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

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.

Comparative intra- and inter-observer reliability of two methods for evaluating intraoperative ultrasonography-based spinal cord hyperechogenicity intensity in degenerative cervical myelopathy

“…The T2W signal intensity of the spinal cord is widely used to assess the impairment status and predict the neurological recovery of DCM [ 6 ]. However, conventional MRI consisting of T1w and T2w anatomical images offer only limited insight into pathological tissue changes, prompting the development of more advanced MRI sequences and emerging methods of imaging and electrophysiology that assess specific features of microstructure and tissue injury for the management of DCM [ 4 , 5 ]. Recently, intraoperative ultrasonography (IOUS) was performed to evaluate and guide surgical decompression, and some IOUS-derived metrics were confirmed to be significantly correlated with the neurological function in DCM [ 7 , 8 ].…”

“…T2W hyperintensity may also reflect transient or permanent microstructural changes such as edema, gliosis, inflammation, demyelination, spongiform changes, necrosis, and cavitation. Conventional MRI has been studied as a tool to assess the severity of spinal cord damage that has occurred, both in terms of correlation with current neurological status and prediction of post-surgical outcomes [ 4 , 5 ]. The T2W signal intensity of the spinal cord is widely used to assess the impairment status and predict the neurological recovery of DCM [ 6 ].…”

Cerebrospinal fluid pressure dynamics reveal signs of effective spinal canal narrowing in ambiguous spine conditions

“…The pathophysiology of DCM is still incompletely understood, and its investigation was defined a key research priority in DCM ( 29 ). Imaging is a major asset in the evaluation of cord distress, providing structural information as well as dynamic parameters, such as CSF flow and cord motion ( 30 ).…”

Development of a core measurement set for research in degenerative cervical myelopathy: a study protocol (AO Spine RECODE-DCM CMS)

“…Degenerative cervical myelopathy (DCM) is a common and often disabling disease 1. Estimated to affect as many as one in fifty adults,1 it develops due to degenerative and/or congenital changes in the cervical spine leading to mechanical stress and a progressive spinal cord injury 2–4. This disease can lead to a wide variety of symptoms, affecting the whole body 5.…”

“…So far, AO Spine RECODE-DCM has established the top research priorities and agreed on a single definition and index term 4 8 21–32. It has also agreed on ‘what’ should be measured in DCM research: that is, a minimum data set, which is comprised core data elements (CDE) and a core outcome set (COS).…”