Epilepsy Flashcards
What is a seizure?
The clinical manifestation of an abnormally excessive and hypersynchronous activity of neurones
Where does the abnormal activity of neurones predominantly occur in seizures?
cerebral cortex
Describe a generalised seizure
initial activation of neurones throughout both hemispheres
Describe a partial seizure
initial activation of a limited number of neurones in a part of 1 hemisphere
Describe a secondary generalised seizure
a partial seizure hat later spreads to involve the majority of 2 cerebral hemispheres
What type of motion does the term ‘myoclonic’ describe?
jerking movements of the body
What type of motion does the term ‘tonic-clonic’ describe?
stiffening, falling and jerking or the body
What would you see in someone having an absence seizure?
staring and blinking without falling
What motion would you see in someone having a secondary generalised seizure?
seizure activity begins in one area then spreads
What would see in someone having a simple partial seizure?
seizure activity while the person is fully alert
How would a partial seizure of the frontal lobe manifest?
Jacksonian seizure (tingling feeling in hand or arm) OR adversive seizures (eyes or head both turn to one side)
How would a partial seizure of the parietal lobe manifest?
tingling in or jerking of leg, arm, face
How would a partial seizure of the occipital lobe manifest?
flashing lights of spots, vomiting
How would a partial seizure of the temporal lobe manifest?
strange smell or taste and altered behaviour
How does an EEG work?
uses scalp electrodes to record the electrical activity along the scalp produced by the firing of neurones within the brain
What is status epilepticus?
a life-threatening condition in which the brain is in a state of persistent seizure (more the 30 mins continuous seizure OR two or more sequential seizures spanning this period without full recovery between them)
How would you intervene in status epilepticus?
injection of GABAa receptor agonist and diazopan
What is epilepsy?
a condition in which seizures recur, usually spontaneously
What happens in ionic excitation?
Na+ and Ca2+ influx
What happens in neurotransmitter excitation?
glutamate and aspartate release
what happens in ionic inhibition?
Cl- influx and K+ efflux
What happens in neurotransmitter inhibition?
GABA release
What is the function of inhibitory interneurons?
allow activity to spread in one direction, but not to spread out sideways
What do inhibitory interneurons release to carry out their function?
GABA (inhibitory neurotransmitter)
What percentage of neurones in the brain are interneurons?
10-20%
What is the structure of GABAa receptors?
ligand-gated chloride channel receptor
What is the structure of GABAb receptors?
G protein-coupled receptor
How many subunits make up a GABAa receptor?
5 (2 alpha, 2 beta and either 1 gamma or 1 delta)
Which types of epilepsy are known to be caused by mutations in GABAa receptor subunits? (5)
CAE, FS, GEFS+, JEM, DS
What change in structure does the gamma2 (Q390X) nonsense mutation cause?
truncated subunit with the loss of 78 C-terminal amino acids
What is SUDEP?
sudden death in epilepsy
What is the action of pilocarpine?
a non-selective muscarinic receptor agonist used to induce an episode of self-sustained SE in previously healthy animals
What are the 3 main modes of action of anti-epileptic drugs?
- suppress action potential
- enhance GABA transmission
- suppression of excitatory transmission
How can AEDs suppress action potentials?
- sodium channel blocker or modulators
- potassium channel openers
How can AEDs enhance GABA transmission?
- GABA uptake inhibitors
- GABA mimetics
How can AEDS suppress excitatory transmission?
glutamate receptor agonist
How do anticonvulsnats act?
- enhancement of GABAergic transmission
- inhibtioin of Na+ channels
- mixed actions
How can we enhance GABAergic transmission?
Enhance action of -GABAA receptors with barbiturates e.g. phenobarbital
- Enhance action of GABAA receptors with benzodiazepines e.g. clonazepam
- Inhibit GABA transaminase - vigabatrin
- Inhibit GABA uptake - tiagabine
What is clonazepam used for?
effective in generalised tonic-clonic absence and partial seizures
What is clorazepate used for?
effective against partial seziures (used in conjunction with other drugs)
Wha is the mechanism of action of benzodiazepines?
increased affinity of GABA for its receptor (increased Cl- current, suppresses seizure focus by raising action potential threshold, strengthens surround inhibition)
Which are the main drugs used for inhibition of Na+ channels?
- phenytoin
- carbamazepine and oxcarbamazepine
- lamotrigine
How is valproate unusual?
effective against both tonic-clonic and absence
What are the mechanisms of action of valproate?
- inhibits Na+ channels
- decreased GABA turnover
- blocks neurotransmitter release by blocking T-type Ca2+ channels
How can foetuses of mothers taking phenytoin be effected?
foetal hydantoin syndrome
What is epilepsia partialis continua?
condition with recurrent motor epileptic seizures that are focal (hands and face), recur every few seconds for extended periods
