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Long-term disability and progression in spinal onset multiple sclerosis


The aim of this study is to investigate the long-term effects of the initial spinal cord (SC) involvement in MS patients. In this retrospective, single-center study, 824 patients with definite MS were screened. A total of 348 patients were excluded for ambiguous documentation of the initial relapse, pediatric onset, diagnosis of primary progressive disease, irregular assessments or visits causing doubt on the onset of progression time, and clinical follow-up duration less than 12 months. Eventually, 476 MS patients were included. Data regarding the demographics, initial symptoms, the degree of recovery from the initial relapse, neuroimaging, cerebrospinal fluid analysis, long-term disability, and progression were collected from the medical registry. The mean duration of follow-up was 7.49 ± 5.30 years. The percentage of patients entering the progressive disease course was 23.3 in the whole group. A total of 157 patients (33.0%) had SC involvement during the first clinical relapse. These patients were significantly older at disease onset (31.69 ± 10.18 vs. 29.55 ± 9.49; p = 0.028), had higher rates of progression (32.5 vs. 18.8%; p = 0.001), and had higher disability scores in long-term follow-up (3.41 ± 2.19 vs. 2.62 ± 1.81; p < 0.001). Mean age at the transition of progressive phase was 41.4 ± 11.2 years. The degree of recovery from the initial relapse significantly affected the long-term disability. The poor recovery from the initial relapse was associated with older onset age and higher EDSS scores. Being older than 40 years during MS onset and poor recovery from the initial relapse exerted an increased risk for progression. The initial SC involvement was related to a more severe relapse with less chance of complete recovery and higher risk for progression. Confirmation of risk factors in different MS cohorts would increase our understanding of the complex disease mechanisms.

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  1. Kremenchutzky M, Rice GP, Baskerville J, Wingerchuk DM, Ebers GC (2006) The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain 129(Pt 3):584–594. doi:10.1093/brain/awh721

    Article  PubMed  CAS  Google Scholar 

  2. Scolding N, Barnes D, Cader S, Chataway J, Chaudhuri A, Coles A, Giovannoni G, Miller D, Rashid W, Schmierer K, Shehu A, Silber E, Young C, Zajicek J (2015) Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol 15(4):273–279. doi:10.1136/practneurol-2015-001139

    Article  PubMed  Google Scholar 

  3. Amato MP, Ponziani G (2000) A prospective study on the prognosis of multiple sclerosis. Neurol Sci 21(4 Suppl 2):S831–S838

    Article  PubMed  CAS  Google Scholar 

  4. Confavreux C, Vukusic S, Adeleine P (2003) Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 126(Pt 4):770–782

    Article  PubMed  Google Scholar 

  5. Mowry EM, Pesic M, Grimes B, Deen S, Bacchetti P, Waubant E (2009) Demyelinating events in early multiple sclerosis have inherent severity and recovery. Neurology 72(7):602–608. doi:10.1212/01.wnl.0000342458.39625.91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G (2010) Evidence for a two-stage disability progression in multiple sclerosis. Brain 133(Pt 7):1900–1913. doi:10.1093/brain/awq076

    Article  PubMed  PubMed Central  Google Scholar 

  7. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121–127

    Article  PubMed  CAS  Google Scholar 

  8. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58(6):840–846. doi:10.1002/ana.20703

    Article  PubMed  Google Scholar 

  9. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302. doi:10.1002/ana.22366

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kurtzke JF (2015) On the origin of EDSS. Mult Scler Relat Disord 4(2):95–103. doi:10.1016/j.msard.2015.02.003

    Article  PubMed  Google Scholar 

  11. Tutuncu M, Tang J, Zeid NA, Kale N, Crusan DJ, Atkinson EJ, Siva A, Pittock SJ, Pirko I, Keegan BM, Lucchinetti CF, Noseworthy JH, Rodriguez M, Weinshenker BG, Kantarci OH (2013) Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis. Mult Scler 19(2):188–198. doi:10.1177/1352458512451510

    Article  PubMed  Google Scholar 

  12. Novotna M, Paz Soldan MM, Abou Zeid N, Kale N, Tutuncu M, Crusan DJ, Atkinson EJ, Siva A, Keegan BM, Pirko I, Pittock SJ, Lucchinetti CF, Noseworthy JH, Weinshenker BG, Rodriguez M, Kantarci OH (2015) Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis. Neurology 85(8):722–729. doi:10.1212/WNL.0000000000001856

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sombekke MH, Wattjes MP, Balk LJ, Nielsen JM, Vrenken H, Uitdehaag BM, Polman CH, Barkhof F (2013) Spinal cord lesions in patients with clinically isolated syndrome: a powerful tool in diagnosis and prognosis. Neurology 80(1):69–75. doi:10.1212/WNL.0b013e31827b1a67

    Article  PubMed  Google Scholar 

  14. Confavreux C, Vukusic S (2006) Age at disability milestones in multiple sclerosis. Brain 129(Pt 3):595–605. doi:10.1093/brain/awh714

    Article  PubMed  Google Scholar 

  15. Binquet C, Quantin C, Le Teuff G, Pagliano JF, Abrahamowicz M, Moreau T (2006) The prognostic value of initial relapses on the evolution of disability in patients with relapsing-remitting multiple sclerosis. Neuroepidemiology 27(1):45–54. doi:10.1159/000094380

    Article  PubMed  CAS  Google Scholar 

  16. Borreani C, Bianchi E, Pietrolongo E, Rossi I, Cilia S, Giuntoli M, Giordano A, Confalonieri P, Lugaresi A, Patti F, Grasso MG, de Carvalho LL, Palmisano L, Zaratin P, Battaglia MA, Solari A, Np Pe (2014) Unmet needs of people with severe multiple sclerosis and their carers: qualitative findings for a home-based intervention. PLoS One 9(10):e109679. doi:10.1371/journal.pone.0109679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Dutta R, Trapp BD (2014) Relapsing and progressive forms of multiple sclerosis: insights from pathology. Curr Opin Neurol 27(3):271–278. doi:10.1097/WCO.0000000000000094

    Article  PubMed  PubMed Central  Google Scholar 

  18. Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers GC, Muraro PA (2016) The relationship of age with the clinical phenotype in multiple sclerosis. Mult Scler 22(13):1750–1758. doi:10.1177/1352458516630396

    Article  PubMed  CAS  Google Scholar 

  19. Scalfari A, Neuhaus A, Daumer M, Ebers GC, Muraro PA (2011) Age and disability accumulation in multiple sclerosis. Neurology 77(13):1246–1252. doi:10.1212/WNL.0b013e318230a17d

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kulu U, Tiftikcioglu BI, Zorlu Y, Cetiner M, Sener U, Tuna G, Kirkali G (2017) Efficacy of different durations of intravenous methylprednisolone treatment in relapses of multiple sclerosis. Noro Psikiyatr Ars 54(1):57–61. doi:10.5152/npa.2016.12382

    Article  PubMed  Google Scholar 

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Correspondence to Bedile Irem Tiftikcioglu.

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This retrospective study was in accordance with the Helsinki Declaration of human rights and was approved by the Regional Committee for Research Ethics (15.03.2016-19-15).

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All subjects gave written informed consent to the use of their clinical data for research studies.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Tiftikcioglu, B.I., Ilgezdi, I., Zorlu, Y. et al. Long-term disability and progression in spinal onset multiple sclerosis. Acta Neurol Belg 118, 217–225 (2018).

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  • Multiple sclerosis
  • Initial relapse
  • Spinal cord
  • Progression
  • Recovery
  • Outcome