Epilepsy and Seizures: Diagnosis and Management

Introduction

A seizure is a transient clinical event caused by abnormal, excessive and synchronous electrical discharge of cortical neurons. Epilepsy is not synonymous with 'a seizure' - it describes a persisting tendency to recurrent, unprovoked seizures, and is generally diagnosed clinically after two unprovoked seizures occurring more than 24 hours apart, or after a single unprovoked seizure where the risk of recurrence is judged high (for example, an epileptiform EEG or a structural brain lesion).¹

Epilepsy affects around 1% of the population and is one of the commonest neurological conditions seen in both primary and secondary care. It is a high-yield exam topic because the diagnosis depends almost entirely on a good history, the drug choices are strongly linked to seizure type and reproductive status, and the social consequences (driving, employment, pregnancy) are frequently tested.

A provoked (acute symptomatic) seizure - caused by an identifiable acute insult such as hypoglycaemia, alcohol withdrawal, or a metabolic derangement - is not epilepsy, and the distinction matters because it changes both prognosis and the need for long-term antiepileptic treatment.

Around 1 in 20 people will have a single seizure at some point, while only about 1 in 100 develops epilepsy - a distinction that explains why a first seizure does not automatically warrant lifelong treatment. Incidence is bimodal, highest in early childhood and again after the age of 60, and in that older group a new seizure is far more likely to have an identifiable structural cause, most often cerebrovascular disease, which is why imaging is more urgent in a first seizure presenting late in life.

Classification

The modern (ILAE) classification starts by asking where the seizure begins.²

Focal seizure semiology by lobe

• Temporal lobe - the commonest focal epilepsy in adults. An epigastric rising sensation, déjà vu, fear, automatisms (lip-smacking, fumbling), and impaired awareness, often with a preceding aura
• Frontal lobe - motor features, often brief, frequent, and occurring in clusters, sometimes with bizarre motor automatisms (kicking, pedalling) that can be mistaken for a non-epileptic attack
• Parietal lobe - sensory disturbance, sometimes spreading (a 'Jacksonian march')
• Occipital lobe - positive visual phenomena, such as flashing lights or simple shapes in one visual field

Aetiology

• Idiopathic/genetic - no structural cause found; many generalised epilepsies (juvenile myoclonic epilepsy, childhood absence epilepsy) fall here and have a genetic basis
• Structural - stroke (the commonest identifiable cause of new epilepsy in older adults), tumour, traumatic brain injury, cortical malformation, mesial temporal sclerosis (strongly associated with febrile seizures in childhood)
• Infectious - previous meningitis or encephalitis, neurocysticercosis (a leading cause of epilepsy worldwide)
• Metabolic - inborn errors of metabolism, particularly in children
• Immune - autoimmune encephalitis (for example anti-NMDA receptor)
• Provoked (not epilepsy) - hypoglycaemia, hyponatraemia, alcohol withdrawal, eclampsia, drug toxicity, fever in young children (febrile convulsion)

Clinical features and history-taking

Diagnosis rests overwhelmingly on the history, and a collateral (eyewitness) account is often more informative than the patient's own recollection, since awareness is frequently impaired during the event itself.

• Before the event: any warning or aura (itself a focal seizure), triggers (sleep deprivation, alcohol, flashing lights, missed medication)
• During the event: duration, tongue biting (lateral tongue biting is relatively specific for a tonic-clonic seizure), incontinence, colour change, eye state (eyes typically open in epileptic seizures, often closed in non-epileptic attacks), limb movements and their pattern
• After the event: post-ictal confusion, drowsiness or headache lasting minutes to hours is typical of a generalised seizure and much less typical of syncope, where recovery is rapid
• Todd's paresis - transient focal weakness after a focal seizure, which can be mistaken for stroke
• Frequency and pattern of previous events, and response to any treatment already tried

Clinical examination

• Full neurological examination, looking for a focal deficit suggesting a structural lesion
• Signs of an underlying cause: neurocutaneous stigmata (neurofibromatosis, tuberous sclerosis), signs of chronic liver disease or alcohol excess
• Cardiovascular examination, since cardiac syncope is an important differential and can itself provoke anoxic seizure-like jerking
• Evidence of injury from the event - tongue laceration, shoulder dislocation, injuries from a fall

Differential diagnosis

Misdiagnosis in either direction is common and consequential, so the differential deserves careful attention.

