Another Important New BNAC CCSVI Study

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Another Important New BNAC CCSVI Study

Postby Squeakycat » Fri Oct 21, 2011 9:53 am

BMC Neurol. 2011 Oct 19;11(1):128. [Epub ahead of print]

Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency.
Zivadinov R, Poloni GU, Marr K, Schirda CV, Magnano CR, Carl E, Bergsland N, Hojnacki D, Kennedy C, Beggs CB, Dwyer MG, Weinstock-Guttman B.

ABSTRACT
BACKGROUND::

The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC).

METHODS:
59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: <.3 mm, .3-.6 mm, .6-.9 mm and >.9 mm.

RESULTS:
CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p<.0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter <.3mm, and increased DFV compared to HC (all p<.0001). Subjects diagnosed with CCSVI had significantly increased DFV (p<.0001), decreased overall ATVV and ATVV of veins with a diameter <.3mm (p<.003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p<.0001) on pre- and post-contrast SWI, but not in HC.

CONCLUSIONS:
MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS.

PMID: 22011402 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22011402
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Re: Another Important New BNAC CCSVI Study

Postby Jugular » Fri Oct 21, 2011 11:15 am

So what distinquishes a pwMS with CCSVI from an HC with CCSVI - severity of CCSVI or decreased venous vasculature? Secondly, what is causing the decreased venous vasculature - MS or CCSVI? Thirdly, will angioplasty which relieves CCSVI, relieve decreased venous vasculature? And lastly, if so, should the criteria for CCSVI be changed to look firstly for decreased venous vasculature and then for ways to improve it through angioplasty?

Fascinating.
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Re: Another Important New BNAC CCSVI Study

Postby cheerleader » Fri Oct 21, 2011 11:37 am

Thanks, Squeaky---
it's a great paper for many reasons....especially the fact that BNAC researchers are now finding CCSVI in 80% of pwMS and 18% of HC....which is closer to Dr. Zamboni's results.

Researchers have been looking at reduced venous visability in MS since the advent of better imaging technology--
Ge had one of the first studies on this--and posited that this result of reduced vasculature might be due to venous vascular occlusions and reduced perfusion.

There exists the possibility, however, that diminished venous vasculature on SWI in MS represents altered venous hemodynamics or venous vascular occlusions (15). A previous study of ours in MS patients found significantly reduced cerebral blood flow in normal appearing white matter using perfusion MRI (16).

http://www.direct-ms.org/sites/default/ ... S%2009.pdf

The chicken and egg debate will continue....which comes first? Brain damage due to MS disease process creating CCSVI or reduced perfusion due to CCSVI creating MS? If we look at perfusion studies in early MS, we find that hypoperfusion occurs early on in the disease process----before the blood brain barrier breakdown and immune activation.

Cerebral Perfusion Changes Precede Blood Brain Barrier Breakdown in MS--
http://www.mendeley.com/research/cerebr ... is/#page-1
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Re: Another Important New BNAC CCSVI Study

Postby Jugular » Fri Oct 21, 2011 11:47 am

Perhaps the chicken or egg dichotomy is false in this case. Maybe it's two bad eggs, CCSVI and something else, who apart cause limited harm, but together 'egg' each other on in a destructive dance.
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Re: Another Important New BNAC CCSVI Study

Postby Squeakycat » Fri Oct 21, 2011 1:22 pm

cheerleader wrote:http://www.direct-ms.org/sites/default/ ... S%2009.pdf

The chicken and egg debate will continue....which comes first? Brain damage due to MS disease process creating CCSVI or reduced perfusion due to CCSVI creating MS? If we look at perfusion studies in early MS, we find that hypoperfusion occurs early on in the disease process----before the blood brain barrier breakdown and immune activation.

cheer


Isn't it really rather silly to say that the chicken and egg problem is still up in the air? I'm not saying that to you Cheer, but to those who are making that case.

Sure, you can do a bunch of studies looking for CCSVI in different groups of MS patients to see if it appears early or late in the disease, and come to all kinds of conclusions which simply reflect your ability to measure CCSVI, not its etiology.

But if you look more directly at the nature of the problems being found in CCSVI, it is pretty hard to figure out how MS inflammation could cause a valve malformation or a septum to form. It just doesn't seem possible that these congenital problems could be caused by an inflammatory disease process unless I'm missing something. The cart has gotten in front of the horse.
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Re: Another Important New BNAC CCSVI Study

Postby David1949 » Fri Oct 21, 2011 2:46 pm

Squeakycat wrote:But if you look more directly at the nature of the problems being found in CCSVI, it is pretty hard to figure out how MS inflammation could cause a valve malformation or a septum to form. It just doesn't seem possible that these congenital problems could be caused by an inflammatory disease process unless I'm missing something. The cart has gotten in front of the horse.


