Epilepsy Flashcards
What is epilepsy?
Neurological disorder where sudden recurrent episodes of sensory disturbance, behavioural change and/or convulsions occur
What occurs when a seizure happens?
Abnormally high excitability of neurons in one or more parts of the brain
What is a focal seizure and examples?
Simple
Complex - loss of consciousness
A seizure where the excitation occurs in one section of the brain
What is a generalised seizure?
Excitation starts from a focal point and spreads to majority of the brain
What are examples of a generalised seizure?
Motor:
Myoclonic - clonic to atonic
Tonic-clonic - tonic to clonic
Non-motor:
absence seizure
How does a generalised tonic-clonic seizure present?
Begins with a tonic phase with muscle stiffness that causes falls
Clonic phase with rhythmic jerking and convulsions
How does an absence seizure look?
Patient stares with a blank expression for a few seconds
What are the features of a myoclonic seizure?
Less dangerous with rapid, jerking of limbs
What are the features of atonic seizures and safety measures?
Loss of muscle tone and strength suddenly causing falls
Protective head gear worn by patients
What are seizures called if they begin as focal and become generalised?
Focal to generalised secondary seizure
Starts with focal symptoms
What are the signs and symptoms of focal seizures?
Motor - lip smacking, jerking, hand rubbing, repetitive chewing/swallowing
ANS (peripheral) - Sweating, gastointestinal changes, flushing and tachycardia
Sensory - Smelling/tasting things, hearing things, seeing things, feeling pins and needles
Cognitive - Intense feeling of fear, fiddling with objects, intense joy, behavioural changes like aggression
What is temporal lobe epilepsy (TLE)?
Most common type of focal seizure
Clouds consciousness and alters perception, which gets confused with mental health
What are the common epilepsy syndromes?
Occur during childhood
West syndrome
Lennox-Gastaut Syndrome (LGS)
Dravet Syndrome
Juvenile Myoclonic Epilepsy
What are the causes of epilepsy classified as?
Idiopathic - genetic component
Symptomatic - underlying cause such as an abnormality
Cryptogenic - unknown cause on investigation
What is reflex epilepsy?
Patients have a predisposition for seizures that are triggered by photic, auditory or environmental changes
Example:
Heat/cold
Loud sounds
Thinking/reading
Eating/chewing
How is epilepsy diagnosed?
Detailed history and account of events from a witness
EEG for diagnosis and to classify the type of epilepsy
Difficult to diagnose as it could be confused with other conditions that cause loss of consciousness
What is a confirmed diagnosis of epilepsy?
2 or more unprovoked or reflex seizures, more than 24 hours apart
1 unprovoked of reflex seizure with a probability of 60% of recurrence over the next 10 years
Diagnosis of an epilepsy syndrome
What is seizure freedom?
Go 12 months without having a seizure
What is a therapeutic effect?
3 x the longest previous interval between seizures on the drug
What are the therapeutic objectives for epilepsy?
Reduce the length of time of seizures
Reduce or control frequency of seizures
Improve impact to quality of life
Minimise risk of ADRs with anti-epileptic drugs
What is the likelihood of success with AED?
50% of patients are seizure free within 12 months of starting monotherapy
10-20% success of seizure freedom with 2nd AED after failure with 1st drug
What considerations are there for carbamazepine?
Plasma levels can take up to 2 weeks to reach a steady state
Start low, go slow
Drug toxicity side effects can be reduced by using modified release
Bioequivalence varies with formulation
What are the monitoring requirements for carbmazepine?
Urea and electrolytes - hyponatraemia
Liver function
FBC
What considerations are there for sodium valproate?
Does not need therapeutic drug monitoring, has no defined therapeutic range
Can increase levels of other antiepileptic drugs - inhibits hepatic enzymes
Can cause hepatotoxicity or worsen it
What is the monitoring for sodium valproate?
Liver function - hepatotoxic
FBC - low WBC and platelets
What are the risks of valproate in pregnancy?
Can cause congenital malformations (spina bifida, cleft palate)
risk of neurodevelopment disorders in childhood
What is included in the PPP?
Risk form signed annually by patient
Patient put on a LARC <1% failure rate and pregnancy excluded
Treatment reviewed by specialist once a year
What are the considerations for phenytoin?
Narrow therapeutic index, likely to cause toxicity
Start low, go slow
Poor side effect profile
Many drug interactions
Bioequivalence varies with formulation
Third line for focal and used in status epilepticus
What is the monitoring for phenytoin?
