ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2024-2-133-141ssmu-5671Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESМикробиота мочевых путей у пациентов с нейрогенной дисфункцией тазовых органов при рассеянном склерозеUrinary tract microbiota in patients with multiple sclerosis and neurogenic pelvic dysfunctionhttps://orcid.org/0000-0002-1652-2925ЛузановаЕ. И.LuzanovaE. I.

Лузанова Екатерина Игоревна – канд. мед. наук, доцент, доцент кафедры нервных болезней 

454092, г. Челябинск, ул. Воровского, 64

64, Vorovskogo Str., Chelyabinsk, 454092

estrochikova@yandex.ruhttps://orcid.org/0000-0001-5848-7235КарповаМ. И.KarpovaM. I.

Карпова Мария Ильинична – д-р мед. наук, доцент, зав. кафедрой нервных болезней 

454092, г. Челябинск, ул. Воровского, 64

64, Vorovskogo Str., Chelyabinsk, 454092

kmi_2008@mail.ruhttps://orcid.org/0000-0001-7086-5657АбрамовскихО. С.AbramovskikhO. S.

Абрамовских Ольга Сергеевна – д-р мед. наук, доцент, зав. кафедрой клинической лабораторной диагностики 

454092, г. Челябинск, ул. Воровского, 64

64, Vorovskogo Str., Chelyabinsk, 454092

abramoschel@mail.ruЧетвернинаЕ. А.ChetverninaE. A.

Четвернина Елена Андреевна – ст. преподаватель, кафедра клинической лабораторной диагностики 

454092, г. Челябинск, ул. Воровского, 64

64, Vorovskogo Str., Chelyabinsk, 454092

elena45r@mail.ruhttps://orcid.org/0000-0001-8141-5547КуприяновС. В.KupriyanovS. V.

Куприянов Семён Вадимович – канд. биол. наук, специалист, отдел научной работы, преподаватель, кафедра биохимии имени Р.И. Лифшица; мл. науч. сотрудник, лаборатория экологии, генетики и охраны окружающей среды 

454092, г. Челябинск, ул. Воровского, 64;634050, Томск, пр. Ленина, 36

64, Vorovskogo Str., Chelyabinsk, 454092;36, Lenina Av., Tomsk, 634050

pfft@mail.ruЮжно-Уральский государственный медицинский университет (ЮУГМУ)РоссияSouth Ural State Medical UniversityRussian FederationЮжно-Уральский государственный медицинский университет (ЮУГМУ); Национальный исследовательский Томский государственный университет (НИ ТГУ)РоссияSouth Ural State Medical University; National Research Tomsk State UniversityRussian Federation202411072024232133141Copyright © Лузанова Е.И., Карпова М.И., Абрамовских О.С., Четвернина Е.А., Куприянов С.В., 20242024Лузанова Е.И., Карпова М.И., Абрамовских О.С., Четвернина Е.А., Куприянов С.В.Luzanova E.I., Karpova M.I., Abramovskikh O.S., Chetvernina E.A., Kupriyanov S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/5671

Рассеянный склероз (РС) является хроническим прогрессирующим заболеванием центральной нервной системы, распространенным среди лиц молодого возраста. Частый симптом болезни – это нейрогенная дисфункция тазовых органов. Молодым людям с диагнозом РС зачастую приходится одновременно принимать решения, связанные с лечением и планированием семьи. Возможность реализации репродуктивных планов тесно связана с урологическими осложнениями заболевания, высоким риском инфекционных процессов мочеполовой системы, сексуальной дисфункцией. Кроме того, многие препараты, изменяющие течение РС, играют значительную роль в увеличении вероятности инфекционных осложнений. В связи с чем актуальной проблемой являются вопросы профилактики инфекций при РС. Эффективная персонализированная профилактика урогенитальных инфекций возможна при четком представлении о составе микробиоты. Методы секвенирования ДНК позволили изменить классические представления о том, что здоровая моча стерильна. Были сформированы представления о бессимптомной бактериурии у здоровых людей, и в последние годы появляются сведения о генитоуробиоме пациентов с неврологическими заболеваниями. Расширение знаний о составе микроорганизмов мочеполовой системы неврологических пациентов необходимы для формирования потенциала здоровьесберегающих технологий. Цель обзора: обобщение известных к настоящему времени сведений о микробиоценозе нижних мочевых путей и влагалища при нейрогенной дисфункции тазовых органов, в том числе при РС, представление данных о связи близко расположенных биотопов и влиянии терапии РС на риски инфекций мочеполовой сферы. 

Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system common among young people. Neurogenic bladder often is a common symptom of the disease. Young people with MS often have to make treatment and family planning decisions at the same time. The possibility of realizing reproductive plans is closely related to urological complications of the disease, high risk of urinary tract infections, and sexual dysfunction. In addition, disease modifying therapies for MS play a significant role in increasing the likelihood of infectious complications. Therefore, the issue of infection prevention in MS is critical. Effective personalized prevention of urogenital infections is possible with a clear understanding of the microbiota composition. DNA sequencing methods have changed the conventional idea that normal urine is sterile and gave rise to the concepts of asymptomatic bacteriuria in healthy people. Moreover, data on the genitourobiome of patients with neurological diseases have recently emerged. Extended knowledge about the microbiology in the genitourinary system of neurological patients is necessary to unleash the capacity of health-preserving technologies. The aim of the review was to integrate currently available data concerning the microbiocenosis of the lower urinary tract and vagina with underlying neurogenic pelvic dysfunction, including MS, as well as to present data on the association between closely located biotopes and the effect of MS therapy on the risks of developing genitourinary infections. 

рассеянный склерознейрогенная дисфункция мочеиспусканиявагинозмикробиотаmultiple sclerosisneurogenic bladdervaginosismicrobiotaРабота выполнена в рамках проекта РНФ № 23-25-10076.ReferencesZangeneh Z., Abdi-Ali A., Khamooshian K., Alvandi A., Abiri R. Bacterial variation in the oral microbiota in multiple sclerosis patients. PLoS One. 2021;16(11):e0260384. DOI: 10.1371/journal.pone.0260384.Zangeneh Z., Abdi-Ali A., Khamooshian K., Alvandi A., Abiri R. Bacterial variation in the oral microbiota in multiple sclerosis patients. PLoS One. 2021;16(11):e0260384. DOI: 10.1371/journal.pone.0260384.Phé V., Chartier-Kastler E., Panicker J.N. Management of neurogenic bladder in patients with multiple sclerosis. Nat. Rev. Urol. 2016;13(5):275–288. DOI: 10.1038/nrurol.2016.53.Phé V., Chartier-Kastler E., Panicker J.N. Management of neurogenic bladder in patients with multiple sclerosis. Nat. Rev. Urol. 2016;13(5):275–288. DOI: 10.1038/nrurol.2016.53.Nelson D.E., Van Der Pol B., Dong Q., Revanna K.V., Fan B., Easwaran S. et al. Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLoS One. 2010;5(11):e14116. DOI: 10.1371/journal.pone.0014116.Nelson D.E., Van Der Pol B., Dong Q., Revanna K.V., Fan B., Easwaran S. et al. Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLoS One. 2010;5(11):e14116. DOI: 10.1371/journal.pone.0014116.Набока Ю.Л., Гудима И.А., Коган М.И., Черницкая М.Л. Микробный спектр мочи молодых здоровых женщин. Урология. 2010;(5):7–10.Набока Ю.Л., Гудима И.А., Коган М.И., Черницкая М.Л. Микробный спектр мочи молодых здоровых женщин. Урология. 2010;(5):7–10.Siddiqui H., Nederbragt A.J., Lagesen K., Jeansson S.L., Jakobsen K.S. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11:244. DOI: 10.1186/1471-2180-11-244.Siddiqui H., Nederbragt A.J., Lagesen K., Jeansson S.L., Jakobsen K.S. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11:244. DOI: 10.1186/1471-2180-11-244.Wolfe A.J., Toh E., Shibata N., Rong R., Kenton K., Fitzgerald M. et al. Evidence of uncultivated bacteria in the adult female bladder. J. Clin. Microbiol. 