Progressive multiple sclerosis in the light of the latest findings


Authors: D. Šťastná 1;  I. Menkyová 1,2;  D. Horáková 1
Authors‘ workplace: Neurologická klinika a Centrum klinických neurověd 1. LF UK a VFN v Praze 1;  II. neurologická klinika LF UK a UNB, Bratislava, Slovensko 2
Published in: Cesk Slov Neurol N 2023; 86(1): 10-17
Category: Review Article
doi: https://doi.org/10.48095/cccsnn202310

Overview

Multiple sclerosis is a serious chronic neurological disease. In pathogenesis, both the inflammatory process and inflammation-triggered neurodegeneration play a role from the beginning. Their ratio is the basis for the clinical phenotype. The latest classification takes this into account and divides MS into relapsing and progressive (primary/secondary), where both phenotypes might be active or inactive. Although neurodegeneration is predominant in progressive forms, an inflammatory component is present in all phenotypes and can be therapeutically influenced. Therefore, it is important to identify progression early and provide adequate therapy. However, the priority remains to influence MS in its early stages to delay the onset of progression and to take a comprehensive approach with attention to a healthy lifestyle and influencing risk factors.

Keywords:

Multiple sclerosis – risk factors – diagnostics – secondary progression – primary progression – progressive multiple sclerosis – disease-modifying drugs – immunomodulatory treatment – immunopathogenesis


Sources

1. Šťastná D, Horáková D. Ovlivnění dlouhodobé progrese roztroušené sklerózy – svítá na lepší časy? Neurol Praxi 2021; 22 (1): 40–44. doi: 10.36290/NEU.2020.104.

2. Lublin FD, Reingold SC, Cohen JA et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83 (3): 278. doi: 10.1212/WNL.0000000000000 560.

3. McKay KA, Kwan V, Duggan T et al. Risk factors associated with the onset of relapsing-remitting and primary progressive multiple sclerosis: a systematic review. Biomed Res Int 2015; 2015: 817238. doi: 10.1155/2015/ 817238.

4. Cree BAC, Oksenberg JR, Hauser SL. Multiple sclerosis: two decades of progress. Lancet Neurol 2022; 21 (3): 211–214. doi: 10.1016/S1474-4422 (22) 00040-0.

5. Voskuhl RR. The effect of sex on multiple sclerosis risk and disease progression. Mult Scler 2020; 26 (5): 554–560. doi: 10.1177/1352458519892491.

6. Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol 2019; 26 (1): 27–40. doi: 10.1111/ENE.13 819.

7. Ramagopalan SV, Dobson R, Meier UC et al. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol 2010; 9 (7): 727–739. doi: 10.1016/S1474-4422 (10) 70094-6.

8. Handel AE, Williamson AJ, Disanto G et al. An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One 2010; 5 (9): 1–5. doi: 10.1371/JOURNAL.PONE.0012496.

9. Loosen SH, Doege C, Meuth SG et al. Infectious mononucleosis is associated with an increased incidence of multiple sclerosis: results from a cohort study of 32,116 outpatients in Germany. Front Immunol 2022; 13: 937583. doi: 10.3389/FIMMU.2022.937583/XML/ NLM.

10. Bjornevik K, Cortese M, Healy BC et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 2022; 375 (6578): 296–301. doi: 10.1126/SCIENCE.ABJ8222.

11. Alfredsson L, Olsson T. Lifestyle and environmental factors in multiple sclerosis. Cold Spring Harb Perspect Med 2019; 9 (4): a028944. doi: 10.1101/CSHPERSPECT.A028944.

12. Palacios N, Alonso A, Brønnum-Hansen H et al. Smoking and increased risk of multiple sclerosis: parallel trends in the sex ratio reinforce the evidence. Ann Epidemiol 2011; 21 (7): 536–542. doi: 10.1016/J.ANNEPIDEM.2011.03. 001.

13. Rosso M, Chitnis T. Association between cigarette smoking and multiple sclerosis: a review. JAMA Neurol 2020; 77 (2): 245–253. doi: 10.1001/JAMANEUROL.2019. 4271.

14. Arneth B. Multiple sclerosis and smoking. Am J Med 2020; 133 (7): 783–788. doi: 10.1016/J.AMJMED.2020. 03.008.

15. Hernán MA, Jick SS, Logroscino G et al. Cigarette smoking and the progression of multiple sclerosis. Brain 2005; 128 (Pt 6): 1461–1465. doi: 10.1093/BRAIN/AWH 471.

16. Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther 2018; 7 (1): 59–85. doi: 10.1007/S40120-017-00 86-4.

17. Vitkova M, Diouf I, Malpas C et al. Association of latitude and exposure to ultraviolet B radiation with severity of multiple sclerosis: an international registry study. Neurology 2022; 98 (24): E2401–E2412. doi: 10.1212/WNL. 0000000000200545.

18. Wesnes K, Myhr KM, Riise T et al. Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis. Mult Scler Relat Disord 2021; 50: 102801. doi: 10.1016/J.MSARD.2021.102801.

