CCSVI--possible new underlying cause of MS?

 
Post new topic   Reply to topic    msspeaks Forum Index -> MS - RESEARCH, ARTICLES, ABSTRACTS, DISCUSSION
View previous topic :: View next topic  
Author Message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Nov 02, 2009 7:33 pm    Post subject: CCSVI--possible new underlying cause of MS? Reply with quote

From Medical News Today, October 26, 2009:

Quote:
Possible New Underlying Cause Of MS Investigated By Neurologists

Neurologists at the University at Buffalo are beginning a research study that could overturn the prevailing wisdom on the cause of multiple sclerosis (MS).

The researchers will test the possibility that the symptoms of MS result from narrowing of the primary veins outside the skull, a condition called "chronic cerebrospinal venous insufficiency," or CCSVI. (For more details on the study, go to http://www.bnac.net/?page_id=496.)

CCSVI is a complex vascular condition discovered and described by Paolo Zamboni, M.D., from Italy's University of Ferrara. In the original Italian patients, CCSVI was found to be strongly associated with MS, increasing the risk of developing MS by 43 fold.

This narrowing restricts the normal outflow of blood from the brain, causing alterations in the blood flow patterns within the brain that eventually causes injury to brain tissue and degeneration of neurons.

"If we can prove our hypothesis, that cerebrospinal venous insufficiency is the underlying cause of MS," said Robert Zivadinov, M.D., Ph.D., UB associate professor of neurology, director of the Buffalo Neuroimaging Analysis Center (BNAC) and principal investigator on the study, "it is going to change the face of how we understand MS."

Michael Cain, M.D., professor and dean of the UB School of Medicine and Biomedical Sciences, said a positive outcome from this trial would have enormous implications for the treatment of MS. "Being able to identify those at risk of developing MS before symptoms take their toll could change the lives of millions of persons who now face inevitable lifestyle restrictions."

Margaret Paroski, M.D., executive vice president and chief medical officer of Kaleida Health, parent of Buffalo General Hospital where the BNAC is located, commented: "... Challenging basic assumptions about diseases has led to some very important discoveries.

"When I was in medical school, we thought peptic ulcer disease was due to stress. We now know that 80 percent of cases are due to a bacterial infection. Dr. Zivadinov's work may lead to a whole different way of thinking about multiple sclerosis."

The preliminary findings were based on a pilot study at the BNAC headed by Zivadinov, and at the Universities of Ferrara and Bologna, Italy, directed by Zamboni and Fabrizio Salvi, M.D, respectively. The study showed that several abnormalities affecting the predominant pathways that return venous blood from the brain to the heart occurred more frequently in MS patients than in controls.

This research, supported by the Hilarescere Foundation of Italy and the BNAC, was conducted to replicate the findings of the Italian investigators.

"Results of this preliminary study, which involved 16 relapsing-remitting MS patients and eight age-and-sex-matched healthy controls, showed that all the MS patients, but none of the controls, had chronic insufficient blood flow out of the brain," said Zivadinov.

Bianca Weinstock-Guttman, M.D., UB associate professor of neurology and a co-principal investigator on the pilot study, added: "The images from this study were acquired using a method called Doppler ultrasound. The method identified anomalies in the venous blood flow associated with strictures, malformed valves and peculiar webs within the large veins of the neck and brain"

Weinstock-Guttman directs the Baird Multiple Sclerosis Center at the Jacobs Neurological Institute (JNI), UB's Department of Neurology. The JNI and BNAC are located in Buffalo General Hospital of Kaleida Health.

Advanced magnetic resonance imaging scanning (MRI) of the MS study patients conducted at the BNAC also identified distinct areas of iron deposits in the brain, and showed that those deposits may be associated with the location of MS lesions and sites of impaired drainage. The scans also revealed increased brain atrophy and changes in the flow of cerebrospinal fluid in the MS patients.

These results, which form the basis of the current larger investigation, were presented at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis held in September in Dusseldorf, Germany

The new study will involve 1,600 adults and 100 children. The cohort will be comprised of 1,100 patients who were diagnosed with possible or definite MS, 300 age-and-sex matched normal controls, and 300 patients with other autoimmune and neurodegenerative diseases. Enrollment in the study has begun and will continue for two years. MS patients from across the U.S. are eligible to participate in the study.

"The prevailing wisdom that central nervous system damage in MS is predominantly the result of abnormal immune responses against the patient's nervous tissue has been challenged by research findings, which have demonstrated a significant neurodegenerative component in MS and the progressive loss of neurons," said Zivadinov.

However, these inflammatory and neurodegenerative processes occur concurrently in MS and vary considerably among patients, making it difficult to identify the cause, or causes of the disease. Consequently, the origin and development of MS remains poorly understood, and its cause remains elusive."

To determine if these preliminary findings can be repeated, Zivadinov and Weinstock-Guttman organized the present study, which will evaluate both the velocity of blood flow through both the brain's blood vessels and the extracranial veins, using Doppler ultrasound.

The technical name of the study is "combined transcranial and extracranial venous Doppler (CTEVD) evaluation in MS and related diseases".

All study subjects will undergo a general clinical examination and a Doppler scan of the head and neck to acquire images of the direction of venous blood flow in different body postures. Participants also will provide blood samples, and complete an extensive environmental questionnaire to identify potential MS risk factors.

All MS patients will undergo MRI of the brain to measure iron deposits in lesions and surrounding areas of the brain using a method called susceptibility-weighted imaging. Iron findings on these images will be related to neuropsychological symptoms. The neuropsychological part of the study will be conducted by Ralph Benedict, Ph.D., professor of neurology and psychiatry at the JNI, UB's Department of Neurology.

A sub-cohort of 250 consecutive patients and controls will undergo MRI of the veins of the neck to confirm diagnosis of CCSVI.

Murali Ramanathan, Ph.D., associate professor in the Department of Pharmaceutical Sciences, UB School of Pharmacy and Pharmaceutical Sciences, will analyze blood samples for proteins and soluble factors associated with central nervous system injury. He also will be looking for other factors of interest in MS research, such as vitamin D metabolites and cigarette smoking, which have been linked to increased risk for developing MS as well as MS disease progression.

The data will be unblinded at three predetermined time-points, with the initial unblinding scheduled for November 2009.

Zivadinov said results of the study may lead to a larger multicenter North-American trial that will evaluate the occurrence of CCSVI in MS.

Source:
Lois Baker
University at Buffalo


The article can be seen here.


Last edited by agate on Wed Mar 31, 2010 5:01 pm; edited 1 time in total
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Nov 09, 2009 10:02 pm    Post subject: News detail from the National MS Society about CCSVI Reply with quote

News Detail from the National MS Society, October 6, 2009 (also in the MS International Federation News, October 13, 2009);

Quote:
Research into Blood Flow in the Brain and Venous Insufficiency, or CCSVI, in MS

A few recent reports have revived ages-old speculation about a possible dysfunction of brain blood flow and/or drainage in individuals who have MS. For example, one study involving 65 people with different types of MS compared with 235 people who were healthy or had other neurological disorders, a strong relationship was found between MS and signs of venous insufficiency – suggesting that blood drainage by veins may be blocked, causing or contributing to nerve tissue damage. This study, by Paulo Zamboni, MD (University of Ferrara - Ferrara, Italy) and colleagues, was published in the June 2009 (J Neurol Neurosurg Psychiatry 2009; 80:392-399). If confirmed, these findings may open up new research avenues into the underlying pathology of MS. Further research is now under way.

The idea that MS may involve a problem in blood circulation was an early idea that was eventually dismissed as more research suggested that immune-system attacks and inflammation played a pivotal role in the damage to nervous system tissues. A few recent studies have posed the idea that lower blood flow in the brain might contribute to nervous system damage.

In the recent study by Dr. Zamboni and colleagues, they screened for abnormalities of blood outflow in major veins draining from the brain to the heart in 65 people with different types of MS, compared with 235 people who were either healthy or who had other neurological disorders. They used sophisticated sonography techniques to detect abnormalities of vein drainage. The investigators found significant evidence of slowed and obstructed drainage in the veins draining the brain in many of those with MS. They also found evidence of the opening of “substitute circles” – where the flow is deviated to smaller vessels to bypass obstructions, and these were often found to have reverse flow (reflux) of blood back into the brain.

The investigators called this venous obstruction “chronic cerebrospinal venous insufficiency,” or CCSVI. The treatment status of the people with MS did not appear to influence whether they showed signs of CCSVI. The authors speculate that the reverse flow of blood back into the brain might set off the inflammation and immune-mediated damage that has been well described in MS.

If confirmed, these findings may open up new research avenues into the underlying pathology of MS, and further research is now underway. One study getting underway was described at the 2009 ECTRIMS meeting in September. It involves a collaboration between researchers in Italy, Buffalo (NY) and Birmingham (AL) who are attempting to treat venous obstruction in 16 individuals using balloon dilation such as has been used for many years to treat blocked arteries.

Many questions remain about how and when this phenomenon might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to suggest that this phenomenon is the cause of MS.

Frequently Asked Questions About CCSVI and MS

Q: Do these reports of a possible association between insufficient vein drainage and MS mean that MS is caused by venous insufficiency?