2012;50(4):1376–1383. DOI: 10.1128/JCM.05852-11.Wolfe A.J., Toh E., Shibata N., Rong R., Kenton K., Fitzgerald M. et al. Evidence of uncultivated bacteria in the adult female bladder. J. Clin. Microbiol. 2012;50(4):1376–1383. DOI: 10.1128/JCM.05852-11.Karstens L., Asquith M., Davin S., Stauffer P., Fair D., Gregory W.T. et al. Does the urinary microbiome play a role in urgency urinary incontinence and its severity? Front. Cell Infect. Microbiol. 2016;6:78. DOI: 10.3389/fcimb.2016.00078.Karstens L., Asquith M., Davin S., Stauffer P., Fair D., Gregory W.T. et al. Does the urinary microbiome play a role in urgency urinary incontinence and its severity? Front. Cell Infect. Microbiol. 2016;6:78. DOI: 10.3389/fcimb.2016.00078.Govender Y., Gabriel I., Minassian V., Fichorova R. The current evidence on the association between the urinary microbiome and urinary incontinence in women. Front. Cell. Infect. Microbiol. 2019;9:133. DOI: 10.3389/ fcimb.2019.00133.Govender Y., Gabriel I., Minassian V., Fichorova R. The current evidence on the association between the urinary microbiome and urinary incontinence in women. Front. Cell. Infect. Microbiol. 2019;9:133. DOI: 10.3389/ fcimb.2019.00133.Коган М.И., Набока Ю.Л., Исмаилов Р.С. Микробиота секрета простаты: сравнительный анализ хронического простатита категорий II и IIIA. Урология. 2020;(2):16–22. DOI: 10.18565/urology.2020.2.16-22.Коган М.И., Набока Ю.Л., Исмаилов Р.С. Микробиота секрета простаты: сравнительный анализ хронического простатита категорий II и IIIA. Урология. 2020;(2):16–22. DOI: 10.18565/urology.2020.2.16-22.Meriwether K.V., Lei Z., Singh R., Gaskins J., Hobson D.T.G., Jala V. The Vaginal and Urinary Microbiomes in Premenopausal Women With Interstitial Cystitis/Bladder Pain Syndrome as Compared to Unaffected Controls: A Pilot Cross-Sectional Study. Front. Cell Infect. Microbiol. 2019;9:92. DOI: 10.3389/fcimb.2019.0009215.Meriwether K.V., Lei Z., Singh R., Gaskins J., Hobson D.T.G., Jala V. The Vaginal and Urinary Microbiomes in Premenopausal Women With Interstitial Cystitis/Bladder Pain Syndrome as Compared to Unaffected Controls: A Pilot Cross-Sectional Study. Front. Cell Infect. Microbiol. 2019;9:92. DOI: 10.3389/fcimb.2019.0009215.Abernethy M.G., Rosenfeld A., White J.R., Mueller M.G., Lewicky-Gaupp C., Kenton K. Urinary microbiome and tokine levels in women with interstitial cystitis. Obstet. Gynecol. 2017;129(3):500–506. DOI: 10.1097/AOG.000000000000189216.Abernethy M.G., Rosenfeld A., White J.R., Mueller M.G., Lewicky-Gaupp C., Kenton K. Urinary microbiome and tokine levels in women with interstitial cystitis. Obstet. Gynecol. 2017;129(3):500–506. DOI: 10.1097/AOG.000000000000189216.Bučević Popović V., Šitum M., Chow C.T., Chan L.S., Roje B., Terzić J. The urinary microbiome associated with bladder cancer. Sci. Rep. 2018;8(1):12157. DOI: 10.1038/s41598-018-29054-w.Bučević Popović V., Šitum M., Chow C.T., Chan L.S., Roje B., Terzić J. The urinary microbiome associated with bladder cancer. Sci. Rep. 2018;8(1):12157. DOI: 10.1038/s41598-018-29054-w.Wu P., Zhang G., Zhao J., Chen J., Chen Y., Huang W. et al. Profiling the urinary microbiota in male patients with bladder cancer in China. Front. Cell Infect. Microbiol. 2018;8:167. DOI: 10.3389/fcimb.2018.00167.Wu P., Zhang G., Zhao J., Chen J., Chen Y., Huang W. et al. Profiling the urinary microbiota in male patients with bladder cancer in China. Front. Cell Infect. Microbiol. 