Epilepsy Flashcards
What is the difference between seizure and epilepsy?
A seizure is a transient occurrence of signs and or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Epilepsy is defined by any of the following:
- at least two unprovoked seizures occurring > 24h apart
- one unprovoked seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures
- diagnosis of an epilepsy syndrome
What are some causes of provoked seizures?
- electrolyte imbalances
- toxic substance/drugs
- traumatic brain injury
- stroke
- CNS infection
- febrile illness
What is the pathophysiology of epilepsy?
Hyperexcitability:
- enhanced predisposition of a neuron to depolarize
- K+, Na+, Ca2+, and CL- ion channels
Hypersynchronization
How do we classify seizures?
Based on mode of onset (focal or generalized) and impairment of consciousness (with or without dyscognitive features)
What is the clinical presentation for focal onset (without dyscognitive features) seizures?
- clonic movements like twitching or jerking
- speech arrest
- feelings of numbness or tingling
- flashing lights
- rising epigastric sensation
- sweating, salivation or pallor
- BP and HR
- hallucinations
- fear, depression etc.
What is the clinical presentation for focal onset (with dyscognitive features)?
- presence of aura
- impaired consciousness
- automatisms like lip smacking
What is the clinical presentation of generalized onset tonic clonic seizures (GTC)?
- begins with stiffening of the limbs (tonic phase), followed by jerking of limbs and face (clonic phase)
- during tonic phase, breathing may decrease or cease -> cyanosis can occur, typically returns during clonic phase
What investigations are used in diagnosis of epilepsy?
- If diagnosis of seizures or epilepsy is considered, epileptiform discharges on Electroencephalogram (EEG) confirm the diagnosis.
- MRI to identify any focal lesions
- biochemical tests -> help to rule out electrolyte abnormalities
When do we usually start pharmacological treatment for epilepsy?
After two unprovoked seizures
What are the non-pharmacological therapies used in epilepsy?
- ketogenic diet (especially in young children)
- vagus nerve stimulation (VNS)
- responsive neurostimulator system (RNS) -> implant a stimulator in the skull
- surgery -> remove a part of the brain
- having a seizure diary
What is the general treatment for epilepsy?
Monotherapy is preferred.
To initiate treatment, start with low dose of a first line AED appropriate for particular seizure type. If seizures continue but no side effects occur, gradually increase the dose of AED.
What are some psychosocial issues associated with epilepsy?
- social stigma (marriage and starting a family)
- employment issues
- prohibited from driving in singapore
- caregiver burden
What are some common seizure triggers?
- hyperventilation
- photostimulation
- physical and emotional stress
- sleep deprivation
- electrolyte imbalance e.g. hypoglycemia, hyponatremia, etc
- sensory stimuli
- infection
- hormonal changes eg during mensus, puberty or pregnancy
- drugs
What is appropriate seizure first aid?
For generalized tonic clonic seizures:
- ease person to floor
- turn person gently onto one side -> help person breathe
- clear the area of anything hard or sharp
- put something soft and flat under his head
- remove eyeglasses
- loosen ties or anything around the neck which may make it hard to breathe
- time the seizure. if last longer than 5 mins, call ambulance.
What are the factors that influence ASM choice?
- seizure type
- co-medication and comorbidity
- patient’s lifestyle and preference
- guidelines, availability and costs
What are the five first line treatment options for focal onset epilepsy?
- carbamazepine
- levetiracetam
- valproate
- lamotrigine
- oxcarbazepine
non-guideline
- phenytoin
- topiramate
- gabapentin
What are the three first line options for generalized tonic clonic epilepsy?
- lamotrigine
- valproate
- carbamazepine
non guideline:
Topiramate
What epilepsy medication should be used if there is comorbid migraine?
Topiramate and valproate.
What epilepsy medication should be used in comorbid depression/anxiety?
Use levetiracetam with caution.
What epilepsy medication should women of child bearing potential avoid?
Valproate.
Consider levetiracetam/lamotrigine
What are the potent enzyme inducers?
- carbamazepine
- phenytoin
- phenobarbital
What is a potent enzyme inhibitor?