A: No. Based on results published about these findings to date, there is not enough evidence to say that obstruction of veins causes MS, or to determine when this obstruction may occur in the course of disease.

Q: If CCSVI turns out to be important in MS, can it be treated?

A: No one knows yet. At least one small study is testing the effects of balloon dilation inside an obstructed vein to determine whether that procedure would be beneficial.

Q: I have MS. Should I be tested for signs of CCSVI?

A: No, unless you are involved in a research study exploring this phenomenon, since at this time there is no proven therapy to resolve any abnormalities that might be observed, and it is still not clear whether relieving venous obstructions would be beneficial.

Q: Does CCSVI make the standard treatments of MS meaningless?

A: No. There is ample evidence proving that the FDA-approved therapies for MS provide benefit for people with most forms of MS.

Q: Will the National MS Society fund research into CCSVI in MS?

A: The National MS Society welcomes research proposals from any qualified investigators whose research questions are relevant to multiple sclerosis. All proposals received are thoroughly evaluated for their relevance and excellence by our volunteer scientific peer review panels. At the present time, we have not been approached for funding any projects related to CCSVI. If we receive a proposal related to CCSVI that is found to be outstanding and relevant to MS, we would likely commit to fund such a study.




The article, which contains links, can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Tue Dec 01, 2009 7:13 pm    Post subject: MS Society of Canada seeks grant proposals for CCSVI & M Reply with quote

The MS Society of Canada is asking for proposals for grants to investigate CCSVI and MS.


Quote:
FOR IMMEDIATE RELEASE

MS Society of Canada announces request for research operating grants related to CCSVI and MS

Toronto, ON – November 23, 2009 – The Multiple Sclerosis Society of Canada announced it will request research operating grants related to chronic cerebrospinal venous insufficiency (CCSVI) and MS.

A recent study released by Dr. Paolo Zamboni, University of Ferrara, Italy, describes CCSVI as a disruption of blood flow in which the venous system is not able to efficiently remove blood from the central nervous system resulting in increased pressure in the veins of the brain and spinal cord which in turn results in damage to these areas.

“These early results are encouraging and show that this warrants more study,” said Yves Savoie, MS Society President and CEO. “This is truly a new avenue to explore in MS research, and we want to be a part of furthering this investigation.”

The MS Society of Canada will issue an invitation for research operating grant proposals on CCSVI related to multiple sclerosis from qualified investigators based in Canadian institutions. Proposals will be evaluated for their scientific merit and relevance to the field of MS.

The competition will open on December 9, 2009.

“There has been tremendous interest and excitement about this study from people with MS, supporters, volunteers and staff across the country. While we acknowledge that the concept of CCSVI as a cause of MS needs to be replicated and validated in larger well-designed studies, the Society looks forward to contributing to this body of work,” said Savoie.

While excited about the potential of the CCSVI study, the findings are preliminary. Thus the MS Society advises that while further research is underway people follow their physician's recommendations and continue their current course of therapies.

...

Contact Information:
Stewart Wong
National Senior Manager, Media and Public Relations
Multiple Sclerosis Society of Canada
Telephone: 416-967-3025
Email: stewart.wong@mssociety.ca

E-mail: info@mssociety.ca
(Please provide your town and province in your e-mail)



The article can be seen here.
Back to top
View user's profile Send private message
cricket52



Joined: 03 Oct 2006
Posts: 343
Location: northern Ontario

PostPosted: Sun Dec 06, 2009 2:46 pm    Post subject: Reply with quote

http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20091120/MS_W5_091120/20091120

This is the W5 program outlining the research and interviewing Dr. Zamboni.
_________________
Cricket
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sun Dec 06, 2009 4:05 pm    Post subject: Reply with quote

Thanks for posting this, cricket! And welcome back--I'd been wondering about you.

In the news clip a patient, Mr. Lipp, is interviewed since having Dr. Zamboni's operation. He radiantly claims that that was 10 months ago and he's had no new attacks since. Then he says that he'll be sure that the treatment has worked after two or three years with no attacks.

I'm not sure about that at all. If two or three years go back with no attacks for him, I should think that his MS might just have been acting that way as it often does. "Now you see it, now you don't."

I hope that Dr. Zamboni's idea turns out to be valid. That would be great news for everybody.
Back to top
View user's profile Send private message
cricket52



Joined: 03 Oct 2006
Posts: 343
Location: northern Ontario

PostPosted: Mon Dec 07, 2009 5:17 am    Post subject: Reply with quote

Hi Agate:

Healthy skepticism is well warranted - more research needs to be done.

What impressed me most is the level of recovery. Dr. Zamboni made it clear the earlier it was done the better, long-term MS patients didn't do as well but still did have some level of improvement.

If all MS'ers have venous stenosis then as a treatment this will shake the MS world. For those who don't - it's research as usual.

Big pharma could lose billions.

I have been lurking - saw my neuro in October. I can drive again - for three years they felt I shouldn't because it was psychiatric. Now it is legitimately neurological I can drive? Makes no sense to me - nothing has changed except a slight steady decline. Oh well. Still no dx but the best guess is MS. If a lesion ever shows it's a fait accomplaie (sp?)

Trust you are well. :)
_________________
Cricket
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Dec 07, 2009 11:10 am    Post subject: Reply with quote

Big pharma would certainly suffer but wouldn't some surgeons be in hog heaven? Wouldn't everyone with MS have to have some corrective surgery?

Please forgive my cynicism. I find all too many people are out to exploit people in need of help.

Congratulations on being back at the wheel--or are you being cautious about actually driving? I notice that you said you can drive--you don't say you are driving.

Many people with MS can't drive because of neurological impairments. I couldn't because of my vision, hearing, and tendency to develop strange problems suddenly, like a sudden loss of control of a hand.

I'm probably doing as well as anyone could expect. The last time I moved (26 years ago!) I promptly got a major UTI that took two months and several rounds of antibiotics to get rid of. The move had been stressful and the weather was very hot.

This time I've had some memory failures and a few instances of really embarrassing confusion, plus a couple of choking episodes and some increased bladder problems. These little bumps in the road were sobering. I was reminded of how fast things can get fairly bad.

All of this will calm down after I've had enough time to get rested up. Or at least that's my hope.
Back to top
View user's profile Send private message
cricket52



Joined: 03 Oct 2006
Posts: 343
Location: northern Ontario

PostPosted: Mon Dec 07, 2009 11:17 am    Post subject: Reply with quote

Hi Agate:

Ha ha - I just went to my mailbox today and received a letter from the Ministry of Transportation only to find that my neurologist decided after all to revoke my license. The reason - motor impairment.

Since I haven't driven for three years I decided not to drive yet. I am aware that my reaction time isn't the best so it is better to be safe than sorry. I had planned to ease back into it.

Still though - it is a bit of a shock. If I had a dx it might be easier to accept. Seeing it on paper makes me realize I just lost a good form of ID. blackeye
_________________
Cricket
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Dec 07, 2009 11:25 am    Post subject: Reply with quote

In the US you can get a state ID card if you don't drive. It can be used exactly like a driver's license. It has your photo on it and other facts about you--date of birth, height, weight, color of eyes and hair, etc.

I have to renew mine every 5 years or so, and now that I'm in a different state I'll have to get one for Oregon. There's a fee but usually not high.

I'm betting Canada has something similar, especially since the trend is to encourage people not to drive.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Dec 07, 2009 3:17 pm    Post subject: (Abstract) Dr. Zamboni's study of CCSVI Reply with quote

An abstract of Dr. Zamboni's study is in PubMed, December 7, 2009. It is an open-label study, which I understand isn't a well-regarded type of study...

Quote:
J Vasc Surg. 2009 Dec;50(6):1348-1358.e3.

A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency

Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F.

Vascular Diseases Center, University of Ferrara, Ferrara, Italy.

OBJECTIVE:

Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS.

METHODS:

Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire.

RESULTS:

Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP.

CONCLUSIONS:

PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.

PMID: 19958985 [PubMed - in process]



The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Dec 19, 2009 3:19 pm    Post subject: (Abstr.) CCSVI severity in PwMS/altered CSF dynamics Reply with quote

Dr. Zamboni and his colleagues have another abstract in PubMed (December 19, 2009):

Quote:


Funct Neurol. 2009 Jul-Sep;24(3):133-8.

The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics

Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R.

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS).

The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001).

This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.

PMID: 20018140 [PubMed - in process]






The abstract can be seen here.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Fri Jan 01, 2010 4:56 pm    Post subject: Reply with quote

I am so excited about this one.

It looks like we may have a new diagnostic test that shows positive in 100% of MS patients and which is very specific to MS. More importantly, it is probably the road to a cure for a lot of people with MS. They just have to get better at doing angioplasty or stints in people`s veins.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Fri Jan 01, 2010 4:58 pm    Post subject: Reply with quote

Sorry to hear about the driving cricket!
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Fri Jan 01, 2010 7:22 pm    Post subject: More on CCSVI (MSIF) Reply with quote

From the MS International Federation newsletter, December 8, 2009:

Quote:
Update: Chronic cerebrospinal venous insufficiency (CCSVI) and MS

Recent reports have sparked a flurry of media attention and revived an old idea of an association between a possible disruption in venous drainage and MS.


