Multiple Sclerosis: Current Perspectives on Disease Mechanisms, Clinical Management, and Therapeutic Advances
DOI:
https://doi.org/10.12775/QS.2026.77.76168Keywords
Multiple sclerosis, autoimmune disorder, demyelination, nonspecific clinical presentation, MRI, immunoregulators, CAR-T, mental health, sexualityAbstract
Background: Multiple sclerosis (MS) is a disease whose incidence has been increasing statistically alongside the development and wider availability of advanced diagnostic methods. Despite extensive research investigating its etiology, clinical course, and therapeutic approaches, considerable uncertainty remains regarding many aspects of the disease.
Aim: This review aims to synthesize current scientific evidence, contextualize recent findings within the existing database of literature, and relate them to the practical needs of patients living with MS.
Materials and Methods: A literature search was conducted using the PubMed, Google Scholar, MEDLINE, and Journal of Education, Health and Sport (JEHS) databases. Relevant studies and meta-analyses addressing various aspects of this complex and heterogeneous disease were identified and analyzed.
Results: The available evidence clearly indicates that, owing to its high diagnostic sensitivity, magnetic resonance imaging (MRI) remains the gold standard for the diagnosis of MS. Therapeutic management continues to rely predominantly on well-established immunosuppressive and immunomodulatory agents, which constitute the cornerstone of current treatment strategies.
Conclusions: Current knowledge has enabled the identification of emerging directions in MS diagnostics, including the increasing use of Visual Evoked Potentials (VEP), Optical Coherence Tomography (OCT), and greater recognition of the nonspecific clinical manifestations that may accompany the disease. This review also highlights existing research gaps concerning more selective therapeutic approaches, such as alemtuzumab, cladribine, and chimeric antigen receptor T-cell (CAR-T) therapy. Furthermore, theoretical and patient-centered domains—including mental health and sexual functioning among individuals with MS—remain insufficiently explored and warrant further investigation in future research.
References
1 Du L, Xi H, Zhang S, Zhou Y, Tao X, Lv Y, Hou X, Yu L. Effects of exercise in people with multiple sclerosis: a systematic review and meta-analysis. Front Public Health. 2024;12:1387658. https://doi.org/10.3389/fpubh.2024.1387658
2 Ordoñez-Rodriguez A, Roman P, Rueda-Ruzafa L, Campos-Rios A, Cardona D. Changes in gut microbiota and multiple sclerosis: a systematic review. Int J Environ Res Public Health. 2023;20(5):4624. https://doi.org/10.3390/ijerph20054624
3 Greenfield AL, Hauser SL. B-cell therapy for multiple sclerosis: entering an era. Ann Neurol. 2018;83(1):13-26. https://doi.org/10.1002/ana.25119
4 Montalban X, Matthews PM, Simpson A, Petrie JL, Sammon C, Ramagopalan S, Disanto G, Kuhle J. Real-world evaluation of ocrelizumab in multiple sclerosis: a systematic review. Ann Clin Transl Neurol. 2023;10(3):302-311. https://doi.org/10.1002/acn3.51732
5 Zakrzewska-Pniewska B, Adamczyk-Sowa M, Brola W, Kalinowska A, Kułakowska A, Losy J, Mirowska-Guzel D, Potemkowski A, Rejdak K, Sarzyńska-Długosz I, Siger M, Zaborski J, Bartosik-Psujek H. Leczenie i postępowanie objawowe w stwardnieniu rozsianym. Rekomendacje Sekcji SM i Neuroimmunologii Polskiego Towarzystwa Neurologicznego. Pol Przegl Neurol. 2019;15(4):191-217. https://doi.org/10.5603/PPN.2019.0033
6 Samjoo IA, Drudge C, Walsh S, Tiwari S, Brennan R, Boer I, Häring DA, Klotz L, Adlard N, Banhazi J. Comparative efficacy of therapies for relapsing multiple sclerosis: a systematic review and network meta-analysis. J Comp Eff Res. 2023;12(7):e230016. https://doi.org/10.57264/cer-2023-0016
7 Ministry of Health (Poland). Chorobowość stwardnienia rozsianego w Polsce [Internet]. Warsaw (Poland): Ministry of Health; [cited 2026 Jun 11]. Available from: https://analizy.mz.gov.pl/html/zpa_sm/chorobowosc.html
