L13-14 Epilepsy

Question 1

seizure vs epilepsy

Answer 1

• transient occurrence of signs and/or sx due to abnormal excessive or synchronous neuronal activity in the brain
  vs
• brain disorder, characterised by an enduring predisposition to generate epleptic seizures

Question 2

key concept for the pathophysiolgy of seizure

Answer 2

hyperexcitability and hypersynchronisation

Question 3

hyperexcitability

Answer 3

enhanced predispostion of a neuron to depolarise

• voltage or ligand-gated K+, Na+, Ca2+, Cl- ion channels: abnormalities in intra- and extracellular substances eg. Na+, K+, O2, glucose, etc.
• excessive excitatory neurotransmitters eg. glutamine, acetylcholine, histamine, cytokines, etc.
• insufficient inhibitory neurotransmitters eg GABA, dopamine

Question 4

hypersynchronisation

Answer 4

(network disorder)
intrinsic organisation of local circuits: hippocampus, the neocortex and the thalamus
- contribute to synchronisation and promote generation of epileptiform activity
- reorganisation: new, sprouting fibers that intrude self-perpetuating excitatory circuits

Question 5

simple partial seizures

Answer 5

focal onset seizures (without dyscognitive features) seizures

Question 6

difference between absence seizures and complex partial seizures (4)

Answer 6

1. absence seizures are never preceded by auras
2. ’’ lasts seconds, rather than minutes
3. ’’ begin frequently and end abruptly
4. produce characteristic EEG pattern: 3Hz waves (specific for absence seizures)

Question 7

epileptiform discharges on EEG ______ diagnosis

Answer 7

if diagnosis of seizures or epilepsy is considered

- a normal eeg does not excl possibility of epilepsy

Question 8

investigations

Answer 8

scalp EEG, MRI with gadolinium, biochemical/toxicology

Question 9

risk factors for seizure recurrence

Answer 9

• epileptiform abnormalities on EEG
• prior brain insult eg stroke, brain trauma
• structural abnormality in the brain imaging
• nocturnal seizure

Question 10

do you start ASM after 1st seizure?

Answer 10

unlikely, unless there is a presence of risk factors

Question 11

after a single unprovoked seizure, recurrence is

Answer 11

approx 30%

- 80-90% of which had a second seizure within 2 years

Question 12

with 2 unprovoked nonfebrile seizures, the risk of recurrence is

Answer 12

approx 70%

- initiate tx

Question 13

non pharmaco tx

Answer 13

• keto diet
• vagus nerve stimulation
• responsive neurostimulator system
• surgery

Question 14

general principles of pharmaco tx

Answer 14

monotherapy preferred

• likely lower incidence of AE
• absence of DDI
• reduced risk of birth defects
• lower cost
• easier to correlate response and AE
• better adherance

Question 15

drug resistant epilepsy

Answer 15

failure of adequate trials of 2 tolerated, appropriately chosen and used ASM drug schedule to achieve sustained seizure freedom
- whether as monotherapy or in combi

Question 16

seizure triggers (9)

Answer 16

• hyperventilation
• photostimulation
• physical and emotional stress
• sleep deprivation
• electrolytes imbalance: hypoglycemia, hypo/hyperNa, hypoCa, hypoMg
• sensory stimuli
• infection
• hormonal changes: time of menses, puberty, or pregnancy
• drugs (decr seizure threshold) eg. theophylline, alc, high-dose phenothiazines, antidepressants esp bupropion, tramadol, carbapenems

Question 17

appropriate seizure first aid: for generalised grand mal

Answer 17

• ease the person to the floor
• turn the person gently onto one side, help the person breathe
• clear the area around the person of anything hard or sharp, prevent injury
• put something soft and flat, like a folded jacket, under his or her head
• remove eyeglasses
• loosen ties or anything around the neck that may make it hard to breathe
• time the seizure, call 911 if the seizure lasts longer than 5 mins

Question 18

migraine

Answer 18

consider topiramate, valproate

Question 19

dep/anx

Answer 19

use levetiracetam with caution

Question 20

women w child-bearing potential

Answer 20

avoid valproate, consider levetiracetam/lamotrigine

Question 21

NICE 1st line agents for new onset, focal onset epilepsy

Answer 21

carbamazepine, levetiracetam, valproate, lamotrigine, oxcarbazepine

Question 22

NICE 1st line agents for new onset, generalised tonic-clonic epilepsy

Answer 22

lamotrigine, valproate, carbamazepine, oxc?

Question 23

tx option: refractory, focal onset epilepsy

Answer 23

clobazam, lacosamide, pregabalin, perampanel

Question 24

tx option: refractory, generalised tonic clonic epilepsy

Answer 24

clobazam, levetiracetam

Question 25

topiramate

Answer 25

possible cognitive adverse effect, possible teratogenicity

Question 26

What ASMs are preferentially avoided for use in pregnancy?

Answer 26

valproate, topiramate, phenytoin

Question 27

phenytoin

Answer 27

possible teratogenicity

Question 28

1st ASM is predominantly cleared via the _____ route?

Answer 28

hepatic

Question 29

Does 1st gen or 2nd gen ASM have more ddi?

