Epilepsy Flashcards
What is epilepsy?
The tendency to have recurrent seizures
Primarily diagnosed after a person has experienced two unprovoked seizures more than 24 hours apart
What is the practical definition of epilepsy based on the International League Against Epilepsy task force?
Epilepsy is a disease of the brain defined by any of the following conditions:
* At least two unprovoked (or reflex [i.e. induced by a specific trigger]) seizures occurring >24 hours apart or
* One unprovoked (or reflex) seizure and a probability of further seizures, similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next ten years, based on neurologist experience or
* Diagnosis of an epilepsy syndrome
When is epilepsy defined as resolved?
In individuals with an age-dependent epilepsy syndrome, who are now past the age criteria for certain syndromes
OR
Those who are seizure free for more than 10 years, with no antiseizure medicines and have not needed antiseizure medicines for the past 5 years
* Withdrawal of medication usually considered after 2 years of seizure freedom on medication
Can epilepsy be cured? If so, how?
The only cure for epilepsy is surgical removal of brain lesion, and only in suitable individuals.
Some epilepsy syndromes of childhood will resolve as the child ages. However, in other cases, the child may go on to develop a different epilepsy syndrome.
Epilepsy is the most common serious neurological condition in the UK.
1. How many people does it affect?
2. Is it higher in males or females?
3. Is incidence higher in lower or higher income countries?
- 600,000
- Incidence is higher in males than females (50.7 vs. 46.2 per 100,000 people)
- Lower income
Epilepsy is the most common at what ages?
- Infancy, often caused by brain damage during birth
- Older age, owing to cerebrovascular disease, with seizures common after stroke
The incidence steadily increases after 50 years old, with the greatest increase seen in those aged over 80 years.
What is the most common cause of epilepsy?
For many people worldwide — perhaps as many as 50% — the cause of their epilepsy is not determined
Less common causes of epilepsy include brain tumours, head injury and/or CNS infections, such as meningitis. In developing countries, infections caused by parasites are the most common cause.
What is the most common cause of epilepsy?
For many people worldwide — perhaps as many as 50% — the cause of their epilepsy is not determined
- It is possible that many epilepsies have an underlying genetic cause, although this may not necessarily be inherited but caused by spontaneous gene mutation
In developing countries, infections caused by parasites are the most common cause
People with epilepsy have higher incidence of what diseases/conditions?
-
CNS-related conditions (depression, anxiety, sleep issues, migraine and memory problems)
- Suicide is up to 3.5–5.8 times greater in epileptic patients
- Up to half of all patients with epilepsy report some form of memory issue. Topiramate also associated with memory problems.
- Somatic conditions (T1DM, ischaemic heart disease, arthritis and gastric bleeds)
Prevalence of epilepsy in people with an intellectual disability (ID) is also as high as 22%
What is forced normalisation?
For people with co-morbid mental health conditions, improving psychosis can result in a worsening of seizure control and, likewise, improvements in seizure control can worsen psychosis
How is epilepsy diagnosed?
- Witness account of seizure
- An electroencephalogram (EEG) is carried out when a person is suspected of having epilepsy based on their clinical history (e.g. after having a seizure)
- MRI may be used to help identify any obvious lesions or scarring in the brain that are causing seizures.
*MRI recommended by NICE if: develops epilepsy before two years of age or as an adult; if focal epilepsy is suspected; or if seizures continue despite medication
What percentage of people will be rendered seizure free after the first AED? (i.e. no seizures for at least 1 year)
What about if they need adjunctive therapy?
Around half
However, the probability of achieving seizure freedom reduces substantially with each subsequent drug
Around 30% of patients will require polytherapy and more than one-third of patients’ epilepsy will remain uncontrolled, which is described as refractory to medication
Drug resistance is more likely in what situations?
If there is an early onset of seizures, focal seizures or multiple seizure types
Evidence does not support any one approach over another for the management of seizures if the first drug does not control the condition or is poorly tolerated.
True or False?
True
There is no agreement on whether drugs with the same mechanism of action should be combined or whether drugs with differing modes of action should be selected.
