Epilepsy and its treatment Flashcards
Epilepsy?
Group of CNS disorders in which recurrent seizures
Occurs due to chronic underyling processes
Affecting motor, sensory and autonomic outputs.
Seziures are paroxysmal?
Sudeen recurrent events
Due ot abnormal, excessive, synchronous discharges from a population of CNS neurones.
Different types of seizures?
Lots of types
Generalised seizures: involves many brain regions.
Mapping of the origin of a seizure?
Mapped electrophysiologically to a focus of origin within the brain
Types of epilepsy?
Lots of types
Primary or secondary
Primary or idiopathic epilepsy?
Cannot be ascribed to a particular cause or incidient.
Secondary or symptomatic epilepsy?
Associated with trauma, neoplasm, infectio, development abnromailites or cerebrovascular disease
Epilepsies are broadly classified into two major categories?
based on the locus
Based on the locus of epileptiform activity in the brain.
- Generalised epilepsy
- Focal epilepsy eg. partical seizures. Originate at a specific brain region.
Epilepsies are broadly classified into two groups based on their aetiology (cause)?
- Idiopathic
- Symptomatic: Environmental factors such as trauma, infection etc
Electroencephalogram?
Records brain waves throuhg scalp, skull etc
Detects rhythms, spikes.
Useful for diagnosing the type of epilepsy
Partial seziures:
3 types?
Focal/local seizures.
- Simple partial seizures: no impairment of consciousness. Can be confined to a single limb or muscle group.
- Complex partial seizures: Confusion, stumbling and falling. Unconscious movement that resemble a tics.
- Parital seizures secondarily generalised: Partial seizure immediately preceding a GTC seizure.
ECG of a partial seizure?
Generalised seizure:
5 types?
No evidence of locus.
- Generalised tonic-clonic: can go on for a long time. Tonic rigidity followed by a tremor.
- Absence: small duration but can have many a day/ Concsciousness altered.
- Myoclonic: Isolated clonic jerks associated with multiple spikes in the EEG.
- Atonic: sudden loss of posture leading to collapse.
- Infantile spasms: Brief recurrent myoclonic jerks. 90% causes before 1yo.
Status epilepticus?
Continous or repetitive seizures lasting 30mins or more.
Inadequate treatment can result in brain damage or death.
Can be caused by drug withdrawal.
Epilepsy sufferers that are infected with fever.
Sedatives as treatment
Initiation of a seizures involves 2 things?
- High frequency bursts of action potentials
- Hypersynchronisation
3 Mechanisms for recruitment of surrounding neurones?
- Increase in extracellular potassium- depolarises neighboring neurones.
- Accumulation of calcium in presynaptic terminals resulting in enhanced transmitter release.
- Depolarisation induced activation of glutamate (NMDA) receptors resulting in calcium influx.
Experimental models of epilepsy
Name the 3 main ones?
- Maximal electric shock test
- PTZ-induced clonic seizures
- Lethargic
Maximal electric shock test?
Model for partial seizures and tonic-clonic seizures in humans.
PTZ-induced clonic seizures?
GABAA receptor antagonist
Model for generalised seizures especially absence seizures
Lethargic mice?
Disruption in VDCC genes
Models for generalised seizures.
Other experimental models of epilepsy?
Minimal metrazol-induced seizures in rats- model myoclonic seizures.
Electrical kindling: model for complex partial seizures.
3 types of neurological channelopathies?
Epilepsy and migraine.
Neuromuscular disorders
Cerebellar atomia
nAChR a7 subunit gene?
Associated with juvenille myoclonic epilepsy
nAChR a4 and beta2 subunit genes?
Autosomal dominant nocturnal frontal lobe epilespy
GABAA recepor a1, gamm2, delta subunit genes?
Generalised epilepsy with febrile seizures
Na channel 1A, 1B & 2A subunit genes?
Generalised epilepsy with fibrile seizures
potassium channel KCNQ2/3 genes?
Benign familial neonatal convulsions
Potassium channel KCNA1 genes?
Parital epilepsy episodic ataxia
Glutamate and GABA synthesis
AS2
Have to transport glutamate into the vesicles.
Vesciles that transport GABA contains GAD too
Neuronal excitability?
The summation of multiple excitatory inputs initiates an AP.
Inhibitory synpases can prevent the excitatory event.
Having an inhibitory event as well as a stimulation event- even if stimulation event goes over threshold-no AP.
Battle between the two.
GABAA receptor?
Lots of binding sites.
GABA site (antagonist can bind- eg. bicuculine)
Transports chloride through.
AS3
Name the 5 binding sites on the GABAA receptor?
Gaba site
Benzodiazepine site
Barbiturate site
Steroid site
Picrotoxinin site
Benzodiazepine?
eg. diazepam
Increases the affinity of GABA for the GABAA receptor.
Used as treatment for some seizure types such as tonic-clonic, myoclonic and absense (clonazepam)
Name the 4 channel types that antiepileptic drugs target?
Calcium
Sodium
GABA
Glutamate
Glutamate
Excitatory
GABA?
Inhibitory
Phenytoin?
Diphenylhydantoin
Blocks tetanic firing through increasing sodium channel inactivity.
Reduces neurotransmitter release.
Carbamazepine?
Like phenytoin
Blocks tetanic firing through increasing sodium channel inactivation
Reuces transmitter release.
Potentiates GABA response.
Valproate?
Blocks tetanic firing through increasing sodium channel inactivation.
Reduces T-type calcium channel activity.
increases GABA levels by inhibiting breakdown.
Used against absence seizures.
Ethosuxamide?
Inhibits T-type calcium channels activity
Used against absence seizures
Lamotrigine?
Blocks sodium channels.
Inhibits the release of excitatory amino acids.
Topiramate?
Blocks sodium channels
Enhances the action of GABA
Gabapentin?
Elevate GABA levels
Binds to the calcium channel sbunits
Used in chronic pain management as well
Vigabatrin?
Inhibits GABA-T
Used to treat partial seizures.
