seizures and epilepsy

Question 1

what is the pathophysiology of epilepsy

Answer 1

epilepsy is a neurological disorder that affects the brain and causes recurrent seizures which occurs due to an abnormal sudden burst of electrical signals resulting in a variety of symptoms depending on the part of brain that is affected

normally, the brain communicates via electrical signals between neurons but in epilepsy, there is hypersensitivity and hypersynchronisation

Question 2

what are the type of seizures

Answer 2

acute
- occurring as a result of an immediately recognisable stimulus (timely assoc of ~1w)

remote
- occurring >1w after a disorder that is known to increase the risk of developing epilepsy

unprovoked
- occurring in the absence of a potentially responsible clinical condition

Question 3

what are the common etiology of epilepsy

Answer 3

structural
- hippocampal atrophy
- brain tumors
- vascular malformations
- glial scarring

neurodegenerative
- alzheimer’s

infectious
- bacterial meningitis
- encephalitis
- neurocysticerosis

metabolic
- inborn errors of metabolism
- mitochondrial disorders

genetic
- dravet syndrome

Question 4

what are the common etiology of acute symptomatic seizures

Answer 4

metabolic
- hypoNa
- hypoCa
- hypoMg
- hypoglycemia

structural
- stroke
- traumatic brain injury

infection/ inflamm
- febrile illness
- CNS infection

toxic substances
- drugs
- alcohol intoxication and withdrawal
- BZP withdrawal

Question 5

what are the phases of a seizure

Answer 5

prodromal
early-ictal “aura” (1-10mins)
ictal (2-3mins)
post-ictal (15mins-2hrs)

Question 6

list seizure triggers

Answer 6

• hyperventilation
• photostimulation
• sensory stimuli
• sleep disturbances
• physical and emotional stress
• infection
• hormonal changes
• drugs that lower seizure threshold (theophylline, alcohol, high dose phenothiazines, carbapenems, tramadol, antidepressants esp bupropion)

Question 7

what is the classification of seizures (ILAE)

Answer 7

mode of onset
- focal (begin in one hemisphere)
- generalized (begin in both hemisphere)
- secondary generalized (begin in one hemisphere then spread to the other)

impairment of consciousness (w/wo dyscognitive features)
- defined as loss of awareness to an external stimuli or inability to respond to external stimuli in a purposeful and appropriate manner

if focal onset with dyscognitive features, it is also called complex partial seizure

if focal onset without dyscognitive features, it is also called simple partial seizure

generalised seizures can be further classified into tonic, clonic, atonic, myoclonic, absence (petite mal), and tonic-clonic (grand mal)

Question 8

what is the clinical presentation of a simple partial seizure

Answer 8

motor
- jerking
- speech arrest

sensory
- visual disturbances
- numbness and tingling
- rising epigastric sensation

autonomic
- sweating, salivation, pallor
- increased HR, BP

psychic
- hallucinations
- flashbacks
- affective sx like fear, anger, irritability, depression

Question 9

differentiate the types of generalized seizures

Answer 9

tonic
- asymmetrical and irregular jerking

clonic
- sudden loss of consciousness, rigid posture (lasts 10-20secs)

myoclonic
- rapid brief contractions of bodily muscles, usually occurring on both sides concurrently

atonic
- classic drop attack

tonic-clonic (grand mal)
- sudden rigid posture f/b jerking
- decreased or ceased breathing during tonic phase
- cyanosis of nail bed, face and lips
- clonic phase ~1min
- noisy and laboured breathing, may bite tongue/ inside of mouth, incontinence
- pt likely feel lethargy, confused, sleepy, and HA after
- takes a few mins to hrs to recover fully

absence (petite-mal)
- basic lapse in awareness that ends abruptly, sometiems mistaken as persistent staring
- lasts a few seconds, no warning and no after effects

