Epilepsy

Introduction

Epilepsy is a neurological condition in which patients experience recurrent epileptic seizures.

During a seizure, synchronised aberrant electrical activity originating from a specific focus spreads throughout the brain. This most commonly manifests with motor or sensory symptoms and is often (but not always) associated with reduced consciousness levels.

It is estimated that over 600,000 people in the UK are living with epilepsy.¹

Aetiology

Pathophysiology

Epileptic seizures result from an imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neuronal signalling at the synaptic level, resulting in a reduced threshold for neurotransmission.

Anatomy

The clinical signs of a seizure (semiology) vary depending on where it begins in the brain (the seizure focus) and where it spreads.

For example, seizures affecting the frontal lobe are associated with abnormal movements (e.g. pelvic thrusting, leg cycling) and vocalisation. In contrast, seizures affecting the temporal lobe are associated with experiencing abnormal sensations (e.g. deja vu), and those involving the occipital lobe are associated with simple visual disturbance.

Risk factors

Structural abnormalities

Structural abnormalities in the brain affecting neurotransmission increase the risk of abnormal electrical activity and seizures. Examples include:

• Head injury
• Stroke
• Space-occupying lesions (e.g. brain tumours)
• Neurodegenerative diseases

These can also occur as part of a genetic syndrome such as tuberous sclerosis or neurofibromatosis.

Neurochemical imbalance

A neurochemical imbalance may also make neurons more likely to fire aberrantly. Genetic disorders affecting neuronal conduction can also cause epilepsy. For example, in Dravet syndrome, a mutation affecting voltage-gated sodium channels involved in neuronal conduction causes epileptic seizures.

Seizure threshold

The threshold for seizure activity in all patients, including those with epilepsy, may be lowered by metabolic or electrolyte abnormalities (e.g. hyponatraemia, hypoglycaemia), central nervous system infection (e.g. encephalitis, meningitis) or alcohol withdrawal. Seizures secondary to one of these conditions are often called provoked seizures.

For some patients with epilepsy, seizures can be induced by environmental factors, such as flashing lights and noise, but this is rare.

Clinical features

Classification of epileptic seizures

The International League Against Epilepsy classifies seizures according to their onset as being focal onset, generalised onset, or unknown onset (Table 1). In all of these categories, seizures may be either motor or non-motor.²

Focal seizures begin from a specific focus. Patients may remain conscious during a focal seizure (retain awareness), or awareness may be impaired. These seizures may have motor or nonmotor onset. Focal seizures may spread to the contralateral hemisphere to become a generalised seizure (secondary generalisation).

Generalised seizures affect both cerebral hemispheres. They are often motor and described according to the presence of characteristic abnormal movements:

• Tonic-clonic: stiffening followed by intermittent jerking movements
• Myoclonic: jerking movements
• Atonic (a.k.a drop attack): sudden loss of muscle tone
• Absence seizures (a.k.a generalised non-motor seizures): a type of generalised seizure characterised by a brief vacant period where the individual is unresponsive, but muscle tone is not usually affected, predominantly affecting children

Table 1. The classification of seizures (ILAE).

*either negative features (e.g. impaired language), or positive features such as déjà vu, hallucinations, illusions, or perceptual distortions

**e.g. anxiety, fear, joy, or change in affect without subjective emotions

History

Most patients who experience a seizure cannot give a history of the event. It is invaluable to gain a collateral seizure history from an eyewitness.

Key features of an epileptic seizure to establish from the history include:

• Prodrome: initial prodrome before seizure onset may involve a sensory aura such as a rising abdominal sensation.
• The seizure itself: usually a period of reduced consciousness with stereotyped semiology (e.g. head deviation and limb jerking); individuals may experience tongue biting, incontinence, automatisms, abnormal speech, laughing or crying.
• Post-ictal period: the termination of a seizure is followed by the post-ictal period, whereby individuals are likely to be confused or disorientated. This can last for hours or even days.

For more information, see the Geeky Medics guide to seizure history taking.

Clinical examination

During a seizure, patients are often unresponsive. Depending on the type of seizure, muscle tone may be increased or decreased.

Post-ictal limb weakness (Todd’s paresis) may occur following a seizure. This can last from a few hours to days. Between seizure episodes, the neurological examination is usually normal, or clinical signs may reflect an underlying epilepsy syndrome (e.g. tuberous sclerosis).

