New Swedish Study Casts Doubt on MS Vascular Theory

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

New Swedish Study Casts Doubt on MS Vascular Theory

Postby malden » Wed Aug 04, 2010 2:20 am

One more new study questioned vascular MS hypothesis and treatment.
This time it come from Swedish MD team from Umeå University Hospital:

Venous and Cerebrospinal
Fluid Flow in Multiple Sclerosis:
A Case-Control Study


Autors:

Peter Sundstrom, MD, PhD,1
Anders Wåhlin, MSc,2 Khalid Ambarki, MSc, PhD,2
Richard Birgander, MD, PhD,2
Anders Eklund, MSc, PhD,2,3,4
and Jan Malm, MD, PhD,1

1 Department of Clinical Neuroscience, Umeå University, Sweden;
2 Department of Radiation Sciences, Umeå University, Sweden;
3 Department of Biomedical Engineering and Informatics, Umeå University Hospital, Sweden;
4 Center for Biomedical Engineering and Physics, Umeå University, Sweden.

The prevailing view on multiple sclerosis etiopathogenesis has been challenged by the suggested new entity chronic cerebrospinal venous insufficiency. To test this hypothesis, we studied 21 relapsing-remitting multiple sclerosis cases and 20 healthy controls with phasecontrast magnetic resonance imaging. In addition, in multiple sclerosis cases we performed contrastenhanced magnetic resonance angiography. We found no differences regarding internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux. Three of 21 cases had internal jugular vein stenoses. In conclusion, we found no evidence confirming the suggested vascular multiple sclerosis hypothesis.

...If MS-CCSVI is an entity associated with MS, the association is likely to be weaker than previously reported, and most importantly, we found no support for a treatment rationale of endovascular procedures like angioplasty or stenting.
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Postby PCakes » Wed Aug 04, 2010 8:57 am

Thus, as exemplified by all the examples cited, no matter what field of science and medicine we consider, even minor differences in how studies are conducted can, and often do, produce opposing results. This leads to confusion, debate and, all too often, strong disagreement over the “right answer” to crucial issues.
- Dr. Lorne Brandes
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Postby 1eye » Wed Aug 04, 2010 9:42 am

This was posted under the name Edward Murray on "The Medical News"

How insightful and as the Anals noted, "important."

How does it advance the science of this if you don't actually attempt to replicate the work of Dr. Zamboni?

I personally tested the CCSVI theory using tarot cards and was "not able to reproduce the findings by Zamboni et al. " I should submit my results to the growing evidence that CCSVI is not real at least when you don't actually test for it.


Tarot has been shown to be unfocussed and inaccurate compared to the more professional parapsychological methods such as Ouija. Never or nonetheless, it fully agrees with this finding.

Zamboni has said on many occasions that researchers, especially those at financial or mental risk, should continue taking their medication.

"Time is brain, and, as we all know, also money, so the conclusion might be reached that brain is money, but we're still not sure." said Dr. Gamblumer of the Hospital for Sick Billionaires, where he is Chief of Neuro-Phrenology.

CCSVI has again been described among the cognoscenti as "unreal".
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Postby selkie » Wed Aug 04, 2010 11:27 am

The Swedish study is being published in a neurological journal. People can make fun of it if they like, but studies like this will confuse the issue for doctors and for patients.

It needs peer review - were the testing protocols the same as Dr. Zamboni's? If not, then that is sloppy science.

In one article I read they used MRIs of the jugulars only; in another I read they used MRVs with and without contrast in the jugulars - so which is it?

And I read only 20 patients in each group.

CCSVI is confusing enough - but since this study has made a neurological journal, it needs to be peer reviewed for validity.
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Postby 1eye » Wed Aug 04, 2010 12:22 pm

Some of these newspapers and journals are not being careful enough of what they print. They all seem to have good reputations, and even though they may put disclaimers under this tripe, I am concerned for their well-earned reputations.

Everyone is so anxious to see publications in scientific journals, I think they are not being discriminating enough.

Good publicity is hard to buy. Especially when consumers are so insensitive as to want to be able walk and talk, eat and drink, read and write. Such demanding people, and such good drugs we are offering.

When I was young I heard Steppenwolf sing "God damn the pusher-man." I was just unaware that I would grow up to see him so powerful. I know what I would compare it to: the quiz shows scandals of the 1950s. Are any of these 'researchers' under real investigation? How about the newspapers?
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Postby selkie » Wed Aug 04, 2010 12:25 pm

Good point, 1eye.
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Postby cheerleader » Wed Aug 04, 2010 12:32 pm

OK...two negative studies, the same two studies we've been discussing on here for three months. Nothing new, nothing has changed...they're just getting regurgitated in the press now.

