Mortality in Childhood Epilepsy

Abstract

Source: Sillanpää M, Shinnar S. Long-term mortality in childhood- onset epilepsy. N Engl J Med. 2010; 363(26): 2522-2529; doi: 10.1056/NEJMoa0911610Investigators from the University of Turku and Turku General Hospital, Finland, conducted a study to determine long-term mortality in adults with a history of childhood epilepsy. Study participants were 245 individuals who were diagnosed with epilepsy at younger than 16 years of age by the end of 1964 and who were living in the area of Turku, Finland. Children were excluded if they had only febrile seizures, other acute symptomatic seizures, or a single unprovoked seizure. Follow-up examinations were conducted and information on seizure frequency and treatment collected every five years up to 2002, and comprehensive data on any deaths were collected including date and time of death, underlying cause of death, and autopsy data, when available. Definitions of the cause of seizures from the International League Against Epilepsy were used to categorize children into those with idiopathic or cryptogenic (of unknown origin) epilepsy and those with epilepsy due to remote symptomatic causes such as cognitive impairment, developmental delay, or a history of major neurologic insult.1 The median duration of follow-up was 40.0 years and the autopsy rate was 70%.By the end of the follow-up period, 24% (60/245) of study participants had died, with a death rate of 6.9 per 1,000 person-years. This rate was three times higher than the expected age-adjusted mortality in the general population. The death rate was significantly lower in individuals who were seizure-free for at least five years and not taking medication for their seizures (1.5 deaths/1,000 person-years) compared to those who either were seizure-free for five years but still taking medication for epilepsy (11.8 deaths/1,000 person-years) or were not seizure-free (15.9 deaths/1,000 person years; P<.001). Individuals with epilepsy due to remote symptomatic causes had a higher death rate than those with idiopathic or cryptogenic epilepsy (11.1 deaths/1,000 person-years vs 3.2/1,000 person-years; P<.001). Other factors, such as type of epilepsy or the presence of cerebral palsy, did not impact the risk of death in individuals with remote symptomatic epilepsy. The cause of death was related to epilepsy in 55% (33/60) of individuals. Sudden, unexplained deaths occurred in 30%, probable or definite seizure in 15%, and accidental drowning in 10%. On multivariate analysis, only the absence of a five-year seizure-free interval was significantly associated with an increased risk of sudden, unexplained death.The authors conclude that individuals who did not achieve a five-year remission of their seizures were at significant risk of sudden, unexplained epilepsy-related death.Dr Geskey has disclosed no financial relationship relevant to this commentary. He is on the Speakers’ Bureau of GlaxoSmithKline. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This important study of the long-term mortality of a prospectively followed cohort of patients with childhood-onset epilepsy – with its 40-year follow-up and access to detailed information surrounding the date, time, and cause of death as well as high autopsy rate – high-lights the consequences of ongoing seizures, particularly in those children with an underlying neurologic disability. Although there were no cases of sudden, unexplained death among children under 14 years of age in this study, sudden, unexplained death in epilepsy (SUDEP) is the leading cause of death in patients with chronic, uncontrolled epilepsy, particularly in adults. It is hypothesized that cardiac arrhythmia, central or obstructive apnea, or primary cerebral shutdown may cause SUDEP.2 Supporting the concept that apnea is a potential etiology of SUDEP, the administration of oxygen prevents sudden death in seizure-prone mice.3 As more research is conducted surrounding the etiology and possible treatment of SUDEP, the most obvious question one can ask (and the study authors pose) is: can epilepsy surgery modify the risk of sudden death in patients with medically refractory epilepsy?