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Cognitive impairment and structural brain changes in patients with clinically isolated syndrome at high risk for multiple sclerosis

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Abstract

Patients with clinically isolated syndrome (CIS), unlike those with multiple sclerosis (MS), have a selective cognitive impairment which is not consistently related to structural brain changes. Our objective was to characterize a profile of cognitive impairment and its association with structural brain changes in patients with CIS who are at high risk of developing MS. Patients with CIS at high risk for MS on interferon-beta (n = 51) and age-, gender-, and education-matched controls (n = 44) underwent comprehensive neuropsychological testing and MRI brain scan with voxel-based morphometry. The CIS group had lower cognitive performance in verbal and nonverbal memory, information processing speed/attention/working memory, and executive and visuo-spatial functions compared to controls (p ≤ 0.040). Lower cognitive performance was present in 18–37 and 14–26% of patients with CIS at high risk for MS depending on the criteria used. Brain volume was reduced predominantly in fronto-temporal regions and the thalamus in the CIS group (p ≤ 0.019). Cognitive performance was not associated with structural brain changes except for the association between worse visuo-spatial performance and lower white matter volume in the CIS group (β = 0.29; p = 0.042). Our results indicated that patients with CIS at high risk for MS may have a pattern of lower cognitive performance and regional brain atrophy similar to that found in patients with MS. Lower cognitive performance may be present in up to one-third of patients with CIS at high risk for MS, but, unlike patients with MS, variability in their cognitive performance may lead to a lack of consistent associations with structural brain changes.

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Acknowledgements

This study was supported by the Ministry of Health, Czech Republic—Internal Grant Agency (NT/12385-5 and NR/9445-3); Ministry of Health, Czech Republic—conceptual development of research organization, University Hospital Motol, Prague, Czech Republic (00064203); Institutional Support of Laboratory Research Grant No. 2/2012 (699002); Institutional Support of Excellence Grant; the project no. LQ1605 (MEYS CR, NPU II); European Regional Development Fund—Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123) and project ICRC-ERA-HumanBridge (No. 316345).

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  1. Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu 84, 150 06, Prague 5, Czech Republic

    Eva Hynčicová, Martin Vyhnálek, Adam Kalina, Lukáš Martinkovič, Tomáš Nikolai, Jakub Hort, Eva Meluzínová & Jan Laczó

  2. International Clinical Research Center, St. Anne’s University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic

    Martin Vyhnálek, Tomáš Nikolai, Jakub Hort & Jan Laczó

  3. Department of Radiology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06, Prague 5, Czech Republic

    Jiří Lisý

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The study was approved by the institutional ethics committee of the Motol University Hospital. Written informed consent was obtained from all subjects participating in the study. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsiniki.

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Hynčicová, E., Vyhnálek, M., Kalina, A. et al. Cognitive impairment and structural brain changes in patients with clinically isolated syndrome at high risk for multiple sclerosis. J Neurol 264, 482–493 (2017). https://doi.org/10.1007/s00415-016-8368-9

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