A recent study published in JAMA Neurology Journal by Yulin Ge, MD showed how pwMS had impaired cerebrovascular function. Dr. Ge is a member of the International Society for Neurovascular Disease. Dr. Ge has been imaging the MS brain for over a decade at NYU, and has found many vascular connections.
Impaired Cerebrovascular Reactivity in Multiple Sclerosis
Now, to explain what Dr. Ge and his fellow researchers at NYU found. CVR is how the brain reacts or responds with blood flow when there is vasodilation in blood vessels. This function is extremely important, as neurons need adequate blood flow to provide glucose and oxygenation. Without this response of adequate cerebral bloodflow (CBF), the brain will not function properly, and neurons can potentially die.
Patients with MS had a significant decrease of cerebrovascular reactivity compared with controls. This decrease in CRV correlated to gray matter atrophy, but did not correlate with white matter lesions.
Their conclusion was that there is an impairment in the cerebrovascular pathophysiology in pwMS, and that inadequate blood flow to neurons may indeed be the cause of neurodegeneration in MS. And that this was a vascular problem, NOT a problem initiated by white matter lesions. Something was wrong with the blood vessels response. Increased blood flow did not happen when it was needed.
Impaired CVR would most certainly cause a delay in cerebral circulation time! These two conditions are intertwined.
Another study on impaired CVR looked at why this might be happening.
A Columbia University study, published last summer, found that when researchers damaged the vascular endothelial cells lining the blood vessels using lasers to cause oxidative stress, they could disrupt blood flow to the brain and affect neurovascular coupling. http://ccsviinms.blogspot.com/2014/06/columbia-researchers-provide-new.html
Did you catch that??
Damaged endothelial cells in blood vessels changes neurovascular coupling, and cerebral blood flow is reduced.
“Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels,” Hillman adds. “This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat.
Endothelial cell death and dysfunction may well be the cause of slowed cerebral blood circulation time in MS. That's all it took in the Columbia study--frying the endothelial cell layer with lasers and slowed down cerebrovascular reactivity, because the endothelial layer could no longer respond with vascodilation and more blood flow to the brain. This is endothelial dysfunction.
Dr. Zamboni has noted that there is a derangement of the endothelial cell layer in the jugular veins and valves in people with CCSVI/MS. This loss of endothelial cells could well be causing the decrease in cerebrovascular reactivity seen in people with MS. And it is caused by CCSVI.
Here are my proposed steps as to why pwMS have delayed cerebral circulation time.
1. Loss of laminar flow, refluxive blood flow and oxidative stress causes endothelial cell death and dysfunction in the vessel walls of both arteries and veins.
2. Without endothelial cells in blood vessels, cerebrovascular reactivity is decreased.
3. This decrease in CVR leads to a slowed cerebral circulation time.
4. Slowed blood flow leads to neuronal cell death and brain atrophy, as well as an hypoxic situation which creates white matter lesions and inflammation. Voila. MS.
The research is out there. If someone could please send this to "The Mouse Doctor" at Barts--he is not taking any responses from me on his blog. But at least he is FINALLY looking at blood flow.
Of course CCSVI could be implicated in CVR and slowed cerebral circulation time in MS.
How to learn more? Test patients, like my husband, who have had venous malformations repaired and see if their cerebral circulation time is closer to normal. My husband's reversal of gray matter atrophy as shown on MRI would seem to imply that there has been healing.
If you want some GREAT news---Dr. John Cooke's team is now figuring out how to create healthy new endothelial cells from fibroblasts, which could then be implanted in patients.
But what do I know?
It's only been seven years since I contacted Dr. Cooke at Stanford and asked him what he thought about endothelial dysfunction in MS.
Again thank you Joan! I am so glad you are in this for the longest haul eva!!ReplyDelete
Unfortunately "Mouse Doctor" only puts up what they want us to see. I gave up on them ages ago but, their last blog got me going and will wonders never cease they left my comment up! Of course their response to my comment "this has nothing to do with CCSV". Then no more comments were allowed. I was going to put YOUR last blog link as a rebuttal. *huge sigh*
Thanks for trying, Shirley! Well, I guess we just have to keep sharing the published research online and getting it to the right people. It's a matter of bringing them into the ISNVD, and then getting their research funded. It's just crazy to say that cerebral blood flow is irrelevent in MS. I hope that's becoming clear.Delete
Hi Joan, thanks for your posts. Your explanations are very lucid and you have a good understanding of the big picture. Have you considered a degree in medicine?ReplyDelete
One of my first directed studies under Dr. Haacke was investigating biological responses to flow and iron in MS. The endothelium in arteries need a certain amount of blood flow or the vessel walls will respond by thickening to maintain constant pressure. Also white blood cells will extravasate in regions of slow flow. In regions of vortex or complex flow, cholesterol and foam cells can aggregate. Cell proliferation and differentiation (what types of cells they divide into) also depend on flow too. Even proper flow increases NO production, a vasodilator. This explains a big reason why exercise helps prevents atherosclersosis.
Now this is all in arteries, surely veins must have similar response but the research is minimal. There are some precocious ideas to the vascular theory in the venous work by JJ Bergan regarding hypertension, valve failure, venous remodeling etc. which you are probably are familiar with.
A month or two ago, I caught a very informative & brainy webinar on neurovascular coupling/endothelium off NeuroImage's website, by Dr. Elizabeth Hillman, and Dr. Mark Nelson. Basically endothelium play a huge role in nerve function, and are involved in all vascular diseases.
Anyhow, glad to see your posts, keep up the good work and we will too. We should be finishing that venous collaterals paper, and there will be a large review of MRI papers with respect to venous flow in Veins and Lymphatics in the near future.
P.S. On a side note, my girlfriend and I just finished HOC season 3. I admit I had no idea what it was when we met you in SF, but we got hooked on the series since then. We were curious if you did the operatic vocals in the recurring parts in the score?
Hey Sean, Thanks for the nice comment. Good to hear from you.ReplyDelete
I think I might be better suited to writing and explaining/encouraging other lay people about how to take care of their hearts and brains and putting researchers together, rather than going back to school...but thanks for the vote of confidence :) Will check out the webinar by Hillman and Nelson. Love all the ways the endothelium is implicated in brain health. Flow is essential, huh?
Yes, that's me wailing away on HOC theme and season 3 score. Jeff keeps me singing, and I keep him jogging and eating lots of plants. Seems to work for us!
All best to you, and hope to see you at a conference or something before too long,
PS...THANKS to you for going to medical school, and working w/Dr. Haacke and all of your hard work. If it weren't for you and your research, I'd have nothing to blog about :)Delete
Thank you always from me here in the UKReplyDelete