Epilepsy

Question 1

What are the causes of epilepsy?

Answer 1

Symptomatic:

Trauma - head injury.
Infection - febrile (caused by fever) seizures in children.
Brain tumour - affected area or adjacent brain regions.

Idiopathic:

Cause is unknown.
Familial - common but most genes involved unknown.

Question 2

What are seizures in general?

Answer 2

Not usually life threatening.

The brain almost always stops the seizure on its own.

Breathing may cease for a few seconds, and the patient may turn blue.

People don’t feel pain during a seizure; muscles may be sore afterward.

Person may be feel disorientated for a while after the seizure.

Question 3

What is convulsion?

Answer 3

Sudden attack of involuntary muscular contractions and relaxations.

Question 4

What is a seizure?

Answer 4

Abnormal central nervous system electrical activity.

Question 5

What is epilepsy?

Answer 5

A group of recurrent disorders of cerebral function characterised by both seizures and convulsions.

Question 6

What are the two types of seizures?

Answer 6

Two broad classifications:

Focal seizures (Partial seizures) - 3 subtypes.

Generalised seizures - 6 subtypes.

Question 7

What are focal seizures / partial seizures?

Answer 7

Remain localised to focus.

Degree of consciousness varies.

Lasts for a few minutes, symptoms depend on brain region involved:

Involuntary muscle contractions such as muscular jerk (e.g. motor cortex).

Abnormal sensory experiences such as smell or taste
(e.g. sensory cortex).

Repetitive movements (smacking of lips) accompanied by changes in mood and behaviour (e.g. temporal cortex).

Question 8

What are generalised seizures?

Answer 8

These tend to be more dangerous than focal seizures / partial seizures.

Excessive electrical activity in both cerebral hemispheres.

Usually originates in the thalamus or brainstem.

Affects the whole body.

Loss of consciousness is common.

Question 9

What are the different types of generalised seizures?

Answer 9

Myoclonic - brief shock-like muscle jerks generalized or restricted to part of one extremity.

Atonic - sudden loss of muscle tone.

Tonic seizures - sudden stiffening of the body, arms, or legs.

Clonic seizures - rhythmic jerking movements of the arms and legs without a tonic component.

Tonic-clonic (grand mal) - the most dramatic of all; tonic phase followed by clonic phase.

Absence (petit mal):

Rapid and brief loss of consciousness.
More common in young children.
Can include the blinking of the eyelids or lip movements.

Status Epilepticus:

A seizure lasting longer than 30 min, or 3 seizures without a normal period in between.
May be fatal.
Emergency intervention required.

Question 10

What drugs affect sodium channels?

Answer 10

Phenytoin
Carmazepine
Sodium valproate
Lamotrigine

Question 11

What drugs affect calcium channels?

Answer 11

Ethosuximide

Gabapentin

Question 12

What drugs affect GABA release and metabolism?

Answer 12

Tiagabine
Vigabatrin
Levetiracetam

Question 13

What is the mechanism of action of Antiepileptic drugs?

Answer 13

3 main categories of therapeutics:

Inhibition of voltage-gated Na+ channels to slow neuron firing.

Enhancement of the inhibitory effects of the neurotransmitter GABA.

Inhibition of calcium channels.

Question 14

What is thought about the neurobiology of epilepsy​?

Answer 14

Plays a central role for the excitatory neurotransmiter glutamate (increased in epilepsy)​.

Inhibitory gamma amino butyric acid (GABA) (decreased)​.

Question 15

What are anti-epileptic drugs (AEDs)?

Answer 15

Control seizures in 70% of patients​.

​Aim is to prevent excessive neuronal discharges without affecting normal neuronal transmission.​

Many current drugs do however cause side effects.​

​Research into new antiepileptic drugs is important​.

​Goal of therapy is to maximise quality of life by eliminating seizures (or diminish seizure frequency) while minimizing adverse drug effects​.

Question 16

What is the mechanism of action of phenytoin?

Answer 16

Use-dependent block of sodium ion channels​.

