Excessive, hypersynchronous activity of neurons in the brain >> convulsions, thought disturbances, twitching.

Epilepsy Flashcards by Eleanor Barnard

What is a seizure?

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

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How are seizures classified?

Based on location within the cerebral cortex.

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What are the 3 main types of seizure?

Generalised
Partial
Secondary generalised

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What is a generalised seizure?

A seizure with initial activation neurons throughout both hemispheres.

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What is a partial seizure?

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

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What is a secondary generalised seizure?

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

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What are the 3 subtypes of partial seizures?

Simple
Complex
With 2* generalisation

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What is a simple partial seizure?

Partial seizure activity while the person is alert.

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What is a complex partial seizure?

Partial seizure activity with change of awareness of the surroundings.

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What are the 5 subtypes of generalised seizures?

Absence
Myoclonic
Tonic-clonic
Tonic
Atonic

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What is characteristic of an absence generalised seizure?

Staring and blinking without falling.

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What is characteristic of a myoclonic generalised seizure?

Jerking movements of the body.

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What is characteristic of a tonic-clonic generalised seizure?

Stiffening, falling and jerking of the body.

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What is characteristic of a tonic or atonic generalised seizure?

Falling heavily to the ground.

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What is the manifestation of a partial seizure dependent on?

The site of origin in the brain.

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

Adversive seizures.

-eyes/head both turn to one side

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

Jacksonian seizure.

-tingling feeling in the hand or arm

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

Tingling/jerking of leg, arm or face.

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

Flashing lights
Spots
Vomiting

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

Strange smell/taste
Altered behaviour
Deja vu
Chewing movements

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What is used to record electrical activity in the brain?

Electroencephalogram (EEG).

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What type of waves does and EEG produce?

Spike-wave discharges.

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

PARTIAL - excess activity only in electrodes from one hemisphere
GENERALISED - excess activity in both hemispheres

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What is status epilepticus (SE)?

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

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What are the 2 definitions of status epilepticus?

- More than 30 mins continuous seizure activity | - 2+ sequential seizures spanning 30 mins without full recovery between seizures

What does status epilepticus increase the risk of?

Future unprovoked seizures.

What is epilepsy?

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

What are the 2 basic mechanism of seizures?

Excitation and inhibition. | -either can cause too much neuronal activity

How does excitation of neurons occur?

- IONIC (Na/Ca influx) | - NEUROTRANSMITTER (glutamate/aspartate release)

How does inhibition of neurons occur?

- IONIC (Cl/K efflux) | - NEUROTRANSMITTER (GABA release)

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

Inhibitory interneurons.

What do inhibitory interneurons release?

GABA. | -neurotransmitter

What does GABA stand for?

Gamma-aminobutyric acid.

What are the 2 types of GABA recpetor?

- GABAa receptors | - GABAb receptors

What are GABAa receptors?

Ligand-gated chloride channel receptors.

What are GABAb receptors?

G protein-coupled receptors.

What structure do GABAa receptors have?

Pentameric structure. | -2a, 2b, 1g/o.

What do the subunits of GABA receptors determine?

Intrinsic properties. | -e.g. affinity for diazepam

Name 4 epilepsies caused by GABAa receptor mutations.

- Childhood absence epilepsy - Febrile seizures - Juvenile myoclonic epilepsy - Dravet syndrome

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

DRAVET SYNDROME. - loss of 78 C-terminal AAs >> more hydrophilic surface - receptor becomes cytosolic protein, not transmembrane

What is Dravet syndrome also known as?

Severe myoclonic epilepsy in infancy. | -variety of seizures in 1st year of life

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

PILOCARPINE. - proconconvulsant drug - non-selective muscarainic receptor agonist

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

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

What is a feature of a4 subunits in GABA receptors?

Desensitise rapidly. | -especially when with b3

What effect does increasing a1 subunits have?

- Increased latency time - Decreased rate of seizure development - Fewer spontaneous seizures

What is the purpose of anti-epileptic drugs?

Decrease the frequency/severity of seizures. | -treat the symptoms of seizures, don't cure

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

- Suppress action potentials - Enhance GABA transmission - Suppress excitatory transmission

How do anti-epileptic drugs suppress action potentials?

- Sodium channel blocker | - Potassium channel opener

How do anti-epileptic drugs enhance GABA transmission?

- GABA uptake inhibitor | - GABA mimetics

How do anti-epileptic drugs suppress excitatory transmission?

-Glutamate receptor antagonists

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

The type of seizure.

What is the most widely used anti-epileptic drug?

Valproic acid.

What seizure types are treated by the following: - Carbamazepine - Phenytoin - Valproic acid

- Partial simple - Partial complex - Generalised tonic clonic

What seizure type is treated by the following: - Ethosuximide - Valproic acid

Absence seizure.

What seizure types are treated by the following: | -Valproic acid

- Atypical absence | - Atonic, myoclonic

What seizure type is treated by the following: - Diazepam - Rectal

Febrile seizures. | -child with a fever

What are the methods of enhancing GABA action?

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

Give an example of a barbiturate.

Phenobarbital.

Give an example of a benzodiazepine.

Clonazepam.

How do benzodiazepines work?

Increase GABA affinity >> suppresses seizures. - Increase CL current - Raise AP - Strengthens surround inhibition

What are possible side effect of benzodiazepines?

- Sedation | - Respiratory depression (IV)

What is diazepam (valium) used to treat?

Status epilepticus. | -IV

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

- Phenytoin - Carbamazepine - Lamotigine

What is the mechanism of action of phenytoin?

Binds to inactivated Na+ channels >> slows down repolarisation.

What anti-epileptic drugs have mixed actions?

- Gabapentin - Valproate - Levetiracetam

What is meant by mixed action?

Combination of the following: - Enchance GABA transmission - Inhibit Na+ channels - Inhibit NT release

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

Valproate.

How is valproate unusual?

Acts against both tonic-clonic and absence seizures.

What are the mechanisms of valproate? (3)

- Inhibits Na+ channels - Decreases GABA turnover - Blocks neurotransmitter release

What is the problem with pregnancy?

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

What is recommended during pregnancy?

- Folic acid | - Monotherapy (rather than drug combination)

Which drugs are absolutely contraindicated during pregnancy? (AVOID)

- Phenytoin | - Valproic acid

What causes foetal hydantoin syndrome?

Mother taking phenytoin during pregnancy (30%).

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

- Growth restriction and microcephaly - Dysmorphic craniofacial features - Limb defects - Developmental defect

What causes foetal valproate syndrome?

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

What proportion of epileptics are seizure free with one drug?

70%.

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

5-10%.

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

20%. | -Refractory epilepsy

What is the mechanism of optogenetics?

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

What can optogenetics do?

Suppress seizures with epilepsy.

What could optogenetics be used to control?

Epilepsia partialis.

What is epilepsia partialis continua?

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

What normally causes epilepsia partialis?

- Large, acute brain lesions due to strokes | - Focal cortical inflammatory processes (children)