The Effect of Epilepsy on Patient Mortality: A Dutch Cohort Study with 40 Years of Follow-up

abstract & commentary

Source: Shackleton DP, et al. Mortality in patients with epilepsy: 40 years of follow up in a Dutch cohort study. J Neurol Neurosurg Psychiatry 1999;66:636-640.

Shackleton and colleagues based in the institute for Epilepsy Diagnosis and Management in Heemsteed, the Netherlands, report the outcome of 1355 persons with epilepsy, first diagnosed between 1953 and 1967, and followed until this study terminated in December 1994. Mean age at entry was 19 years with a range of 6 months to 70 years; 746 patients were male, 609 were female, and mean follow-up was 28 years. Sixty percent of initial admissions to the study were younger than 21 years of age. Overall, during the 14 years of patient admissions and the 40 years that the study lasted, 38,665 person years were examined and 404 patients died (normal expected death rate = 128), an increase over expected mortality to 3.2 per 1000. Admission to the Institute’s care included a substantial number of patients with symptomatic epilepsy. Accordingly, the mortality rate during patients’ first registered treatment year amounted to a high of 16 per 1000 persons. After the first year, the rate declined to 6.9-7.0 times the normal for the ensuing nine-year follow-up. After that, follow-up mortality rates averaged 1.9 in patients living up to the final calculated 25 years of follow-up in the study.

The causes of symptomatic epilepsy in patients dying in the first two years related 19% to brain malignant neoplasms and stroke. After that, those factors fell to 15% of all mortality. Intrinsic epilepsy accounted for 21% of the mortality among these patients throughout the total follow-up study. Road traffic and other accidents averaged 13% of deaths. Overall seven patients, all older than age 20, committed suicide.

During the first two years of follow-up of all entering patients, primary epilepsy carried a 6.8 per 1000 mortality. After two years, this high figure dropped to 3.1 per 1000 and remained there throughout the entire analysis. Uncontrollable seizures may have precipitated such poor outcomes, but respiratory difficulties and/or cryptic acute primary brain disease in children also may have contributed to the remarkably high early rate.

Shackleton et al make several points. Their death rate was higher than those reported in some other series, but most of the latter dealt with an older median age at onset. (As noted above, 60% of all entering patients in this series were < 20 years old.) The death rate was high with epilepsy starting before 20 years, but also within the first years after onset (i.e., ³ 4 times the rates of subsequent years). Shackleton et al state that other centers have emphasized other primary brain disease as precipitating both death and complications of seizures, but they firmly state that epilepsy itself occupied 21% of their mortality among patients throughout the study. As they emphasize, approximately 1% of newly diagnosed intrinsic epilepsy patients will sooner or later die from the disease. Moreover, in their opinion, "If we also included causes of death indirectly related to epilepsy such as accidental deaths and suicides...the proportion of epilepsy related death...becomes larger than those deaths related to...malignant CNS neoplasms, cerebral vascular disease, other CNS illnesses."


Shackleton et al take the position that epilepsy resulting from other diseases of the brain importantly contributes to deaths. In their opinion, many of these systemic illnesses also have occurred in patients susceptible to seizures. Their high mortality rate in younger persons perhaps emphasizes that epilepsy, by itself, can importantly be fatal. Regrettably, they don’t describe the details of the high mortality rate affecting patients with primary epilepsy during the first two years of their disease. —fp

Intrinsic epilepsy accounted for what percentage of mortality among patients in the 40-year Dutch follow-up study?

a. 20%

b. 21%

c. 13%

d. 15%