Amyotrophic lateral sclerosis: mortality risk during the course of the disease and prognostic factors

https://doi.org/10.1016/S0022-510X(97)00238-4Get rights and content

Abstract

We performed a historical cohort study of 307 untreated patients with probable or definite amyotrophic lateral sclerosis in order to investigate whether the mortality risk changed during the disease course and to identify prognostic factors at diagnosis. Patients were diagnosed in 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 estimated 5- and 10-year survival of 20 and 8%, respectively. Mortality was at its maximum in the second year after diagnosis and declined considerably 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 females. Patients with initial respiratory muscle weakness, had the worst prognosis with a median survival of only 2 months. The significantly greater mortality of older patients proved not to result from a rise in expected mortality only. In conclusion, the annual mortality risk in ALS does not remain constant throughout the disease and depends on age at diagnosis, site of onset, diagnostic delay, but also on the time since diagnosis. These findings may have consequences for the planning of symptomatic care and the design and analysis of therapeutic trials.

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons (Leigh and Ray-Chaudhuri, 1994). It leads to progressive weakness and severe disability within a few years. The diagnosis usually carries a poor prognosis with a median survival of 1–3 years from diagnosis (Christensen et al., 1990, Norris et al., 1993) and of 2–4 years from initial weakness (Tysnes et al., 1991, Chancellor et al., 1993, Eisen et al., 1993, Haverkamp et al., 1995). The course of the disease is reported to be slowly progressive with a linear decline of muscle strength (Munsat et al., 1988) and a constant risk of death (Christensen et al., 1990, Norris et al., 1993). This is at odds with clinical experience that a substantial proportion of patients survive diagnosis 5 or more years (Mulder and Howard, 1976, Christensen et al., 1990, Norris et al., 1993) and that these patients seems to have a better prognosis than those who have been diagnosed more recently. Furthermore, survival is known to vary considerably and is considered to be difficult to predict in individual cases, but how and why patients differ is not yet clear. Clinical characteristics related to survival probably include age (Juergens et al., 1980, Uebayashi et al., 1983, Kondo and Hemmi, 1984, Caroscio et al., 1987, Jablecki et al., 1989, Christensen et al., 1990, Chancellor et al., 1993, Eisen et al., 1993, Norris et al., 1993, Haverkamp et al., 1995) and site of onset (Mulder and Howard, 1976, Uebayashi et al., 1983, Kondo and Hemmi, 1984, Mortara et al., 1984, Caroscio et al., 1987, Christensen et al., 1990, Chancellor et al., 1993, Norris et al., 1993).

In order to study the mortality risk throughout the disease and identify prognostic factors related to mortality, we performed a historical cohort study of untreated patients with ALS, who were referred to one of the university hospitals in The Netherlands.

Section snippets

Patients

We retrieved the hospital records of consecutive patients who had been diagnosed as having ALS or motor neuron disease between January 1, 1970 and January 1, 1988. All available clinical data were reviewed for confirmation of the diagnosis. Patients who fulfilled the clinical diagnostic criteria for probable or definite ALS (Brooks, 1994) were eligible for the study: upper and lower motor neuron signs; insidious onset and progression of weakness; involvement of at least two body regions

Patients

The study cohort consisted of 307 patients, 170 males and 137 females. We excluded 173 patients, coded under the diagnostic category of ALS or motor neuron disease, but who did not fulfil the clinical diagnostic criteria of probable or definite ALS, including 47 patients with progressive spinal muscular atrophy, one with progressive bulbar palsy, 16 with primary lateral sclerosis, 20 with multisystem atrophy, one with a suspected postpoliomyelitis syndrome, 17 with ALS-mimic syndromes (Louwerse

Discussion

We found that the mortality risk of patients with ALS did not remain constant through the disease. Mortality was at its maximum in the second year after diagnosis and declined considerably thereafter. Patients who survived diagnosis 6 years or more, had almost the same life expectancy as their healthy coevals. In addition, we observed associations between mortality and age at diagnosis, site of onset, and the delay from initial weakness to diagnosis. The better prognosis of patients presenting

Acknowledgements

The authors are indebted to Prof. M. Vermeulen, for advice and support.

References (26)

  • D.R. Cox

    Regression models and life tables

    J. R. Stat. Soc. B

    (1972)
  • A. Eisen et al.

    Duration of amyotrophic lateral sclerosis is age dependent

    Muscle Nerve

    (1993)
  • S.S. Gubbay et al.

    Amyotrophic lateral sclerosis. A study of its presentation and prognosis

    J. Neurol

    (1985)
  • Cited by (0)

    1

    Participating centers (principal investigators of The Netherlands ALS Consortium): Academic Hospitals of Rotterdam (P.A. van Doorn and H.F.M. Busch), Utrecht (J.H.J. Wokke and F.G.I. Jennekens), Leyden (J.J.G.M. Verschuuren and A.R. Wintzen), Nijmegen (A. Keyser and G.W.A.M. Padberg), University of Amsterdam (M. de Visser and J.M.B.V. de Jong), Maastricht (C.J. Höweler and J.S.H. Vles), Groningen (A.E.J. de Jager and H.J.G.H. Oosterhuis), and of the Free University of Amsterdam (C.H. Polman and J.C. Koetsier), The Netherlands.

    View full text