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Just published--Jugular flow in pwMS with stenotic veins.
This IS NOT CCSVI, per se, because it is not about the Zamboni criteria... doppler ultrasound was not utilized to check for refluxive flow or intraluminal defects. This was purely a testing of blood flow and stenotic veins.
68% of pwMS had stenotic veins.

Important to note--the pwMS who had stenotic jugular veins had a total IJV flow of less than 8 mL/s. with the subdominant jugular taking only 3 mL/s of blood back to the heart.
Blood flow in normals with average size brain is 12.5 mL/s in the supine position.
That's a lot less blood draining from MS brains.
http://jp.physoc.org/content/560/1/317.full.pdf


http://www.jvir.org/article/S1051-0443(11%2901343-1/abstract?elsca1=etoc&elsca2=email&elsca3=1051-0443_201201_23_1&elsca4=m

Patients with Multiple Sclerosis with Structural Venous Abnormalities on MR Imaging Exhibit an Abnormal Flow Distribution of the Internal Jugular Veins
E. Mark Haacke, PhD, Wei Feng, PhD, David Utriainen, BS, Gabriela Trifan, MD, Zhen Wu, MD, Zahid Latif, RT, Yashwanth Katkuri, MS, Joseph Hewett, MD, David Hubbard, MD
Received 28 April 2011; received in revised form 15 September 2011; accepted 17 September 2011.
Abstract
Purpose
To evaluate extracranial venous structural and flow characteristics in patients with multiple sclerosis (MS).

Materials and Methods
Two hundred subjects with MS from two sites (n = 100 each) were evaluated with magnetic resonance (MR) imaging at 3 T. Contrast-enhanced time-resolved MR angiography and time-of-flight MR venography were used to assess vascular anatomy. Two-dimensional phase-contrast MR imaging was used to quantify blood flow. The MS population was divided into two groups: those with evident internal jugular vein (IJV) stenoses (stenotic group) and those without (nonstenotic group).

Results
Of the 200 patients, 136 (68%) showed IJV structural abnormalities, including unilateral or bilateral stenoses at different levels in the neck (n = 101; 50.5%) and atresia (n = 35; 17.5%). The total IJV flow normalized to the total arterial flow of the stenotic group (56% ± 22) was significantly lower than that of the nonstenotic group (77% ± 14; P < .001). The arterial/venous flow mismatch in the stenotic group (12% ± 15) was significantly greater than that in the nonstenotic group (6% ± 12; P < .001). The ratio of subdominant venous flow rate (Fsd) to dominant venous flow rate (Fd) for the stenotic group (0.38 ± 0.27) was significantly lower than for the nonstenotic group (0.59 ± 0.23; P < .001). The majority of the stenotic group (67%) also had an Fsd of less than 3 mL/s, a Fd/Fsd ratio greater than 3:1, and/or a total IJV flow rate of less than 8 mL/s.

Conclusions
MR imaging provides a noninvasive means to separate stenotic from nonstenotic MS cases. The former group was more prevalent in the present MS population and carried significantly less flow in the IJVs than the latter.

A control group would've helped us make sense of these numbers! Unless they are considering the nonstenotic MS group to be the controls.
It's great to see the research come in.

I would disagree that it is not CCSVI. The doppler testing was only a way to test for CCSVI. Here is Dr. Zamboni's definition of CCSVI syndrome:

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenosies of the internal jugular and/or azygous veins (IJVs-AZ) with opening of collaterals and insufficient drainage proved by reduced cerebral blood flow and increased mean transit time in cerebral MRI perfusional study.

http://phleb.rsmjournals.com/content/25 ... l.pdf+html

Stenoses of the jugulars are certainly being discussed in Dr. Haacke and Dr. Hubbard's paper, as is insufficient drainage! I don't mind though if they don't label it CCSVI in the header, if that avoids the matter of proving CCSVI legit or not, and avoids any kneejerk dismissal of the evidence and research.