Answer 29

1st gen, significant protein binding

Question 30

which of the 2nd gen ASMs experience DDI?

Answer 30

LEV (few, 55%), TPM (dose dependent, 15%), CLB (80-90%)

Question 31

Are 2nd gen ASMs usually cleared renally/hepatically?

Answer 31

renally

Question 32

Which of the 2nd gen ASMs are eliminated hepatically?

Answer 32

LTG (100%)

Question 33

for patients who require >200mg/day of TPM

Answer 33

potentially significant DDI

Question 34

what kind of interaction is easily overlooked, since it is not captured by most CPOE platforms or pharmacy system?

Answer 34

deinduction interactions - when enzyme-inducing ASM is discontinued, activity of affected enzymes will return to baseline - drugs that are metabolised by the affected enzymes may required dose adjustment

Question 35

what is usually the main limiting factor in the tx of epilepsy?

Answer 35

adverse effects

Question 36

Chronic adverse effect of gingival hyperplasia is usually observed in patients receiving what therapy?

Answer 36

phenytoin

Question 37

Chronic adverse effect of hirsutism is usually observed in patients receiving what therapy?

Answer 37

phenytoin

Question 38

Chronic adverse effect of alopecia is usually observed in patients receiving what therapy?

Answer 38

valproate

Question 39

Chronic adverse effect of encephalopathy is usually observed in patients receiving what therapy?

Answer 39

phenytoin at high doses, or phenobarbitone

Question 40

Chronic adverse effect of peripheral neuropathy is usually observed in patients receiving what therapy?

Answer 40

phenytoin at high doses, also a/w cbz and pb

Question 41

How to reverse chronic adverse effect peripheral neuropathy?

Answer 41

May or may not improve with decrease in ASM doses

Question 42

How can peripheral neuropathy be reversed?

Answer 42

May respond to folate supplementation

Question 43

Is chronic adverse effect increased weight gain reversible?

Answer 43

Gradually reverses spontaneously with discontinuation of treatment

Question 44

Which ASM is indicated as a possible pharmacological agent for weight loss?

Answer 44

Topiramate

Question 45

Chronic adverse effect of increased weight gain is usually observed in patients receiving what therapy?

Answer 45

val

Question 46

Chronic adverse effect of anorexia and weight loss is usually observed in patients receiving what therapy?

Answer 46

topiramate and felbamate

Question 47

Is chronic adverse effect increased weight loss and anorexia reversible?

Answer 47

reversible with discontinuation of drug

Question 48

Chronic adverse effect of osteomalaccia is usually observed in patients receiving what therapy?

Answer 48

phenytoin, phenobarbitone, cbz, maybe val

Question 49

Chronic adverse effect of blood dyscrasis is usually observed in patients receiving what therapy?

Answer 49

isolated cases associated with nearly all ASMs

Question 50

Chronic adverse effect of megaloblastic anaemia is usually observed in patients receiving what therapy?

Answer 50

phenytoin (predominantly), also a/w cbz and phenobarbitone

Question 51

Chronic adverse effect of neonatal congenital defects is usually observed in patients receiving what therapy?

Answer 51

- a/w phenytoin, pb, tpm (malformation risks) | - val (cognition)

Question 52

What is the main hypothesis for the mechanism by which ASM induce skin reactions?

Answer 52

Unclear: ASM with an aromatic ring can form an arene-oxide intermediate - become immunogenic through interactions with proteins or cellular macromolecules

Question 53

indications for ASM TDM

Answer 53

1. To establish an individual's 'therapeutic range' 2. To assess lack of efficacy 3. To assess potential toxicity 4. To assess loss of efficacy (breakthrough seizures)

Question 54

ref range of phenytoin

Answer 54

10-20mg/L

Question 55

ref range of val

Answer 55

50-100mg/L

Question 56

ref range of cbz

Answer 56

4-12mg/L

Question 57

ref range of pb

Answer 57

15-40mg/L

Question 58

epilepsy is considred to be resolved for

Answer 58

indiv who had an age-dependent epilepsy syndrome - but now part the applicable age who have remained seizure-free for the last 10 years - w no seizure meds for the last 5 years

Question 59

status epilepticus

Answer 59

condition resulting either from - failure of the mech responsible for seizure termination - from the initiation of mech which lead to abnormally prolonged seizures

Question 60

tonic clonic SE: operational dimension 1

Answer 60

5 min | - when a seizure is likely to be prolonged leading to continuous seizure activity

Question 61

tonic clonic SE: operational dimension 2

Answer 61

30 mins - when a seizure may cause LT consequences (incl neuronal injury, neuronal death, alteration of neuronal networks and functional deficits)

Question 62

5-20 mins: initial therapy phase

Answer 62

benzodiazepine, first line: - im midazolam - iv lorazepam - iv diazepam others: iv pb, rectal diazepam, intranasal midazolam (not avail in sg)

Question 63

20-40 min: sec therapy phase

Answer 63

single dose: - iv fosphenytoin - iv valproic acid - iv levetiracetam otherwise, iv pb

Question 64

40-60min: third therapy phase

Answer 64

no clear evidence to guide therapy in this phase | - repeat second line therapy or anesthetic doses of: thiopental, midazolam, pb, profolol (all w cont EEG monitoring)