Epilepsy in Adults

Epilepsy is characterised by the occurrence of at least 2 unprovoked episodes of periodic disturbance in neurological function, often with altered consciousness, due to abnormal excessive electrical discharge within the brain. Accurate diagnosis is essential but misdiagnosis remains a problem. A wrong diagnosis of epilepsy can cause severe restrictions on a patient's lifestyle as well as unnecessarily risk side effects from long term medication. Seizures can be classified as being generalised or partial:¹

• Generalised seizures may be tonic/clonic (grand mal), isolated tonic or clonic, myoclonic (brief, shock-like muscle contractions) or absence (petit mal).
• Partial may be divided into simple partial (motor or sensory) with retained awareness or complex partial (impaired awareness). Partial seizures may progress into generalised seizures. There is a separate article covering Temporal Lobe Epilepsy.

• In European studies, the incidence of first unprovoked seizures ranges from 40-70 per 100,000 persons.
• The incidence is highest in children under ten years old and in the elderly.
• The prevalence of individuals receiving treatment for epilepsy is about 1 in 200, and lifetime prevalence is between 2% and 5% of the population.²
• The prevalence is increased in lower socio-economic groups.

Accurate history taking is essential with particular reference to an eyewitness if possible. Must include family history, past medical history, medication history as well as alcohol and illicit drugs.

• Generalised seizures cause a disturbance in consciousness.
• The classic grand mal seizure progresses through tonic, clonic and post-ictal phases. The post-ictal phase is often associated with headache and drowsiness. Grand mal seizures are often associated with tongue-biting and incontinence.
• Petit mal seizures cause an interruption to mental activity for less than 30 seconds. They rarely persist into adulthood.
• Complex partial seizures may have features of:
  • Motor: automatism, lip smacking, plucking at clothes, hair
  • Sensory: transient paraesthesiae
  • Autonomic: odd epigastric sensation, nausea, abnormal taste or smell
  • Psychiatric: unreality, deja vu, fear.

Symptoms

• There may be a clear precipitating cause, e.g. inadequate sleep, alcohol abuse or medications such as tricyclic antidepressants, which lower the seizure threshold.
• Possible seizure related symptoms include:
  • Sudden falls
  • Involuntary jerky movements of limbs whilst awake
  • Blank spells
  • Unexplained incontinence of urine with loss of awareness, or in sleep
  • Odd events occurring in sleep, e.g. fall from bed, jerky movements, automatisms
  • Episodes of confused behaviour with impaired awareness
  • Possible simple partial seizures
  • Epigastric fullness sensation
  • Deja vu
  • Premonition
  • Fear
  • Elation, depression
  • De-personalisation, derealisation
  • Inability to understand or express language (written or spoken)
  • Loss of memory, disorientation
  • Olfactory, gustatory, visual, auditory hallucinations
  • Focal motor or somatosensory deficit, or positive symptoms (jerking, tingling).

Signs

• Examination is usually unremarkable.
• Check for any neurological or cerebrovascular signs.
• Skin examination may reveal cafe-au-lait spots (neurofibromatosis), port wine stain (Sturge-Weber Syndrome) or adenoma sebaceum (tuberous sclerosis).

Whatever the cause, the patient may have amnesia for both the event and its exact circumstances. Causes include:

• Epileptic seizure:
  • Most are idiopathic; seizures due to underlying diseases affecting the brain are more likely to have a focal onset.
  • Cerebrovascular disease such as cerebral infarction, cerebral haemorrhage, and venous thrombosis.
  • Head injury: head trauma is more significant when it occurs with loss of consciousness lasting longer than 30 minutes, post-traumatic amnesia lasting longer than 30 minutes, focal neurological findings, or neuro-imaging findings suggesting a structural brain injury.
  • Post cranial surgery.
  • CNS infections such as meningitis or encephalitis.
  • Neurodegenerative diseases: epilepsy is more common in people with Alzheimer's disease or multi-infarct dementia.
  • Autoimmune disease.
  • Brain neoplasm.
  • Genetic diseases.
  • Drugs: e.g. phenothiazines, isoniazid, tricyclic antidepressants; binge alcohol drinking; drug (e.g. benzodiazepines) or alcohol withdrawal.
  • Metabolic medical disorders such as uraemia, hypoglycaemia, hyponatraemia, hypernatraemia, hypercalcaemia and hypocalcaemia.
• Non-epileptic events:
  • Syncope
  • Cardiac arrhythmias
  • Transient ischaemic attack
  • Migraine
  • Drop attacks
  • Sleep disorders: narcolepsy
  • Hyperventilation
  • Transient global amnesia
  • Movement disorder
  • Paroxysmal vertigo
  • Convulsive syncope (decreased cardiac output reducing cerebral perfusion with loss of consciousness and convulsive motor activity)
  • Pseudoseizures.

