EPIDEMIOLOGY

Epidemiology measures the distribution and dynamics of conditions within the general population, including the incidence, prevalence and outcomes.^1–3 Establishing the precise epidemiological characteristics of epilepsy presents significant challenges arising from methodological problems.^4,5 These include inconsistent diagnostic definitions, causality attribution amid high comorbidity, underreporting due to stigma, limited healthcare access and selection bias.^2,6,7 Despite these hurdles, estimates show that epilepsy affects over 70 million people worldwide, and approximately 5 million new cases occur annually.⁸ Incidence and prevalence vary regionally due to differences in risk factors: CNS infections and parasites in Low‐ and Middle‐Income Countries (LMIC) and stroke in High‐Income Countries (HIC), healthcare infrastructure and demographic profiles.⁹ Epilepsy risk factors differ significantly according to a person’s age, region of origin and sex, reflecting underlying differences in biological predispositions, environmental exposures and access to healthcare.^5,10–12 Epidemiological studies identify risk factors, while clinical series more often identify causes.^1–3 Estimating epilepsy epidemiology and outcomes requires careful consideration of many contributing factors to avoid or mitigate methodological challenges.

INCIDENCE

The incidence of epilepsy, the rate of new cases within a specific population, is usually measured per 100,000 people per year.^2,13 It is a crucial epidemiological indicator, but its precise measurement is difficult due to methodological and logistical issues.⁸ Its incidence follows a bimodal distribution, with peaks in children and in older adults. The second incidence peak, in older age groups, is now higher than the peak in early life.¹⁴

Historically, epilepsy was mainly seen as a condition of the paediatric range, as most cases started in childhood or adolescence. A significant demographic shift has occurred over the last four to five decades.^5,8 This demographic change has significantly impacted the age‐specific incidence, which has increased in older people and decreased in the paediatric age group.^12–14 This shift is not uniform within the paediatric population; while there has been a notable rise in incidence during the first year of life, a decrease has been observed in the following ten years.^5,10 The underlying causes for these demographic changes remain unclear. Potential contributing factors include healthier lifestyles, advances in obstetric, perinatal, and paediatric care, earlier intervention for CNS infections, and widespread vaccination programs. The natural history of specific syndromes may have changed. For instance, a decline in the incidence of hippocampal sclerosis (HS),¹⁵ a common risk factor of focal drug‐resistant epilepsy (DRE), may be linked to improved management of febrile seizures in HIC. The observed increase in incidence among children under the age of one is likely attributable to improved survival rates of newborns experiencing severe intrauterine and perinatal complications.

Beyond age, geographical location significantly influences incidence, often driven by socioeconomic factors.¹⁶ Global pooled incidence is around 80 cases per 100,000 annually, ranging from lower rates in HIC to higher rates in LMIC with people in the lower socioeconomic strata in HIC also having higher incidence.¹⁷ These regional differences are likely multifactorial, potentially including perinatal insults, traumatic brain injuries, CNS infections and parasites, deprivation and genetic factors.^5,9,10,18 Genetic factors, cerebrovascular events, cognitive disorders and brain tumours are the leading risk factors in HIC. Conversely, perinatal insults, traumatic brain injury (TBI), CNS infections and parasitic disorders are more prominent in LMIC, where a more significant proportion of cases are considered preventable (CNS infections, TBI and perinatal insults) compared to HIC.¹⁹ In LMIC, parasitic infections account for up to a third of cases in endemic areas.

The cumulative incidence, or lifetime risk of developing epilepsy, is between 3 and 5% in HIC. Additionally, isolated seizures occur in approximately 20 per 100,000 people each year, although reliable data are mainly from HIC.^2,3,5,8

Men tend to have a slightly higher incidence, possibly due to greater exposure to TBI from occupational hazards and violence, as well as higher rates of alcohol misuse and cerebrovascular disease risk associated with smoking and hypertension. Women face risks related to hormonal influences, such as catamenial epilepsy and autoimmune‐related seizures.

Epilepsy affects about one‐fifth of people with learning disabilities, with a higher rate in those with more severe disabilities.²⁰ Approximately one‐third of people with epilepsy and learning disabilities develop seizures before age 20, and another third after age 65. Epilepsy accounts for roughly a quarter of neurological consultations in HIC and is likely even higher in LMIC.⁵ About a third of children and a fifth of adults with epilepsy have co‐occurring learning or other neurological disabilities, highlighting the complex interplay between epilepsy and other conditions.