19. Preiningerova JL, Zakostelska ZJ, Srinivasan A et al. Multiple sclerosis and microbio­me. Biomolecules 2022; 12 (3): 433. doi: 10.3390/BIOM12030433.

20. Takewaki D, Yamamura T. Gut microbio­me research in multiple sclerosis. Neurosci Res 2021; 168: 28–31. doi: 10.1016/J.NEURES.2021.05.001.

21. Krejsek J. Roztroušená skleróza mozkomíšní, úloha střevní mikrobio­ty v poškozujícím zánětu. Cesk Slov Neurol N 2019; 82 (2): 141–147. doi: 10.14735/amcsnn2019 141.

22. Dyment DA, Sadovnick AD, Ebers GC. Genetics of multiple sclerosis. Hum Mol Genet 1997; 6 (10): 1693–1698. doi: 10.1093/HMG/6.10.1693.

23. Harirchian MH, Fatehi F, Sarraf P et al. Worldwide prevalence of familial multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord 2018; 20: 43–47. doi: 10.1016/J.MSARD.2017.12.015.

24. Beecham AH, Patsopoulos NA, Xifara DK et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 2013; 45 (11): 1353–1362. doi: 10.1038/NG.2770.

25. Jersild C, Svejgaard A, Fog T. HL-A antigens and multiple sclerosis. Lancet 1972; 1 (7762): 1240–1241. doi: 10.1016/S0140-6736 (72) 90962-2.

26. Schmidt H, Williamson D, Ashley-Koch A. HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol 2007; 165 (10): 1097–1109. doi: 10.1093/ AJE/KWK118.

27. Prat E, Tomaru U, Sabater L et al. HLA-DRB5*0101 and -DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype. J Neuroimmunol 2005; 167 (1–2): 108–119. doi: 10.1016/J.JNEUROIM.2005.04. 027.

28. Lincoln MR, Montpetit A, Cader MZ et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 2005; 37 (10): 1108–1112. doi: 10.1038/NG1647.

29. Jia X, Madireddy L, Caillier S et al. Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis. Ann Neurol 2018; 84 (1): 51–63. doi: 10.1002/ANA.25263.

30. Bjornevik K, Munger KL, Cortese M et al. Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis. JAMA Neurol 2020; 77 (1): 58–64. doi: 10.1001/JAMANEUROL.2019.3238.

31. Luchetti S, Fransen NL, van Eden CG et al. Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis. Acta Neuropathol 2018; 135 (4): 511–528. doi: 10.1007/S00401-018-1818-Y/FIGURES/9.

32. Giovannoni G, Popescu V, Wuerfel J et al. Smouldering multiple sclerosis: the “real MS”. Ther Adv Neurol Disord 2022; 15: 17562864211066751. doi: 10.1177/17562 864211066751.

33. Macaron G, Ontaneda D. Dia­gnosis and management of progressive multiple sclerosis. Biomedicines 2019; 7 (3): 56. doi: 10.3390/BIOMEDICINES7030 056.

34. Thompson AJ, Carroll W, Ciccarelli O et al. Charting a global research strategy for progressive MS-An international progressive MS Alliance proposal. Mult Scler 2022; 28 (1): 16–28. doi: 10.1177/13524585211059766.

35. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996; 46 (4): 907–911. doi: 10.1212/WNL.46.4.907.

36. Wildner P, Stasiołek M, Matysiak M. Differential dia­g­nosis of multiple sclerosis and other inflammatory CNS diseases. Mult Scler Relat Disord 2020; 37: 101452. doi: 10.1016/J.MSARD.2019.101452.

37. Thompson AJ, Baranzini SE, Geurts J et al. Multiple sclerosis. Lancet 2018; 391 (10130): 1622–1636. doi: 10.1016/S0140-6736 (18) 30481-1.

38. Thompson AJ, Banwell BL, Barkhof F et al. Dia­g­nosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17 (2): 162–173. doi: 10.1016/S1474-4422 (17) 30470-2.

39. Ramanujam R, Zhu F, Fink K et al. Accurate classification of secondary progression in multiple sclerosis using a decision tree. Mult Scler 2021; 27 (8): 1240–1249. doi: 10.1177/1352458520975323.

40. Benedict RHB, Deluca J, Phillips G et al. Validity of the symbol digit modalities test as a cognition performance outcome measure for multiple sclerosis. Mult Scler 2017; 23 (5): 721–733. doi: 10.1177/1352458517690 821.

41. Kalinowski A, Cutter G, Bozinov N et al. The timed 25-foot walk in a large cohort of multiple sclerosis patients. Mult Scler 2022; 28 (2): 289–299. doi: 10.1177/135 245 85211017013.

42. Feys P, Lamers I, Francis G et al. The nine-hole peg test as a manual dexterity performance measure for multiple sclerosis. Mult Scler 2017; 23 (5): 711–720. doi: 10.1177/1352458517690824.