Liver function
FBC
ECG and BP (IV) - cardiovascular issues (brady and hypo)
What are the considerations for lamotrigine?
Rash can occur so titrate dose slowly
Synergistic effect with valproate for reducing seizures
Less side effects and interactions
What are the considerations for levetiracetam?
No monitoring required
Few ADRs and well tolerated
Can mask cognitive and behavioural issues related to brain injury
What are considerations for gabapentinoids (pregabalin and gabapentin)?
Mainly used for neuropathic pain
No monitoring involved, few ADRs
Renally excreted so dose adjustments for impairment is key
What are the considerations for benzodiazapines?
Pam and lam drugs
Used to terminate seizure activity or status epilepticus
Leads to dependency and tolerance
Can be used when switching from one AED to another (short-term)
Sedation effect - diazepam has a long half-life
Clabazam - least sedating
What is the treatment for status epilepticus in community and hospital?
Buccal midazolam or rectal diazepam
IV lorazepam
What are the next steps if the patient does not respond to status epilepticus treatment?
Call 999
Give a second dose of benzos if the seizure does not stop within 5 to 10 minutes of first dose
If second dose does not work give:
IV levetiracetam (least side effects)
IV phenytoin
or IV sodium valproate
What are the non-pharmacological treatment options?
Drug-resistant epilepsy on max. doses of AED:
Resective epilepsy surgery
or vagus nerve stimulation with antiepileptic drugs
What is the treatment for generalised tonic-clonic seizure?
First-line: sodium valproate
Boys/men, girls under 10 unlikely to need treatment when older
Alternative: Lamotrigine or levetiracetam
Girls and women of child-bearing age
Second-line add-on: Any of the above or clobazam
What is the treatment for focal seizures?
First -line: Lamotrigine or levetiracetam
Second-line: carbamazepine or oxcarbazepine
Third line: Lacosamide
What is the treatment for absence seizures?
First-line: Ethosuxamide
Second-line: sodium valproate
Third: Lamotrigine or levetiracetam
What is the treatment for myoclonic seizures?
First-line: sodium valproate
Second-line: Levetiracetam
Third-line: Add-on with lamotrigine
Which AEDs reduce the effectiveness of hormonal contraceptives?
Carbamazepine
Phenytoin
COC with 50micrograms or more is recommended
Avoid progesterone-only
Which drugs for women reduce the effect of lamotrigine?
Oestrogen-containing contraceptives
HRT
Which supplement reduces the chance of neural tube defects with AEDs?
Folate supplements
What should be done for patients if monotherapy or combination fails?
Allow the patient to choose the regimen that was most comfortable for them
In terms of seizure control vs ADRs
What is refractory epilepsy?
Drug-resistant or intractable
Failure to respond to two attempts with AED to achieve sustained seizure freedom
High seizure burden
Which drugs are therapeutic drug monitoring useful for?
Carbamazepine and phenytoin
Plasma levels correlate to efficacy
When is therapeutic drug monitoring conducted?
Starting treatment- to get a baseline
Monitor adherence
Toxicity
Manage PK interactions
Pregnancy, organ failure and status
What is status epilepticus?
When a seizure lasts for 5 minutes or longer
Repeated convulsions without recovery of consciousness
What are the complications of status epilepticus?
Brain death or injury
Catecholamine surge: arrhythmias, tachycardia, high BP
Hypoglycaemia
Lactic acidosis
What must you do if someone is having refractory status epilepticus?
Admit them into the ICU
Induce a coma
Which AEDs have to be given for a specific brand?
Carbamazepine, phenytoin and phenobarbital
Primidone
How should treatment be switched for intolerance or ADRs?
Gradually reduce and stop 1st AED then start 2nd AED with a gradual increase
How should treatment be switched for poor seizure control with no interaction?
Start 2nd AED and gradually increase, then gradually reduce and stop 1st AED
How should treatment be switched for poor seizure control with possible interaction?
Start 2nd AED and gradually increase and at the same time gradually reduce and stop the 1st
How long should it take for AEDs to be stopped?
2-3 months
Longer for phenobarbital and benzos
What drug interactions are important for AEDs?
Older AEDs are inducers of CYP450 enzymes
Lower the plasma concentration of many drugs
Which drugs lower seizure threshold?
Tricyclic antidepressants - amitriptyline (SSRI)
Tramadol - SNRI
Ciprofloxacin
What are the signs of anti-epileptic hypersensitivity?
Occur within 2-8 weeks of exposure
Rash, fever, swollen lymph nodes and organ failure
Stop drug immediately
