Epilepsy

TL;DR. A seizure is what happens when a population of brain cells fires in abnormal synchrony instead of in the ordinary, staggered pattern that produces thought and movement. Epilepsy is the tendency to have unprovoked seizures repeatedly. What the seizure looks like depends entirely on which part of the brain is involved: a convulsion if it spreads to the whole cortex, a few seconds of blankness if it involves the circuits of attention, a strange smell or a wave of fear if it starts in the temporal lobe. About 50 million people have epilepsy, around 70 percent become seizure-free on medication, and in low-income countries roughly three-quarters of people with epilepsy receive no treatment at all despite drugs that cost a few dollars a year.

Key takeaways

• Epilepsy affects roughly 50 million people worldwide, and about 80 percent live in low- and middle-income countries, where the treatment gap can exceed 75 percent.
• A single seizure is not epilepsy. Around 10 percent of people have a seizure at some point; epilepsy is diagnosed after two unprovoked seizures, or one with a high recurrence risk.
• Roughly 70 percent become seizure-free with medication. For the third who do not, surgery can be curative when the seizures come from one removable focus.
• Neurocysticercosis, a larval tapeworm infection of the brain, is the single largest preventable cause of epilepsy worldwide.
• SUDEP (sudden unexpected death in epilepsy) is real, is strongly associated with uncontrolled convulsive seizures, and is discussed with patients far too rarely.
• Sodium valproate causes major birth defects in about 10 percent of exposed pregnancies and neurodevelopmental problems in 30 to 40 percent. This is one of the most serious avoidable drug harms in modern medicine.

What it is

In short: A seizure is one event; epilepsy is the tendency to have them, and what a seizure looks like depends entirely on where in the brain it starts.

A seizure is a transient episode of signs or symptoms caused by abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disease characterised by an enduring predisposition to generate seizures: two or more unprovoked seizures more than 24 hours apart, one unprovoked seizure with a high probability of further ones, or a defined epilepsy syndrome.

Provoked seizures (from alcohol withdrawal, low blood sugar, low sodium, high fever in young children, head injury, or drugs) are not epilepsy, and the treatment is the cause.

Seizures are classified by where they start:

Status epilepticus is a seizure lasting more than 5 minutes, or repeated seizures without recovery in between. It is a medical emergency with mortality around 20 percent, because prolonged seizure activity causes neuronal injury and systemic complications.

Don't be confused: not every convulsion is epilepsy. Syncope (fainting) can produce brief jerking as the brain is transiently underperfused, and is far commoner. Functional (dissociative) seizures, previously called pseudoseizures, are real episodes that are not caused by abnormal electrical discharges; they arise from a different mechanism, are associated with prior trauma in many patients, and require psychological rather than antiseizure treatment. Distinguishing them takes video EEG, not intuition, and getting it wrong in either direction causes years of inappropriate treatment.

The history

In short: A Hippocratic text argued in 400 BCE that it was not a sacred disease, and the supernatural interpretation outlasted that argument by two thousand years.

Epilepsy has been recognised and misinterpreted longer than almost any disease. A Babylonian text, the Sakikku (about 1050 BCE), describes seizure types accurately and attributes them to spirits.

Around 400 BCE, the Hippocratic text On the Sacred Disease made an argument that reads as strikingly modern: "It is not, in my opinion, any more divine or more sacred than other diseases, but has a natural cause... men call it divine merely because they do not understand it." The supernatural interpretation nonetheless persisted for two thousand years, and in much of the world it persists now, with real consequences for how people with epilepsy are treated.

What actually goes wrong

In short: Excitation overwhelms inhibition and a population of neurons fires in synchrony, from causes ranging from scarring to a tapeworm cyst.

The brain balances excitation (mostly glutamate) against inhibition (mostly GABA). Neurons normally fire in complex, desynchronised patterns. A seizure is a failure of that balance in which a population of neurons depolarises together and recruits its neighbours, producing a self-sustaining wave of hypersynchronous activity.

