AAN early report on 3 CCSVI studies

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AAN early report on 3 CCSVI studies

Postby jean-la-grenouille » Thu May 26, 2011 10:33 am

Don't know if this has already been posted :

MS Research Progress Takes Center Stage at American Academy of Neurology’s Annual Meeting

Here is the link to the report :

http://mssociety.ca/en/research/medmmo_20110511.htm

quote related to CCSVI :

Research Toward Restoring Function
— CCSVI and MS

Five studies, including three posters and two platform presentations, related to studies of CCSVI (chronic cerebrospinal venous insufficiency) and MS. Read more about CCSVI (MS Society of Canada: http://mssociety.ca/en/releases/nr_20100611.htm and http://ccsvi.ca)

Mei Lu, MD (Cleveland Clinic Cerebrovascular Center), a member of one of seven teams (http://www.nationalmssociety.org/news/n ... x?nid=3339) being supported to investigate CCSVI by the National MS Society (USA) and the MS Society of Canada, was lead author of a poster on factors, both physiological and technical, that can complicate screening for vein blockages using Doppler sonography (ultrasound) technology:

They found that findings were often dependent on which operator conducted the ultrasound evaluation.

The team reported that heartbeat irregularities, stages of breathing, head position and pressure applied by the operator could alter results.

The team also reported that the state of hydration of the subject (whether they drank adequate amounts of fluids) could also impact results of several of the criteria used to determine CCSVI.

They concluded that these complications may help explain the mixed results reported thus far related to CCSVI and MS, and that having consensus guidelines would help improve the standardization of ultrasound assessments related to CCSVI. (Abstract P01.263)

A platform presentation by the team of Florian Connolly, MD (Humboldt University, Berlin) described a study that measured venous blood flow and narrowing with Doppler sonography in 96 people with MS (75 relapsing-remitting, 21 secondary-progressive) and 20 healthy controls.

As in a previous study published in 2010, in this larger sample of people they were unable to detect individuals who met more than one criterion for CCSVI.

Except for one person with MS, blood flow direction was normal in internal jugular vein and vertebral veins.

As in the previous study, the team found that blood volume flow tended to be higher in the upright position in people with MS compared to the healthy controls. (Abstract S01.001)

A poster from Yuval Karmon, MD, Robert Zivadinov, MD, and colleagues (University of Buffalo) focused on details from Phase I of what is planned as a controlled clinical trial of angioplasty to treat CCSVI (PREMiSe trial). This phase was an open-label evaluation comparing the use of three imaging methods (Doppler sonography, intravascular ultrasound, and catheter venography) to detect valve abnormalities of the internal jugular vein in 10 people with relapsing MS who fulfilled criteria for CCSVI.

They found that Doppler sonography was a sensitive tool for detecting internal jugular valve abnormalities, and that its findings were comparable to invasive intravascular ultrasound.

They found valve dysmobility frequently in this sample of patients diagnosed with CCSVI.

According to the investigators, the next phase will include more people and will be a blinded and controlled study of angioplasty. Results of that trial will be released after they have completed the study. (Abstract P04.187)

A platform presentation from Katayoun Alikhanim MD (University of Calgary) and colleagues from across Canada focused on a study of the frequency of neck vein abnormalities in 67 people who visited an MS clinic (34 MS, 20 not MS, 7 possible MS, 6 CIS) using contrast-enhanced MR venography.

The radiologist was blinded as to the condition of each patient.

Abnormalities were found in 7 out of 34 with MS, 4 out of 20 not MS, 0 out of 7 possible MS and 1 out of 6 CIS.

Those with MS with vein abnormalities were more likely to be older (average age about 52 years) and to have more disability (average EDSS 6.17) compared to those with normal veins (46 years, 3.57 EDSS). (Abstract S01.006)

A poster from Kresimir Dolic, MD, and colleagues (University of Buffalo) described a study to compare vein findings using Doppler sonography and MR venography and determine whether they were complementary. The study included 150 people with MS (104 relapsing-remitting, 38 secondary-progressive, 8 primary-progressive) and 63 healthy controls matched for age and sex.

They found that Doppler sonography was more sensitive for detecting internal jugular vein flow abnormalities, while MR venography was more sensitive for detecting collateral veins.

98 (67.12%) of people with MS and 18 (28.57%) of healthy controls met criteria for CCSVI.