• EEG with photic stimulation and hyperventilation:
  • To support a diagnosis of epilepsy if the clinical history suggests it.
  • To help determine seizure type and epilepsy syndrome.
  • To assess the risk of seizure recurrence after a first unprovoked seizure.
  • If an EEG is necessary, it should usually be performed only after the second epileptic seizure. It should not be used to exclude a diagnosis of epilepsy or in the case of probable syncope (as there is a risk of false-positive result).
• Neuroimaging:
  • To identify structural abnormalities that cause certain types of epilepsy.
  • Not used routinely when a diagnosis of idiopathic generalised epilepsy has been made.
  • MRI: is the imaging investigation of choice for people with epilepsy. It is particularly important for children:
    • Who have developed epilepsy before the age of 2 years.
    • Who have any suggestion of a focal onset from history, examination or EEG (unless there is clear evidence of benign focal epilepsy).
    • In whom seizures continue in spite of first-line medication.
  • CT scan is an alternative to MRI:
    • If MRI is contraindicated or unavailable.
    • In an acute situation, to determine whether a seizure has been caused by an acute neurological lesion or illness.
• Single proton emission computed tomography (SPECT).
• Positron emission tomography (PET).
• Blood tests (including glucose, electrolytes, calcium, renal function, liver function) and urine biochemistry to exclude other diagnoses and to determine an underlying cause of the epilepsy.
• ECG, echocardiography and other non-neurological investigations if the diagnosis is uncertain.

Non-pharmacological support

• New and ongoing diagnosis of epilepsy may have psychological and social consequences as well as the obvious physical ones.
• Disease education and explanation are important as well as education about triggers, first aid, free prescriptions.
• Support groups and referral to an epilepsy liaison nurse can be useful.
• Provide regular structured review by a specialist at least once a year, but probably more frequently (every 3-12 months) depending on need.

Drug Treatment

• Use monotherapy whenever possible.
• The formulation or brand of AED should not be changed (variations in bioavailability or different pharmacokinetic profiles may increase the potential for reduced effect or excessive side effects).
• Asymptomatic minor abnormalities in blood test results are not necessarily an indication for changes in medication.
• Indications for monitoring AED blood levels:
  • Detection of non-adherence to the prescribed treatment
  • Suspected toxicity
  • Adjustment of phenytoin dose
  • Management of pharmacokinetic interactions
  • Specific clinical conditions (e.g. status epilepticus, organ failure or pregnancy).
• Withdrawing treatment:
  • May be considered after 2 years seizure free.
  • Refer for specialist advice before discontinuing especially as risk of further seizure may have significant social and psychological consequences (e.g. driving, employment).
  • The decision to withdraw medication should be taken by the patient and the specialist after a full discussion of the risks and benefits of withdrawal.
  • Withdraw gradually (over 2-3 months or longer); be aware of possible seizure recurrence .
  • Withdraw one drug at a time.
  • Agree with the patient a fail-safe plan of action if seizures recur (last dose reduction reversed, medical help sought).
• First line anti-epileptic drugs:
  • Generalised tonic-clonic seizures only: carbamazepine, lamotrigine, sodium valproate, topiramate
  • Focal epilepsies: carbamazepine, lamotrigine, oxycarbazepine, sodium valproate, topiramate
  • Benign epilepsy with centrotemporal spikes: carbamazepine, lamotrigine, oxycarbazepine, sodium valproate
  • Benign epilepsy with occipital paroxysms: carbamazepine, lamotrigine, oxycarbazepine, sodium valproate
  • Continuous spike wave of slow sleep: clobazam, clonazepam, ethosuximide, lamotrigine, sodium valproate, steroids
  • Myoclonic astatic epilepsy: clobazam, clonazepam, sodium valproate, topiramate.

Surgery

• Modern techniques for the accurate localisation of epileptic discharge and the recognition of specific seizure patterns has increased the role of surgery in the management of drug-resistant epilepsy.
• Operations include temporal lobectomy, hemispherectomies and division of the corpus collosum.
• Vagal nerve stimulation with a stimulator attached to the left vagus nerve has been shown to reduce the number of seizures in patients with chronic partial seizures.

• Some anti-epileptic medication (hepatic enzyme inducers) interact with the contraceptive pill (both COC and POP).
• If possible use an anti-epileptic which doesn't do this (e.g. sodium valproate).
• If this is unavoidable, the present recommendation is to use 50mcg of oestrogen preparations in the combined pill and to run 3 or 4 packs together ("tri-cycling").
• Progesterone only pills are not recommended if on hepatic enzyme inducer (at least double the dose of POP should be used in patients on enzyme inducers who are unwilling or unsuitable for other methods).
• A double dose of levonorgestrel should be used when emergency contraception is required.
• Depo-injections can be used, but should be scheduled every 10 weeks rather than 12 weekly.
• Women should be counselled about the increased risk of pregnancy (contraceptive failure) and any harmful effects of medication on fetus.

Pre-conception counselling

• Essential for all women of child bearing age.
• Consider referral for specialist opinion before conception to reduce or change drug treatment if possible.
• Counsel about the balance between the possible harm done by medication compared with that done by seizures (to both mother and fetus).
• Fetal malformations (most commonly neural tube defects, cleft lip/palate and cardiac malformations) occur in 4% of those diagnosed with epilepsy but not taking medication and increases to 6% when taking medication (polytherapy with certain drugs can have a much higher risk).
• Recommend folic acid 5 mg per day before conception and up to 12 weeks.

• DVLA recommends avoiding driving for 1 year after a seizure.
• Allowed to drive If only nocturnal seizures for 3 years.
• If medication is being withdrawn, must stop driving until 6 months after medication free.
• Group 2 drivers need to be seizure free for 10 years, not be on any anti-epileptic drug during that time and have no continuing liability to epilepsy.

There is an increased risk of sudden death, probably due to unwitnessed seizures.

• Remission becomes less likely with longer persistence of seizures.
• Factors suggesting a poorer prognosis include a combination of complex partial and tonic-clonic seizures, clustering of seizures, abnormal physical signs, and the presence of learning difficulties.