That failure can arise from many causes:

Neurocysticercosis is worth explaining because it links epilepsy to sanitation. Humans acquire the pork tapeworm Taenia solium by eating undercooked infected pork, and become carriers of the adult worm. If tapeworm eggs from a carrier's faeces are then ingested, by that person or someone else, the larvae migrate and encyst in tissue, including the brain. When those cysts degenerate, they provoke inflammation and seizures. It is a disease of pig farming plus poor sanitation, endemic in Latin America, sub-Saharan Africa, and parts of Asia, and it accounts for roughly 30 percent of epilepsy in endemic regions.

What it does to the body

In short: Beyond the seizure itself: injuries, cognitive and psychiatric comorbidity, and a real risk of sudden death that patients are rarely told about.

During a seizure: depends on type, as above. During a convulsion, breathing is irregular, oxygen falls, and the person may bite their tongue or be injured by falling. After it, the postictal state brings confusion, headache, muscle ache, and profound tiredness, sometimes for hours, and occasionally a temporary weakness of one side (Todd's paresis) that mimics stroke.

Injuries: fractures, burns, head injury, dental damage, and drowning. Drowning risk is elevated enough that bathing alone is discouraged in favour of showering.

Cognitive and psychiatric comorbidity is substantial and underappreciated. Depression and anxiety are two to three times more common than in the general population, partly reactive and partly sharing underlying neurobiology. Memory impairment is common, particularly in temporal lobe epilepsy and as a side effect of medication. Children with epilepsy have higher rates of learning difficulties and ADHD.

SUDEP (sudden unexpected death in epilepsy): a person with epilepsy is found dead, usually in bed, usually prone, with no other explanation. It occurs at roughly 1 per 1,000 patient-years overall and considerably higher in those with frequent uncontrolled convulsive seizures. The mechanism is thought to involve post-seizure suppression of breathing and cardiac rhythm disturbance. Risk falls with seizure control, which is the main reason it should be discussed: it makes adherence and treatment escalation feel worth it, rather than being an abstraction.

Is it deadly?

Epilepsy raises mortality roughly two to three fold above the general population. The causes are SUDEP, status epilepticus, accidents (drowning, falls, burns, road traffic), suicide (rates are elevated), and the underlying condition where epilepsy is symptomatic of a tumour or stroke.

Most of that excess is concentrated in people with poorly controlled seizures, which makes achieving control the central goal, and it is achievable in most people.

Is it contagious?

No. Epilepsy cannot be caught, and this belief still causes real harm. Surveys in several countries have documented people believing epilepsy is transmitted through saliva, breath, or contact, leading to children being excluded from school and adults refused employment or marriage. Some traditions have discouraged helping someone during a seizure for fear of contagion, which converts a survivable event into an injury or a drowning.

The one genuine link: the infections that cause epilepsy can be transmissible. Neurocysticercosis comes from tapeworm eggs shed by a human carrier, so sanitation and food handling matter. Meningitis, encephalitis, and cerebral malaria can also cause epilepsy.

Who gets it

Age: incidence is bimodal, highest in early childhood and again after 60, where stroke, tumours, and neurodegeneration dominate the causes. Epilepsy in older people is now the fastest-growing group and is frequently missed, because a brief episode of confusion in an 80-year-old gets attributed to dementia or a "funny turn."

Poverty and geography: about 80 percent of people with epilepsy live in low- and middle-income countries, reflecting higher rates of birth injury, head trauma, central nervous system infections, and neurocysticercosis. WHO estimates that up to 75 percent of people with epilepsy in low-income countries receive no antiseizure treatment, despite phenobarbital costing on the order of a few dollars per year.

Risk factors: birth injury and neonatal seizures, head trauma (risk proportional to severity), stroke, brain infections, brain tumours, family history, and febrile seizures in childhood (which usually carry a low risk of later epilepsy, though prolonged ones carry more).

Treatment, and how it works

In short: Around 70 percent become seizure-free on medication, and for the rest surgery can be curative and is referred far too late.

Medication

Antiseizure medications (ASMs) raise the threshold for abnormal synchronous firing. They do not treat the underlying cause, and stopping them usually allows seizures to return in people who have not entered remission.