Why should dosage frequency of antiepileptic drugs be kept as low as possible?
To promote adherence.
Why may large doses of antiepileptic drugs require frequent dosing?
To avoid adverse effects associated with high plasma-drug concentrations.
When switching from one antiepileptic drug to another, what should be done?
Check diagnosis before starting alternative drug
The first drug should be slowly withdrawn only when the new regimen has been established.
For what indication is the MHRA advice on maintaining specific products of antiepileptic drugs relative to?
Epilepsy
Does not apply to other indications
The side effect profiles of many of the ASMs (including newer ASMs) are similar, regardless of the drug’s mechanism of action.
How should suspected adverse reactions to antiepileptic drugs be reported?
On an MHRA Yellow Card.
When may it be necessary to dispense a product from a different manufacturer?
When there are supply problems, in order to maintain treatment continuity.
What are the three risk-based categories for antiepileptic drugs?
Category 1: Patient should be maintained on a specific brand.
Category 2: Supply of a specific brand based on clinical judgement.
Category 3: Unnecessary to supply a specific brand.
For which antiepileptic drugs should a patient be maintained on a specific brand? (category 1)
CP3
carbamazepine, phenytoin, phenobarbital, primidone
For which antiepileptic drugs should supply of a specific brand be based upon clinical judgement? (Category 2)
Valproate, lamotrigine, topiramate, clobazam, zonisamide, clonazepam, perampanel, retigabine, rufinamide, oxcarbazepine, eslicarbazepine,
For which antiepileptic drugs is it unnecessary to supply a specific brand? (Category 3)
Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide, vigabatrin.
Antiepileptic drugs are associated with a small increase in risk of what psychological side effect? (MHRA alert)
Suicidal thoughts and behavior.
Symptoms may occur as early as 1 week after starting treatment
Seek medical advice and do not stop treatment.
If a patient on antiepileptic drugs develops suicidal thoughts and behaviors, what should they do?
Seek medical advice.
Do not stop treatment.
How soon since starting antiepileptic drug treatment may patients experience suicidal thoughts and behaviours?
As soon as one week after starting treatment.
Most antiepileptics, when used in the usual dosage, can be given twice daily.
Which antiepileptics have a long half-life which means they can be used once daily?
Lamotrigine, perampanel, phenobarbital, and phenytoin
(LP3)
Abrupt withdrawal of antiepileptic drugs should be avoided. How should antiepileptic drugs be withdrawn?
Withdraw under specialist supervision.
Highest risk of rebound seizures: barbiturates and benzodiazepines
Reduction in dosage should be gradual to prevent rebound seizures, usually over at least three month and longer for benzos and barbiturates
Withdraw one at a time.
Even in patients who have been seizure-free for several years, there is a significant risk of seizure recurrence on drug withdrawal.
How long can it take for the withdrawal of barbiturates?
Over 3 months.
What is the main risk with withdrawal of antiepileptic drugs?
Significant seizure recurrence.
Withdraw of antiepileptic drugs from a seizure-free patient may be considered after the patient has been seizure-free for how long?
At least two years
What vehicles can patients with epilepsy drive?
They can drive vehicles apart from large goods vehicles or passenger vehicles.
What conditions must be satisfied before a patient with epilepsy can drive?
If first unprovoked/single isolated seizure:
- Do not drive for 6 months
- Can drive after 6 months once assessed by specialist as fit to drive and no further risk of seizures
If established epilepsy:
- May drive if compliant with treatment and follow up
- They must be seizure free for 1 year (or have a pattern of seizures established for 1 year where there is no influence on their level of consciousness or the ability to act) or have established a three-year period of only asleep attacks if the patient previously had seizures whilst awake or 1 year history of sleep seizures occurring only ever while asleep
- Must have no history of unprovoked seizures
When does the DVLA recommend that patients with epilepsy do not drive?
Patients with epilepsy should not drive during medication changes, withdrawal of medication, or 6 months after last dose.
If a seizure occurs during withdrawal/change, license revoked for 1 year
- Can be reinstated after 6 months if treatment restarted and no seizures have occured in that period
Which antiepileptic drugs are associated with an increased risk of teratogenicity?
