Epilepsy

Question 1

Define epilepsy

Answer 1

A neurological disorder representing a brain state that supports recurrent, unprovoked seizures

Question 2

Define seizure

Answer 2

Abnormal paroxysmal changes in electrical activity of brain

Large scale synchronous discharges of neuronal networks

Question 3

Define epileptogenesis

Answer 3

Process of brain developing epilepsy: going from normal function to generation of abnormal epileptic activity

Question 4

Define focal onset epilepsy

Answer 4

Seizures arise from specific cortical area

Question 5

Define generalised onset epilepsy

Answer 5

Seizures that don’t originate from specific cortical area

Question 6

Define status epilepticus

Answer 6

Form of epilepsy that is life threatening medical emergency

Question 7

How much of the brain is affected by tonic clonic seizure

Answer 7

Whole brain

Question 8

State (in order) phases of tonic clonic seizure

Answer 8

Premonition
Pre-tonic-clonic phase
Tonic phase
Clonic phase
Postical period

Question 9

What happens in premonition phase of tonic clonic seizure

Answer 9

Knowledge that seizure is imminent

Question 10

What happens in the pre tonic clonic phase

Answer 10

Few myoclonic jerk

Brief clonic seizures

Question 11

What happens in tonic phase

Answer 11

Cyanosis
Tonic contraction of axial musculature
Upward eye deviation
Tonic limb contraction
Epileptic cry
Resp muscle contraction

Question 12

What happens in clonic phase

Answer 12

Jerks of increased amplitude followed by relaxation

Question 13

What happens in the postical period

Answer 13

Lethargy
Muscle tone
Headache
Muscle soreness

Question 14

Name some structural changes that occur in epilepsy

Answer 14

Reorganisation of tissue in temporal lobe

Loss of Chandelier cells

Question 15

How is hippocampus changed in epilepsy

Answer 15

Prominent loss of cells in CA2+ CA3 hippocampal areas

Hippocampus is sclerotic

Question 16

What structural change may kead to reverberent excitatory circuit

Answer 16

Sprouting of mossy fibres of granule cells

Question 17

What are chandlier cells

Answer 17

Chandelier cells are a special population of interneurones

GABAergic cells

Question 18

Function of chandlier cells

Answer 18

Control activity of cortical pyramidal cells and synapse on axon initial segment of pyramidal cell

Question 19

What is the effect of losing chandlier cells

Answer 19

Loss of inhibitory chandelier cells increases abnormal excitatory activity

Question 20

What 3 cellular mechanisms linked to development of epilepsy, and what is each one mediated by

Answer 20

Abnormal neuronal excitability (ion channel)
Decreased neuronal inhibitor (GABA dependent)
Increased neuronal excitation (glutamate dependent)

Question 21

What receptors are related to paroxysmal depolarising shift

Answer 21

NMDA gluatamate receptor

Question 22

What is the role of glial cells in this case

Answer 22

Important role in glutamate transport and clearance through glutamate transports such as EAAT1/EAAT2

Question 23

What 3 things happen because of primary insult

Answer 23

Gliosis
Neuron death
Mossy fibre sprouting

Question 24

What does gliosis cause

Answer 24

Cytokine and growth factor release
Changes in receptor and ion channel expression
Neurone death

Question 25

What does neurone death cause

Answer 25

Cytokine and growth factor release | Mossy fibre sprouting

Question 26

What does cytokine and growth factor release cause

Answer 26

Changes in receptor and ion channel expression | Mossy fibre sprouting

Question 27

What is the function of mTOR pathway

Answer 27

Major regulator of growth and homeostasis

Question 28

What is the function of REST pathway

Answer 28

Negative regulation of expression of genes in CNS

Question 29

Do interneurones tend to be GABAergic or glutamergic

Answer 29

GABAergic

Question 30

Name 7 drugs that target sodium channels

Answer 30

``` Phenyltoin (peter) Carbamazepine (calmly) Sodium volproate (spoke, very) Lamotrigine (lightly) Topiramate (tony) Lacosamide (lets go to the) Zonisamide (zoo) ```

Question 31

What is the absence seizure

Answer 31

Looks like daydreaming

Question 32

Which 2 epilepsy drugs stabilise the inactivated state of the channels as well as their primary MOA (sodium channels)

Answer 32

Phenyltoin | Carbamazepine

Question 33

What kind of seizure can sodium valproate be used to treat

Answer 33

All

Question 34

How does lacosamide work

Answer 34

Blocks inactivated state of channel

Question 35

How does topiramate work

Answer 35

Augmentation of GABA transmission | Inhibition of glutamate AMPA receptor signalling

Question 36

Which 2 drugs can't be used in absence seizures

Answer 36

Phenyltoin | Carbamezepine

Question 37

Name 2 drugs that target calcium channels

Answer 37

Ethosuximide | Gabapentin/ pregabalin

Question 38

How does ethossuximide work

Answer 38

Used in absence seizures blocks T type calcium channels

Question 39

How does pregabalin work

Answer 39

Targets alpha 2 delta subunit of calcium channels

Question 40

Does pregabalin increase or decrease GABA

Answer 40

Increase

Question 41

What are benzodiazepines

Answer 41

GABA receptor positive allosteric modulator

Question 42

Give an example of benzodiazepine

Answer 42

Clonazedam

Question 43

Side effect of clonazedam

Answer 43

Sedation

Question 44

How do barbiturates work

Answer 44

GABAa receptor positive allosteric modulator

Question 45

Name 2 barbiturates used to treat epilepsy

Answer 45

Phenobarbitone | Stiripentol

Question 46

Side effect of phenobarbitone

Answer 46

Leads to liver enzyme induction

Question 47

Name a drug that targets neurotransmitter release, how does it work

Answer 47

Levetriracetam | Binds to synaptic protein SU2A modulating NT release

Question 48

Name a drug that targets neurotransmitter uptake

Answer 48

Tiagabine

Question 49

Mechanism of action of tiagabine

Answer 49

Inhibits GABA uptake | INhibits GAT-1 transporter for GABA

Question 50

Name a drug that targets NT synthesis

Answer 50

Vigabatrin

Question 51

How does vagabatrin work

Answer 51

Inhibition of GABA transamine therefore protects GABA | Overall inhibits GABA metabolism