Epilepsy Flashcards
What is a seizure?
A SEIZURE is an episode of neurological dysfunction of abnormal firing of neurones manifesting as changes in motor control/sensory perception/behaviour/autonomic function.
What is epilepsy?
EPILEPSY is the condition of recurrent, spontaneous seizures arising from abnormal, synchronous and sustained electrical activity in the brain.
Aetiology of epilepsy?
- Idiopathic epilepsy – genetic cause
- Symptomatic epilepsy (e.g. Head injury/stroke)
- Up to 50% have no apparent cause
- Up to 40% may have a genetic component
Diagnosis of epilepsy?
First step of diagnosis is to establish if paroxysmal event was actually a seizure or something else.
Good history taking and witnesses are useful
Epilepsy is spontaneous and recurrent.
Diagnosis should be made by a specialist (NICE, 2012)
There is no single diagnostic tool, good history taking is key
Clinical diagnosis decision is based upon:
- Description of attack – witness accounts/video footage
- Family history – Genetic cause?
- Blood tests – low Na
- ECG – cardiac cause? Syncope?
- Medication history
- -> Legal and illicit drugs can cause seizures
- -> Overdose of some drugs can lead to seizures
- -> Many commonly prescribed drugs can lower seizure threshold
Neuroimaging and EEGs for epilepsy:
- MRI is better than CT
- Visualisation of structural abnormalities
- Important in those <2 years or adults who develop seizures, and those refractory to AEDs
- NICE recommend should be performed within 4 weeks
- EEGs should never be used in isolation
- Main role is to classify epilepsy
- 10% of epileptic patients never show changes
- 2-4% of healthy people can have abnormal EEGs.
Classification of Seizures:
- May have more than one type of epilepsy
- Depend on the location and focus on the pathways involved
- Failure to classify can lead to inappropriate treatment and treatment failure.
Two Main Types:
1) Partial seizures
- Simple partial seizures – maintain consciousness
- Complex partial seizures – don’t maintain consciousness, aura
- With Secondary Generalisation
2) Generalised seizures
- Tonic (muscle tense)/Clonic (limb shaking, biting tongue)
- Absence – short
- Myoclonic – limb jerking
- Atonic – drop attacks
Seizure triggers:
- Fatigue
- Lack of sleep
- Stress
- Alcohol
- Flashing lights (photosensitive epilepsy)
- Excitement
- Menstruation
- Missing meals
- Some medications
Nice guidelines on PHARMACOLOGICAL MANAGEMENT in epilepsy:
- Always initiated by a specialist, after a diagnosis
- Monotherapy should be used where possible
Start low, go slow - Adjunctive (add on) treatment should only be considered when monotherapy has failed
- AEDs are not usually started after a first seizure (except if quite clear abnormality
Aim of Therapy in epilepsy?
- Single Agent
- Lowest Dose
- Minimum Side Effects
Treatment should be tailored to the individual taking into account:
Patient factors
- Epilepsy syndrome
- Seizure type
- Co-morbidity
- Lifestyle
- Gender
- Age
- Preferences of individual/family/carers
Drug Factors
- Side effect profile
- Dose
- Treatment schedule
- Formulation
- Interactions
Generalised Tonic/Clonic 1st line treatment:
Carbamazepine, Lamotrigine, Na Valproate, Oxcarbazepine
Tonic or Atonic 1st line treatment:
Na Valproate
Absense siezure 1st line treatment:
Ethosuximide, Lamotrigine, Na Valproate
Myoclonic seizure 1st line treatment:
Levetiracetam, Na Valproate, Topiramate
Focal seizure type 1st line treatment:
Carbamazepine, Lamotrigine, Levetiracetam, Oxcarbazepine, Na Valproate
Describe sodium valproate:
1st line therapy in multiple seizure types
Initially 600mg/day in 1 - 2 divided doses increased gradually every 3 days
MHRA: Should be avoided in pregnant women and women of childbearing potential due to risk of neurodevelopmental defects.
Dosage forms = EC tablets, MR tablets, liquid, granules, IV
IV dose = Oral doses
Monitor for signs of liver, blood, pancreatic disorders
Side Effects – nausea, gastric irritation, diarrhoea, weight gain, hair loss
Describe carbamazepine:
- 1st line treatment for focal seizures
- Initially 100-200mg 1-2times daily increased slowly every 2 weeks.
- Monitor for blood, liver or skin disorders
- Available via PO and PR routes: 125mg suppository is equivalent to 100mg orally
- Metabolism at CYP3A4 – potent inducer (interactions)
- Side effects – Headache, N+V, drowsiness, dizziness, rash, ataxia, hyponatraemia
- -> Dose related, can be dose limiting
- -> Can be reduced by using MR tabs
Describe lamotrigine:
- Used for focal and generalised seizures
- Initially 25mg/day and slowly titrated every two weeks
- Serious skin reactions
- -> Increase dose slowly
- -> More common when also on valproate or in first 8 weeks of treatment
- Lamotrigine considered one of safest AEDs in pregnancy
- Oral route only
- Side effects – nausea, vomiting, diarrhoea, dry mouth, skin reactions
Describe Levetiracetam:
- Used for partial seizures and adjunctive therapy for myoclonic seizures and tonic-clonic seizures
- 250mg/day, increased every 1-2 weeks to max 1.5g BD
Little metabolism, not affecting CYP450
–> Therefore few interactions - Good oral bioavailability, therefore no dose alteration between oral and IV
- Side effects: Nasopharyngitis, somnolence, fatigue, dizziness, headache
- -> Low mood, irritability, depression are common reasons for discontinuation
Describe phenytoin:
- Not recommended by NICE for first line
- Role in refractory seizures and status epilepticus
- Initially 3-4mg/kg/day (usual dose 200-500mg/day)
Dose adjusted according to levels and effect - Narrow therapeutic index with saturable kinetics
- Half life 4-72 hours (depends on dose). Steady state reached after 7-10days
- Extensive hepatic metabolism
- Strong inducer of CYP450 - interactions
- Highly protein bound – albumin
- Interactions with enteral feeding
- Capsules and IV = Phenytoin sodium
- Liquid, chewable tablets = phenytoin base
- -> 100mg phenytoin sodium = 92mg phenytoin
- -> Need to be careful when switching formulations
Side effects – N+V, constipation, drowsiness, parasthesia, gingival hyperplasia, acne, hirsuitism, coarsening of facial features.