Prolongs their inactive state which prevents further action potential generation​.

Reduces the synaptic release of glutamate and enhances the release of GABA​.

​Effective in many forms of epilepsy - but not in absence seizures.​

​Highly bound to plasma proteins (about 90%).
Non-linear relationship between dose and plasma concentration.
Extreme variations in plasma concentration.
Toxic effects.
Therapeutic drug monitoring is essential​.

Question 17

What are the adverse effects of phenytoin?

Answer 17

Nystagmus (involuntary and jerky repetitive movements of the eyeballs) - occurs early in treatment​.

Gingival hyperplasia - increase in the size of the gingiva (gums)​.

​Hirsutism - excessive body hair.​

​Diplopia - double vision (dose related)​.

​Ataxia - lack of voluntary coordination of muscle movements (dose related).​

​Sedation (dose related).​

​Foetal abnormalities when taken by the mother during pregnancy​.

Question 18

What is the mechanism of action of carbamazepine?

Answer 18

Similar profile to that of phenytoin, but with fewer unwanted side-effects.​

Blocks sodium channels​ and decreases neurotransmitter release​.

Long considered drug of choice for partial and generalised seizures, but is being superseded by newer agents​

Effective in many forms of epilepsy - but not in absence seizures.​

Main side-effects include sedation, ataxia, mental disturbances, water retention.​

Question 19

What is the mechanism of action of sodium valproate​?

Answer 19

Suppress repetitive neuronal firing through inhibition of voltage-sensitive sodium ion channels​.

Suppresses thalamic excitability by inhibiting transient low threshold calcium ion channels​.

Enhances GABA in CNS by inhibiting the catabolic enzyme GABA transaminase.​

Effective in all forms of epilepsy, but drug of choice in treatment of absences seizures.​

Relatively few side effects which include alopecia (hair loss) and liver damage (rare but serious). ​

Question 20

What is the mechanism of action of lamotrigine?

Answer 20

Inhibits release of glutamate. ​

Suppress repetitive neuronal firing by inhibition of voltage-sensitive sodium ion channels​.

Used in the treatment of partial seizures, tonic-clonic and absences seizures​.

​Relatively few unwanted side effects: mainly nausea, sedation, ataxia and skin rashes.​

Question 21

What is the mechanism of action of ethosuximide?

Answer 21

Reduces low threshold calcium ion currents (T-Type Ca2+ channels) in thalamic neurons​.

Effective in the treatment of absences seizures.​

Relatively few unwanted side effects: mainly nausea and anorexia.​

Question 22

What is the mechanism of action of gabapentin​?

Answer 22

Blocks Ca2+ ion channels.​

Inhibits depolarisation-induced calcium influx at nerve terminals leading to decreased glutamate release.​

Effective in the treatment of partial seizures.​

​Relatively few unwanted side effects: mainly nausea and sedation. ​​

Question 23

What is the mechanism of action of tiagabine​?

Answer 23

​​Inhibits the GABA transporter (GAT) responsible for removing extracellular levels of GABA​.

Increased levels of GABA in synapses​.

Increased inhibitory transmission​.

​Used in the treatment of partial seizures. ​

Relatively few unwanted side effects: mainly nausea, sedation and ataxia.​

Question 24

What is the mechanism of action of vigabatrin​?

Answer 24

Reversible inhibitor of the enzyme GABA aminotransferase (enzyme that degrades GABA).​

Increased levels of GABA released at synaptic sites​.

Enhanced neuronal inhibition​.

Used in the treatment of partial seizures.

Well tolerated generally​

Side effects:​
​
Drowsiness​.
Dizziness​.
Weight gain.​ ​

Question 25

What is the mechanism of action of levetiracetam?

Answer 25

Binds to synaptic vesicular protein SV2A which alters synaptic neurotransmitter release​.

​Used in the treatment of partial seizures.

Side effects​:

Somnolence - sleepiness​.
Asthenia - abnormal physical weakness or lack of energy​.
Dizziness.​