A recent study by Zamboni et al, (published in J Neurology Neurosurgery Psychiatry. 2009 Apr; 80 (4): 392-9. Epub. 2008 Dec 5) on 65 people with different types of MS compared with 235 people who were healthy or had other neurological disorders, found a robust correlation between having MS and signs of venous insufficiency - suggesting that drainage of oxygen depleted blood by veins may be impaired in the central nervous system, causing or contributing to nerve tissue damage.

The investigators called this condition "chronic cerebrospinal venous insufficiency" (CCSVI). The treatment status of the people with MS did not appear to influence whether they showed signs of CCSVI. Venous drainage of the brain and spinal cord was examined using an ultrasound technique (Doppler). The researchers also noted that patterns of venous obstruction differed between people at different stages and courses of MS although there was no clear relation between severity of MS and extent of occlusion. The authors suggest that the abnormal venous drainage of blood back from the brain and spine might set off the inflammation and immune-mediated damage that is characteristic of MS.

If these findings were confirmed and shown to have an impact on the disease process, they would open up new avenues of research into the underlying pathology of MS and raise the possibility of new treatments. While the early data is interesting, the proposed mechanism is highly speculative. The main limitations are that the study is done on a small number of people and on those who already have clinical MS. Therefore it is not possible to distinguish whether the venous obstructions are the cause of MS or are part of the physiological changes in the central nervous venous system that result from MS. The concepts surrounding CCSVI and MS are still relatively new and require validation in much larger, well-designed scientific studies before they can be accepted as established. Further research is now underway.

Researchers at Buffalo University, New York are recruiting 1,700 adults and children from USA and Canada to test a link between CCSVI and MS. The MS Society of Canada have issued a request for research operating grants on CCSVI in relation to MS.

Several of MSIF’s member societies have commented on the findings, including those in


Canada

Germany

Ireland

Italy

USA

The most recent comment on the UK MS society’s website, includes criticism of some of the methodology of the study.

Q: Does CCSVI cause MS?
A: At this point there is not enough evidence to draw conclusions on CCSVI and MS. Based on what has been published to date, we can only say that in some people MS may occur in association with impaired venous drainage of the central nervous system. There is not enough evidence to determine whether obstruction of veins causes MS, or is caused by MS, or even to determine when this obstruction may occur in the course of disease.

Q: How has CCSVI been treated?
A: Surgical procedures for CCSVI in MS have used "balloons" to open up obstructed veins or inserted stents into veins to help keep them open. These procedures are still very experimental, have been performed on only a very small number of patients and involve risks of bleeding or the formation of abnormal blood clots. The safety and beneficial effects of this treatment can only be assessed by a large scale clinical trial.

Q: Will the treatment of CCSVI be useful for the various forms of MS?
A: As research on this question is at a very early stage, it is currently unknown whether this type of treatment will be useful in any form of MS. More clinical studies are needed before it will be considered for approval in treating people with MS.

Q: I have MS. Should I be tested for signs of CCSVI?
A: No, unless you are involved in a research study exploring this phenomenon, since at this time there is no proven therapy to resolve any abnormalities that might be observed, and it is still not clear whether relieving venous obstructions would be beneficial for the treatment of MS.


Source: MSIF, German MS Society, Italian MS Society, MS Ireland, MS Society of Canada, UK MS Society and US National MS Society





The article can be seen here.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sat Jan 02, 2010 9:36 am    Post subject: Reply with quote

Well, clearly ,at least four studies need to be done.
A) Is it really 100% of MS patients that have thisÉ Is it really 0% of people withot MSÉ
B) Is it present in people with MS from the beginningÉ (those with MRI lesions at frst attack)
C) Does it predict MS in people without MRI lesions at the beginningÉ
D) How well does angioplasty workÉ They should compare treated versus placebo as well as treated people with complications versus treated people without complications.

I think they could to A, B, and D in just two years. C, unfortunatly, would take longer.

This really sounds right to me.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sat Jan 02, 2010 1:18 pm    Post subject: Reply with quote

I sorta like this review of the issues.

http://ms-info.ca/node/15499
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sun Jan 03, 2010 3:14 pm    Post subject: Reply with quote

This article describes the test pretty well.

http://jnnp.bmj.com/content/80/4/392/T4.expansion.html
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sun Jan 03, 2010 3:45 pm    Post subject: Reply with quote

Thanks for posting this!

This link might be a more direct route to the actual article:

http://jnnp.bmj.com/content/80/4/392.full
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Mon Jan 04, 2010 1:49 pm    Post subject: Reply with quote

Well...

I appled by internet to be part of the study down in buffalo. Tey are looking for people that fulfill the McDonald criteria for MS who want to undergo Zamboni's tests, to see how well they can reproduce them.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Jan 04, 2010 3:06 pm    Post subject: Reply with quote

When will you know if you've been accepted?

Good luck! And I hope you'll keep us posted here as things develop.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Mon Jan 04, 2010 6:10 pm    Post subject: Reply with quote

They say that they will be contacting people after they process the first 500 patients...end of January. Hopefully, they a smart enough to use the first groupto stablish a criteria to test on the second group.

This Zamboni stuff must be old news to you, but I hadn't been thinking about MS for quit a while.

It can be unhealthy though for me to wonder too much what the test results would be. Has all of my heavy drinking cleared out my veins so they will find nothing...is that why I have been doing so well lately, both clinically and MRI-wise? Or, will they find something that I will just need to find a way to get treated for? I really can't allow myself to think abot this too much, or I wil just obsess about the prospects of beig cured, beause it looks so promising to me...and I have just HATED some of the MS symptoms that I have had inthe past.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Jan 09, 2010 12:00 am    Post subject: CMSC weighs in on CCSVI Reply with quote

This is from the CMSC (Consortium of Multiple Sclerosis Centers)--thanks to Cherie Binns, who forwarded it to me:



Quote:
Are you getting phone calls about the "Liberation Treatment"?

We asked Dr. Alex Rae-Grant, CMSC website's Project Leader for Neurology, to share his expertise and views about this article "The Liberation Treatment: A whole new approach to MS". Here is his reply:

Multiple sclerosis, even in 2009, remains mysterious and has escaped our full understanding. Why do certain people get it? Why does it affect the brain and spinal cord in the way it does? What causes it? The recent interesting work by Zamboni et al raises an idea from far out in left field; could MS be caused, or at least accompanied by narrowing or blockage of the veins that drain the brain and spinal cord? OK, so none of the 50 years of research in MS so far have suggested this. And people who are known to have blockage of the veins draining the brain (cortical vein thrombosis) don't get MS. Pathological studies of MS patients have never suggested this. But on the other hand, it's probably good for us to have an open mind, especially when there are new ideas that can be tested, and possibly ones that have a therapeutic option.

Before we all run out suggest that people with MS get stents in their veins, there may be a few steps along the way.

1.It will be important for other centers to independently confirm or refute the ultrasound and or venographic findings of Zamboni et al. This work is beginning at the present time. Adequate care in selecting age and sex matched controls and making sure the tests are not biased will be key.

2.It will be important to understand, if this finding is true, what proportion of the MS population may have such problems. Many in the MS field have felt there are more than one disease within our population; even if 20% of our patients have a venous insufficiency problem, this would be revolutionary.

3.Any therapeutic claims need to have an unbiased methodology to prove benefit. We know that the placebo effect is strong in MS particularly when we are talking about symptoms and not measurable aspects of the disease such as MRI. A randomized trial of therapy in people shown to have such 'stenoses' would be both ethical and necessary before potentially hundreds of thousands of people are subjected to invasive procedures with measurable risk.

The work of Zamboni et al deserves a long, hard, look; it would be wrong to either clamber on board the bus, or to dismiss this out of hand.


About Dr. Alex Rae-Grant

Alex Rae-Grant, MD, recently transitioned from his long-term position at Lehigh Valley Hospital to the Cleveland Clinic. At Lehigh Valley Hospital, he was President of the Medical Staff, Chair of the Ethics Committee, Chief of the Division of Neurology, and founded the Multiple Sclerosis Center of the Lehigh Valley. His role at Cleveland Clinic's Mellon Center is to oversee education about multiple sclerosis in the northeastern Ohio region, assist with clinical trials and be involved with resident and student education at the clinic. He works with regional physicians and Mellen Center staff to distribute approaches to treatment for various aspects of MS.

He was recently awarded the Teacher of the Year award by the neurology residents at the Cleveland Clinic. He is co-director of the neurology clerkship at the Cleveland Clinic and is a Clinical associate professor of medicine at the Cleveland Clinic Lerner College of Medicine. He has previously co-authored two textbooks in neurology, Neurology for the House Officer and 5 Minute Consult in Neurology.


Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sat Jan 09, 2010 10:02 am    Post subject: Reply with quote

This is what the Multiple Sclerosis Society of Canada says

Quote:

Chronic cerebrospinal venous insufficiency (CCSVI) and MS: Overview and FAQ
Overview
Last updated: 2009-12-17

News Flash

The Request for Research Operating Grants on Chronic Cerebrospinal Venous Insufficiency in Relation to Multiple Sclerosis is now open.
Read the application process for the Request for Research Operating Grants. Please note the update on the Review Process of Full Applications.





