Epilepsy Flashcards

1
Q

Define seizures.

A

abnormal, paroxysmal changes in electrical activity of the brain –> reflect large scale synchronous discharges of neuronal networks

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2
Q

Define epileptogenesis.

A

Process by which normal brain function progresses towards generation of abnormal electrical activity

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3
Q

How many people have epilepsy worldwide? What fraction of these are resistant to treatment?

A

65 million

1/3 are resistant to treatment

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4
Q

What is status epilpeticus? How is it treated?

A

form of epilepsy which is life-threatening (medical emergency)
Seizures last longer than 5 minutes, or have multiple seizures within 5 minutes without regain of consciousness

treated with IV lorazepam or diazepam

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5
Q

Describe the different stages of a tonic-clonic seizure.

A
  1. Premonition: vague sense that a seizure is imminent
  2. Pre-tonic-clonic phase: few myoclonic jerks/brief clonic seizures
  3. Tonic phase: tonic contraction of axial musculature (upward eye deviation, pupillary dilatation, tonic contraction of limbs, cyanosis, resp muscle contract + contraction of jaw)
  4. Clonic phase: jerks of increasing amplitude followed by relaxation
  5. Postictal phase: generalised lethargy, reduced muscle tone, headaches, muscle soreness
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6
Q

What structural changes of the brain occur in temporal lobe epilepsy?

A
Reorganisation of tissue (loss of cells in CA2/CA3 hippocampal areas)
Hippocampal sclerosis (loss of neurones, distortion + compression of layers, gliosis, different tract orientation)
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7
Q

Why is the loss of chandelier cells associated with epilepsy?

A

Chandelier cells are GABAergic interneurones

loss of these cells increases the risk of abnormal excitatory activity

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8
Q

List some secondary causes of epilepsy.

A
Craniotomy 
TBI
Stroke 
Aneurysm
Brain tumour 
CNS infections
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9
Q

Give examples of cellular mechanisms linked to the development of epilepsy.

A

Abnormal neuronal excitability (ion channels)
Reduced neuronal inhibition (GABA-dependent)
Increased neuronal excitation (glutamate-dependent)

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10
Q

Which major signalling pathways have been associated with the mechanism of epileptogenesis?

A

mTOR pathway

REST pathway

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11
Q

What mutations (in ion channels) have been associated with epilepsy?

A

SCN1B - increased in-flow of Na+, same outflow of K+

KCNQ2, KCNQ3 - normal Na+ inflow, more K+ outflow (benign familial neonatal convulsions)

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12
Q

Perampanel is an antagonist of which receptor?

A

(selective non-competitive antagonist) AMPA

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13
Q

Which drugs can be used to treat focal seizures?

A

Carbamazepine
Lamotrigine
Sodium valproate

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14
Q

Which drugs can be used to treat myoclonic seizures?

A

Sodium valproate
Clonazepam
Levetiracetam

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15
Q

Which drugs can be used to treat tonic-clonic seizures?

A

Carbamazepine
Lamotrigine
Sodium valproate

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16
Q

Which drugs can be used to treat absence seizures?

A

Ethosuximide

Sodium valproate

17
Q

Which anti-epileptic drug has zero order kinetics?

A

Phenytoin

18
Q

What ion channel does phenytoin act on?

A

Na+ channels

19
Q

What ion channel(s) does carbamazepine act on?

A

Na+ channels

20
Q

What ion channel(s) does sodium valproate act on?

A

Na+ channels

21
Q

What ion channel(s) does lamotrigine act on?

A

Na+ and Ca2+ channels

- also inhibits release of glutamate

22
Q

What is the MOA of topiramate?

A
  • Acts on Na+ channels
  • Augments GABAa
  • Inhibits glutamate AMPA/Kainate signalling
23
Q

What ion channel(s) does lacosamide act on?

A

Na+ channels

24
Q

What ion channel(s) does zonisamide act on?

A

Na+ and Ca2+ channels

25
Q

What is the MOA of ethosuximide?

A

Targets T-type Ca2+ channels

26
Q

What is the MOA of gabapentin?

A

Acts on alpha2delta subunit of Ca2+ channels

27
Q

What type of drug is clonazepam?

A

Benzodiazepine

28
Q

What type of drugs are phenobarbitone and stiripentol?

A

Barbiturate

29
Q

What is the MOA of levotiracetam?

A

Binds to synaptic protein SV2A

30
Q

What is the MOA of tiagabine?

A

Targets GAT-1 transporter (inhibits GABA reuptake)

31
Q

What is the MOA of vigabatrin?

A

Inhibits GABA transaminase and therefore inhibits the breakdown of GABA

32
Q

What receptor does felbamate act on?

A

NMDA receptor