Epilepsy

What it is

Epilepsy is a chronic non-communicable disease of the brain that affects people of all ages¹. A seizure happens when many nerve cells (neurons) send signals at the same time, much faster than normal, temporarily disrupting how the brain works¹⁰.

A single seizure does not mean a person has epilepsy: up to 10% of people worldwide have one seizure during their lifetime¹. In practice, epilepsy is diagnosed after at least two unprovoked seizures more than 24 hours apart, after one unprovoked seizure when the risk of further seizures is high, or when a recognised epilepsy syndrome is identified⁴.

New cases are most common in infants and in older people². Epilepsy has been surrounded by stigma for centuries, and people with epilepsy and their families still face discrimination in many parts of the world¹.

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Temporal lobeHippocampus

Focal seizures can begin in any part of the cortex. The temporal lobe is the most frequent site in people who need epilepsy surgery, and surgery can control seizures better than continued medicines in temporal lobe epilepsy^8,19.

Scarring of the hippocampus (hippocampal sclerosis) was the most common finding in adults who had surgery for drug-resistant focal epilepsy¹⁹.

Signs and symptoms

Seizures vary according to where in the brain the abnormal activity starts and how far it spreads¹. They are classified as focal (starting in one area of the brain), generalised (involving networks on both sides from the outset) or of unknown onset⁵.

• Focal seizures with retained awareness: movements of one part of the body, sudden unexplained emotions, or sensations such as smells or tastes that are not real¹⁰.
• Focal seizures with impaired awareness: a dream-like state, and repetitive behaviours such as blinking, mouth movements or walking in a circle, called automatisms¹⁰.
• Absence seizures: brief episodes of staring into space, sometimes with slight twitching¹⁰.
• Tonic-clonic seizures: stiffening of the body followed by rhythmic jerking of the limbs and loss of consciousness¹⁰.
• Myoclonic and atonic seizures: sudden jerks, or a sudden loss of muscle tone that can cause falls¹⁰.
• After a seizure, people may feel confused, tired or have a headache for some time.

Causes and risk factors

Causes are grouped as structural, genetic, infectious, metabolic, immune and unknown, and no cause is found in about half of people¹. Epilepsy is not contagious¹.

• Brain injury before or around birth, such as lack of oxygen¹.
• Brain malformations and genetic conditions¹.
• Severe head injury, stroke and brain tumours¹.
• Brain infections such as meningitis, encephalitis or neurocysticercosis (a tapeworm infection of the brain), which contribute to higher rates in low- and middle-income countries¹.
• Seizure triggers in people who already have epilepsy include stress, sleep deprivation, alcohol or alcohol withdrawal, missed meals and, for some, flashing lights¹⁰.

Genetics

Genetic factors make an important contribution to many epilepsies. More than 500 genes have been associated with epilepsy, which has led to more precise diagnoses and, in some cases, targeted therapies³. Some variants are inherited, while others arise new in the child, known as de novo variants¹⁰.

Many single-gene epilepsies involve genes for ion channels, the molecular gates that control the flow of charged particles into and out of nerve cells¹⁰. For example, Dravet syndrome, a severe childhood epilepsy, is caused mainly by loss of one working copy of the SCN1A gene, which encodes a sodium channel¹³.

For common epilepsies, many variants each add a small amount of risk. A genome-wide association study of nearly 30,000 people with epilepsy identified 26 risk regions, with clear differences between the genetic architecture of focal and generalised epilepsies¹².

What happens in the brain

Normal brain function depends on a balance between excitatory signals, which make neurons more likely to fire, and inhibitory signals, which calm them; the main excitatory messenger is glutamate and the main inhibitory one is GABA¹⁵. A long-standing proposal is that seizures arise when this balance tips, with more glutamate and/or less GABA signalling¹⁴. Genetic studies implicate the connections (synapses) of both excitatory and inhibitory neurons in common generalised epilepsies¹².

Researchers distinguish epileptogenesis, the gradual process by which an injury or genetic change transforms normal brain circuits into ones prone to seizures, from ictogenesis, the mechanisms that start an individual seizure³. After a head injury or stroke, for example, the brain’s attempts at repair can create abnormal nerve connections that lead to seizures¹⁰.

Seizures can affect the brain’s control of breathing, heart rhythm and arousal, which is one reason why they can occasionally be fatal³.

How it is diagnosed

A detailed history and a reliable eyewitness account of the episode are the cornerstones of diagnosis². Misdiagnosis is common, because fainting and other conditions can resemble seizures³. In India, the ICMR Standard Treatment Workflow advises diagnosis from a detailed eyewitness history in primary care, with referral to a specialist when warning signs are present¹⁶; in the United Kingdom, NICE advises that people with a first suspected seizure be seen by a specialist within two weeks⁹.

• Electroencephalogram (EEG), which records the brain’s electrical activity through scalp electrodes, can support the diagnosis and identify the seizure type, but a normal EEG does not rule out epilepsy⁹.
• Sleep-deprived or ambulatory (portable, up to 48 hours) EEG may be used if a routine EEG is normal and doubt remains⁹.
• Video-EEG monitoring, which records seizures on camera alongside the EEG, helps clarify the nature of events¹⁰.
• MRI (magnetic resonance imaging) can reveal structural causes such as scarring, malformations or tumours^9,10.
• Blood tests check for triggers such as low blood sugar, and genetic or antibody testing may be offered in selected cases⁹.

How scientists study it

Current treatments

Research frontiers

Living with the condition and seeking help

Most people with epilepsy live full lives. Taking medicines regularly, keeping a seizure diary and having an individual care plan help; risks from bathing, swimming, heights and driving should be discussed with the care team.

Emergency services should be called if someone has a seizure for the first time, if it lasts longer than is usual for them, or longer than five minutes when their usual pattern is unknown¹¹. Status epilepticus, a prolonged seizure or repeated seizures without recovery in between, is a medical emergency^10,16. In India, the national emergency number is 112 and the ambulance number is 108^17,18.

People with epilepsy have up to three times the risk of premature death of the general population¹. Sudden unexpected death in epilepsy (SUDEP) is rare but more frequent when seizures are poorly controlled, and taking medicines as prescribed may reduce the risk¹⁰.