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MRI analysis that measures the activity of the glymphatic system may offer a noninvasive method for diagnosing unexplained brain pressure.

A new study led by investigators from Mass General Brigham shows that a brain waste “clean-up” system is influenced by intracranial pressure. The system, called the glymphatic system, was unrecognized until 2012 and helps circulate fluid and remove waste from the brain. Using magnetic resonance imaging (MRI), the research team found that changes in this fluid flow may help doctors better diagnose intracranial hypertension (IIH) less invasively and more reliably than the current standard approaches. Their results are published in the Journal of Neuro-Ophthalmology.

When the pressure inside the skull is too high, but doctors cannot find another cause, they diagnose IIH. IIH is an increasingly recognized condition characterized by symptoms including headaches, vision loss, and pulsatile tinnitus that is more common in women between the ages of 15 and 45 with higher body weight. If the intracranial pressure stays high, it can damage the optic nerves.

“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,” said lead study author Marc Bouffard, MD, a neuro-ophthalmologist at Mass Eye and Ear, a member of the Mass General Brigham healthcare system. “Our research points to a noninvasive test that could help us more reliably and objectively diagnose it.”

This research is part of the IIH Research and Treatment Initiative, a new program launched at Mass General Brigham focused on understanding IIH, improving diagnosis, and finding new treatment options. The initiative is led by members of Mass General Brigham’s Department of Neurology, including Dr. Bouffard, Robert Mallery, MD, and Bart Chwalisz, MD. Their team brings together clinical care and research to understand what causes IIH and develop new treatments for it.

Their latest study investigates the role of the glymphatic system in IIH. Using an MRI brain scan analysis called DTI-ALPS (diffusion tensor imaging analysis along the perivascular space), the researchers measured how easily fluid moves along the spaces surrounding blood vessels in the brain—key pathways for the glymphatic system.

Mass General Brigham researchers, in conjunction with collaborators from Beth Israel Deaconess Medical, derived ALPS indices from MRI scans of 40 adults. These included people at every stage of IIH and healthy volunteers. The study revealed changes in glymphatic activity depending on the stage of IIH. Glymphatic activity was lower in people with recent-onset IIH, higher in those with long-standing untreated IIH, and normal in people with well-controlled IIH. The changes they observed may resolve after IIH is cured.

“It has been hypothesized—by us and others—that glymphatic dysfunction might cause IIH, but if that were true we would expect to see an inverse relationship between glymphatic transit and intracranial pressure. Instead, what we found suggests glymphatic changes are more likely influenced by high pressure inside the head with changes that could be adaptive. These findings help to shape and update thinking about the recently recognized glymphatic system’s role in this enigmatic disease,” Bouffard said.

The researchers believe that ALPS indices or other measures of glymphatic activity could be used to diagnose IIH noninvasively. They note a study limitation is that the results describe a single dimension of glymphatic flow, and they are planning studies to incorporate MRI indices to define the glymphatic system’s activity in a more comprehensive manner, imaging arterial pulsation and cerebrospinal fluid transit.

Their group is also preparing future studies, including clinical trials, to test new treatment strategies and reduce the burden of symptoms for people with IIH.

“These patients have a lot of burdensome symptoms. Current treatments are hard to tolerate and can have a lot of side effects,” said Mallery, who is also an attending neuro-ophthalmologist in the Mass General Brigham Department of Neurology. “By learning more about the mechanisms of the disease, we hope to identify and develop better treatments for IIH.”