Chronic cerebrospinal venous insufficiency (CCSVI) describes a hypothetical disruption of blood flow in which the venous system is not able to efficiently remove blood from the central nervous system resulting in increased pressure in the veins of the brain and spinal cord which in turn results in damage to these areas. Recent reports have revived the idea of an association between inadequate venous drainage and multiple sclerosis.

The MS Society of Canada is aware of recent reports on the subject of CCSVI that may open up new avenues of research including new therapies for MS. While the early data shows promise, it is important to acknowledge that the concepts surrounding CCSVI and multiple sclerosis are still relatively new and requires replication and validation in much larger, well-designed scientific studies before they can be accepted as established.

The MS Society of Canada is closely monitoring all research related to CCSVI and will post new information on www.mssociety.ca.

FAQ
What is CCSVI?

Chronic cerebrospinal venous insufficiency (CCSVI) is a term used to describe a hypothetical situation in which the venous system is not able to efficiently remove blood from the central nervous system. It is stated that this is related to narrowing of small venous structures in the neck, chest and spine.

Why is there a sudden interest in CCSVI and MS?

Media attention and a few recent reports have revived speculation about a possible dysfunction of brain blood flow and/or drainage in individuals who have MS. In particular, one study involving 65 people with different types of MS compared with 235 people who were healthy or who had other neurological disorders, a robust relationship was found between having MS and signs of venous insufficiency – suggesting that blood drainage by veins may be impaired, contributing to nerve tissue damage. This study, by Paolo Zamboni, MD (University of Ferrara - Ferrara, Italy) and colleagues, was published in 2009. (J Neurology Neurosurgery Psychiatry. 2009 Apr; 80 (4): 392-9. Epub. 2008 Dec 5.)

The investigators called this venous obstruction “chronic cerebrospinal venous insufficiency” or CCSVI. The treatment status of the people with MS did not appear to influence whether they showed signs of CCSVI. The authors speculate that the abnormal venous drainage of blood back from the brain and spine might set off the inflammation and immune-mediated damage that is characteristic of MS.

Do these reports of a possible association between insufficient vein drainage and MS mean that MS is caused by venous insufficiency?


Not necessarily. Based on what has been published so far, we can only say that MS may occur in association with impaired venous drainage of the central nervous system. This impairment, if truly present, could cause MS but it is possible that it is incidental to the disease. More study is needed.

How has CCSVI been treated?

Researchers involved with CCSVI have used “balloons” to open up narrowed veins or inserted stents into veins to help keep them open. This work is at a very early stage and has been performed on only a very small number of patients. It requires passing a catheter (wire) through the veins to the area of venous narrowing so that it can be widened and is not without risk including the chance of bleeding or the formation of abnormal blood clots.

Will the treatment of CCSVI be useful for the various forms of MS?

Whether this type of treatment will be useful in any form of MS is currently unknown as research on this question is at a very early stage. Much more work needs to be done.

What is the MS Society’s position on CCSVI?

The MS Society of Canada believes that this topic opens up new avenues of research in MS including the possibility of new treatments. Although the early data are of great interest, it is important to acknowledge that the concept of CCSVI as a cause of MS and the use of stents or balloons to widen veins as treatments, are ideas that are far from being accepted by most researchers in the field. The early results need to be replicated and validated in much larger well-designed studies.

The MS Society of Canada is closely monitoring all research related to CCSVI and will post new information on www.mssociety.ca.

Does the MS Society currently fund research into CCSVI?

The MS Society of Canada will issue an invitation for research operating grant proposals on CCSVI related to multiple sclerosis from qualified investigators based in Canadian institutions. Proposals will be evaluated for their scientific merit and relevance to the field of MS.

The Request for Research Operating Grants on Chronic Cerebrospinal Venous Insufficiency in Relation to Multiple Sclerosis is now open. Read the application process for the Request for Research Operating Grants.

What is the selection process to receive operating grants related to CCSVI and MS and how will approved grants receive funding from the MS Society?

The MS Society of Canada's MS Research Program invests only in research that is of the highest level of scientific excellence and relevance to MS. All research grants are adjudicated through a rigorous peer-review process that involves leading MS research experts from around the world. This process is precisely designed to identify research that will most ably investigate the cause and cure for MS on numerous fronts - from prevention to symptom management to repair. The Medical Advisory Committee makes recommendations for funding through the MS Research Program and based on available resources generated through donations, grants are awarded. Although the MS Society is unable to direct donor giving to any one specific research grant, such as the newly established CCSVI competition, all donations to the MS Research Program help ensure that recommended grants are awarded funding. This process also ensures the continued integrity of the program and upholds the mandate of the MS Society of Canada to excel in our effort to end MS.

Does the MS Society recommend people travel to get potential treatments related to this new idea?

The MS Society believes that this is a question to be addressed by the individual to their neurologist/physician. It is noteworthy that the treatment ideas in question are very new and not scientifically established.


--------------------------------------------------------------------------------

"As President and CEO of the MS Society, I am aware of the tremendous interest across Canada and around the world caused by the recent news coverage of the CCSVI study. Indeed I share your excitement and hope in the preliminary findings of this study. I also celebrate and respect the integrity of our research funding programs which will continue to ensure that the very best projects are selected and supported."

Yves Savoie
President and chief executive officer
President, Ontario Division



I think that the quote from Yves Savoie says a lot. But, it is definitely prematurefor hospitals to start treating everyone with MS with balloon angioplasty. However, we do live in a country where doctors can do pretty much any sugery that they want. So, they have to research this, or somebody might just open a private ngioplast clinic and start treating people...it would be much better to have good clinical trial evidence first. Unless the other Canadians understand somethng that I do not, the way our medcal system is set up necessitates clinical trials on this treatment so that patients don't end up gong for unnecessary surgery.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Mon Jan 11, 2010 11:00 am    Post subject: Reply with quote

There is already a petition to make the procedure available. Once there is better evidence, therecan be no question of the strength of the patiet lobby, unless the evidence shows the procedure to be inefective.

http://www.msliberation.ca/MS_Liberation_Group/Welcome.html
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Jan 11, 2010 11:43 am    Post subject: Reply with quote

I may be impossibly naive but aren't there government funds and funds from philanthropic organizations available for research into theories that are not totally off the wall?

It's too bad that this Dr. Haacke has to wait for people to donate. I hope he's been applying for any grants that are lying around.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Jan 30, 2010 6:57 pm    Post subject: MS Society news detail--update on pursuing CCSVI Reply with quote

From the (US) MS Society, January 19, 2010:

Quote:


UPDATE: Next Steps In Pursuing CCSVI (Venous Insufficiency) Research in MS – Letters of Intent Received from International Request for Research Applications -- Full Grant Applications Will Be Submitted by February 9

Summary:

Recent reports are calling attention to the idea that a phenomenon called CCSVI, a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paulo Zamboni from the University of Ferrara in Italy. Based on the results of his initial preliminary findings, Dr. Zamboni states that this pilot study warrants a subsequent larger and better controlled study to definitively evaluate the possible impact of CCSVI on the disease process in MS.

The National MS Society is actively pursuing the CCSVI lead and Dr. Zamboni's request that his pilot studies be followed up by larger and better controlled research to determine what the impact of CCSVI might be on the MS disease process.

It has been proposed by Dr. Zamboni, but not yet proven, that CCSVI may be corrected through endovascular surgery, which involves inserting a tiny balloon or stent into blocked veins in order to permit the flow of blood out of the brain and spinal cord, a procedure that has been called “liberation therapy” in some reports.

The National MS Society is undertaking the funding of new research on CCSVI in MS and has invited investigators worldwide to apply for grants that would explore this lead. In response to a January 6 deadline, the National MS Society and the MS Society of Canada received numerous letters of intent from investigators from seven countries. These letters of intent, which briefly describe the proposed research, will be reviewed and those that meet grant guidelines will be invited to submit full research proposals.

CCSVI Research Funding Timeline

January 12, 2010 – Investigators whose letter of intent meet guidelines are invited to submit full research proposals with a deadline of February 9, 2010.

May 2010 – International panel of experts conducts an expedited review of all applications received through this special request for applications.

June 2010 – Funding decisions announced.

July 1, 2010 – Anticipated start date for funding of any successful research applications.

The applications will undergo an accelerated review process by an international panel being convened in cooperation with other MS Societies to ensure an expedited, coordinated response. If this hypothesis is confirmed, it may open up new research avenues into the underlying pathology of MS and new treatment approaches to therapy.

Background:

In a recent study by Dr. Zamboni and colleagues, the team evaluated abnormalities of blood outflow in major veins draining from the brain and spinal cord to the heart in 65 people with different types of MS, compared with 235 people who were either healthy or who had other neurological disorders. They used sophisticated sonography techniques to detect abnormalities of venous drainage. The investigators reported evidence of slowed and obstructed drainage in the veins draining the brain and spinal cord in many of those with MS. They also found evidence of the opening of “substitute circles” – where the flow is deviated to smaller vessels to bypass obstructions, and these were often found to have reverse flow (reflux) of blood back into the brain.