Arterial/venous flow mismatch...how is that possible? It is a closed system. I don't understand this although obviously it is possible if that is what they found.

Thanks for posting this, Cheer!

right, Cece. Should have been more clear.
This doesn't mean that those with MS and without stenotic veins do not have CCSVI...they simply do not have stenotic veins. They could still have CCSVI.
Hope that's more precise an explanation for why I said this paper is not about CCSVI (or maybe not more clear..)
I also just noticed that dania posted the paper earlier...
http://www.thisisms.com/forum/chronic-c ... 18892.html
oops.

The arterial/venous flow mismatch might about the 2nd half of the cardiac cycle having to compensate for low flow, to get blood out of the brain, but to be honest, I'm not really clear on it.
Here's Dr. Haacke's power point presentation from this summer. Maybe it has the answer?
http://www.ms-mri.com/presentations/nyc ... ms-2pm.pdf
am considering buying this one for further clarification...
cheer

cheerleader wrote:This doesn't mean that those with MS and without stenotic veins do not have CCSVI...they simply do not have stenotic veins. They could still have CCSVI.

Yes, that is more clear, if CCSVI is being defined based on the flow abnormalities and not the structural abnormalities.

I suppose using MS patients without stenoses as the comparison keeps it the same in case both the stenotic MS group and the nonstenotic MS group have reduced perfusion due to neurological atrophy or reduced cerebral use, if that is occuring. So what this paper says is that, no, in patients with stenoses, flow is reduced, and it is not due to having MS, because the MS patients without stenoses did not have the same degree of reduced flow.

Arterial/venous flow mismatch...how is that possible? It is a closed system. I don't understand this although obviously it is possible if that is what they found.


hmm maybe their are lesions in this system that inhibit out put flow. Just guessing

OK...reading up more on this. It's about the "compliance mismatch" between arteries and veins.
The CNS is a closed loop system, as Cece states, and compliance mismatch is a noted problem in other ways--
as in a stenting situation within an artery, where pulsatile flow can occur
http://www.jbiomech.com/article/S0021-9290(04%2900441-5/abstract

Here's more on vascular compliance---
http://www.cvphysiology.com/Blood%20Pressure/BP004.htm

So, the "mismatch" is the smooth, laminar flow of blood into the brain via the arteries, vs. the pulsatile or disturbed blood flow back to the heart via stenotic veins.
Here's Dr. Haacke talking about this problem... I transcribed it from his presentation online.

We can get the cross-sectionals for every vessel...we can calculate the total cardiovascular input into the brain and the venous out put from the brain. Here's a case of normals, where we're looking at the major veins, they flow at about 10cm per second. They don't have these wild swings associated with them. Here's a case.... all four of the major veins in this individual have come to almost zero or reflux flow, and so because of that, in order to get that blood out, talk about a stress on your system, the flow has to double in the 2nd half of the cardiac cycle and becomes 20 cm per second in order to get it out. I've actually seen flow as high as 60 cm per second in an MS case because of this type of problem."

https://www.facebook.com/note.php?note_ ... 1&comments

cheerleader wrote:OK...reading up more on this. It's about the "compliance mismatch" between arteries and veins.
The CNS is a closed loop system, as Cece states, and compliance mismatch is a noted problem in other ways--
as in a stenting situation within an artery, where pulsatile flow can occur
http://www.jbiomech.com/article/S0021-9290(04%2900441-5/abstract

This is exactly what I was thinking. Veins are more compliant because they have less smooth muscle and more flexible walls. So they can absorb the backward pressure from reflux and the periodic (pulsatile) hypertension by expanding (ballooning outward). There is a periodic increase in venous pressure and the overall flow rate, averaged over time, of the blood through the head, is lower because the vein walls are absorbing the energy that would normally go into moving blood. The brain suffers the effects of slow flow, because on average the blood has less kinetic energy to get it through brain tissue. The energy pushing blood through brains comes from the heart. Some of it is getting converted to potential energy (pressure and heat) by expanding veins, stenoses, and reflux. So both arterial and venous blood flow (it's a closed system) have to slow down compared to their rates in other parts of the body and in "healthy controls". Oxygen consumption staying the same, the parts of the brain that are more oxygen/food-starved will be the parts downstream. The worst may be the jugulars! Sounds like a self-re-enforcing problem.

