Putting the Pieces Together

In my last blog post, I asked WHY cerebral circulation time might be doubled in people with MS.  In this post, I'm going to attempt to answer this question, using recent peer-reviewed research.  Because the answers are out there, we just need to put the pieces together.

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
http://archneur.jamanetwork.com/article.aspx?articleid=1893478

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.
http://phl.sagepub.com/content/early/2014/06/27/0268355514541980.abstract

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.
http://multiple-sclerosis-research.blogspot.com/2015/02/is-ms-starving-brain.html

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.
http://www.genengnews.com/gen-news-highlights/fibroblast-transformed-endothelial-cells-show-promise-for-damaged-tissue-repair/81250576/

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.
http://ccsvi.org/index.php/helping-myself/endothelial-health
Joan

Cerebral Circulation---2x slower in people with MS

A brand new blinded study has found that it takes almost twice as long for blood to flow from the heart, through the brain, and back to the heart in people with MS, when compared to normals.

Cerebral Circulation Time is Prolonged and Not Correlated with EDSS in Multiple Sclerosis Patients: A Study Using Digital Subtracted Angiography 
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0116681&representation=PDF'

Cerebral circulation time (CCT) in people with MS was not tied to disability, or length of time with an MS diagnosis.  Slowed CCT was found in all people with MS, when compared to age matched controls.

Forty four control subjects showed a median time of 2.8 seconds for cerebral circulation.  The 80 patients with MS had a median time of 4.8 seconds.

This research was conducted by the neuroimaging and neurointerventional units of the University of Siena General Hospital, edited by neurologist Dr. Orhan Aktas of the University of Dusseldorf and published in PLoS ONE in February 2015.  Both the testing neuroradiologist and the data examiner were completely blinded as to whether the participants had MS or were healthy.

Cerebral hypoperfusion, or slowed blood flow, has been noted in multiple sclerosis for decades.  Many have theorized that this slowed blood flow is a result of damage to the MS brain.  That inflammation, lesions, edema and loss of neurons would lead to less perfusion.  But this has only been a theory.

What is revolutionary about this new, blinded study--is the evidence that cerebral hypoperfusion occurs in the earliest stages of MS, and precedes white matter lesions and neurodegeneration.  This slowed blood flow appears to be the very first step in the MS disease process.  Hypoperfusion is not a result of MS, it may be the cause.

The researchers state that slowed cerebral blood flow is "pathognomonic."  Pathognomonic (patho, meaning disease and gnomonic meaning judge) means that this is a specific marker for MS.

The absence of a significant association between CCT and disease duration, disease onset, lesion and brain volume, EDSS and age could suggest that the high intravascular resistance is a constant finding in MS patients, possibly taking place at an early stage of the disease. 

Therefore, cerebrovascular changes are not solely the result of a late chronic inflammatory process. Indeed, if the microvascular dysfunction was a consequence of lesion load or brain atrophy, high CCT values would be expected to increase with EDSS and disease duration.

In conclusion, the absence of a correlation between lesion volume and CCT confirms that hemodynamic alteration is not related to parenchymal lesion and other MS-linked clinical features, but rather, is a pathognomonic feature of disease. 

This is the second peer-reviewed, published and blinded study to show cerebral circulation time is markedly slower in pwMS when compared to normals.  The first study was published in 2012, and utilized doppler ultrasound, rather than angiography.   
http://www.ncbi.nlm.nih.gov/pubmed/22357894

We know that hypoperfusion is damaging to delicate brain tissue.  We see links to neurodegeneration, white matter lesions and cerebral atrophy is hypoxic (lowered oxygen) situations where hypoperfusion is present--such in altitude sickness, carbon monoxide poisoning and cocaine overdose.  The brain needs a constant supply of oxygen and glucose, and when blood flow is disrupted, damage occurs. Researchers have seen hypoperfusion and ischemic injury in MS for many years.

Dr. Zamboni and Dr. Zivadinov published a study in 2010 showing how severity of CCSVI was linked to severity of hypoperfusion:

To the best of our knowledge, this pilot study is the first to report a significant relationship between the presence and severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.

http://ccsviinms.blogspot.com/2011/03/dr.html

I've been summarizing the research of MS as a disease of primary hypoperfusion for six years now.
http://ccsviinms.blogspot.com/2009/12/hypoperfusion-decreased-blood-flow-in.html

Dr. Bernhard Juurlink proposed MS as a disease of hypoperfusion in 1998
http://ccsviinms.blogspot.com/2010/08/blood-flow-and-white-matter-lesions.html

Neurological researchers can no longer claim that cerebral blood flow is not important.  New technologies are allowing us to see how hypoperfusion and slowed cerebral circulation time is impacting the brain.

There is a very real and measurable vascular connection to MS and diseases of neurodegeneration.
And new research is showing us how important the heart-brain connection is.

Why does it take a full two seconds longer for blood to return to the heart in people with MS?  We need answers.

