Flow & anatomical abnormalities in MS vs Controls using MRI

[brocktoon]

Hello everyone,

I am delighted to present this work fresh off the presses. Within the paper lies clear differences in venous anatomy in the MS and HC samples, but most importantly in jugular flow between the two. Also elucidated are the pitfalls of the Rodger and Traboulsee studies. Specifically, using individual IJV flow and percent stenosis method, instead of total IJV (and normalized IJV flow to arterial flow) and using fixed area for determining stenosis.

Some of you are privy to this already if you were at ISNVD or at the NCS conference in Sherbrooke. I welcome any criticisms you may have as well.


Jugular Venous Flow Abnormalities in Multiple Sclerosis Patients Compared to Normal Controls

Link

http://onlinelibrary.wiley.com/doi/10.1 ... 3/abstract

& PDF (note: will eventually be free to public from PubMed)

http://onlinelibrary.wiley.com/doi/10.1 ... .12183/pdf
http://www.ncbi.nlm.nih.gov/pubmed/25316522

[1eye]

Hello brocktoon!

Thank you for all your hard work. To me, you and Dr. Haacke deserve a Nobel prize for this.

It is pretty futile to try to argue with your conclusions. It will be tried, in editorial comments in journals, in the press, and elsewhere. But really, all that's left is for somebody to verify your results any which way they can.

That is a signal piece of scientific thinking, normalizing to arterial blood flow. That was the stroke of genius that broke this controversy wide open.

In my own words: when you compare jugular blood flow to a norm established by using the same group of patients' arterial blood flow (which should be the same), "MS" patients with CCSVI have a lower jugular flow.

What it does to a person to have venous blood flow rerouted through spinal and collateral veins has yet to be determined. It may be that blood flow overall is less than it would be without the stenosis. It may be that certain parts of the brain which require the higher blood flow of open jugulars, have less efficient waste removal.

One thing is clear from your work. People with these stenoses and whatever other problems they may bring, are more likely (much more likely) to have been diagnosed with "MS". Whatever that might mean, and I think many of us here are familiar with it. Regardless of what it means medically (many, many different things to different people). Regardless of what may be causing stenoses in jugulars.

Making these stenotic jugulars work better is necessary, and perhaps the very first treatment most "MS" patients should receive. It is a disease-modifying treatment of the very first order.

If they want the financial benefits of people going back to work, clear, perhaps permanently, of the symptoms caused by jugular inefficiency, they had best start paying for these treatments. Now. The treatment might still be anachronistically called experimental. Those perhaps more visionary in the insurance business will know that the earlier this is treated, the more they stand to gain.

Your work corroborates and verifies the work of Dr. Paulo Zamboni in an in-controvertible way. Shouting can begin any time.

[1eye]

ABSTRACT
BACKGROUND

To determine if extracranial venous structural and flow abnormalities exist in patients with multiple sclerosis (MS).
METHODS

Magnetic resonance imaging was used to assess the anatomy and function of major veins in the neck in 138 MS patients and 67 healthy controls (HC). Time-of-flight MR angiography (MRA) was used to assess stenosis while 2-dimensional phase-contrast flow quantification was used to assess flow at the C2/C3 and C5/C6 levels. Venous flow was normalized to the total arterial flow. The MS patients were divided into stenotic (ST) and nonstenotic (NST) groups based on MRA assessment, and each group was compared to the HC group in anatomy and flow.
RESULTS

The MS group showed lower normalized internal jugular vein (IJV) blood flow (tIJV/tA) than the HC group (P < .001). In the MS group, 72 (52%) were classified as ST while 66 (48%) were NST. In the HC group, 11 (23%) were ST while 37 (77%) were NST. The ST-MS group had lower IJV flow than both HC and NST-MS groups.
CONCLUSION

After categorizing the MS population into two groups based upon anatomical stenosis, as determined from an absolute quantification of IJV cross section, clear differences in IJV flow between the ST-MS and HC samples became evident. Despite the unknown etiology of MS, abnormal venous flow was noted in a distinct group of MS patients compared to HC.

[Cece]

Congrats on what appears to be well-thought-out successful research.

There has been a great deal of conflicting ccsvi research based on noninvasive doppler studies so if MRA is a superior imaging method because it can be standardized, then that would be a step forward.

Also elucidated are the pitfalls of the Rodger and Traboulsee studies. Specifically, using individual IJV flow and percent stenosis method, instead of total IJV (and normalized IJV flow to arterial flow) and using fixed area for determining stenosis.

Has there been any cooperative response from Rodger or Traboulsee or interest in reanalyzing their data with this method?

[brocktoon]

That is a signal piece of scientific thinking, normalizing to arterial blood flow. That was the stroke of genius that broke this controversy wide open.