You would be able to see this pulsatile expansion of veins (which end up staying expanded eventually - progression?), except these vessels are inside the skull. I would have thought Dr. Haacke would have seen it on MRI series. I think it might be more noticeable, say, during a relapse, and maybe in the more recently diagnosed.

A vein surrounded by pressurized fluid (CNS fluid? I remember lesions as being peri-ventricular.) is a Starling resistor, with the concomitant increase in viscosity.

So, reading all this...it's all about normal flow rate. Could it be that in the cases where balllooning/stenting does not show improvement the flow rate is not normalized?? (high speed??)

Between which ranges should the blood flow??

If this is true; the goal should be to normalize blood flow, not resolving stenosis etc.

Correct me if i'm wrong, in my opinion it's all about transport; delivering 'food' (oxygen etc) and removing 'garbage'. If the flow is not a correct rate then you eventually get a problem...

Just my thoughts....

So, reading all this...it's all about normal flow rate. Could it be that in the cases where balllooning/stenting does not show improvement the flow rate is not normalized?? (high speed??)

Between which ranges should the blood flow??

If this is true; the goal should be to normalize blood flow, not resolving stenosis etc.

Correct me if i'm wrong, in my opinion it's all about transport; delivering 'food' (oxygen etc) and removing 'garbage'. If the flow is not a correct rate then you eventually get a problem...

Just my thoughts....

I think so. Oxygen, glucose keep oligodendrcytes alive and phagocytes away. Compress the hose in one spot and it has to ballon out somewhere upstream...

They need parameters of what is normal or healthy, so that after treatment we can know if our flow is within normal or not.

Agree, Cece. Although it was not published as part of this abstract, normal venous return through jugulars in the supine position has been noted in other studies.

[quote="cheerleader"}
Important to note--the pwMS who had stenotic jugular veins had a total IJV flow of less than 8 mL/s. with the subdominant jugular taking only 3 mL/s of blood back to the heart.

Blood flow in normals with average size brain is 12.5 mL/s in the supine position.
That's a lot less blood draining from MS brains.
http://jp.physoc.org/content/560/1/317.full.pdf

Dr. Haacke is testing normals at his Detroit site, and healthy people can go there, be tested and help the research.

{quote]Who: To qualify, you must be between 20 and 59 years of age and must have:
No serious medical problems or metal in your body
No prior history of psychiatric illness
No personal history of drug or alcohol abuse
No personal history of kidney problems
Not pregnant or nursing
What: Eligible participants will undergo a MRI examination to act as a control for a research study looking at Multiple Sclerosis

Where: Harper University Hospital, Detroit, MI

http://www.mrc.wayne.edu/volunteer.htm

cheer

Where: Harper University Hospital, Detroit, MI

Legend has it about 58 years ago on New Years Eve, at Harper in Detroit, my mother's doctor had a party to get to, so he induced my mother to bring me into the world. I was a runt of a baby, at 5 1/2 lbs. I missed being a 1954 newborn by about 6 hours.

That's a lot less blood draining from MS brains.

I know, because you used the word "flow", and the unit "ml/sec", that you know we are talking about less per unit of time. That is important. What goes in, still does come out. It's just that it takes longer. The kinetic energy is getting used up, so the oxygen flow is too slow too. Expansion of veins in size over time, does that explain atrophy, or is it only the dying nerves? Dr. Zivadinov has also found that capillaries die off/go missing.