2018;8:167. DOI: 10.3389/fcimb.2018.00167.Коган М.И., Набока Ю.Л., Рыжкин А.В., Васильев О.Н. Микробиота/микробиом мочи и рак мочевого пузыря. Онкоурология. 2020;16(2):97–103. DOI: 10.17650/1726-9776-2020-16-2-97-103.Коган М.И., Набока Ю.Л., Рыжкин А.В., Васильев О.Н. Микробиота/микробиом мочи и рак мочевого пузыря. Онкоурология. 2020;16(2):97–103. DOI: 10.17650/1726-9776-2020-16-2-97-103.Mehta M., Goldfarb D.S., Nazzal L. The role of the microbiome in kidney stone formation. Int. J. Surg. 2016;36:607–612. DOI: 10.1016/j.ijsu.2016.11.024.Mehta M., Goldfarb D.S., Nazzal L. The role of the microbiome in kidney stone formation. Int. J. Surg. 2016;36:607–612. DOI: 10.1016/j.ijsu.2016.11.024.Finucane T.E. «Urinary tract infection» – requiem for a heavyweight. J. Am. Geriatr. Soc. 2017;65(8):1650–1655. DOI: 10.1111/jgs.14907.Finucane T.E. «Urinary tract infection» – requiem for a heavyweight. J. Am. Geriatr. Soc. 2017;65(8):1650–1655. DOI: 10.1111/jgs.14907.Curtiss N., Balachandran A., Krska L., Peppiatt-Wildman C., Wildman S., Duckett J. Age, menopausal status and the bladder microbiome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2018;228:126–129. DOI: 10.1016/j.ejogrb.2018.06.011.Curtiss N., Balachandran A., Krska L., Peppiatt-Wildman C., Wildman S., Duckett J. Age, menopausal status and the bladder microbiome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2018;228:126–129. DOI: 10.1016/j.ejogrb.2018.06.011.Komesu Y.M., Amundsen C.L., Richter H.E., Erickson S.W., Ackenbom M.F., Andy U.U. et al. Refractory urgency urinary incontinence treatment in women: impact of age on outcomes and complications. Am. J. Obstet. Gynecol. 2018;218(1):111. e1–111.e9. DOI: 10.1016/j.ajog.2017.10.006.Komesu Y.M., Amundsen C.L., Richter H.E., Erickson S.W., Ackenbom M.F., Andy U.U. et al. Refractory urgency urinary incontinence treatment in women: impact of age on outcomes and complications. Am. J. Obstet. Gynecol. 2018;218(1):111. e1–111.e9. DOI: 10.1016/j.ajog.2017.10.006.Nicolle L.E., Gupta K., Bradley S.F., Colgan R., DeMuri G.P., Drekonja D. et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the infectious diseases society of America. Clin. Infect. Dis. 2019;68(10):e83–e110. DOI: 10.1093/cid/ciy1121.Nicolle L.E., Gupta K., Bradley S.F., Colgan R., DeMuri G.P., Drekonja D. et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the infectious diseases society of America. Clin. Infect. Dis. 2019;68(10):e83–e110. DOI: 10.1093/cid/ciy1121.Averbeck M.A., Iacovelli V., Panicker J., Schurch B., Agro E.F. Urodynamics in patients with multiple sclerosis: A consensus statement from a urodynamic experts working group. Neurourol. Urodyn. 2020;39(1):73–82. DOI: 10.1002/nau.24230.Averbeck M.A., Iacovelli V., Panicker J., Schurch B., Agro E.F. Urodynamics in patients with multiple sclerosis: A consensus statement from a urodynamic experts working group. Neurourol. Urodyn. 2020;39(1):73–82. DOI: 10.1002/nau.24230.Вялкова А.А., Гриценко В.А. Инфекция мочевой системы у детей: современные аспекты этиологической диагностики и лечения. Российский вестник перинатологии и педиатрии. 2017;62(1):99–108. DOI: 10.21508/1027-40652017-62-1-99-108.Вялкова А.А., Гриценко В.А. Инфекция мочевой системы у детей: современные аспекты этиологической диагностики и лечения. Российский вестник перинатологии и педиатрии. 2017;62(1):99–108. DOI: 10.21508/1027-40652017-62-1-99-108.Pan Y.J., Lin T.L., Chen C.T., Chen Y.