Can amyotrophic lateral sclerosis progression really pause? A cohort study using the medical research council scale

Abstract

Objective: To assess the frequency and predictors of plateaus in ALS progression as assessed by the Medical Research Council (MRC) Scale. Methods: All patients attending the ALS Center of Turin, with a diagnosis between 2007 and 2014 were considered. At each visit, muscle strength was evaluated in several muscles and assessed using the MRC scale. Concomitant ALSFRSr scores were retrieved. Plateaus were calculated as a stable overall MRC or ALSFRSr score lasting at least 6, 12 or 18 months. Results: According to MRC scale scores, 122 (22.8%), 71 (13.2%) and 59 (11.0%) patients experienced a plateau lasting at least 6, 12 and 18 months. ALSFRSr scores revealed similar estimates [134, (25.0%), 89 (16.6%) and 67 (12.5%), respectively]. Plateaus were more frequent at high scores and appeared a median of 24.6 months (IQR 6.7–47.7) after the diagnosis. Only the predominant upper motor neuron phenotype (OR 4.06, 95% CI 2-06–8.10, p-value <0.001) and diagnostic delay OR 1.03, 95% CI 1.01–10.5, p-value = 0.005) were significantly correlated with their appearance. Discussion: Plateaus in ALS progression as assessed using either ALSFRSr or MRC scale are not infrequent and should be expected especially in less aggressive phenotypes. Similar results were found both using the MRC scale and the ALSFRSr scores, suggesting a comparable reliability of these scales in grasping the disease progression.

Keywords:

• Amyotrophic lateral sclerosis
• epidemiology
• cohort studies
• progression studies
• survival analyses

Author contributions

RV participated to study conception and design, data collection, data analysis, interpretation of results and writing of the manuscript.

LS, FP participated to data collection, study design, interpretation of results and revision of the manuscript.

A Canosa, UM, MCT, MG participated to data collection and revision of the manuscript.

A Calvo, CM and A Chiò participated to study design, interpretation of results and revision of the manuscript.

Declaration of interest

Rosario Vasta, Luca Solero, Antonio Canosa, Umberto Manera, Maria Claudia Torrieri, Maurizio Grassano, Francesca Palumbo: no disclosures.

Andrea Calvo has received research support from the Italian Ministry of Health (Ricerca Finalizzata). Cristina Moglia has received research support from the Italian Ministry of Health (Ricerca Finalizzata). Adriano Chiò serves on the editorial advisory board of Amyotrophic Lateral Sclerosis and Neurological Sciences and has received research support from the Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Turin and the European Commission (Health Seventh Framework Programme) and serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Denali Therapeutics, Amylyx, and Cytokinetics.

Additional information

Funding

This work was in part supported by the Italian Ministry of Health [Ministero della Salute, Ricerca Sanatoria Finalizzata, grant RF-2016-02362405], the European Commission’s Health Seventh Framework Programme [FP7/2007-2013 under grant agreement 259867], the Italian Ministry of Education, University and Research [Progetti di Ricerca di Rilevante Interesse Nazionale, PRIN, grant 2017SNW5MB], the Joint Programme – Neurodegenerative Disease Research (ALS-Care, Strength and Brain-Mend projects), granted by the Italian Ministry of Education, University and Research. This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the “Rita Levi Montalcini” Department of Neuroscience, University of Torino, Italy.