S12 Epilepsy Flashcards
What are seizures?
Clinical manifestation of an abnormally excessive and hyper synchronous activity of neurones located in cerebral cortex.
How are seizures classified by site?
Generalised: initial activation of both hemispheres.
Partial: initial activation of 1 hemisphere.
Secondary generalised: a partial that spreads to involve both hemispheres.
What is a myoclonic, tonic, atonic, simple and complex seizure?
Myoclonic: jerky. Tonic: stiffening. Atonic: falling to ground heavily. Simple: while alert. Complex: change in awareness.
What is status epilepticus and why is it important?
State of persistent seizure: >30mins continuous seizure or >2 sequential seizures in 30mins without full recovery.
Medical emergency, longer it is, less likely it will stop. Confers greater risk for future unprovoked seizures.
Which two basic mechanisms underly seizures?
Too much excitation - Na+, Ca+, glutamate, aspartate.
Too little inhibition - Cl-, K+, GABA.
Which cells prevent brain activity from spreading out sideways?
Inhibitory interneurones, release GABA. 10-20% of cells.
What is the structure of GABA?
5 subunits: 2 α, 2 β, one γ/δ.
GABAA (Cl- channel) or GABAB (G protein-coupled).
Which types of epilepsy are caused by mutation in GABAA receptor subunits?
CAE - childhood absence FS - pure febrile GEFS+ - generalised + FS JME - juvenile myoclonic DS - Dravet syndrome
What effect does GABRG2(Q390X) have? What does it lead onto?
Truncation of GABA. More hydrophilic, changes transmembrane protein to globular cytosolic protein.
Dravet syndrome/ sever myoclonic epilepsy in infancy.
How does status epilepticus change the abundance of receptors in the brain?
Decrease in α1 and increase in α4 subunits in γ containing GABAA receptors. α4 desensitises rapidly
What are the three modes of action for anti epileptics and how do they work?
Suppress action potential (Na+ blocking, K+ opening).
Enhance GABA transmission (GABA uptake inhibitor/ mimentics).
Suppression of excitatory transmission (glutamate receptor antagonist).
Which drug is commonly used for most adult seizures?
Valproic acid.
What is the drug of choice for febrile seizures?
Rectal diazepam.
Main unwanted effects of benzodiazepines?
Sedation, tolerance, dependance, respiratory depression.
How does valproate work?
Inhibits Na+ channels.
Inhibits GABA transaminase, increasing synaptic levels.
Blocks neurotransmitter release by blocking Ca+ channels.
