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Perivascular Diffusivity Suggests Dynamic and Modifiable Glymphatic Transit in Idiopathic Intracranial Hypertension.

Marc A Bouffard1, Donnella S Comeau, Mahsa A Avanaki

  • 1Department of Neurology (MAB, RMM, BKC), Mass General Brigham, Boston, Massachusetts; Department of Ophthalmology (MAB, BA, JFR, RMM), Massachusetts Eye and Ear, Boston, Massachusetts; Departments of Radiology (DSC, MAA, NJ, AB, DCA, Y-MC) and Neurology (BA), Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Radiology (KLR), Massachusetts Eye and Ear, Boston, Massachusetts; Department of Metabolism and Systems Science (OG), University of Birmingham, Birmingham, United Kingdom; and Department of Radiology (JNF), Massachusetts General Hospital, Boston, Massachusetts.

Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society
|January 6, 2026
PubMed
Summary

Glymphatic transit changes in idiopathic intracranial hypertension (IIH) vary with disease stage and may aid diagnosis. Diffusion tensor imaging indices show potential for radiographic assessment of glymphatic function in IIH patients.

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Area of Science:

  • Neuroimaging
  • Nephrology
  • Radiology

Background:

  • Glymphatic transit abnormalities are suggested in idiopathic intracranial hypertension (IIH).
  • Previous characterization of glymphatic transit across the IIH disease course is incomplete, leading to debate on its relevance.
  • Clarifying glymphatic transit's role in IIH is crucial for understanding pathophysiology and diagnosis.

Purpose of the Study:

  • To investigate if glymphatic transit varies across the IIH disease course.
  • To determine if glymphatic transit correlates with intracranial pressure.
  • To assess the diagnostic potential of radiographic glymphatic transit measurements in IIH.

Main Methods:

  • Diffusion tensor imaging along the perivascular space (ALPS) was used to measure perivascular diffusivity and generate glymphatic transit indices (ALPS-indices).
  • A cohort of healthy controls and IIH participants (untreated, treated, or cured) were studied cross-sectionally.
  • Untreated IIH participants were further stratified into acute (<6 months) and chronic (≥6 months) disease duration.

Main Results:

  • A positive, nonlinear correlation was found between ALPS-indices and disease duration in untreated IIH.
  • ALPS-indices differed significantly across acute, chronic, and treated IIH groups, and between IIH patients and healthy controls.
  • ALPS-indices positively correlated with opening pressures in chronic IIH and demonstrated high diagnostic accuracy for distinguishing untreated IIH from controls.

Conclusions:

  • Changes in glymphatic transit are likely a consequence, not a cause, of IIH.
  • Radiographic indices, specifically ALPS-indices, show promise for the diagnostic evaluation of glymphatic transit in IIH.
  • ALPS-indices provide a physiologically valid measure of human glymphatic transit.