45 - Cellular Basis of Epilepsy

Question 1

Lifetime prevalence of epileptic seizure globally

Answer 1

9%

Question 2

Groups in which epilepsy is more common

Answer 2

Under-developed countries, lower socioeconomic groups

Question 3

Standardised mortality rate of epileptics versus general population

Answer 3

~3x (risk is higher in those with more poorly-controlled epilepsy)

Question 4

What is an epileptic seizure?

Answer 4

A transient occurrence of clinical signs and/or symptoms due to excessive and hyper-synchronous activity of populations of neurons in the brain.

Question 5

Broad type of neuronal firing in epilepsy

Answer 5

Discrete group of neurons begin firing synchronously, innervate another group of neurons which then also begin firing synchronously. These innervate first set of neurons, and this forms a loop of oscillatory firing.

Question 6

Secondary seizure

Answer 6

Where synchronised firing from the initial epileptic focus spreads to other regions.

Question 7

What is epilepsy?

Answer 7

A group of neurological diseases with enduring alterations in the brain resulting in abnormally increased predisposition to seizures.

Having a single seizure does not equal epilepsy.

Question 8

Proportion of epileptics who have a genetic basis

Answer 8

~30% (also called idiopathic or primary)

Question 9

Things that can cause structural/metabolic epilepsy

Answer 9

Brain tumour, encephalitis (symptomatic or secondary epilepsy)

Question 10

Name for epilepsy of unknown aetiology

Answer 10

Cryptogenic (EG meso-temporal sclerosis - a type of hippocampal sclerosis)

Question 11

What is a seizure to epilepsy?

Answer 11

A symptom

Question 12

ILAE classifications of seizures
1
2
3

Answer 12

1) Focal/partial
2) Generalised
3) Unclassifiable

Question 13

Focal/partial seizures

Answer 13

Arise in a limited number of cortical neuron within one hemisphere.
Can spread to involve the whole brain.

Question 14

Generalised seizures

Answer 14

Appear to arise simultaneously in both hemispheres

much more likely to be a genetic basis

Question 15

ILAE classifications of epilepsies
1
2
3

Answer 15

1) Genetic (idiopathic)
2) Structural/metabolic (symptomatic)
3) Unknown

Question 16

Genetic (idiopathic) epilepsy
1
2
3
4

Answer 16

Underlying brain is structurally and functionally normal.
–Usually onset during childhood/teenage and may remit.
–Usually respond well to medication.
–Likely have a genetic basis - ion channels

Question 17

Structural/metabolic epilepsy
1
2
3

Answer 17

Seizures result from some identifiable structural/functional brain abnormality.
–Uncommonly remit, and often incompletely controlled with medication.
- Can sometimes be treated with surgery

Question 18

Complex partial seizures

Answer 18

Arise in temporal limbic areas.

Lead to altered conscious state.

Question 19

Current broad concept of what leads to epilepsy
1
2
3

Answer 19

• Disturbance in the balance between inhibition and excitation of cortical neurones and neuronal networks.
– either increases or decreases in neuronal inhibition or excitation.
• Result in neuronal networks that fire in an uncontrolled, hypersynchronous, self sustained manner.
• May result from a wide variety of causes:
– Genetic, congenital/developmental, traumatic, infectious,
metabolic, drugs etc.

Question 20

Brain mechanics that can be altered, leading to epilepsy 
1
2
3
4

Answer 20

•Alterations in neuronal network components
– Loss of inhibitory neurons
– Gain of excitatory neurons
(neurogenesis)
– Aberrant sprouting (after a brain injury, axons can get disconnected, and this can go wrong)

• Alterations in intrinsic neuronal cellular excitability
• Alterations synaptic transmission
• Alterations in the extra-neuronal environment (EG astrocytes not taking up glutamate properly)

Question 21

Location of the hippocampus

Answer 21

Medial temporal lobe

Question 22

Most-sensitive structure to inducing seizure activity

Answer 22

Hippocampus

Question 23

Epileptic remodelling in the hippocampus
1
2
3

Answer 23

Fewer neurons in the dentate gyrus.
Hypertrophy of glial cells.
Increased connections to other hippocampal areas

Question 24

4 main subregions of hippocampus

Answer 24

CA1, CA2, CA3, dentate gyrus

Question 25

Effect of a seizure on probability of subsequent seizures

Answer 25

A seizure (from drugs, fever, etc) makes a subsequent seizure more likely

Question 26

Peaks for onset of epilepsy (age)

Answer 26

Smaller peak in childhood (drops after 20)

Largest peak is after 60 - 80 years old

Question 27

Aetiology of early-childhood-onset epilepsy

Answer 27

Congenital or perinatal CNS insults (EG infection)

Question 28

Aetiology of late childhood, early adulthood-onset epilepsy

Answer 28

Idiopathic or genetic

Question 29

Aetiology of adult-onset epilepsy

Answer 29

Mostly symptomatic (i.e. trauma, ischaemia, tumours, haemorrhage, degenerative diseases).

Question 30

Proportion of genetic epilepsies that are of a Mendelian monogenetic inheritance pattern

Answer 30

5-10%

affecting most important genes for proteins in the brain can lead to altered neuronal function, therefore epilepsy

Question 31

Most-common type of inheritance of genetic epilepsies

Answer 31

Complex genetic inheritance.

Combination of genetic influences and environmental factors.

Question 32

Most useful imaging modality for epilepsy

Answer 32

High resolution MRI

Question 33

Five major groups of structural pathologies that can lead to epilepsy

Answer 33

–Medial temporal sclerosis 198 (49.1%)
–Malformations of cortical development 82 (20.3%)
–Low grade tumours 58 (14.4%)
–Vascular Malformations 39 (9.7%)
–Encephalomalacia (post-traumatic) 20 (5.0%)

Question 34

Medial temporal sclerosis
1
2
3

Answer 34

Most common pathology in adults with partial epilepsy.
Resistant to drugs.
MRI features:
– Hippocampal atrophy, increased T2 signal, decreased T1
signal, loss of internal architecture

Question 35

Focal cortical dysplasia

Answer 35

Focal regions of disturbed cortical development adn architecture,
Uncertain aetiology

Question 36

MRI features of focal cortical dysplasia 
1
2
3
4

Answer 36

–Focal thickening of the cerebral cortex.
–Blurring of the grey/white interface.
–gyral abnormalities e.g. polymicrogyria, macrogyria.
–May be associated with a region of increased T2 signal

Question 37

Periventricular nodular heterotopia

Answer 37

A generalised malformation due to abnormal neuronal migration.
–Nodular masses of grey matter diffusely lining the ventricular walls.
•Bilateral or focal
–Cortex and neurological function usually normal.
–Can be inherited (bilateral)
•X-linked dominant form (FLNA gene).
•Autosomal recessive form (ARFGEF2)

Question 38

Most common low grade tumour contributing to epilepsy

Answer 38

Gliomas

Question 39

Cavernoma

Answer 39

A tangled mass of tightly arranged abnormal vessels made of common hypocellular walls.