Valproate, phenytoin, primidone, phenobarbital, lamotrigine, carbamazepine.
CP3-LV
Which antiepileptic drug is associated with the greatest risk of congenital malformations and long-term developmental disorders?
Valproate
Carbamazepine, phenobarbital, phenytoin and topiramate also have an increased risk (the risk for carbamazepine, phenobarbital, and topiramate is dose dependent)
In which patients should valproate not be used unless there is no safer alternative?
People under 55 years (males or females)
Especially pregnant women, female children and women of childbearing potential.
How should antiseizure medicines be monitored?
- Drug-specific parameters (e.g. LFTs for sodium valpoate) are indicated before therapy and periodically in the first 6 months after starting. There is no further guidance on when they should be monitored.
- NICE recommends that FBC, U+Es, LFTs are taken for enzyme-inducing drugs every 3-5 years
- Bone metabolic tests every 2-5 years for adults taking enzyme-inducing ASMs and valproate
There is no rationale for regular plasma drug monitoring in patients taking ASMs, although there are some instances when it is indicated
There is no evidence to support a certain frequency of review in patients with epilepsy. Current NICE guidelines suggest annual review with a patient’s GP or epilepsy specialist
Considerations during medication review with patients taking ASMs?
List some enzyme inducing ASMs.
Carbamazepine (and analogues - eslicarbazepine, oxcarbazepine)
Perampanel (at a dose of 12 mg daily or more)
Phenobarbital
Phenytoin
Primidone
Rufinamide
Topiramate (at a dose of 200 mg daily or more)
What are some possible indications for ASM therapeutic drug monitoring?
- Dose optimisation of initially prescribed treatment, including patients on phenytoin therapy and in cases of suspected toxicity
- Uncontrolled seizures
- Children
- Pregnancy
- Older age
- Changes in ASM formulation, including when switching from branded to generic
- Pathological states leading to possible alterations in ASM pharmacokinetics (e.g. in hepatic or renal disease);
- Pharmacokinetic interactions (e.g. when multiple ASMs are used together).
What teratogenic malformation is associated with topiramate use and when is it likely to occur?
An increased risk of cleft palate when taken in the first trimester of pregnancy.
What advice should be given to pregnant women who also have epilepsy?
Advice about effective contraception methods to avoid unplanned pregnancies.
Women who want to become pregnant should be referred to a specialist.
Do not stop treatment abruptly.
What is the likelihood of a woman who is taking antiepileptic drugs having a baby with no malformations?
At least 90%. It is important not to stop taking essential treatment.
Parents should receive advice on caring for their baby to reduce seizure-associated risks. This includes avoiding bathing the baby alone and changing the baby on the floor.
What is the percentage of congenital malformations and neurodevelopmental disorders with valproate?
Congenital malformations = approx. 10% risk with valproate
(6% and 4–5% for phenytoin and carbamazepine, respectively)
Neurodevelopmental disorders = approx. 30–40% risk
In the case of women who are treated with sodium valproate or valproic acid, who become pregnant, what course of action is required?
An urgent consultation is required to reconsider the benefits and risks of valproate therapy.
When is folate supplementation advised in pregnancy? Why?
Before conception and throughout the first trimester (first 12 weeks)
5mg for patients taking antiepileptic drugs.
Women who have seizures during the second half of the pregnancy should be assessed for what, before changing any treatment for epilepsy?
Eclampsia.
Eclampsia is the onset of seizure in a woman with pre-eclampsia. Pre-eclampsia is a hypertensive disorder of pregnancy that presents with three main features: new onset of high blood pressure, large amounts of protein in the urine or other organ dysfunction, and oedema.
Routine injection of which vitamin at birth minimises the risk of neonatal hemorrhage associated with antiepileptic drugs?
Vitamin K.
What effects may be seen in babies born to women who have been taking antiepileptic drugs?
Withdrawal effects.
Particularly benzodiazepines and phenobarbital.
Can mothers on antiepileptic drugs breastfeed?
