Tracking White and Gray Matter Degeneration along the Spinal Cord Axis in Degenerative Cervical Myelopathy

Abstract

This study aims to determine tissue-specific neurodegeneration across the spinal cord in patients with mildmoderate 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, tissuespecific 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.

Quantitative MR Markers in Non-Myelopathic Spinal Cord Compression: A Narrative Review

“…Some also found deficits in RD and MTR pointing to the demyelination [8,28,82] and AD alteration due to axonal injury as the primary alteration at MCL [8]. Rostral secondary changes in DCM patients presented as lower FA and higher diffusivity measures in dorsal columns and lateral corticospinal tracts and changes in 1 H-MRS ratios at C2/3 level point to remote Wallerian degeneration above the compression level [8,32,39,40,42,43,75,103,104]. Subtle remote changes at C2/3 level between NMDC and HC were then revealed by the multi-compartment Ball-and-Sticks diffusion model, 1 H-MRS, and MTR [8,28,32].…”

“…SC volumetry adds to the compression metrics at MCL when assessing changes above and below the compression levels. So far, studies demonstrated gradual reduction of SC, WM and GM volumes at C2/3 above the compression level in DCM and NMDC relative to HC and each other (Figure 2) [8,32,[39][40][41][42][43], pointing to more severe Wallerian neurodegeneration and atrophy in DCM than NMDC [8,41] with similar changes in DCM also caudally at T11-L1 level [43]. However, morphometric and volumetric metrics might suffer from inter-subject variability due to anatomical and biological factors such as age, sex, height or weight, which showed significant correlations in healthy subjects and patients with SC compression [2,[44][45][46].…”

“…Multiple studies [23,25,26,30,36,38,42,55,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80] and reviews [23,24] covered DTI in symptomatic DCM patients, whereas a limited number of works focused on NMDC patients [8,[25][26][27][28][29][30] (Table 2). So far, NMDC studies have also suffered from a lack of nomenclature and inclusion criteria consistency that differs between regions and countries (Table 1).…”

“…Besides direct changes at MCL, studies have also focused on remote neurodegeneration above the compression level in both NMDC and DCM patients. DCM studies [8,39,40,42,43,75] consistently detected decreased FA and increased diffusivity measures at C2/C3 level in dorsal and lateral WM tracts compared to HC, whereas only two DCM studies showed changes also in rostral GM [8,40]. The recent NMDC study detected similar changes at C3 level, i.e., decreased FA and increased MD and RD in dorsal and lateral tracts and increased diffusivity measures in GM between DCM and NMDC patients [8].…”

Brain Structural and Functional Dissociated Patterns in Degenerative Cervical Myelopathy: A Case-Controlled Retrospective Resting-State fMRI Study

“…In the past decade, researchers have relied on conventional cervical spine MRI to monitor and determine spinal cord structural changes in DCM patients, e.g., high signal intensity on T2-weighted MR ( 8 , 9 ). Its utility remains controversial as the information obtained from the spinal cord area is limited, i.e., the small cross-sectional area ( 10 – 12 ). Therefore, researchers set their sights on resting-state functional MRI for exploring brain alterations in patients with DCM ( 13 – 15 ).…”