Prognostic Categories for Amyotrophic Lateral Sclerosis

Abstract

Objectives To generate a prognostic classification method for Amyotrophic Lateral Sclerosis (ALS) from a prognostic model built using clinical variables from a population register. Materials and Methods We carried out a retrospective multivariate analysis of 713 patients with ALS over a 20 year period from the South-East England Amyotrophic Lateral Sclerosis (SEALS) population register. Patients were randomly allocated to ‘discovery’ or ‘test’ cohorts. A prognostic score was calculated using the discovery cohort and then used to predict survival in the test cohort. This score was used as a predictor variable in subsequent survival analyses, either as a raw value for a Cox regression or split into four prognostic categories (good, moderate, average, poor). Results A prognostic score generated from one cohort of patients predicted survival for a second cohort of patients (r2=0.72). Six variables were included in the survival model: age at onset, diagnostic delay, El Escorial category, use of riluzole, gender and site of onset. Cox regression demonstrated a strong relationship between these variables and survival (χ2 80.8, df 1, p<0.0001, n=343) in the test cohort. Kaplan-Meier analysis demonstrated a significant difference in survival between clinical categories (log rank 161.932, df 3, p<0.001). Conclusion It is possible to correctly classify patients into prognostic categories using clinical data easily available at time of diagnosis.

Natural history and clinical features of sporadic amyotrophic lateral sclerosis in China

“…Many other predictors, such as treatment with NIPPV, that may influence the survival time and improve the cognitive function of patients with ALS have been found previously,1 15 26 27 but no significant effect of treatment with NIPPV was observed in our analysis. Our study demonstrates that the Airlie House status at diagnosis is directly related to the rate of disease progression, in agreement with the findings of other studies 28 29. Since a diagnosis of definite ALS is indicative of more widespread clinical involvement, it is reasonable that a diagnosis of definite ALS at presentation carries a significantly poorer prognosis compared with all other diagnostic categories 1…”

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“…The challenge of defining ALS in an individual has befuddled clinicians and researchers for 150 years . New markers are needed to shorten time to diagnosis, define clinical subtypes, prognosticate and measure progression.…”

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“…Accurate prognosis would aid these decisions. There are prognostic categories based on age and region of onset, diagnostic delay, El Escorial classification, riluzole use, and gender . However, each category has broad ranges for disease progression rates and survival times, which confound attempts to predict prognosis in individuals.…”

“…Death results from respiratory failure. Our insight into pathogenesis is limited, resulting in frustration for the clinician and patient when the affected individual inevitably asks, “Why did I get this?” Lack of knowledge regarding pathogenesis also prevents physicians from providing accurate prognostic information for individuals despite attempts to construct prognostic algorithms . Disease course is highly variable, with survival ranging from months to decades …”