Towards a comprehensive etiopathogenetic and pathophysiological theory of multiple sclerosis

Background: Multiple sclerosis (MS) is a neurodegenerative disease caused by dysfunction of the immune system that affects the central nervous system (CNS). It is characterized by demyelination, chronic inflammation, neuronal and oligodendrocyte loss and reactive astrogliosis. It can result in physical disability and acute neurological and cognitive problems. Despite the gains in knowledge of immunology, cell biology, and genetics in the last five decades, the ultimate etiology or specific elements that trigger MS remain unknown. The objective of this review is to propose a theoretical basis for MS etiopathogenesis.Methods: Search was done by accessing PubMed/Medline, EBSCO, and PsycINFO databases. The search string used was "(multiple sclerosis* OR EAE) AND (pathophysiology* OR etiopathogenesis)". The electronic databases were searched for titles or abstracts containing these terms in all published articles between January 1, 1960, and June 30, 2019. The search was filtered down to 362 articles which were included in this review.Results: A framework to better understand the etiopathogenesis and pathophysiology of MS can be derived from four essential factors; mitochondria dysfunction (MtD) & oxidative stress (OS), vitamin D (VD), sex hormones and thyroid hormones. These factors play a direct role in MS etiopathogenesis and have a modulatory effect on many other factors involved in the disease.Conclusions: For better MS prevention and treatment outcomes, efforts should be geared towards treating thyroid problems, sex hormone alterations, VD deficiency, sleep problems and melatonin alterations. MS patients should be encouraged to engage in activities that boost total antioxidant capacity (TAC) including diet and regular exercise and discouraged from activities that promote OS including smoking and alcohol consumption.