ALS patients with concurrent neuroinflammatory disorders; a nationwide clinical records study

Abstract

Objective:To determine if inflammation in proximity of the motor unit may contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS). Methods: We identified all patients diagnosed in Sweden with concurrent ALS and multiple sclerosis (MS), myasthenia gravis (MG), inflammatory polyneuropathies (IP), or dermatopolymyositis (DMPM) during 1991–2014 according to the Swedish Patient Register (N = 263). We validated medical records for 92% of these patients (18 records were not retrieved and three did not contain enough information) and compared patients with a confirmed overlap (N = 28) with an independent sample of patients with solely ALS (N = 271). Results: Ninety-one patients were deemed as not having ALS (34.6%). Among the remaining 151 with validated ALS, 12 had also a confirmed MS diagnosis, nine a confirmed MG diagnosis, four a confirmed IP diagnosis, and three a confirmed DMPM diagnosis. Seventeen of the patients were women and 11 were men. Seventy-nine percent of the patients with a confirmed overlap had MS, MG, IP, or DMPM diagnosed prior to ALS. Compared to patients with only ALS, the concurrent patients were significantly older at symptoms onset, had higher prevalence of bulbar onset, but used Riluzole and noninvasive ventilation less frequently. Conclusions: We found that a high concurrence of ALS and MS/MG/IP/DMPM diagnoses is largely due to diagnostic uncertainty. A minority of patients had a true concurrence, where MS, MG, IP, and DMPM preceded the ALS diagnosis, which might be due to chance alone. Four patients were diagnosed with MG shortly after onset of ALS, suggesting that neurodegeneration might trigger autoimmunity.

Keywords:

• Amyotrophic lateral sclerosis
• multiple sclerosis
• myasthenia gravis

Acknowledgements

We are grateful for the help received from thehospitals that provided us with the requested medical records and would also like to thank Amanda Regodón Wallin for her contribution to the data extraction of the general Swedish ALS patients used as comparison group in this study.

Disclosure statement

Dr. Fredrik Piehl has received research grants from Biogen, Genzyme, Merck KGaA, and Novartis, and fees for serving as Chair of DMC in clinical trials with Parexel, outside the submitted work. Dr. Elisa Longinetti, Dr. Olafur Sveinsson, Dr. Rayomand Press, Dr. Weimin Ye, Dr. Caroline Ingre, and Dr. Fang Fang report no disclosures.

Additional information

Funding

This study was funded by the Swedish Research Council (grant No: 2019-01088), the Ulla-Carin Lindquist Foundation, and the Karolinska Institutet (Senior Researcher Award to Fang Fang).