PBL 3

Question 1

What is a convulsive seizure

Answer 1

another name for tonic clonic: involve the whole body (gran mal seizures).

Question 2

what is an unprovoked seizure

Answer 2

seizure that first occurs 6 months following a traumatic brain injury or stroke.

Question 3

What is secondary epilepsy

Answer 3

resulting from a condition/procedure that are high risk for developing epilepsy (craniotomy, traumatic brain injury, stroke, brain tumour, CNS infection etc.

Question 4

What conditions can cause secondary epilepsy

Answer 4

craniotomy, traumatic brain injury, stroke, brain tumour, CNS infection

Question 5

what is an epileptic seizure

Answer 5

the clinical event that occurs when there is an excessive, sustained and synchronized electrical discharge in a network of neurons.

Question 6

name two types of epilepsy

Answer 6

focal

General

Question 7

What is the difference between focal and generalised epilepsy

Answer 7

focal - usually confined to one hemisphere and thus one cortical region

general - goes over both hemispheres

Question 8

name two focal seizures

Answer 8

• simple parietal seizure

- complex parietal seizure

Question 9

describe what a simple partial seizure is

Answer 9

Simple Partial Seizures
 Seizure limited to focal area.
o Symptoms therefore depend on area affected.

 No loss of consciousness.

 Associated with focal structural disease including developmental abnormalities, strokes, trauma and tumours.

Question 10

describe what a complex partial seizure is

Answer 10

 Altered awareness (often debatable) = dyscognitive symptoms.
 Associated with automatisms (purposeless and repetitive movements).
 Most commonly involved structure is the temporal lobes.

Question 11

where does generalised epilepsy originated from

Answer 11

• suggested it is in the somatosensory cortex

Question 12

When does generalised epilepsy come about

Answer 12

• starts at a young age

Question 13

describe absent seizures

Answer 13

 Unresponsiveness and behaviour arrest.
 Usually occurs in childhood.
 May occur many times each day, lasting about 5 seconds.

Question 14

describe tonic clonic seizures

Answer 14

 Prior patients my experience aura
o A simple partials seizure with vague symptoms
This type of seizure usually has two phases:

Tonic Phase: lasts about 10-40 seconds.
 Patient becomes very rigid: all muscles undergo tonic, sustained contraction.
o Patient falls to the floor
 Respiratory muscles and laryngeal muscles also contract: patient may let out a cry/grunt as air is forced out of chest through vocal cords.
o Patient can become cyanotic.

Clonic Phase: muscles go into strong, rhythmic contractions of about 2-3 minutes. 
	Jerky breathing and tachycardia. 
	May be accompanied
o	Urinary and faecal incontinence. 
o	Tongue biting

Coma Period: patient’s breathing gradually becomes normal and color returns to normal.
 Length related to previous tonic-clonic seizures.
 When patients awake: may be confused and have a headache.

or
• Premonition (a vague sense that a seizure is imminent) this is sometimes called aura
• Pre-tonic-clonic phase (a few myoclonic jerks or brief clonic seizures)
• Tonic phase (tonic contraction of the axial musculature; upward eye deviation and pupillary dilatation; tonic contraction of the limbs; cyanosis; respiratory muscle contraction - “epileptic cry”; tonic contraction of jaw muscles)
• Clonic phase - jerks of increasing amplitude followed by relaxation (sphincter opening may occur)
• Postictal period (generalized lethargy; decreased muscle tone, headaches, muscle soreness)

Question 15

What is status epileptics

Answer 15

 Occurs if seizures continue with patient regaining consciousness (+5 minutes) or recurrent seizures over the same time with incomplete recovery between them.
 If generalized this condition is a medical emergency.

Question 16

describe paroxysmal depolarising shift

Answer 16

 Occurs in neurons in which uncontrolled/sustained discharges occur.
 In the PDS the membrane is depolarized by 30-40mV, and remains so for a few seconds.
o May be accompanied by a burst of action potentials.
 May be caused by activation of the glutamate receptors of the NMDA type.