That's an excellent point. I think we can easily envision CCSVI causing MS, but how would MS cause CCSVI?
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Re: Another Important New BNAC CCSVI Study

Postby Cece » Fri Oct 21, 2011 3:56 pm

The argument that MS might cause CCSVI tends to be made by those who consider CCSVI to be a stricture of the vein itself and not as intraluminal abnormalities. The idea is that there is less cerebral perfusion, therefore less outflow, therefore narrower veins. Or inflammation from the brain has led to inflammation in the veins, narrowing them. I have not heard anyone suggesting MS causes CCSVI who can talk specifically about the valves and the intraluminal abnormalities such as septums and then pitch a theory that MS is causing intraluminal abnormalities. It is possible that neurologists do not know what an intraluminal abnormality is.
MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS.

Is a higher number of venous stenoses indicative of CCSVI severity? Percentage of stenosis is also a major factor. Two low grade stenoses would not be as severe a CCSVI situation as two high grade stenoses. A high grade stenosis in the dominant larger vein would be a more severe CCSVI situation than a high grade stenosis in the non dominant vein.

Is this suggesting that the CCSVI is causing the reduced metabolism and morphological changes in the brain?
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Re: Another Important New BNAC CCSVI Study

Postby cheerleader » Fri Oct 21, 2011 4:02 pm

Cece wrote:The argument that MS might cause CCSVI tends to be made by those who consider CCSVI to be a stricture of the vein itself and not as intraluminal abnormalities.

Is this suggesting that the CCSVI is causing the reduced metabolism and morphological changes in the brain?


I have the full paper, and the posits are that the MS disease creates hypometabolism of brain tissue and this leads to less blood flow and CCSVI, or CCSVI strictures create hypoperfusion and reduced visability of vasculature....
but Cece makes a GREAT point.
In studies, like the one from the Cleveland Clinic, announced today---intraluminal defects are found in the veins of pwMS at much higher rates than normals. These are not "strictures" or "stenosis" created by hypovolemia or inflammation---these intraluminal defects are truncular venous malformations, as we see in other congenital venous disease.
onward!
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Re: Another Important New BNAC CCSVI Study

Postby Cece » Fri Oct 21, 2011 4:30 pm

cheerleader wrote:I have the full paper, and the posits are that the MS disease creates hypometabolism of brain tissue and this leads to less blood flow and CCSVI, or CCSVI strictures create hypoperfusion and reduced visability of vasculature....

ok, I had thought it might be that CCSVI causes the hypometabolism, which would fit with the possibility of reduced glucose being available because of the diminished flow, but that is not where they were going with it.

I have been part of the CCSVI discussion for almost two years, and it has been onward and onward this whole time. The research keeps coming in. I like the way the research is going, and I like how quick it really has been, although I would always prefer quicker.
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Re: Another Important New BNAC CCSVI Study

Postby 1eye » Fri Oct 21, 2011 9:21 pm

Dr. Zamboni has been saying since 2009 at least that CCSVI is part of a whack of congenital defects, some of which are in the cerebro-spinal outflow. Yet many people are still saying it doesn't exist. Radiological evidence does not seem to sway them. I think this is the greatest mass self-delusion since the second world war.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
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Re: Another Important New BNAC CCSVI Study

Postby CureOrBust » Sat Oct 22, 2011 4:51 am

Although its really off-topic, I think we have to be careful of not acting like those that you are deriding. People are quick to point fingers at neuro's for dismissing CCSVI to quickly, and just because we do not see it now how MS could possibly cause CCSVI, I think we can not presume that it is not at all possible; but I do think the ball is in their court.
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Re: Another Important New BNAC CCSVI Study

Postby cheerleader » Sat Oct 22, 2011 8:35 am

CureOrBust wrote:Although its really off-topic, I think we have to be careful of not acting like those that you are deriding. People are quick to point fingers at neuro's for dismissing CCSVI to quickly, and just because we do not see it now how MS could possibly cause CCSVI, I think we can not presume that it is not at all possible; but I do think the ball is in their court.


Cure--I think the frustration and anger for many of us is the amount of time this is taking. Dr. B.B. Lee said in 2009 that CCSVI malformations looked to him to be the same intraluminal truncular venous malformations he saw in Budd Chiari, like webs, inverted valves, septa, etc. Now, it almost 2012 and Dr. Robert Fox says, hey! You're right, these are intraluminal defects that might change hemodynamics. This could have been accomplished so much sooner if neurologists did not feel they had to reinvent the wheel to learn what VENOUS specialists already know.

