Metabolic and Structural Alterations in the Motor System Following Spinal Cord Injury: An In-Vivo 1H-MR Spectroscopy Investigation

Abstract

Spinal cord injury (SCI) disrupts spinal tracts and neuronal pathways, including those in the primary motor cortex (M1) and the lumbar cord enlargement (LCE) involved in motor control. This study sought to determine whether metabolite concentrations deviate between SCI and healthy controls (HC) in M1 and LCE using proton magnetic resonance spectroscopy (¹H-MRS) and structural MRI, and if these correlate with clinical impairment. Sixteen chronic SCI (mean age: 54.7 ± 14.8y) and 19 HCs (mean age: 53.2 ± 18.8y) underwent ¹H-MRS to quantify metabolites along with T₁- and T₂*-weighted MRI to assess tissue structural changes. Associations between metabolic and structural changes and clinical impairment were also assessed. Patients showed significant atrophy in both white matter of the LCE (HC: 37.7 ± 4.7 mm², SCI: 33.9 ± 3.7 mm², Δ = −10.1%, p = 0.015) and gray matter (HC: 20.9 ± 2.1 mm², SCI: 19.4 ± 1.5 mm², Δ = −7.2%, p = 0.022). Total N-acetylaspartate (tNAA) with respect to total creatine (tCr) was reduced in M1 of SCI (HC: 1.94 ± 0.21, SCI: 1.77 ± 0.14, ∆ = −8.8%, p = 0.006) and in the LCE (HC: 2.48 ± 0.76, SCI: 1.81 ± 0.80, ∆ = −27.0%, p = 0.02). In conclusion, reduced tNAA/tCr in both the atrophied LCE and M1 suggests widespread neuronal changes including cell atrophy and/or cell loss after injury. These findings provide in vivo evidence for retrograde and trans-synaptic neurodegeneration, which may underline the atrophy observed in the motor system in SCI. Ultimately, this highlights the potential for metabolic and structural biomarkers to improve the monitoring of subtle neurodegeneration following SCI and to enhance future regenerative treatment strategies.