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

Abstract Objective 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. Methods A total...

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Main Authors: Fenyang Chen, Zhiliang Zhang, Jianliang Miao, Yvting Zhang, Ding Wang, Juncheng Yan, Lei Pan, Haiqi Ye, Zhongxiang Ding, Xiuhong Ge
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Medical Imaging
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Online Access:https://doi.org/10.1186/s12880-025-01801-2
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author Fenyang Chen
Zhiliang Zhang
Jianliang Miao
Yvting Zhang
Ding Wang
Juncheng Yan
Lei Pan
Haiqi Ye
Zhongxiang Ding
Xiuhong Ge
author_facet Fenyang Chen
Zhiliang Zhang
Jianliang Miao
Yvting Zhang
Ding Wang
Juncheng Yan
Lei Pan
Haiqi Ye
Zhongxiang Ding
Xiuhong Ge
author_sort Fenyang Chen
collection DOAJ
description Abstract Objective 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. Methods 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. Results 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). Conclusion 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.
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spelling doaj-art-82d9cfcc05f14b72b29d64329bbffa4d2025-08-20T03:04:17ZengBMCBMC Medical Imaging1471-23422025-07-0125111310.1186/s12880-025-01801-2Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamicsFenyang Chen0Zhiliang Zhang1Jianliang Miao2Yvting Zhang3Ding Wang4Juncheng Yan5Lei Pan6Haiqi Ye7Zhongxiang Ding8Xiuhong Ge9Department of Medical Imaging, Section One of Air Force Hangzhou Special Crew Sanatorium of PLA AIR ForceDepartment of Radiology, Zhejiang HospitalDepartment of Medical Imaging, Section One of Air Force Hangzhou Special Crew Sanatorium of PLA AIR ForceDepartment of Radiology, Shaoxing City Keqiao District TCM Hospital Medical Alliance General HospitalDepartment of Neurosurgery, Hangzhou First People’s Hospital Affiliated of Westlake University School of MedicineDepartment of Rehabilitation, Hangzhou First People’s Hospital Affiliated of Westlake University School of MedicineDepartment of Radiology, Hangzhou First People’s Hospital Affiliated of Westlake University School of MedicineDepartment of Radiology, Hangzhou First People’s Hospital Affiliated of Westlake University School of MedicineDepartment of Radiology, Hangzhou First People’s Hospital Affiliated of Westlake University School of MedicineDepartment of Radiology, Hangzhou First People’s Hospital Affiliated of Westlake University School of MedicineAbstract Objective 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. Methods 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. Results 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). Conclusion 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.https://doi.org/10.1186/s12880-025-01801-2Classical trigeminal neuralgiaGlymphatic systemBrain-CSF couplingChoroid plexus volumeNeurofluidic dynamics
spellingShingle Fenyang Chen
Zhiliang Zhang
Jianliang Miao
Yvting Zhang
Ding Wang
Juncheng Yan
Lei Pan
Haiqi Ye
Zhongxiang Ding
Xiuhong Ge
Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamics
BMC Medical Imaging
Classical trigeminal neuralgia
Glymphatic system
Brain-CSF coupling
Choroid plexus volume
Neurofluidic dynamics
title Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamics
title_full Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamics
title_fullStr Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamics
title_full_unstemmed Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamics
title_short Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: a multimodal MRI study of brain-CSF functional and structural dynamics
title_sort glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia a multimodal mri study of brain csf functional and structural dynamics
topic Classical trigeminal neuralgia
Glymphatic system
Brain-CSF coupling
Choroid plexus volume
Neurofluidic dynamics
url https://doi.org/10.1186/s12880-025-01801-2
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