AMYOTROPHIC-LATERAL-SCLEROSIS - MORTALITY RISK DURING THE COURSE OF THE DISEASE AND PROGNOSTIC FACTORS

We performed a historical cohort study of 307 untreated patients with probable or definite amyotrophic lateral sclerosis in order to investi gate whether the mortality risk changed during the disease course and to identify prognostic factors at diagnosis. Patients were diagnosed i n one of the academic hospitals in The Netherlands and followed-up for at least 6 years after diagnosis. The median survival from diagnosis was 1.4 years (95% confidence interval, 1.3-1.6 years) with an estimat ed 5- and 10-year survival of 20 and 8%, respectively. Mortality was a t its maximum in the second year after diagnosis and declined consider ably thereafter. Observed mortality approached the expected mortality in patients who survived diagnosis 6 or more years. In univariate and multivariate analyses, young age, limb onset, and a long delay between initial weakness and diagnosis were associated with lower mortality. The better prognosis of limb-onset patients was not observed in female s. Patients with initial respiratory muscle weakness, had the worst pr ognosis with a median survival of only 2 months. The significantly gre ater mortality of older patients proved not to result from a rise in e xpected mortality only. In conclusion, the annual mortality risk in AL S does not remain constant throughout the disease and depends on age a t diagnosis, site of onset, diagnostic delay, but also on the time sin ce diagnosis. These findings may have consequences for the planning of symptomatic care and the design and analysis of therapeutic trials. ( C) 1997 Elsevier Science B.V.