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syposium control and movement > Epilespy > Flashcards

Epilespy Flashcards

1
Q

What is a seizures?

A

The clinical manifestation of an abnormally excessive and hypersynchronous activity of neurones located predominantly in the cerebral cortex

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2
Q

Why do epileptic seizures manifest in different ways?

A

It depends on their site of origion and subsequent spread.

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3
Q

How does epileptic seuizures occur?

A

The cortical discharges can be transmitted to the muscles, causing twitches or convulsions

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4
Q

What are the 3 classification of seizures?

A

Generalized (
Partial
Secondary generalized

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5
Q

What is the generalized classification of seizures?

A

With initial activation of neurones throughout both hemispheres

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6
Q

What is the partial classification of seizures?

A

With the initial activation of a limited number of neurones in a part of 1 hemisphere

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7
Q

What is secondary generalized seizures?

A

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

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8
Q

What is a tonic-clonic seizure?

A

Typical type with stiffening, fallng and jerking of the body –> example of generalized seizure

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9
Q

What occurs with a complex seizure?

A

Type of partial seizure were there is seizure activity with change in awareness of surroudnings

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10
Q

What is the manifestation of partial seizuredependent on?

A

Depends on the site of origion

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11
Q

What is electroencephalogram?

A

Electroencephalography (EEG) uses scalp electrodes to record the electrical activity along the scalp produced by the firing of neurones within the brain.

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12
Q

What is status epolepticus?

A

Status epilepticus (SE) is a life-threatening condition in which the brain is in a state of persistent seizure

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13
Q

What has to occur for a person to be defined as having status epilepticus?

A

More than 30 mins continuous seizure activity OR

Two or more sequential seizures spanning this period without full recovery between seizures

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14
Q

What is the complication of status epilepticus?

A

SE is a medical emergency because the longer a seizure lasts, the less likely it is to stop on its own

SE confers greater risk for future unprovoked seizures

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15
Q

What is the treatment for status epilepticus?

A

Injection of GABAa receptor agonist

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16
Q

What is a definition of epilepsy?

A

Epilepsy can then be defined as a condition in which seizures recur, usually spontaneously; a single seizure episode is not considered as epilepsy, i.e. 2 or more unprovoked seizures

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17
Q

What caues to much neuronal activity and therefore seizures?

A

Excitation –> to much
Ionic—Na+, Ca2+ influx
Neurotransmitter—glutamate, aspartate release

Or

Inhibition (too little)
Ionic—CI- influx, K+ efflux
Neurotransmitter—GABA release

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18
Q

What is the normal status quo of the brain?

A

Normally in the brain very small numbers of brain cells are active at any given time –> tightly focused the activity and not allowed to spread.

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19
Q

What allows brain activity to spread in one direction but not to spread out sideways?

A

A group of brain cells called inhibitory interneurones

They release the inhibitory neurotransmitter GABA

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20
Q

What percentage of neurones are interneurones?

A

Just 10–20%

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21
Q

What happens in the absence of inhibitory nternurones?

A

The initially localized hyperexcitability spreads into surrounding neuronal networks after involving more and more neurones, cause a clinically visible seizure

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22
Q

GABA is a major inhibitory neurotransmitter found in 30% of syanapses and acts on two different receptors. What are they and which one is targete dby epileptic drugs?

A

GABAa–> affects ligand gated chloride channel receptor

GABAb –> G protein coupled receptor

Epileptic drugs act on to GABAa to prevent the brain waves and seizures

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23
Q

What are the normal 5 subunits of GABAa receptor?

A

Pentameric: typical in vivo subunit composition is two α, two β and one γ or δ subunit

24
Q

What determines the intrinisc properties of the GABAa channels? What is the implications of this?

A

It is effected by the GABAa subunit composition –> which effects the ability of different drugs on the receptor

25
Q

What are the different types of known epilepsies causes by GABAa receptor mutation?

A

CAE (childhood absence epilepsy)
FS (pure febrile seizures)
GEFS+ (generalized epilepsy with febrile seizures plus)
JME (juvenile myoclonic epilepsy)
DS (Dravet syndrome – also know as SMEI (severe myoclonic epilepsy in infancy))

26
Q

What is the characteristic of Dravet syndrome?

A

Patients experience frequent seizures, poor seizure control, and developmental delays. -

27
Q

What is the action of antiepileptic drugs?

A

A drug which decreases the frequency and/or severity of seizures in people with epilepsy

Treats the symptom of seizures, not the underlying epileptic condition

Correct classification of seizures leads to correct Anti epileptic drug selection

28
Q

What are the mode of actions of antiepileptic drugs?

A

1)Suppress action potential:
Sodium channel blocker or modulator
Potassium channel opener

  1. Enhance GABA transmission
    GABA uptake inhibitor
    GABA mimetics
  2. Suppression of excitatory transmission
    Glutamate receptor antagonist
29
Q

What are the different actions that a anticonvulsant can have?

A

Enhancement of GABAergic transmission

Inhibition of Na+ channels

Mixed actions–> Combination of some or all of the above and also inhibiting neurotransmitter release

30
Q

What is the choice of drug for partial or partial complex seizure?

