Epilepsy

Question 1

What is epilepsy

Answer 1

Disorder of the CNS characterised by recurrent, sudden large increases in electrical activity (electrical seizures) that may be localised or generalised. Electroencephalogram diagnoses epilepsy.

Question 2

What do symptoms depend on

Answer 2

The CNS region, e.g. if motor cortex is included area of seizure then uncontrolled movements would be expected
Whether the seizure is localised in one hemisphere or a particular part of the brain or is generalised throughout the brain
If localised initially, whether the seizure then becomes generalised by spreading to other regions of the CNS

Question 3

What is a partial seizure

Answer 3

if the seizure is restricted to a limited region. Simple if the subject remains conscious and aware or complex is consciousness is impaired.

Question 4

What is a primarily generalised seizure

Answer 4

most of the CNS is involved but no focus can be distinguished

Question 5

What is a secondarily generalised seizure

Answer 5

most of the CNS is involved but the excitation has spread from an initial focus

Question 6

How many children have seizures and how many go on to develop epilepsy

Answer 6

2-5% of children experience one or more seizures. 10% go on to develop some form of epilepsy in adulthood.

Question 7

What is tonic clonic seizure

Answer 7

a motor seizure, impaired awareness, generalised onset, 2-5 minutes. Sudden stiffening of muscles, followed by a fall and jerking movements

Question 8

What is a temporal lobe seizure

Answer 8

focal onset seizure of temporal lobe, characterised by emotional, sensory or memory related phenomena. No loss of awareness. Developing as the seizure spreads throughout the temporal lobe impairing consciousness to become a focal or bilateral generalised tonic clonic seizure

Question 9

What is an absence seizure

Answer 9

non-motor seizure with impaired awareness. Generalised onset, common in children. Repeated periods of sudden loss of awareness.

Question 10

What is status epilepticus

Answer 10

seizure does not spontaneously stop. Lasts > 30 minutes

Question 11

What are epilepsy syndromes in children

Answer 11

Generalised epilepsy with febrile seizure plus 
Lennox-Gastaut syndrome (multiple seizures and intellectual disability)
Dravet syndrome (epilepsy caused by hot temperature)

Question 12

What is benign febrile epilepsy linked to

Answer 12

mutation in KCNQ2 and KCNQ3 , which encodes voltage gated potassium channels.

Question 13

What is GEFS+ linked to

Answer 13

SCN1B, a gene that encodes an accessory subunit of the voltage gated sodium channel

Question 14

What does paroxysmal depolarising shift do

Answer 14

Initiates seizures. Epilepsy is often described as being due to an imbalance between glutamate-mediated excitation and GABA-mediated inhibition.

Question 15

What happens with surround inhibition

Answer 15

mediated by interneurons through feedback pathways has the effect of limiting spread of the input signalling. Increase GABA to improve inhibition.

Question 16

What happens with no surround inhibition

Answer 16

No surround inhibition - diverging synaptic connections of neurones in a relay nucleus can lead to spreading as well as blending of information flowing out of the nucleus

Question 17

What do sodium channel blockers do

Answer 17

Tonic clonic, partial and temporal lobe seizures

Carbamazepine, phenytoin, lacosamide

Question 18

What are the side effects of carbamazepine and phentonin

Answer 18

increase the frequency of absence seizures

Question 19

How do voltage gated sodium channels work

Answer 19

Drugs will reduce the likelihood of action potentials firing at high frequencies but have relatively little effect at low frequencies. Drug binds at inactivated state and stabilise it. Increases the refractoriness of the cell and limits the maximum frequency at which the cell can fire.

Question 20

What treats tonic clonic and absence seizures

Answer 20

Sodium valproate: mechanism uncertain. Combines a weak blocking action on voltage gated sodium channels with a weak inhibition of GABA transaminase.
Lamotrigine: Use dependent sodium channel blocker

Question 21

What does enhancing the activity of GABAergic system treat

Answer 21

Tonic clonic, partial, temporal

Question 22

What drugs treat GABergic systems

Answer 22

Benzos
Barbiturates
Vigabartin
Tiagabin
Gabapentin, pregablin
Retigabine
Perampanel
Leveiracetam

Question 23

What do benzodiazepiens do

Answer 23

enhance GABA activity. Bind to regulatory site on the GABAa receptor and increase the affinity of the receptor for GABA.

Question 24

What do barbiturates do

Answer 24

Prolongs GABA-activated Cl- channels opening when GABAa receptor is occupied

Question 25

What does vigabatrin do

Answer 25

contraindicated for absences): inhibits GABA transaminase

Question 26

What does tiagabin do

Answer 26

(contraindicated for absences): inhibits GABA uptake an therefore increases the concentration of GABA in extracellular space

Question 27

What do gabapentin and pregablin do

Answer 27

molecular target voltage-gated Ca2= channels, compromise NT release

Question 28

What does retigabine do

Answer 28

provoking the opening of k+ channels of the KCNQ type so the anticonvulsant effect is probably due to stabilisation of the resting membrane potential of neurones

Question 29

What perampanel do

Answer 29

Antagonist of AMPA

Question 30

What does vagal stimualtion do

Answer 30

electrical stimuli to affect vagus nerve. Activated by a magnet to deliver a predefined program of stimuli to abort an ongoing or impending attack.

Question 31

What is a ketogenic diet

Answer 31

high fat, low carb. Used in children