Z.A. GONCHAROVA¹, Yu.Yu. POGREBNOVA¹, Yu.V. TRINITATSKIY², T.V. SYCHEVA²

 ¹Rostov State Medical University, Rostov-on-Don

²Rostov regional clinical hospital, Rostov-on-Don

 Contact details:

 Goncharova Z.A. — MD, Associate Professor, Professor of the Department of Nervous Diseases and Neurosurgery, Head of the Neurology Center

Address: 29 Nakhichevansky av., Russian Federation, Rostov-on-Don, 344000, tel.: +7-909-421-22-46, e-mail: centrms@mail.ru

To optimize the management of patients with familial multiple sclerosis (MS) by identifying the clinical and epidemiological features of the disease course.

Material and methods. The object of the study was 2253 patients with clinically reliable MS according to McDonald criteria (2010, 2017) living in the Rostov region. Statistical analysis of the results was processed using the application package Excel, Statistics 13.0 MacOSX (Apple Inc., USA). Data analysis was carried out using the 2 criterion. The significance of differences was assessed using the Student’s t-test; the differences were considered statistically significant at p < 0,05.

Results. 108 family cases were identified in the analyzed population of the Rostov region (2 or more MS patients in a family). The overall risk of recurrence among the population of the Rostov region was 4,8%, the family risk of recurrence was 2,7%. The M:F ratio is 1:3,5, the age of debut in the first generation exceeded the age of debut in subsequent generations on average by 5,9 (0,1) years. The duration of the first remission in the family MS group (2,4 (1,0) years), and the average rate of progression was 0.5 (0,1) points per year.

Conclusions. In most families, the «ancestor» of MS was a woman, this fact indicates a possible role of mitochondria in the pathogenesis of the disease. Genealogical analysis of the evidence in favor of non-mendelian types of inheritance. A burdened family history is an unfavorable prognostic factor for the course of MS, which should be taken into account when determining the patient’s management tactics.

Key words: Multiple sclerosis, epidemiology, familial multiple sclerosis.

