MRI study links glymphatic system dysfunction to idiopathic intracranial hypertension

A press release from Mass General Brigham, Boston, reported that the so-called “waste clean-up system,” in the brain (ie, the glymphatic system) is affected negatively by elevated intracranial pressure.

This system helps circulate fluid in the brain and removes waste. The authors of a new study, led by first author Marc A. Bouffard, MD, recently published in the Journal of Neuro-Ophthalmology,¹ reported that changes in the flow of fluid in the brain seen on magnetic resonance imaging (MRI) may aid in the diagnosis of idiopathic intracranial hypertension (IIH). He is from the Department of Neurology, Mass General Brigham, and the Department of Ophthalmology, Massachusetts Eye and Ear, both in Boston.

This work was done in collaboration with researchers from Beth Israel Deaconess Medical, Boston.

IIH, which occurs more commonly in women with higher body weight ranging in age from 15 to 45 years, is characterized by high intracranial pressure and symptoms such as unrelenting headaches, visual disturbances, and tinnitus. Because the increased pressure affects the optic nerve, the visual damage can be irreversible if IIH is not addressed in a timely fashion. The increased intracranial pressure is considered idiopathic when no clear cause can be identified.

“Preliminary work suggests that glymphatic transit is abnormal and dynamic in IIH, although its incomplete characterization across the disease course has led to debate as to its pathophysiologic relevance,” the investigators explained.

They conducted their study to clarify if glymphatic transit varies across IIH's disease course, is correlated with intracranial pressure, and might be measured radiographically to aid diagnosis,” they explained.

MRI study

In their study, the investigators measured the changes in the flow of fluid in the glymphatic system and generated indices of glymphatic transit using an MRI brain scan analysis called diffusion tensor image analysis along the perivascular space (DTI-ALPS). The goal was to see how easily the fluid is able to move in the spaces around the blood vessels in the brain.

The study included healthy controls and participants with IIH; the patients were stratified as untreated, treated, or cured IIH. Those with untreated IIH were substratified as "acute" if imaged before 6 months from onset or "chronic" if imaged 6 months or later after onset, they explained.

What did DTI-ALPS show?

The study included 40 adult participants with all stages of IIH.

Bouffard and colleagues reported, “We identified a positive, nonlinear correlation between the ALPS-indices and disease duration in patients with untreated IIH. The ALPS-indices differed between participants with chronic, treated, and acute IIH, in descending order. The healthy controls exhibited lower ALPS indices than participants with chronic IIH and higher ALPS-indices than participants with acute IIH. The ALPS-indices were 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.”

In commenting on the findings, Bouffard said, “IIH is becoming more common, but it is difficult to diagnose, and it can lead to permanent vision loss. That combination makes the need for better diagnostic tools especially important. Our research points to a noninvasive test that could help us more reliably and objectively diagnose it.”

They also pointed out that DTI-ALSP is more reliable than lumbar punctures.

The study concluded, “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.”

This research is part of the IIH Research and Treatment Initiative, a new philanthropy-funded program launched at Mass General Brigham focused on understanding IIH, improving diagnosis, and finding new treatment options, according to the press release.

Reference:

1. Bouffard MA, Comeau DS, Avanaki MA et al. Perivascular diffusivity suggests dynamic and modifiable glymphatic transit in idiopathic intracranial hypertension. J Neuroophthalmol. 2026; published online ahead of print DOI: 10.1097/WNO.0000000000002434