1. German/Doepp/Doppler Study:
In the current issue of the Annals, Florian Doepp, M.D., and colleagues in Germany performed an extended extra- and trans-cranial color-coded sonography study on 56 MS patients (36 female; 20 male) and 20 control subjects (12 female; 8 male). The analysis included extra-cranial venous blood volume flow (BVF), internal jugular vein (IJV) flow analysis during Valsalva maneuver (VM), as well as tests included in the CCSVI criteria.



As I've said before, the problem with the Doepp study was position of the doppler wand. It assessed jugular vein narrowing in the “sagittal” plane (the ultrasound probe is placed parallel to the length of the vessel). The Zamboni technique uses the “transverse” plane ( the probe is placed at a 90 degree angle to the length of the vessel) to look for narrowing, webs, or abnormal valves that Dr. Zamboni believes are often missed in the sagittal plane examination.

If the wand is used in the sagittal manner--it picks up collateral flow...that's how the doppler technician at Stanford gave Jeff a "normal" result, but MRV showed it was a tortuous collateral, not the jugular vein (which was 95% gone) taking the blood back.

Here's Dr. Brandes on it--via Dr. Zamboni:
http://healthblog.ctv.ca/post/When-stud ... mples.aspx

2. Amsterdam/VU/MRV study

The problem with the VU (all MRV) study was addressed by Dr. Roel Beelen of Belgium. He questioned the statistical significance of a small study and the independence of the researchers.

He wrote an open letter to the VU-team, questioning the statistical power and the method of their research. Dr. Beelen MD, checked 107 patients with MS and discovered ccsvi in about 90% of the cases. He also did treatment, including some stents. No complications. Publication will follow later.

Here is his letter---and the link to the thread discussing this on ThisIsMS.com
http://www.thisisms.com/ftopic-11029-15.html


"Through a journalist my attention was just drawn to a report in a Dutch current affairs program on CCSVI.

In this report, there are quite a few disturbing elements.

1. They conclude from a very limited group of 20 people that there is no causal link. I wonder, what's the objective "statistical power" of a series of 20 patients.
2. The evaluation of the 20 patients, was it all done by the same team? Were the results independently verified?

Although our series is a long follow-up, I would like to show some results of our series of patients:

107 patients with confirmed MS were screened for CCSVI, in 97 patients CCSVI non-invasive (CT, Duplex) diagnosed (independently diagnosed by vascular surgeon and radiologist).

81 patients

* 64-balloon dilatation
* 2 Valvulotome
* 8 cutting balloon
* 7 stenting

No complications

29 patients are monitored, using Doppler and using an internationally validated questionnaire (MSQOL-54 instrument) and after treatment as reported by every individual of these 29 patients, the quality of life has improved. Statistically, this is even more significant.

When the last patient in this group has reported, (one year follow up) results will be openly published.

Despite these figures both by us and in other centers, how can you, with a much smaller number of patients, go on saying that there is no link between MS and CCSVI? Would't it be logical to consider this theory, because of the spectacular results? Currently I still believe that CCSVI may not be the primary cause of MS, but in certain forms of MS it surely plays a very important role in the development of MS. I therefore call for a comprehensive inter-disciplinary dialogue so that the MS patients by a combination of classical pharmacological treatment and interventional treatment, can get the optimal treatment of the moment.

Yours sincerely,

Roel Beelen, M.D.
Aalst


We could go back and forth forever...and there will be studies saying aye and studies saying nay. Dr. Brandes' column (linked above) explains this eloquently. My main concern is that when the vascular doctors publish their studies, will they receive the same media and medical community publicity?

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: New Swedish Study Casts Doubt on MS Vascular Theory

Postby Lyon » Wed Aug 04, 2010 12:59 pm

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Postby Drury » Wed Aug 04, 2010 1:00 pm

Here here Cheer.

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Postby Lyon » Wed Aug 04, 2010 1:03 pm

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Postby malden » Wed Aug 04, 2010 3:10 pm

cheerleader wrote:OK...two negative studies, the same two studies we've been discussing on here for three months. Nothing new, nothing has changed...they're just getting regurgitated in the press now.


What are you talking about? What two studies? German and Amsterdam? Here we are talking about Swedish study, and Amsterdam is not in Sweden, it's in Netherlands (Holland).

