Lecture 4 - epilepsy Flashcards
what is epilepsy?
seizures - a transient occurrence of signs and/or symptoms due to normal abnormal excessive or synchronous neuronal activity in the brain.
some seizures can hardly be noticed while others are totally disabling - generally depends of area of the brain the seizure occurs in.
but a seizure does not equal epilepsy. seizure can occur for many reasons eg diabetes, stroke etc.
what is the clinical definition of epilepsy?
- at least two unprovoked seizures occuirgn >24 hrs
- If a person experiences one unprovoked seizure or a reflex seizure, the likelihood of having more seizures within the next 10 years is comparable to the general recurrence rate of at least 60% after two unprovoked seizures..
- diagnosis of epilepsy syndrome
what are the classification of generalised seizures?
absence - altered awareness
tonic/clonic- combined
clonic - bilaterally rhythmic jerking
tonic - bilaterally increased tone in limbs
atonic - sudden loss of muscle tone
myoclonic - single or series of muscle contraction
what is status epileptics?
status epileptics happens when there is failure of mechanisms responsible to terminate seizure or when there is initiation of processes in the brain that lead to abnormally prolonged seizures.
It is a condition that can have long term consequences including neuronal death. neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
what is the classification of focal seizures
aura, motor, autonomic and awareness/ responsiveness
what is the difference between generalised seizures and focal seizures?
generalised seizures - arising within and rapidly engaging bilaterally distributed networks in both hemispheres. whereas focal seizures are originating in networks limited to one hemisphere
what causes epilepsy? x6
genetic - dravets syndrome (mutation in gene which affects sodium channels responding to lower voltage and neuronal is more excitable)
structural - acquired or genetic (brain injury following car crash, stroke leading to brain changes)
metabolic - glutamate transporter deficiency
immune - rasmussen syndroom autoimmune disease - targets AMP receptors extra sensitive so increased excitability
infectious - bacterial and viral encephalitis
(leadign cause)
unknown
what are co morbidities associated with epilepsy? x5
stroke, migraines/ headaches, and dementia al have a bidirectional relationship and neurological comorbidity.
traumatic brain injury can cause epilepsy
epilepsy can cause ASD
epilepsy can cause ADHD
multiple sclerosis - epilepsy doesn’t cause ms
what are the seizure sequence and underlying clues in the mechanisms to how a seizure starts in the brain?
stage 1 - initiation - abnormal voltage-gated channels (sodium channels) - excess excitability
stage 2 - synchronisation - excess excitability causes excess neurotransmitter leading to abnormal receptor-operated channels
stage 3- propagation - recruitment of neurones via anatomical connections
what principle is sued to design antiepileptic drugs?
increasing glutamate activity or reducing GABA activity can lead to seizures. The GABA antagonist pentylenetetrazole reduces amount of GABA in the brain, which causes excess glutamate, leading to seizures. antiepileptic drugs are used to redress this imbalance
what are strategies for the treatment of epilepsy?
inhibitor of voltage- gated sodium channels, promote inhibitory neurotransmission or inhibition of voltage-gated calcium channels.
describe how excitation works through the Brain under normal conditions
Excitation causes sodium channels to become activated and causing depolarisation. the action passes down the axon which causes neurotransmitter release. this is under the control of excitatory Drive of glutamate and also through inhibitory drive through GABA
what drugs that cause inhibition of voltage gated sodium channels?
phenytoin, carbamazepine and oxycarbazepine are all sodium channel primary targets
lamotrigine is also a sodium channel primary target but HVA Ca2+ channels is also a target
how do antiepileptic drugs cause reduced excitatory?
they stabilise inactivated state of sodium channels for longer, so can’t be reactivated to induce more excitability and action
what drugs are used for the enhancement of GABA action and what are their actions?
BSDs - increase the frequency of opening GABAa channels
phenobarbital- increases the probability of opening GBAa channels
vigabatrin - inhibits GABA transaminase
tiagabine - inhibits GABA transamine
all have GABA function as their primary target
what as drugs are used for inhibition of voltage gated calcium channels what are their actions and other targets?
ethosuzimide inhibits the T type calcium channels
prcegablin inhibits HVA calcium channels and may target glutamate receptors
gabapentin inhibits HVA calcium channels and can target Voltage gated, sodium channels and GABA turnover.
explain how blocking calcium helps seizures
blocking calcium channels causes reduced glutamate release which is the cause foe excitability, and therefore redresses balance of normal activity in the brain
what are other drugs that have different mechanisms of action in addressing the balance of activity ?
sodium valproate - affects calcium, sodium and GABA channels
leviracetam affects calcium, GABA channels
felbatmate affects calcium, sodium, GABA and glutamate receptors
perampanel only affects glutamate receptors
what are the treatment guidelines for generalised seizures and trasnsport mechansim?
1st line - sodium valproate
alternative is lamotrigine, topiramate. contraindications with valporate and pregnancy
diffusion and carrier mediated trasnport
what are the treatment guidelines for focal seizures and trasnport mechanism?
1st lien - lamotrigine,
alternative - levetiracetam, carbamazepine
contraindications - patent dependant side effects
Carrier-mediated transport
what are the treatment guidelines for absence seizures and trasnport mechanism?
1st line - ethosuximide
alternative - sodium valproate, lamotrigine
patient dependant side effects
diffusion
what are the treatment guidelines for status epileptics and trasnport mechanism?
1st line - midalozam buccally or intranasally
alternative - lorazepam, diazepam
patient dependant side effects
diffusion
what is the treatment guideline for atonic-tonic seizure treatment?
1st line - sodium valproate
alternative - lamotrigine
what is the treatment guideline for myoclonic seizures?
1st lien - sodium valproate
alternative - levetiracetam, 2nd lamotrigine l
