Epilepsy Flashcards
What is epilepsy?
A disorder of the CNS characterised by recurren, sudden large increases in electrical activity (electrical seizures) that may be localised or generalised.
Prevalence of epilepsy?
How many people suffer!
- 2-5% of kids suffer 1 or more seizure (benign febreile convulsions) and of those 10% go onto to develop some form of adult epilepsy.
0.5 - 1% of adults have active epilepsy (men more likely as have jobs where more likely to bang head).
Incidence of epilepsy?
How many new cases per year?
0.1%
More common in children or elderly.
What do the symptoms of epilepsy depend on?
CNS region that the seizure occurs in.
Whether localised or general and if local - does it then spread?
Define partial.
Localised to a limited region.
Define primarily generalised.
Most CNS involved - no apparent focus.
Define secondarily generalised.
Most CNS involved - spread from initial focus.
Define simple.
Subject remains conscious.
Define complex.
Consciousness is impaired.
What tends to precede a seizure?
An aura - a smell, a tune.
These may be subcortical seizures.
What are absence seizures?
Primarily generalised, common in children, sudden loss of awareness for approx 30 seconds.
What are tonic clonic seizures?
Primarily generalised, 2-5 minutes.
Sudden stiffening ('tonic') of muscles. A fall. Jerking ('clonic') movements.What are simple partial seizures?
Focal cortical seizures…jerking movements beging in extremities —> body (jacksonian march). May be sensory rather than motor symptoms.
What is temporal lobe epilepsy?
Focal seizure of temporal lobe.
- Simple focal; emotional, sensory or memory.
- Complex focal - impairs conciousness…my be secondarily generalised to provoke tonic clonic.
Most common.
What is status epilepticus?
The seizure doesn’t spontaneously stop. 30 mins or more.
What are syndromes?
Collection of signs and symptoms to more closely identify a particular condition and optimise the theraputic approach.
Type and pattern Frequency Location of focus Physical and mental symptoms. Age of onset Gender Prognosis.
What could the causes of seizures be?
1) Idiopathic - not known.
2) Cryptogenic - can’t be proved.
3) Symptomatic - band head, tumor, stroke or drug abuse.
Does epilepsy have a genetic link?
Yes - 2-3x more likely if a close relative suffers.
What channelopathy is present in benign febrile seizures?
Mutation in KCNQ2 and 3 - voltage gated potassium channel.
What channelopathy is present in familial generalised epilepsy with febrile seizures plus (carries on into adulthood)?
Mutant SCN1B - encodes the Beta subunit of the Na+ channel.
Explain the kainic acid injection model?
Leads to chronic epileptic behaviour.
Explain kindling model.
Repeated low intensity electrical stimulation (to amygdala or hippocampus) that leads to chronic epileptic behaviour.
The frequency of stimulation is critical.
Focal synchronous excitation that occur to initiate a seizure involve…
1) increased synaptic transmission
2) decreased surround inhibition
What is the cellular mechanism that initiates a focal seizure?
Paroxysmal depolarising shift (PDS)
The mechanism is unknown but the ability of PDS to spread to neighbouring cells to generate a synchronous focus implies a failure of inhibitory feedback through local interneurones.
What is epilepsy without surround inhibition?
spreading and blending of info from the nucleus.
What is epilepsy WITH surround inhibition?
mediated by interneurones - through feedback pathways has the effect of limiting spread of input signalling. It has a focussing effect.
Causes greater inhibition on its neighbour than its neighbour causes on it.
What are the 2 princicples for treating tonic clonic - partial, or temporal lobe seizures?
And what is the problem with them?
Enhance the activity of GABAergic system.
Use Dependant block of Voltage gated sodium channels.
May cause absence seizures.
What drugs would you use to enhance the activity of the GABAergic system (and therefore treat tonic clonic, partial or temporal lobe seizures)?
Benzodiazepines - eg diazepamk. Bind to regulatory site on GABAa and increase the affinity of the receptor for GABA
Barbituates - phenobarbitone. Prolongs the time the GABA activated Cl- channel stays open.
Vigabatrin - inhibits GABAtransaminase
Tiagabin - inhibits GABA uptake.
How would use block use dependent voltage gated sodium channels?
Carbamazepine, phenytoin - decrease likelihood of AP firing at high frequencies…little effect at low frequencies. (Bind to inactivated state and prolongs inactivation, decrease the max frequency they fire at).
How would you treat status epilepticus?
Diazepam.
How would you treat absence seizures?
Ethosuximide - mechanism is uncertain. Block t-type VOCC in thalamic neurones.
What drugs would you use for both tonic-clonic and absence seizures.
Lamotrigine - used dependant block of sodium channels.
Sodium valproate - weak blocker of voltage operated sodium channels and weak inhibition of GABA transaminase.
Gabapentin?
Binds to the alpha2delta subunit VOCC - comprimse NT release.
Levetiracetam?
Binds to synaptic vesicle protein, SV2A, affects neurotransmission.
Retigabine?
Provoke K+ channel opening.
Premapanel?
AMPA antagonist.
What are the non-therapeutic methods of treating epilepsy?
Ketogenic diet - high fat, low carb - to control seizures in kids.
Vagal stimulation - can abort impending or ongoing attacks.
Surgery - remove tissue that habours focus - limit spread of excitation.
