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Year 2 C&M symposia > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

What is a seizure?

A

Excessive, hypersynchronous activity of neurons in the brain&raquo_space; convulsions, thought disturbances, twitching.

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2
Q

How are seizures classified?

A

Based on location within the cerebral cortex.

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3
Q

What are the 3 main types of seizure?

A
  • Generalised
  • Partial
  • Secondary generalised
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4
Q

What is a generalised seizure?

A

A seizure with initial activation neurons throughout both hemispheres.

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5
Q

What is a partial seizure?

A

A seizure with the initial activation of a limited number of neurons in a part of 1 hemisphere.

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6
Q

What is a secondary generalised seizure?

A

A partial seizure that later spreads to involve the majority of the 2 cerebral hemispheres.

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7
Q

What are the 3 subtypes of partial seizures?

A
  • Simple
  • Complex
  • With 2* generalisation
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8
Q

What is a simple partial seizure?

A

Partial seizure activity while the person is alert.

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9
Q

What is a complex partial seizure?

A

Partial seizure activity with change of awareness of the surroundings.

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10
Q

What are the 5 subtypes of generalised seizures?

A
  • Absence
  • Myoclonic
  • Tonic-clonic
  • Tonic
  • Atonic
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11
Q

What is characteristic of an absence generalised seizure?

A

Staring and blinking without falling.

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12
Q

What is characteristic of a myoclonic generalised seizure?

A

Jerking movements of the body.

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13
Q

What is characteristic of a tonic-clonic generalised seizure?

A

Stiffening, falling and jerking of the body.

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14
Q

What is characteristic of a tonic or atonic generalised seizure?

A

Falling heavily to the ground.

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15
Q

What is the manifestation of a partial seizure dependent on?

A

The site of origin in the brain.

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16
Q

How does a partial seizure originating in the anterior frontal lobe present?

A

Adversive seizures.

-eyes/head both turn to one side

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17
Q

How does a partial seizure originating in the posterior frontal lobe present?

A

Jacksonian seizure.

-tingling feeling in the hand or arm

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18
Q

How does a partial seizure originating in the parietal lobe present?

A

Tingling/jerking of leg, arm or face.

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19
Q

How does a partial seizure originating in the occipital lobe present?

A
  • Flashing lights
  • Spots
  • Vomiting
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20
Q

How does a partial seizure originating in the temporal lobe present?

A
  • Strange smell/taste
  • Altered behaviour
  • Deja vu
  • Chewing movements
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21
Q

What is used to record electrical activity in the brain?

A

Electroencephalogram (EEG).

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22
Q

What type of waves does and EEG produce?

A

Spike-wave discharges.

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23
Q

How can you tell the difference between a partial and generalised seizure from an EEG?

A
  • PARTIAL - excess activity only in electrodes from one hemisphere
  • GENERALISED - excess activity in both hemispheres
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24
Q

What is status epilepticus (SE)?

A

Life threatening condition where brain is in a state of persistent seizures.

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25
Q

What are the 2 definitions of status epilepticus?

A
  • More than 30 mins continuous seizure activity

- 2+ sequential seizures spanning 30 mins without full recovery between seizures

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26
Q

What does status epilepticus increase the risk of?

A

Future unprovoked seizures.

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27
Q

What is epilepsy?

A

Condition in which seizures recur (2+), usually spontaneously.
-a single seizure is not considered as epilepsy

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28
Q

What are the 2 basic mechanism of seizures?

A

Excitation and inhibition.

-either can cause too much neuronal activity

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29
Q

How does excitation of neurons occur?

A
  • IONIC (Na/Ca influx)

- NEUROTRANSMITTER (glutamate/aspartate release)

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30
Q

How does inhibition of neurons occur?

A
  • IONIC (Cl/K efflux)

- NEUROTRANSMITTER (GABA release)

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31
Q

What group of brain cells are responsible for allowing activity to spread in one direction?

A

Inhibitory interneurons.

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32
Q

What do inhibitory interneurons release?

A

GABA.

-neurotransmitter

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33
Q

What does GABA stand for?

A

Gamma-aminobutyric acid.

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34
Q

What are the 2 types of GABA recpetor?

A
  • GABAa receptors

- GABAb receptors

35
Q

What are GABAa receptors?

A

Ligand-gated chloride channel receptors.

36
Q

What are GABAb receptors?

A

G protein-coupled receptors.

37
Q

What structure do GABAa receptors have?

A

Pentameric structure.

-2a, 2b, 1g/o.

38
Q

What do the subunits of GABA receptors determine?

A

Intrinsic properties.

-e.g. affinity for diazepam

39
Q

Name 4 epilepsies caused by GABAa receptor mutations.

A
  • Childhood absence epilepsy
  • Febrile seizures
  • Juvenile myoclonic epilepsy
  • Dravet syndrome
40
Q

What can a GABRG2(Q390X) nonsense mutation in a GABAa receptor lead to?

A

DRAVET SYNDROME.

  • loss of 78 C-terminal AAs&raquo_space; more hydrophilic surface
  • receptor becomes cytosolic protein, not transmembrane
41
Q

What is Dravet syndrome also known as?

A

Severe myoclonic epilepsy in infancy.

-variety of seizures in 1st year of life

42
Q

Give an example of a drug that can be used on animals to induce status epilepticus.

A

PILOCARPINE.

