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Unraveling the complexity of amyotrophic lateral sclerosis survival prediction

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Last modified
  • 05/15/2025
Type of Material
Authors
    Stephen R. Pfohl, Emory UniversityRenaid B. Kim, Emory UniversityGrant S. Coan, Emory UniversityCassie Mitchell, Emory University
Language
  • English
Date
  • 2018-06-14
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2018 Pfohl, Kim, Coan and Mitchell.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1662-5196
Volume
  • 12
Grant/Funding Information
  • This study was funded by National Institutes of Health grants NS081426, NS069616, and NS098228 to CM.
Supplemental Material (URL)
Abstract
  • Objective: The heterogeneity of amyotrophic lateral sclerosis (ALS) survival duration, which varies from <1 year to >10 years, challenges clinical decisions and trials. Utilizing data from 801 deceased ALS patients, we: (1) assess the underlying complex relationships among common clinical ALS metrics; (2) identify which clinical ALS metrics are the “best” survival predictors and how their predictive ability changes as a function of disease progression. Methods: Analyses included examination of relationships within the raw data as well as the construction of interactive survival regression and classification models (generalized linear model and random forests model). Dimensionality reduction and feature clustering enabled decomposition of clinical variable contributions. Thirty-eight metrics were utilized, including Medical Research Council (MRC) muscle scores; respiratory function, including forced vital capacity (FVC) and FVC % predicted, oxygen saturation, negative inspiratory force (NIF); the Revised ALS Functional Rating Scale (ALSFRS-R) and its activities of daily living (ADL) and respiratory sub-scores; body weight; onset type, onset age, gender, and height. Prognostic random forest models confirm the dominance of patient age-related parameters decline in classifying survival at thresholds of 30, 60, 90, and 180 days and 1, 2, 3, 4, and 5 years. Results: Collective prognostic insight derived from the overall investigation includes: multi-dimensionality of ALSFRS-R scores suggests cautious usage for survival forecasting; upper and lower extremities independently degenerate and are autonomous from respiratory decline, with the latter associating with nearer-to-death classifications; height and weight-based metrics are auxiliary predictors for farther-from-death classifications; sex and onset site (limb, bulbar) are not independent survival predictors due to age co-correlation. Conclusion: The dimensionality and fluctuating predictors of ALS survival must be considered when developing predictive models for clinical trial development or in-clinic usage. Additional independent metrics and possible revisions to current metrics, like the ALSFRS-R, are needed to capture the underlying complexity needed for population and personalized forecasting of survival.
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Research Categories
  • Engineering, Biomedical

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