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Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study

  • Functional Neuroradiology
  • Published:
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Abstract

Purpose

Brain involvement in X-linked Charcot-Marie-Tooth disease (CMTX) has been previously reported. We studied the brain structural and functional integrity using a multimodal neuroimaging approach in patients with no current central nervous system (CNS) symptoms, in order to further delineate the disease’s phenotype.

Methods

Seventeen CMTX patients with no current CNS symptoms and 24 matched healthy controls underwent brain magnetic resonance imaging (MRI). Structural integrity was evaluated performing Gray matter analysis with voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI). Functional integrity was evaluated with resting-state functional MRI (rs-fMRI).

Results

Decreased gray matter density was detected in CMTX patients compared to healthy controls in bilateral hippocampus, left thalamus, left postcentral gyrus, left superior parietal lobule, left cerebellum crus I and II, and vermis VI. DTI analysis showed increased fractional anisotropy and radial diffusivity in the right anterior insula and increased axial diffusivity in right cerebellum crus I in CMTX patients. rs-fMRI revealed decreased spontaneous neural activity on left precentral gyrus in patients compared to healthy controls.

Conclusion

Advanced magnetic resonance (MR) neuroimaging techniques in CMTX patients revealed structural and functional involvement of multiple motor and extra-motor brain areas. MR neuroimaging techniques have the potential to delineate the CNS phenotype of a peripheral neuropathy like CMTX.

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Data availability

All the imaging and clinical data are available upon request.

Code availability

MATLAB toolboxes and FMRIB Software Library (FSL) software are publicly available.

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Acknowledgements

We would like to thank all patients and healthy controls for their generosity to participate in the present study.

Funding

FC is supported by the EU-IKY Scholarship Program (European Social Fund-ESF), the Greek “Reinforcement of Postdoctoral Researchers” grant (5033021) of the “Human Resources Development Program, Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF 2014–2020).

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    Authors and Affiliations

    1. 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

      Efstratios Karavasilis, Eirini Pantou, Dimitrios Filippiadis & Georgios Velonakis

    2. Laboratory of Medical Physics, Medical School, National and Kapodistrian University of Athens, Athens, Greece

      Foteini Christidi

    3. 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece

      Georgia Angelopoulou, Dimitrios Kasselimis, Marianthi Breza & Constantin Potagas

    4. Neurogenetics Unit, 1st Department of Neurology, School of Medicine, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece

      Zoi Kontogeorgiou, Georgia Karadima & Georgios Koutsis

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    2. Foteini Christidi
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    3. Eirini Pantou
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    4. Georgia Angelopoulou
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    5. Dimitrios Kasselimis
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    6. Marianthi Breza
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    7. Zoi Kontogeorgiou
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    8. Dimitrios Filippiadis
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    9. Constantin Potagas
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    10. Georgia Karadima
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    11. Georgios Koutsis
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    12. Georgios Velonakis
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    Contributions

    Georgios Velonakis and Georgios Koutsis contributed to the study conception and design. Material preparation was performed by Efstratios Karavasilis, Georgios Velonakis, Georgios Koutsis, Marianthi Breza and Constantin Potagas, method preparation was performed by Georgios Velonakis, Efstratios Karavasilis, Dimitrios Filippiadis, clinical data collection was performed by Georgia Angelopoulou, Dimitrios Kasselimis, Zoi Kontogeorgiou, Georgia Karadima, Georgios Koutsis imaging data collection and evaluation were performed by Efstratios Karavasilis, Irene Pantou, Dimitrios Fillipiadis, Georgios Velonakis, the image post-processing and statistical analysis were performed by Efstratios Karavasilis and Foteini Christidi. The first draft of the manuscript was written by Efstratios Karavasilis, Georgios Velonakis, Foteini Christidi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

    Corresponding author

    Correspondence to Efstratios Karavasilis.

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    The authors declare no competing interests.

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    This cross-sectional study was approved by the local ethical committee and conducted according to the Declaration of Helsinki and its later amendments.

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    All participants provided informed consent for their participation.

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    All participants provided informed consent for the publication of results.

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    Cite this article

    Karavasilis, E., Christidi, F., Pantou, E. et al. Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study. Neuroradiology 64, 543–552 (2022). https://doi.org/10.1007/s00234-021-02730-x

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