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Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis

  • Stefano MagonEmail author
  • Charidimos Tsagkas
  • Laura Gaetano
  • Raihaan Patel
  • Yvonne Naegelin
  • Michael Amann
  • Katrin Parmar
  • Athina Papadopoulou
  • Jens Wuerfel
  • Christoph Stippich
  • Ludwig Kappos
  • M. Mallar Chakravarty
  • Till Sprenger
Original Communication

Abstract

Background

Volume loss in the deep gray matter (DGM) has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and is thought to progress throughout the disease course.

Objective

To investigate the impact and predictive value of volume loss in DGM and thalamic subnuclei on disability worsening in patients MS over a 6-year follow-up period.

Methods

Hundred and seventy-nine patients with RRMS (132 women; median Expanded Disability Status Scale, EDSS: 2.5) and 50 with SPMS (27 women; median EDSS: 4.5) were included in the study. Patients underwent annual EDSS assessments and annual MRI at 1.5 T. DGM/thalamic subnuclei volumes were identified on high-resolution T1-weighted. A hierarchical linear mixed model for each anatomical DGM area and each thalamic subnucleus was performed to investigate the associations with disability scores. Cox regression was used to estimate the predictive properties of volume loss in DGM and thalamic subnuclei on disease worsening.

Results

In the whole sample and in RRMS, volumes of the thalamus and the striatum were associated with the EDSS; however, only thalamic volume loss was associated with EDSS change at follow-up. Regarding thalamic subnuclei, volume loss in the anterior nucleus, the pulvinar and the ventral anterior nucleus was associated with EDSS change in the whole cohort. A trend was observed for the ventral lateral nucleus. Volume loss in the anterior and ventral anterior nuclei was associated with EDSS change over time in patients with RRMS. Moreover, MS phenotype and annual rates of volume loss in the thalamus and ventral lateral nucleus were predictive of disability worsening.

Conclusion

These results highlight the relevance of volume loss in the thalamus as a key metric for predicting disability worsening as assessed by EDSS (in RRMS). Moreover, the volume loss in specific nuclei such as the ventral lateral nucleus seems to play a role in disability worsening.

Keywords

Multiple sclerosis Volumetric MRI Thalamus Deep gray matter Thalamic subnuclei 

Notes

Compliance with ethical standards

Conflicts of interest

Charidimos Tsagkas, Chakravarty M. Mallar, Christoph Stippich, Amann Michael and Raihaan Patel have no disclosures. Naegelin Yvonne: Her employer, the University Hospital Basel received payments for lecturing from Celgene GmbH and Teva Pharma AG that were exclusively used for research support, not related to this study. K. Parmar: Her institution (University Hospital Basel) received speakers’ honoraria from Novartis and ExceMED and travel support by Novartis Switzerland. Laura Gaetano was a temporary employee of Novartis AG and she is currently an employee of F. Hoffmann-La Roche (her current institution was not involved in this project at any time). Athina Papadopoulou has received speaker-fee from Sanofi-Genzyme and travel support from Bayer AG, Teva, Roche and ECTRIMS. Her research was/is being supported by the University of Basel, the Swiss Multiple Sclerosis Society, the Swiss National Science Foundation and the “Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung”. J. Wuerfel: CEO of MIAC AG, Basel, Switzerland; speaker honoraria (Bayer, Biogen, Novartis, Teva); advisory boards and research grants (Biogen, Novartis); supported by the German Ministry of Science (BMBF/KKNMS) and German Ministry of Economy (BMWi). Ludwig Kappos’ institution (University Hospital Basel) has received research support and payments that were used exclusively for research support for Dr Kappos’ activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare, Celgene, CLC Behring, Genentech, GeNeuro, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono, Pfizer, Receptos, F. Hoffmann-La Roche, Sanofi- Aventis, Santhera, Siemens, Teva, UCB, and XenoPort; licence fees for Neurostatus 4 products; research grants from the Swiss Multple Sclerosis Society, the Swiss National Research Foundation, the European Union, and the Roche Research Foundation. The current (DKD Helios Klinik Wiesbaden) or previous (University Hospital Basel) institutions of Till Sprenger have received payments for speaking or consultation from: Biogen Idec, Eli Lilly, Allergan, Actelion, ATI, Mitsubishi Pharma, Novartis, Genzyme, and Teva. Dr. Sprenger received research grant s from the Swiss MS Society, Novartis Pharmaceuticals Switzerland, EFIC-Grünenthal grant, and Swiss National Science foundation. Stefano Magon is currently an employee of F. Hoffmann-La Roche (his current institution was not involved in this project at any time). He has received research support from Swiss Multiple Sclerosis Society, Swiss National Science Foundation, University of Basel and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung University Hospital Basel.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Stefano Magon
    • 1
    • 2
    Email author
  • Charidimos Tsagkas
    • 1
    • 2
  • Laura Gaetano
    • 1
    • 2
  • Raihaan Patel
    • 3
    • 4
  • Yvonne Naegelin
    • 1
  • Michael Amann
    • 1
    • 2
    • 6
  • Katrin Parmar
    • 1
    • 2
  • Athina Papadopoulou
    • 1
    • 5
  • Jens Wuerfel
    • 2
    • 6
  • Christoph Stippich
    • 7
  • Ludwig Kappos
    • 1
  • M. Mallar Chakravarty
    • 3
    • 4
    • 8
  • Till Sprenger
    • 1
    • 9
  1. 1.Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, Department of NeurologyUniversity Hospital Basel and University of BaselBaselSwitzerland
  2. 2.Medical Image Analysis Center AGBaselSwitzerland
  3. 3.Cerebral Imaging Centre–Douglas Mental Health University InstituteVerdunCanada
  4. 4.Department of Biomedical EngineeringMcGill UniversityMontrealCanada
  5. 5.NeuroCure Clinical Research Center, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität BerlinHumboldt-Universität Zu Berlin, and Berlin Institute of HealthBerlinGermany
  6. 6.Department of Biomedical EngineeringUniversity BaselBaselSwitzerland
  7. 7.Department of Neuroradiology, University Hospital ZurichUniversity of ZurichZurichSwitzerland
  8. 8.Department of PsychiatryMcGill UniversityMontrealCanada
  9. 9.Department of NeurologyDKD HELIOS Klinik WiesbadenWiesbadenGermany

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