• Vasovagal syncope - a clear trigger (prolonged standing, pain, venepuncture), preceding prodrome of nausea and visual greying/dimming, brief myoclonic jerks are common and do not mean epilepsy, rapid recovery
• Cardiac syncope - sudden, without warning, may occur seated or supine, cardiac history or family history of sudden death, warrants ECG in everyone with unexplained loss of consciousness
• Psychogenic non-epileptic seizures (PNES/dissociative seizures) - typically longer duration, fluctuating or asynchronous movements, eyes often closed and resisting opening, pelvic thrusting, and preserved awareness with rapid reorientation are all more suggestive than definitive
• Hypoglycaemia
• Migraine with aura - spreads over minutes rather than seconds, and is followed by headache
• Transient ischaemic attack - negative rather than positive symptoms
• Panic attacks
• Sleep phenomena - parasomnias, cataplexy

Investigations

• Blood glucose - immediately, in any first seizure or collapse
• U&Es, calcium, magnesium, LFTs - to exclude a metabolic provoking cause
• ECG - in everyone with transient loss of consciousness, to look for an arrhythmia or long QT syndrome mimicking or coexisting with seizures
• EEG - supports the diagnosis and helps classify the epilepsy syndrome, but a normal interictal EEG does not exclude epilepsy, and an abnormal one does not by itself confirm it; it is a supportive test interpreted alongside the history
• MRI brain - the imaging investigation of choice, to look for a structural cause (mesial temporal sclerosis, tumour, vascular malformation, cortical dysplasia); CT is used acutely if a structural lesion needs urgent exclusion
• Prolactin - a level taken 10-20 minutes after the event can support a diagnosis of epileptic (particularly tonic-clonic) seizure if raised, though it is not routinely relied upon and is normal in focal seizures and PNES

Management

When to start treatment

Treatment is usually not started after a single unprovoked seizure unless the risk of recurrence is judged high (an abnormal EEG, a structural brain abnormality, or a definite neurological deficit), since roughly half of patients never have a second seizure at all. Long-term antiepileptic treatment is generally started once a diagnosis of epilepsy is confirmed (i.e. after a second unprovoked seizure).

Two aspects of counselling matter as much as drug choice and are frequently examined. The first is safety advice to reduce harm from a future seizure: showering rather than bathing, avoiding swimming alone, caution with heights, ladders and open fires, and supervision of young children during bathing. The second is teaching family or friends basic seizure first aid - protecting the head, not restraining the person or putting anything in their mouth, timing the seizure, placing them in the recovery position once convulsions stop, and calling an ambulance if it lasts beyond five minutes or a second seizure follows.

Sudden Unexpected Death in Epilepsy should also be discussed rather than avoided. Current guidance is that risk should be raised sensitively with all patients, because the principal modifiable factors - medication adherence, avoiding sleep deprivation and alcohol excess, and achieving control of nocturnal generalised seizures - are all things the patient can act on.

Drug choice by seizure type

General principles

• Start with monotherapy at a low dose, titrating up before considering a second agent
• Withdrawal is considered after at least 2 years free of seizures, undertaken slowly and with specialist input, since abrupt withdrawal risks rebound seizures and status epilepticus
• Lifestyle advice: sleep hygiene, alcohol moderation, avoiding known triggers, safety advice (showers rather than baths, caution with swimming and heights)
• Contraception: enzyme-inducing antiepileptics (carbamazepine, phenytoin) reduce the efficacy of the combined pill and the progesterone-only pill - alternative or additional contraception is needed
• Pre-conception counselling and folic acid 5 mg for anyone of childbearing potential planning pregnancy, reviewed with a specialist

Non-pharmacological options

• Vagal nerve stimulation - for drug-resistant epilepsy not suitable for resective surgery
• Epilepsy surgery - resection of a clearly localised epileptogenic focus (for example, mesial temporal sclerosis) in carefully selected drug-resistant patients
• Ketogenic diet - most established in drug-resistant epilepsy in children

Complications

• Status epilepticus - a seizure lasting more than 5 minutes, or repeated seizures without recovery in between (covered separately)
• SUDEP (Sudden Unexpected Death in Epilepsy) - rare but the leading cause of epilepsy-related death, more likely with poorly controlled nocturnal tonic-clonic seizures; risk-reduction discussions (medication adherence, nocturnal supervision) are part of routine care
• Injury - fractures, burns, drowning
• Psychosocial impact - loss of driving licence, employment restrictions, stigma, depression and anxiety, which are common and under-recognised
• Antiepileptic drug side effects - teratogenicity (valproate), osteoporosis with enzyme-inducing drugs, hyponatraemia (carbamazepine), and idiosyncratic reactions such as Stevens-Johnson syndrome (lamotrigine, especially with rapid titration)

Red flags

Prognosis

Around 70% of people with epilepsy achieve good seizure control on appropriate antiepileptic treatment, often with monotherapy. The remainder have drug-resistant epilepsy, defined as failure of two appropriately chosen and tolerated drugs, and should be referred to a specialist epilepsy service to consider further investigation, alternative drug combinations, or surgery. Idiopathic generalised epilepsies of childhood (particularly childhood absence epilepsy) often remit by adulthood, whereas focal epilepsy due to a fixed structural lesion is more likely to require long-term treatment.

Drug-resistant epilepsy is defined as failure of two appropriately chosen, adequately dosed and tolerated antiepileptic drugs to achieve sustained seizure freedom, and reaching that point should prompt referral rather than the addition of a third agent in primary or general care. The probability of achieving seizure freedom falls sharply with each subsequent drug tried, whereas carefully selected patients with a resectable focus - most notably mesial temporal sclerosis - can achieve seizure freedom with surgery. Referral is frequently made far later than it should be.