The investigators call this venous obstruction “chronic cerebrospinal venous insufficiency,” or CCSVI. The treatment status of the people with MS (i.e., whether or not they were on an MS disease modifying drug) did not appear to influence whether they showed signs of CCSVI. The authors speculated that the reverse flow of blood back into the brain might set off the inflammation and immune-mediated damage that has been well described in MS. This study was published in June 2009 (J Neurol Neurosurg Psychiatry 2009; 80:392-399).

It is proposed, but not yet proven, that CCSVI may be corrected through endovascular surgery. This surgery is being called “liberation therapy” in some reports. One study getting underway was described at the 2009 ECTRIMS meeting in September. It involves a collaboration between researchers in Italy, Buffalo (NY) and Birmingham (AL) who are attempting to treat venous obstruction in 16 individuals using balloon dilation such as has been used for many years to treat blocked arteries.

In a small, open-label study by Dr. Zamboni and colleagues published in December, the team evaluated the safety and preliminary outcomes of vascular surgery (percutaneous transluminal angioplasty) in 35 individuals with relapsing-remitting MS, 20 with secondary-progressive MS, and 10 with primary-progressive MS. (J Vasc Surg 2009; 50:1348-1358) They reported some positive impacts and suggested that controlled trials were necessary to better determine potential safety and benefits of this procedure.

Next Steps:

The National MS Society has prompted communications between MS Societies worldwide and leveraged resources to ensure an open exchange of information and a coordinated and expedited approach to conducting and evaluating additional research on CCSVI. On December 16, 2009, the Society released a worldwide Request for Applications to the scientific community to explore CCSVI, and is collaborating with the MS Society of Canada and possibly other societies to convene an international panel of experts to conduct an accelerated review of proposals. We are also working with our sister MS Societies around the world to assure that our research strategies are coordinated. Through an internationally coordinated and expedited review process, new CCSVI research projects are expected to begin July 1, 2010. (See Research Funding Timeline above for more details.)

According to the Buffalo Neuroimaging Analysis Center, although 500 subjects have already been selected for their initial combined transcranial and extracranial venous doppler evaluation study, they are still seeking participants for a larger-scale clinical study with the aim of evaluating the prevalence of venous obstruction in people with MS. This study does not involve treatment of obstructions.

To get the quickest answers and most reliable results about benefits and risks of any surgical procedure that might attempt to address blood flow in or out of the brain, it is crucial that such surgery be performed only as part of controlled trials, especially since there have been anecdotal reports of surgical attempts to treat CCSVI in people with MS resulting in adverse events, including one reported death.

Many questions remain about how and when this phenomenon might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to prove that this phenomenon is the cause of MS.

Frequently Asked Questions About CCSVI and MS

Q: What is the National MS Society’s view of CCSVI?

A: In trying to find the cause and more effective treatments for a disease as complex and unpredictable as multiple sclerosis, the Society is steadfast in its commitment to pursue all promising avenues of research that can lead to improved treatments and ultimately, a cure. It is important for researchers to think outside the box and we believe Dr. Zamboni has done this. His hypothesis is a path that must be more fully explored and Dr. Zamboni himself has stated that additional research is essential to evaluate it.

Q: Will the National MS Society fund research into CCSVI in MS?

A: The National MS Society is pursuing follow-up research in how CCSVI might be involved in the MS process and we have invited investigators from around the world whose research is relevant to MS to submit proposals to apply for grants that would explore this lead. These applications will undergo an accelerated review process.

Q: Do the reports of a possible association between insufficient vein drainage and MS mean that MS is caused by venous insufficiency?

A: No. Based on results published about these findings to date, there is not enough evidence to say that obstruction of veins causes MS, or to determine when this obstruction may occur in the course of disease.

Q: If CCSVI turns out to be important in MS, can it be treated?

A: No one knows yet. Surgical procedures for CCSVI in MS are still experimental and should be undertaken only as part of formal clinical trials that include all of the standard safeguards that are followed in such trials.

Q: How can I get involved in research on CCSVI in MS?

A: A larger-scale clinical study is getting underway in Buffalo, New York and is now recruiting participants nationwide with the aim of evaluating the prevalence of venous obstruction in people with MS. This study does not involve treatment of venous obstructions.

Q: I have MS. Should I be tested for signs of CCSVI?

A: We do not recommend testing for signs of CCSVI unless you are involved in a research study exploring this phenomenon, since at this time there is no proven therapy to resolve any abnormalities that might be observed, and it is still not clear whether relieving venous obstructions would be beneficial.

Q: Does CCSVI make the standard treatments of MS meaningless?

A: No. There is ample evidence proving that the FDA-approved therapies for MS provide benefit for people with most forms of MS.

Q. How can I continue to be informed of CCSVI developments as they occur?

A: As new information becomes available about CCSVI, it will be posted on the National MS Society’s Web site, http://www.nationalMSsociety.org.


Back to top
View user's profile Send private message
cricket52



Joined: 03 Oct 2006
Posts: 343
Location: northern Ontario

PostPosted: Sun Jan 31, 2010 9:04 am    Post subject: Reply with quote

Similar studies will be taking place simultaneously in Canada. In three days one of the selected hospital received 10,000 requests from MS patients inquiring about CCSVI and the study.

The hard part about this are the MS patients who have decided to go off their DMD's thinking this will happen overnight. CCSVI treatment might have potential it's too soon to drop all other meds.

What rankles me is the attitude of some of the elite MS researchers. For the few patients who have undergone this procedure the results speak for themselves. It clearly has potential to make the QOL better for many MS patients. Of course the media is being blamed for presenting his findings and interviewing his patients. The 'other side' got their airtime too so why are their feather so ruffled?

I still think it is a viable treatment and I still think big phara will do all it can to discredit any research that will hurt their bottom line. The MS Society of Canada has taken a moderate and fair stance. Time will tell whether or not this treatment works.

For those who have been treated sucessfully it is indeed a touching and positive change for them. Their joy in receiving back their lives, if only for a season, has vicariously become the joy of all MS patients who hope for a cure.
_________________
Cricket
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sun Jan 31, 2010 9:35 am    Post subject: Reply with quote

Very well said, cricket!
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Thu Feb 04, 2010 9:34 am    Post subject: Reply with quote

The more I think about this, the more I think that the buffalo team may find some well sought-after answers.

If CCSVI is a symptom of MS, then we would expect the same type of abnormality in everyone's veins who have CCSVI and MS...they might all appear to have abnoralties remembling vericoe veins on magnetic resonace venoscopy.

If, on the other hand, MS is caused by CCSVI, then we might expect a variety of different types of blockages to be associated with MS...In some atients it might look more like blood clots, and, in others it might look more like varicose veins. For that matter, they hould also look at MS patients wih antiphospholipid syndrome, which causes coting in the veins, I believe.

They have already analysed 500 patients, and they are already starting a small treatment group, 30 patients. I wonder if they have already found evidence that CCSVI is the common denominator to MS, but that CCSVI can have a number of different underying causes.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Fri Feb 05, 2010 9:28 am    Post subject: Reply with quote

This test sound quite involved not to mention difficult.

http://csvi-ms.net/files/multiple%20sclerosis-USG.pdf

He does note that there are a variety of structural abnormalities that can be found. This seems to suggest to me that he is rightabout CCSVI eing the cause of MS, plus, when I consider the fact that 8% of patients with antiphospholipid syndrome, which causes venous obstructions, have a neurological synrome inistinguishable from MS...hmmm, he is really to somethig here, I think.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Fri Feb 05, 2010 3:30 pm    Post subject: Reply with quote

A lot of informationon what is going on in ccvsi research.

http://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=2944&CFID=3116489&CFTOKEN=23588997
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sat Feb 06, 2010 12:26 pm    Post subject: Reply with quote

That was written by a charity group in the UK that does telephone counciling of MS patients. "The Multiple Sclerosis Resource Center:

Registered Charity No 1033731
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sat Feb 06, 2010 3:03 pm    Post subject: Reply with quote

Matt wrote:
This test sound quite involved not to mention difficult.

http://csvi-ms.net/files/multiple%20sclerosis-USG.pdf

He does note that there are a variety of structural abnormalities that can be found. This seems to suggest to me that he is rightabout CCSVI eing the cause of MS, plus, when I consider the fact that 8% of patients with antiphospholipid syndrome, which causes venous obstructions, have a neurological synrome inistinguishable from MS...hmmm, he is really to somethig here, I think.


That lin dosn't eem to work for Joan. It i a technical article about how to perform Combined Transcranial and Extracranial Venous Doppler written by doctor Zamboni.

Th remark abut antiphospholipid syndrome and MS...I will have to look for the link again. The phenomenon is also kown as lupoid sclerosis, because 38% of patients with SLE have antiphospholipid syndrome (no doubt, different researchers have found different prevalences). There is a whole lot written about this, so I don't even know what links are the better links for me to give.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Feb 06, 2010 5:56 pm    Post subject: Reply with quote

The link is working for me, Matt. My problem is that there's no indication in the document of who the author is, or where it appeared or when.

