Deciphering the Role of Glial Cell-Specific Metabolites as Biomarkers in Early Cervical Myelopathy- Insights from in vivo MRS study.

Background: Early degenerative cervical myelopathy (DCM) presents a diagnostic dilemma due to its variability in presentation, overlap with other clinical conditions, and lack of specific clinical tests. Although magnetic resonance imaging (MRI) is the preferred imaging modality, its ability to detect early cervical myelopathy remains uncertain due to its inability to detect microstructural changes at an early spondylotic stage. Magnetic Resonance Spectroscopy (MRS) is a novel, non-invasive spinal imaging technique that provides metabolic and biochemical information regarding spinal cord function.

Purpose: This study aims to determine the diagnostic role of MRS and Diffusion Tensor Imaging (DTI) in patients with DCM. Additionally, we intend to explore the role of MRS metabolites/ratio as molecular biomarkers for the early detection of DCM.

Study design: Prospective observational study PATIENT SAMPLE: The study includes a sample size of 89 subjects (20 asymptomatic volunteers and 69 patients with different grades of DCM.

Outcome measures: Predictability of MRS and DTI in identifying early DCM. The severity of myelopathy was assessed using the modified Japanese Orthopaedic Association (mJOA) score.

Methods: The study populations were classified according to their mJOA scores: Group 1 included asymptomatic volunteers with no clinical features of cervical myelopathy. Group 2 included patients with a score of 15 to 17 (mJOA "mild") presenting with early symptoms of myelopathy, like arm pain, hand numbness and clumsiness with/ without the symptoms of radiculopathy. Group 3 included patients with mJOA "moderate" myelopathy score of 12 to 14, presenting with symptoms like gait instability and a decrease in hand dexterity. Group 4 included patients with mJOA "severe" score of less than or equal to 11, presenting with advanced symptoms like walker/wheelchair-dependence, loss of hand dexterity, and bladder disturbances. We then looked at MR Imaging in these symptomatic patients to evaluate stenosis. Single voxel MRS was placed at the C2 level, and DTI parameters were measured at the site of maximum compression. MRI parameters like the compression level, presence of signal hyperintensity, grading of stenosis, and compression ratio were also analysed in T2W MRI images.

Results: Among the 89-study population, 20 asymptomatic volunteers in group 1 and 23 patients each in groups 2, 3 and 4 were included. Among the various parameters, there was a statistically significant difference between the groups for various MRS metabolite ratios, namely NAA/Cr (P= 0.008), Cho/Cr (P=0.025), Cho/NAA (P<0.001), Cr/NAA (P <0.001) and MIn/NAA (P=0.003) as well as DTI parameters namely FA (P= 0.010) and ADC (P=0.011). A significant linear correlation was observed between the severity of myelopathy (mJOA score) and the following parameters: Cho/NAA (R²=0.510, P=0.000), MIn/NAA (R²=0.393, P=0.002), Cr/NAA (R²=0.354, P=0.007), FA (R²= -0.331, P=0.012), ADC (R²=0.321, P=0.015), Cho/Cr (R²=0.289, P=0.029) and NAA (R²= -0.288, P=0.030). Among the various metabolites, we observed that the glial cell-specific metabolites (Cho, Cr and MIn) with respect to the neuron-specific metabolite, NAA, had good correlation in early identification of DCM patients presenting with mild to moderate disease severity. ROC analysis showed that glial cell-specific metabolites ratio(Cho/NAA, Cr/NAA, MIn/NAA) had good AUC for identifying both mild (0.725, 0.770, 0.765) and moderate (0.825, 0.736, 0.760) myelopathy.

Conclusion: Our study highlights that MRS-based Glial cell-specific metabolites ratio (Cho/NAA, Cr/NAA, and MIn/NAA) can be reliable molecular biomarkers for identifying early degenerative cervical myelopathy.