Co-occurrence of amyotrophic lateral sclerosis and multiple sclerosis: a rare but interesting association

Multiple sclerosis (MS) is an inflammatory demyelinating disease with highly variable clinical course and usual onset in younger age, caused by genetic and environmental factors. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects motor neurons in the brain and spinal cord, resulting in gradual loss of voluntary muscle and respiratory control. Both ALS and MS exhibit distinct underlying causes and disease mechanisms, despite some shared clinical effects. About 10% of ALS are linked to genetic factors, such as C9orf72, the remaining sporadic ones being potentially influenced by environmental, toxic and oxidative stress, while MS is an autoimmune disorder where the immune system leads to inflammation and attacks the myelin sheath, genetic predisposition and viral infections playing a role in its susceptibility. The co-occurrence of ALS and MS is extremely rare, with 46 cases being reported in the available literature from 1986 to 2024, while in the earlier literature, cases with coincidental muscular atrophy simulating ALS were described. In the overwhelming majority, ALS manifested between one and 41 years after the onset of MS; only in four cases was ALS present before detection of MS. The concurrence of MS and ALS can be explained by similarities in their pathogenesis related to neurodegeneration, inflammation, and/or genetic susceptibility. The role of rare genetic ALS forms in this comorbidity deserves further studies. The shared inflammatory component with a cascade of oxidative stress and other noxious mechanisms leads to progressive motor and bulbar or other symptoms that underscore the potential for cross-disease research to yield insights applicable to both conditions and their relations to immune-mediated disorders.