The increased risk of death linked to childhood-onset epilepsy appears to be substantial, and it persists into adulthood, according to a report in the Dec. 23 issue of the New England Journal of Medicine.
In a cohort of 245 Finnish patients diagnosed as having epilepsy in the early 1960s and followed until 2002, overall mortality was 24% – three times higher than would be expected in the general population of the same age, said Dr. Mattii Sillanpaa of the departments of pediatrics and neurology at the University of Turku, Finland, and his associates.
"Few studies have evaluated long-term mortality in well-characterized cohorts of children with epilepsy," and most of those have been retrospective and have not included autopsy confirmation of other causes of death. Dr. Sillanpaa and his colleagues assessed mortality in a group of patients evaluated between 1961 and 1964 at a median age of 3 years who were then followed prospectively for a median of 40 years; 70% of the study subjects who died underwent autopsy.
A total of 122 patients had idiopathic or cryptogenic epilepsy and 123 had "remote symptomatic epilepsy" associated with a major neurologic abnormality or insult. At final follow-up or death, 110 patients (45%) were in 5-year terminal remission and were not receiving any medication, 28 (11%) were in 5-year terminal remission and were receiving medication, and 107 (44%) were not in 5-year remission.
A total of 60 patients died, for an overall mortality of 24% and a rate of death of 6.9 per 1,000 person-years.
Death was directly related to epilepsy in 33 patients (55% of those who died), and was not related to epilepsy but to an underlying neurologic problem or another disease in the remaining 26 patients (45% of those who died). In one patient, the cause of death was unknown. The former group included 18 patients with "sudden, unexplained death in epilepsy," 9 with definite or probable seizure, and 6 with accidental drowning.
"With the use of the alternative classification of sudden, unexplained death in epilepsy, which includes possible or definite seizures as long as the seizures were not status epilepticus, 38% of the deaths were due to sudden, unexplained death in epilepsy, 7% were due to status epilepticus, and 10% were due to accidental drowning," they said.
Sudden, unexplained death occurred in 9% of the overall cohort, at a median age of 25 years. The cumulative risk of sudden, unexplained death was 7% at 40 years.
As expected, mortality was significantly higher in patients who had remote symptomatic epilepsy (11.1 deaths per 1,000 person-years) than in those with cryptogenic epilepsy (2.9 per 1,000 person-years) or idiopathic epilepsy (3.5 per 1,000 person-years).
"More than three-quarters of the deaths occurred in subjects who were not in 5-year terminal remission and in the groups with epilepsy due to remote symptomatic causes: these included 21 of the 26 deaths not directly related to epilepsy and 24 of the 33 deaths related to epilepsy," the investigators said (N. Engl. J. Med. 2010;363:2522-9).
"Our data alone do not provide support for aggressive treatment to prevent sudden, unexplained death in patients with epilepsy. However, studies of epilepsy surgery in adults with medically refractory partial epilepsy have shown that the rates of sudden, unexplained death are substantially lower among those who become seizure free after surgery than among those who do not, suggesting that the risk is potentially modifiable," they added.
This study was supported by a grant from the Finnish Epilepsy Research Foundation. No financial disclosures were reported.