TY - JOUR
T1 - A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]
T2 - Mechanical Stress, Vulnerability and Time
AU - Davies, Benjamin M.
AU - Mowforth, Oliver
AU - Gharooni, Aref Ali
AU - Tetreault, Lindsay
AU - Nouri, Aria
AU - Dhillon, Rana S.
AU - Bednarik, Josef
AU - Martin, Allan R.
AU - Young, Adam
AU - Takahashi, Hitoshi
AU - Boerger, Timothy F.
AU - Newcombe, Virginia F.J.
AU - Zipser, Carl Moritz
AU - Freund, Patrick
AU - Koljonen, Paul Aarne
AU - Rodrigues-Pinto, Ricardo
AU - Rahimi-Movaghar, Vafa
AU - Wilson, Jefferson R.
AU - Kurpad, Shekar N.
AU - Fehlings, Michael G.
AU - Kwon, Brian K.
AU - Harrop, James S.
AU - Guest, James D.
AU - Curt, Armin
AU - Kotter, Mark R.N.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research priorities were organized and funded by AO Spine through the AO Spine Knowledge Forum Spinal Cord Injury, a focused group of international Spinal Cord Injury experts. AO Spine is a clinical division of the AO Foundation, which is an independent medically-guided not-for-profit organization. Study support was provided directly through the AO Spine Research Department.MRNK is supported by a NIHR Clinician Scientist Award and BMD a NIHR Clinical Doctoral Research Fellowship. P.F. is funded by a SNF Eccellenza Professorial Fellowship grant (PCEFP3_181362/1)VFJN is supported by an Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship. This report is independent research arising from a Clinician Scientist Award, CS-2015-15-023, supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. JB was supported by the Czech Health Research Council grants NV18-04-00159 and by the Ministry of Health of the Czech Republic project for conceptual development in research organizations, ref. 65269705.
Funding Information:
Further details on this priority, including how it was prioritized, why it was prioritized, and on-going research activity can be found at www.aospine.org/recode/biological-basis. We thank Dr Robert Farr (London Institute, UK) and Prof. Michael Sutcliffe (University of Cambridge) for support with regards to the physical models. We thank Aimee Hutchinson [www.aimeehutchinson.com], Medial Illustrator, for the anatomical drawings of the cervical spine, and Iwan Sadler (Myelopathy.org) for assistance with producing the figures. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research priorities were organized and funded by AO Spine through the AO Spine Knowledge Forum Spinal Cord Injury, a focused group of international Spinal Cord Injury experts. AO Spine is a clinical division of the AO Foundation, which is an independent medically-guided not-for-profit organization. Study support was provided directly through the AO Spine Research Department.MRNK is supported by a NIHR Clinician Scientist Award and BMD a NIHR Clinical Doctoral Research Fellowship. P.F. is funded by a SNF Eccellenza Professorial Fellowship grant (PCEFP3_181362/1)VFJN is supported by an Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship. This report is independent research arising from a Clinician Scientist Award, CS-2015-15-023, supported by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. JB was supported by the Czech Health Research Council grants NV18-04-00159 and by the Ministry of Health of the Czech Republic project for conceptual development in research organizations, ref. 65269705.
Publisher Copyright:
© The Author(s) 2021.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - cervical
KW - degeneration
KW - disability
KW - disc herniation
KW - myelopathy
KW - ossification posterior longitudinal ligament
KW - questionnaire
KW - recovery
KW - spondylosis
KW - spondylotic
KW - stenosis
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U2 - 10.1177/21925682211057546
DO - 10.1177/21925682211057546
M3 - Article
AN - SCOPUS:85125812403
VL - 12
SP - 78S-96S
JO - Global Spine Journal
JF - Global Spine Journal
SN - 2192-5682
IS - 1_suppl
ER -