A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]: Mechanical Stress, Vulnerability and Time

Author:

Davies Benjamin M.1ORCID,Mowforth Oliver1ORCID,Gharooni Aref-Ali1ORCID,Tetreault Lindsay2,Nouri Aria3ORCID,Dhillon Rana S.4,Bednarik Josef5ORCID,Martin Allan R.6,Young Adam1,Takahashi Hitoshi7,Boerger Timothy F.8ORCID,Newcombe Virginia FJ9,Zipser Carl Moritz10,Freund Patrick10,Koljonen Paul Aarne11ORCID,Rodrigues-Pinto Ricardo1213ORCID,Rahimi-Movaghar Vafa14,Wilson Jefferson R.15ORCID,Kurpad Shekar N8,Fehlings Michael G.15ORCID,Kwon Brian K.16,Harrop James S.17,Guest James D.18,Curt Armin10,Kotter Mark R. N.1

Affiliation:

1. Department of Neurosurgery, University of Cambridge, Cambridge, UK

2. New York University, Langone Health, Graduate Medical Education, Department of Neurology, New York, NY, USA

3. Division of Neurosurgery, Geneva University Hospitals, University of Geneva, Genève, Switzerland

4. Department of Neurosurgery, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia

5. Department of Neurology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic

6. Department of Neurosurgery, University of California Davis, Sacramento, CA, USA

7. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan

8. Department of Neurosurgery, Medical College of Wisconsin, Wauwatosa, WI, USA

9. Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK

10. University Spine Center, Balgrist University Hospital, Zurich, Switzerland

11. Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

12. Spinal Unit (UVM), Department of Orthopaedics, Centro Hospitalar Universitário do Porto - Hospital de Santo António, Porto, Portugal

13. Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal

14. Department of Neurosurgery, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran

15. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada

16. Vancouver Spine Surgery Institute, Department of Orthopedics, The University of British Columbia, Vancouver, BC, Canada

17. Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA

18. Department of Neurosurgery and the Miami Project to Cure Paralysis, The Miller School of Medicine, University of Miami, Miami, FL, USA

Abstract

Study Design Literature Review (Narrative) Objective To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5. Methods Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual’s susceptibility, including the proposal of a new framework. Results Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with visualized cord compression show clinical myelopathy, and the amount of cord compression only weakly correlates with disability. We propose that DCM is better represented as a function of several interacting mechanical forces, such as shear, tension and compression, alongside an individual’s vulnerability to spinal cord injury, influenced by factors such as age, genetics, their cardiovascular, gastrointestinal and nervous system status, and time. Conclusion Understanding the disease pathobiology is a fundamental research priority. We believe a framework of mechanical stress, vulnerability, and time may better represent the disease as a whole. Whilst this remains theoretical, we hope that at the very least it will inspire new avenues of research that better encapsulate the full spectrum of disease.

Publisher

SAGE Publications

Subject

Neurology (clinical),Orthopedics and Sports Medicine,Surgery

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