Epilepsy Flashcards
What are the first, new, and third line drugs for use in generalised seizures?
First: valproate, (ethosuxomide for absence)
New AEDs: lamotrigine, topiramate, levetiracetam
Second line: clonazepam/clobazam
What are the first, new, and third line drugs for use in focal seizures?
First: carbamazepine, phenytoin, valproate
New: Any
Third: clonazepam/clobazam, barbituates
How can therapeutic drug monitoring be helpful?
- Check compliance
- In pregnancy
- If someone does not have seizure control on a drug and they are near the upper reference limit, unlikely to gain control with dose escalation
What proportion of patients are in remission from their epilepsy after two years, if you stop their AED (so long as they have already been in remission for two years on the drug?)
60%
Less likely if previously unsuccessful withdrawal, abnormal EEG, syndrome like Juvenille Myoclonic Epilepsy
What impact do AEDs have on fertility?
- Women and men with epilepsy have reduced fertility (?social factors)
- Endocrine abnormalities
- Increase SHBG
- Increase PCOS in valproate in epilepsy
- Obesity and insulin resistance
- Hyperandrogenism associated with VPA - effect of epilepsy/seizure on HPA axis?
What is the mechanism of impaired hormonal contraception in AEDS?
Carbamazepine, phenytoin, phenobarbitone, primidone (topiramate, oxcarbazepine) promote oestrogen and progesterone metabolism
There is no evidence that using the higher dose ethinyloestradiol is ok
Implanon not effective
High dose depot medroxyprogesterone works
Mirena has an acceptable failure rate
AEDs and birth defect. Which agent is worse? What does the data show?
No AED exposure- about 3% risk Monotherapy (any)- 6% High dose valproate - 10% Conflicting data on polytherapy Levetiracetam low risk No proof for folate supplementation General increase in most types of birth defects but there are some specific associations
What birth defects does valproate cause?
Neural tube defects Hypospadias congenital heart defects craniofacial gen/u skeletal defects
What is the mechanism that explains valproate dose effect?
Beta oxidation of VPA saturates at approx 800mg per day–>more excreted as glucuronide–>more reactive than products of beta oxidation
Does folate protect against congenital malformation in AED?
No
Lamotrigine levels do what doing pregnancy?
By second ten week period of pregnancy, substantial decrease in levels relative to dose, then increase again quickly after delivery
Which is the AED where levels go down during pregnancy and then bounce back very quickly after delivery?
Lamotrigine
How are the delivery and post natal periods in AED patients?
No increase in obstetric complications
Seizure control generally stable
Breast feeding- may have significant levels in milk of levetiracetam, lamotrigine, but no proven effect on cognition.
Are there any long term neurocognitive effects for infants of mothers on AED during pregnancy?
valproic acid has a dose related effect on IQ
carbamazepine conflicting data
polytherapy may be worse
phenytoin, phenobarbitone, primidone associated with lower IQ but not clearly independent of maternal IQ
Emerging literature suggests an association between valproic acid and autism/behavioural problems
What is the association between AEDs and fractures?
Increase risk of osteoporotic fractures with cumulative dose, whatever the agent with OR of 2
This is independent from the increased trauma related to seizures.
Advice about bone health in epilepsy
smoking cessation
exercise
calcium and vitamin D- check levels and supplement
bone densiometry
What proportion of newly diagnosed epilepsy will not respond to one, two, three or multiple drug therapies?
36% not seizure free
What is “drug resistant epilepsy.”
Failure of adequate trials of two or more tolerated and appropriately chosen and used AED to sustain seizure freedom. (Either at same time or sequential.)
In basic terms, how do you identify if someone with drug resistant epilepsy is a candidate for epilepsy surgery?
identify epileptogenic zone. Then identify the eloquent cortex. No part of the eloquent zone can be removed.
What are the most common MRI findings in epilepsy?
Mesial temporal sclerosis malformation of cortical development low grade tumour vascular malformation post traumatic changes
What is ictal SPECT?
Radiotracer injected during seizure. Localisation based on focal hypoperfusion of the region of the epileptogenic zone. Well established in TLE- correctly lateralises in 90%
What is the likelihood of temporal lobe epilepsy patient becoming seizure free post temporal lobectomy?
60-70% seizure free or substantial reduction
What is the leading cause of epilepsy?
Stroke, then dementia
What is juvenille myoclonic epilepsy?
First thing in the morning or when tired–>seizures
most common form of childhood epilepsy
Valproate good
avoid phenytoin or carbamazepine