In my own words: when you compare jugular blood flow to a norm established by using the same group of patients' arterial blood flow (which should be the same), "MS" patients with CCSVI have a lower jugular flow.

Precisely, and though we may have some normals with stenosis and low flow, what their symptoms in 10-20 years should be investigated, but it is too soon to tell.

The normalization is critical and helps account for the physiological differences in people indirectly (age, mass, gender etc). In the workings are a few papers with added normals and about 450 more MS cases, we noted similar arterial flow between all groups, ms-subtypes, and stenosis classification. To come, is categorizing and quantifying venous collateral flow, we have already noted the clear differences in paraspinal venous flow in the MS sample. Not surprisingly that collateral flow type is inflated. Also, we want to normalize arterial flow to the brain volumes which will show that similar arterial flow in large vessels between groups is not a confounding factor.

Thank you again for your kind words, it means a lot.

[brocktoon]

"Has there been any cooperative response from Rodger or Traboulsee or interest in reanalyzing their data with this method?"


Not to my knowledge, but the gauntlet has been thrown!

[1eye]

Can anybody get this link http://www.thisisms.com/forum/chronic-c ... 25432.html to Anne Kingston? I think she might want to know.

[brocktoon]

Can anybody get this link http://www.thisisms.com/forum/chronic-c ... 25432.html to Anne Kingston? I think she might want to know.

I will forward to her, I spoke with her at Sherbrooke about this when it was only a talk at the time.

[cheerleader]

Fantastic work from the team, brocktoon! Was exciting to hear you present in Sherbrooke and speak at ISNVD in Feb.--- and great to see this research finally published! You guys are incredible brainiacs---and good people, too.

As an FYI to 1eye's comment about "certain parts of the brain" that might be impacted by this insufficient venous return--the thalamus is turning out to be the area of interest of MS neurologists--they note thalamic atrophy and iron deposition in this critical brain region for those with MS.
http://www.ncbi.nlm.nih.gov/pubmed/23613615
http://www.ncbi.nlm.nih.gov/pubmed/17875909
http://www.ncbi.nlm.nih.gov/pubmed/24819917

In fact, some researchers are now looking at how "novel" MS drugs address this loss of brain tissue, and getting research funding!
http://www.buffalo.edu/news/releases/2013/03/028.html

I think one place to look might be at how insufficiency of the deep cerebral veins and a widened third ventricle, due to altered venous hemodynamics, is impacting this region.
http://www.upright-health.com/thalamus.html

I asked Dr. Zivadinov at ISNVD why he was looking at the thalamus for his drug research, but not for CCSVI investigations. Didn't get an answer. Maybe you can find out why!

Here's hoping,
cheer/Joan
(PS--Jeff's thalamus and third ventricle now look perfectly normal on MRI. Going on 6 years since venous repair at Stanford.)

[1eye]

This might seem off-the-wall, but...

I was prompted by a notice about the upcoming ECTRI"MS", and I thought I'd share.

You see, they are doing work on parasitic infections apparently. I can not do any investigating myself, but I have been wondering since reading Dr. Schelling's paper, about one thing: the size of the Dawson's fingers. They are not microscopic at all. I think he even calls them macroscopic. They seem to extend outward from the ventricle.

I have been wondering since watching "House MD" #1: what if they were right? Specifically, we seem to have unexplained modifications from the normal size and shape of our veins. These would seem to favor something which hangs around slow-moving blood. Plus if there's one thing parasites really like, it's a blood meal. What if the reason for stenosis, webs, septa, etc., were a parasitic organism which has evolved a way to slow blood down even more than normal physiology does, by attacking veins and making them morph in reaction?

Even better than that, what if the key to treating "MS" were a simple pill, that works right away, and you don't have to take any more? Like in "House MD"#1?

Just wondering about those "anatomical abnormalities".

[1eye]

I cannot believe the lack of excitement here. This is an unmistakeably correct study and penetrating analysis. It completely verifies the work Dr. Zamboni did years ago. It gives the lie to most if not all of the negative studies, explaining some of their most egregious methodology errors. It demonstrates how the truth will out, especially where science and mathematics are concerned.

I think this thread should be used as a place to record our support for these researchers, by every person who has a diagnosis of "MS" spending their scarce dollars to each buy a copy of this paper. You will not be disappointed, and will hasten the progress of this inquiry.

I hereby make public my real name. I will stand by every word I have ever written here. I am Chris Sullivan, of Penfield Drive in Kanata Ontario Canada. I have a brother named Mike, who is an NDP member of the parliament of Canada (by the way he spent yesterday in lock-down). He has on occasion talked about me in the House (see Hansard). Our friend Kirsty Duncan has talked at length about all of you there (see Hansard).

I paid full price for my copy of this paper, and recommend you do the same. I can be reached by PM, if anyone is really too poor to buy a copy. I can email you a copy, in a pinch, but I'd rather you supported these people with dollars.