Question 17

how glutamate and GABA can lead to epilepsy

Answer 17

 One of the most important theories in epilepsy is that seizures occur due to an imbalance between the excitatory (glutamate) and inhibitory (GABA) neurotransmitter systems.

Question 18

describe how glutamate and GABA lead to epilepsy

Answer 18

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.

Question 19

name the structural changes that occur in epilepsy

Answer 19

• reorganisation of the tissue in temporal lobe epilepsy
• sprouting of mossy fibres of granule cells
• neurogenesis
• chandelier cells

Question 20

describe the structural changes that occur in epilepsy

Answer 20

Reorganisation of the tissue in temporal lobe epilepsy:
• Loss of CA2 and CA3 hippocampal areas.
• Possible sclerotic hippocampus.

Sprouting of Mossy Fibres of Granule Cells
• Leads to reverbant excitatory circuits.

Neurogenesis
• Formation of new neurons (also in response to epilepsy episodes) change circuits.

Chandelier Cells
 Widespread, inhibitory interneurons that inhibit pyramidal cells.
o Express high levels of GABA Transporter GAT-1.
 In some forms of epilepsy there is a loss of chandelier cells, impacting excitability of pyramidal cells.
o Often sufficient in patients with lower average numbers of inhibitory neurons.

Another cause may be an intrinsic increased neuronal excitability, specifically abnormalities in the membrane.

Question 21

What is the non pharmalogical treatment for epilepsy

Answer 21

a. Non-pharmalogical treatment.
Surgical
 Resection of seizure onset zone in brain.
 If patient has failed 2 AEDs often drug treatment will not work.
o Patients with focal epilepsy will be referred.
 Corpus Callosotomy
o Can be used in patients with drop attacks/atonic seizures.

Vagus Nerve Stimulation
 Can reduce seizures by more than 50% in most patients that have the treatment.

Ketogenic Diet.

Question 22

all AEDS……

Answer 22

ALL AEDs HAVE THE POTENTIAL TO BE TERATOGENIC

 Patients should know that abnormality is low and not different from the general population

Question 23

what are the safer anti epileptic drugs in pregnancy

Answer 23

 Carbamazepine and Iamotrigine are generally the safest anti-epileptic drugs in pregnancy.

Question 24

What are the risks of major congenial malformations with anti epileptic drugs

Answer 24

 Carbamazepine: 2.2%
 Iamotrigine: 3.2%

(!) Valproate: 6.2% vs 3.5% in untreated women with epilepsy

Question 25

What drug is not recommenced for epilepsy in a pregnant women

Answer 25

 Valproate is NOT RECOMMENDED.

Question 26

What is the risk of epilepsy to the baby and mother

Answer 26

Therefore, the risk of epilepsy to the mother far outweigh the theoretical risks of AEDs.
 In general seizures are well tolerated by the fetus but the risk to the mother is greater.
o Main risk is if baby does not receive oxygen.

Question 27

What is pregnancy impact of seizure frequency

Answer 27

 AED blood levels may fall.
 Altered oestrogen and progesterone may have an effect.
 Sleep deprivation increases, which increases the risk of seizures.

Question 28

What are the prescription guidelines for epilepsy

Answer 28

Focal seizures with or without generalisation - carbamazepine, sodium valproate, iamotrigine

tonic clonic - carbamazepine, lamotrigine, sodium valproate

absence. - ethosuximide, sodium valproate

myoclonic seizures - sodium valproate, clonazepam, levetiracetam

Question 29

What drugs cannot be used in absence seizures

Answer 29

phenytoin and carbamazepine have actions on both sodium and calcium channels. They cannot be used in absence seizures.

