The Connection Between Sleep Disturbances and the Glymphatic System

Patients wake up “groggy” in the morning because they do not get enough slow-wave sleep, the stage where the glymphatic system drains toxins from the brain, says Stephen Silberstein, MD, professor of neurology and director of the Jefferson Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

In this podcast, Karl Doghramji, MD, director, Sleep Disorder Center, professor of psychiatry, Thomas Jefferson University, interviews Dr Silberstien about the importance of sleep in the production of body homeostasis and the glymphatic system's ability to drain buildup of toxins in the brain.

Karl Doghramji, MD, is Professor of Psychiatry, Neurology, and Medicine at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania, and Medical Director of the Jefferson Sleep Disorders Center at Thomas Jefferson University Hospital, also in Philadelphia. Dr Doghramji is also Program Director of the Fellowship in Sleep Medicine.

Stephen Silberstein, MD, FACP, is Professor of Neurology and Director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia, PA; one of the few academic centers in the country. Involved with migraine research and clinical trials. He is author of over 400 peer-reviewed publications.

A Fellow of the American College of Physicians, the American Academy of Neurology, and the American Headache Society (AHS). Served the AHS as President, Treasurer, and Board of Directors member. He is the 2016 Lifetime Achievement Award recipient by AHS. Chairman within the World Federation of Neurology and President of the Philadelphia Headache Society.

Dr. Silberstein is the senior editor of the 8th edition (and the upcoming 9th edition) of Wolff’s Headache and Other Head Pain, Associate Editor of Cephalalgia and CNS Drugs, and a present or prior member of the Editorial Board of Headache, Cephalalgia, Acta Neurologica Scandanavia, Journal of Neurology, Neurosurgery and Psychology, and Topics in Pain Management.

Read the transcript:

Karl Doghramji: Welcome, everyone, to this video on the Psych Congress Network. My name is Dr Karl Doghramji. I'm director of the Sleep Disorder Center at Thomas Jefferson University. I'm also a professor of psychiatry.

I'm delighted today to introduce our guest Dr Stephen Silberstein. Dr Silberstein is professor of neurology and director of the Jefferson Headache Center at the Thomas Jefferson University. Dr Silberstein is an international expert in the area of headache, and we're delighted to have him today. Welcome, Steve.

Stephen Silberstein, MD: Thank you very much for having me.

Dr Doghramji: Today we're going to be discussing a topic which is, I'm sure, of great interest to all of us clinicians. That is the area of sleep and headache. We're also going to be specifically discussing the role of the glymphatic system in the generation of disturbances of both sleep and headache.

Before we do that, I'd like to mention a couple of brief words about sleep and the importance of this topic. For many years, we've known that sleep is an important area of functioning. Certainly, loss of sleep produces all sorts of abnormalities in human beings, difficulties with mentation, focus, mood. Animals deprived of sleep eventually end up losing function and even die.

What we have not known, though, is what is the mechanism by which these derangements are produced. Why is sleep so important in the production of body homeostasis?

One of the important clues in this whole question came to us a number of years ago with the discovery of the glymphatic system. Can you clarify to us what is the glymphatic system?

Dr Silberstein: Sure. We know in most of the body when there are toxins or problems or breakdown of blood products, it's the lymphatic system that delivers that to the nodes and to the spleen and takes care of it. It also guards against infections, and antibodies can be produced that way. Until recently, we had no similar system in the brain.

Now we know it. It's called the glymphatic system based on lymphatics. Also, it goes through astrocytes and glial cells, so glial lymphatic. Let me give you an overview. Classically, spinal fluid is made in the lateral ventricles, and then it's pumped into the subarachnoid space.

How does the system work? Surrounding the arteries and veins is a perivascular space. What's important is the fact that norepinephrine shrinks it, and low norepinephrine opens it. During the day, our norepinephrine levels are high, and it shrinks. At night, the norepinephrine's low, and it opens up.

Secondly, spinal fluid goes into the perivascular space. Then it's transferred into astrocytes through a channel called the aquaporin-4 channel, which is crucial. Once it gets into the aquaporin-4 channel into the astrocytes, it then diffuses into the interstitial space.

Basically, what it's continually doing is washing waste products out from the interstitial space. It then goes to the perivascular space around the veins, enters the veins, and is washed out. Basically speaking, the glymphatic system is a drainage system for the brain.

Dr Doghramji: Steve, the glymphatic system, the drainage aspect from the brain, it's important because these toxins can accumulate in the brain and produce negative aspects of the neurons of the brain. Is that correct? It's important to get rid of these toxins.

Dr Silberstein: Correct. The best example is if you keep a small rodent alive and not let him sleep, it'll die. These toxins will accumulate acutely like that.

Many people believe it's a defectiveness of the glymphatic system that may result in Alzheimer disease because the tau proteins can accumulate. They're not washed out, and they cause a degeneration in the brain. The glymphatic system has a cleansing and protective benefit for the brain.

Dr Doghramji: Is it correct that most of this cleansing occurs during sleep? Is that correct?

Dr Silberstein: Correct. What happens is, and it's been shown in many studies, that the passage of fluid through the glymphatic system is dependent on the stage of sleep. Most of it occurs during slow-wave sleep.

If you do not get adequate sleep and enough slow-wave sleep, I believe that the reason you wake up groggy in the morning is because the glymphatic system hasn't got all that, "crap out of your brain."

Dr Doghramji: That's fascinating information. The buildup of these poisons—sleep is so critical for the elimination of these poisons. Do we have any data to back this up? In other words, do we have data suggesting that better sleep, in some way, increases the elimination of these poisons from the brain?

Dr Silberstein: A lot of animal models clearly show you can do that. You can also inject 2 kinds of dyes, 1 dye in the spinal fluid and the other intracellularly. What you can show is, depending on the stage of sleep, the dye in the CSF won't go into the intracellular space unless you're in slow-wave sleep. That's clearly been shown.