I have been off this forum a lot lately because I have been test-pacing a Walk-Aide, and reading the book "Rise and Shine". This guy had drop-foot and massive energy loss following a catastrophic car accident (his wife was killed). One of his many surgeries was the removal of 1 rib on each side of his chest. The reasoning was that nerves were being compressed elsewhere from the rib cage, because blood vessels (probably veins, because of the higher compliance) were being compressed by those ribs. The surgeon called it "bilateral thoracic outlet syndrome". Sound familiar? His foot-drop remained, and is being treated using a device similar to the Walk-Aide. His energy and cognition has drastically improved, and he is back at work. I saw him in his Ted Talk, after seeing the link here.

I read his book "Rise and Shine". He suffered many injuries and multi-factorial problems, treated to varying extents by various means, mostly not drugs. His problems were symptoms rooted in a lot of places, including massive brain injury. Many of them resembled "MS".

There is a lot of use of the term "drain" in describing venous blood-flow. Drains are usually thought of as gravity-fed, leading downwards. That is only true above the heart. Below the heart, venous drainage is against gravity when we are upright, leading upwards away from the feet.. So downstream below the heart is upward, and downstream above the heart is down. Venous blood drains downward only above heart-level, and instead, drains upward below the heart. Clear as mud? Good. So in Simon Lewis' case, ribs below the heart might have been expanding blood vessels upstream, impinging on nerves even further upstream, below the stenosis, towards the feet. Ribs above the heart would affect the diameter of veins even further upward, and might even affect nerves an other tissue *in the brain*.

I think Simon's brain was more damaged on the left (his personality, writing style, descriptions, cognition). Which foot was more affected? Remember he still has his foot-drop, after the ribs were removed. That might also indirectly imply which ribs were removed. I will look in his book and at the video for the answer.

There are "crossovers" (left-right) in the brain (because of the corpus callosum?) but the nerves and blood vessels below the neck seldom cross over.

Hello Cheerleader,
Thanks for posting the paper. I will need to spend many hours to get my head around this. I guess they are writing about stenotic vein valves ?? As well as your point that this is not Zamboni's CCSVI criteria, we should also remember that MRV with 3T machines and experts at the level of this team are not available in most local hospitals ! I hope they will work on converting this finding into tests which can be used in local clinics.
Kind regards,
MarkW

MarkW wrote:I guess they are writing about stenotic vein valves ??

MRV would show structure of the vein, and there are methods to show flow, but it would not show intraluminal abnormalities from within the vein such as the valves. The presence of stenotic valves would have to be decipered from the other information.

I swear, it was easier back when there were only a few papers on CCSVI, all by Zamboni's team! More papers, more complexities, some conflicting information, different means of imaging, different types of researchers (vascular surgeons, neurologists, physicists, cardiologists, IRs). I want more research, and more and more, but I also want to understand it and keep up.

With this one, it's the division of the pwMS into the stenotic and nonstenotic groups that I keep coming back to. Who are these pwMS with nonstenotic jugulars? It could be that their stenoses are simply missed on MRV, and would be better diagnosed using a different method, but that the fact that they have better flow than the people with stenotic jugulars might argue that the nonstenotic group were truly nonstenotic. (I saw my own Haacke MRV: I would have been in the stenotic jugulars group!) If we had a healthy controls comparison group, we could see if the nonstenotic MS group were the same as the healthy controls, or if they fell somewhere in between the healthy controls and the stenotic MS group. This would indicate that there might be unseen abnormalities in the nonstenotic MS group, such as septums or webs that reduced flow but did not show on MRV or abnormalities in unimaged places such as the azygous vein or a compressed renal vein; or it could be interpreted as the flow in MS patients being worse than that in healthy controls due to atrophy or diminished needs of the brain in pwMS. It would be more informative if the nonstenotic MS group actually had flow equal to the healthy controls. I would not bet on that outcome, but without it having been checked, it is left unknown.

I feel I might want to reread all the papers we've had thus far, to be better situated to understand the incoming research, as I expect there to be more coming out of ISET and SIR and ISNVD!