Multiple sclerosis is a primarily inflammatory disorder of the central nervous system (CNS) that causes damage to myelin and axons. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving primarily motor neurons in the cerebral cortex, brainstem, and spinal cord. The unusual combination of ALS and MS and an increased co-occurrence of ALS and MS has been reported, also in patients with hexanucleotide repeat expansions of C9ORF72. Whether inflammation is a cause or effect of the primary pathology of MS, similar immunological profiles have been observed in both diseases. Both characteristic and adaptive arms of the immune response have been implicated in the pathogenesis of MS. Generalized activation of microglia, astrocytes and autoreactive T and B lymphocytes play a role in maintaining disease. Pro-inflammatory cell populations are important in ALS too. RT-PCR in ALS patients of spinal cord white and gray matter has shown increased glial expression of toll-like receptor proteins. Raised serum and CSF IL-12 and IL-17, levels in ALS patients, and high serum IL-23 levels point towards a similar cytokine and T-cell activation profile being present in both ALS and MS. Regardless of whether inflammation is a primary or secondary cause of pathology, the molecular basis of axonal loss in both diseases may converge on similar mechanisms. Similar to ALS, MS pathology demonstrates activated microglia and astrocytes known to produce NO and reactive oxygen species. Axonal loss, the substrate for irreversible neurological disability, is a shared pathological feature in both conditions with intriguing similarities emerging in the molecular and cellular pathways leading to axonal demise.
Neurology Letters