- valproate
What are some epilepsy drugs with no effects on CYP?
- gabapentin
- levetiracetam
- pregabalin
What is a moderate CYP inducer?
- topiramate
What is something to note about discontinuing ASM?
If discontinuing an enzyme inducing/inhibiting ASM, need to adjust the doses of affected medications.
What is the bioavailability of phenytoin?
F = 1.
- complete absorption, but slow.
- reduced at higher doses
- reduced by NGT and feeds interaction (space out 1-2 hours between feeds and medication)
Is phenytoin protein bound?
Yes, phenytoin is highly albumin bound. In low albumin, free phenytoin increases.
Need to correct for albumin level (low albumin)
What is the kinetics for phenytoin?
zero order kinetics, capacity-limited clearance.
concentration increment is not proportional to dose increment.
Is valproate protein bound?
Yes, valproate is highly albumin bound.
Saturable protein binding within therapeutic range.
Total valproate conc increases in non linear fashion with dosage increase.
Unbound/free valproate conc increases in a linear fashion with dosage increases.
What is auto-induction for carbamazepine?
- Carbamazepine induces its own metabolism.
- Clearance increases and half life shortens.
- Maximum autoinduction occurs 2-3 weeks after dose initiation.
Hence, do not start with desired maintenance dose at first dose, gradually increase over initial few weeks.
What are some dose/plasma concentration related adverse effects of ASM?
- CNS (somnolence, fatigue, dizziness, visual disturbances, etc)
- GI (nausea vomiting) - carbamazepine and valproate
- psychiatric (behavioural disturbances) - levetiracetam
- cognition (speech fluency) - topiramate
What are some idiopathic/hypersensitivity related adverse effects of ASM?
- blood dyscrasia (aplastic anemia and agranulocytosis)
- hepatotoxicity (phenytoin, valproate and carbamazepine)
- pancreatitis (valproate)
- lupus like reaction
- exfoliative dermatitis
- toxic epidermal necrolysis/SJS
(most likely to occur in first few months of tx)
What are some chronic/systemic adverse effects of ASM?
- gingival hyperplasia (phenytoin)
- hirsutism (children and young adults on chronic phenytoin therapy)
- alopecia (valproate)
- encephalopathy (phenytoin, phenobarbitone)
- peripheral neuropathy (phenytoin, carbamazepine and phenobarbitone)
- increased weight gain (valproate)
- anorexia and weight loss (topiramate)
- osteomalacia (phenytoin, phenobarbitone and carbamazepine - enzyme inducer - increased clearance of vit D)
Which ASM are associated with neonatal congenital defects?
- phenytoin, phenobarbitone and topiramate
- valproate affects cognition
What is an important adverse effect some ASMs can cause?
suicidal ideation.
What are some ways to prevent hypersensitivity reactions from ASM?
- pharmacogenetic testing for carbamazepine -HLA-B1502 allele
- follow dosing guidelines for lamotrigine - slow titration
- identify cross sensitivity reaction (ASM with aromatic rings)
What can levetiracetam cause?
Irritability and aggression
Why do we need TDM for ASM?
- plasma conc correlates much better than dose with clinical effects
- assessment of therapeutic response is difficult bc ASM tx is prophylactic
- not easy to recognize signs of toxicity
- substantial PK variability
- no lab markers for clinical efficacy or toxicity
How does ASM affect the use of oral contraceptives?
- potent enzyme inducers may render OC ineffective -> alternative methods required
- for pts on lamotrigine, OC may lower lamotrigine conc, resulting in breakthrough seizures
Should mothers taking ASM breastfeed?
Encourage to breastfeed
When can ASM be discontinued?
After a minimum of two years without a seizure
When is epilepsy considered to be resolved?
- had age dependent epilepsy but now past the applicable age
- remained seizure free for the last 10 years, with no seizure medicines for the last 5 years
What is status epilepticus?
- cannot stop having seizures
What drug do we use to treat status epilepticus?
benzodiazepines (e.g. midazolam, lorazepam or diazepam)