  • proconconvulsant drug
  • non-selective muscarainic receptor agonist
43
Q

How does status epilepticus alter GABAa receptor composition in the mice tested?

A

Alters the abundance of subunits in dentate granule cells (hippocampus).
-Decreases a1, increases a4.

44
Q

What is a feature of a4 subunits in GABA receptors?

A

Desensitise rapidly.

-especially when with b3

45
Q

What effect does increasing a1 subunits have?

A
  • Increased latency time
  • Decreased rate of seizure development
  • Fewer spontaneous seizures
46
Q

What is the purpose of anti-epileptic drugs?

A

Decrease the frequency/severity of seizures.

-treat the symptoms of seizures, don’t cure

47
Q

What are the modes of action of anti-epileptic drugs? (3)

A
  • Suppress action potentials
  • Enhance GABA transmission
  • Suppress excitatory transmission
48
Q

How do anti-epileptic drugs suppress action potentials?

A
  • Sodium channel blocker

- Potassium channel opener

49
Q

How do anti-epileptic drugs enhance GABA transmission?

A
  • GABA uptake inhibitor

- GABA mimetics

50
Q

How do anti-epileptic drugs suppress excitatory transmission?

A

-Glutamate receptor antagonists

51
Q

What is the type of anti-epileptic drug dependent on?

A

The type of seizure.

52
Q

What is the most widely used anti-epileptic drug?

A

Valproic acid.

53
Q

What seizure types are treated by the following:

  • Carbamazepine
  • Phenytoin
  • Valproic acid
A
  • Partial simple
  • Partial complex
  • Generalised tonic clonic
54
Q

What seizure type is treated by the following:

  • Ethosuximide
  • Valproic acid
A

Absence seizure.

55
Q

What seizure types are treated by the following:

-Valproic acid

A
  • Atypical absence

- Atonic, myoclonic

56
Q

What seizure type is treated by the following:

  • Diazepam
  • Rectal
A

Febrile seizures.

-child with a fever

57
Q

What are the methods of enhancing GABA action?

A
  • Enhance action of GABAa receptors (barbiturates/benzodiazepines)
  • Inhibit GABA transaminase (vigabatrin)
  • Inhibit GABA uptake (tiagabine)
58
Q

Give an example of a barbiturate.

A

Phenobarbital.

59
Q

Give an example of a benzodiazepine.

A

Clonazepam.

60
Q

How do benzodiazepines work?

A

Increase GABA affinity&raquo_space; suppresses seizures.

  • Increase CL current
  • Raise AP
  • Strengthens surround inhibition
61
Q

What are possible side effect of benzodiazepines?

A
  • Sedation

- Respiratory depression (IV)

62
Q

What is diazepam (valium) used to treat?

A

Status epilepticus.

-IV

63
Q

Which anti-epileptic drugs act by inhibiting Na+ channels? (3)

A
  • Phenytoin
  • Carbamazepine
  • Lamotigine
64
Q

What is the mechanism of action of phenytoin?

A

Binds to inactivated Na+ channels&raquo_space; slows down repolarisation.

65
Q

What anti-epileptic drugs have mixed actions?

A
  • Gabapentin
  • Valproate
  • Levetiracetam
66
Q

What is meant by mixed action?

A

Combination of the following:

  • Enchance GABA transmission
  • Inhibit Na+ channels
  • Inhibit NT release
67
Q

Which drug is not chemically related to other anti-epileptics?

A

Valproate.

68
Q

How is valproate unusual?

A

Acts against both tonic-clonic and absence seizures.

69
Q

What are the mechanisms of valproate? (3)

A
  • Inhibits Na+ channels
  • Decreases GABA turnover
  • Blocks neurotransmitter release
70
Q

What is the problem with pregnancy?

A

Drugs may harm baby, but seizures may also cause harm.

71
Q

What is recommended during pregnancy?

A
  • Folic acid

- Monotherapy (rather than drug combination)

72
Q

Which drugs are absolutely contraindicated during pregnancy? (AVOID)

A
  • Phenytoin

- Valproic acid

73
Q

What causes foetal hydantoin syndrome?

A

Mother taking phenytoin during pregnancy (30%).

74
Q

What are the symptoms of foetal hydantoin syndrome? (4)

A
  • Growth restriction and microcephaly
  • Dysmorphic craniofacial features
  • Limb defects
  • Developmental defect
75
Q

What causes foetal valproate syndrome?

A

Mother taking valproate during pregnancy (6-9%).

76
Q

What proportion of epileptics are seizure free with one drug?

A

70%.

77
Q

What proportion of epileptics are seizure free with 2+ drugs?

A

5-10%.

78
Q

What proportion of epileptics still have seizures with anti-epileptic drugs?

A

20%.

-Refractory epilepsy

79
Q

What is the mechanism of optogenetics?

A

Halorhodopsins (Cl- channels) are activated by yellow light&raquo_space; open and allow Cl- to enter.

80
Q

What can optogenetics do?

A

Suppress seizures with epilepsy.

81
Q

What could optogenetics be used to control?

A

Epilepsia partialis.

82
Q

What is epilepsia partialis continua?

A

Rare brain disorder&raquo_space; recurrent motor epileptic seizures that are focal (hands and face).

83
Q

What normally causes epilepsia partialis?

A
  • Large, acute brain lesions due to strokes

- Focal cortical inflammatory processes (children)

Year 2 C&M symposia (11 decks)

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