People with MS had evidence of collateral veins more often than healthy controls. (Abstract P05.071)
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Re: AAN early report on 3 CCSVI studies

Postby frodo » Thu May 26, 2011 11:02 am

Wow. Thanks
Last edited by frodo on Fri May 27, 2011 1:29 am, edited 1 time in total.
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Postby scorpion » Thu May 26, 2011 11:32 am

More studies finding not much of anything. Zamboni needs to step up and admit his study was flawed and then maybe some of this foolishness will go away.
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Postby Johnnymac » Thu May 26, 2011 12:41 pm

Scorpion says:
More studies finding not much of anything. Zamboni needs to step up and admit his study was flawed and then maybe some of this foolishness will go away.



You really kinda make yourself look bad with the above statement, there are numerous things here that could be argued significant.


They found valve dysmobility frequently in this sample of patients diagnosed with CCSVI.

I think we're all learning that its these valve abnormalities that are the culprit in a lot of CCSVI positive patients, this is very important as it influences what proper diagnostics and treatment methods are to be performed and studied.


As in the previous study, the team found that blood volume flow tended to be higher in the upright position in people with MS compared to the healthy controls

Interesting thing about this study to me is the extreme opposite findings of everyone else. They find only 1 person out of 96 who met more than 1 criteria of the zamboni protocol? This is a stark difference to other studies and to me suggest it was flawed in some way, perhaps operator?


They found that findings were often dependent on which operator conducted the ultrasound evaluation.


We keep hearing this, I think we have to give it some credence and understand its going to take time to train new technicians, and those technicians will need to perform this testing dozens if not hundreds of time to fine tune their technique.

The team reported that heartbeat irregularities, stages of breathing, head position and pressure applied by the operator could alter results.


Again, many outside influences with ultrasound (and venogrophy for that matter). There are going to be things that cause false positive and false negative in testing. They will get better and managing these influences as the operators get more practice and are more aware of what those influences are. Studies like this will help a lot of technicians know what nuances to watch for when testing for CCSVI.


The team also reported that the state of hydration of the subject (whether they drank adequate amounts of fluids) could also impact results of several of the criteria used to determine CCSVI.


Again, more learning. They will get better at this.


They concluded that these complications may help explain the mixed results reported thus far related to CCSVI and MS, and that having consensus guidelines would help improve the standardization of ultrasound assessments related to CCSVI.


A call for standardization of ultrasound assessment. Amen....but, something that you must keep in mind. The doctors and technicias are learning as we're going, this 'standard' needs to be carefully constructed, by the most experienced individuals.

A platform presentation from Katayoun Alikhanim MD (University of Calgary) and colleagues from across Canada focused on a study of the frequency of neck vein abnormalities in 67 people who visited an MS clinic (34 MS, 20 not MS, 7 possible MS, 6 CIS) using contrast-enhanced MR venography.

The radiologist was blinded as to the condition of each patient.

Abnormalities were found in 7 out of 34 with MS, 4 out of 20 not MS, 0 out of 7 possible MS and 1 out of 6 CIS


Contrast enhanced MRV is going to tell very little if anything about valve issues, this can not be a sole qualifer for CCSVI diagnosis or not.

98 (67.12%) of people with MS and 18 (28.57%) of healthy controls met criteria for CCSVI.


I'd say that is pretty strong evidence of association.

People with MS had evidence of collateral veins more often than healthy controls.

evidence of vein abnormalities in those with MS vs controls.
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Postby jean-la-grenouille » Thu May 26, 2011 12:44 pm

Anyone can read and makes his own thought.
After reading this report, i still believe CCSVI is more prevalent in people with MS.
7 studies have begun in Canada, this deals with 3 of them.
The SCSP has published an article about these studies a few month ago. They said they would published results every semester. (2 years studies).
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Postby scorpion » Thu May 26, 2011 1:55 pm

