neuro: epilepsy

Question 1

epilepsy is a disease of the brain defined by any of the following conditions:

Answer 1

• At least two unprovoked seizures occurring>24 h apart
• One unprovoked seizure and a probability of further seizures similar to the general
  recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10
  years
• Diagnosis of an epilepsy syndrome

Question 2

provokedseizure

Answer 2

events occurring in close temporal rs with an acute CNS insult: metabolic, toxic, structural, infectious, inflammation

Question 3

drugs that decr seizure threshold

Answer 3

TCA, carbapenems, baclofen

Question 4

safety considerations: phenytoin

Answer 4

a/w incr risk of serious skin reactions in people of Han Chinese or Thai family background

Question 5

safety considerations: cbz

Answer 5

a/w incr risk of serious skin reactions in people of Han Chinese, Thai, European, Japanese family background

Question 6

safety considerations: LT treatment with some antiseizure meds such as cbz, phenytoin, primidone and sodium valproate

Answer 6

a/w decr bone mineral density and incr risk of osteomalacia
- ca and vit D supplementation for person at risk

Question 7

antiseizure meds for women and girls

Answer 7

teratogenic: sodium valproate, topiramate, phenytoin

impair effectiveness of hormonal contraceptives: cbz, oxcarbazepine, phenytoin, topiramate
(estrogen-containing hormonal contraceptives can imapair effectiveness of lamotrigine

breastfeeding is generally safe and should be encouraged

Question 8

generalised tonic clonic/ grand mal: tonic phase

Answer 8

stiffening of the limbs, breathing may decr or cease altogether, cyanosis of nail beds&lips&face

Question 9

generalised tonic clonic/ grand mal: clonic phase

Answer 9

jerking of limbs and face, lasts 1 min, after which the brain is extremely hyperpolarised and insensitive to stimuli
- incontinence may occur, along w biting of the tongue or inside of the mouth, breathing may be noisy and appear to be laboured
- following the seizure, pt may have headache and appear lethargic/confused/sleep

Question 10

myoclonic

Answer 10

Involves rapid, brief contractions of bodily muscles,
usually occurring on both sides of the body
concurrently
- On occasion, may involve just one arm or one foot

Question 11

absence generalised seizure / petit mal

Answer 11

• Usually manifests as basic lapse in awareness that begins and ends
  abruptly
• Sometimes mistaken as persistent staring
• Lasts only a few seconds 􀂲 no warning, no after-effects
• Often undetected even if there 50-100 attacks per day
• More common in children than in adults
• First onset usually occurs at 4-12 years old; rarely after 20 years old
• May be mistaken for complex

Question 12

absence seizures vs complex partial seizures

Answer 12

absence:
1. are never preceded by auras
2. last seconds (rather than minutes)
3. begin frequently and end abruptly
4. produce characteristic EEG pattern ‘3Hz spike waves’

Question 13

generalised atonic seizure

Answer 13

• most severe form is the classic drop attack (astatic
  seizure) in which all postural tone is suddenly lost,
  causing collapse to the ground like a rag doll
• short episode and followed by immediate recovery
• occur at any age, and are always associated with diffuse
  cerebral damage and learning disability

Question 14

risk of second seizure is higher in the presence of:

Answer 14

• epileptiform abnormalities on EEG
• Prior brain insult (e.g. stroke, brain trauma)
• Structural abnormality in brain imaging
• Nocturnal seizure

Question 15

non-pharmacological treatment for epilepsy

Answer 15

• ketogenic deit
• vagus nerve stimulation
• responsive neurostimulator system
• surgery

Question 16

AED that requires slow titration

Answer 16

lamotrigine and topiramate

Question 17

AED that undergoes autoinduction

Answer 17

carbamazepine

Question 18

AED to use in pt w migraine

Answer 18

topiramate, valproate

Question 19

AED to use in caution for pt w depression or anxiety

Answer 19

levetiracetam: can cause irritability and aggresion

Question 20

women w childbearing potential

Answer 20

avoid valproate, use l/l

Question 21

If the first AED produces an adverse drug reaction or is not tolerated at low doses or does
not improve seizures consider

Answer 21

substitution

Question 22

if the patient tolerates the first or second AED but with a
suboptimal response, consider

Answer 22

combination

Question 23

ketogenic diet

Answer 23

may be used for pt who cannot tolerate or have not responded well to AED treatment
􀂃 Comprises low carbohydrate, high fat in diet
􀂃 Induction of ketosis
􀂃 Prevention of seizures (used mainly in young children 􀂲 evidence)
􀂃 Challenging to adhere long term

