Glymphatic System Dysfunction Associated with Inflammatory Factors in Asymptomatic Neurosyphilis

This study seeks to delineate glymphatic system-related alterations in individuals with Asymptomatic Neurosyphilis (ANS) and to elucidate their correlation with inflammatory responses, with the objective of identifying early neuroimaging biomarkers indicative of neurosyphilis infection.

In this prospective analysis, 33 patients with ANS and 29 matched healthy controls (HC) were enrolled from The Second Hospital of Nanjing. All participants underwent Magnetic Resonance Imaging (MRI) scanning. The diffusion tensor image analysis along the perivascular space (DTIALPS) indices and normalized enlarged perivascular spaces (EPVS) volume were quantified and compared between the ANS and HC groups. Furthermore, correlations were assessed between imaging-derived metrics and inflammatory profiles from both Cerebrospinal Fluid (CSF) and peripheral blood samples.

Marked differences in DTI-ALPS indices and normalized EPVS volume were evident between the ANS and HC groups. Post hoc analyses revealed that the ANS group exhibited significantly reduced DTI-ALPS indices (1.40 vs 1.60, p = 0.0001) and elevated normalized EPVS volume (2.28 vs. 2.05, p = 0.0355) relative to healthy individuals. In ANS, unadjusted analyses suggested that normalized EPVS volume demonstrated a positive correlation with CSF nucleated cell count (r = 0.413, p = 0.017), and a significant inverse relationship was observed between DTI-ALPS values and CSF lactate dehydrogenase (LDH) concentrations (r = -0.385, p = 0.027). However, after False Discovery Rate (FDR) correction, these correlations did not reach statistical significance.

The findings demonstrate, to our knowledge, for the first time, significant glymphatic system-related impairment in ANS. The reduced DTI-ALPS index suggests diminished glymphatic activity, while increased normalized EPVS volume points to structural perivascular alterations. The exploratory correlations between these imaging metrics and CSF inflammatory markers indicate a potential relationship between glymphatic system-related dysfunction and neuroinflammation in early neurosyphilis.

Taken together, these findings indicate that distinct alterations in DTI-ALPS indices and normalized EPVS volume may represent novel neuroimaging biomarkers for the early detection and clinical evaluation of ANS. Utilization of these imaging indices could potentially enhance diagnostic precision and inform prognostic assessment in affected patients.