In vivo Molecular Signatures of Cervical Spinal Cord Pathology in Degenerative Compression

Abstract

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy ( 1 H-MRS).Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HC). MRS voxel was centered at C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (p FWE <0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p <0.05). While ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), Myo-inositol/tNAA, glutamate+glutamine/tNAA and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HC. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376<r<-0.259). Myo-inositol/tNAA correlated with myelopathy symptoms (r = -0.670), whereas CSC volume did not. Short-echo 1 H-MRS provided neurochemical signatures of CSC impairment that reflected compression severity and clinical significance. While volumetry only reflected clinically manifest myelopathy (DCM), MRS detected neurochemical changes already before the onset of myelopathy symptoms. Supplementary material is available for this article.

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

“…However, these studies included no more than 35 participants [96,101,104], and did not involve NMDC patients. Recent 1 H-MRS study in 60 NMDC patients with or without electrophysiological changes and radiculopathy but without myelopathic symptoms (mJOA scale =18) showed, for the first time, increased tCr/tNAA and myo-Ins/tNAA ratios above the stenosis level in NMDC relative to HC pointing to neurochemical changes detectable in clinically silent subjects (Figure 3B) [32]. The high sensitivity of this study arises from superior accuracy in semi-LASER voxel localization [105], improved signal-to-noise ratio at high-field 3T scanner, and cardiac triggering minimizing bias from surrounding tissue and cardiac pulsations [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].…”

“…Adapted from [8], CC BY-NC; (c) Singlevoxel magnetic resonance spectroscopy ( 1 H-MRS) measuring metabolic concentrations from above the compression level C2/3 (red box). Adapted from [32], CC BY-NC.…”

“…Adapted from [8], CC BY-NC (https://creativecommons.org/licenses/by-nc/4.0/); B) Between-group difference in neurometabolies ratios gained from single-voxel magnetic resonance spectroscopy ( 1 H-MRS) from above the compression level C2/3. Adapted from [32], CC BY-NC.…”

“…The alteration of metabolite profile reflects microstructural or metabolic pathophysiological processes [97]. Metabolite ratios (e.g., myo-inositol (myo-Ins)/N-acetylaspartate (NAA)) could be more sensitive to SC pathology than the metabolites referenced to the water signal particularly when the two metabolites' changes in different direction, for instance, when increased myo-Ins due to the gliosis/astrocytosis compensates the neuronal loss, which per se causes NAA decrease [32,98]. 1 H-MRS in the SC is challenged by the small transversal SC diameters, which is further diminished at the compression level.…”