If Dr. Zamboni wrote it, you must have got that information about authorship from somewhere.

That's the information it would be helpful to have. People like to get more information sometimes, but if there's no way to do that, they give up on that particular source--and might even say it's not a reliable source, since no information about its authorship is given.

Sorry to be such a PITA. I've found that Internet sources can be slippery.
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sat Feb 06, 2010 6:04 pm    Post subject: Reply with quote

I guess I was wrong. It was written by doctor Simka


http://csvi-ms.net/en/content/how-perform-doppler-examination-multiple-sclerosis-patient-dr-simka
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sun Feb 07, 2010 9:33 am    Post subject: Reply with quote

A news letter explaining that they have made some groundbreking discoveries down in buffalo.

http://www.bnac.net/wp-content/uploads/2010/02/bnac_newsletter_02-04-2010.pdf
Back to top
View user's profile Send private message
Matt



Joined: 21 May 2006
Posts: 961

PostPosted: Sun Feb 07, 2010 1:56 pm    Post subject: Reply with quote

So, basd on the dsign of their study and their "excitement", we can almost predict what they have found...lesion location and Iron deposiion correlate to the pattern of reflux or venous overload in patients with MS. If they have found this, then that would be a major piece of evidence in support of the idea that CCSVI is the cause of MS.

If the have also found some patients with aquired CCVSI (caused by a tumor or deep vein thrombosis), that would also be evidence. It will be interesing to see what they found.

I also have my guesses about what the second phase of the study might be all about...prognostication. If older patients have the same reflux patterns as younger patients, then different reflux patterns can be compared in older patients to find out which patterns predict a better or poorer prognosis. If this test is useful n determining prognosis, then it will be made available to the general population of MS patients pretty soon, I should think.

Just my predictions. We will find out about the first phase in a week.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Fri Feb 12, 2010 9:43 am    Post subject: Reply with quote

A friend saw a news story on the BBC news about CCSVI. It was probably this (February 10):

http://news.bbc.co.uk/2/hi/health/8509106.stm
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Tue Feb 23, 2010 6:52 pm    Post subject: Dr. Ben Thrower's remarks on CCSVI Reply with quote

The Winter issue of MS Focus, the periodical from the MS Foundation, contains some remarks by Dr. Ben Thrower (MSF Senior Medical Adviser) about CCSVI:

http://virtual.angstromgraphics.com/publication/?i=30882

You'll need to navigate to pages 59-60 of the document.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Fri Mar 12, 2010 7:04 pm    Post subject: CCSVI Update (Rocky Mountain MS Center) Reply with quote

From the Rocky Mountain MS Center eMS News, March 11, 2010:

Quote:
CCSVI Update

After one fatality and another close call, researchers at Stanford University have stopped all treatments for chronic cerebrospinal venous insufficiency (CCSVI). The halt was reported in February's edition of the journal Annals of Neurology.

The death, which occurred in August 2009, was the result of a brain hemorrhage following a stenting procedure. Another patient underwent emergency open heart surgery in November 2009 after a dislodged jugular vein stent wound up in the right ventricle of the heart.

As stated in the last edition of eMS News [see post below], studies on CCSVI and their suggested relevance to MS have, to date, been preliminary and need to be confirmed before patients undergo invasive procedures to correct what is currently only a hypothesized problem. With the halt of the Stanford University procedures, the University of Buffalo remains the only university that we are aware of that continues to look into CCSVI and MS. However, the National MS Society anticipates funding several additional research teams to investigate this topic, which will hopefully bring clarity to this question in the near future.




Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Fri Mar 12, 2010 7:10 pm    Post subject: Breaking News - CCSVI (Rocky Mountain MS Center, February 4) Reply with quote

From Rocky Mountain MS Center eMS News, February 4, 2010:

Quote:
CCSVI
Breaking News


By Dr. John Corboy, Co-Director of the Rocky Mountain MS Center at Anschutz Medical Campus

Chronic cerebrospinal venous insufficiency (CCSVI) is now a term familiar to most of us. On February 10, 2010, the University of Buffalo released study results from the first U.S. study looking into the possible link between MS and restricted blood flow from the brain. The theory was initially introduced by an Italian researcher, Dr. Paulo Zamboni, who theorized that the narrowing of the extracranial veins is related to—or possibly causes—MS.
CCSVI, as defined by Dr. Zamboni, is the narrowing of veins—and consequent obstruction of blood flow—between the brain and spinal cord, and the heart. The thought is that the abnormal flow of blood through the central nervous system (CNS) damages brain and spinal tissue, thus explaining the nerve damage characteristic of MS. Dr. Zamboni’s original study included 65 MS patients and 235 controls. The physician’s study findings suggested that the venous condition was strongly linked to MS, and may increase the risk of MS by 43 fold.
The recently released results are from the first phase of the University of Buffalo study, which began in April 2009 and included 500 study participants. The second phase of the study will include an additional 500 patients. This second group of patients will be assessed with more advanced diagnostic tools than those used in the first phase. Therefore, the recently released study results are preliminary.

Study participants included individuals with a diagnosis of MS (most with RRMS), clinically isolated syndrome (CIS), “other neurologic diseases” (OND), and healthy controls. Participants were tested for CCSVI through the use of ultrasound (Doppler) scans of the head and neck. This made it possible for study investigators to evaluate the direction of venous blood flow. Study participants with MS also received MRI scans, which measured iron deposits in brain lesions and surrounding areas.

Overall, researchers found that more than 55% of the 500 study participants exhibited restricted blood flow. More specifically, up to 62.4% of MS patients in the study (excluding the 10.2% of patients who were border line) exhibited signs of CCSVI compared to 25.9% of healthy controls. Study results also suggested a correlation between disease progression and CCSVI, although little information on that is available at this time.

It remains unclear whether CCSVI is a risk factor for MS or a result of MS—that’s to say the narrowing of veins is a consequence of the MS disease process. Further studies are necessary before researchers will begin to uncover the answer to that question.

The NMSS has set aside a significant amount of money to study this further, with a grant review in May, 2010. Many outstanding issues and questions remain. They include: whether the apparent venous changes are a cause or a result of MS; whether the small drops in pressure detected by Dr. Zamboni after stenting are truly capable of inducing changes pathologically; whether it is possible to induce MS-like pathology by constricting veins in an animal model of MS; how venous backflow might induce MS pathology; why immunotherapies would work if the underlying problem is venous constriction; whether stenting produces favorable outcomes in controlled studies; and many others.





Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 4:19 pm    Post subject: (Abstract) CCSVI: follow-up study in a patient w/MS Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):189-92.

Chronic cerebro-spinal venous insufficiency: report of transcranial magnetic stimulation follow-up study in a patient with multiple sclerosis

Plasmati R, Pastorelli F, Fini N, Salvi F, Galeotti R, Zamboni P.

Department of Neurology, Bellaria Hospital, Bologna, Italy2 Vascular Diseases Centre, University of Ferrara, Italy - rosaria.plasmati@ausl.bo.it.

The pyramidal pathway is frequently affected early on in multiple sclerosis (MS) and impaired motor performance is a major cause of disability. Pyramidal tract function can be assessed using transcranial magnetic stimulation (TMS). TMS supports the diagnosis of MS, detecting corticospinal tract involvement and monitoring its course with or without treatment.

Whether any relationship exists between the TMS outcome measure and minimally invasive treatment of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments in MS patients, has never been investigated.

We report the clinical and transcranial magnetic stimulation follow-up of a patient during a relapse in relapsing-remitting MS. She underwent percutaneous balloon angioplasty of the associated chronic cerebrospinal venous insufficiency (CCSVI), due to membranous obstruction of the proximal azygous vein, with severe stenosis of the left internal jugular vein.

Treatment of the associated CCSVI made a parallel improvement in both clinical and neurophysiological parameters, allowing us to avoid high dose steroid therapy. The relationship between the clinical and neurophysiological course on the one hand, and haemodynamic correction of the associated CCSVI on the other, calls for further exploration on a [larger] number of patients.

The impact of CCSVI on the different neuro-physiological parameters has not been fully estimated, but the intriguing case here reported suggests that it may be greater than previously assumed. The demonstration of a modification of the cerebrovenous function with both clinical manifestation and via TMS suggests that the hampered cerebral venous return may contribute to the clinical course of MS.

PMID: 20351675


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 4:33 pm    Post subject: (Abstract) Hemodynamic patterns of CCSVI in MS:... Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):183-8.

Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis. Correlation with symptoms at onset and clinical course

Bartolomei I, Salvi F, Galeotti R, Salviato E, Alcanterini M, Menegatti E, Mascalchi M, Zamboni P.

Center for Rare and Neuroimmunitary Diseases, Department of Neurological Science, Bellaria Hospital, Bologna, Italy - fabrizio.salvi@gmail.com.

AIM:

Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). CCSVI is detected by transcranial and extracranial color-Doppler high-resolution examination (TCCS-ECD) and venography that permit identifying five types of venous malformations and four major (A-D) hemodynamic patterns of anomalous extracranial-extravertebral venous outflow.