Question 24

AED with possible cognitive adr

Answer 24

topiramate: usually speech fluency

Question 25

AED to use in hepatic impairment

Answer 25

gabapentin, pregabalin, levetiracetam, topiramate, clobazem

Question 26

AED to use in renal impairment

Answer 26

carbamazepine, phenobarbitol, phenytoin, valproate lamotrigine

Question 27

AED with no DDI`

Answer 27

gabapentin, pregabalin, levetiracetam

Question 28

potent enzyme inducers

Answer 28

1st gen - carbamazepine - phenytoin - phenobarbitol

Question 29

potent enzyme inhibitor

Answer 29

valproate

Question 30

moderate cyp inducer

Answer 30

oxcarbazepine, topiramate

Question 31

moderate cyp inhibitors

Answer 31

oxcarbazepine, topiramate

Question 32

When an enzyme inducing ASM is discontinued, activity of affected enzymes

Answer 32

return to baseline - drugs that are metabolised by the affected enzymes may require dose adj

Question 33

issue w enzyme-induced AED: ddi

Answer 33

- antidepressants and antipsychotics - immunosuppressive therapy - antiviral therapy - chemotherapeutic agent

Question 34

phenytoin correction for

Answer 34

albumin < 40g/L

Question 35

carbamazepine pk

Answer 35

􀂃 Undergoes autoinduction (induces its own metabolism) 􀂃 Clearance increase and half-life shorten 􀃆 carbamazepine concentration decline and stabilize in accord with the new clearance and half-life 􀂃 Maximal autoinduction usually occurs 2-3 weeks after dose initiation 􀂃 Implication: 􀂃 Do not start with desired maintenance dose at the first dose, but gradually increase over the initial few weeks

Question 36

absence of myoclonic seizures, do not use:

Answer 36

cbz, gbt, oxcarbazepine, phenytoin, pregabalin

Question 37

AED that may cause behavioural disturbances

Answer 37

levetiracetam

Question 38

AED that can cause n/v

Answer 38

carbamazepine, valproate

Question 39

rare but serious idosyncratic reactions of AED

Answer 39

􀂃 Blood dyscrasia (Aplastic anaemia, agranulocytosis 􀂃 Hepatotoxicity (1st-generation ASMs 􀂲 phenytoin, valproate, carbamazepine) 􀂃 Pancreatitis (e.g., sodium valproate) 􀂃 Lupus-like reaction 􀂃 Exfoliative dermatitis 􀂃 Toxic epidermal necrolysis/Stevens-Johnson syndrome

Question 40

AED that has been a/w pancreatitis

Answer 40

sodium valproate

Question 41

chronic SE of phenytoin

Answer 41

gingival hyperplasia (gum enlargement): may be observed in almost half of all patients receiving chronic phenytoin therapy hirsutism: commonly observed in children and young adults on chronic phenytoin therapy encephalopathy: most commonly a/w prolonged phenytoin treatment at high doses ^ may also occur w phenobarbitone peripheral neuropathy: patients on LT phenytoin treatment at high doses experience sensory loss - may or may not improve w decr in AED dose, may respond with folate supplementation ^ may also occur w phenobarbitone and cbz osteomalacia: incr clearance of vit D, leading to secondary hyperPTH, incr bone turnover, and reducing bone density ^ often a/w phenytoin, phenobarbitone and cbz (hepatic enzyme inducers)

Question 42

chronic SE of valproate

Answer 42

alopecia increased weight gain, gradually reverses spontaneously with discontinuation of treatment

Question 43

chronic SE of topiramate

Answer 43

anorexia and weight loss, reversible w discontinuation of drug - actl indicated as a possible weight loss agent

Question 44

other isolated adr a/w nearly all AED

Answer 44

blood dyscrasias, megaloblastic anemia (altho predominantly in pt receiving phenytoin, but also a/w cbz and phenobarbitone)

Question 45

AEDs causing neonatal congenital defects

Answer 45

malformation risk: topiramate, phenytoin, phenobarbitone cognition: valproate

Question 46

AED that requires pharmacogenetic testing

Answer 46

carbamazepine: HLA-B*1502 testing - prior to starting - strong assoc btw carriage and risk of cbz-induced sjs/ten

Question 47

lamotrigine initial dosing

Answer 47

risk of severe cutaneous reaction higher with high starting dose, rapid dose escalation, concomittant valproate - in pt taking valproate: 25mg EOD to maintenance dose of 100-200mg/d - in pt not taking anyth else: 25mg OD, maintenance of 225-375mg/d in 2 divided doses - in pt taking smth else but not valproate: 50mg/d to maintenance of 300-500mg/d in 2 divided doses

Question 48

aromatic AED

Answer 48

cbz, ltg, oxcarbazepine, phenytoin, phenobarbital

Question 49

non-aromatic AED

Answer 49

val, levetiracetam, gabapentin, topiramate

Question 50

ref range of phenytoin

Answer 50

10-20mg/L

Question 51

ref range of valproate

Answer 51

50-100mg/L

Question 52

ref range of cbz

Answer 52

4-12mg/L

Question 53

ref range of phenobarbitone

Answer 53

15-40mg/L

Question 54

when can we consider discontinuing AEDs?

Answer 54

after a person has been seizure free for 2yrs

Question 55

epilepsy is considered to be resolved for indiv who had

Answer 55

an age-dependent epilepsy syndrome but are not past the applicable age or remained seizure-free for last 10 yrs, w no seizure meds for last 5 yrs