Joan

Still skiing, Dr. Miller

This month is the 8 year anniversary of Jeff's diagnosis with Multiple Sclerosis.  (Although we now believe Jeff has had MS since childhood, when he lost his peripheral vision.  Throughout his life, he would exhibit other common MS symptoms, but he wasn't officially diagnosed until age 43.)

We are happy to share that he remains MS progression free, is still jogging, working full days, traveling the world, composing, performing and conducting,
and yes, Dr. Miller, Jeff is still skiing.

Neurologist Aaron Miller confronted me at the CCSVI Alliance table at the American Academy of Neurology Brain Fair in 2013.  He walked up to our exhibitor's table, looked me in the eye and laughed in my face.  "You can't possibly believe this!"  he sputtered.

I told him that for many, there was a vascular connection to MS.  That my husband had regained his balance and energy and was able to return to walking, then biking, then jogging and eventually skiing.  All thanks to his successful venoplasty treatment which repaired his stenotic dural sinus and jugular veins and his implimentation of the endothelial health program.  Dr. Miller guffawed,  "That's ridiculous!   There's nothing to the vascular business.  Veins?  We've discredited it all.  Well, let's hope he keeps skiing! Ha!!"

He smirked at me as he walked back into the conference, where he was presenting on the latest oral drugs for MS.

"The future has never looked brighter for [people with] MS," says Aaron Miller, M.D., medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center in New York City. And, he adds, "I anticipate that in the [near future], we'll have perhaps another four new multiple sclerosis drug treatments."
http://www.healthcommunities.com/multiple-sclerosis/treatment.shtml

Dr. Miller would end up backing away from one of the new oral medicines, Gilenya--after there were six deaths linked to the drug.

The deaths have “made me a little more cautious,” Aaron Miller, chief medical officer of the U.S. National Multiple Sclerosis Society and a medical director at New York’s Mount Sinai Hospital, told Bloomberg News. “I am not somebody who has recommended Gilenya as a first-line drug prior to these reports, and I’m still not recommending it as a first-line drug until we get more data,” Dr. Miller added. Miller treats about 800 patients and has prescribed Gilenya to about 30.
http://www.newsinferno.com/doctors-back-off-gilenya-amid-safety-woes/

Dr. Miller was ready to embrace these new oral MS medicines, which he admits were lacking data, and promote them at conferences and prescribe them to his patients. Yet he deemed my husband's pursuit of vascular health and repair of a venous malformation "ridiculous."

Are MS specialists really concerned about their patients' health?  If so, they might want to consider the following:

Matt Embry is now 20 years past his MS diagnosis, with no progression.  He still runs marathons and works full time.  He has never taken any disease modifying medications.  He's offering his program, called MS Hope, for free.  He has a website and Facebook page, where the program his father, Dr. Ashton Embry, compiled for him using peer-reviewed MS research, is now offering continued hope and health to those with MS.
http://www.mshope.com

Matt, Dr. Terry Wahls, Dr. George Jelinek and many others are speaking out about how nutrition, lifestyle, exercise, UV rays, vitamin D and smoking cessation can help people with MS maintain health and mobility.  And they are publishing their results in medical journals.
http://terrywahls.com
http://www.overcomingmultiplesclerosis.org

The International Society for Neurovascular Diseases will meet in March to discuss the ongoing studies on cerebral perfusion and CCSVI.
http://www.isnvd.org/d/Napoli

The keynote speaker for the ISNVD conference is Dr. Mat Daemen, Professor at the Academic Medical Center in Amsterdam and Project Leader at the Cardiovascular Research Institute in the Netherlands.  His recent publication,  “The Heart and the brain: an intimate and underestimated relation” discusses the important relationship between blood flow and the brain, and the lack of understanding of this connection, due to the non-collaborative and myopic approach of medical research.

The apparent lack of appreciation of the link between cardiac and brain (dys)function is probably due to monodisciplinary approach by cardiologists and neurologists and by the reductionist approach of modern medical research.  
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547419/

Despite the MS treatment machine and pharmaceutical companies' best efforts, the vascular and environmental research continues.  Patients are finding healing and sharing with others.  People are donating money to directly fund the research which interests them and are participating in this grass roots movement.    There are things that people with MS can do for themselves today, which will make a difference in their disease progression tomorrow.

If I was an MS doctor and someone told me that their 50 year old husband with MS had returned to skiing after having trouble walking and balancing, I might sit down with them and learn more.
Not laugh in their face and deride them, wishing them ill.

If I was an MS Society and a young man from my country began sharing his program for health and healing after having had MS for 20 years, I might ask him to speak to people with MS and help them.  Not consider his information a threat.

If I was an MS researcher, and a world-reknowned vascular specialist (who was collaborating with NASA) could show me how venous reflux was impacting the brains of people with MS, I might work with him.  Not spend millions on studies ignoring his protocol, just to prove this condition didn't exist.

But I am none of those things.
I've got no money in this game.  Just skin, and skis.

Joan