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Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome

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Abstract

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.

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Acknowledgments

The authors thank the patients who participated in this study. We thank the other Clinical Centers and investigators who participated in the SET study: (1) M. Vachova, S. Machalicka, and J. Kotalova from KZ a.s. Hospital, Teplice; (2) Y. Benesova, P. Praksova, and P. Stourac from University Hospital, Brno, Bohunice; (3) M. Dufek from St. Anne’s University Hospital, Brno; (4) E. Meluzinova, J. Pikova, and E. Houzvickova from Charles University in Prague, 2nd Faculty of Medicine, Motol; (5) D. Zimova from Charles University in Prague, 3rd Faculty of Medicine, Kralovske Vinohrady; (6) J. Sucha from University Hospital, Plzen; (7) V. Sladkova and J. Mares from University Hospital, Olomo. The SET study was supported by Czech Ministries of Education and Health (NT13237-4/2012, PRVOUK-P26/LF1/4, RVO-VFN64165/2012) and Biogen Idec.

Conflicts of interest

Dr. Blahova Dusankova, Mr. Bergsland, Mr. Hagemeier, and Dr. Ramasamy report no disclosures. Dr. Uher received financial support for conference travel and honoraria from Biogen Idec. Dr. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva as well as support for research activities from Biogen Idec. Dr. Tyblova received compensation for travel and honoraria from Biogen Idec, Sanofi Aventis, Teva, and Merck Serono. Dr. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec. Dr. Kalincik received compensation for conference travel and honoraria from Novartis, Biogen Idec, Sanofi Aventis, Teva, and Merck Serono. Drs. Seidl, Vaneckova, and Krasensky received financial support for research activities from Biogen Idec. Dr. Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme, and Teva as well as support for research activities from Biogen Idec and Merck Serono. Dr. Zivadinov received financial support for research activities from Teva Pharmaceuticals, Biogen Idec, Claret Medical, Genzyme, Novartis, and Greatbatch. He received personal compensation from Biogen Idec, Novartis, Genzyme, and EMD Serono for speaking and consultant services.

Ethical standard

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic

    Tomas Uher, Jana Blahova-Dusankova, Dana Horakova, Michaela Tyblova & Eva Havrdova

  2. Department of Neurology, Buffalo Neuroimaging Analysis Center, The Jacobs Neurological Institute, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High St, Buffalo, NY, 14203, USA

    Tomas Uher, Niels Bergsland, Ralph H. B. Benedict, Deepa P. Ramasamy, Jesper Hagermeier & Robert Zivadinov

  3. IRCCS, Don Gnocchi Foundation, Milan, Italy

    Niels Bergsland

  4. Department of Medicine, Melbourne Brain Centre, University of Melbourne, Melbourne, Australia

    Tomas Kalincik

  5. Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia

    Tomas Kalincik

  6. Department of Radiology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic

    Zdenek Seidl, Manuela Vaneckova & Jan Krasensky

  7. MR Imaging Clinical Translational Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Robert Zivadinov

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  1. Tomas Uher
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  2. Jana Blahova-Dusankova
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  3. Dana Horakova
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  4. Niels Bergsland
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  5. Michaela Tyblova
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  6. Ralph H. B. Benedict
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  7. Tomas Kalincik
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  14. Robert Zivadinov
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Correspondence to Robert Zivadinov.

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Uher, T., Blahova-Dusankova, J., Horakova, D. et al. Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome. J Neurol 261, 1735–1744 (2014). https://doi.org/10.1007/s00415-014-7413-9

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  • DOI: https://doi.org/10.1007/s00415-014-7413-9

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