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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

  • Tim Sinnecker
  • Esther Ruberte
  • Sabine Schädelin
  • Vera Canova
  • Michael Amann
  • Yvonne Naegelin
  • Iris-Katharina Penner
  • Jannis Müller
  • Jens Kuhle
  • Bernhard Décard
  • Tobias Derfuss
  • Ludwig Kappos
  • Cristina Granziera
  • Jens Wuerfel
  • Stefano Magon
  • Özgür YaldizliEmail author
Original Communication

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.

Keywords

Multiple sclerosis MRI Lateral ventricle volume Thalamic atrophy Periventricular white matter lesion 

Notes

Acknowledgements

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

Compliance with ethical standards

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.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Tim Sinnecker
    • 1
    • 2
    • 3
  • Esther Ruberte
    • 3
  • Sabine Schädelin
    • 4
  • Vera Canova
    • 1
  • Michael Amann
    • 3
  • Yvonne Naegelin
    • 1
  • Iris-Katharina Penner
    • 5
  • Jannis Müller
    • 1
    • 2
  • Jens Kuhle
    • 1
  • Bernhard Décard
    • 1
  • Tobias Derfuss
    • 1
  • Ludwig Kappos
    • 1
  • Cristina Granziera
    • 1
    • 2
  • Jens Wuerfel
    • 3
  • Stefano Magon
    • 1
    • 2
    • 3
  • Özgür Yaldizli
    • 1
    • 2
    • 6
    Email author
  1. 1.Neurologic Clinic and Policlinic, Departments of MedicineUniversity Hospital Basel and University of BaselBaselSwitzerland
  2. 2.Translational Imaging in Neurology [ThINK] Basel, Department of Medicine and Biomedical EngineeringUniversity Hospital Basel and University of BaselBaselSwitzerland
  3. 3.Medical Image Analysis Center Basel AGBaselSwitzerland
  4. 4.Clinical Trial Unit, Department of Clinical ResearchUniversity Hospital Basel and University of BaselBaselSwitzerland
  5. 5.Department of NeurologyUniversity Hospital DüsseldorfDüsseldorfGermany
  6. 6.Department of NeurologyUniversity Hospital BaselBaselSwitzerland

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