cellular basis of epilepsy

Question 1

define epilepsy

Answer 1

a group of neurological diseases with enduring alterations in the brain resulting in abnormally increased predisposition to seizures
Subtypes:
-genetic (idiopathic/primary)
-structural/metabolic (symptomatic/secondary)
-unknown (cryptogenic)

Question 2

define seizures?

Answer 2

clinical manifestations resulting from paroxysmal excessive, synchronous, abnormal firing of patterns of neurons.

Question 3

lifetime prevalence of seizures?

Answer 3

9%.

Increased in underdeveloped countries and lower socioeconomic groups.

Question 4

explain Sudden unexplained death in epilepsy (SUDEP)

Answer 4

brain shutdown following neurological discharge of seizure suppresses respiration sufficiently –> causes secondary cardiac asystole

most at risk for patients experiencing tonic clonic seizures at night time

Question 5

what is an epileptic seizure

Answer 5

a transient occurrence of clinical signs/symptoms due to hyper-synchronous, oscillatory, excessive activity of populations of neurons in the brain

Question 6

by ILAE classification of seizures, what are partial (focal) seizures?

Answer 6

arise in a limited number of cortical neurons within one hemisphere …may eventually spread to other regions of the brain become generalized.
–>still classified as a focal seizure
(tend to be caused by an abnormal part of brain)

Question 7

by ILAE classification of seizures, what are generalized seizures?

Answer 7

appear to arise simultaneously in both hemispheres (usually genetic basis)

Question 8

seizures that arise from of a brain that is structurally and functionally normal are classified as?

Answer 8

Genetic (idiopathic) seizures

• usually respond well to medication
• arise in youth/teenage hood and often remit

Question 9

seizures arising from a structural/functional abnormality are classified as?

Answer 9

structural/metabolic (symptomatic)

• dont respond well to medication
• rarely remit

Question 10

What characterizes “unknown seizures”

Answer 10

different from idiopathic and structural. no genetic basis, nothing structurally wrong. responds well to meds, but generally don’t remit.

Most common form of seizures!

Question 11

what is the acute cause of epilepsy?

Answer 11

disturbance in balance between excitation and inhibition of cortical neurons and neuronal networks due to:

• neurogenesis
• aberrant sprouting
• alterations in extraneuronal environment
• alterations in synaptic transmission

Question 12

what is the role of the hippocampus in epilepsy?

Answer 12

• involved in learning and memory

- most sensitive structure to induce seizures in human and animal models

Question 13

explain epileptogenesis leading to seizures

Answer 13

seizures beget seizures.

neurobiological changes (axon sprouting, glial changes, loss of cells, ion channel expression) continue to the point where the circuit triggers into an oscillatory pattern until seizures start to occur—> seizures loop and accelerate process of neuronal remodelling

neurobiological changes follow first epileptic event or vice versa? mystery….

Question 14

describe the bimodal curve of epilepsy age of onset

Answer 14

first smaller peak at birth, next peak occuring after 60 yrs old

Question 15

what is the likely aetiology of epilepsy with onset in adulthood?

Answer 15

trauma, ischaemia, tumours, hemorrhage, degenerative disease

Question 16

what is the likely aetiology of epilepsy with onset in late childhood, early adulthood?

Answer 16

idiopathic/genetic

Question 17

what is the likely aetiology of epilepsy with onset in infancy/early childhood?

Answer 17

congenital/perinatal CNS insults

Question 18

T/F: majority of genetic-rooted epileptic diseases follow mendelian inheritance pattern

Answer 18

FALSE. Only 10%. Majority are ore complex, rooted in genes related to ligand-gated ion channels, non-ion channel genes, voltage-gate ion channels

Likely a genetic predisposition even on those epilepsy cases that arise following trauma.

Question 19

what is the most sensitive diagnostic technique in patients with focal epilepsy?

Answer 19

MRI can detect focal lesion in 70% of cases refractory to medical Tx.

Question 20

most common structural lesion identified on MRI in patients with medically refractory focal epilepsy?

Answer 20

Mesial temporal sclerosis (aka hippocampal sclerosis) (50%)

Then…Malformation of cortical development (20%), low grade tumours (15%), vascular malformations (10%),
post-traumatic encephalomalacia (5%)

Question 21

common clinical and imaging features of mesial temporal sclerosis

Answer 21

• medically refractory
• common in adults with partial epilepsy
• good outcomes with surgery

-MRI shows hippocampal atrophy, increased T2 signal, decreased T1 signal, loss of internal architecture

Question 22

what is a focal cortical dysplasia? MRI features?

Answer 22

focal regions of disturbed cortical development and architecture–>develops hyper excitable circuit–>epilepsy

• focal thickening of cerebral cortex
• blurring of gray/white matter interface
• increased t2-signal

Question 23

compare/contrast T2 vs T1-weighted imaging for MRI

Answer 23

T2-weighted imaging is good for highlighting pathology. Tissues filled with Water (ex. CSF) appear bright and tissues with fat (ex white matter) appear darker.

T1-weighted is the opposite. Good for demonstrating anatomy.

Question 24

which type of low-grade tumour is most common in patients presenting with partial epilepsy? Which site is most common for these?

Answer 24

Glioma (70%).

Most common in cortical over subcortical region. Esp in centro-tempro-parietal region

Question 25

best medical treatment for epilepsy?

Answer 25

Tegritol and Epilim

• ->decrease the freq/severite of seizures
• ->treat symptoms, not underlying condition

NB: tolerability issues. no anti-epileptogenic tx or disease modifying tx available.

Question 26

what type of epilepsy syndrome is ideal candidate for Sx?

Answer 26

Focal epilepsy where the focus of seizures can be localized to a specific region of the brain that could be resected without significant risks