Epilepsy Flashcards
Define epilepsy
A neurological disorder representing a brain state that supports recurrent, unprovoked seizures
Define seizure
Abnormal paroxysmal changes in electrical activity of brain
Large scale synchronous discharges of neuronal networks
Define epileptogenesis
Process of brain developing epilepsy: going from normal function to generation of abnormal epileptic activity
Define focal onset epilepsy
Seizures arise from specific cortical area
Define generalised onset epilepsy
Seizures that don’t originate from specific cortical area
Define status epilepticus
Form of epilepsy that is life threatening medical emergency
How much of the brain is affected by tonic clonic seizure
Whole brain
State (in order) phases of tonic clonic seizure
Premonition Pre-tonic-clonic phase Tonic phase Clonic phase Postical period
What happens in premonition phase of tonic clonic seizure
Knowledge that seizure is imminent
What happens in the pre tonic clonic phase
Few myoclonic jerk
Brief clonic seizures
What happens in tonic phase
Cyanosis Tonic contraction of axial musculature Upward eye deviation Tonic limb contraction Epileptic cry Resp muscle contraction
What happens in clonic phase
Jerks of increased amplitude followed by relaxation
What happens in the postical period
Lethargy
Muscle tone
Headache
Muscle soreness
Name some structural changes that occur in epilepsy
Reorganisation of tissue in temporal lobe
Loss of Chandelier cells
How is hippocampus changed in epilepsy
Prominent loss of cells in CA2+ CA3 hippocampal areas
Hippocampus is sclerotic
What structural change may kead to reverberent excitatory circuit
Sprouting of mossy fibres of granule cells
What are chandlier cells
Chandelier cells are a special population of interneurones
GABAergic cells
Function of chandlier cells
Control activity of cortical pyramidal cells and synapse on axon initial segment of pyramidal cell
What is the effect of losing chandlier cells
Loss of inhibitory chandelier cells increases abnormal excitatory activity
What 3 cellular mechanisms linked to development of epilepsy, and what is each one mediated by
Abnormal neuronal excitability (ion channel)
Decreased neuronal inhibitor (GABA dependent)
Increased neuronal excitation (glutamate dependent)
What receptors are related to paroxysmal depolarising shift
NMDA gluatamate receptor
What is the role of glial cells in this case
Important role in glutamate transport and clearance through glutamate transports such as EAAT1/EAAT2
What 3 things happen because of primary insult
Gliosis
Neuron death
Mossy fibre sprouting
What does gliosis cause
Cytokine and growth factor release
Changes in receptor and ion channel expression
Neurone death
What does neurone death cause
Cytokine and growth factor release
Mossy fibre sprouting
What does cytokine and growth factor release cause
Changes in receptor and ion channel expression
Mossy fibre sprouting
What is the function of mTOR pathway
Major regulator of growth and homeostasis
What is the function of REST pathway
Negative regulation of expression of genes in CNS
Do interneurones tend to be GABAergic or glutamergic
GABAergic
Name 7 drugs that target sodium channels
Phenyltoin (peter) Carbamazepine (calmly) Sodium volproate (spoke, very) Lamotrigine (lightly) Topiramate (tony) Lacosamide (lets go to the) Zonisamide (zoo)
What is the absence seizure
Looks like daydreaming
Which 2 epilepsy drugs stabilise the inactivated state of the channels as well as their primary MOA (sodium channels)
Phenyltoin
Carbamazepine
What kind of seizure can sodium valproate be used to treat
All
How does lacosamide work
Blocks inactivated state of channel
How does topiramate work
Augmentation of GABA transmission
Inhibition of glutamate AMPA receptor signalling
Which 2 drugs can’t be used in absence seizures
Phenyltoin
Carbamezepine
Name 2 drugs that target calcium channels
Ethosuximide
Gabapentin/ pregabalin
How does ethossuximide work
Used in absence seizures blocks T type calcium channels
How does pregabalin work
Targets alpha 2 delta subunit of calcium channels
Does pregabalin increase or decrease GABA
Increase
What are benzodiazepines
GABA receptor positive allosteric modulator
Give an example of benzodiazepine
Clonazedam
Side effect of clonazedam
Sedation
How do barbiturates work
GABAa receptor positive allosteric modulator
Name 2 barbiturates used to treat epilepsy
Phenobarbitone
Stiripentol
Side effect of phenobarbitone
Leads to liver enzyme induction
Name a drug that targets neurotransmitter release, how does it work
Levetriracetam
Binds to synaptic protein SU2A modulating NT release
Name a drug that targets neurotransmitter uptake
Tiagabine
Mechanism of action of tiagabine
Inhibits GABA uptake
INhibits GAT-1 transporter for GABA
Name a drug that targets NT synthesis
Vigabatrin
How does vagabatrin work
Inhibition of GABA transamine therefore protects GABA
Overall inhibits GABA metabolism