43. Oh J, Ontaneda D, Azevedo C et al. Imaging outcome measures of neuroprotection and repair in MS: a consensus statement from NAIMS. Neurology 2019; 92 (11): 519–533. doi: 10.1212/WNL.0000000000007099.

44. Ontaneda D, Fox RJ, Chataway J. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives. Lancet Neurol 2015; 14 (2): 208–223. doi: 10.1016/S1474-4422 (14) 70264-9.

45. Andělová M, Vodehnalová K, Krásenský J et al. Kli­nicko-radiologický paradox u roztroušené sklerózy – význam vyšetření míchy. Cesk Slov Neurol N 2021; 84 (6): 547–554. doi: 10.48095/CCCSNN2021547.

46. Andelova M, Vodehnalova K, Krasensky J et al. Brainstem lesions are associated with diffuse spinal cord involvement in early multiple sclerosis. BMC Neurol 2022; 22 (1): 270. doi: 10.1186/s12883-022-027 78-z.45.

47. Elliott C, Wolinsky JS, Hauser SL et al. Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions. Mult Scler 2019; 25 (14): 1915–1925. doi: 10.1177/1352458518814117.

48. Saidha S, Al-Louzi O, Ratchford JN et al. Optical coherence tomography reflects brain atrophy in multiple sclerosis: a four-year study. Ann Neurol 2015; 78 (5): 801–813. doi: 10.1002/ANA.24487.

49. Novakova L, Zetterberg H, Sundström P et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology 2017; 89 (22): 2230–2237. doi: 10.1212/WNL.0000000000004 683.

50. Martin SJ, McGlasson S, Hunt D et al. Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case-control studies. J Neurol Neurosurg Psychiatry 2019; 90 (9): 1059–1067. doi: 10.1136/JNNP-2018-319190.

51. Uher T, Havrdova E, Benkert P. Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis. Mult Scler 2021; 27 (13): 2001–2013. doi: 10.1177/13524585211047977.

52. Sun MJ, Liu N, Xie QF et al. A candidate bio­marker of glial fibrillary acidic protein in CSF and blood in differentiating multiple sclerosis and its subtypes: a systematic review and meta-analysis. Mult Scler Relat Disord 2021; 51: 102870. doi: 10.1016/J.MSARD.2021.102 870.

53. Ayrignac X, le Bars E, Duflos C et al. Serum GFAP in multiple sclerosis: correlation with disease type and MRI markers of disease severity. Sci Rep 2020; 10 (1): 10923. doi: 10.1038/s41598-020-67934-2.

54. Lorscheider J, Buzzard K, Jokubaitis V et al. Defining secondary progressive multiple sclerosis. Brain 2016; 139 (Pt 9): 2395–2405. doi: 10.1093/BRAIN/AWW 173.

55. Andelova M, Vodehnalova K, Krasensky J et al. Brainstem lesions are associated with diffuse spinal cord involvement in early multiple sclerosis. BMC Neurol 2022; 22 (1): 270. doi: 10.1186/S12883-022-027 78-Z.

56. Fambiatos A, Jokubaitis V, Horakova D et al. Risk of secondary progressive multiple sclerosis: a longitudinal study. Mult Scler 2020; 26 (1): 79–90. doi: 10.1177/135 2458519868990.

57. Brown JWL, Coles A, Horakova D et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA 2019; 321 (2): 175–187. doi: 10.1001/JAMA.2018.20 588.

58. Tomas U, Krasensky J, Malpas Ch et al. Evolution of brain volume loss rates in early stages of multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2021; 8 (3): e979. doi: 10.1212/NXI.0000000000000979.

59. Tremlett H, Zhao Y, Rieckmann P et al. New perspectives in the natural history of multiple sclerosis. Neurology 2010; 74 (24): 2004–2015. doi: 10.1212/WNL.0B013E3181E3973F.

60. Riederer F. Ocrelizumab versus placebo in primary progressive multiple sclerosis. J Fur Neurol Neurochir Und Psychiatr 2017; 18 (1): 30–31. doi: 10.1056/nejmoa1606468.

61. Kappos L, Bar-Or A, Cree BAC et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet 2018; 391 (10127): 1263–1273. doi: 10.1016/S0140-6736 (18) 30475-6.

62. Hughes J, Jokubaitis V, Lugaresi A et al. Association of inflammation and disability accrual in patients with progressive-onset multiple sclerosis. JAMA Neurol 2018; 75 (11): 1407–1415. doi: 10.1001/JAMANEUROL.2018. 2109.

63. Kalincik T, Lizak N, Malpas CB et al. Association of sustained immunotherapy with disability outcomes in patients with active secondary progressive multiple sclerosis. JAMA Neurol 2020; 77 (11): 1398–1407. doi: 10.1001/JAMANEUROL.2020.2453.

64. Naismith RT, Bermel RA, Coffey CS et al. Effects of ibudilast on MRI measures in the phase 2 SPRINT-MS study. Neurology 2021; 96 (4): e491–e500. doi: 10.1212/WNL.0000000000011314.

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Paediatric neurology Neurosurgery Neurology

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