The neurobehavioural comorbidities of epilepsy: can a natural history be developed?

Summary Epilepsy is a common neurological disorder that can be complicated by neurobehavioral comorbidities, which include cognitive impairment, psychiatric disorders, and social problems. Although such comorbidities are traditionally thought to arise predominantly from the effects of recurrent seizures, iatrogenic effects of medications, and adverse social reactions to epilepsy (eg, stigma), there is a growing body of evidence that other factors are involved. These influences include altered neurodevelopment of the brain, cognition, and behaviour; exacerbation of the comorbidities due to decades of medically intractable epilepsy; and possible acceleration of common age-associated changes, leading to uncertain and understudied outcome in old age. This Review summarises, from a lifespan perspective, the evidence for the neurodevelopmental origins of these comorbidities, how they develop over time, and their endpoints, with an emphasis on future clinical and research challenges.