title: Theories of the etiology of multiple sclerosis: a critical review.
abstract: In summary, research studies to date have not identified a unitary cause of MS; rather, genetic predisposition (particularly, inherited immunoregulatory abnormalities) and environmental links in the causal chain of disease (antigenic exposures, trauma, or other insults) have been postulated to interact with each other and with additional host susceptibility factors (acquired faulty immune system regulation, age, nutritional status, endocrine status, etc.). Two mechanisms have been proposed as their final common pathway: dysmyelination (i.e., defective myelin production) and inadequate myelin maintenance. Myelin production, turnover rate, and neurological function are all apparently normal prior to disease onset, although studies addressing possible preexisting lipoprotein metabolic defects have not been performed in MS patients as in laboratory animals. The demyelination process characteristic of the disease appears to result from inadequate maintenance due to an active degradative process, rather than from deficient formation or a simple passive metabolic imbalance between anabolic and catabolic processes, as had been suggested by Sperry and Waelsch (205). Among other lines of evidence, it is offered that deficient replacement postpubertally would not explain the rapid onset of symptoms often seen in MS. Accelerated myelin destruction could be due either to faulty regulation of the rate-limiting enzymes, for which there is no substantiation, or to immune system malfunction, for which the evidence is mounting. Immune system attack seems to be both humoral and cell-mediated, but the triggers remain unknown. This article has briefly but critically reviewed toxins, trauma, thrombosis, subacute fat embolism, viruses, and biochemical factors in the etiology of MS, with emphasis on hormonal and other types of mediation of the immune response.
mesh_terms: D000367:Age Factors; D000920:Antibody-Dependent Cell Cytotoxicity; D004032:Diet; D004781:Environmental Exposure; D005260:Female; D005802:Genes, MHC Class II; D005838:Genotype; D006728:Hormones / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007120:Immunochemistry; D007126:Immunoglobulin Allotypes; D008214:Lymphocytes / Q000145:classification; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D014118:Toxins, Biological / Q000494:pharmacology; D014780:Viruses / Q000472:pathogenicity; D014808:Vitamin D Deficiency / Q000150:complications; D014947:Wounds and Injuries
chemical_list: D006728:Hormones; D007126:Immunoglobulin Allotypes; D014118:Toxins, Biological