What do we know about the variability in survival of patients with amyotrophic lateral sclerosis?

ABSTRACT

Introduction

ALS is a fatal neurodegenerative disease. However, patients show variability in the length of survival after symptom onset. Understanding the mechanisms of long survival could lead to possible avenues for therapy.

Areas covered

This review surveys the reported length of survival in ALS, the clinical features that predict survival in individual patients, and possible factors, particularly genetic factors, that could cause short or long survival. The authors also speculate on possible mechanisms.

Expert opinion

a small number of known factors can explain some variability in ALS survival. However, other disease-modifying factors likely exist. Factors that alter motor neurone vulnerability and immune, metabolic, and muscle function could affect survival by modulating the disease process. Knowing these factors could lead to interventions to change the course of the disease. The authors suggest a broad approach is needed to quantify the proportion of variation survival attributable to genetic and non-genetic factors and to identify and estimate the effect size of specific factors. Studies of this nature could not only identify novel avenues for therapeutic research but also play an important role in clinical trial design and personalized medicine.

KEYWORDS:

• Amyotrophic lateral sclerosis
• neurodegeneration
• survival
• genetics
• immune system
• metabolism
• natural history
• epidemiology

Article highlights

• ALS patients vary in length of survival

• Patients with typical ALS have shorter survival than those with other ALS subtypes

• Patients with rapid progression of clinical features have shorter survival

• Some genetic variants are associated with length of survival

ALS cohorts with detailed recording of longitudinal symptoms of those with ALS together with matched biological samples for genetic and ‘omic analyses are needed to identify specific factors associated with survival.

Supplementary material

Supplemental data for this article can be accessed here.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.