MULTIPLE SCLEROSIS: SOME ASPECTS ON PATHOGENESIS AND MORPHOLOGY
About the author:
Filenko B. M., Roiko N. V., Proskurnia S. A., Sovhyria S. M., Vynnyk N. I.
Type of article:
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.
multiple sclerosis, pathogenesis, morphology
- Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 2006;5:932-6.
- Guseva EY, Zavalyshyna YA, Bojko AN, redaktory. Rasseyannyj skleroz: klynycheskoe rukovodstvo. Moskva: Real Tajm; 2011. 520 s. [in Russiаn].
- Lytvynenko NV, Pinchuk VA, Sylenko GY, Blazhivska YuV, Bordyug YO. Kognityvnyj profil` paciyentiv iz rozsiyanym sklerozom. Problemy ekologiyi ta medycyny. 2012;16(3-4):13-5. [in Ukrainian].
- Shmydt TE, Yakhno NN. Rasseyannyj skleroz: rukovodstvo dlya vrachej. 5-e yzd. Moskva: MEDpress-ynform; 2016. 272 s. [in Russiаn].
- Hammond SR, English DR, McLeod JG. The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia. Brain. 2000;123:968-74.
- Simon KC, Munger KL, Ascherio A. Vitamin D and multiple sclerosis: epidemiology, immunology, and genetics. Current opinion in neurology. 2012;25(3):246-51.
- Hedström AK, Hillert J, Olsson T, Alfredsson L. Smoking and multiple sclerosis susceptibility. Eur J Epidemiol. 2013;28(11):867-74. Available from: https://doi.org/10.1007/s10654-013-9853-4
- Handel AE, Williamson AJ, Disanto G, Dobson R, Giovannoni G. Smoking and Multiple Sclerosis: An Updated Meta-Analysis. PLOS ONE [Internet]. 2011;6(1):e16149. Available from: https://doi.org/10.1371/journal.pone.0016149
- Hayes CE, Acheson ED. A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Medical Hypotheses. 2008;71(1):85-90.
- Ruth AM. Environmental risk factors in multiple sclerosis aetiology. The Lancet Neurology. 2004;3(12):709-18.
- Gilden DH. Infectious causes of multiple sclerosis. The Lancet Neurology. 2005;4(3):195-202.
- Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: The role of infection. Ann Neurol. 2007;61:288-99.
- Popova EV, Bojko AN, Hachanova NV, Sharanova SN. Vyrus Epshtejna-Barr v patogeneze rasseyannogo skleroza (obzor). Zhurnal nevrologyy i psyxyatryy im. S.S. Korsakova. Speczvypusk. 2014;114(2):29-34. [in Russiаn].
- Alvarez-Lafuente R, De Las Heras V, Bartolome M. Human herpesvirus 6 and multiple sclerosis: a one-year follow-up study. Brain Pathol. 2006;16:20-7.
- Bagos PG, Nikolopoulos G, Ioannidis A. Chlamydia pneumoniae infection and the risk of multiple sclerosis: a meta-analysis. Mult Scler. 2006;12:397-411.
- Hernán MA, Zhang SM, Lipworth L, Olek MJ, Ascherio A. Multiple Sclerosis and Age at Infection with Common Viruses. Epidemiology. 2001;12(3):301-6.
- Schneider R. Neuronal degeneration in a viral model of multiple sclerosis. J. Neurosci. 2009;29:153-4.
- Huseby ES, Liggitt D, Brabb Th, Schnabel B, Öhlén C, Goverman J. A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis. Journal of Experimental Medicine. 2001;194(5):669-76.
- Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain. 2006;129(8):1953-71.
- de Bakker PI, McVean G, Sabeti PC, Miretti MM, Green T, Marchini J, et al. A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nat Genet. 2006;38(10):1166-72.
- Hemmer B, Archelos JJ, Hartung H-P. New concepts in the immunopathogenesis of multiple sclerosis. Nat. Rev. Neurosci. 2002;3:291-301.
- Steinman L. Multiple sclerosis: a two-stage disease. Natl. Immunol. 2001;2:762-4.
- Dong C, Flavell RA. Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res. 2000;2:179-88.
- Zavalyshyn YA, Peresedova AV. Rasseyannyj skleroz: sovremennaya koncepcyya patogeneza i patogenetycheskogo lechenyya. Annaly klynycheskoj i eksperymentalnoj nevrologyy. 2007;1(1):32-40. [in Russiаn].
- Minagar A, Alexander JS Blood-brain barrier disruption in multiple sclerosis. Mult Scler. 2003;9(6):540-9.
- Fazekas F, Enzinger C, Wallner-Blazek M. Gender Differences in MRI Studies on Multiple Sclerosis. J. Neurol. Sci. 2009;286:28-30.
- Tomassini V, Pozzilli C. Sex Hormones, Brain Damage and Clinical Course of Multiple Sclerosis. J. Neurol. Sci. 2009;286:35-9.
- Predtechenskaya AV, Nekrasova MF. Rol` polovyh steroydov v patogeneze rasseyannogo skleroza. Vestnyk NGU. Seryya: Byologyya, klynycheskaya medycyna. 2011;9(3):211-8. [in Russiаn].
- Neuhaus O, Archelos JJ, Hartung H-P. Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection. Trends Pharmacol. Sci. 2003;24:131-8.
- Filippi M, Bozzali M, Rovaris M. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain. 2003;126:433-7.
- Bo L. The histopathology of grey matter demyelination in multiple sclerosis. Acta Neurologica Scandinavica. 2009;120:51-7.
- Strukov AI, Syerov VV. Patologichna anatomiya 4-e vyd. Kharkiv: Fakt; 1999. 864 s. [in Ukrainian].
- Bo L, Vedeler C, Nyland H, Traff B. Subpial Demyelination in the Cerebral cortex of Multiple Sclerosis Patients. J. Neuropath. Exp. Neurol. 2003;62(7):723-32.
- Gilmore CP, Bo L, Owens T, Lowe J, Esiri MM, Evangelou N. Spinal Cord Gray Matter Demyelination in Multiple Sclerosis – A Novel Pattern of Residual Plaque Morphology. Brain Pathology. 2006;16:202-8.
- Shmydt TE. Patogenez, lechenye i vedenye bolnykh rasseyannym sklerozom. Nevrologycheskyj zhurnal. 2003;3:46-9. [in Russiаn].
- Paz Soldan MM, Rodriguez M. Heterogeneity of pathogenesis in multiple sclerosis: implications for promotion of remyelination. The Journal of infections diseases. 2002;186(2):248-53.
- Nedzved GK, Nedzved MK. O nozologycheskoj samostoyatelnosty rasseyannogo skleroza. Nejroymmunologyya. 2003;1(2):103-4. [in Russiаn].
- Haikova ON, Bysaha HN, Onyshchenko LS, Chykurova AA. Kharakterystyka hlyalnyh reaktsyi pry rasseiannom skleroze. Neiroymmunolohyia. 2003;1(2):35-6. [in Russiаn].
- Pronina OМ, Koptev MM, Bilash SМ, Yeroshenko HA. Response of hemomicrocirculatory bed of internal organs on various external factors exposure based on the morphological research data. Svit medytsyny ta biolohiyi. 2018;63(1):153-7.
Publication of the article:
«Bulletin of problems biology and medicine» Issue 1 Part 1 (148), 2019 year, 65-70 pages, index UDK 616.832-004.2