L16 - Epilepsy Flashcards Preview

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Flashcards in L16 - Epilepsy Deck (19):
1

Epilepsy definition:

Abnormal excessive electrical discharge from neurons.

An imbalance between excitation and inhibition in the brain

2

Loss of consciousness?

Often associated but not always produced.

3

Stats

0.5-1% population affected.
1 in 20 will have a seizure at some stage in their life.
Children often grow out of it.

4

Classification:
Focal

Focal = partial, only affects part of the brain.

Manifestation will depend on the part of the brain affected.

"focal aware seizure"
"focal impaired awareness seizure"
depending on level of consciousness

5

Causes of focal seizure

Cavernous angioma
Tumour
Hippocampal sclerosis
Focal cortical dysplasia (neurons never developed)
Subependymal grey matter heterotopia (neurons failed to migrate)

6

Classification:
Generalised

Affects extensive covering of both hemispheres.

Manifestations vary greatly

7

EEG

Record electrical activity from scalp.
50% of patients will show a normal EEG

Only used to classify seizure type.

Following a seizure there is large EEG suppression. This can be fatal

8

Excitatory transmission:
glutamatergic

calcium enters synaptic cleft and triggers exocytosis -- glutamate binds to AMPA and NMDA receptors
AMPA receptors open and partially depol to dislodge Mg2+ so NMDA receptors open
Ca2+ influx

9

Inhibitory transmission:
GABAergic

GABAA receptor binds 2 GABA

Opens Cl- channel = hyperpolarisation of neurons

10

Mutation in V-gated K+ channels:

Benign familial neonatal epilepsy

11

Mutation in V-gated Na+ channels:

• Severe myoclonic epilepsy of infancy (Dravet’s syndrome) – SCN1A
• Benign familial neonatal epilepsy – SCN2A
• Generalised epilepsy with febrile seizures – SCN1A, SCN1B, SCN2A
• Early onset absence seizures – SCN1B

12

Mutation in Ca2+ channels:

• Absence seizures due to abnormal activation of T-type Ca2+ channels in thalamus

13

Mutation in NAChR:

• Autosomal dominant nocturnal frontal lobe epilepsy

14

Mutation in GABAA receptor:

• Generalised epilepsy with febrile seizures

15

Drugs inducing seizures: (3)

Blockade of GABAa receptors e.g. picrotoxin
Activation of glutamate receptors (unblocks NMDA receptors by low Mg) e.g. kainite
Blockage of K channels e.g. 4-aminopyridine

16

Drugs to treat seizures (4)

Na+ channel blockers on presynaptic cell (prevent extended depolarisation)

Enhanced GABA neurotransmission (increased inhibition)

Ca2+ channels e.g. sodium valproate

Block glutamate transmission

17

Auto-antibody-induced epilepsy syndromes (3)

• Anti-voltage gated potassium channels
− E.g. focal impaired awareness seizures, limbic encephalitis, facio-brachial dystonic seizures, hyponatraemia

• Anti-NMDA receptor
− E.g. psychiatric features, dyskinesia, focal impaired awareness seizures

• Anti-GAD, anti-AMPA

18

Effects of seizures:
Kindling

Repetitive initial exposure to brain stimulation will cause seizures, and eventually the seizures will continue even without stimulation

19

Effects of seizures:
Rearrangement

Excitatory axons have collateral branches that sprout during neuronal death to fill dendritic regions.

Can form recurrent excitatory connections to alter normal balance between inhibition and excitation