I think the people who look bad are the ones who still talk as though there is no doubt CCSVI is connected to MS when some of the studies are questioning whether it even exists. I think the people who look bad are the ones out picketing at MS Societty fundraiser events for a theory that seems to be losing steam with each new study that is released. The people who look bad are the ones encouraging people not to donate to MS agencies who do not want to pour millions of dollars into research that looks to be hitting a dead end. What looks bad is someone who looks at studies, brushes over the evidence showing facts they do not want see, and grabs ahold of whatever small thing they can find in hopes that their conclusions are not challenged. If these studies were the first to be released instead of Zamboni's "groundbreaking" discovery there would not be the CCSVI Alliance, a CCSVI forum, or articles about the wonders of liberation. Zamboni started this now he needs to come forward and explain why no one is able to duplicate his study. The likey explanation is he saw what he wanted to see and the rest is history. Seriously it is time for people to put aside their pride and admit this CCSVI thing is not what they thought it was but I can not see that happenig due to some of the egos.
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Postby cheerleader » Thu May 26, 2011 2:42 pm

This is a recap of information presented in Hawaii at the American Academy of Neurology meeting, composed by the MS Society of Canada.

The most interesting study presented was the angioplasty study in Buffalo, where CCSVI was found in 10 pw RMMS, who were then treated by angioplasty.

Venography is the gold standard. This study proves that once again.

Here are some selections from the paper:
Catheter Venography and PTA
Catheter venography was performed only in patients with MS after the Doppler sonography examination showed that all patients with MS fulfilled 2 venous hemodynamic criteria.1 It was performed via catheterization of the left iliac femoral vein and comprised visualization of the lumbar veins, left renal vein, azygous vein, and IJVs.3

Significant stenosis was considered to be any venous lumen reduction 50%.
We investigated the following IJV anomalies: annulus, a significant circumferential stenosis of the venous wall; septum/valve malformation, anomalous valve apparatus causing significant flow obstacles at the level of the junction of the brachiocephalic trunk; membranous obstruction, a membrane almost completely occluding a vein; hypoplasia, an underdeveloped long venous segment; twisting, severe stenosis as a consequence of a twisted venous segment; and agenesis, complete anatomic absence of a venous segment.

Catheter venography was conducted by an interventional radiologist.
The presence of at least 1 of these anomalies in the IJVs was considered an abnormal examination finding when compared with MRV and Doppler sonography. Catheter venography was used as a criterion standard for comparison with MRV and Doppler sonography.

IJV Findings in Patients with MS and Healthy Controls
at Baseline and Follow-Up
Table 1 and Figs 1 and 2 show TOF, TRICKS, Doppler sonography, and catheter venography findings, at baseline and follow- up, in the left and right IJVs of patients with MS. At baseline, abnormalities were found in all patients with MS on Doppler sonography and catheter venography, in 30% of patients on TOF, and in 40% on TRICKS. All patients presented with 2 venous hemodynamic criteria on Doppler sonography, and the mean number of venous hemodynamic criteria was 4. Catheter venography of the right IJV showed the presence of an annulus in 4 patients, a septum in 3 patients, and no abnormalities in 3 patients. Catheter venography findings of the patients with MS in the left IJV were the following: annulus (5), septum (3), membrane (1), malformed valve (1), and normal examination findings (1).
All patients with MS underwent PTA at baseline.


Here is the full paper:
link

It's not about ego. It's about research. And as long as venous malformations are being found in pwCCSVI, there will continue to be more research. That's why there's a CCSVI Alliance and clinical trials underway around the world.
cheer
Last edited by cheerleader on Thu May 26, 2011 2:46 pm, edited 1 time in total.
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby Johnnymac » Thu May 26, 2011 2:45 pm

Your outright dismissal is a little hypocritical of the position you take is it not? It takes doubters to balance the science and push for real numbers but outright dismissal that it even exists is more than being a doubter. To each their own, ccsvi is still a theory, albeit one with a lot of real science going for it. One of these days the medical world will figure this mystery out.

What do you think is the cause of ms? Just curious what your current thoughts on the matter are.
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Postby 1eye » Thu May 26, 2011 2:48 pm

Johnnymac wrote:Scorpion says:
...

You really kinda make yourself look bad with the above statement, there are numerous things here that could be argued significant.

Not even worth quoting, really...
As in the previous study, the team found that blood volume flow tended to be higher in the upright position in people with MS compared to the healthy controls

Interesting thing about this study to me is the extreme opposite findings of everyone else. They find only 1 person out of 96 who met more than 1 criteria of the zamboni protocol? This is a stark difference to other studies and to me suggest it was flawed in some way, perhaps operator?

