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Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study

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Abstract

The aim of the study was to estimate the rate of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to investigate variables predicting conversion in a cohort of patients presenting with symptoms suggestive of MS. Patients with a first symptom suggestive of MS in the preceding 6 months and exclusion of other diseases were enrolled in an observational prospective study from December 2004 through June 2007. Conversion from CIS to MS according to both McDonald and Clinically Defined Multiple Sclerosis (CDMS) criteria was prospectively recorded until March 2010. The multivariate Cox proportional hazard model was used to assess the best predictive factors of conversion from CIS to MS. Among 168 patients included in the analysis, 122 converted to MS according to McDonald criteria whereas 81 converted to MS according to CDMS criteria. The 2-year probability of conversion was 57 % for McDonald Criteria and 36 % for CDMS criteria. Variables at enrolment significantly associated with conversion according to McDonald criteria were age and positivity for Barkhof criteria, and according to Poser’s CDMS criteria, age, positivity for Barkhof criteria and no disease modifying therapy. In this large prospective cohort study the conversion rate from CIS to MS in patients presenting with recent symptoms suggestive of MS was within the range of previous observational studies and lower than that reported in the placebo arm of randomized trials. We confirm the prognostic value of MRI in addition to the previous experimental data on the protective role of disease-modifying therapies.

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Acknowledgments

This study was supported with an unconditional grant by Biogen Idec and by Department of Neurological Sciences of the University of Bologna. None of the authors received fees for the participation to the study. Authors have ownership of the data. The study was recognized as “no profit” by all ethical committees to whom it was submitted. We thank Yghea CRO for the precious help.

Conflicts of interest

Prof. Roberto D’Alessandro reports no disclosure. Dr. Luca Vignatelli reports no disclosure. Prof. Alessandra Lugaresi is a Biogen Dompé, Merck Serono and Bayer Schering Advisory Board Member. She received travel grants and honoraria from Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi Aventis and Teva and research grants from Bayer Schering, Biogen Dompé, Merck Serono, Novartis and Sanofi Aventis. She has also received travel and research grants from the Associazione Italiana Sclerosi Multipla and is a Consultant of “Fondazione Cesare Serono”. Dr. Franco Granella received speaking honoraria from Biogen Idec and travel grants from Biogen Idec, Merck Serono, Sanofi Aventis and Novartis. He received research support from Biogen Idec and Merck Serono. Dr. Elisa Baldin reports no disclosure. Prof. Maria-Rosalia Tola received research funding from Sanofi-Aventis and compensation for consultancy or speaking from Biogen, Sanofi-Aventis, Merk serono, Novartis, Sanofi-Aventis. Dr. Susanna Malagù received travel grants from Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi Aventis and Teva, honoraria from Bayer Schering and Biogen Dompè and research grants from “Fondazione Cesare Serono”. Dr. Luisa Motti reports no disclosure. Dr. Walter Neri reports no disclosure. Dr. Galeotti reports no disclosure. Dr. Mario Santangelo reports no disclosure. Dr. Laila Fiorani has received travel grants from Bayer Schering, Biogen Dompé, Merck Serono, Novartis, Sanofi Aventis. Dr. Enrico Montanari reports no disclosure. Dr. Cinzia Scandellari reports no disclosure. Dr. Maria Donata Benedetti reports no disclosure. Dr. Maurizio Leone reports no disclosure.

Ethical standard

In the paper it is well reported that the study was approved by all ethical committees.

Author information

Authors and Affiliations

  1. Department of Neurological Sciences, Neuroepidemiology Unit, University of Bologna, Via U. Foscolo 7, 40100, Bologna, Italy

    Roberto D’Alessandro, Luca Vignatelli & Elisa Baldin

  2. City of Bologna Local Health Trust, Bologna, Italy

    Luca Vignatelli

  3. Dipartimento di Neuroscienze ed Imaging, Centro Sclerosi Multipla, Clinica Neurologica, Università “G.d’Annunzio”, Chieti, Italy

    Alessandra Lugaresi

  4. Department of Neurosciences, Multiple Sclerosis Centre, University of Parma, Parma, Italy

    Franco Granella

  5. UO Neurologia, AOU S.Anna, Ferrara, Italy

    Maria Rosaria Tola

  6. UO Neurologia, Ospedale Bufalini, Cesena, Italy

    Susanna Malagù

  7. UO Neurologia, AO Santa Maria Nuova, Reggio Emilia, Italy

    Luisa Motti

  8. UO di Neurologia, AUSL di Forlì, Forlì, Italy

    Walter Neri

  9. UO di Neurologia, Ospedale santa Maria delle Croci, Ravenna, Italy

    Massimo Galeotti & Laila Fiorani

  10. UO di Neurologia, Ospedale Ramazzini, Modena, Italy

    Mario Santangelo

  11. UO di Neurologia, Ospedale Civile–Località Vaio, Fidenza, Parma, Italy

    Enrico Montanari

  12. UOSD Riabilitazione e Sclerosi Multipla, Villa Mazzacorati, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Cinzia Scandellari

