




Senior investigator Daniel Reich trained as both a neurologist and radiologist, and his expertise is in inflammatory brain disease. The connection between the immune system and the brain is at the core of what he says he spends most of his time thinking about: multiple sclerosis. The immune system appears to modulate or even underlie many neurologic diseases, and the cells of the central nervous system produce waste that needs to be washed away just like other metabolically active cells. This discovery should make it possible to study how the brain does that, how it circulates white blood cells, and how these processes may go awry in diseases or play a role in aging.







Daniel Reich / National Institute of Neurological Disorders and Stroke

Wouldn’t neurosurgeons, at some point in their meticulous down-to-the-millimeter dissecting of brains, have stopped and said, “Hey ... what’s this thing?”

The lymph vessels probably escaped detection because they’re inside a thick membrane, the dura mater, which is the consistency of leather. They run alongside blood vessels that are much larger, and on MRI the signal that creates the images is dominated by the blood vessels.

Reich adds the other obvious but important factor: “And, I mean, no one was looking for them.”

The assumption was never that the brain doesn’t drain waste. The major pathway taught in medical school is that waste around cells goes into cerebrospinal fluid—the clear fluid that bathes the brain and spinal cord—and from there gets absorbed directly into the blood through structures called arachnoid granulations. Reich also explained that some fluid is understood to drain through tiny pores in our skulls, mostly at the top of our noses, and then get absorbed into the lymphatic system through the mucous membranes of the nose, and then, from there, go down into the lymph nodes of the neck.

It now seems clear that there is a third pathway through which byproducts get out of the brain—and it may be the most important—through these specialized vessels in the dura mater.

“Looking back, those other two really seem insufficient,” said Reich.

It remains a mystery exactly how that lymph fluid gets into these vessels. There are a lot of open questions that show how far we are from fully understanding many neurologic disorders—or even basic day-to-day functioning of the nervous system.

But this pathway appears crucial to life and health. A 2013 study in Science found that glymphatic flow seems to increase by almost double during sleep (in mice). Sleep disturbances are a common feature in Alzheimer’s and other neurologic disorders, and it’s possible that inadequate clearing of the brain’s waste products is related to exacerbating or even causing the disease. In a 2016 study, also in mice, glymphatic dysfunction appeared to cause accumulation of Alzheimer-related amyloid proteins.

The flow of glymphatic fluid can change based on a person’s intake of omega-3 fatty acids, a study showed earlier this year. Preliminary findings like these together suggest a pathway through which nutrition and sleep can be related to neurologic disorders. Optimizing this glymphatic flow could become a central theme for the future of neurologic health.

“If all of this is true, there probably is a connection between these two systems, glymphatic and lymphatic,” Reich said. “And that would be one of the major functions of cerebrospinal fluid.”

This is all interesting to scientists and anatomy enthusiasts—both in terms of highlighting the potential for future work and highlighting how little we really know about what happens inside our skulls. But beyond the academic, what does it mean for the millions of people with neurologic diseases that are linked to the immune system?

Reich wants to be careful not to overpromise on what this all means, because he spends a lot of his time fielding questions from people with MS who are desperate for a breakthrough.

“The study shows that these vessels exist. We haven’t shown that they’re involved in any disease process,” he said in the careful hedge-based language of a scientist, “but it’s reasonable to think that they might be.”