This study is:
Received: 2 May 2010; Revised: 4 June 2010; Accepted: 17 June 2010
Published Online: 2 Aug 2010 in Annals of Neurology, Volume 68.

How you can discussing something here for three months if that was public published some days ago?

Look's like you are cuting/pasting from somewere else thread.
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Postby Motiak » Wed Aug 04, 2010 3:21 pm

The problem with studies like this is my instinct would be that upon finding little to no abnormalities/problems in flow I would expect them to bring Zamboni in to look over their work. But that doesn't happen. So, I can't realistically draw a conclusion either way (pro CCSVI or against CCSVI) from these scientific studies because I have two parties telling me two completely opposite things.

So, I have two things that I rely on:

1. I feel like it's a lot harder to make a mistake and find an abornmality than it is to make a mistake and find nothing. It's like my wife's OB said when trying to discover the gender of our child via ultrasound, if you don't see anything, that doesn't necessarily mean it's a girl but if you see something, well, that's pretty much guaranteed to be a boy. So, I am innately more skeptical when they find little to no abnormalities.

2. Anecdotal evidence from patients on these forums makes me believe in a causal relationship with the good and bad stories that we hear. When I hear someone getting relief from symptoms that points to a causal relationship and when I hear someone getting worse after the procedure that also points to a causal relationship. I just feel like the treatment options that we have now are not very effective.
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Re: New Swedish Study Casts Doubt on MS Vascular Theory

Postby 1eye » Wed Aug 04, 2010 3:27 pm

scorpion wrote: Seriously you guys are ridiculous.


This person regularly refers to the people in this Forum as 'guys'. But as I hope my Lysistrata sketch was careful to emphasize, most of us guys are actually of the female persuasion. That is one of the unfairness-es of a male-dominated profession trying to maintain control of this particular patient population.

It seems unfair that they are so afflicted, but perhaps these vascular ideas help explain why, and also why men tend to get a more symptomatic course. Women have a monthly bleed that results in new blood being created to replace it. Far-fetched, perhaps, but these stem cells create new and naive immune cells too.
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Re: New Swedish Study Casts Doubt on MS Vascular Theory

Postby scorpion » Wed Aug 04, 2010 3:30 pm

1eye wrote:
scorpion wrote: Seriously you guys are ridiculous.


This person regularly refers to the people in this Forum as 'guys'. But as I hope my Lysistrata sketch was careful to emphasize, most of us guys are actually of the female persuasion. That is one of the unfairness-es of a male-dominated profession trying to maintain control of this particular patient population.

It seems unfair that they are so afflicted, but perhaps these vascular ideas help explain why, and also why men tend to get a more symptomatic course. Women have a monthly bleed that results in new blood being created to replace it. Far-fetched, perhaps, but these stem cells create new and naive immune cells too.


lol. Thanks for pointing that out one eye. I will try to do better!
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Postby cheerleader » Wed Aug 04, 2010 3:55 pm

Malden--
apologies. I did not reply to the Swedish study. you're right, I cut and pasted from the general thread. And I've been to the Netherlands and Amsterdam many times, since Jeff's kind of a big deal over there with the Metropole Orchestra, etc, so I do know the difference....

OK. Got the Swedish paper...
Here's some interesting stuff.

All 41 subjects underwent identical 2-dimensional PC- MRI scans to assess blood and CSF flows. Blood flow of the internal carotid arteries, the vertebral arteries, and the IJVs were imaged at the C2–C3 level using a velocity sensitization of 70cm/s. The blood measurement section was placed perpendicularly to the flow direction as determined by a sagittal 2-dimensional angiographic scout image. CSF flow was imaged
using a velocity sensitization of 20cm/s and measurement sec-
tion placed perpendicular to the cerebral aqueduct.



this isn't going to show very much, C2-C3 is a tiny piece of real estate. They just looked at a very small area in the neck ....and according to Dr. Haacke, if you're using MRV, it needs to be--

a 2D time-of-flight MRV through the head and neck down to the subclavian

a time resolved MRA/MRV of the head and neck coronally to the aortic arch

flow quantification through the straight sinus, the jugular (upper and lower) and coronally through the jugular/subclavian and brachiocephalic veins in one plane, to check for reflux flow and slow flow




So, this study is really not going to find many problems...and they didn't, although they admit they found slowed perfusion in the MS patients, and that there should be "further studies" done to clarify this

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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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