13 - Epilepsy Flashcards
What is epilepsy?
Neurological disorder that represents a brain state that supports recurrent, unprovoked seizures
What are seizures?
abnormal, paroxysmal changes in the electrical activity of the brain; they reflect large scale synchronous discharges of neuronal networks
What is the prevalence of epilepsy in the UK?
1% prevalence in the UK
What is focal onset
Where the seizure affects one hemisphere of the brain
What is generalised onset
The seizure effects both cerebral hemisphere
What is status elipticus
A form of epilepsy which is a life-threatening medical emergency
Seizures which last >5 mins or >1 seizure in 5 mins, without regaining consciousness
Stages of a tonic clonic seizure
Premonition Pre-tonic-clonic phase Tonic Phase Clonic Phase Postictal period
Premonition
Vague sense that a seizure is about to happen
Pre-tonic-clonic phase
A few myoclonic jerks or breif seizures
Tonic Phase
Tonic contraction of axial musculature causing contraction of the limbs, cyanosis, pupillary dilation, respiratory muscle contraction and contraction of the jaw muscles
Clonic phase
Jerks of increasing amplitude
followed by relaxation - sphincter opening may occur
Postictal period
generalised lethargy
decreased muscle tone
headache
muscle soreness
How to diagnose epilepsy
Occurrence of 2 or more seizures
witness is essential
Which area of hippocampus is there cell loss in epilepsy
CA2
CA3
What will you see in an MRI of epileptic
Loss of neurones
distortion and compression of layers, gliosis, different tract orientation
What are chandelier cells
interneurons which are GABAergic cells
Control activity of cortical pyramidal cells
What happens to chandelier cells in epilepsy and what does this cause
Loss of inhibitory chandelier cells increases the risk of abnormal excitatory activity
Conditions with high risk of epilepsy
Craniotomy Traumatic Brain Injury Stroke Brain Tumour Aneurysm CNS infection
Cellular mechanisms linked to development of epilepsy
Abnormal neuronal excitability - Ion channels
Decreased neuronal inhibition - GABA
Increased neuronal excitation - Glutamate
What role do glial cells have in epilepsy
Role in glutamate transport and clearance via glutamate transporters EAAT1 and EAAT2
Phenytoin
SODIUM CHANNEL BLOCKER
Stabilises inactivated state of channels; dose –dependent or zero order or saturation kinetics; liver enzyme induction; not used in absence seizures
Carbamazepine
SODIUM CHANNEL BLOCKER
Stabilises the inactivated state of channels; liver enzyme induction; hypersensitivity reactions; not used in absence seizures
Sodium Valporate
SODIUM CHANNEL BLOCKER
Can be used in all types of seizures
Lamotrigine
SODIUM CHANNEL BLOCKER
Also activity at calcium channels; presynaptic inhibition of glutamate release – Favourable in pregnancy
Topiramate
SODIUM CHANNEL BLOCKER
Also active at AMPA and kainite glutamate receptors
Lacosamide
SODIUM CHANNEL BLOCKER
Binds to the inactivated state of channels
Zonisamide
SODIUM CHANNEL BLOCKER
Blocks calcium channels too
Ethosuximide
CALCIUM CHANNEL BLOCKER
Used in absence seizures(Petit mal), blocks T-type calcium channels
Gabapentin (pregabalin)
CALCIUM CHANNEL BLOCKER
Also increases GABA levels– Target the a2δ subunit
Clonazepam
BENZODIAZEPINE
GABAA receptor positive allosteric modulators –> Sedation
Phenobarbitone
BARBITURATE
GABAA receptor positive allosteric modulators
Stiripentol
Similar to barbiturate
Levetiracetam
NTS RELEASE
Binds to the synaptic protein SV2A; modulates neurotransmitter release
Tiagabine
NTS UPTAKE
Inhibits GAT-1 transporter for GABA
Vigabatrin
NTS SYNTHESIS
Inhibition
What do you treat focal seizures with
carbamazepine, lamotrigine, sodium valproate
What do you treat tonic clonic seizures with
carbamazepine, lamotrigine, sodium valproate
What do you treat absence seizures with
ethosuximide, sodium valproate
What do you treat Myoclonic Seizures with
sodium valproate, clonazepam, levetiracetam
