Structure and Function - Week 8 Seizures and Epilepsy Flashcards
Whta is a seizure? (3)
External manifestation (and primary symptom) of epilepsy
The clinical manifestation of an abnormally excessive and hypersynchronous activity of neurones located predominantly in the cerebral cortex
The cortical discharges can be transmitted to the muscles, causing twitches or convulsions
How are seizures classified? (3)
The new basic seizure classification is based on 3 key features:
Where seizures begin in the brain
Level of awareness during a seizure
Other features of seizures
What are generalised seizures? (2)
Previously called primary generalized, with initial activation of neurones throughout both hemispheres
What are focal seizures (2)
Previously called partial seizures, with initial activation of a limited number of neurones in a part of 1 hemisphere
What are focal to bilateral seizures (2)
Previously called secondary generalized, a focal seizure that later spreads to involve the majority of the 2 cerebral hemispheres
What are unknown set seizures (2)
If the onset of a seizure is not known, the seizure falls into the unknown onset category. Later on, the seizure type can be changed if the beginning of a person’s seizures becomes clear
Describe the signs and symptoms of focal seizures (3)
Depend on the cortical region(s) involved:
seizures can originate in different brain structures that are responsible for motor, sensory, cognitive, and autonomic systems
What are focal aware seizures (2)
Previously called simple partial, when awareness remains intact, even if the person is unable to talk or respond during a seizure
What are focal impaired awareness seizures (2)
Previously called complex partial, when awareness is impaired or affected at any time during a seizure, even if a person has a vague idea of what happened
What are focal awareness unknown seizures (2)
When it is not possible to know if a person is aware or not, for example if a person lives alone or has seizures only at night
What are generalised seizures (4)
The thalamocortical circuitry is involved early in the attack and results in synchronized firing of neurones brain-wide
The resulting discharges spread immediately to involve all areas of the cortex at virtually the same moment
The resulting seizures are bilaterally symmetrical, often violent rhythmic shaking of body parts, and consciousness is impaired from the outset
These are all presumed to affect a person’s awareness or consciousness in some way
What is status epilepticus (5)
A life-threatening condition in which the brain is in a state of persistent seizure
More than 30 mins continuous seizure activity OR
Two or more sequential seizures spanning this period without full recovery between seizures
SE is a medical emergency because the longer a seizure lasts, the less likely it is to stop on its own
SE confers greater risk for future unprovoked seizures
What can be used to diagnose epilepsy? (1)
EEG
What are the basic mechanisms underlying seizures (2)
Excitation
Inhibition
Describe epidemiology of seizures (4)
Incidence: approximately 80/100,000 per year
Lifetime prevalence: 9% (1/3 are benign febrile convulsions)
The risk of recurrence of seizures is about 30-35% after the first unprovoked seizure
The risk of recurrence is about 60% after second seizure
What is epilepsy? (2)
Defined as a condition in which seizures recur, usually spontaneously; a single seizure episode is not considered as epilepsy, i.e. 2 or more unprovoked seizures
Describe the classification of epilepsy (3)
Idiopathic Cause unknown (presumed genetic)
Symptomatic Cause identified (e.g. brain tumour)
Cryptogenic Pathology suspected but not identified (e.g. patient has been concussed)
What are anti epileptic drugs? (2)
A drug which decreases the frequency and/or severity of seizures in people with epilepsy
Treats the symptom of seizures, not the underlying epileptic condition
Correct classification of seizures leads to correct AED selection
What are the modes of action of anti epileptic drugs (8)
Suppress action potential
- Sodium channel blocker or modulator
- Potassium channel opener
Enhance GABA transmission
- GABA uptake inhibitor
- GABA mimetics
Suppression of excitatory transmission
- Glutamate receptor antagonist
What are the main mechanisms of action of anticonvulsants (3)
Enhancement of GABAergic transmission
Inhibition of Na+ channels
Mixed actions
Combination of some or all of the above and also inhibiting neurotransmitter release
What are GABA receptors (3)
GABA (g-aminobutyric acid)
Major inhibitory neurotransmitter
Found at ~30% of synapses
Acts via GABAA or GABAB receptors
Describe the difference between GABA A and B receptors (4)
Check notes week 8
Describe the structure of GABA A receptors (3)
Pentameric: typical in vivo subunit composition is two α, two β and one γ or δ subunit
How can GAABergic transmission be enhanced (3)
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
Describe mechanism of action of benzodiazepine (4)
Increase affinity of GABA for its receptor
Increases Cl- current (opening frequency)
Suppresses seizure focus by raising action potential threshold
Strengthens surround inhibition – prevents spread
Describe the problem with benzodiazepines (4)
Main unwanted effect is sedation
Significant problem of tolerance and dependence
Avoid long-term use
Can get respiratory depression if used i.v.
Describe the toxicity and unwanted effect of benzodiazepine (4)
Generally safe in overdose
Not lethal – cause prolonged sleep
Unless taken with other CNS depressants
With ethanol – respiratory depression
In case of overdose – flumazenil (a BZ-site antagonist)
Unwanted effects
Drowsiness, confusion, amnesia, poor co-ordination
Long acting (e.g. diazepam) – next day