-Y., Hsieh P.-F., Hsu C.-R. et al. Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp. Sci. Rep. 2015;5:15573. DOI: 10.1038/srep15573.Pan Y.J., Lin T.L., Chen C.T., Chen Y.-Y., Hsieh P.-F., Hsu C.-R. et al. Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp. Sci. Rep. 2015;5:15573. DOI: 10.1038/srep15573.Набока Ю.Л., Коган М.И., Гудима И.А., Митусова Е.В., Джалагония К.Т., Иванов С.Н. Существует ли взаимосвязь между микробиотой мочи, влагалища и кишечника при инфекции верхних мочевых путей? Вестник урологии. 2019;7(1):38–45. DOI: 10.21886/2308-6424-2019-7-1-38-45.Набока Ю.Л., Коган М.И., Гудима И.А., Митусова Е.В., Джалагония К.Т., Иванов С.Н. Существует ли взаимосвязь между микробиотой мочи, влагалища и кишечника при инфекции верхних мочевых путей? Вестник урологии. 2019;7(1):38–45. DOI: 10.21886/2308-6424-2019-7-1-38-45.Nielsen K.L., Stegger M., Kiil K., Godfrey P.A., Feldgarden M., Lilje B. et al. Whole-genome comparison of urinary pathogenic Escherichia coli and faecal isolates of UTI patients and healthy controls. Int. J. Med. Microbiol. 2017;307(8):497–507. DOI: 10.1016/j.ijmm.2017.09.007.Nielsen K.L., Stegger M., Kiil K., Godfrey P.A., Feldgarden M., Lilje B. et al. Whole-genome comparison of urinary pathogenic Escherichia coli and faecal isolates of UTI patients and healthy controls. Int. J. Med. Microbiol. 2017;307(8):497–507. DOI: 10.1016/j.ijmm.2017.09.007.Fouts D.E., Pieper R., Szpakowski S., Pohl H., Knoblach S., Suh M.-J. et al. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J. Transl. Med. 2012;10:174. DOI: 10.1186/1479-5876-10-174.Fouts D.E., Pieper R., Szpakowski S., Pohl H., Knoblach S., Suh M.-J. et al. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J. Transl. Med. 2012;10:174. DOI: 10.1186/1479-5876-10-174.Dong Q., Nelson D.E., Toh E., Diao L., Gao X., Fortenberry J.D. et al. The microbial communities in male first catch urine are highly similar to those in paired urethral swab specimens. PLoS One. 2011;6(5):e19709. DOI: 10.1371/journal.pone.00197095.Dong Q., Nelson D.E., Toh E., Diao L., Gao X., Fortenberry J.D. et al. The microbial communities in male first catch urine are highly similar to those in paired urethral swab specimens. PLoS One. 2011;6(5):e19709. DOI: 10.1371/journal.pone.00197095.Филиппова Е.С., Баженов И.В., Зырянов А.В. Влияет ли ботулинотерапия на микробиом мочи больных нейрогенным мочевым пузырём? Результаты метагеномного секвенирования. Вестник урологии. 2020;8(3):85–96. DOI: 10.21886/2308-6424-2020-8-3-85-96.Филиппова Е.С., Баженов И.В., Зырянов А.В. Влияет ли ботулинотерапия на микробиом мочи больных нейрогенным мочевым пузырём? Результаты метагеномного секвенирования. Вестник урологии. 2020;8(3):85–96. DOI: 10.21886/2308-6424-2020-8-3-85-96.Lapides J., Diokno A.C., Silber S.J., Lowe B.S. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J. Urol. 1972;107(3):458–461. DOI: 10.1016/s0022-5347(17)61055-3.Lapides J., Diokno A.C., Silber S.J., Lowe B.S. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J. Urol. 1972;107(3):458–461. DOI: 10.1016/s0022-5347(17)61055-3.Vasudeva P., Madersbacher H. Factors implicated in pathogenesis of urinary tract infections in neurogenic bladders: some revered, few forgotten, others ignored. Neurourol. Urodyn. 2014;33(1):95–100. DOI: 10.1002/nau.22378.Vasudeva P., Madersbacher H. Factors implicated in pathogenesis of urinary tract infections in neurogenic bladders: some revered, few forgotten, others ignored. Neurourol. Urodyn. 