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Published on: May 23, 2018
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.
Background:
Preliminary work suggests that glymphatic transit is abnormal and dynamic in idiopathic intracranial hypertension (IIH), although its incomplete characterization across the disease course has led to debate as to its pathophysiologic relevance. We seek to clarify whether glymphatic transit varies across IIH's disease course, correlates with intracranial pressure, and might be measured radiographically to aid diagnosis.
Methods:
Diffusion tensor imaging along the perivascular space (ALPS) was used to measure perivascular diffusivity and generate indices of glymphatic transit (ALPS-indices). We studied healthy controls and participants with IIH cross-sectionally, the latter stratified into untreated, treated, or cured IIH. Participants with untreated IIH were substratified as "acute" if imaged <6 months from onset or "chronic" if imaged ≥6 months from onset.
Results:
Forty participants were studied. We identified a positive, nonlinear correlation between ALPS-indices and disease duration in patients with untreated IIH. ALPS-indices differed between participants with chronic, treated, and acute IIH, in descending order. Healthy controls exhibited lower ALPS-indices than participants with chronic IIH and higher ALPS-indices than participants with acute IIH. ALPS-indices correlated positively with lumbar puncture opening pressures in participants with chronic IIH. Receiver-operating-characteristic curves demonstrated high areas-under-the curve in distinguishing between participants with untreated IIH and controls.
Conclusions:
These data support the hypothesis that changes in glymphatic transit are likely a result rather than a cause of IIH, that radiographic indices of glymphatic transit may be leveraged diagnostically, and that ALPS-indices measuring perivascular diffusivity are likely a physiologically valid reflection of glymphatic transit in humans.