We investigated possible correlation between such hemodynamic patterns and both the symptoms at onset and clinical course in patients with MS and CCSVI.

METHODS:

TCCS-ECD, selective venography and clinical records of 65 patients affected by definite MS and CCSVI were reviewed.

RESULTS:

The four hemodynamic patterns of CCSVI were unevenly (P<0.0001) distributed with respect to the types of clinical presentation and course. In particular the Type A or B patterns were common in patients with onset of optic neuritis, but rare in patients presenting with spinal cord symptoms who typically showed a type D pattern. Also, the type A or type B hemodynamics were more common in patients with a relapsing-remitting course than in patients with a secondary-progressive course and rare in patients with a primary-progressive course. The C hemodynamic pattern was not observed in patients with a primary- progressive course who showed a remarkable prevalence of the type D pattern.

CONCLUSION:

The distribution of venous malformations and the resulting hemodynamic pattern show correlation with symptoms at onset and clinical course in patients with MS and CCSVI.

PMID: 20351674


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 4:41 pm    Post subject: (Abstract) Chronic fatigue, CCSVI & MS Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):176-82.

Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study

Malagoni AM, Galeotti R, Menegatti E, Manfredini F, Basaglia N, Salvi F, Zamboni P.

Vascular Diseases Center, University of Ferrara, Ferrara, Italy - mlgnmr@unife.it.

AIM:

Chronic fatigue (CF) severely affects patients with multiple sclerosis (MS), but its pathogenesis remains elusive and the effectiveness of available treatments is modest. We aimed to evaluate the effect on CF of the balloon dilatation of stenosing lesions affecting the main extracranial veins configuring the chronic cerebrospinal venous insufficiency (CCSVI), a condition strongly associated with MS.

METHODS:

Thirty-one MS consecutive patients (16 males, age 46.2+/-9.4 years) with associated CCSVI and CF underwent the endovascular procedure. Fatigue was assessed using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) at baseline (T0) and one (T1), six (T6) and twelve (T12) months after the procedure. In ambulatory patients (N.=28), mobility was evaluated using the 6-min walking test at T0 and T1.

RESULTS:

[something is missing here] and MFIS scores significantly improved from preoperative values, and the positive trend was maintained at one year (FSS: T0=5.1+/-1.0 to T12=3.5+/-1.8, P<0.001; MFIS-total score: T0=34.9+/-14.8 to T12=22.5+/-13.7, P<0.001; MFIS-Physical subscale: T0=21.2+/-8.0 to T12=13.5+/-9.7 P<0.001; MFIS-Cognitive subscale: T0=9.2+/-9.5 to T12=6.0+/-6.3, P=0.03; MFIS-Psychosocial subscale: T0=4.5+/-2.1 to T12=2.5+/-2.1, P<0.001). Six-min walking distance (6MWD) at T1 improved significantly (332+/-190m to 378+/-200m, P=0.0002).

In addition, an inverted correlation between 6MWD and MFIS-physical subscale variations was found in the subgroup of patients (N.=8) with no lower limb motor impairment (r=-0.74, P=0.035).

CONCLUSION:

The reestablishment of cerebral venous return dramatically reduced CF perception in a group of MS patients with associated CCSVI, suggesting that CF is likely the symptom of CCSVI.

PMID: 20351673


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 4:46 pm    Post subject: (Abstract) CCSVI & iron deposition...in PwMS Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):158-75.

Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study

Zivadinov R, Schirda C, Dwyer MG, Haacke ME, Weinstock-Guttman B, Menegatti E, Heininen-Brown M, Magnano C, Malagoni AM, Wack DS, Hojnacki D, Kennedy C, Carl E, Bergsland N, Hussein S, Poloni G, Bartolomei I, Salvi F, Zamboni P.

Buffalo Neuroimaging Analysis Center, University at Buffalo, Buffalo, NY, USA - rzivadinov@bnac.net.

AIM:

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. The aim of this study was to investigate the relationship between CCSVI and iron deposition in the brain of MS patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter structures and lesions, as measured by susceptibility-weighted imaging (SWI), and to preliminarily define the relationship between iron measures and clinical and other magnetic resonance imaging (MRI) outcomes.

METHODS:

Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI.

RESULTS:

All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume.

CONCLUSION:

The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS.

PMID: 20351672


The abstract can be seen here.

Added 4/9/10: This abstract is on the docket for presentation at the AAN conference in Toronto, April 10-17.


Last edited by agate on Thu Apr 15, 2010 6:23 pm; edited 2 times in total
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 4:50 pm    Post subject: (Abstract) Iron stores & cerebral veins in MS... Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):149-57.

Iron stores and cerebral veins in MS studied by susceptibility weighted imaging

Haacke EM, Garbern J, Miao Y, Habib C, Liu M.

Department of Radiology, Wayne State University, Detroit, MI, USA2 Department of Radiology, the First Affiliated Hospital, Dalian Medical University, Dalian, China - nmrimaging@aol.com.

AIM:

In this paper, we seek to determine whether the iron deposition as seen by susceptibility weighted imaging (SWI) in the basal ganglia and thalamus of patients with multiple sclerosis is greater than the iron content measured in normal subjects (individuals unaffected by multiple sclerosis). As increased iron content may result from increased venous pressure, such information would add credence to the concept of Zamboni et al (1) that MS is caused by chronic cerebrospinal venous insufficiency.

METHODS:

Fourteen MS patients were recruited for this study with a mean age of 38 years ranging from 19 to 66 year-old. A velocity compensated 3D gradient echo sequence was used to generate SW images with a high sensitivity to iron content. We evaluated iron in the following structures: substantia nigra, red nucleus, globus pallidus, putamen, caudate nucleus, thalamus and pulvinar thalamus.

Each structure was broken into two parts, a high iron content region and a low iron content region. The measured values were compared to previously established baseline iron content in these structures as a function of age.

RESULTS:

Twelve of fourteen patients had an increase in iron above normal levels and with a particular pattern of iron deposition in the medial venous drainage system that was associated with the confluence of the veins draining that structure.

CONCLUSION:

Iron may serve as a biomarker of venous vascular damage in multiple sclerosis. The backward iron accumulation pattern seen in the basal ganglia and thalamus of most MS patients is consistent with the hypothesis of venous hypertension.

PMID: 20351671


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 4:56 pm    Post subject: (Abstract) Extracranial venous flow anomalies in MS... Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):140-8.

CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study

Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojnacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Ramanathan M, Zivadinov R.

Vascular Diseases Center, University of Ferrara-Bellaria Neurosciences, Ferrara and Bologna, Italy - zmp@unife.it.

AIM:

We previously reported unexpectedly robust associations between vascular haemodynamic (VH) anomalies in the principal extracranial cerebral veins, causing chronic cerebrospinal venous insufficiency (CCSVI), and multiple sclerosis (MS). The aim of this study was to investigate the relationship between the VH changes and MRI measures of MS disease severity in a cross sectional survey.

METHODS:

The number of anomalous VH criteria were measured using an echo-color Doppler, whereas CSF flow, atrophy and lesion measures were obtained from quantitative magnetic resonance imaging (MRI) analysis in sixteen consecutive relapsing-remitting MS patients, (mean age: 36.1+/-SD 7.3 years, disease duration: 7.5+/-1.9 years and median EDSS: 2.5) and in 8 healthy controls (HC) with similar age and sex distributions.

RESULTS:

All 16 MS patients investigated and none of the HCs met the VH criteria for CCSVI (P<0.0001). MS patients showed significantly lower net CSF flow compared to the HC (P=0.038) that was associated with number of anomalous VH criteria present (r=0.79, P<0.001). Moreover, increases in the number of anomalous VH criteria present were negatively associated with lower whole brain volume (Spearman R=-0.5, P=0.05).

CONCLUSION:

VH changes occur more frequently in MS patients than controls. Altered VH is associated with abnormal CSF flow dynamics and decreased brain volume.

PMID: 20351670


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 5:26 pm    Post subject: (Abstract) Diagnosis of CCSVI... Reply with quote

From PubMed, March 31, 2010:

Quote:


Int Angiol. 2010 Apr;29(2):127-39.

Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls

Hojnacki D, Zamboni P, Lopez-Soriano A, Galleotti R, Menegatti E, Weinstock-Guttman B, Schirda C, Magnano C, Malagoni AM, Kennedy C, Bartolomei I, Salvi F, Zivadinov R.

The Jacobs Neurological Institute, State University of New York, Buffalo, NY, USA - rzivadinov@bnac.net.

AIM:

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of primary veins outside the skull that restrict normal outflow of blood from the brain. CCSVI was recently described as highly prevalent in patients with multiple sclerosis (MS) and can be non-invasively diagnosed by Doppler sonography (DS) and invasively by selective venography (SV).

The aim of this paper was to investigate the value of neck magnetic resonance venography (MRV) for the diagnosis of CCSVI compared to DS and SV in patients with MS and in healthy controls (HC).

METHODS:

Ten MS patients and 7 HC underwent DS, 2D-Time-Of-Flight venography (TOF) and 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS). MS patients also underwent SV. The internal jugular veins (IJVs) and the vertebral veins (VVs) were assessed by both MRV sequences, and the findings were validated against SV and DS. SV has been considered the diagnostic gold standard for MS patients.

