PBL 3: A difficult decision

Question 1

What is epilepsy?

Answer 1

An epileptic seizure is the clinical event that occurs when there is an excessive, sustained and synchronised electrical discharge in a network of neurones

Question 2

What are the two categories of epilepsy?

Answer 2

Focal

Generalised

Question 3

What are characteristics of focal epilepsy?

Answer 3

Seizures that arise from specific cortical region, spreading to other areas or not
Occurs at any age

Question 4

What are characteristics of generalised epilepsy?

Answer 4

Seizures that do not seem to arise from a specific region
Manifestation of bilateral discharges that result from a fast synchronisation of cortical networks
Often starts at young age

Question 5

What are the classification of partial seizures?

Answer 5

Simple partial
Complex partial
Partial seizure with secondary generalisation

Question 6

What are the classification of generalised seizures?

Answer 6

Absence
Tonic-clonic
Statis epilepticus

Question 7

What is a simple partial seizure?

Answer 7

When activity is limited to a focal area

No loss of consciousness

Question 8

What happens in complex partial seizure?

Answer 8

Altered awareness
Semi autonomic movements (automatisms)
Associated with temporal structures

Question 9

What happens in partial seizures with secondary generalisation?

Answer 9

Spread over cerebral cortex
Originates in non-eloquent part of brain
Spreads v quickly

Question 10

What is an absence seizure?

Answer 10

Occurs in childhood
Possibly many times a day
Lasts 5s

Question 11

What may a patient experience before a tonic-clonic seizure?

Answer 11

Aura

Question 12

How long does the tonic phase last?

Answer 12

10-40s

Question 13

What happens in tonic phase?

Answer 13

Patient becomes rigid as muscles undergo tonic, sustained contraction
Patient falls rigidly

Question 14

Why may a grunt be heard in tonic phase?

Answer 14

respiratory + laryngeal muscles contract so grunt is heard as air leaves chest through taut vocal cords

Question 15

What may happen to patient in tonic phase?

Answer 15

Cyanotic

Question 16

What happens after clonic phase?

Answer 16

Coma period

Question 17

What happens during clonic phase?

Answer 17

Muscles go into strong, rhythmic contractions

Question 18

What accompanies limb jerking in clonic phase?

Answer 18

Urinary + faecal incontinence as well as tongue biting and frothing at mouth

Question 19

Why is there tachycardia in clonic phase?

Answer 19

Breathing is jerky and inefficient

Question 20

How long does clonic phase last?

Answer 20

2-3m

Question 21

What is status epilepticus?

Answer 21

Seizure lasting 30m or more or recurrent seizures over the same time with incomplete recovery between them
MEDICAL EMERGENCY

Question 22

What mutation can cause epilepsy?

Answer 22

Ion channels e.g. Na+, K+, Ca2+, GABAa

E.g. SCN1B mutation

Question 23

Is there a genetic basis in epilepsy?

Answer 23

Yes

Question 24

What are the 3 main mechanisms by which anti epileptic drugs work?

Answer 24

Modulation of intrinsic membrane conductances
Primarily voltage gated cationic channels
Suppression of excitatory amino acid-mediated synaptic transmission

Question 25

What are the 3 states of sodium channels?

Answer 25

Depolarisation: closed Closed/inactivated: spontaneously after depolarisation Hyperpolarisation: resting and closed

Question 26

What drugs target sodium channels?

Answer 26

Carbamazepine Phenytoin Idea is to increase refractory period

Question 27

What are the types of calcium channels?

Answer 27

L P/Q N T

Question 28

Which calcium channel requires less depolarisation to be activated?

Answer 28

T

Question 29

Which GABA is fast and slow?

Answer 29

``` GABAa = fast GABAb = slow ```

Question 30

What is GABAa permeable to?

Answer 30

Cl-

Question 31

What does opening og GABAa lead to?

Answer 31

Hyperpolarisation as Cl- is usually higher extracellularly than intracellularly

Question 32

Where is GABAb expressed?

Answer 32

Pre and post synaptically

Question 33

What does activation of GABAb do?

Answer 33

Inhibition of adenylyl cyclase Voltage-gated Ca2+ Activation of inward K+ channels

Question 34

What do potassium channels do?

Answer 34

Repolarise neurons following action potentials

Question 35

What does phenytoin do to potassium channels?

Answer 35

Selectively block outward K+ channels so are rpo-convulsant | Repolarisation takes longer to occur

Question 36

What receptors do glutamate work on

Answer 36

Ionotropic e.g. NMDA, AMPA, kainite receptors | Metabotropic

Question 37

What are NMDA receptors permeable to?

Answer 37

Ca2+ and Na+ ions

Question 38

What are NMDA receptors extremely sensitive to?

Answer 38

Glutamate and may be activated by extra-synaptic glutamate if in high quantities (this is called spill over)

Question 39

Give an example of an NMDA receptor drug

Answer 39

Carbamazepine

Question 40

What are AMPA and Kainate receptors associated with?

Answer 40

Channels are that permeable to sodium ions

Question 41

Give examples of AMPA and Kainate receptor drugs

Answer 41

Topiramate/phenobarbitone (inhibits AMPA/kainite receptors)

Question 42

What is surgical options of the brain?

Answer 42

Resection of seizure onset zone in brain | Corpus callostomy

Question 43

When won't drug treatment work?

Answer 43

If patient has failed 2 AEDs (patients with focal epilepsy will be referred)

Question 44

When is corpus callostomy used?

Answer 44

When patients have drop attacks/atonic seizures

Question 45

What are other non-pharmalogical treatments?

Answer 45

Vagus nerve stimulation | Ketogenic diet

Question 46

Which are the safest AEDs in pregnancy?

Answer 46

Carbamazepine | Lamotrigine

Question 47

What drug is not recommended in epilepsy?

Answer 47

Valproate

Question 48

How can pregnancy impact seizure frequency?

Answer 48

AED blood levels fall Altered oestrogen and progesterone Sleep deprivation

Question 49

What is main risk to baby?

Answer 49

Doesn't receive oxygen

Question 50

Which calcium channels are expressed post synaptically?

Answer 50

T

Question 51

What are structural changes in epilepsy?

Answer 51

Reorganisation of the tissue in temporal lobe epilepsy Sprouting of mossy fibres of granule cells Neurogenesis Chandelier cells

Question 52

What is a paroxysmal Depolarising shift?

Answer 52

Occurs in neurons with uncontrolled/sustained discharges occur Membrane is depolarised by 30-40mV accompanied by burst of action potentials

Question 53

What causes a Paroxysmal depolarising shift?

Answer 53

Activation of the glutamate receptors of the NMDA type

Question 54

What is an important theory to why seizures occur?

Answer 54

Imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmitter systems

Question 55

What supports the theory of an imbalance in neurotransmitters?

Answer 55

o GABA antagonists and glutamate agonists are triggers for seizures. o Drugs that encourage GABA transmission are antiepileptics. o In prolonged seizures glutamate levels rise and GABA levels fall. o Rise in CSG GABA are seen to correlate with action of antiepileptic Vigabatrin