Abstract
This study aims to determine tissue-specific neurodegeneration across the spinal cord in patients with mild-moderate degenerative cervical myelopathy (DCM). Twenty-four mild-moderate DCM and 24 healthy subjects were recruited. In patients, a T2-weighted scan was acquired at the compression site, whereas in all participants a T2*-weighted and diffusion-weighted scan was acquired at the cervical level (C2-C3) and in the lumbar enlargement (i.e., rostral and caudal to the site of compression). We quantified intramedullary signal changes, maximal canal and cord compression, white (WM) and gray matter (GM) atrophy, and microstructural indices from diffusion-weighted scans. All patients underwent clinical (modified Japanese Orthopaedic Association; mJOA) and electrophysiological assessments. Regression analysis assessed associations between magnetic resonance imaging (MRI) readouts and electrophysiological and clinical outcomes. Twenty patients were classified with mild and 4 with moderate DCM using the mJOA scale. The most frequent site of compression was at the C5-C6 level, with maximum cord compression of 38.73% ± 11.57%. Ten patients showed imaging evidence of cervical myelopathy. In the cervical cord, WM and GM atrophy and WM microstructural changes were evident, whereas in the lumbar cord only WM showed atrophy and microstructural changes. Remote cervical cord WM microstructural changes were pronounced in patients with radiological myelopathy and associated with impaired electrophysiology. Lumbar cord WM atrophy was associated with lower limb sensory impairments. In conclusion, tissue-specific neurodegeneration revealed by quantitative MRI is already apparent across the spinal cord in mild-moderate DCM before the onset of severe clinical impairments. WM microstructural changes are particularly sensitive to remote pathologically and clinically eloquent changes in DCM.
Highlights
Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury and can lead to spinal cord dysfunction
This study aims to determine tissue-specific neurodegeneration across the spinal cord in patients with mildmoderate degenerative cervical myelopathy (DCM)
Remote cervical cord WM microstructural changes were pronounced in patients with radiological myelopathy and associated with impaired electrophysiology
Summary
Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury and can lead to spinal cord dysfunction. Degenerative changes of the spine lead to a progressive stenosis of the cervical spinal canal[1,2] with ensuing spinal cord compression. Cord compression triggers a cascade of pathophysiological processes (ischemia, inflammation, neuronal, and oligodendroglial apoptosis) at the site of compression producing irreversible neural tissue damage (cervical myelopathy)[3] as well as secondary anterograde and retrograde degeneration of spinal pathways[4] above and below the compression site.[5,6,7]. To detect tissue at risk and prevent irreversible tissue damage in the early stages of DCM, there is a pressing need to determine tissue integrity and the underlying pathophysiology[3] at and remote to the site of spinal cord compression. Quantitative MRI (qMRI) techniques can provide biomarkers sensitive to spinal cord tissue integrity[9] and underlying pathology in DCM7,10 and help in clinical decision making (i.e., early surgery vs. conservative treatment)
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