8 Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: a comprehensive review. J Autoimmun. 2015;64:13-25. https://doi.org/10.1016/j.jaut.2015.06.010
9. Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV. An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One. 2010;5(9):e12496. https://doi.org/10.1371/journal.pone.0012496
10 Lang HLE, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P, Søndergaard L, Svejgaard A, Wucherpfennig KW, Stuart DI, Bell JI, Jones EY, Fugger L. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol. 2002;3(10):940-943. https://doi.org/10.1038/ni835
11 Tracy SI, Kakalacheva K, Lünemann JD, Luzuriaga K, Middeldorp J, Thorley-Lawson DA. Persistence of Epstein-Barr virus in self-reactive memory B cells. J Virol. 2012;86(22):12330-12340. https://doi.org/10.1128/JVI.01699-12
12 Giovannoni G, Cutter G, Sormani MP, Belachew S, Hyde R, Koendgen H, Knappertz V, Tomic D, Leppert D, Herndon R, Wheeler-Kingshott CAM, Ciccarelli O, Selwood D, Verdun di Cantogno E, Ben-Amor AF, Matthews P, Carassiti D, Baker D, Schmierer K. Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses. Mult Scler Relat Disord. 2017;12:70-78. https://doi.org/10.1016/j.msard.2017.01.007
13. Pearce JMS. Historical descriptions of multiple sclerosis. Eur Neurol. 2005;54(1):49-53. https://doi.org/10.1159/000087387
14 Karussis D. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun. 2014;48-49:134-142. https://doi.org/10.1016/j.jaut.2014.01.022
15 Lassmann H. Pathology and disease mechanisms in different stages of multiple sclerosis. J Neurol Sci. 2013;333(1-2):1-4. https://doi.org/10.1016/j.jns.2013.05.010
16 Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338(5):278-285. https://doi.org/10.1056/NEJM199801293380502
17 Prineas JW, Kwon EE, Cho ES, Sharer LR, Barnett MH, Oleszak EL, Hoffman B, Morgan BP. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50(5):646-657. https://doi.org/10.1002/ana.1255
18 Correale J, Gaitán MI, Ysrraelit MC, Fiol MP. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. 2017;140(3):527-546. https://doi.org/10.1093/brain/aww258
19 Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol. 2019;26(1):27-40. https://doi.org/10.1111/ene.13819
20 Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. 2017;19(1):1-10. https://doi.org/10.22074/cellj.2016.4867
21 Oliva Ramirez A, Keenan A, Kalau O, Worthington E, Cohen L, Singh S. Prevalence and burden of multiple sclerosis-related fatigue: a systematic literature review. BMC Neurol. 2021;21(1):468. https://doi.org/10.1186/s12883-021-02396-1
22 Olek MJ, Howard J. Evaluation and diagnosis of multiple sclerosis in adults. In: UpToDate. Waltham (MA): UpToDate Inc. Accessed 2026 Jun 7. Available from: https://www.uptodate.com/contents/evaluation-and-diagnosis-of-multiple-sclerosis-in-adults
23 Shah P. Symptomatic management in multiple sclerosis. Ann Indian Acad Neurol. 2015;18(Suppl 1):S35-S42. https://doi.org/10.4103/0972-2327.164827
24 Chwastiak LA, Ehde DM. Psychiatric issues in multiple sclerosis. Psychiatr Clin North Am. 2007;30(4):803-817. https://doi.org/10.1016/j.psc.2007.07.003
25 Ford H. Clinical presentation and diagnosis of multiple sclerosis. Clin Med (Lond). 2020;20(4):380-383. https://doi.org/10.7861/clinmed.2020-0292
26 Boski N, Gulati V, Raj R, Gulati P. Multiple sclerosis-minimizing errors in radiological diagnosis. Neurol India. 2021;69(6):1539-1546. https://doi.org/10.4103/0028-3886.333497
27 Okuda DT, Siva A, Kantarci O, Inglese M, Katz I, Tutuncu M, Keegan BM, Donlon S, Hua LH, Vidal-Jordana A, Montalban X, Rovira A, Tintoré M, Amato MP, Brochet B, de Seze J, Brassat D, Vermersch P, De Stefano N, Sormani MP, Pelletier D, Lebrun C, Radiologically Isolated Syndrome Consortium (RISC), Club Francophone de la Sclérose en Plaques (CFSEP). Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One. 2014;9(3):e90509. https://doi.org/10.1371/journal.pone.0090509
28 Cohen JA. 2024 revision of the McDonald diagnostic criteria for MS: substantial and substantive changes. Mult Scler. 2025;31(11):1269-1275. https://doi.org/10.1177/13524585251351860