Actually, if that is the case, that to me is another smoking gun. Normal people have more flow when prone. Abnormal (CCSVI) people have more flow when upright, because they have had to create collateral paths to accept the flow that will not pass through its normal passage in the prone position. When they get back into the upright position the collateral veins have much more force driving blood through them and so the flow, even in the stenotic IJVs, is greater. The likelihood of reflux, and elastic changes, due to the daily changing load, on veins which do not have the evolution behind their structure and strength that real jugular veins do, is going to be greater.

What drives flow? Gravity, muscular pumping, the heart. Why would the flow be greater when lying down? Only if the resistance was lower (free-flowing, full IJVs), since the pumps are not pumping as hard. But in the case of people who are not normal, the resistance is not lower, so the flow is not greater. QED.
People with MS had evidence of collateral veins more often than healthy controls.

The first smoking gun.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
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Postby scorpion » Thu May 26, 2011 4:06 pm

cheerleader wrote:This is a recap of information presented in Hawaii at the American Academy of Neurology meeting, composed by the MS Society of Canada.

The most interesting study presented was the angioplasty study in Buffalo, where CCSVI was found in 10 pw RMMS, who were then treated by angioplasty.

Venography is the gold standard. This study proves that once again.

Here are some selections from the paper:
Catheter Venography and PTA
Catheter venography was performed only in patients with MS after the Doppler sonography examination showed that all patients with MS fulfilled 2 venous hemodynamic criteria.1 It was performed via catheterization of the left iliac femoral vein and comprised visualization of the lumbar veins, left renal vein, azygous vein, and IJVs.3

Significant stenosis was considered to be any venous lumen reduction 50%.
We investigated the following IJV anomalies: annulus, a significant circumferential stenosis of the venous wall; septum/valve malformation, anomalous valve apparatus causing significant flow obstacles at the level of the junction of the brachiocephalic trunk; membranous obstruction, a membrane almost completely occluding a vein; hypoplasia, an underdeveloped long venous segment; twisting, severe stenosis as a consequence of a twisted venous segment; and agenesis, complete anatomic absence of a venous segment.

Catheter venography was conducted by an interventional radiologist.
The presence of at least 1 of these anomalies in the IJVs was considered an abnormal examination finding when compared with MRV and Doppler sonography. Catheter venography was used as a criterion standard for comparison with MRV and Doppler sonography.

IJV Findings in Patients with MS and Healthy Controls
at Baseline and Follow-Up
Table 1 and Figs 1 and 2 show TOF, TRICKS, Doppler sonography, and catheter venography findings, at baseline and follow- up, in the left and right IJVs of patients with MS. At baseline, abnormalities were found in all patients with MS on Doppler sonography and catheter venography, in 30% of patients on TOF, and in 40% on TRICKS. All patients presented with 2 venous hemodynamic criteria on Doppler sonography, and the mean number of venous hemodynamic criteria was 4. Catheter venography of the right IJV showed the presence of an annulus in 4 patients, a septum in 3 patients, and no abnormalities in 3 patients. Catheter venography findings of the patients with MS in the left IJV were the following: annulus (5), septum (3), membrane (1), malformed valve (1), and normal examination findings (1).
All patients with MS underwent PTA at baseline.


Here is the full paper:
link

It's not about ego. It's about research. And as long as venous malformations are being found in pwCCSVI, there will continue to be more research. That's why there's a CCSVI Alliance and clinical trials underway around the world.
cheer


Why is the study with the smallest number of participants, from what I can see, the most interesting? Because the results were at least in the ballpark of what you wanted to see? How did you come to the conclusion that THIS study proves venography is the gold standard yet many others have used it and basically found nothing?? I am just concerned that resources for legitimate research are being wasted on what is beginning to look like another dead end in the MS research world. Do we keep doing research on CCSVI for the next ten years in hopes that there is SOME bit of evidence linking it to MS in some small way??
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Postby 1eye » Thu May 26, 2011 4:41 pm

As in the previous study, the team found that blood volume flow tended to be higher in the upright position in people with MS compared to the healthy controls

Why? Collateral veins, unlike IJVs, do not collapse when you become upright. Another smoking gun.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
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Postby jean-la-grenouille » Fri May 27, 2011 9:25 am

I also wonder why pwMS have a higher blood flow when they stand up, compared to ealthy subjects. It is clear that blood flow is important in MS.