Question 10

what are the classical characteristics of a seizure

Answer 10

• aura
• cyanosis
• loss of consciousness
• generalized stiffness of the limbs and body
• jerking of limbs
• tongue biting
• urinary incontinence
• post-ictal confusion
• muscle soreness

Question 11

what are the type of investigations conducted for seizures

Answer 11

• scalp EEG (essential tool for diagnosis and classification)
• video EEG (to correspond what’s happening inside with outside)
• MRI (to identify presence of focal lesions)
• toxicology/ biochemical (to rule out electrolyte imbalances, CK elevated after GTC)

Question 12

what are the goals of therapy for epilepsy

Answer 12

• absence of epileptic seizures
• absence of ASM s/e
• attainment of optimal QoL

Question 13

what are the non-pharmacological management for epilepsy

Answer 13

• ketogenic diet (low carb high fat to induce a state of ketosis such that the body utilises fat for energy instead of using glucose)
• vagus nerve stimulation (VNS) (electrodes around left branch of vagus nerve connected to a programmable stimulator to provide cyclical stimulation)
• responsive neurostimulator system (RNS) (implantable device below scalp with implantable leads into brain to provide brief pulses of stimulation based on patient-specific pattern)
• surgery

Question 14

what are the key points relating to seizure first aid for grand mal seizures

Answer 14

• ease the person to the floor
• lie the person onto their side to help with breathing
• clear surrounding area of sharp or hard objects to prevent injury
• place a soft and flat item under head
• remove eyeglasses and loosen ties
• time the seizure, call 995 if >5mins

DO NOT
- hold down or stop movements
- put objects into mouth
- give mouth to mouth
- offer water until fully alert

Question 15

list common examples of first gen and second gen ASM

Answer 15

first gen
- CBZ
- PB
- VPA
- PHT

second gen
- LTG
- LEV
- TPM
- GBP

Question 16

what are the agents used for each type of seizures

Question 17

what are the key PK characteristics of relevant ASM to note

Answer 17

CBZ
- autoinduction
- elimination by H
- inducer of 1A2, 2C, 3A4, UGT

PB
- elimination by H
- inducer of 1A, 2A6, 2B, 3A, UGT

PHT
- complete but slow A
- highly protein bound, must correct if hypoalbuminemia
- elimination by H
- inducer of 2C, 3A, UGT

VPA
- saturable protein binding
- elimination by H
- inhibitor of 2C9, UGT

LTG
- elimination by H

LEV
- elimination by half R

TPM
- elimination by half R, moderate inducer of 3A, moderate inhibitor of 2C19

GBP
- elimination by R

PGB
- elimination by R

Question 18

what are the common ddi for ASM

Answer 18

• antidepressants and antipsychotics
• immunosuppressive therapy
• antiviral
• chemo

Question 19

what are the s/e and monitoring for each ASM

Answer 19

CBZ
- N/V, osteopenia, hypoNa, SJS (HLAB*1502), CNS
- monitor osteopenia, serum Na, lipid

PHT
- gingival hyperplasia, hirsutism, SJS, osteopenia, arrhythmia, CNS
- monitor osteopenia, lipid

VPA
- N/V, osteopenia, weight gain, pancreatitis, thrombocytopenia, CNS
- monitor osteopenia, LFTs, PLT count

LTG
- HA, insomnia, tremor, rash, CNS

LEV
- psychiatric sx

GBP
- weight gain, peripheral edema

TPM
- weight gain, nephrolithiasis, impaired speech fluency, CNS
- monitor metabolic acidosis

Question 20

what are some CNS side effects of ASMs

Answer 20

nystagmus, ataxia, somnolence, fatigue, dizziness, visual disturbances

Question 21

what are the ref ranges for ASM

Answer 21

PHT
- 10-20mg/L

VPA
- 50-100mg/L

CBZ
- 4-12mg/L

PB
-15-40mg/L

Question 22

which ASM is most suitable for pregnancy and which ASM pose a risk for congenital malformations

Answer 22

LEV/ LTG ok

no VPA
also CBZ, PB, TPM