Epilepsy and its treatment Flashcards

1
Q

Epilepsy?

A

Group of CNS disorders in which recurrent seizures

Occurs due to chronic underyling processes

Affecting motor, sensory and autonomic outputs.

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2
Q

Seziures are paroxysmal?

A

Sudeen recurrent events

Due ot abnormal, excessive, synchronous discharges from a population of CNS neurones.

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3
Q

Different types of seizures?

A

Lots of types

Generalised seizures: involves many brain regions.

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4
Q

Mapping of the origin of a seizure?

A

Mapped electrophysiologically to a focus of origin within the brain

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5
Q

Types of epilepsy?

A

Lots of types

Primary or secondary

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6
Q

Primary or idiopathic epilepsy?

A

Cannot be ascribed to a particular cause or incidient.

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7
Q

Secondary or symptomatic epilepsy?

A

Associated with trauma, neoplasm, infectio, development abnromailites or cerebrovascular disease

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8
Q

Epilepsies are broadly classified into two major categories?

based on the locus

A

Based on the locus of epileptiform activity in the brain.

  1. Generalised epilepsy
  2. Focal epilepsy eg. partical seizures. Originate at a specific brain region.
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9
Q

Epilepsies are broadly classified into two groups based on their aetiology (cause)?

A
  1. Idiopathic
  2. Symptomatic: Environmental factors such as trauma, infection etc
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10
Q

Electroencephalogram?

A

Records brain waves throuhg scalp, skull etc

Detects rhythms, spikes.

Useful for diagnosing the type of epilepsy

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11
Q

Partial seziures:

3 types?

A

Focal/local seizures.

  1. Simple partial seizures: no impairment of consciousness. Can be confined to a single limb or muscle group.
  2. Complex partial seizures: Confusion, stumbling and falling. Unconscious movement that resemble a tics.
  3. Parital seizures secondarily generalised: Partial seizure immediately preceding a GTC seizure.
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12
Q

ECG of a partial seizure?

A
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13
Q

Generalised seizure:

5 types?

A

No evidence of locus.

  1. Generalised tonic-clonic: can go on for a long time. Tonic rigidity followed by a tremor.
  2. Absence: small duration but can have many a day/ Concsciousness altered.
  3. Myoclonic: Isolated clonic jerks associated with multiple spikes in the EEG.
  4. Atonic: sudden loss of posture leading to collapse.
  5. Infantile spasms: Brief recurrent myoclonic jerks. 90% causes before 1yo.
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14
Q

Status epilepticus?

A

Continous or repetitive seizures lasting 30mins or more.

Inadequate treatment can result in brain damage or death.

Can be caused by drug withdrawal.

Epilepsy sufferers that are infected with fever.

Sedatives as treatment

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15
Q

Initiation of a seizures involves 2 things?

A
  1. High frequency bursts of action potentials
  2. Hypersynchronisation
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16
Q

3 Mechanisms for recruitment of surrounding neurones?

A
  1. Increase in extracellular potassium- depolarises neighboring neurones.
  2. Accumulation of calcium in presynaptic terminals resulting in enhanced transmitter release.
  3. Depolarisation induced activation of glutamate (NMDA) receptors resulting in calcium influx.
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17
Q

Experimental models of epilepsy

Name the 3 main ones?

A
  1. Maximal electric shock test
  2. PTZ-induced clonic seizures
  3. Lethargic
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18
Q

Maximal electric shock test?

A

Model for partial seizures and tonic-clonic seizures in humans.

19
Q

PTZ-induced clonic seizures?

A

GABAA receptor antagonist

Model for generalised seizures especially absence seizures

20
Q

Lethargic mice?

A

Disruption in VDCC genes

Models for generalised seizures.

21
Q

Other experimental models of epilepsy?

A

Minimal metrazol-induced seizures in rats- model myoclonic seizures.

Electrical kindling: model for complex partial seizures.

22
Q

3 types of neurological channelopathies?

A

Epilepsy and migraine.

Neuromuscular disorders

Cerebellar atomia

23
Q

nAChR a7 subunit gene?

A

Associated with juvenille myoclonic epilepsy

24
Q

nAChR a4 and beta2 subunit genes?

A

Autosomal dominant nocturnal frontal lobe epilespy

25
Q

GABAA recepor a1, gamm2, delta subunit genes?

A

Generalised epilepsy with febrile seizures

26
Q

Na channel 1A, 1B & 2A subunit genes?

A

Generalised epilepsy with fibrile seizures

27
Q

potassium channel KCNQ2/3 genes?

A

Benign familial neonatal convulsions

28
Q

Potassium channel KCNA1 genes?

A

Parital epilepsy episodic ataxia

29
Q

Glutamate and GABA synthesis

A

AS2

Have to transport glutamate into the vesicles.

Vesciles that transport GABA contains GAD too

30
Q

Neuronal excitability?

A

The summation of multiple excitatory inputs initiates an AP.

Inhibitory synpases can prevent the excitatory event.

Having an inhibitory event as well as a stimulation event- even if stimulation event goes over threshold-no AP.

Battle between the two.

31
Q

GABAA receptor?

A

Lots of binding sites.

GABA site (antagonist can bind- eg. bicuculine)

Transports chloride through.

AS3

32
Q

Name the 5 binding sites on the GABAA receptor?

A

Gaba site

Benzodiazepine site

Barbiturate site

Steroid site

Picrotoxinin site

33
Q

Benzodiazepine?

A

eg. diazepam

Increases the affinity of GABA for the GABAA receptor.

Used as treatment for some seizure types such as tonic-clonic, myoclonic and absense (clonazepam)

34
Q

Name the 4 channel types that antiepileptic drugs target?

A

Calcium

Sodium

GABA

Glutamate

35
Q

Glutamate

A

Excitatory

36
Q

GABA?

A

Inhibitory

37
Q

Phenytoin?

A

Diphenylhydantoin

Blocks tetanic firing through increasing sodium channel inactivity.

Reduces neurotransmitter release.

38
Q

Carbamazepine?

A

Like phenytoin

Blocks tetanic firing through increasing sodium channel inactivation

Reuces transmitter release.

Potentiates GABA response.

39
Q

Valproate?

A

Blocks tetanic firing through increasing sodium channel inactivation.

Reduces T-type calcium channel activity.

increases GABA levels by inhibiting breakdown.

Used against absence seizures.

40
Q

Ethosuxamide?

A

Inhibits T-type calcium channels activity

Used against absence seizures

41
Q

Lamotrigine?

A

Blocks sodium channels.

Inhibits the release of excitatory amino acids.

42
Q

Topiramate?

A

Blocks sodium channels

Enhances the action of GABA

43
Q

Gabapentin?

A

Elevate GABA levels

Binds to the calcium channel sbunits

Used in chronic pain management as well

44
Q

Vigabatrin?

A

Inhibits GABA-T

Used to treat partial seizures.