Addressing modifiable risk factors offers intervention opportunities.¹⁹ In LMIC, these measures would include improving perinatal care, TBI prevention, and enhancing basic sanitation alongside parasite control, which could significantly reduce new cases. In HIC, focusing on stroke prevention and early dementia detection is essential. The primary causes of epilepsy differ across the lifespan, from genetic and perinatal factors in childhood to vascular and degenerative factors in older age,²¹ with environmental exposures contributing to higher male risk and regional disparities highlighting the importance of preventable causes in LMIC versus age‐related causes in HIC. To decrease the global burden of epilepsy, targeting these potentially modifiable factors, particularly in LMIC, would have a significant impact

PREVALENCE

Prevalence refers to the number of people with active epilepsy within a defined population at a specific point in time. Unlike incidence, which counts only new cases, prevalence reflects the pool of existing cases, balanced by factors like remission, migration, and premature mortality.^1–5

The estimated point prevalence of active epilepsy ranges from 4 to 10 people per 1,000 people worldwide. LMIC usually report higher rates (8–10/1,000), probably due to a combination of elevated incidence from preventable factors, such as neurocysticercosis and perinatal insults and limited access to treatment, which may delay remission. In contrast, HIC generally show lower prevalence (4–7/1,000), attributed to better healthcare access and higher antiseizure medication (ASM)‐related remission rates.^1,3,5,9,10

The lifetime prevalence (1–2%) is significantly lower than expected when extrapolated from the cumulative incidence (3–5% lifetime risk). This discrepancy is referred to as the epilepsy epidemiological paradox.³ This highlights two crucial factors: seizure remission, with over two‐thirds of people achieving sustained seizure freedom with ASM, and premature mortality, as people often die prematurely, particularly in LMIC. Declining paediatric incidence reduces childhood prevalence. Conversely, a rising geriatric incidence associated with conditions like stroke and dementia increases prevalence in older adults, especially in HIC.²¹ The efficacy of ASM, with a majority of people achieving seizure control, contrasts with the third who develop DRE.^5,10,22 Spontaneous remission is also common in specific self‐limited epilepsy syndromes, such as epilepsy with centrotemporal spikes.⁵ Conditions directly related to epilepsy, such as sudden unexpected death in epilepsy (SUDEP) and status epilepticus, along with comorbidities like depression and stroke, contribute to a reduced overall prevalence by increasing premature death in this population. In LMIC, mortality rates are significantly higher than in HIC due to untreated infections and limited access to emergency medical care.^23,24 In addition, undiagnosed cases, particularly non‐convulsive seizures, and under‐reporting due to social stigma can skew prevalence estimates.^2,5

In HIC, the prevalence in the paediatric age range has significantly declined (by around a fifth in recent decades).^5,10,25,26 Improved ASM adherence and the availability of epilepsy surgery, such as for HS, may also contribute to higher remission rates and potentially lower prevalence. Conversely, in LMIC, prevalence appears to be stagnant or increasing.²⁷ For example, neurocysticercosis accounts for a substantial proportion (up to a third) of cases in certain endemic regions. There is a large treatment gap in LMIC, with limited access to adequate ASM treatment, with only about a quarter receiving it, resulting in active epilepsy in a greater proportion of the population.^5,19

The epidemiological paradox likely arises from several factors.¹⁵ Firstly, remission plays an important role, with a substantial number of childhood‐onset epilepsy cases resolving by adulthood.²⁵ Secondly, premature mortality disproportionately affects younger adults with epilepsy, reducing the overall prevalence in older age groups. Lastly, more accurate diagnostic criteria may have excluded non‐epileptic events from the prevalent pools, thus contributing to more accurate estimates.

NATURAL HISTORY AND OUTCOMES

The risk of a recurrence after a first untreated seizure is considerable. About half will have a further unprovoked seizure in the next two years, with the first six months carrying the highest risk. Several key factors significantly predict this recurrence.^2,4,22 The presence of structural brain abnormalities, such as lesions evident on MRI, and epileptiform EEG patterns doubles the risk of subsequent seizures. A previous history of brain insult and an abnormal neurological examination are also significant predictors of recurrence.

Within five years of the onset of seizures and with appropriate ASM treatment, up to 80% of people may achieve long‐term seizure remission.^2,4,22 Up to half of these individuals remain seizure‐free after treatment discontinuation. However, in about a fifth, epilepsy never remits. Age at onset is not a universal prognostic predictor, but many epilepsies starting in the first year of life have a less favourable prognosis. Conversely, most people whose seizures begin in old age have an excellent prognosis for seizure remission.

Predictors of the risk of unprovoked seizures progressing to chronic epilepsy include focal seizures, early childhood onset, high seizure frequency before or during early treatment, and a poor early response to treatment. The presence of learning disability, a history of neonatal seizures, and atonic or tonic‐atonic seizures also suggest a less optimistic outlook.⁵

Early access to care, correct diagnosis and appropriate therapy are associated with improved outcomes. In LMIC, despite significant diagnosis and treatment gaps, spontaneous remission has been reported in up to a third of people with untreated epilepsy.^5,18

People with epilepsy have a consistently reduced life expectancy.^23,24 The risk of premature death is highest shortly after diagnosis but remains elevated long‐term, with people younger than 40 years facing a disproportionately higher risk. Several factors contribute to this increased mortality, including seizure severity and type (convulsive seizures linked to accidents, SUDEP, and status epilepticus) and treatment‐related factors like ASM polytherapy and poor adherence. Causes of death are diverse, driven by comorbidities and epilepsy‐related events. Epilepsy‐related deaths are a smaller proportion overall but are higher in children and significantly elevated in people with DRE.

