epilepsy Flashcards
what is epilepsy
repeated occurance of sudden excessive or synchronous discharges in cerebral cortical neurones resulting in a disruption of consciousness, disturbance of
characterised by recurrent epileptic seizures
what causes epileptic seizures
seizures resulting from excessive activity of neurones in the brain
seizures are sudden short events involving a change in a persons awareness of where they are or what they are doing
epileptic attacks result from abnormal hyperexcitability of neurones, often originating in a localised area of the brain, called the epileptic focus
what are 2 types of epilepsy, what causes them
symptomatic or idiopathic
symptomatic indicates a probable cause exists such as: cerebrovascular lesions, perinatal or postnatal trauma, CNS infections, tumours or congenital malformations of the CNS
idiopathic indicates no obvious cause can be found; usually due to another neurological condition, gene factors are probably responsible
what are 2 main categories of seizures
partial: begins with local discharge in one area of the brain
primary generalised: begins with widespread electrical discharge that involves both sides of brain at once
what are subcategories of primary generalised seizures and how are they characterised
primary generalised
absence (petit mal): brief interruption of consciousness and motor activity, thalami-cortical mechanism
tonic-clonic (grand mal): loss of consciousness, convulsions
myoclonic: brief contraction of muscle groups, may accompany other seizures
atonic: sudden loss of muscle tone, may be widespread or local
what are the subcategories of partial seizures
simple partial: motor spasms, sensory hallucination, most common in frontal cortex
complex partial: impaired consciousness, possible automatisms, most common in temporal lobes
secondary generalised: partial spreading to generalised
what is status epilepticus
repeated seizures with no recovery between attacks
causes additional problems such as metabolic disturbance and neuronal damage
what to brain happens during epileptogenesis
the epileptic focus in some neurones may undergo synchronous, repetitive depolarisations called paroxysmal depolarisation shifts, this synchronous activity is propagated to connected brain regions
transition from normal spiking paroxysmal depolarisation shifts may involve changes in intrinsic properties of neurones
increase in calcium and sodium channel activity and decrease in potassium channel activity can promote bursting
how does epileptogenesis effect synapses
causes changes in synaptic efficacy:
more EPSPs lead to excessive activation of NMDARs, fewer IPSPs result in loss of GABA mediated inhibition
paroxysmal depolarisation shifts may all cause changes in synaptic connectivity
what are mutations that can possibly cause idiopathic epilepsy
mutations in voltage gated sodium channels e.g in gene SCN1A, mutations cause gain of function causing impaired inactivation
mutations in voltage gated potassium channels e.g in gene KCNA1, causing loss of function, reducing potassium efflux which causes repolarisation of neurone
voltage gated chloride channels e.g in gene CCLCN2, mutations causing loss of function of these cause decrease in IPSPs
GABAa receptor: mutation in genes examples GABRA1, causing reduction in function due to increased desensitisation or failed insertion into membrane
nAchRs: mutation in gene such as CHRNA4, mutations causing gain of function such as prolong opening
what is the aim of anti epileptic drugs
must dampen the neuronal hyperexcitability that leads to or sustains an epileptic attack, this can be done by reducing excitation or enhancing inhibitory influences
reduction in excitation can result from decreased activity of voltage gated sodium and calcium channels or decreased efficacy of excitatory synapses
enhanced inhibition is acheived by increased efficacy of inhibitory synapses or increase in potassium channel activity
what are categories of establised (older) anti epileptics, give an example of each
hydantoins: phenytoin
dibenzapines: carbamazepine
succinimides: ethosuximide
barbiturates: phenobarbitone
bentos: diazepam, clonazepam
fatty acids: sodium valproate
what are examples of newer anti epileptics
lamotrigine, gabapentin
how do anti epileptics effect sodium channels, which drugs do this
inhibition of sodium channels in hyperexcitable cells can be achieved without affecting normal electrical activity
phenytoin and carbamazepine have this action
lamotrigine is an example of a newer drug which also has this action
ethosuximide reduces excitability by action on voltage gated sodium channels and possibly clacium channels in the thalamus which explains its effectiveness against absence seizures generated by thalamic oscillations
gabapentin was developed as a GABA agonist, however does not bind to GABA receptors, it is effective in partial and generalised seizures possibly by modifying sodium channels, main effect is block of calcium channels though
what drugs target chloride channels, what is their mechanism
phenobarbitone may hyperpolarise neurones by directly increasing chloride influx, through stimulation of GABA receptors with and without presence of GABA, this action is not restricted to the epileptic focus and results in general sedation