Yes if on monotherapy
If they are on combination therapy or if there are other risk factors (e.g. premature birth), seek specialist advice
What should babies born to mothers taking antiepileptic drugs be monitored for?
Sedation, feeding difficulties, adequate weight gain, developmental milestones, adverse effects associated with the specific antiepileptic drug.
If suspected adverse reactions to antiepileptic drugs occur in breastfed children, what monitoring should be carried out?
Serum-drug concentration.
If toxicity to an antiepileptic drug occurs in breastfed children, what course of action may be required?
The introduction of formula feeds to limit drug exposure or weaning off of breastmilk altogether.
What is antiepileptic hypersensitivity syndrome?
How long after exposure to a specific antiepileptic drug may patients experience the symptoms of AHS?
A rare but potentially fatal syndrome associated with some antiepileptic drugs
Results in fever, rash, lymphadenopathy, vasculitis, multiorgan failure
May present between 1 and 8 weeks after starting treatment
What drugs are associated with an increased risk of antiepileptic hypersensitivity syndrome?
Carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide
CP3, L2, R+O1
What action should be taken if signs or symptoms of antiepileptic hypersensitivity syndrome occur?
The drug should be withdrawn immediately and expert advice should be sought.
Do not re-expose.
What are the two main types of seizures?
Focal (70%) and generalised.
Focal seizures can become generalised.
Define focal seizures.
The abnormal electrical activity begins in a localised area, the ‘focus’
- Can become generalised
The type of seizure depends on where in the brain that focus is and how far from the focus the seizure activity propagates
More refractory to treatment and are more likely to go undiagnosed than generalised seizures
How can focal seizures be further categorized?
Focal aware/simple partial seizures and focal impaired/complex partial seizures.
Define focal aware/simple partial seizures.
Focal seizures where the patient remains conscious throughout the seizure.
They are able to talk, follow instructions and remember the seizure
For someone having a focal aware/simple partial seizure how does it present if the following are affected:
1. Temporal lobes
2. Frontal cortex
1. Temporal lobes
May experience an intense unpleasant sensation, such as smelling a strong smell or feeling an overwhelming sense of déjà -vu
2. Frontal cortex
Seizure is often movement related, so the person may display peddling or kicking movements, their head may turn to one side or they may adopt a strange bodily position
Define focal impaired awareness/complex partial seizures.
Focal seizures where the patient loses consciousness/is partially responsive and cannot remember what happened after the seizure has passed.
The person might be able to hear you, but not fully understand what you say or be able to respond to you. They may not react as they would normally.
Define generalized seizures.
Seizures where most or all of the brain is affected.
Arise simultaneously from both cerebral hemispheres of the brain, leading to an immediate loss of consciousness
How can generalized seizures be further categorized?
Absence seizures, myoclonic seizures, clonic seizures, atonic seizures, tonic seizures, tonic-clonic seizures.
Define absence seizures.
Seizures where the patient loses awareness of their surroundings, usually for up to 15 seconds.
- May appear to pause mid-sentence stare off to distance or continue walking but not be aware
- More common in children but can occur in adults
May have tens to hundreds of absence seizures a day
Define myoclonic seizures.
Seizures causing the patient’s arms, legs or upper body to jerk or twitch, brief loss of consciousness.
Lasts fraction of a second but can happen in clusters
Often happen after waking
Define clonic seizures.
Similar twitching of the arms, legs or upper body as myoclonic seizures except for longer. May last for up to two minutes.
Define atonic seizures.
Seizures where all of the muscles suddenly relax, resulting in possible injury due to a forwards fall.
Lasts ~15 seconds
Overview of the four main anti-seizure medicines
When is buccal midazolam used?
How should it be prescribed?
Despite not being licensed for use in adults in the UK, buccal midazolam is recommended by NICE for prevention of status epilepticus
Prescribe by brand
* The two different salts (hydrochloride - buccolam - and maleate - epistatus) which are not interchangeable
* Adult patients should be dispensed the highest strength product unless otherwise stated. The dose should not be made up with multiple administrations of lower strengths.
* Should not be kept in the fridge
