Evidence-based review on the natural history of the epilepsies

The present review discusses clinically important evidence for unstable remission/relapse patterns and for causes of premature mortality in patients with epilepsy. Although two of three patients become seizure-free with antiepileptic drugs (AEDs), as many as 20-40% of newly diagnosed patients with epilepsy become seizure-free without or with minimal AED treatment. Sadly, the proportion of those not becoming seizure-free despite treatment does not seem to have improved substantially over the past 50 years. There is emerging evidence that natural history of epilepsies is more complex than previously thought. Although two-thirds of patients follow stable patterns, that is, become seizure-free early and remain seizure-free (48%), or have refractory epilepsy all their life (19%), one in every three patients has an unstable course of epilepsy. Patients with an unstable course will either enter remission only after many years of having seizures (19%) or will relapse despite continued treatment (14%). Remote symptomatic epilepsy carries the highest risk of premature mortality. It remains unclear, however, why sudden unexplained death occurs more often in adults than in children and controversy exists whether entering remission prevents premature mortality. Studies of the natural history of newly diagnosed epilepsy show unexplained fluctuations of remission and relapse in as many as one in three patients and, sadly, no substantial improvement of epilepsy treatment in the past 50 years. The premature mortality of epilepsy is high and more work is needed to prevent it.