29 Brownlee WJ, Maccarrone D, Nistri R, Yam C, Wilson H, Wright S, et al. Performance of the 2024 McDonald Criteria in patients under evaluation for suspected multiple sclerosis. Neurology. 2026;106(6):e214688. https://doi.org/10.1212/WNL.0000000000214688
30 European Medicines Agency. Tysabri (natalizumab): summary of product characteristics [Internet]. 2026 [cited 2026 Jun 3]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/tysabri
31 European Medicines Agency. Gilenya (fingolimod): summary of product characteristics [Internet]. 2026 [cited 2026 Jun 3]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/gilenya
32 European Medicines Agency. Ocrevus (ocrelizumab): summary of product characteristics [Internet]. 2025 [cited 2026 Jun 3]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ocrevus
33 European Medicines Agency. Avonex (interferon beta-1a): summary of product characteristics [Internet]. [cited 2026 Jun 4]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/avonex
34 Teva Pharmaceuticals Europe B.V. Copaxone (glatiramer acetate): summary of product characteristics [Internet]: Teva Pharmaceuticals Europe B.V.; [cited 2026 Jun 3]. Available from: https://www.medicines.org.uk/emc/product/7046/smpc#gref
35 European Medicines Agency. Aubagio (teriflunomide): summary of product characteristics [Internet]. [cited 2026 Jun 3]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/aubagio
36 European Medicines Agency. Lemtrada (alemtuzumab): summary of product characteristics [Internet]. [cited 2026 Jun 3]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/lemtrada
37 European Medicines Agency. Mavenclad (cladribine): summary of product characteristics [Internet]. [cited 2026 Jun 3]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/mavenclad
38 Fischbach F, Richter J, Pfeffer LK, Fehse B, Berger SC, Reinhardt S, Kuhle J, Badbaran A, Rathje K, Gagelmann N, Borie D, Seibel J, Ayuk F, Friese MA, Heesen C, Kröger N. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med (N Y). 2024;5(6):550-558.e2. https://doi.org/10.1016/j.medj.2024.03.002
39 Ortuño-Sahagún D, Hermosillo-Abundis C, Reyes-Mata MP, Arias Carrión Ó. CAR T cells for multiple sclerosis: engineering T cells to disrupt chronic B cell-driven neuroinflammation. Mult Scler Relat Disord. 2025;104:106812. https://doi.org/10.1016/j.msard.2025.106812
40. Konitsioti AM, Prüss H, Laurent S, Fink GR, Heesen C, Warnke C. Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review. J Neurol. 2024;271(10):6526-6542. https://doi.org/10.1007/s00415-024-12642-4
41 Maciejowska-Szydło K, Puz P. Early prognostic factors in multiple sclerosis: clinical and therapeutic implications. Medicina (Kaunas). 2026;62(3):475. https://doi.org/10.3390/medicina62030475
42 Çinar BP, Yorgun YG. What we learned from the history of multiple sclerosis measurement: Expanded Disability Status Scale. Noro Psikiyatr Ars. 2018;55(Suppl 1):S69-S75. https://doi.org/10.29399/npa.23343
43 Guerra T, Copetti M, Achille M, Ferri C, Simone M, D’Alfonso S, et al. Refining prognostic factors in adult-onset multiple sclerosis: a narrative review of current insights. Int J Mol Sci. 2025;26(16):7756. https://doi.org/10.3390/ijms26167756
44 Hedström AK, Olsson T, Alfredsson L. Determinants and prognostic value of onset symptoms in multiple sclerosis. J Neurol. 2025;273(1):2. https://doi.org/10.1007/s00415-025-13536-9
45 Kuutti K, Laakso SM, Viitala M, Atula S, Soilu-Hänninen M. Mortality and causes of death for people with multiple sclerosis: a Finnish nationwide register study. J Neurol. 2025;272(5):370. https://doi.org/10.1007/s00415-025-13112-1
46 Tafti D, Ehsan M, Xixis KL. Multiple sclerosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [updated 2024 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499849/
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Copyright (c) 2026 Bartosz Seroczyński, Anna Zyskowska, Gabriela Pyrka, Julia Szopa, Marta Sikorra, Aleksandra Cichowicz, Karolina Paprocka, Bartosz Mikołajek, Justyna Morawska, Arleta Gieniec

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