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 ¼ 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 ¼ 28) with an independent sample of patients with solely ALS (N ¼ 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.

Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis

“…Indeed, concurrent MG may occur in a small proportion of patients with onset of motorneuron disease. 26…”

Mitochondrial and Endoplasmic Reticulum Alterations in a Case of Amyotrophic Lateral Sclerosis Caused by TDP-43 A382T Mutation

“…However, large epidemiological studies suggested an association between MS and ALS [ 25 , 26 ], with an increased risk of MS among children of ALS patients [ 27 , 28 ]. If co-occurrence of ALS and MS is often due to diagnostic uncertainty [ 29 ], in validated cases of co-occurrence, the MS-related neuroinflammatory symptoms occurred years before ALS onset, leading to hypothesize that, in a small subgroup of ALS patients with defined clinical characteristics, neurodegeneration may be triggered by preceding neuroinflammation around the motor unit [ 29 ]. Thus, it could be possible that the inflammatory pathways activated by mitochondrial dysfunctions can contribute to neuroinflammation observed in MS, and in ALS.…”

Medication use and risk of amyotrophic lateral sclerosis—a systematic review

“…As previous reviews have summarized the existing literature on the roles of specific diseases, including cardiometabolic and inflammatory diseases, on the risk of ALS [60,61], in the present review, we focused on medication use as potential risk factor for ALS. However, because among the studies included in the present review, few have made efforts to address the concern of indication bias, it remains largely unknown whether it is the use of a specific medication or its underlying disease that is the real relevant factor for ALS.…”