Epilepsy Extra Information

Question 1

What are seizures and epilepsy the result of?

Answer 1

An imbalance between excitation and inhibition within certain regions of the CNS.

Question 2

What are 6 aetiologic categories for epilepsy?

Answer 2

Genetic
Structural
Metabolic
Infectious
Immune
Unknown

Question 3

What is a structural aetiology?

Answer 3

Abnormal findings on neuroimaging, inferred to cause the patient’s seizures with concordant electro clinical assessments and/or clinical findings.
May be acquired or genetic.

Question 4

What is an acquired structural aetiology?

Answer 4

Acquired from causes that include hypoxic-ischaemia, encephalopathy, stroke, trauma and infection.

Question 5

What is a genetic structural aetiology?

Answer 5

Belong to a broad range of disorders ranging from single-nucleotide mutations such as missense, framshift and nonsense mutations, copy number variations by de novo or inherited DNA deletion or duplication to chromosomal copy numbers abnormalities.

Question 6

When is an epilepsy considered of genetic origin?

Answer 6

If there is a known or presumed specific disease-causing variant in a gene or copy number variant where seizures is the common phenotype.

Question 7

Study by Wang showed how many genes are associated with epilepsy?

Answer 7

977

Question 8

What 4 categories can the epilepsy genes be categorised into?

Answer 8

Categorised according to their phenotype.
Epilepsy genes - genes that cause epilepsies or syndromes with epilepsy as the core symptom.
Neurodevelopment associated epilepsy genes - genes associated with both brain development malformations and epilepsy.
Epilepsy-related genes - genes associated with both physical or other systemic abnormalities and epilepsy or seizures.
Putatively associated with epilepsy - genes that require further variation.

Question 9

What 3 general categories can epilepsy be put into?

Answer 9

Genetic generalised epilepsy (GGE)
Focal epilepsy (FE)
Epileptic encephalopathy

Question 10

When do GGE syndromes tend to start?

Answer 10

In childhood and are characterised by generalised seizures that involve both sides of the brain.

Question 11

In GGE, what 3 large recurrent deletions have been found on what chromosomes?

Answer 11

15q13.3
16p13.11
15q11.2
These three deletions also have an association with autism and schizophrenia.

Question 12

Describe epileptic encephalopathy.

Answer 12

Severe, early onset conditions characterised by refractory seizures, developmental delay or regression associated with ongoing epileptic activity and generally has a poor prognosis.
To this class of epilepsies belongs to a group of disorders resulting from mutations in genes encoding ion channels.

Question 13

What genes encode the ion channels implicated in benign familial neonatal seizures, benign familial infantile epilepsy and Dravet syndrome?

Answer 13

KCNQ2
SCN2A
SCN1A

Question 14

What do KCNQ2 genes code for, what does it do under normal conditions and what does loss of function mean?

Answer 14

Voltage-gated potassium channels that produce the M current which under normal conditions induces a hyper polarising shift in membrane voltage.
Loss of its function increases neuronal hyperexcitability leading to spontaneous seizure activity as seen in KO mice.

Question 15

What does the SCN1A gene code for and what does its dysfunction lead too?

Answer 15

Encodes for NaV1.1 - one of nine alpha subtypes of VGSC expressed in GABAergic neurons.
Dysfunction = reduced excitability of GABAergic neurons resulting in brain hyperexcitability in patients with Dravet syndrome.

Question 16

What does an infectious aetiology relate too?

Answer 16

A patients with epilepsy not a patients with seizures due to an acute infection of the CNS.
In this context seizures are induced by brain alterations in response to neurotropic infectious agents that attack the CNS.

Question 17

What is the concept of metabolic aetiology of epilepsy?

Answer 17

Results directly from a known or presumed metabolic derangement in which seizures are a core symptom of the disorder.

Question 18

What is immune aetiology?

Answer 18

Can be suspected in patients with epilepsy of unknown origin when they are seropositive for neural specific antibodies and have evidence of autoimmune-mediated CNS inflammation.

Question 19

How are immune responses implicated in seizure induction and the development of epilepsy?

Answer 19

Both innate and adaptive immune responses are activated in the epileptic brain by resident immune cells and their secreted mediators as well as leukocytes being infiltrated from the periphery.
Peripheral inflammation potentiates epileptic discharges via changes in ion and glutamate homeostasis and also via migration of pro-inflammatory molecules to the BBB.