“ALS reversals”: demographics, disease characteristics, treatments, and co-morbidities

Abstract

Objective: To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with “amyotrophic lateral sclerosis (ALS) reversals” and those with typically progressive ALS. Methods: Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. Results: ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. Conclusions: When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study.

Keywords:

• Amyotrophic lateral sclerosis
• motor neuron disease
• disease reversal
• epidemiology
• case control

Acknowledgements

The authors are grateful to all of the patients and families of patients living with ALS who shared their stories in hopes that they might help other PALS. Without their time and interest, this study would not have been possible. We also appreciate the assistance of Edwin Iversen, PhD and the Duke University Statistical Consulting Center for their statistical methods support. This work was supported by the LVH ALS Foundation [grant number 1].

Declaration of interest

Daniel Harrison, Paul Mehta, Elijah Stommel, Beatrice Nefussy, and Jesse Crayle report no disclosures. Michael A van Es serves on the Motor Neurone Disease Association biomedical research advisory panel, has consulted for Biogen and has received travel grants from Baxalta and funding sources include the Netherlands Organization for Health Research and Development (Veni scheme), The Thierry Latran Foundation, the ALS Foundation Netherlands. Vivian Drory received research grants from the Israel Ministry of Science and Technology and Adelis Foundation. She is a paid consultant for Eyecontrol. Leonard H van den Berg has research grants from the Netherlands ALS Foundation. He serves on the Scientific Advisory Boards of Biogen, Cytokinetics and Orion. Richard Bedlack has research support from the ALS Association, the Motor Neurone Disease Association, Cytokinetics, Neuraltus, and GlaxoSmithKlein; he is a paid consultant for the ALS Association, Avanir, Cytokinetics, Neuraltus, Ultragenyx, Mallinkrodt and Brainstorm Cell.

Supplementary material available online