Beyond seizure control, epilepsy carries a significant psychosocial burden, often leading to adverse outcomes. Up to a fifth of adults with newly diagnosed epilepsy experience additional cognitive impairments. Psychiatric comorbidities are common, with up to a fifth experiencing anxiety or depression at any time and up to 6 % having severe psychiatric disorders.

On the social level, people with epilepsy often have issues with education, employment, and relationships.⁵ Young people may underachieve academically and have lower social competencies. Schooling problems can have lifelong repercussions, often resulting in unemployment or underemployment. People with epilepsy have unemployment levels at least twice that of the general population. Psychosocial consequences include low self‐esteem, social isolation, and poor psychological health, leading to a poor quality of life.

Most people achieve remission with appropriate treatment, however, factors such as structural brain lesions, specific epileptic syndromes, and early‐onset seizures indicate potentially poorer outcomes. The psychosocial challenges associated with epilepsy significantly amplify the overall burden of the disease, particularly in under‐resourced settings. Addressing modifiable factors, including prompt treatment initiation and efforts to reduce stigma, could substantially improve the quality of life for people living with epilepsy.

COMORBIDITIES OF EPILEPSY

Epilepsy frequently co‐occurs with psychiatric, cognitive, or somatic disorders.^5,10,26–30 While comorbidity typically describes additional conditions alongside a primary “index” disease, this concept is nuanced in epilepsy. Seizures are often a symptom of an underlying cause, making their designation as an index disease problematic. Epilepsy and its comorbidities often share complex, bidirectional relationships which arise from overlapping biological and social factors. Labelling co‐occurring conditions as epilepsy‐related can distort their relationships, as they might share common biological pathways or even directly contribute to epileptogenesis.^27,28 Given the heterogeneity of epilepsy, the presence of co‐existing conditions varies considerably among individuals. Viewing epilepsy as a symptom within a broader context emphasises the need for holistic management. Addressing the root causes alongside seizure control, necessitates interdisciplinary care, and demands attention to social determinants of health.²⁶

Over half of people with epilepsy have comorbidities, leading to worse health outcomes.^10,26 The risk of neuropsychiatric disorders – including depression, anxiety, bipolar disorder, attention deficit hyperactivity disorder, sleep disorders, and dementia – and pain disorders is eight times higher than in controls. Conditions such as asthma, autoimmune diseases, arthritis, heart disease, chronic lung disease and diabetes are also more prevalent in epilepsy.^10,28 Among children, nearly half have co‐occurring developmental or psychiatric conditions or other neurological disorders.

Psychiatric comorbidities significantly contribute to early mortality in people with epilepsy.^10,28–30 Endocrine, psychiatric, and respiratory comorbidities are associated with a reduced likelihood of achieving seizure freedom. ASM do not increase the risk of suicide, but epilepsy, particularly of temporal lobe origin, does. In children, autism and cognitive disability predispose to poorer long‐term seizure outcomes. Health‐related quality of life is inversely related to the presence of comorbidities, with depression and anxiety explicitly associated with lower quality of life and a higher risk of unemployment. Intellectual disabilities, depression, and attention deficit hyperactivity disorder are linked to poor social adjustment and academic performance, regardless of the severity or type of epilepsy.

The association between stroke and cardiovascular diseases is well‐established. People with epilepsy have a higher risk of stroke, myocardial infarction, and sudden cardiac death compared to controls. Similarly, people with Alzheimer’s disease (AD) have an increased epilepsy risk.²¹ There is growing evidence for a higher‐than‐expected risk of cognitive impairment in people with epilepsy, likely due to a combination of the underlying condition, treatment, and brain dysfunction or damage.⁵

Chronic exposure to ASM may also have health consequences, mainly contributing to the development of comorbidities. Enzyme‐inducing ASM are associated with cardiovascular problems and reduced bone density. People with epilepsy have an increased risk of cardiac arrhythmias and sudden death than controls. Chronic exposure to certain ASM, particularly phenobarbital, phenytoin, and valproic acid, is linked to the development of tremors and ataxia. Comorbidities arising from chronic ASM exposure seem less common with newer ASM. Sufficient time may not have passed for complete certainty, but current risk–benefit assessments support using newer ASM, especially in older adults.

Epilepsy frequently co‐occurs with several psychiatric, cognitive, and somatic disorders, impacting health outcomes and quality of life. Due to these comorbidities increasing the risks of neuropsychiatric issues, somatic problems, and premature mortality, people with epilepsy need holistic, interdisciplinary management addressing root causes and social determinants.