Differential diagnoses

Differential diagnoses to consider in the context of epilepsy include:

• Dissociative seizures (functional seizures or non-epileptic attacks): a type of functional neurological disorder (FND). Functional seizures often have distinctive diagnostic features and a lack of abnormal electrical activity in the brain during an event. Features of functional seizures include long duration of the seizure (compared to epileptic seizures, which usually last <90 seconds), quick recovery, retained awareness with bilateral arm movements, back arching, eye-opening during events and a sensation of detachment from reality (dissociation).
• Vasovagal episodes: prodrome of dizziness followed by loss of consciousness; in some cases, jerking movements may be seen during a vasovagal faint but are very brief, and patients recover quickly without a postictal period. 

Investigations

Bedside investigations

Relevant bedside investigations include:

• Basic observations (vital signs): to identify hypoxia and haemodynamic instability
• Capillary blood glucose: to identify hypoglycaemia, an important reversible cause of seizures

Laboratory investigations

Relevant laboratory investigations include:

• Full blood count: neutrophil cell count may also often be raised after a generalised seizure
• Urea & electrolytes: to identify reversible causes (uraemia, hyponatraemia)
• Bone profile: to identify hypercalcaemia
• Venous blood gas: due to prolonged muscle contraction, lactate is raised following a tonic-clonic seizure (although it can also be raised in prolonged functional seizures)

Imaging investigations

Neuroimaging (CT/MRI head) is used to identify any underlying predisposing factors such as previous stroke or tuberous sclerosis. For most patients with epilepsy, neuroimaging is normal.

Electrical and visual recordings

Relevant investigations include:

• Electroencephalogram (EEG): large numbers of electrodes are placed on the patient’s head to detect electrical activity and identify patterns suggestive of a seizure
• Video-telemetry (VT): video recordings combined with EEG recordings are made over several days of monitoring to capture and characterise seizure semiology
• Patient videos: given the widespread usage of smartphones, patients and family members can film events and share these with clinicians

Diagnosis

To be diagnosed with epilepsy, patients should have experienced two or more unprovoked seizures more than 24 hours apart or have been diagnosed with an epilepsy syndrome. Experiencing a single seizure is usually insufficient to reach a diagnosis of epilepsy.

Management

The goal of epilepsy management is to reduce the frequency of seizures as much as possible with minimal side effects.

For more information on managing a seizure, see the Geeky Medics guide to the emergency management of seizures.

Patient education and emotional support are essential due to the risks associated with epileptic seizures and the restrictions this imposes on daily life. For more information, see the Geeky Medics guide to epilepsy counselling.

Medical management

Epilepsy is managed with daily anti-seizure medications, primarily targeting sodium channels or modulation of GABAergic neurotransmission (examples include sodium valproate or lamotrigine).

Patients are usually also offered rescue medications (such as buccal midazolam) to be administered in the event of a seizure that does not self-terminate within five minutes.

Surgical management

Patients experiencing debilitating seizures refractory to medications may be offered surgical management to physically obstruct neurotransmission. This may involve resection of either the epileptogenic focus, a lobe of the brain or, in rare cases, an entire hemisphere. Alternatively, surgical division of the corpus callosum (corpus callosotomy) can be performed. 

Complications

Complications of epilepsy include:

• Accidental self-injury such as superficial bruising and laceration, broken bones, head injury and burns or scalds from the local environment may occur during a seizure
• Status epilepticus is defined as an epileptic seizure lasting longer than five minutes or multiple seizures without an intervening return to consciousness over a five minute period; convulsive status epilepticus is an emergency and may require general anaesthesia if unresponsive to first and second-line pharmacological intervention.
• Sudden death in epilepsy (SUDEP) is when a person diagnosed with epilepsy (most commonly tonic-clonic seizures) dies unexpectedly, and no other cause is established; this usually occurs during the night and is unwitnessed.

Key points

• Epilepsy is a neurological condition in which patients experience recurrent epileptic seizures
• Epileptic seizures are characterised by abnormalities on EEG, and are usually managed with anti-seizure medications
• Most seizures present with motor disturbance and reduced consciousness level, but there is a wide variety of seizure types depending on the area of the brain affected
• Patient education and emotional support are essential due to the risks associated with epileptic seizures and the restrictions this imposes on daily life
• Complications include accidental injury from seizures, status epilepticus and sudden death (SUDEP)

Reviewer

Dr Neil Ramsay

Neurology registrar

Editor

Dr Chris Jefferies

References

1. Epilepsy Research. Epilepsy statistics. Available from: [LINK]
2. International League Against Epilepsy (ILAE). ILAE 2017 Classification of Seizure Types Checklist. Available from: [LINK]