Multiple sclerosis: some aspects on pathogenesis and morphology

Abstract

Multiple sclerosis (MS) is a chronic, progressive demyelinating disease of the central nervous system. Currently, the etiology of multiple sclerosis is unknown and considered as the multifactorial disease. Genetic and immunological factors, viral infection and influence of exogenous factors play the crucial role. Genetic susceptibility to multiple sclerosis is confirmed by numerous findings of genealogical, twin and population studies. It has been established that intoxication and diet are considered the most possible external factors. Recently, the impact of insolation and associated vitamin D deficiency, as the main factor of geographical dissemination, smoking and ecological characteristics of the habitat of patients have been the issue for discussion. Viral hypothesis for the development of multiple sclerosis appears to be of main importance, since high IgG concentration to many viruses has been found in the cerebrospinal fluid and blood of more than 90% of patients with MS. Currently, no etiological theory and unambiguous consensus on the pathogenesis of lesions in multiple sclerosis exists. Apparently, no single view on the mechanism of the onset and development of this disease is given. Immunologists consider multiple sclerosis as an autoimmune disease when the specific T-lymphocytes that are myelin antigens activate the inflammatory response in the central nervous system, which eventually leads to demyelination and subsequent damage to the axons. Currently, the studies of the role of genetic disorders are at the forefront in the development of multiple sclerosis. This is substantiated by more frequent detection of A3, B7, DW2, DR2 antigens in patients with MS as compared with healthy people. It is hypothesized that the occurrence of certain combination of tissue histocompatibility antigents in single chromosome and gene of susceptibility to MS is crucial in the onset of the disease. Currently, the pathogenesis of MS is seen as a phased process, involving the initial inflammatory phase, which is accompanied by demyelination, and the neurodegenerative phase. The specific pathomorphological changes in multiple sclerosis are caused by activation of immunological reactions, including macrophages, B-lymphocytes with production of antibodies, which leads to the myelin sheath damage. Immunopathological reaction in MS leads not only to the destruction of myelin, but also to the development of vascular inflammatory and proliferative processes of the derivatives of mesenchyme and glia with subsequent formation of the multiple sclerosis plaques. Macroscopically, no specific changes are revealed during the external examination of the brain and spinal cord in multiple sclerosis, though, sometimes, the edema and thickening of pia mater is noted. The mass of the brain can be reduced. Convolutions of brain are narrowed; sulci between them are broad and deep, indicating about growing atrophic processes. Ependyma is usually smooth, shiny, in some cases is tuberous, due to the subependimal gliosis. Histologically, three types of the plaques are distinguished depending on the stage of morphogenesis: the acute plaques (active foci of demyelination), chronic (inactive foci) and chronic foci with signs of activation. Edema, inflammation, re- and demyelination, gliosis, damage to axons is observed in the development of multiple sclerosis. Demyelination and death of axons lead to atrophy of the brain and spinal cord. Morphologically, the nature and progress of the pathological process, developed in multiple sclerosis, is heterogeneous. It is known that autoimmune responses in MS, manifested by the foci of demyelination, are involved in the pathogenesis of other diseases of the nervous system (inflammatory, vascular, etc.). In addition, the cause of the myelin disintegration can be a chronic hypoxia and metabolic disorders. They are crucial in the differentiated diagnosis of the disease. Multifactorial nature of multiple sclerosis to a certain extent reflects heterogeneity of the demyelinating process.;Сучасна імунологія розглядає розсіяний склероз як аутоімунне захворювання. Макроскопічно під час зовнішнього огляду головного та спинного мозку при розсіяному склерозі характерних змін не відмічають, інколи виявляють набряк і потовщення м’яких мозкових оболонок. Гістологічно, в залежності від стадії морфогенезу, розрізняють три типи бляшок: гострі бляшки (активні осередки демієлінізації), хронічні (неактивні осередки) і хронічні вогнища з ознаками активізації. Гострі активні бляшки формуються внаслідок гострого периваскулярного запалення і проявляються руйнуванням мієліну, набряком тканини мозку. Хронічна неактивна бляшка чітко окреслена, характеризується збільшенням кількості астроцитів, відсутністю активної деструкції мієліну, зменшенням кількості олігодендроцитів, аксональною дегенерацією. З’являються ознаки периваскулярного склерозу. Хронічні активні бляшки характеризуються появою по периферії хронічної неактивної бляшки макрофагів, внаслідок прогресуючого розпаду мієліну, а також Т-лімфоцитів і реактивних астроцитів. Таким чином, при розвитку розсіяного склерозу спостерігаються такі процеси, як набряк, запалення, де- і ремієлінізація, гліоз, ураження аксонів. Демієлінізація і загибель аксонів призводять до атрофії головного і спинного мозку.