  13. UOC di Neurologia dU, Centro Malattie Demielinizzanti, Borgo Roma, Aziende Ospedaliera Universitaria Integrata, Verona, Italy

    Maria Donata Benedetti

  14. SCDU Neurologia, AOU Maggiore della Carità, Novara, Italy

    Maurizio Leone

  15. Gertrude H. Sergievsky Center, Columbia University, New York, USA

    Elisa Baldin

Authors
  1. Roberto D’Alessandro
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  2. Luca Vignatelli
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  3. Alessandra Lugaresi
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  4. Elisa Baldin
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  5. Franco Granella
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  6. Maria Rosaria Tola
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  7. Susanna Malagù
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  8. Luisa Motti
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  9. Walter Neri
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  10. Massimo Galeotti
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  11. Mario Santangelo
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  12. Laila Fiorani
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  13. Enrico Montanari
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  14. Cinzia Scandellari
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  15. Maria Donata Benedetti
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  16. Maurizio Leone
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Corresponding author

Correspondence to Roberto D’Alessandro.

Additional information

For the GERONIMUS Study Group (members of this study group are listed in "Appendix").

Appendix: GERONIMUS Coinvestigators

Appendix: GERONIMUS Coinvestigators

Katia Mattarozzi, PhD (Dipartimento di Psicologia, Università di Bologna, Psycologic testing coordination); Marianna Pattini, MD (Centro Sclerosi Multipla, U.O di Neurologia, Ospedale Civile –Località Vaio, Site investigators); Caterina Senesi, MD (Centro Sclerosi Multipla Dipartimento di Neuroscienze,Università di Parma, site investigator); Concetta Feo, (U.O.S Neurofisiologia, U.O. Neurologia, Ospedale Santa Maria Nuova, site investigator); Sergio Stecchi, MD; Lucia La Mola; Renzo Balugani, MD (UOSD Riabilitazione-Sclerosi Multipla, Villa Mazzacorati, IRCCS Istituto delle Scienze Neurologiche, Bologna, site investigators); Fabio Pizza, MD (Dipartimento di Scienze Neurologiche, Università di Bologna, site investigator); Laura Delaj, MD; Silvia De Pasqua, MD; Rita Rinaldi, MD (U.O Neurologia, Dipartimento Neuro-Senso-Motorio, Policlinico S.Orsola-Malpighi, Bologna, site investigators); Eleonora Baldi, MD, Luisa Caniatti, MD, Paola Milani, Psychologist (Dipartimento di Neuroscienze,Azienda Ospedaliero Universitaria S. Anna, Ferrara, site investigators and psychologic testing); Vittoria Mussuto, MD; Monica Manzoni, Psycologist (U.O. Neurologia, Ospedale Santa Maria della Scaletta, Imola, site investigators); Mario Casmiro, MD; Claudia Guerrini (Ospedale per gli Infermi,AUSL Ravenna, Faenza, site investigators); Laura Mambelli (U.O. di Neurologia, Presidio Ospedaliero G.B. Morgagni-L. Pierantoni, Forlì, site investigator); Paola Naldi, MD; Laura Collimedaglia, Psychologist (SCDU Neurologia, A.O.U. “Maggiore della Carità”, Novara, site investigators); Erika Pietrolongo, PhD; Valeria Di Tommaso, MD; Giovanna DeLuca, MD; Daniela Travaglini, MD (Centro Sclerosi Multipla, Clinica Neurologica, Dipartimento di Neuroscienze e Imaging, Università “G. d’Annunzio”, Chieti, site investigators and psychological testing); Francesca Rossi, MD; Alberto Gajofatto, MD (Unità Operativa Complessa di Neurologia, Borgo Roma, Verona, site investigators); Marco Pastore Trossello, MD; Luca Faccioli, MD; Luca Spinardi, MD (SSD Neuroradiologia, AOSP, Bologna, MRI review).

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D’Alessandro, R., Vignatelli, L., Lugaresi, A. et al. Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study. J Neurol 260, 1583–1593 (2013). https://doi.org/10.1007/s00415-013-6838-x

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  • DOI: https://doi.org/10.1007/s00415-013-6838-x

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