Overview

Seizure is the medical term for a vast array of symptoms that occur during a period of excessive electrical activity in the brain, which can be observed on electroencephalogram (EEG). Typically, seizures last less than two minutes and may or may not be associated with the individual losing consciousness. 

Seizures that last more than five minutes are considered Status Epilepticus which can cause permanent brain damage if not treated promptly. Symptoms range from uncontrollable shaking in the entire body (tonic-clonic seizure) to momentary loss of awareness or strange feelings and sensations. Up to 1 in 10 people will experience a seizure in their lives. Provoked seizures result from temporary physiological states, which can include high fevers, low blood sugar, infections of the brain or alcohol withdrawal.¹

About 25% of people that experience seizures suffer from a medical condition known as epilepsy which is characterised by two or more unprovoked seizures.² Epilepsy can result from visible brain lesions such as traumatic injury, stroke or tumours. However, in up to 60% of cases, and particularly in first time childhood seizures, there is no discernible cause. Treatment for epilepsy involves managing the underlying cause if present and/or prescribing medications that reduce seizure frequency.³

In this article, we will provide some insight and scientific information on the key features of seizures and epilepsy and their clinical implications.

^{What is epilepsy?}

Epilepsy is a serious global issue. In 2020 it affected 50 million people worldwide, 80% of which in developing countries.⁴ Over 120,000 people die of epilepsy each year, greatly affected by poor management and inability to access anti-seizure medications and interventions.⁵ In the United Kingdom 40-60% of deaths due to epilepsy are possibly preventable.⁶ Sudden unexpected death in epilepsy (SUDEP) is a complication characterised by seizure-related cardiorespiratory arrest.⁵

Early diagnosis and management of epilepsy and associated neurological conditions is fundamental to improving quality of life and preventing premature death. Distinguishing between provoked and unprovoked seizures and investigating reversible or treatable causes is fundamental to prescribing the appropriate interventions and combating excess mortality.

Understanding seizures

A seizure refers to a neurological phenomenon characterised by a burst of excessive electrical activity in the brain which can manifest in different ways. Normally after a neuron fires it undergoes a cooling off period where it is less likely to depolarise and fire again. Research indicates that epilepsy possibly results from a failure in this feedback mechanism. Different factors appear to be involved in development of seizures, including brain matter damage, abnormalities in ion channels and complex interplay between excitatory and inhibitory neurotransmitters such as Glutamate and Gamma-aminobutyric acid (GABA), respectively.⁷

As many as 10% of people will experience a seizure at some point in their lives and after the first time seizure, 40% of individuals will go on to have another one.^1,8 On average, the incidence of seizures is 7.7 per 10,000 per year. Approximately 3.5 of those are considered provoked ( attributed to a temporary health state that affects brain activity. 

Provoked seizures

Provoked seizures are not usually a sign of an underlying neurological illness and can have different causes.¹ Some of these include:

• Fever
• Withdrawal from alcohol and certain sedatives and anticonvulsants
• Metabolic disturbances (e.g. hypo- or hyperglycaemia, electrolyte abnormalities, hepatic encephalopathy, mitochondrial disorders)
• Toxic exposures 
• Eclampsia
• Hypertensive encephalopathy
• Transplant rejection
• Electroconvulsive therapy
• Brain inflammation due to infections or autoimmune disorders (e.g. Lupus)⁹

^{Unprovoked seizures}

A diagnosis of epilepsy is made after a person experiences two unprovoked seizures. Epilepsy and unprovoked seizures can be due to many neurological conditions and factors, including:

• Traumatic brain injury
• Brain tumours
• Stroke
• Vascular disorders (e.g. arteriovenous malformations (AVMs) or cerebral aneurysms)
• Alzheimer's Disease and Dementia
• ncephalitis
• Genetic and developmental conditions 
• Multiple sclerosis (MS)
• Epilepsy of unknown cause^1,10

^{Seizure types}

Seizures can be divided into different types depending on the symptoms they present with. The following table provides a summary of how seizures can manifest and the corresponding denominations⁽¹¹ Following a seizure, patients typically experience what is known as the Post-ictal period,characterised by confusion, fatigue, headache, speech difficulties and potential psychosis.¹²