A

Carbamazepine
Phenytoin
Valproic Acid

31
Q

What is the choice of drug for generalised tonic clonic seizure?

A

Carbamazepine
Phenytoin
Valproic Acid

32
Q

What is the choice of drug for absence seizure?

A

Ethosuximide

Valproic Acid

33
Q

What is the choice of drug for Atypical absence
Atonic, myoclonic
seizure?

A

Valproic Acid

34
Q

What is the choice of drug for febrile seizures?

A

Diazepam and rectal

35
Q

What are the various methods of enhancing GABA action?

A

Enhance action of GABAA receptors with barbiturates e.g. phenobarbital

Enhance action of GABAA receptors with benzodiazepines e.g. clonazepam

Inhibit GABA transaminase - vigabatrin

Inhibit GABA uptake – tiagabine

36
Q

Give examples of different types of Benzodiazepines and there action?

A

Clonazepam
Effective in generalized tonic-clonic, absence and partial seizures

Clorazepate
Effective against partial seizures
Used in conjunction with other drugs

Diazepam (Valium) and lorazepam
Effective against status
epilepticus when given i.v.

37
Q

What is the mode of action of benzodiazepines?

A

Increase affinity of GABA for
its receptor by:

Increases Cl- current (opening frequency)

Suppresses seizure focus by raising action potential threshold

Strengthens surround inhibition – prevents spread

38
Q

What is the side effect of benzodiazepine?

A

Sedation

39
Q

What is the complications of taking benzodiazepines?

A

Significant problem of tolerance and dependence
Avoid long-term use

Can get respiratory depression if used i.v.

40
Q

Gve 4 examples of drugs that inhibit sodium channels?

A

Phenytoin
Carbamazepine and oxcarbamazepine
Lamotrigine

Common way in which epileptic drugs act

41
Q

What is the mechanism of action of phenytoin?

A

Phenytoin binds to the inactivated state and slows down its recovery

42
Q

What occurs during action potential of voltage dependent sodium channel?

A

Closed – before activation
Open – during depolarisation
Inactivated – shortly after the peak of depolarisation

Na+ channels do not recover from the inactivated state until the membrane has repolarised

43
Q

Give 3 examples of AED that have mixed actions?

A

Gabapentin
Valproate (valproic acid)
Levetiracetam

44
Q

what is unusual about valproate?

A

Not related chemically to the other classes of anti-epileptics
Unusual in that it is effective against both tonic-clonic and absence

45
Q

What other illness can valproate be used in?

A

Useful in bipolar depressive illness

46
Q

How is valproate taken?

A

Taken orally

Well absorbed

47
Q

What is the different mechanisms of Valproate? (3)

A

Inhibits Na+ channels but weaker than phenytoin

Decreased GABA turnover
Inhibition of succinic semialdehyde dehydrogenase and thereby indirectly inhibiting GABA transaminase
May lead to increased synaptic GABA levels

Blocks neurotransmitter release by blocking T-type Ca2+ channels

48
Q

Should antiepileptics drugs be given in pregnancy?

A

Seizure very harmful for pregnant women

Monotherapy usually better than drug combination

Folic acid is recommended to be given for every pregnant women with epilepsy

49
Q

What AED should definetly not be given to a pregnant lady?

A

Phenytoin, valproic acid are absolutely contraindicated and oxcarbamazepine is better than carbamazepine

50
Q

What drug mainly causes Foetal hydantoin sydndrome?

A

Up to 30% of children whose mothers are taking phenytoin during pregnancy develop FHS

51
Q

What is the presentation of foetal hydantoin syndrome?

A

Intrauterine growth restriction with microcephaly

Minor dysmorphic craniofacial features and limb defects including hypoplastic nails and distal phalanges (birth defects)

A smaller population will have growth problems and developmental delay, or mental retardation

Heart defects and cleft lip may also be featured

52
Q

What other drug may cause Foetal hydantoin syndrome?

A

Carbamazepine can cause this but reports have been less common

53
Q

What is the increase chance of developing Foetal Valproate Syndrome (FVS) if the mother is taking valporic acid?

A

There is a 6-9% risk of congenital malformations in infants exposed to VPA prenatally, compared to 2-3% in the general population

54
Q

What is optogenetic stimulation?

A

It is the introduction of halorhopdsins into the brain taht reacts to yellow light and allows the chlordie to enter the cell and hyperpolarize the neurones.

55
Q

What is Epilepsia partialis continua?

A

A rare type of brain disorder

Patient experiences recurrent motor epileptic seizures that are focal (hands and face)

Recur every few seconds or minutes for extended periods (days or years)

56
Q

What is the cause of Epilepsia partialis continua?

A

Usually due to large, acute brain lesions resulting from strokes in adults and focal cortical inflammatory processes in children

57
Q

Is there any treatment for epilepsia partialis continua?

A

They are very medication and therapy-resistant, and the primary therapeutic goal is to stop secondary generalization

syposium control and movement (11 decks)

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