Epilepsy Flashcards
what is epilepsy?
a chronic disorder characterised by recurrent seizures” (Gastaut, 1973).
what is the cause of epilepsy
A neuronal hyperexcitability disorder arising from excess excitability or disinhibition
what is the moa of picrotoxin
Picrotoxin antagonizes the GABAA receptor channel directly, which is a ligand-gated ion channel concerned chiefly with the passing of chloride ions across the cell membrane. Therefore picrotoxin prevents Cl- channel permeability and thus promtes an inhibitory influence on the target neuron.
what is the types of seizures and how are they characterised ?
Principal types of seizure:
Partial seizures:
Generalised seizures
Most commonly characterised by impairment of motor activity (convulsions), consciousness, perception and/or behaviour
Different types of epilepsy affect these domains to a differing extents.
what is the difference between epilepsy and seizure?
Epilepsy is a disorder that has many symptoms
Seizure is the principal symptom of epilepsy
Seizure: a convulsion caused by epileptiform brain activity.
what is convulsion
Convulsion:
‘A sudden, violent, irregular movement of a limb or of the body, caused by involuntary contraction of muscles’.
Does not necessarily have to be epileptic in origin (see also serotonin syndrome).
what is isolated seizures?
what are there possible triggers
Many individuals will experience an isolated seizure as a result of exposure to different stimuli.
An isolated seizure is not considered to be epilepsy
Possible triggers of isolated seizure include:
CNS infection/inflammation
Stroboscopic lighting
Metabolic dysfunction
Head injury
Fever (especially in children)
Drug-related (prescription and recreational)
Whilst an isolated seizure is not epilepsy, one or more isolated seizures can increase a person’s risk of developing epilepsy
what are the different seizure types?
Generalised: involves the whole brain (e.g. tonic-clonic or absence seizures)
Partial: Just involves one specific brain area - twitching, jerking , tingling
Secondary generalisation: partial seizures can spread to affect the whole brain.
Simple/complex: whether consciousness is impaired/affected.
what are the characteristics of generalised tonic clonic seizures?
Generalised tonic-clonic seizures:
Used to be called grand mal
Limb extension and rigidity, respiration stops, defaecation, micturation and salivation often occur (~1 min).
Followed by violent synchronous jerks (~2-4 mins).
Patient gradually regains consciousness after a few more minutes and is likely to feel confused, ill and disorientated.
what are the characteristics of generalised absence seizures?
Less physically dramatic but may occur more frequently.
Patient typically ceases any action, stares vacantly ahead, unaware of surroundings, dangers, other people.
Patient recovers very quickly with no after-effects.
what are the characteristics of partial seizures?
Seizure discharge begins and typically remains restricted to a local brain area.
Accompanied by simple symptoms (involuntary movements, abnormal sensory experiences) but rarely loss of consciousness.
e.g. Jacksonian epilepsy, psychomotor epilepsy.
how to decide when to treat epilepsy?
Check lecture slide for flow diagram - week 20 slide 23
When does >1 isolated seizure become epilepsy?
Decision to treat is complex as:
All current drugs have significant side-effects
A diagnosis of epilepsy has legal ramifications (driving, employment, pregnancy etc.)
what is the aims of pharmacotherapy and treatment stratergy?
Render patient seizure-free or minimise number of breakthrough seizures
Maximise quality of life
what are the principal treatments for epilepsy and targets and examples ?
Sodium channel blockers
Action potential generation is dependent upon the opening of voltage-gated sodium channels.
Inhibition of these channels has been found to prevent or ameliorate seizures.
e.g. phenytoin, carbamazepine, carisbamate, valproate
Enhancement of GABA actions
Enhancement of GABA-mediated Cl- channels increase inhibition and attenuates seizures.
e.g. phenobarbitone, diazepam
Others also available (SV2A-mediated, Ca2+ channel effects; see Rang & Dale): i.e. Levetiracetam
Also ketogenic diet and vagal nerve stimulation
GABA : metatrophic
GABA antagonisr : ionotrophic
Clinical need for new AEDs
Gowers reported that seizures treated with bromide were refractory in ~36% of patients (Gowers, 1881)
> 40 AEDs have been licensed since that time
No new AEDs are superior in efficacy to 1st generation treatments (e.g. PMID 17903391 & 16886973)
No new AEDs are superior in tolerability to 1st generation treatments (PMID: 15842952)
