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Glymphatic system dysfunction in multiple sclerosis: A systematic review and meta-analysis.

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Glymphatic system (GS) dysfunction, indicated by lower diffusion tensor imaging-based analysis along the perivascular space (DTI-ALPS) values, is linked to increased disease severity in multiple sclerosis (MS). This non-invasive imaging technique may help monitor MS progression.

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DTI-ALPSGlymphatic systemMOGADMultiple sclerosisNMOSD

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Area of Science:

  • Neuroscience
  • Radiology
  • Immunology

Background:

  • The glymphatic system (GS) is vital for clearing waste from the brain.
  • GS dysfunction is implicated in neurological conditions like multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and MOG antibody-associated disease (MOGAD).

Purpose of the Study:

  • To assess glymphatic dysfunction in MS, NMOSD, and MOGAD using diffusion tensor imaging-based analysis along the perivascular space (DTI-ALPS).

Main Methods:

  • A systematic literature search was conducted across major databases up to March 10, 2025.
  • Studies comparing ALPS index values between patients and healthy controls were reviewed.
  • Relationships between glymphatic function and clinical/MRI markers were analyzed.

Main Results:

  • Meta-analysis showed significantly lower ALPS index in people with MS (PwMS) compared to healthy controls, indicating impaired glymphatic function.
  • Lower ALPS index correlated inversely with disease duration, disability (EDSS), and white matter lesion volume in MS.
  • Preliminary data suggest reduced glymphatic function in NMOSD and MOGAD, but require cautious interpretation due to limited data.

Conclusions:

  • Research supports glymphatic dysfunction in PwMS, correlating with disease activity.
  • DTI-ALPS is a promising non-invasive biomarker for evaluating glymphatic activity and monitoring disease progression.
  • Larger studies with standardized protocols are needed to validate these findings.