Signs of overdose - Nystagmus, ataxia, diplopia, slurred speech, confusion, hyperglycaemia
- Desirable plasma-phenytoin concentration = 10-20mg/litre
Antiepileptics are divided into three categories according to the importance of maintaining a consistent supply of a particular manufacturers product/brand:
Category 1: Includes phenytoin, carbamazepine, phenobarbital,
Specific measures are necessary to ensure consistent supply of a particular product
Category 2: Includes sodium valproate, lamotrigine, oxcarbazepine
The need for continued supply based on clinical judgement
Category 3: Includes levetiracetam, lacosamide, gabapentin
No specific measures required
Women and epilepsy:
Antiepileptics interact with hormonal medications
- Can reduce effectiveness as enzyme inducers. E.g. Carbamazepine, phenytoin
- Oral contraceptives and EHC can reduce effectiveness of lamotrigine.
- May need to increase dose of lamotrigine
- Some AEDs are teratogens/can cause birth/developmental defects
- These drugs are to be avoided in women of childbearing potential and pregnant women
- Pharmacokinetics can be altered in pregnancy
- All women on AEDs should be offered folic acid 5mg OD before any possibility of pregnancy
- Some women have increased seizure frequency around menstruation
- Side effects of some AEDs may be undesirable
Epilepsy and Older People: Pharmacokinetic and pharmacodynamic issues
Polypharmacy
Co-morbidity
Consider using lower doses of AEDs
If on carbamazepine, this should be modified release
What is Status Epilepticus?
Medical emergency associated with significant morbidity and mortality
Efficient and effective treatment is key
Aim of treatment is seizure termination
Generalised Convulsive Status Epilepticus is defined as a tonic clonic seizure which lasts longer than 30 minutes or repeated tonic clonic seizures within 30 minutes with little or no recovery in between
Status Epilepticus - Treatment
- IV Lorazepam 0.1mg/kg (usually 4mg), repeated once after 10-20 minutes if seizure continues
- -> Give usual AEDs if already on treatment
- -> Alternatives to lorazepam are IV diazepam or buccal midazolam
- Phenytoin IV 20mg/kg over 20 minutes (or phenobarbital if already on phenytoin)
- General anaesthesia if above does not work
Treatment Failure and Resistance:
If treatment fails despite maximal doses - Check compliance - Has brand/formulation changed? See MHRA guidance - Check diagnosis (NICE) Wrong treatment for seizure type? - ?brain tumour - Alcohol/drug misuse
None of the above?
- Change to second line therapy
- Initiate second drug, increase to therapeutic dose then wean first drug
- Avoid abrupt withdrawal of AEDs – risk of rebound seizures
Combination Therapy:
Combination therapy should only be initiated by a specialist after treatment failure with monotherapy
Many newer drugs have demonstrated efficacy as ‘add-on’ therapy
If combination therapy doesn’t work….
Revert to regimen that provided the best balance of tolerability and efficacy
May be monotherapy or combination therapy
Problems with combination therapy:
- Drug interactions
- -> Potent inducers/inhibitors of hepatic enzymes
- -> Drug-Drug interactions between AEDs
- Increased toxicity
- -> Interactions can increase plasma concentration
- -> Additive side effects
- Identifying ADRs
Can be difficult to differentiate - Non—compliance
Increased pill burden
Unpleasant side effects
Treatment withdrawal:
- Joint decision taken by patient and family/carers
- Under the guidance of a specialist
Must be seizure free for 2 years before considering withdrawal
- Withdrawal must be carried out slowly over months
- One drug at a time if on combination therapy
A failsafe plan must be in place in case seizures recur.
- Last dose reduction is reversed and medical advice sought
Information for patients:
- All aspects of care discussed prior to treatment
- Importance of compliance explained – even when seizure free
- Dosing schedule and dose titration
Signs and symptoms of adverse effects
- Blood disorders
- Liver dysfunction
- Skin disorders
- Brands and formulations
- MHRA/NICE
- OTC and other medications
Social Aspects of Diagnosis:
- Employment
Cannot be refused employment under Equality Act 2010 but employers must consider health and safety
Driving
- If you have a seizure you must stop driving and tell the DVLA
- Group 1 license: cars and motorbikes, after one year seizure free (on/off AEDs)
Can learn to drive at 17 if one year seizure free
Consider side effects of AEDs such as drowsiness
- Alcohol
–> Interactions with AEDs
May trigger seizures
