Epilepsy (15) Flashcards Preview

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Flashcards in Epilepsy (15) Deck (66):
1

Seizures

Abnormally excessive and hyper synchronous activity of neurones located predominantly in cerebral cortex

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Twitches/convulsions

Cortical discharges transmitted to muscles

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Classification of seizures

1. Generalised
2. Partial
3. Secondary generalised

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Generalised

Initial activation of neurones throughout both hemispheres (tonic clonic/clonic/atonic)

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Partial

Initial activation of a limited number of neurones in a part of 1 hemisphere (absence/myoclonic/simple/complex)

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Secondary generalised

Partial seizure that later spread to involve majority of 2 cerebral hemispheres

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Manifestation of partial seizure in parietal lobe

Tingling/jerking in leg, arm, face

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Manifestation of partial seizure in occipital lobe

Flashing lights/spots, vomiting

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Manifestation of partial seizure in temporal lobe

Strange smell or taste, altered behaviour, deja vu, lip smacking/chewing movements

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Manifestation of partial seizure in frontal lobe

- Adversive seizures (Eyes/head both turn to one side)
- Jacksonian seizure (tingling feeling in hand/arm)

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EEG

Electroencephalogram

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EEG uses

Scalp electrodes to record electrical activity along scalp - firing of neurones within brain, series of electrical impulses originating in brain are amplified and summed into waves (Spike-wave discharges)

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Status epliepticus

State of persistent seizure, more than 30 mins/2+ without full recovery

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Why is SE a medical emergency?

The longer a seizure lasts, less likely it will stop on its own and more likely to reoccur in future

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Treatment for SE

GABAa receptor agonist e.g. diazepam

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Epilepsy

2 or more unprovoked seizures

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Mechanisms underlying seziures

Excitation or inhibition > too much neuronal activity > seizure

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Excitation (too much)

Ionic - Na+, Ca2+ influx, neurotransmitter - glutamate, aspartate release

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Inhibition (too little)

Ionic - Cl-influx, K+ efflux
neurotransmitter GABA release

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Inhibitory interneurones

Allow activity to spread in one direction but not sideways, release inhibitor neurotransmitter GABA

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GABA

Major inhibitory neurotransmitter, found at 30% of synapses, acts via GABAa or GABAb

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GABAa

Ligand-gated chloride channel receptor

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GABAb

G protein-coupled receptor

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What determines intrinsic properties of each channel

GABAR subunit

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Types of epilepsies caused by mutation in GABAa receptor subunits

- Childhood absence epilepsy (CAE)
- FS (pure febrile seizures)
- GEFS+ (generalised epilepsy with febrile seizures plus)
- JME (juvenile myoclonic epilepsy)
- DS (Dravet syndrome - SMEI severe myoclonic epilepsy in infancy)

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Dravet syndrome associated with which mutation

GABRG2(Q390X) > loss of 78 C-terminal aa (changes it from transmembrane protein to a globular cytosolic protein)

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Febrile seizures

Associated with fever

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Tonic-clonic/grand mal

Generalised

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Myoclonic seizure

Involuntary twitching of a muscle/group of muscles

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Absence seizure

Lapses of awareness, staring, last only a few seconds, common in children

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Complex partial seizure

Feeling deja vu, fear, euphoria/depersonalization

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Tonic seizure

Tone is greatly increased, arms/legs sudden stiff movements, during sleep usually involved most/all of brain

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Post-status epileptics animal models single episode of status epileptics is used to incite

Epilpetogenesis (via pilocarpine)

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Pilocarpine is a

Pro-convulsant drug, non-selective muscarinic receptor agonist

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Purpose of anti epileptic drugs

Decreases frequency and/or severity of seizures in people with epilepsy, treats symptom of seizures not underlying epileptic condition

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Modes of action of anti-epileptic drugs

1. Suppress action potential
2. Enhance GABA transmission
3. Suppression of excitatory transmission

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Suppress action potential using

Sodium channel blocker/modulator, potassium channel opener

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Enhance GABA transmission

GABA uptake inhibitor, GABA mimetics

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Suppression of excitatory transmission

Glutamate receptor antagonist

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Main mechanisms of action

1. Enhancement of GABAergic transmission
2. Inhibition of Na+ channels
3. Mixed actions

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Anti epileptics for partial simple and complex seizures

Carbamazepine, phenytoin, valproic acid

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Anti epileptics for Generalised tonic clonic

Carbamazepine, phenytoin, valproic acid

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Anti epileptics for Absence seizures

Ethosuximide, valproic acid

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Anti epileptics for Atypical absence, atonic, myoclonic seizures

Valproic acid

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Anti epileptics for Febrile seizures

Diazepam, rectal

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Enhancing GABAergic transmission

- Enhance action of GABAa receptors with barbiturates (phenobarbital)/benzodiazepines (clonazepam)
- Inhibit GABA transaminase (vigabatrin)
- Inhibit GABA uptake (tiagabine)

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Benzodiazepines

- Clonazepam
- Clorazepate
- Diazepam (valium) and Iorazepam

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Clonazepam effective against

Generalised tonic-clonic, absence and partial seizures

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Clorazepate effective against

Partial seizures (used with other drugs)

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Diazepam (valium) and lorazepam effective against

Status epilepticus when give IV

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Mechanism of action of benzodiazepines

Increase affinity of GABA for its receptor (increases Cl- current, supresses seizure focus by raising action potential threshold, strengthens surround inhibition - prevents spread)

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Problems with benzodiazepines

Sedation, tolerance and dependence, respiratory depression (iv)

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Inhibition of Na channels

Phenytoin, Carbamazepine and oxcarbamazepine, Lamotrigine

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Phenytoin

- During an action potential voltage-dependent Na channel (closed, open, inactivated)
- Na channels don't recover from inactivated state until membrane has repolarised
- Binds to inactivated state and slows down its recovery

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Mixed actions

Gabapentin, Valproate, Levetiracetam

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Valproate effective for?

Tonic-clonic and absence (bipolar)

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How is valproate taken?

Orally, well absorbed

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Mechanism of action of valproate

- Inhibits Na channels
- Decreased GABA turnover (inhibition of succinic semialdehyde dehydrogenase - inhibit GABA transaminase, increased synaptic GABA)
- Blocks neurotransmitter release by blocking Ca2+ channels

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Antiepileptics and pregnancy

Monotherapy, folic acid recommended, Phenytoin and Valporate not allowed, oxcarbamazepine

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Foetal hydantoin syndrome caused by

Taking phenytoin (sometimes carbamazepine)

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Foetal hydantoin syndrome symptoms

Intrauterine growth restriction with microcephaly, dysmorphic craniofacial features and limb defect (hypoplastic nails and distal phalanges), growth problems and developmental delay, heart defects and cleft lip

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Foetal valproate syndrome (FVS)

6-9% risk of congenital defects

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Optogenic stimulation used for

Partial seizures, use of halorhodopsin similar to GABAa hyperpolarise the neurone in reaction to yellow light

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Epilespia partialis continua

Rare, recurrent motor epileptic seizures that are focal (hands and face)

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Epilespia partialis continua caused by

Large, acute brain lesions from strokes

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Treatment for Epilespia partialis continua

Medication and therapy-resistant, stop secondary generalisation