Multiple Sclerosis – The Vascular Connection
From Rindfliesch's discovery of the central vessel in the MS lesion in 1863, to Dr. Paolo Zamboni's discovery of Chronic Cerebrospinal Venous Insufficiency, 150 years of MS research on blood flow and perfusion of the central nervous system. The heart and the brain are connected.
Wednesday, June 3, 2015
A "Stunning Discovery"
We are living in very exciting times. During the past few years, researchers have changed what was thought to be known about the brain - specifically how it cleanses and protects itself.
Textbooks are being re-written as we speak.
These discoveries are truly earth-shattering, and especially important for people with neurodegenerative diseases like MS, Alzheimer's, Parkinson's, and dementia.
New technologies have allowed researchers to see exactly how the brain cleanses itself while we sleep, via the newly defined "glymphatic" system, which relies on the sleep state to remove toxins, proteins, and metabolites from brain tissue. Before this discovery, it was unknown how the lymphatic system functioned in the central nervous system. Researchers had assumed the brain was cleansed with cerebrospinal fluid, but they really weren't sure how this took place. Now it is known that there is a specialized CSF/lymphatic system in the brain, which has been called the "glymphatic" system because of the importance and reliance on the glial cells.
This discovery was made at the University of Rochester, and is currently rocking the world of sleep specialists. It explains the link between sleep problems and neurodegenerative disease, and provides some answers as to why sleep is so essential for brain health.
I was able to visit Dr. Nedergaard's lab where this discovery was made, and to see how she and her associates are taking this research forward into translational medicine and potential treatments. As Dr. Nedergaard told me, good sleep and adequate drainage of the brain are key to brain health. Nothing can be done to help the brain heal (via stem cells or medications) until these mechanistic systems are functioning adequately.
Now, a stunning discovery has been made at the University of Virginia School of Medicine, which parallels the work done by Dr. Nedergaard. Researchers have now seen previously undetected vessels that carry immune cells in the CNS. Seeing these vessels was like finding a new planet in our galaxy. Researchers thought they understood how the brain's immune system functioned and how the CNS was "immune privileged" - but in reality, they were completely wrong.
The relationship between the brain and the immune system has long puzzled researchers. For some time, scientists thought that immune cells only showed up in the brain during an infection. The brain is considered “immune privileged, ”such that when exposed to foreign material, it takes longer to mount an immune response than does the rest of the body. Furthermore, to date, traditional lymphatic vessels had not been found there.
This stunning new research shows that the brain and central nervous system is no different from the rest of the body. We now can study how the immune system works in the brain, and how these lymphatic vessels allow or inhibit immune cells in brain tissue.
What do these newly discovered lymphatic cleansing and immunological systems share?
They are lymphatic vessels and rely on veins.
That's right. The glymphatic system which cleanses our brain utilizes paravenous spaces, and the newly discovered immune system in the CNS drains along the dural sinuses.
In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, and are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes.
Kipnis described them (the newly discovered vessels) as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."
Kipnis and his colleagues found that vessels expressing markers of lymphatic vessels elsewhere in the body ran along the dural sinuses, drainage lines in the brain that collect outgoing blood and CSF, emptying these fluids into the jugular vein. They also found that the vessels contained immune cells.
Lymphatic ducts drain lymph into veins in the neck (the right and left subclavian veins at their junctures with the internal jugular veins). Valves in the lymphatic ducts at their junctures with the veins prevent the entrance of blood into the lymphatic vessels.
The implication of these discoveries is monumental. If lymphatic vessels do not have adequate drainage, due to a stenotic dural sinus, jugular stenosis, mechanical impingement or venous problems, the brain's immune system, and cleansing system will not function properly.
The venous system which drains the brain is essential for perfusion, cleansing, and proper immune function.
"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG).
The brain is like every other tissue in our body; it needs adequate venous drainage so that lymphatic drainage can occur.
The images below show normal venous structure on the left, contrasted to Jeff's stenotic jugular veins, pinched off dural sinus and inefficient, curly collateral veins on the right, as they looked on MRV prior to his venoplasty treatment.
Jeff has had no MS progression and a healing of most of his MS symptoms after successful stenting of his veins six years ago.
Endovascular stenting of the venous sinus is an approved treatment for intracranial hypertension, and a recent review shows the benefits.
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Article Credit: Joan. “Multiple Sclerosis--the vascular connection” ccsviinms.blogspot.com. Joan, published 3 June 2015. Accessed 20 September 2015. <http://ccsviinms.blogspot.com/2015/06/a-stunning-discovery.html?m=1>
Image Credit: Joan. MRV scan of husband Jeff’s vascular system. <http://ccsviinms.blogspot.com/2015/06/a-stunning-discovery.html?m=1>. Published 3 June 2015. Accessed 20 September 2015.
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