Epilepsy Flashcards
What is a seizure?
Excessive, hypersynchronous activity of neurons in the brain»_space; convulsions, thought disturbances, twitching.
How are seizures classified?
Based on location within the cerebral cortex.
What are the 3 main types of seizure?
- Generalised
- Partial
- Secondary generalised
What is a generalised seizure?
A seizure with initial activation neurons throughout both hemispheres.
What is a partial seizure?
A seizure with the initial activation of a limited number of neurons in a part of 1 hemisphere.
What is a secondary generalised seizure?
A partial seizure that later spreads to involve the majority of the 2 cerebral hemispheres.
What are the 3 subtypes of partial seizures?
- Simple
- Complex
- With 2* generalisation
What is a simple partial seizure?
Partial seizure activity while the person is alert.
What is a complex partial seizure?
Partial seizure activity with change of awareness of the surroundings.
What are the 5 subtypes of generalised seizures?
- Absence
- Myoclonic
- Tonic-clonic
- Tonic
- Atonic
What is characteristic of an absence generalised seizure?
Staring and blinking without falling.
What is characteristic of a myoclonic generalised seizure?
Jerking movements of the body.
What is characteristic of a tonic-clonic generalised seizure?
Stiffening, falling and jerking of the body.
What is characteristic of a tonic or atonic generalised seizure?
Falling heavily to the ground.
What is the manifestation of a partial seizure dependent on?
The site of origin in the brain.
How does a partial seizure originating in the anterior frontal lobe present?
Adversive seizures.
-eyes/head both turn to one side
How does a partial seizure originating in the posterior frontal lobe present?
Jacksonian seizure.
-tingling feeling in the hand or arm
How does a partial seizure originating in the parietal lobe present?
Tingling/jerking of leg, arm or face.
How does a partial seizure originating in the occipital lobe present?
- Flashing lights
- Spots
- Vomiting
How does a partial seizure originating in the temporal lobe present?
- Strange smell/taste
- Altered behaviour
- Deja vu
- Chewing movements
What is used to record electrical activity in the brain?
Electroencephalogram (EEG).
What type of waves does and EEG produce?
Spike-wave discharges.
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
What is status epilepticus (SE)?
Life threatening condition where brain is in a state of persistent seizures.
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»_space; 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»_space; 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»_space; 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»_space; 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»_space; 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)
