Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients

Abstract

Our objective was to elucidate the clinical factors affecting functional decline and survival in Japanese amyotrophic lateral sclerosis (ALS) patients. We constructed a multicenter prospective ALS cohort that included 451 sporadic ALS patients in the analysis. We longitudinally utilized the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) as the functional scale, and determined the timing of introduction of a tracheostomy for positive-pressure ventilation and death. A joint modelling approach was employed to identify prognostic factors for functional decline and survival. Age at onset was a common prognostic factor for both functional decline and survival (p < 0.001, p < 0.001, respectively). Female gender (p = 0.019) and initial symptoms, including upper limb weakness (p = 0.010), lower limb weakness (p = 0.008) or bulbar symptoms (p = 0.005), were related to early functional decline, whereas neck weakness as an initial symptom (p = 0.018), non-use of riluzole (p = 0.030) and proximal dominant muscle weakness in the upper extremities (p = 0.01) were related to a shorter survival time. A decline in the ALSFRS-R score was correlated with a shortened survival time (p < 0.001). In conclusion, the factors affecting functional decline and survival in ALS were common in part but different to some extent. This difference has not been previously well recognized but is informative in clinical practice and for conducting trials.

Key words::

• ALS
• ALSFRS-R
• functional decline
• survival

Acknowledgements

We thank all the patients with ALS who participated in this study. We also thank all the doctors and staff who participated in JaCALS.

This study was supported by Health and Labour Sciences Research grants from the Ministry of Health, Labour and Welfare of Japan, and Grants- in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

A part of this study is the result of ‘Integrated Research on Neuropsychiatric Disorders’ carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Table I and Figure 1.