Understanding epilepsy

Epilepsy is a neurological condition that affects about 1% of the world population and results in recurrent unprovoked seizures. Epilepsy can be acquired by conditions such as e tumours, MS or neurovascular abnormalities. In 60% of cases, the cause is not known. Certain brain infections such as viral encephalitis and cerebral malaria also frequently result in the development of permanent epilepsy after the infection is treated. Age-related and genetic factors may also play a role.⁴

Sometimes Epilepsy can be due to a serious neurological condition that can pose a danger to the patient. In addition, Epilepsy itself can lead to several complications that affect a person's physical, psychological, and social well-being. Some of these include:

• Injury risk during seizures
• Status Epilepticus
• SUDEP
• Cognitive Impairment due to repeated seizures
• Increased risk of mental health disorders such as depression and anxiety. The stress and stigma associated with epilepsy can lead to social isolation and exacerbate these conditions.
• Decreased quality of life and financial difficulties due to inability to carry out daily social and professional activities¹³

Diagnosis of epilepsy

The diagnosis of epilepsy usually involves observing how seizures begin on electroencephalogram (EEG) and identifying/ruling out any underlying causes. 

Brain imaging techniques such as Computed Tomography (CT) or Magnetic Resonance imaging (MRI) are often used to visualise injuries or structural abnormalities. Although doctors often try to identify a specific type of epileptic syndrome, this is not always achievable.³

Treatment of epilepsy

Epilepsy treatment involves addressing the underlying cause, reducing seizure frequency and fostering patient well-being through psychosocial interventions such as counselling and support groups.³ 

Anticonvulsant drugs such as Valproic Acid, Phenytoin and Lamotrigine can effectively control seizures in 69% of patients. Doctors will typically choose the most appropriate drug based on the type of seizures.¹⁴ Benzodiazepine sedatives are also used as emergency intervention if Status Epilepticus occurs. 

In addition to medications, patients may also be recommended lifestyle modifications such as getting adequate sleep, managing stress and avoiding known seizure triggers. 

If more conventional treatments fail, brain surgery or implantation of a neurostimulation device can also be considered.³

Key differences between seizures and epilepsy 

Having a single first-time seizure does not necessarily mean one has epilepsy. Seizures can have many causes and it is fundamental for health professionals to be able to identify contributing factors and correctly apply diagnostic criteria. The International League Against Epilepsy as the presence of one of these requisites:

• At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
• One unprovoked (or reflex) seizure and an estimated risk of reoccurrence of over 60% due to genetic factors
• Being diagnosed with an epilepsy syndrome¹⁵

In some cases, particularly in the elderly, epilepsy can be caused by underlying neurological conditions that require specific interventions such asumour resection, thrombolysis and stroke prevention.. 

Non-epileptic seizures can also have many causes, many of which have specific treatments. 

Reversible causes of provoked seizures include metabolic disturbances, high fevers, and exposure to toxins. Identifying the most likely issues present by conducting the necessary investigations can prevent mortality and facilitate choosing the correct diagnosis and management.¹⁶

Summary

Seizures are a serious neurological problem associated with abnormal electrical activity in the brain, which can result in different presentations, such as focal neurological deficits, loss of awareness or generalised uncontrollable shakes. 

The most common cause of seizures is epilepsy, a condition characterised by one or two unprovoked seizures. Epilepsy affects up to 1% of people and can be due to specific syndromes or acquired brain conditions but most often the cause is unknown. 

Epilepsy is a major global health challenge as it is associated with 1.6-4.1-fold greater mortality risk as well as many psychosocial burdens across the developed and developing world.

Despite the overlap between seizures and epilepsy, it is important for patients and clinicians to be aware that the two are not the same and that seizures have many different causes. Genetic and environmental factors should be considered as well as investigations to identify life-threatening conditions should be used for diagnosing patients correctly. As many as 40% of people who have an unprovoked seizure go on to have another one so monitoring and early intervention are fundamental. If a diagnosis of epilepsy is present, clinicians should promptly focus on treating any underlying causes and managing symptoms to promote well-being and life expectancy.