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Multimodal assessment of normal-appearing corpus callosum is a useful marker of disability in relapsing–remitting multiple sclerosis: an MRI cluster analysis study

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Abstract

Background and purpose

Corpus callosum (CC) is frequently involved in relapsing–remitting multiple sclerosis (RRMS). Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) allow to study CC macrostructural and microstructural tissue integrity. Here, we applied a data-driven approach to MRI and DTI data of normal-appearing CC in RRMS subjects, and subsequently evaluated if differences in tissue integrity corresponded to different levels of physical disability and cognitive impairment.

Methods

74 RRMS patients and 20 healthy controls (HC) underwent 3 T MRI and DTI. Thickness and fractional anisotropy (FA) along midsagittal CC were extracted, and values from RRMS patients were fed to a hierarchical clustering algorithm. We then used ANOVA to test for differences in clinical and cognitive variables across the imaging-based clusters and HC.

Results

We found three distinct MRI-based subgroups of RRMS patients with increasing severity of CC damage. The first subgroup showed callosal integrity similar to HC (Cluster 1); Cluster 2 had milder callosal damage; a third subgroup showed the most severe callosal damage (Cluster 3). Cluster 3 included patients with longer disease duration and worst scores in Expanded Disability Status Scale. Cognitive domains of verbal memory, executive functions and processing speed were impaired in Cluster 3 and Cluster 2 compared to Cluster 1 and HC.

Conclusions

Within the same homogeneous cohort of patients, we could identify three neuroimaging RRMS clusters characterized by different involvement of normal-appearing CC. Interestingly, these corresponded to three distinct levels of clinical and cognitive disability.

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Author notes

  1. Stefania Barone and Maria Eugenia Caligiuri contributed equally to the manuscript.

Authors and Affiliations

  1. Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy

    Stefania Barone, Paola Valentino, Alfredo Granata, Enrica Filippelli & Tiziana Tallarico

  2. Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Catanzaro, Italy

    Maria Eugenia Caligiuri, Andrea Cherubini, Carmelina Chiriaco, Rita Nisticò & Aldo Quattrone

  3. Neuroscience Research Center, University Magna Graecia, Catanzaro, Italy

    Maria Eugenia Caligiuri & Aldo Quattrone

Authors
  1. Stefania Barone
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  2. Maria Eugenia Caligiuri
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  3. Paola Valentino
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  4. Andrea Cherubini
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  5. Carmelina Chiriaco
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  6. Alfredo Granata
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  7. Enrica Filippelli
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  8. Tiziana Tallarico
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  9. Rita Nisticò
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  10. Aldo Quattrone
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Corresponding author

Correspondence to Paola Valentino.

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Ethical standards

All study procedures involving human subjects were approved by the local Institutional Review Board, and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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All the study participants gave written informed consent prior to their inclusion in the study.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Barone, S., Caligiuri, M.E., Valentino, P. et al. Multimodal assessment of normal-appearing corpus callosum is a useful marker of disability in relapsing–remitting multiple sclerosis: an MRI cluster analysis study. J Neurol 265, 2243–2250 (2018). https://doi.org/10.1007/s00415-018-8980-y

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  • DOI: https://doi.org/10.1007/s00415-018-8980-y

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