Epilepsy - Clinical Lecture Flashcards
What are seizures?
- External manifestation (and primary symptom) of epilepsy
- Clinical manifestation of an abnormally excessive and hypersynchronous activity of neurones located predominantly in the cerebral cortex.
What are the 2 basic mechanisms underlying seizures?
- Excitation (too much)
2. Inhibition (too little)
How can excitation lead to a seizure?
o Ionic –> enhanced Na+, Ca2+ influx into neurons
o Neurotransmitter –> increased release of glutamate, aspartate (excitatory neurotransmitters) into synaptic cleft
Which 2 excitatory neurotransmitters can lead to seizures?
glutamate, aspartate
How can inhibition lead to seizures?
o Ionic –> insufficient Cl- influx into neuron, or insufficient K+ efflux
o Neurotransmitter –> insufficient release of GABA (inhibitory neurotransmitter)
What is the main inhibitory neurotransmitter in the CNS?
GABA
Is increased excitability always synonymous with seizure? Why?
No - the increased excitability could be in inhibitory neurons
What are inhibitory interneurones?
These brain cells allow activity to spread in one direction, but not to spread out sideways (counterbalance hyperexcitability)
- When the brain is working normally, very small numbers of brain cells are active at any given time
- The activity is kept tightly focussed as it flows through successive brain regions and is not allowed to spread out (by inhibitory interneurones)
What happens if inhibitory interneurones are dysfunctional?
• If inhibitory interneurones are dysfunctional, the localised hyperexcitability is not counterbalanced and can involve more and more neurones, causing a seizure
o When activity spreads out sideways, too many cells become active at one –> epileptic seizure
Which ion is used as a measure of excitation?
Ca2+
Which inhibitory neurotransmitter do inhibitory interneurones release?
GABA
How is magnesium involved in epilepsy?
Magnesium is a potential modulator of seizure activity because of its ability to antagonise excitation. Some studies have shown that people with epilepsy have lower magnesium levels than people without epilepsy.
What are anti-epileptic drugs?
A drug that decreases the frequency and/or severity of seizure sin people with epilepsy by treating the symptoms of seizures, not the epileptic condition
What is essential for correct AED selection?
Correct classification of the seizure
What are the 3 main modes of action of AEDs?
- Suppress action potential
- Enhance GABA transmission
- Suppress excitatory transmission
What are the 2 ways in which an AED can suppress action potential?
Block sodium channel or modulate it
Potassium channel opener
What are 2 examples of AEDs that block sodium channel or modulate it in order to suppress action potential?
Carbamazepine, oxcarbamazepine
Mechanism of action of Carbamazepine?
Carbamazepine is a sodium channel blocker. It binds preferentially to voltage-gated sodium channels in their inactive conformation, which prevents repetitive and sustained firing of an action potential.
What are the 2 ways in which an AED can enhance GABA transmission?
GABA uptake inhibitor OR inhibit GABA transaminases
GABA mimetics, enhance action of GABA receptors
What are GABA transaminases?
GABA transaminase enzymes comprise a family of transaminases which degrade the neurotransmitter GABA
What is an example of an AED that inhibits GABA transaminases?
vigabatrin
What is an example of an AED that inhibits GABA uptake?
tiagabine
What are GABA mimetics?
GABA-like drugs (inhibitory effect) –> enhance action of GABA receptors
What are 2 classes of AEDs that function as GABA-mimetics?
- Barbiturates
* Benzodiazepaines e.g. clonazepam
How can AEDs suppress excitatory transmission?
Via a Glutamate receptor antagonist
In practice, the most common AEDs used have which mechanisms of action?
- Enhancement of GABAergic transmission
- Inhibition of Na+ channels
- Mixed actions –> Combination of some or all of the above and also inhibiting neurotransmitter release
What is a partial simple seizure?
A partial seizure happens when unusual electrical activity affects a small area of the brain –> does NOT affect awareness
What is a partial complex seizure?
Seizures that ARE associated with impairment in consciousness
First line of AEDs in partial simple and partial complex seizures?
Carbamazepine
Phenytoin
Valproic Acid
What is a tonic-clonic seizure?
Tonic-clonic seizures involve both tonic (stiffening) and clonic (twitching or jerking) phases of muscle activity.
First line of AEDs in tonic-clonic seizure?
Carbamazepine
Phenytoin
Valproic Acid
What is an absence seizure?
Where you lose awareness of your surroundings for a short time –> causes you to blank out or stare into space for a few seconds.
First line of AEDs in an absence seizure?
Ethosuximide
Valproic acid
What is an atonic seizure?
A type of seizure that causes sudden loss of muscle strength - can cause the person to fall to the ground.