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Prognostic factors for the course of functional status of patients with ALS: a systematic review

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Abstract

The progressive course of amyotrophic lateral sclerosis (ALS) results in an ever-changing spectrum of the care needs of patients with ALS. Knowledge of prognostic factors for the functional course of ALS may enhance clinical prediction and improve the timing of appropriate interventions. Our objective was to systematically review the evidence regarding prognostic factors for the rate of functional decline of patients with ALS, assessed with versions of the ALS Functional Rating Scale (ALSFRS). Two reviewers independently assessed the methodological quality of the thirteen included studies using the Quality in Prognosis Studies (QUIPS) tool. The overall quality of evidence for each prognostic factor was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, considering risk of bias, imprecision, inconsistency, indirectness, and publication bias. The quality of evidence for the prognostic value of age at onset, site of onset, time from symptom onset to diagnosis, and ALSFRS-Revised baseline score was low, mainly due to the limited data and inconsistency of results in the small number of studies included. The prognostic value of initial rate of disease progression, age at diagnosis, forced vital capacity, frontotemporal dementia, body mass index, and comorbidity remains unclear. We conclude that the current evidence on prognostic factors for functional decline in ALS is insufficient to allow the development of a prediction tool that can support clinical decisions. Given the limited data, future prognostic studies may need to focus on factors that have a predictive value for a decline in ALSFRS(-R) domain scores, preferably based on internationally collected and shared data.

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Conflicts of interest

H. Creemers, A. Beelen, and H. Grupstra declare that they have no conflict of interest. F. Nollet serves on the editorial board of the Journal of Rehabilitation Medicine and the scientific advisory board of the Anna Fund. L.H. van den Berg received travel grants and consultancy fees from Baxter; serves on scientific advisory boards for Prinses Beatrix Spierfonds, Thierry Latran Foundation, and Biogen Idec; serves on the editorial board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration and the Journal of Neurology, Neurosurgery & Psychiatry; and receives research support from the Prinses Beatrix Spierfonds, Netherlands ALS Foundation, VSB Fonds, Adessium Foundation, the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 259867 and the Netherlands Organization for Health Research and Development (ZonMw). The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Rehabilitation, Academic Medical Center Amsterdam, Netherlands ALS Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    Huub Creemers, Hepke Grupstra, Frans Nollet & Anita Beelen

  2. Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Netherlands ALS Center, PO Box 85500, 3508 GA, Utrecht, The Netherlands

    Leonard H. van den Berg

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  1. Huub Creemers
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Correspondence to Huub Creemers.

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Creemers, H., Grupstra, H., Nollet, F. et al. Prognostic factors for the course of functional status of patients with ALS: a systematic review. J Neurol 262, 1407–1423 (2015). https://doi.org/10.1007/s00415-014-7564-8

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