Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF...

To investigate whether dysfunction of the glymphatic system and altered neurofluidic dynamics contribute to the pathophysiology of classical trigeminal neuralgia (CTN), and to explore the potential interplay between brain-CSF coupling and structural brain changes.

A total of 131 patients with CTN and 106 age- and sex-matched healthy controls were recruited. All participants underwent multimodal MRI, including high-resolution structural imaging, resting-state functional MRI, and diffusion tensor imaging. Key indices included choroid plexus (CP) volume as a proxy for CSF production, global BOLD-CSF coupling as a measure of functional neurofluidic interaction, and the DTI-based ALPS index reflecting glymphatic clearance. Additional markers included peak width of skeletonized mean diffusivity (PSMD) and global gray/white matter and CSF volume. Partial correlation analyses were performed between imaging metrics and clinical assessments.

CTN patients showed significantly increased CP volume (P = 0.022) and gBOLD-CSF coupling (P < 0.001), along with reduced bilateral ALPS indices (P = 0.002, P = 0.004). PSMD and CSF volume were elevated (P < 0.001, P < 0.001), while gray and white matter volumes were reduced (P = 0.028, P = 0.009). gBOLD-CSF coupling correlated positively with depression, anxiety, and pain-related disability scores (P < 0.001), and negatively with MMSE (P = 0.022).

This study provides multimodal MRI evidence of glymphatic dysfunction and neurofluidic alterations in CTN, supporting a conceptual framework in which disrupted brain-CSF interaction may influence peripheral sensory modulation through a putative brain-CSF-ganglion pathway. These results may inform mechanistic hypotheses and guide future research on the neurofluidic underpinnings of neuropathic pain, potentially providing new insights into the pathogenesis of CTN.