Sudden unexpected death in epilepsy: evidence-based analysis of incidence and risk factors

To provide an evidence-based analysis of the risk factors and incidence of SUDEP, and to assess methodological aspects and sources of variation in studies dealing with SUDEP.

An expert in library resources and electronic databases comprehensively searched Medline, Index Medicus, and the Cochrane library. We included case-control or cohort studies focusing on SUDEP in children or adults, published in the English language. Two reviewers independently applied study eligibility criteria and extracted data, resolving disagreements through discussion.

Of 404 citations identified, 83 potentially eligible articles were reviewed in full text and 36 studies fulfilled eligibility criteria (29 cohort and 8 case-control studies). In studies using non-SUDEP deaths as controls the most consistent risk factors were a seizure preceding death, and subtherapeutic antiepileptic drug levels. In studies that used persons living with epilepsy as controls the main risk factors for SUDEP were youth, high seizure frequency, high number of antiepileptic drugs and long duration of epilepsy. The annual incidence of SUDEP ranged from 0 to 10:1000. It was highest in studies of candidates for epilepsy surgery and epilepsy referral centers (2.2:1000-10:1000), intermediate in studies including patients with mental retardation (3.4:1000-3.6:1000), and lowest in children (0-0.2:1000). The incidence was similar in autopsy series (0.35:1000-2.5:1000) and in studies of epilepsy patients in the general population (0-1.35:1000). The median proportion of SUDEP in relation to overall mortality in epilepsy was 40 and 4% in high- and low-risk groups, respectively.

Although studies on SUDEP are heterogeneous in methodology, consistent patterns in incidence and risk factors emerge. Low- and high-risk patient groups are identified, which determine the relative contribution of SUDEP to overall mortality in epilepsy. In addition to patient population, risk factors for SUDEP depend on the type of controls used for comparison (dead versus live patients with epilepsy). Risk factors found in different studies are not necessarily contradictory, but are often complementary.