Epilepsy Flashcards
What does the term epilepsy refer to
The term epilepsy refers to a disorder of brain function characterized by the periodic and unpredictable occurrence of seizures.
Paroxysmal alteration in brain activity- time limited- clinically detectable event (seizure).
What is meant by a seizure
The term seizure refers to a transient alteration of behaviour due to the disordered, synchronous, and rhythmic firing of populations of brain neurones.
What are drugs that treat seizures termed
The pharmacological agents in current clinical use for inhibition of seizures are referred to as anticonvulsant or antiepileptic drugs.
What is important to remember about seizures
More than one seizure
Seizures must occur in the absence of abnormal metabolic states (most people will seizure if they are hyponatraemic).
Highest incidence in early and late life
Are febrile convulsions in childhood classed as epilepsy
No, but if prolonged, they may predispose to epilepsy.
Where do seizures arise from and what can they be classified into
Seizures are thought to arise from the cerebral cortex and they can be classified into partial seizures, those beginning focally at a cortical site, and generalized seizures, those that involve both hemispheres widely from the outset. The behavioural manifestations of a seizure are determined by the functions normally served by the cortical site at which the seizure arises.
Describe what may occur in a seizure involving the motor cortex
Thus, for example, a seizure involving the motor cortex is associated with clonic jerking of the body part controlled by this region of the cortex.
Describe the difference between simple and complex partial seizures
A simple partial seizure is associated with preservation of consciousness, whilst a complex partial seizure is associated with impairment of consciousness (temporal lobe).
Describe simple partial seizures
May arise from an intracerebral structural defect and causes motor or sensory symptoms localised to one body part
May spread to adjacent areas as the electrical activity spreads to contiguous regions of the cortex (Jacksonian march).
An underlying structural defect may be found.
Describe seizures arising in the medial temporal lobe
May cause disturbances in smell and taste, visual hallucinations and a sense of déjá vu.
May evolve to tonic-clonic (secondary generalisation)
weakness following the event can last from minutes to hours (Todd’s paresis).
What type of seizures are included in primary generalised epilepsy
Examples of generalized seizures include absence, myoclonic and tonicclonic seizures.
Describe the potential causes of epilepsy
Epilepsy is a neurological disorder associated with abnormal neurotransmitter function in the brain. A decrease in GABAmediated inhibition or an increase in glutamate-mediated excitation in the brain may result in seizure activity. Indeed, both glutamate and GABA are thought to play key roles in the brain mechanisms causing epilepsy in man.
What is meant by generalised epilepsy
whole brain engulfed simultaneously by abnormal electrical activity
Describe tonic-clonic seizure
tonic maintained muscle contraction - holding still after collapse to floor; clonic rhythmic contractions 20-30s after the tonic contraction; followed by laboured breathing - grand mal
Sudden tonic contraction of muscles- with upward eye deviation
Initial EEG changes are bilateral.
Describe absence seizures
usually children, lose concentration and gaze rises.
AKA petit mal
Brief interruption of activity sometimes with complex motor activity (fumbling clothes)
No collapse
EEG shows 3 p/s spike-and-wave activity.
Describe myoclonic seizures
individual jerks of muscle
Describe atonic seizures
lose all muscle tone and fall forward to face/head - quick recovery
Describe the different types of partial seizures
Simple: causes contralateral muscle twitching/contractions
Complex: arises in temporal lobe, hard to treat; partial TLOC/unawareness, pluck at clothes and comb hair, aimless wandering, blank face, automatic actions
Secondarily generalised: generalised that began as partial
Describe the pharmacological evidence for the role of NTs in epilepsy
Impairment of GABA-mediated inhibition causes seizures in animals e.g. impairment of synthesis, release (tetanus toxin) or postsynaptic action (bicuculline, picrotoxin).
Enhancement of GABA-mediated inhibition leads to seizure suppression e.g. central (i.c.v.) administration of GABA or inhibition of the GABA metabolizing enzyme GABA-T (vigabatri
Many clinically useful anticonvulsant drugs are known to act, at least in part, by potentiating central GABA-mediated inhibition e.g. benzodiazepines, phenobarbital (see Section 3).
Central (i.c.v.; focal) administration of glutamate or glutamate receptor agonists causes seizure-like activity in animals.
Glutamate receptor antagonists are anticonvulsant in experimental models of epilepsy.
Some therapeutically effective anticonvulsant drugs act partly by blocking glutamate-mediated excitation in the brain e.g. phenobarbital.
Describe the biochemical evidence for the role of NTs in epilepsy
Cobalt-induced seizures in rodents are associated with ↑ glutamate release and with ↓ GABA concentration, ↓ GAD activity and ↓ GABA uptake (probably reflecting GABA neurone loss) at the seizure focus.
Audiogenic seizures in mice (DBA/2 mice) are associated with ↑ glutamate receptor binding in the brain and with ↓ GABA release from depolarized brain slices.
The baboon Papio papio, which is highly sensitive to photically induced seizures, has a lower than normal CSF GABA concentration.
Describe GABA synapses
inhibitory CNS synapses found on the cell body - GABA has a similar structure to glutamate
Produced from glutamate using glutamic acid decarboxylase to remove carboxylic acid group
GABA released and binds with GABAA Receptors to hyperpolarise post-synaptic membrane, increasing the excitation threshold (IPSP)
GABA Transporters on glial cells take up cleft GABA, to allow conversion to succinate semialdehyde using GABA transaminase
Describe the use of Valproate
Weak effect on GABA aminotransferase (inhibiting it)and Na+ channels (stabilising neuronal membrane, preventing depolarisation)
Can be used for most seizures, especially absence
Describe the use of Phenoarbital
Binds to GABAa receptors, potentiating the effect of normal GABA
Inhibits glutamate-mediated excitation
All types except absence
Describe the use of benzodiazepines (clonazepam, diazepam).
potentiates the effects of GABA binding
All types
Diazepam used i.v to control status epilepticus
Describe the use of vigabatrin
Inhibits GABA aminotransferase
All types
Appears to be useful in patients who are resistant to other drugs
Describe the use of Tigabine
Inhibits GABA reuptake
Focal seizures
Describe the offset effects of Tigabine
Dopamine D1 and 2
5-HT
Muscarinic
What is status epilepticus
Seizures occurring in series with no recovery of consciousness, or a seizure lasting more than 30 minutes.
Why do drugs that inhibit GAT prevent
Re-uptake of GABA- more can bind
What is the issue of having affinity for other receptors
Side effects