Drug choice depends on seizure type, and getting it wrong makes things worse: carbamazepine and other sodium channel blockers can aggravate absence and myoclonic seizures. Ethosuximide is first line for childhood absence epilepsy; levetiracetam and lamotrigine are common broad- spectrum choices; valproate is highly effective for generalised epilepsies and carries the pregnancy problem described below.

Outcome: roughly 50 percent become seizure-free on the first drug, and around 70 percent overall with medication. The probability of success falls sharply after two well-chosen drugs have failed, which is the definition of drug-resistant epilepsy and the point at which referral for surgical evaluation should happen rather than trying a seventh drug.

Surgery and devices

Resective surgery for drug-resistant focal epilepsy, where the seizure focus can be localised and safely removed. For temporal lobe epilepsy with hippocampal sclerosis, a randomised trial found roughly 58 percent of surgical patients seizure-free at one year versus 8 percent with continued medication. Surgery remains substantially underused, with typical delays of 15 to 20 years between diagnosis and referral.

Laser interstitial thermal therapy offers a minimally invasive alternative for some foci.

Neurostimulation for those who are not surgical candidates: vagus nerve stimulation, responsive neurostimulation (electrodes that detect seizure onset and deliver a counter-stimulus), and deep brain stimulation of the anterior thalamic nucleus. These typically reduce seizure frequency rather than eliminating seizures.

The ketogenic diet and its variants (modified Atkins, low glycaemic index) are genuinely effective, particularly in childhood epilepsies, and specifically effective in glucose transporter type 1 deficiency, where the brain cannot import glucose and ketones are the alternative fuel. It is demanding and requires dietitian supervision.

Status epilepticus

A time-based protocol: benzodiazepine (lorazepam, midazolam, including buccal or intranasal routes usable by families) at 5 minutes, a second-line intravenous agent (levetiracetam, valproate, or fosphenytoin, shown in the ESETT trial to be roughly equivalent) at around 20 minutes, and anaesthesia with intubation if seizures persist.

What treatment costs

In short: Valproate in pregnancy is one of the most serious avoidable drug harms in modern medicine, and two other drugs have ancestry-specific genetic risks.

• Valproate in pregnancy. Exposure in the womb causes major congenital malformations in roughly 10 percent of pregnancies (versus 2 to 3 percent background) and neurodevelopmental disorders, including reduced IQ and autism, in 30 to 40 percent. The harms were suspected from the 1980s and acted on decisively only in the 2010s; regulatory reviews in the UK, France, and elsewhere concluded that tens of thousands of children were affected. Valproate is now subject to pregnancy prevention programmes in many countries and should not be used in women of childbearing potential unless other options have failed and contraception is assured. It is a case study in how long it can take for a known harm to change practice.
• Lamotrigine: rash, and rarely Stevens-Johnson syndrome, which is why the dose is escalated very slowly.
• Carbamazepine: severe skin reactions are strongly associated with HLA-B*15:02, common in people of Han Chinese, Thai, and other Southeast Asian ancestry. Testing before prescribing is standard in those populations and has measurably reduced these reactions. Another clean pharmacogenomic success.
• Levetiracetam: irritability, aggression, and mood change in a significant minority, often the reason it is stopped.
• Topiramate: cognitive slowing and word-finding difficulty, weight loss, kidney stones, and a pregnancy risk profile that is also now restricted.
• Vigabatrin: irreversible peripheral visual field loss, limiting it to specific indications.
• Enzyme-inducing drugs (carbamazepine, phenytoin, phenobarbital) reduce the effectiveness of hormonal contraception and many other drugs, and affect bone health long term.

What the person can do

In short: Learn seizure first aid, protect sleep, take medication consistently, and plan pregnancy well in advance rather than stopping treatment on discovering one.

