Epilepsy

Question 1

Name the most important excitatory and inhibitory neurotransmitters in the brain and their associated receptors

Answer 1

Excitatory;
- Glutamate via NMDA receptor (Depolarise membrane via Na and Ca influx)

Inhibitory;
- GABA via GABAa receptor (Hyperpolarise membrane via Cl channels)

Question 2

What are 2 causes of an imbalance of neurotransmitters, leading to seizures

Answer 2

• Loss of inhibitory signals via GABA

- Too many excitatory signals (NMDA/ Glutamate)

Question 3

Not everyone who has a seizure has epilepsy

Who can diagnose epilepsy?

Answer 3

Specialists only, as it is very significantly life-changing

Question 4

Describe the diagnostic criteria for Epilepsy

Answer 4

• At least 2 unprovoked/ reflex seizures occurring >24hrs apart

OR

• One unprovoked seizure and a probability of further seizures similar to the general recurrence risk after 2 unprovoked seizures (at least 60% over next 10 years)

Question 5

Compare the types of Focal Onset seizures

Partial Mal seizure

Answer 5

Aware- Consciousness not impaired, Motor/ Somatosensory/ Psychic symptoms

Impaired awareness- Consciousness impaired, possibly confused

Question 6

Compare the types of Generalised onset seizures

Grand Mal seizure

Answer 6

Tonic-clonic: Hypertonia followed by jerking/ shaking

Myoclonic: Muscles jerking

Absence (Petit Mal): Abrupt loss of awareness

Atonic: Loss of all muscle tone (often collapse)

Question 7

Compare Generalised and Focal seizures in regards to parts of brain affected

Answer 7

Generalised;
- Originate and spread within both hemispheres

Focal;
- Originate within and limited to one hemisphere (so consciousness less likely to be impaired)

Question 8

What’s a provoked seizure?

Answer 8

Due to another medical condition

Drug use + withdrawal, Alcohol withdrawal, Trauma, Metabolic disturbances etc

Question 9

Describe the initial management of a seizure

Answer 9

Airway- Patent? Adjuncts needed?

Breathing- Sats, O2

Circulation- HR, BP

Disability- Consciousness, Glucose

Exposure- Recovery position?

Question 10

Once a seizure begins, how long do you wait before giving seizure terminating drugs?

Answer 10

5 mins (most self terminate without drug use)

Question 11

Define Status Epilepticus

Answer 11

A seizure lasting more than 5mins, or multiple seizures without a complete recovery between them

Question 12

Describe the pharmacological treatment for Status Epilepticus

Answer 12

0-15 mins;
- Full dose Benzodiazepine

0-15 mins;
- 2nd Full dose Benzodiazepine

15-45 mins;

• 2nd line Anti-epileptic (Phenytoin, Levetiracetam- Monitoring for these, can cause low BP and Arrythmias)
• Consider IV Thiamine if they drank alcohol

45+ mins;
- Thiopentone, ONLY in presence of Anaesthetist and in suitable environment

Question 13

When do Benzodiazepines work best?

List 3 ADRs

Answer 13

When membrane potential is positive (in seizures)

• Addiction
• CVS Collapse
• Airway issues

Question 14

List 4 indications of Benzodiazepines

Answer 14

• Seizures
• Anxiolytic properties
• Sleep aids
• Alcohol withdrawal

Question 15

List 3 Benzodiazepines used in treating Status Epilepticus

Answer 15

• Diazepam (rectal)
• Lorazepam (IV)
• Midazolam (Buccal/ Intranasal)

(Oral or IM preparations can work)
(NOT a guideline: Get fast acting Benzos into patient however possible)

Question 16

List 2 investigations for Epilepsy

Answer 16

• EEG (Abnormal in many without Epilepsy, a single scan may show abnormalities in as few as 30% of epileptics)
• MRI (Generally not required, used to look for abnormalities that can explain epilepsy)

Question 17

Name 6 AEDs (Anti-Epileptic Drugs)

Answer 17

• Benzodiazepines (for seizure termination)
• Phenytoin
• Carbamazepine
• Levetiracetam (safe in pregnancy)
• Lamotrigine
• Sodium Valproate (1st line for generalised seizures)

Question 18

How does Carbamazepine/ Tegretol work?

(Used for epilepsy, Bipolar, chronic pain sometimes)

List 3 ADRs

Answer 18

• Na channel blocker
• Joint pain
• Suicidal thoughts
• Bone marrow failure

Question 19

How does Phenytoin work?

List 3 ADRs

Answer 19

• Na channel blocker
• Bone marrow suppression
• Hypotension
• Arrhythmias

Question 20

List 2 indications for Phenytoin and why we need to be careful when dosing it

Answer 20

• Status Epilepticus
• Adjunct in General seizures
• Exhibits Zero Order kinetics

Question 21

How does Sodium Valproate (Epilim, Depakote) work?

List 3 ADRs

Answer 21

• Na channel blocker, Ca channel blocker, GABA Agonist
• Liver failure
• Pancreatitis
• Lethargy

Question 22

How does Lamotrigine work?

List 2 indications

Answer 22

• Na channel blocker, Ca channel blocker
• Focal epilepsy
• When Valproate is contraindicated in generalised epilepsy

Question 23

How does Levetiracetam (Keppra) work?

List 2 uses

Answer 23

• Binds to synaptic vesicle glycoprotein, stops the release of neurotransmitters into synapse
• Focal seizures
• Generalised seizures

Question 24

List 6 general ADRs of AEDs

Answer 24

• Tiredness/ drowsiness
• N+V
• Mood changes + suicidal thoughts
• Increases risk of Osteoporosis
• Rashes, including Steven-Johnson Syndrome (especially Phenytoin and Carbamazepine)
• Anaemia, Thrombocytopenia, Marrow failure

Question 25

List some DDIs of AEDs

Answer 25

Carbemezapine and Phenytoin;

• May decrease effectiveness of oral contraceptive pills
• May decreases effectiveness of some antibiotics

Valproate;
- Can increase [plasma] of other AEDs

• Ideally, patients on AEDs should not drink alcohol

Question 26

List 2 AEDs that are CYP Inducers and 1 that is a CYP Inhibitor

Answer 26

Inducers;
- Phenytoin
- Carbamazepine
(Also Barbiturates- not prescribed anymore)

Inhibitors;
- Valproate

Question 27

All AEDs carry a risk of congenital malformation.

Which has the highest risk?
Which 2 have the lowest risk?

Answer 27

Highest risk;
- Valproate

Lowest risk;

• Lamotrigine
• Levetiracetam

Question 28

How does Carbamazepine influence its own metabolism?

Answer 28

Induces it’s own CYP enzyme overt time, increasing it’s own metabolism