileptic drugs - act at NTr/ion channels

Brain surgery - remove hyperexcitable seizure focus/sever connections in abnormal large scale networks

Neuromodulation

• Deep Brain Stimulation
• Vagus nerve stimulation
• both alter properties of large scale brain networks

Question 7

Antiepileptic drugs

Answer 7

REDUCE EXCITATION/INCREASE INHIBITION

Generally act on GABA
VGKC opening - retigabine
VGNC closed - phenytoin, carbamazepine, lacosamide, lamotrigine
VGCC closed - gabapentin