Priority 5 from the Degenerative Cervical Myelopathy PSP

UNCERTAINTY: What is the pathophysiology of DCM? What are the mechanisms of neurologic injury and the molecular and anatomical consequences? (JLA PSP Priority 5)
Overall ranking	5
JLA question ID	0097/5
Explanatory note	DCM is a progressive disease caused by age-related degeneration of the facet joints, intervertebral disks, or vertebral bodies; hypertrophy of the ligamentum flavum; ossification of the posterior longitudinal ligament; and/or progressive cervical kyphosis. These changes ultimately narrow the spinal canal and reduce the space available for the spinal cord. Mechanical compression of the cord can result in a cascade of pathophysiological events, including ischemia, endothelial cell impairment, disruption of the blood-spinal cord barrier, neuroinflammation and apoptosis. Longstanding compression of the cord can lead to axonal demyelination, gliosis, scarring, degeneration of the corticospinal tracts, interneuronal loss and atrophy of the anterior horn cells. Despite this knowledge, further work is required to fully elucidate the pathophysiology of DCM and determine important therapeutic targets that might enhance recovery.
Evidence	No systematic reviews, scoping reviews or guidelines identified. Several literature reviews identified on the topic, including Karadimas SK, Erwin WM, Ely CG, Dettori JR, Fehlings MG. Pathophysiology and natural history of cervical spondylotic myelopathy. Spine (Phila Pa 1976). 2013 Oct 15;38(22 Suppl 1):S21-36.
Health Research Classification System category	Neurological

Extra information provided by this PSP
Original uncertainty examples	What is the aetiology? ~ Why does DCM cause neurological impairment? What are the exact structures and neural pathways that are affected? ~ What spinal cord pathological changes underlie motor and sensory deficits in CSM? ~ What causes DCM?
Submitted by	Spinal Surgeons x 12, Other healthcare professionals x 6, People with DCM and their supporters x 3

PSP information
PSP unique ID	0097
PSP name	Degenerative Cervical Myelopathy
Total number of uncertainties identified by this PSP.	76 (To see a full list of all uncertainties identified, please see the detailed spreadsheet held on the JLA website)
Date of priority setting workshop	20 November 2019