The question of causation needs to be addressed, and I do not believe it is deriding for us to say---BUT the venous doctors already know how intraluminal defects cause liver failure in Budd Chiari....WHY do the neurologists need to reinvent the wheel, once again, to explain the failure of the brain and spine? Precious time, for many pwMS, is being wasted over this seeming turf war---which is based more on semantics, than science.
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Re: Another Important New BNAC CCSVI Study

Postby CureOrBust » Sat Oct 22, 2011 5:33 pm

Trust me, I understand the anger and frustration with how long this is all taking, as you would know, I have been personally actively following this since the 2008 Zamboni article. I also have an understanding (but not an agreement with) neurologists knee jerk reaction at new ideas on a disease they think they have a good understanding of (think Snake Venom and Bee Sting therapy). I am just making the point I guess of a quote which I thought was from Sun Tzu in the "Art of War"
Sun Tzu wrote:Never underestimate your enemy
I have not read the book, but a lot of people quote him in situations other than actual war.
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New BNAC CCSVI Study

Postby MarkW » Tue Nov 01, 2011 8:12 am

The whole provisional paper is available:
http://www.biomedcentral.com/content/pdf/1471-2377-11-128.pdf
While this is not a definitve explanation of what CCSVI syndrome does to pwMS, it is evidence to say that treating CCSVI syndrome (safely) should be undertaken while more research is conducted. Please do not imply too much from this paper, it is early research.
Happy reading,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Another Important New BNAC CCSVI Study

Postby cheerleader » Tue Nov 01, 2011 8:51 am

Mark--
Thanks for linking the full paper.
Actually, the research into reduced venous vasculature visibility in MS has been ongoing for several years. Ge, Haacke, Zivadinov and many other imagers have noted this on susceptablility weighted imagery. What is new is the linking of this phenomena to CCSVI. Here is an abstract presented at the 2010 ECTRIMS--the predecessor of the paper presented this year.


http://registration.akm.ch/einsicht.php ... KEN_ID=900
Background: The venous vasculature of the brain parenchyma is significantly less visible on susceptibility-weighted imaging (SWI) in patients with multiple sclerosis (MS) compared to healthy controls (HC), as previously described.

Objective: To investigate the relation between the altered venous vasculature visibility in the brain parenchyma and Cine Cerebrospinal Fluid (CSF) Imaging and Perfusion Weighted Imaging (PWI) MRI metrics in patients with relapsing-remitting (RR) and secondary-progressive (SP) MS disease course, and HC.
Methods: Fifty nine (59) MS patients [41 RR and 18 SP] and thirty three (33) age- and sex-matched HC were scanned on a 3T GE scanner using CSF imaging, PWI and SWI. Mean age at scan was 44.3 yrs, mean disease duration 13.2 yrs and median EDSS 2.5. CSF flow rates (positive, negative and net), Mean Transit Time (MTT), Cerebral Blood Flow (CBF) maps and Cerebral Blood Volume (CBV) maps were calculated. 3D multi-scale line filter was used to extract the venous vasculature from SWI images. Absolute venous volume (AVV) was estimated in milliliters (ml); relative venous intracranial fraction (VIF) was calculated to correct for head size and amount of brain atrophy. Vein volumes were classified by vein radius: <0.3mm, 0.3-0.6mm, 0.6-0.9mm and >0.9 mm. Voxel brain average distance-from-vein (DFV) maps were calculated.
Results: MS patients showed reduced AVV, volume of veins with diameter <0.3mm and VIF (p< .05) and increased DFV (all p< .001) with respect to HC. In MS patients lower AVV, volume of veins with diameter <0.3mm and VIF, and higher DVF were strongly related to lower net negative flow (Spearman r = .48 to .61, p< .001) and higher net positive flow (r = .53 to .64, p< .001). A similar relation was found with an increased MTT (gray matter: r = .36 to .43, p< .01; white matter: r = .40 to .46, p< .001) and a decreased CBF (gray matter: r = .38 to .45, p< .01; white matter: r = .37 to .49, p< .001). The relationships were consistently stronger in RR than SP MS patients. No significances where found for HC.

Conclusions: This study showed that lower brain parenchyma venous vasculature visibility on SWI is related to altered hemodynamic CSF flow and hypoperfusion in patients with MS. The events contributing to these findings are probably occurring early in the disease process. Further studies are needed to elucidate relationship between reduction of venous vasculature and the hemodynamic MRI parameters in MS patients.


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