When enough people have a copy of the whole document, we can discuss it in detail. Meantime I think the pursuit of competent treatment for this abnormality should be the prime goal of anyone suffering from "MS". Even in its infancy, I think this treatment should be choice number one. If enough of us demand it, insurance should pay. They'd be crazy (and possibly libel) not to.

I am not a doctor, and I do not recommend being treated without being tested (though I do think every "MS"er should be tested). The test may be the best thing you ever did for yourself. If you can afford the Haacke protocol, knowledge is power, and the more power the better. Remember many ultrasound operators do not know how to do this. Consult MarkW of Oxford's list of best practitioners. Good luck, all, and don't forget to buy the paper. After you do, let us know here in this thread.

[Cece]

I cannot believe the lack of excitement here. This is an unmistakeably correct study and penetrating analysis. It completely verifies the work Dr. Zamboni did years ago. It gives the lie to most if not all of the negative studies, explaining some of their most egregious methodology errors. It demonstrates how the truth will out, especially where science and mathematics are concerned.

The more talk like this, the more excited I get.
My original concerns were that the number of psMS in the nonstenotic group was higher than expected, and also concerns about the accuracy of MRI in measuring flow, but the results are so provocative.

& PDF (note: will eventually be free to public from PubMed)

a third option in addition to paying or pm'ing for the article is patiently waiting for the article
but all your points are clear ones

[brocktoon]

also concerns about the accuracy of MRI in measuring flow, but the results are so provocative.

I assure you it is leaps and bounds more consistent than ultrasound. Generally in MR there is up to 10% error per vessel, depending on which one it is, but that error reduces when you total values. ie total arterial or jugular flow. We have those values as an appendix in the paper.

[1eye]

I cannot believe the lack of excitement here. This is an unmistakeably correct study and penetrating analysis. It completely verifies the work Dr. Zamboni did years ago. It gives the lie to most if not all of the negative studies, explaining some of their most egregious methodology errors. It demonstrates how the truth will out, especially where science and mathematics are concerned.

The more talk like this, the more excited I get.
My original concerns were that the number of psMS in the nonstenotic group was higher than expected, and also concerns about the accuracy of MRI in measuring flow, but the results are so provocative.

& PDF (note: will eventually be free to public from PubMed)

a third option in addition to paying or pm'ing for the article is patiently waiting for the article
but all your points are clear ones

A fourth option might be to donate actual dollars to the folks doing the research. It seems to be leading down many fruitful avenues. But I warn you: if you donate to McMaster university you may be reminded every year when they do their fund-raising. They will not forget you. Just kidding, it is a worthy cause.

[vesta]

I cannot believe the lack of excitement here. This is an unmistakeably correct study and penetrating analysis. It completely verifies the work Dr. Zamboni did years ago. It gives the lie to most if not all of the negative studies, explaining some of their most egregious methodology errors. It demonstrates how the truth will out, especially where science and mathematics are concerned.

I think this thread should be used as a place to record our support for these researchers, by every person who has a diagnosis of "MS" spending their scarce dollars to each buy a copy of this paper. You will not be disappointed, and will hasten the progress of this inquiry.

I hereby make public my real name. I will stand by every word I have ever written here. I am Chris Sullivan, of Penfield Drive in Kanata Ontario Canada. I have a brother named Mike, who is an NDP member of the parliament of Canada (by the way he spent yesterday in lock-down). He has on occasion talked about me in the House (see Hansard). Our friend Kirsty Duncan has talked at length about all of you there (see Hansard).

I paid full price for my copy of this paper, and recommend you do the same. I can be reached by PM, if anyone is really too poor to buy a copy. I can email you a copy, in a pinch, but I'd rather you supported these people with dollars.

When enough people have a copy of the whole document, we can discuss it in detail. Meantime I think the pursuit of competent treatment for this abnormality should be the prime goal of anyone suffering from "MS". Even in its infancy, I think this treatment should be choice number one. If enough of us demand it, insurance should pay. They'd be crazy (and possibly libel) not to.

I am not a doctor, and I do not recommend being treated without being tested (though I do think every "MS"er should be tested). The test may be the best thing you ever did for yourself. If you can afford the Haacke protocol, knowledge is power, and the more power the better. Remember many ultrasound operators do not know how to do this. Consult MarkW of Oxford's list of best practitioners. Good luck, all, and don't forget to buy the paper. After you do, let us know here in this thread.

Thanks to brocktoon, 1eye, Cece and cheerleader. I just bought the paper so will now read it. It IS exciting, but MS politics will be slow to adjust to the research. Too many vested interests. Thanks all.

Question: Does this study demonstrate that ALL MS patients present slow blood perfusion compared to controls regardless of whether they have stenosis or not? Thanks