2014;33(1):95–100. DOI: 10.1002/nau.22378.Moiola L., Barcella V., Benatti S., Capobianco M., Capra R., Cinque P. et al. The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement. Mult. Scler. 2021;27(3):331–346. DOI: 10.1177/1352458520952311.Moiola L., Barcella V., Benatti S., Capobianco M., Capra R., Cinque P. et al. The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement. Mult. Scler. 2021;27(3):331–346. DOI: 10.1177/1352458520952311.Mesgarof M.A., Fattahi M.R., Hemmati Z., Iranmehr A., Azizi H., Rahimi S. Genitourinary infectious complications in patients with multiple sclerosis and their association with disease modifying therapies. Translat Res. Urol. 2022;4(2):98–103. DOI: 10.22034/tru.2022.346350.1114.Mesgarof M.A., Fattahi M.R., Hemmati Z., Iranmehr A., Azizi H., Rahimi S. Genitourinary infectious complications in patients with multiple sclerosis and their association with disease modifying therapies. Translat Res. Urol. 2022;4(2):98–103. DOI: 10.22034/tru.2022.346350.1114.De Medeiros Junior W.L.G., Demore C.C., Mazaro L.P., de Souza M.F.N., Parolin L.F., Melo L.H. et al. Urinary tract infection in patients with multiple sclerosis: an overview. Mult. Scler. Relat. Disord. 2020;46:102462. DOI: 10.1016/j.msard.2020.102462.De Medeiros Junior W.L.G., Demore C.C., Mazaro L.P., de Souza M.F.N., Parolin L.F., Melo L.H. et al. Urinary tract infection in patients with multiple sclerosis: an overview. Mult. Scler. Relat. Disord. 2020;46:102462. DOI: 10.1016/j.msard.2020.102462.Hellgren J., Risedal A., Källén K. Rituximab in multiple sclerosis at general hospital level. Acta Neurol. Scand. 2020;141(6):491–499. DOI: 10.1111/ane.13225.Hellgren J., Risedal A., Källén K. Rituximab in multiple sclerosis at general hospital level. Acta Neurol. Scand. 2020;141(6):491–499. DOI: 10.1111/ane.13225.Chisari C.G., Sgarlata E., Arena S., Toscano S., Luca M., Patti F. Rituximab for the treatment of multiple sclerosis: a review. J. Neurol. 2022;269(1):159–183. DOI: 10.1007/s00415-020-10362-z.Chisari C.G., Sgarlata E., Arena S., Toscano S., Luca M., Patti F. Rituximab for the treatment of multiple sclerosis: a review. J. Neurol. 2022;269(1):159–183. DOI: 10.1007/s00415-020-10362-z.Coles A.J., Twyman C.L., Arnold D.L., Cohen J.A., Confavreux C., Fox E.J. et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: A randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–1839. DOI: 10.1016/S0140-6736(12)61768-1.Coles A.J., Twyman C.L., Arnold D.L., Cohen J.A., Confavreux C., Fox E.J. et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: A randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–1839. DOI: 10.1016/S0140-6736(12)61768-1.Reder A.T., Oger J.F., Kappos L., O’Connor P., Rametta M. Shortterm and long-term safety and tolerability of interferon β-1b in multiple sclerosis. Mult. Scler. Relat. Disord. 2014;3(3):294–302. DOI: 10.1016/j.msard.2013.11.005.Reder A.T., Oger J.F., Kappos L., O’Connor P., Rametta M. Shortterm and long-term safety and tolerability of interferon β-1b in multiple sclerosis. Mult. Scler. Relat. Disord. 2014;3(3):294–302. DOI: 10.1016/j.msard.2013.11.005.Cree B.A., Goldman M.D., Corboy J.R., Singer B.A., Fox E.J., Arnold D.L. et al. Efficacy and safety of 2 fingolimod doses vs glatiramer acetate for the treatment of patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA Neurol. 