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New and enlarging white matter lesions adjacent to the ventricle system and thalamic atrophy are independently associated with lateral ventricular enlargement in multiple sclerosis

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Abstract

Objective

To investigate the association between new or enlarging T2-weighted (w) white matter (WM) lesions adjacent to the ventricle wall, deep grey matter (DGM) atrophy and lateral ventricular enlargement in multiple sclerosis (MS).

Methods

Patients derived from the Genetic Multiple Sclerosis Associations study. Lateral ventricles and DGM were segmented fully automated at baseline and 5 years follow-up using Automatic Lateral Ventricle delineation (ALVIN) and Multiple Automatically Generated Templates brain segmentation algorithm (MAgeT), respectively. T2w and T1w lesions were manually segmented. To investigate the association between lesion distance to the ventricle wall and the lateral ventricle volume, we parcellated the WM into concentric periventricular bands using FMRIB Software Library. Associations between clinical and MRI parameters were assessed in generalized linear models using generalized estimating equations for repeated measures.

Results

We studied 127 MS patients. Lateral ventricles enlarged on average by 2.4%/year. Patients with new/enlarging T2w WM lesions between baseline and follow-up at 5 years had accelerated lateral ventricular enlargement compared with patients without (p = 0.004). This was true in a multivariable analysis adjusted for age, gender, and whole brain atrophy. When looking at the T2w lesions in different periventricular bands, we found the strongest association between new/enlarging T2w lesions and lateral ventricle enlargement for WM lesions adjacent to the ventricle system (p < 0.001). Moreover, and indepedent of new/enlarging WM lesions, DGM atrophy was associated with ventricular enlargement. In a multivariable analysis, this was driven by thalamic atrophy (p < 0.001).

Conclusion

New/enlarging T2w lesions adjacent to the ventricle system and thalamic atrophy are independently associated with lateral ventricular enlargement in MS.

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Acknowledgements

We thank all patients participated in the Genetic Multiple Sclerosis Associations study.

Author information

Author notes

  1. Tim Sinnecker and Esther Ruberte are equally contributed first authors.

  2. Stefano Magon and Özgür Yaldizli are equally contributed last authors.

Authors and Affiliations

  1. Neurologic Clinic and Policlinic, Departments of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland

    Tim Sinnecker, Vera Canova, Yvonne Naegelin, Jannis Müller, Jens Kuhle, Bernhard Décard, Tobias Derfuss, Ludwig Kappos, Cristina Granziera, Stefano Magon & Özgür Yaldizli

  2. Translational Imaging in Neurology [ThINK] Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland

    Tim Sinnecker, Jannis Müller, Cristina Granziera, Stefano Magon & Özgür Yaldizli

  3. Medical Image Analysis Center Basel AG, Basel, Switzerland

    Tim Sinnecker, Esther Ruberte, Michael Amann, Jens Wuerfel & Stefano Magon

  4. Clinical Trial Unit, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland

    Sabine Schädelin

  5. Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany

    Iris-Katharina Penner

  6. Department of Neurology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    Özgür Yaldizli

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  1. Tim Sinnecker
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Corresponding author

Correspondence to Özgür Yaldizli.

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Conflicts of interest

Tim Sinnecker is part-time employee of the Medical Image Analysis Center Basel. Esther Ruberte has nothing to disclose. Sabine Schädelin has nothing to disclose. Vera Canova has nothing to disclose. Michael Amann has nothing to disclose. Yvonne Naegelin has nothing to dislose. Iris-Katharina Penner has nothing to disclose. Jannis Müller has nothing to disclose. Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation [320030_160221], University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva. Bernhard Décard received travel support and/or fees for the institution [University Hospital Basel] from advisory boards or speaker fees from Allmirall, Biogen, Genzyme, Roche, Teva and Novartis, that were used exclusively for research support. Tobias Derfuss received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme; he received research support from Biogen, Novartis, Swiss National Research Foundation, University of Basel, and Swiss MS Society. Ludwig Kappos´s institution [University Hospital Basel] received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation. Cristina Granziera has nothing to disclose. Jens Wuerfel is CEO of the Medical Image Analysis Center Basel. Stefano Magon is employee from F. Hoffmann-La Roche AG. Özgür Yaldizli´s institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme, Biogen and Novartis Poland exclusively used for support of research and educational activities.

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Sinnecker, T., Ruberte, E., Schädelin, S. et al. New and enlarging white matter lesions adjacent to the ventricle system and thalamic atrophy are independently associated with lateral ventricular enlargement in multiple sclerosis. J Neurol 267, 192–202 (2020). https://doi.org/10.1007/s00415-019-09565-w

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