The Role of the Glymphatic System in Cervical Spondylotic Myelopathy

Study Design: Prospective cohort study. Objective: To provide a primer of the glymphatic system, discuss its potential relevance in evaluating spinal diseases like cervical spondylotic myelopathy (CSM), and describe possible imaging markers of the glymphatic system derived from advanced diffusion-weighted imaging (dMRI), namely diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI). Summary of Background Data: The glymphatic system is a recently described physiological process that plays an integral role in macroscopic waste clearance in the CNS through cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange. Chronic spinal cord compression in CSM leads to pathophysiological consequences that theoretically affect the glymphatic system, and advanced dMRI may be well positioned to characterize these changes. Methods: This single-center study enrolled participants (control and CSM) from 2018 through 2020. All participants underwent clinical assessments and dMRI, followed by DTI and DBSI analyses, preoperatively and 2 years postoperatively. CSF flow was characterized by DTI-derived apparent diffusion coefficient (ADC) and ISF flow by DBSI-derived extra-axonal axial diffusivity (EA-AD) and radial diffusivity (EA-RD). Imaging parameters were compared among participants. Results: Forty-two patients with CSM [23 (55%) mild, 9 (24%) moderate, 10 (21%) severe] and 20 control patients were included. Preoperatively, ADC was significantly lower in CSM (2.59±0.4 µm 2 /ms) than control (3.08±0.34 µm 2 /ms) patients ( P <0.01). Conversely, EA-AD and EA-RD were significantly higher in CSM (2.53±0.33; 0.48±0.13 µm 2 /ms) compared with control (2.27±0.2; 0.40±0.04 µm 2 /ms) patients (both P <0.01). Two years postoperatively, only EA-RD significantly decreased for CSM patients (Δ-0.04±0.12 µm 2 /ms, P <0.01). More severe CSM preoperatively was associated with lower baseline ADC (ρ=0.49, P <0.001) and higher baseline EA-RD (ρ=−0.35, P =0.005). Conclusions: The pathophysiology of CSM may affect the glymphatic system because of chronic spinal cord compression that decreases CSF bulk flow, leading to compensatory increases in ISF flow. Although research in this topic remains nascent, greater glymphatic system function observed on dMRI may correspond with greater disease burden. Future studies examining the role of the glymphatic system in spinal cord pathology are critical to better understanding how these noninvasive imaging biomarkers can improve patient outcomes in CSM. Level of Evidence: Level II.