The CCSVI research is in an early stage, and original studies have not been replicated so far. However, several studies at least confirme a venous dysfonction among those with MS.

No one can say CCSVI is the cause of MS, nore it is a hoax. Time will tell.
I state CCSVI is more than a hope, it is linked to MS and leads to a better understanding of MS.
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Re: re

Postby cheerleader » Fri May 27, 2011 9:50 am

Jean--Here is Dr. Zamboni's explanation---It's about the change that happens due to positional variation. Normals have working jugular veins, and their blood does not defer to collaterals when supine. Because of this, when they go to upright, they have less pressure than pwMS, therefore, less flow. This is NORMAL. The jugulars take blood more quickly from the brain to the heart, relieveing pressure. Because pwMS do not have this relief of pressure, the vertebrals take more blood flow when they are upright. Seeing my husband's collateral veins when he was supine was enough evidence for him to seek treatment....

Published in the Annals of Neurology-
http://www.ncbi.nlm.nih.gov/pubmed/21061390

Regarding ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis. Intraluminal Jugular Septation’’ Paolo Zamboni, MD

I read with interest the article titled ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis’’ by Doepp and coworkers.1 Contrary to their conclusions, I believe that the authors’ results are a further validation of venous flow irregularities in multiple sclerosis (MS) patients.

One of the major regulators of cerebral venous outflow is posture, due to the gravitational gradient between the cerebral parenchymal veins and the base of the neck (␣30mmHg).2 The authors demonstrate a much larger change in blood flow volume in normal subjects compared to MS patients when the subjects go from a supine to an upright position. They find a change of 128ml/min and 56ml/min for the right and left sides, respectively, for MS patients. But they find a much larger change of 266ml/min and 105ml/min for their normal subjects. This result actually suggests the presence of chronic cerebrospinal venous insufficiency (CCSVI). Possible causes include intra-luminal septum, membrane, and immobile valve affecting the hydrostatic pressure gradient in the upright position. The presence of such blockages in the extracranial and extravertebral cerebral veins has been proven also by using catheter venography, the unquestionable gold standard in medicine.3,4

There was a trend toward significance (0.06) when comparing the mean global cerebral blood flow (CBF) in MS patients with that in controls. However, the level of significance is under- estimated by the low control sample, 20 versus 56 patients. The reduction in CBF in MS, meaning in practical terms stasis, might become significant by simply increasing the control sample.

Both the above-reported results correspond with the reduction in CBF and in cerebral blood volume with increased mean transit time, assessed by means of magnetic resonance imaging (MRI) perfusion study.5
The authors failed to demonstrate CCSVI through the assessment of the criteria originally proposed by our group. However, it seems the latter were not precisely assessed. For instance, the authors exchange the parameter for defining stenosis we used in angiographic studies (>50% lumen reduction) with those used in Doppler ultrasonography. In addition, the frequent detection of intraluminal jugular septation is not described by the authors. The latter is the most common cause of flow blockage, and can only be diagnosed with high resolution ultrasonographic probes capable to explore the jugular in the supraclavicular fossa (Fig. 1) 3-4. Clearly, a complete understanding of the system is required before drawing conclusions about the lack of venous abnormalities, and this requires ultra- sound, MRI, and catheter venography. This underscores the urgency of establishing an internationally accepted protocol. In the attempt to achieve this cultural osmosis, my group is available to travel to Berlin and rescan with German colleagues the entire series by the means of the proposed methodology.

cheer
Last edited by cheerleader on Fri May 27, 2011 9:59 am, edited 1 time in total.
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Postby Johnnymac » Fri May 27, 2011 9:56 am

Why does the right side differ so much from the left side in flow volume (on both pwMS and HC)? Could 'ccsvi' on the right side be more heavily associated with progressive forms of MS since that side seems to carry a larger load?
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Postby cheerleader » Fri May 27, 2011 10:01 am

Johnnymac wrote:Why does the right side differ so much from the left side in flow volume (on both pwMS and HC)? Could 'ccsvi' on the right side be more heavily associated with progressive forms of MS since that side seems to carry a larger load?


Johnny--the researchers are looking at this very thing. Siskin and simka and others are finding the right and left variations in CCSVI and trying to see how it links to disability. I'll dig up the papers and be back...
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http://ccsviinms.blogspot.com
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