Question 30

1. Briefly describe 3 possible cellular mechanisms implicated in the generation of seizures. (3 marks)

Answer 30

Increased excitation (e.g. hyperactivity of glutamatergic transmission) 
Decreased inhibition (e.g. deficit in GABAergic transmission) 
Intrinsic neuronal hyper excitability (related to altered electrical properties of the neuronal membrane)

Question 31

2. What is the “paroxysmal depolarizing shift” and what receptors are involved? (2 marks)

Answer 31

The resting membrane potential of neurons becomes depolarized by 30-40 mV, causing a sustained burst of action potentials (1 mark)

This involves most likely the activation of NMDA glutamate receptors (elevated glutamate levels are associated with epileptic foci). (1 mark)

Question 32

3. Name one non-pharmacological method for treating epilepsy. (1 mark)

Answer 32

Surgical interventions (focal removal of affected areas, or more extensive surgical removal; also, deep brain stimulation or vagal nerve stimulation). 
Students may also mention dietary methods, e.g. ketogenic diet.

Question 33

What is the mechanism of action of Tiagabine? (1 mark)

Answer 33

The GAT-1 GABA transporter (reuptake system)

Question 34

5. What is ethosuximide and what is it used for? (2 marks)

Answer 34

Anticonvulsant drug (blocks T-type calcium channels); used to treat absence (petit mal) seizures

Question 35

. Name an anticonvulsant drug with zero-order kinetics. (1 mark)

Answer 35

Phenytoin

Question 36

what drugs block sodium channels

Answer 36

• phenytoin
• carbamexapine
• sodium valproate

Question 37

describe how the sodium channels work

Answer 37

 Bind to the inner pore of the sodium channel in its inactivated state (immediately after depolarization). Zero order kinetics seen in phenytoin.
 Leads to an increased refractory period (delay in time taken to return to resting state).

 All types of seizures (not to be used in pregnancy). = sodium valproate

Question 38

what drugs block calcium channels

Answer 38

Phenytoin
Carbamazepine
Ethosuximide used in absence seizures.
Zonasamide
Topiramate (also increases GABA transmission and inhibits glutamate and works on sodium channels)
Iamotrigine (inhibition of glutamate release)
Levetiracetam
Gabapentin

Question 39

How does levetiracetam work

Answer 39

• Binds to synaptic vesicle glycoprotein, SV2A and inhibits presynaptic calcium channels, reducing neurotransmitter release.

Question 40

how does gabapetin work

Answer 40

• Alpha 2 Delta subunit of calcium channels.

Question 41

how does topiramate and lamotrigine work

Answer 41

 N and P/Q-type channels: expressed at presynaptically.

 Mediate calcium entry for neurotransmitter release.

Question 42

how does phenytoin, caramazepine, ethosuximide, zonasamide

Answer 42

 T-type calcium channels: require less depolarization to be activated, mainly post-synaptically.
 They allow post-depolarization calcium influx and are slowly inactivated. Inhibiting these channels causes prolongation of calcium influx post-depolarization.

Question 43

How do benzodiazepines work and given an example

Answer 43

Clonazepam

 Expressed post-synaptically, lead to fast inhibitory transmission (hyperpolarization) through influx of Cl- (higher extracellularly than intracellularly).
 Stops propagation of electrical activity in cerebral cortex.
 Acts as a positive modulator by increasing frequency of receptor opening.

Question 44

How do barbiturates work

Answer 44

Phenobarbitone

 Acts as to cause prolonged receptor opening and therefore more hyperpolarization.
 At high concentration: directly activates the channels which causes an anaesthetic effect.

Question 45

how does vigabatrin work

Answer 45

• Synthesis: inhibits GABA Transaminase leads to an increase in GABA levels (increased GABA desensitises GABA autoreceptors, reducing inhibitory feedback on release).

Question 46

how does tiagabine

Answer 46

• Uptake: Inhibits GAT-1 (transporter involved in removing GABA from the synaptic cleft).

Question 47

how does perampanel and felbamate work

Answer 47

• Antagonist of AMPA receptors (involved in channels that are permeable to sodium ions).