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Shackleton DP, Westendorp RG, Kasteleijn-Nolst Trenité DG, Vanden-broucke JP. Mortality in patients with epilepsy: 40 years of follow up in a Dutch cohort study. J Neurol Neurosurg Psychiatry. 1999 May;66: 636-40.
In adults with newly diagnosed epilepsy, are all-cause mortality and epilepsy-specific mortality increased during short-term and long-term follow-up?
Inception cohort followed for up to 41 years (mean 28 y).
Community- and hospital-based epilepsy institute in the Netherlands.
1455 patients (54% men) with newly diagnosed epilepsy who first visited the institute between 1953 and 1967. Mean age at diagnosis was 19 years (range 6 mo to 70 y). Follow-up was 93% (1355 patients, 55% men). A neurologist confirmed epilepsy by using patient history and the results of electroencepha-lography. Exclusion criterion was pre-vious remote, symptomatic, unprovoked seizures.
Assessment of prognostic factors
Age, age at diagnosis, sex, date of first hospitalization in the epilepsy institute, and duration of disease.
Main outcome measures
Mortality was categorized as all-cause and cause-specific (from cancer, respiratory disease, cardiovascular disease, central nervous system disease [epilepsy and nonepilepsy], and external causes [suicide, all accidents, and traffic accidents]). Observed deaths were compared with the number of expected deaths in the general population, ad-justed for age, sex, and calendar year. Standardized mortality ratios (SMRs) were calculated.
During follow-up, of the 128 deaths expected in the general population, 404 deaths occurred. 18 of 53 deaths (34%) were related to epilepsy in the first 2 years, and 110 of 351 deaths (32%) were related to epilepsy after 2 years. Mortality rates were higher than expected in the first 2 years and lower thereafter (Table). Risk for death was greater if epilepsy was diagnosed before 20 years of age (SMR 24, 95% CI 19 to 29).
Patients with epilepsy had an increased risk for short-term and long-term mortality, largely because of causes un- related to epilepsy.
Source of funding: Dutch Commissie Landelijke Epilepsie Onderzoek (CLEO).
For correspondence: Dr. D.G. Kasteleijn-Nolst Trenité, Stichting Epilepsie Instellingen Nederland, "Meer en Bosch," "de Cruquius-hoeve" Achterweg 5, 2103 SW Heemstede, The Netherlands. FAX 31-23-5294324.
Abstract and Commentary also published in ACP Journal Club. 1999;131:75.
Death associated with epilepsy for up to 41 years of follow-up
Patients No. of Follow-up Mortality Standardized mortality ratio
deaths (95% CI)
All 404 Total All-cause 3.2 (2.9 to 3.5)
Men 266 Total All cause 3.6 (3.1 to 4.0)
Women 138 Total All-cause 2.6 (2.2 to 3.0)
All 53 £ 2 y All-cause 16 (12 to 20)
351 > 2 y All-cause 2.8 (2.5 to 3.1)
17 £ 2 y Central nervous system 155 (89 to 239)
97 > 2 y Central nervous system 42 (34 to 51)
This population-based, inception cohort study, which included 38 665 patient-years, explores an important question: To what extent is the excess death in patients with epilepsy directly attributable to the dis- order? Some of the results confirm previous findings of a 3-fold increase in all-cause mortality, and this rate is higher immediately after diagnosis of epilepsy, in men, and in younger patients (1, 2).
Although death certificates tend to be im- precise for obtaining data on the cause of death, this source does not invalidate the results of Shackleton and colleagues' study. Epilepsy was deemed directly responsible in 128 of 404 deaths (32%). How large is this epilepsy-specific risk for death? Not very, considering the expected number of deaths for the given population. Although the epilepsy-specific mortality rate in the first 2 years of follow-up was 6.8/1000 person-years, it subsequently decreased to 3.1/1000 person-years. Furthermore, the number of observed epilepsy-specific deaths was identical to the number of expected deaths in 38 665 person-years in the general population (SMR = 1).
However, this may not be the entire story. In epilepsy surgery centers, mortality rates are 4 times higher in patients with uncontrolled seizures than in those who are seizure-free (3). Does this finding apply to population-based analyses? Unfortunately, severity and treatment of epilepsy were not independently evaluated in this or other studies. Until this is done, the message to patients with epilepsy and to their clinicians is that increased death seems to be caused largely by factors unrelated to epilepsy.
Samuel Wiebe, MD
University of Western Ontario
London, Ontario, Canada
1. Hauser WA, Annegers JF, Elveback LR. Mortality in patients with epilepsy. Epilepsia. 1980;21:399-412.
2. Cockrell OC, Johnson AL, Sander JW, et al. Mortality from epilepsy: results from a prospective population-based study. Lancet. 1994;344:918-21.
3. Sperling MR, Feldman H, Kinman J, Liporace JD, O'Connor MJ. Seizure control and mortality in epilepsy. Ann Neurol. 1999;46:45-50.
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