2021;78(1):48–60. DOI: 10.1001/jamaneurol.2020.2950.Cree B.A., Goldman M.D., Corboy J.R., Singer B.A., Fox E.J., Arnold D.L. et al. Efficacy and safety of 2 fingolimod doses vs glatiramer acetate for the treatment of patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA Neurol. 2021;78(1):48–60. DOI: 10.1001/jamaneurol.2020.2950.Butzkueven H., Kappos L., Wiendl H., Trojano M., Spelman T., Chang I. et al. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J. Neurol. Neurosurg. Psychiatry. 2020;91(6):660–668. DOI: 10.1136/jnnp-2019-322326.Butzkueven H., Kappos L., Wiendl H., Trojano M., Spelman T., Chang I. et al. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J. Neurol. Neurosurg. Psychiatry. 2020;91(6):660–668. DOI: 10.1136/jnnp-2019-322326.Makris G.M., Mene J., Fotiou A., Xyla V., Battista M.J., Sergentanis T.N. Gynecological adverse effects of natalizumab administration: Case report and review of the literature. Mult. Scler. Relat. Disord. 2018;25:46–49. DOI: 10.1016/j.msard.2018.07.024.Makris G.M., Mene J., Fotiou A., Xyla V., Battista M.J., Sergentanis T.N. Gynecological adverse effects of natalizumab administration: Case report and review of the literature. Mult. Scler. Relat. Disord. 2018;25:46–49. DOI: 10.1016/j.msard.2018.07.024.Rommer P., Zettl U., Kieseier B., Hartung H., Menge T., Frohman E. et al. Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Clin. Exp. Immunol. 2014;175(3):397–407. DOI: 10.1111/cei.12206.Rommer P., Zettl U., Kieseier B., Hartung H., Menge T., Frohman E. et al. Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Clin. Exp. Immunol. 2014;175(3):397–407. DOI: 10.1111/cei.12206.Brimelow R.E. Modifying therapies for the treatment of relapse-remitting multiple sclerosis. Br. J. Healthc. Manag. 2017;23(10):468–476.Brimelow R.E. Modifying therapies for the treatment of relapse-remitting multiple sclerosis. Br. J. Healthc. Manag. 2017;23(10):468–476.Filikci Z., Jensen R.M., Sellebjerg F.T. Inflammatory vaginitis associated with long-term rituximab treatment in a patient with multiple sclerosis. BMJ Case Rep. 2022;15(11):e250425. DOI: 10.1136/bcr-2022-250425.Filikci Z., Jensen R.M., Sellebjerg F.T. Inflammatory vaginitis associated with long-term rituximab treatment in a patient with multiple sclerosis. BMJ Case Rep. 2022;15(11):e250425. DOI: 10.1136/bcr-2022-250425.Lee J.M., Han M.H. Patient experience and practice trends in multiple sclerosis – clinical utility of fingolimod. Patient Prefer Adherence. 2015;9:685–693. DOI: 10.2147/PPA.S57354.Lee J.M., Han M.H. Patient experience and practice trends in multiple sclerosis – clinical utility of fingolimod. Patient Prefer Adherence. 2015;9:685–693. DOI: 10.2147/PPA.S57354.Rafiee Zadeh A., Askari M., Azadani N.N., Ataei A., Ghadimi K., Tavoosi N. et al. Mechanism and adverse effects of multiple sclerosis drugs: a review article. Part 1. Int. J. Physiol. Pathophysiol. Pharmacol. 2019;1(4):95–104.Rafiee Zadeh A., Askari M., Azadani N.N., Ataei A., Ghadimi K., Tavoosi N. et al. Mechanism and adverse effects of multiple sclerosis drugs: a review article. Part 1. Int. J. Physiol. Pathophysiol. Pharmacol. 2019;1(4):95–104.Roman C., Menning K. Treatment and disease management of multiple sclerosis patients: A review for nurse practitioners. J. Am. Assoc. Nurse Pract. 2017;29(10):629–638. DOI: 10.1002/2327-6924.12514.Roman C., Menning K. Treatment and disease management of multiple sclerosis patients: A review for nurse practitioners. J. Am. Assoc. Nurse Pract. 2017;29(10):629–638. DOI: 10.1002/2327-6924.12514.

The authors declare that there are no conflicts of interest present.