Seizure first aid, which everyone should know:

• Do: time it, cushion the head, remove nearby hazards, loosen anything tight around the neck, and once the jerking stops, roll them onto their side to keep the airway clear. Stay until they are fully alert and orient them calmly.
• Do not: put anything in the mouth. The belief that people swallow their tongue is false, and forcing objects between the teeth breaks teeth and jaws and risks the helper's fingers.
• Do not restrain the person or try to stop the movements.
• Call an ambulance if the seizure lasts more than 5 minutes, if a second follows without recovery, if it is the person's first seizure, if there is injury or trouble breathing, if it happened in water, or if the person is pregnant.

Living with epilepsy:

• Take medication consistently. Missed doses are the commonest cause of breakthrough seizures.
• Protect sleep. Sleep deprivation is one of the most reliable triggers, particularly for juvenile myoclonic epilepsy.
• Limit alcohol, and be aware that seizures often occur during withdrawal the following day rather than during drinking.
• Keep a seizure diary, including possible triggers, which materially improves treatment decisions.
• Manage practical safety: shower rather than bathe, do not swim alone, use the back hotplates on a cooker, and take care at heights.
• Know your driving rules, which vary by country and typically require a seizure-free period.
• Discuss pregnancy in advance if relevant, ideally long before conception, including folic acid and drug choice. Most women with epilepsy have normal pregnancies on appropriate medication, and uncontrolled seizures also carry risk, so the answer is planning, not stopping treatment unilaterally.
• Ask about SUDEP. Many patients want this information and are not given it.

Living with it

Epilepsy's social burden exceeds its medical one for many people. Employment rates are lower than the condition warrants, driving restrictions limit work and independence, and disclosure is fraught. In several countries epilepsy remained legal grounds for annulment of marriage into the late twentieth century, and in some settings people with epilepsy are still excluded from schooling. WHO and the International League Against Epilepsy have made stigma reduction an explicit programme goal, on the basis that it, rather than the seizures, is what most limits lives.

What's next

• Precision treatment by cause. Everolimus for epilepsy in tuberous sclerosis, fenfluramine and cannabidiol for Dravet and Lennox-Gastaut syndromes, and ketogenic therapy for GLUT1 deficiency are early examples of treating the mechanism rather than the seizure.
• Genetic diagnosis as routine in early-onset epilepsy, which changes drug choice (avoiding sodium channel blockers in SCN1A-related Dravet syndrome, for example).
• Antisense oligonucleotides targeting specific genetic epilepsies, in early trials.
• Better surgical targeting with stereo-EEG and improved imaging, and closing the referral gap for the many patients who would benefit.
• Seizure prediction and detection using wearables, which already detect convulsive seizures and alert caregivers, with prediction still an open problem.
• Closing the treatment gap. The single largest available gain is not technological: it is getting cheap, effective, off-patent drugs to the tens of millions of people who currently receive nothing.

Sources and notes

Prevalence, distribution, and treatment gap figures are from WHO's epilepsy fact sheet and the Intersectoral Global Action Plan on epilepsy and other neurological disorders (approximately 50 million people affected, about 80 percent in low- and middle-income countries, treatment gap up to 75 percent in low-income settings). ILAE classification, 2017. On the Sacred Disease, Hippocratic corpus, circa 400 BCE. Phenytoin discovery: Merritt and Putnam, 1938. Temporal lobectomy trial: Wiebe et al., NEJM, 2001 (58 percent versus 8 percent seizure freedom). Drug-resistant epilepsy definition and response rates: Kwan and Brodie, NEJM, 2000. ESETT: Kapur et al., NEJM, 2019. Valproate teratogenicity: Meador et al. NEAD study and subsequent regulatory reviews (UK MHRA, EMA). HLA-B*15:02 and carbamazepine: Chung et al., Nature, 2004, and subsequent screening programmes. SUDEP incidence: Harden et al., AAN/AES practice guideline, 2017. Neurocysticercosis contribution to epilepsy: Ndimubanzi et al. and WHO estimates.

Open questions. Why some people with structural lesions develop epilepsy and others do not is unresolved, and no treatment yet prevents epilepsy after brain injury (antiepileptogenesis remains the field's holy grail). Reliable seizure prediction has not been achieved.

Next: three more diseases of the nervous system, including one that a virus almost certainly causes. 👉