Epilepsy and anti epileptic drugs

Question 1

What is a seizure?

Answer 1

• Clinical manifestation of abnormal excessive excitation and synchronisation of a group of neurones within the brain
• Sudden and temporary

Question 2

What causes seizures?

Answer 2

• Loss of inhibitory signalling (GABA)
• Unchecked excitatory signalling
• Abnormally synchronised oscillations
• Post-tetanic potentiation
• Synaptic plasticity feedback mechanisms

Question 3

Where do seizures occur?

Answer 3

• Anywhere in the brain
• Location of uncontrolled signalling dictates how a seizure presents

Question 4

What can cause non-epileptic seizures?

Answer 4

• Drugs
• CNS infection
• Alcohol
• Hypoglycaemia
• Pyrexia
• Psychological
• Need to treat seizure AND underlying condition

Question 5

What are psychological seizures?

Answer 5

• Dissociative seizures
• Caused by extreme emotional stress and many sufferers are epileptic

Question 6

What are some conditions which may present with similar features to epilepsy?

Answer 6

• Vasovagal syncope
• Cardiac arrhythmias
• Panic attack
• TIA
• Migraine

Question 7

What are some differentials for epilepsy in children?

Answer 7

• Febrile convulsions
• Breath-holding attacks
• Night terrors
• Stereotyped/ritualistic behaviour especially in those with a learning disability

Question 8

What is epilepsy?

Answer 8

• A transient occurrence of signs and symptoms due to abnormal excessive or synchronous activity in the brain
• A disorder of the brain characterised by an enduring predisposition to generate epileptic seizures

Question 9

What are the risk factors of epilepsy?

Answer 9

• Premature birth
• Complicated febrile seizure
• Genetic conditions e.g. tuberous sclerosis, neurofibromatosis
• Head trauma, infection, tumour
• Cerebrovascular disease
• Dementia and neurodegenerative disorders

Question 10

How do we define epilepsy?

Answer 10

• Epilepsy is a tendency towards recurrent seizures unprovoked by a systemic or neurological insult
• At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
• One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures

Question 11

What are the next steps that need to be made after a patient has a seizure?

Answer 11

• Urgent referral following first suspected seizure
• Assess risk of second seizure
• Provide information on recognising a further seizure
• First aid and safety guidance

Question 12

How do we make an epilepsy diagnosis?

Answer 12

• Detailed patient history - eyewitness accounts/video
• Electroencephalogram (EEG) +/- video
• Neuroimaging - MRI first choice, CT, (PET/CT)

Question 13

What are the symptoms of a focal aware seizure?

Answer 13

• Motor, somatosensory or psychic symptoms
• Consciousness is not impaired

Question 14

What are the characteristics of a focal impaired awareness seizure?

Answer 14

• Temporal lobe
• Psychomotor
• Consciousness is impaired

Question 15

What are the characteristics of clonic, tonic or tonic-clonic seizures?

Answer 15

• Initial rigid extensor spasm
• Respiration stops
• Defaecation
• Micturition and salivation occur
• This is the tonic phase
• Violent synchronous jerks
• This is the clonic phase

Question 16

What is a myoclonic seizure?

Answer 16

• Seizures of a muscle or a group of muscles

Question 17

What are the characteristics of an absence seizure?

Answer 17

• Abrupt loss of awareness of surroundings
• Little motor disturbance

Question 18

What is an atonic seizure?

Answer 18

• Loss of muscle tone/strength

Question 19

What is prodrome?

Answer 19

• Early signs or symptoms a seizure may be coming hours to days before

Question 20

What is aura?

Answer 20

• A focal aware seizure leading to a secondary generalised seizure

Question 21

What does ictal mean?

Answer 21

• During a seizure
• Interictal means between seizures

Question 22

What is the post-ictal period?

Answer 22

• Begins as seizure subsides - lasts minutes to hours
• E.g. confusion, lack of consciousness, fatigue, headache, anxiety, frustration, embarrassment, muscle aching etc.

Question 23

Give some examples of sodium channel blockers?

Answer 23

• Carbamazepine
• Phenytoin
• Sodium valproate
• Lamotrigine

Question 24

How do sodium channel blocker work?

Answer 24

• Use-dependant blockade of Na+ channels
• Reduces Ca2+ influx
• Decreases glutamate
• Useful in most types of epilepsy

Question 25

What are the adverse side effects of sodium channel blockers?

Answer 25

• Dizziness
• Skin rash
• Eosinophilia
• Leukopenia
• Hyponatraemia

Question 26

What are the contraindications of sodium channel blockers?

Answer 26

• Teratogenic - cause neural tube defects, bone marrow depression, AV conduction issues

Question 27

What are the DDIs of sodium channel blockers?

Answer 27

• Autoinduces its own metabolism to t1/2 reduces - increases dose
• It is a CYP3A4 inducer so decreases combined oral contraceptive pill effect and increases warfarin metabolism
• CYP3A4 inhibitors such as clarithromycin, diltiazem decrease carbamazepine concentration

Question 28

Give some examples of other antiepileptics?

Answer 28

• Levetiracetam

Question 29

What is the mechanism of action of phenytoin?

Answer 29

• Primarily use-dependant blockade of Na+ channels
• Used less often chronically now
• 2nd line in status epilepticus

Question 30

What are the adverse side effects of phenytoin?

Answer 30

• Dizziness
• Skin rash
• Visual disturbances
• Gingival hyperplasia
• Arrhythmia

Question 31

What are the contraindications of phenytoin?

Answer 31

• Teratogenic - facial and digital defects, acute porphyrias, bone marrow depression

Question 32

What are the elimination kinetics of phenytoin?

Answer 32

• Zero order elimination kinetics
• Need to measure plasma concentration of drug (saliva sampling possible too

Question 33

What are the DDIs of phenytoin?

Answer 33

• CYP inducer and decreases plasma concentration of many drugs
• E.g. COCP, Abx, other AEDs