REFERENCES

1. Gusev E.I., Boyko A.N., Zavalishin I.A. Epidemiologicheskie issledovaniya rasseyannogo skleroza: metod. rekomendatsii MZRF [Epidemiological studies of multiple sclerosis: method. recommendations of the MZRF], 2003.
2. Gusev E.I., Zavalishin I.A., Boyko A.N. Rasseyannyy skleroz i drugie demieliniziruyushchie zabolevaniya [Multiple sclerosis and other demyelinating diseases]. Miklosh, 2004.
3. Zaplakhova O.V., Timasheva Ya.R., Bakhtiyarova K.Z. et al. Clinical and molecular genetic analysis of a case of familial multiple sclerosis in the Republic of Bashkortostan. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. Spetsvypuski, 2017, vol. 117, no. 2, pp. 31–41 (in Russ.).
4. Rima R. A Rare Case of Familial Multiple Sclerosis. J Neurol Disord, 2015.
5. Mohammad H.H., Farzad F., Payam S. Worldwide Prevalence of Familial Multiple Sclerosis: A Systematic Review and Meta-Analysis. Mult Scler Relat Disord., 2018, vol. 20, pp. 43–47.
6. Vanesa P., Matías-GuiuJ.A., Torre-Fuentes L. Familial Multiple Sclerosis and Association with Other Autoimmune Diseases. Brain Behav, 2017, vol. 19, no. 8 (1).
7. Rodriguez A.R., Anibarro L.G., Soto M.D. et al. Familial Multiple Sclerosis: An Epidemiological Study in Pontevedra, Spain. Neurol, 2018, vol. 90 (15), p. 2.396.
8. Binzer M., Forsgren L., Holmgren G. et al. Familial clestering of multiple sclerosis in a Northern Swedish Rural District. J Neurol Neurosurg Psych, 1994, vol. 57, pp. 497–499.
9. Charcot J.-M. Histologie de la sclérose en plaques. Gaz Hopitaux, 1868, vol. 41, pp. 554–555
10. Kurtzke J.F. Familial incidence and geography in multiple sclerosis. Acta Neurologica Scandinavica, 1965, vol. 41 (2), pp. 127–139.
11. Zaplakhova O.V., Magzhanov R.V., Rakhmatullin A.R. et al. A rare case of familial multiple sclerosis in the Republic of Bashkortostan. Vestnik NGU. Seriya: Biologiya, klinicheskaya meditsina, 2015, vol. 13, no. 1, pp. 52–55 (in Russ.).
12. IMSGC. Evidence for Polygenic Susceptibility to Multiple Sclerosis — The Shape of Things to Come. The American Journal of Human Genetics, 2010, vol. 86 (4), pp. 621–625.
13. Karnaukh V.N., Barabash I.A. The course of multiple sclerosis in the Amur region according to a prospective study for the period 1970–2007. Dal’nevostochnyy meditsinskiy zhurnal, 2009, vol. 1, pp. 71–72 (in Russ.).
14. Farrall M. Mapping genetic susceptibility to multiple sclerosis. The Lancet, 1996, vol. 3, no. 48 (90 43), pp. 1674–1675.
15. Suslina Z.A., Zakharova M.N., Zavalishin I.A. et al. Protocol of management of patients «Multiple sclerosis». Problemy standartizatsii v zdravookhranenii, 2006, vol. 2, pp. 25–98 (in Russ.).
16. Istanbul brain hospital. Rasseyannyy skleroz [Istanbul brain hospital. Multiple sclerosis], available at: https://npistanbul.com/ru/rasseyannyy-skleroz-rs.2020
17. Koch-Henriksen N., Rasmussen S., Stenager E. et al. The Danish Multiple Sclerosis Registry. History, data collection and validity. Dan. Med. Bull, 2001, vol. 48, pp. 91–94.
18. O’Gorman C., Lin R., StankovichJ. et al. Modelling genetic susceptibility to multiple sclerosis with family data. Neuroepidemiology, 2013, vol. 40 (1), pp. 1–12.
19. Ebers G.C., Sadovnick A.D., Dyment D.A. et al. Parent-of-origin effect in multiple sclerosis: observations in half-siblings. The Lancet, 2004, vol. 363, pp. 1773–1774.
20. Criswell L., Pfeiffer K., Lum R. et al. Analysis of Families in the Multiple Autoimmune Disease Genetics Consortium (MADGC) Collection: the PTPN22 620W Allele Associates with Multiple Autoimmune Phenotypes. The American Journal of Human Genetics, 2005, vol. 76 (4), pp. 561–571.
21. Willer C., Dyment D., Risch N. et al. Twin concordance and sibling recurrence rates in multiple sclerosis. Proceedings of the National Academy of Sciences, 2003, vol. 100 (22), pp. 12 877–12 882.
22. Goncharova Z.A., Balyazin V.A., Sekhveĭl S.M. et al. Clinical and epidemiological features of multiple sclerosis in children of the Rostov region. Voprosy prakticheskoy pediatrii, 2011, vol. 6 (6), pp. 47–50 (in Russ.).
23. Goncharova Z.A. Kliniko-epidemiologicheskaya kharakteristika rasseyannogo skleroza (prospektivnoe 20-letnee issledovanie): avtoref. dis…. dokt. med. nauk [Clinical and epidemiological characteristics of multiple sclerosis (prospective 20-year study). Synopsis of dis. Dr med. sciences]. Ivanovo, 2013. 41 p.
24. Goncharova Z.A., Fomina-Ertousova M.A. Family cases of multiple sclerosis in the patient population of the Rostov region. Neyroimmunologiya, 2007, vol. 5 (2), pp. 80-1 (in Russ.).
25. Sadovnick A., Yee I., Guimond C. et al. Age of onset in concordant twins and other relative pairs with multiple sclerosis. American journal of epidemiology, 2009, vol. 170 (3), pp. 289–296.
26. Guseva E.I., Zavalishina I.A., Boyko A.N. Rasseyannyy skleroz [Multiple sclerosis]. Real Taym., 2011. 520 p.
27. Westerlind H., Ramanujam R., Uvehag D. Modest Familial Risks for Multiple Sclerosis: A Registry-Based Study of the Population of Sweden. Brain, 2014, vol. 137 (3), pp. 770–778.
28. Korobko D.S., Malkova N.A., Bulatova E.V. et al. The influence of genetic factors on the phenotypic expression of multiple sclerosis. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova (Rasseyannyy skleroz), 2013, vol. 113, no. 2, pp. 10–16 (in Russ.).
29. Song J., Westerlind H., McKay K.A. et al. Familial risk of early-and late-onset multiple sclerosis: a Swedish nationwide study. J. Neurol, 2019, vol. 266 (2), pp. 481–486.
30. Vanesa P., Matias-Guiu J.A., Torre-Fuentes L. Differences in age of diagnosis in familial multiple sclerosis. Multiple Sclerosis, 2019, vol. 34, p. 91.
31. Zavalina T.V., Trushnikova T.N., Shutov A.A. Family observation of multiple sclerosis in the Perm region. Byulleten’ sibirskoy meditsiny, 2009, vol. 8, no. 1 (2), pp. 103–105 (in Russ.).
32. Goncharova Z.A., Pogrebnova Yu.Yu., Dolgiy B.A. Dynamics of epidemiological indicators of multiple sclerosis in Rostov-on-Don. Zhurnal nevrologii i psikhiatrii, 2018, vol. 8, no. 2, p. 135 (in Russ.).
33. Bakhtiyarova K.Z. Rasseyannyy skleroz v respublike Bashkortostan: kliniko-epidemiologicheskoe i molekulyarno-geneticheskoe izuchenie: avtoref. disc. … dokt. med. nauk [Multiple sclerosis in the Republic of Bashkortostan: clinical-epidemiological and molecular-genetic study. Synopsis of dis. Dr med. sciences]. Moscow, 2007. 42 p.
34. Goncharova Z.A., Pogrebnova Yu.Yu. Clinical and epidemiological features of familial multiple sclerosis. Saratov J. Med. Sci. Res, 2020, vol. 1, pp. 416–419 (in Russ.).
35. Masterman T., Ligers A., Olsson T. et al. HLA- DR15 is associated with lower age at onset in multiple sclerosis. Annals of Neurology, 2000, vol. 48 (2), pp. 211–219.