RESULTS:

All MS patients and none of the HC presented CCSVI, according to the DS criteria. This was confirmed by SV. For CCSVI diagnosis, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, whereas the figures were 40%, 85%, 58%, 80% and 50% for 3D-TRICKS, and 30%, 85%, 52%, 75% and 46% for 2D-TOF in the IJVs. In MS patients, compared to SV, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, 75%, 95%, 94% and 100%, whereas the figures were 31%, 100%, 45%, 100% and 26% for 3D-TRICKS and 25%, 100%, 40%, 100% and 25% for 2D-TOF in the IJVs.

CONCLUSION:

The use of MRV for diagnosis of CCSVI in MS patients has limited value, and the findings should be interpreted with caution and confirmed by other imaging techniques such as DS and SV.

PMID: 20351669


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 5:36 pm    Post subject: (Abstract) Reproducibility of color Doppler in CCSVI... Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):121-6.

The reproducibility of colour Doppler in chronic cerebrospinal venous insufficiency associated with multiple sclerosis

Menegatti E, Genova V, Tessari M, Malagoni AM, Bartolomei I, Zuolo M, Galeotti R, Salvi F, Zamboni P.

Vascular Diseases Centre, University of Ferrara, Italy - menegatti.erica@gmail.com.

AIM:

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome described in multiple sclerosis (MS) patients, characterized by stenosis of the main extracranial veins with hampered cerebral venous outflow. In the original description echo-colour Doppler [was?] demonstrated to be an ideal non- invasive tool for screening CCSVI patients, but the reproducibility was not assessed. The aim of this study is to assess the variability coefficient between trained and in not trained echo-colour Doppler operators.

METHODS:

Thirty-six (36) subjects, matched for age and gender, were subset in 3 groups (group A, 12 healthy controls, HC; group B, 12 multiple sclerosis patients, MS; group C, 12 patients with other neurological disease, OND) underwent echo-colour Doppler screening for CCSVI according to an original protocol previously described. The inter observer variability rate was assessed by comparing respectively trained vs not trained operators, and trained vs trained operators, by using the same echo-colour Doppler equipment. In addition, by scanning 15 subjects after one month from the first session, intra observer coefficient was also assessed in trained operator.

RESULTS:

The inter observer variability rate[s] between trained and not trained echo-colour Doppler operators were not completely satisfactory (K coefficient 0.47 95% CI 0.27-0.68). On the other hand the inter observer agreement between trained operators was much more reliable (K coefficient 0.80 95% CI 0.59-1.01). Finally, the intra observer variability rate in trained operators was 0.93, (95% CI 0.80-1.06) confirming a highly satisfactory agreement.

CONCLUSION:

Echo-colour Doppler is a powerful, non-invasive and reproducible tool for screening CCSVI-MS but it needs special training.

PMID: 20351668


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 5:43 pm    Post subject: (Abst.) Internal jugular vein morphology & hemodynamics. Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):115-20.

Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis.
Al-Omari MH, Rousan LA.

Radiology Department, King Abdullah University Hospital, Jordan University of Science and Technology, Jordan.

AIM:

The aim of this study is to compare the hemodynamics and the morphology of the internal jugular veins using Colour-Doppler and B-mode sonongraphy in multiple sclerosis patients (MS) and in controls.

METHODS:

The internal jugular veins of 25 MS patients and 25 controls were examined using colour Doppler and B-mode ultrasound in sitting and supine positions, recording the changes in hemodynamics and the presence or absence of morphological changes. The presence of at least two of the extracranial Zamboni criteria in the same individual was considered positive for evidence of chronic cerebrospinal venous insufficiency (CCSVI).

RESULTS:

According to the described criteria, 92% of the MS patients showed abnormal findings and 84% of them showed evidence of CCSVI. However, only 24% of the controls showed abnormal findings, [and] none of them showed evidence of CCSVI (OR=7.25, 95% CI 2.92-18.01, P<0.0001).

CONCLUSION:

Hemodynamic abnormalities and morphological changes involving the internal jugular vein are strongly associated with MS. These findings can be demonstrated by non-invasive, cost effective Doppler ultrasound criteria.

PMID: 20351667


The abstract can be seen here.


Last edited by agate on Thu Apr 01, 2010 12:20 pm; edited 1 time in total
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 5:59 pm    Post subject: (Abstract) Extracranial Doppler sonographic CCSVI criteria Reply with quote

From PubMed, March 31, 2010:

Quote:


Int Angiol. 2010 Apr;29(2):109-14.

Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis

Simka M, Kostecki J, Zaniewski M, Majewski E, Hartel M.

Department of Angiology, Private Healthcare Institution SANA, Pszczyna, Poland - mariansimka@poczta.onet.pl.

AIM:

The aim of this open-label study was to assess extracranial Doppler criteria of chronic cerebrospinal venous insufficiency in multiple sclerosis patients.

METHODS:

Seventy patients were assessed: 49 with relapsing-remitting, 5 with primary progressive and 16 with secondary progressive multiple sclerosis. The patients were aged 15-58 years and they suffered from multiple sclerosis for 0.5-40 years. Sonographic signs of abnormal venous outflow were detected in 64 patients (91.4%).

RESULTS:

We found at least two of four extracranial criteria in 63 patients (90.0%), confirming that multiple sclerosis is strongly associated with chronic cerebrospinal venous insufficiency. Additional transcranial investigations may increase the rate of patients found positive in our survey. Reflux in internal jugular and/or vertebral veins was present in 31 cases (42.8%), stenosis of internal jugular veins in 61 cases (87.1%), not detectable flow in internal jugular and/or vertebral veins in 37 cases (52.9%) and negative difference in cross-sectional area of the internal jugular vein assessed in the supine vs. sitting position in 28 cases (40.0%). Flow abnormalities in the vertebral veins were found in 8 patients (11.4%). Pathologic structures (membranaceous or netlike septa, or inverted valves) in the junction of the internal jugular vein with the brachiocephalic vein were found in 41 patients (58.6%), in 15 patients (21.4%) on one side only and in 26 patients (37.1%) bilaterally.

CONCLUSION:

Multiple sclerosis is highly correlated with chronic cerebrospinal venous insufficiency. These abnormalities in the extracranial veins draining the central nervous system can exist in various combinations. The most common pathology in our patients was the presence of an inverted valve or another pathologic structure (like membranaceous or netlike septum) in the area of junction of the IJV with the brachiocephalic vein.

PMID: 20351666


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Mar 31, 2010 6:03 pm    Post subject: (Abstract) Reply with quote

From PubMed, March 31, 2010:

Quote:
Int Angiol. 2010 Apr;29(2):95-108.

Embryological background of truncular venous malformation in the extracranial venous pathways as the cause of chronic cerebro spinal venous insufficiency

Lee AB, Laredo J, Neville R.

Department of Vascular Surgery, Georgetown University Hospital, Washington DC, USA.

The truncular venous malformation (VM) represents an embryologically defective vein where developmental arrest has occurred during the vascular trunk formation period in the 'later stage' of the embryonic development. A relatively simple truncular VM lesion such as a venous web at the hepatic venous outlet causes portal hypertension giving a profound damage/impact to the liver. A similar condition involving the head and neck venous system may cause chronic cerebro-spinal venous insufficiency (CCSVI) and may be involved in the development or exacerbation of multiple sclerosis.

PMID: 20351665


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Fri Apr 02, 2010 2:44 pm    Post subject: Reply with quote

The editorial by Ashton Embry, Ph.D., in the same issue of the journal International Angiology, can be seen here.

I'm sorry that Ashton Embry, Ph.D., has weighed in so prominently on this CCSVI question. He is not really qualified in neurology or cardiovascular medicine. He has a Ph.D. in geology as I understand it.

For more about him, see this Geological Survey of Canada Webpage.

Moreover, at the end of his editorial he says:
Quote:
It seems that currently CCSVI treatment, like all nondrug therapies for MS, will have to be done outside of conventional neurological practices.


And he goes on to say:

Quote:
The most important therapy persons with MS can use before and after CCSVI treatment is to use nutritional strategies which offset CCSVI, BBB
breakdown and autoimmune reactions. These nutritional strategies are found on the Direct-MS website (http://www.direct-ms.org/recommendations.html).


That is Ashton Embry's Website. People with MS are being pointed toward it as a source of reliable nutrition information.

There are recipes on the Website, and many people claim to have good results from the Best Bet Diet that is advocated there. However, the recipes include no nutrition information (calories, protein, fat, carbs, potassium, iron, fiber, etc.).
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Thu Apr 08, 2010 4:52 pm    Post subject: Hypoperfusion of brain parenchyma & CCCSVI severity in M Reply with quote

To be presented at the annual conference of the AAN in Toronto, April 10-17, 2010:

Quote:
Hypoperfusion of Brain Parenchyma Is Strongly Associated with the Severity of Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis

Paolo Zamboni, Italy, Eric Menegatti, Ferrera, Italy, Bianca Weinstock-Guttman, Michael G. Dwyer, Claudiu Schirda, Buffalo, NY, Anna Maria Malagoni, Ferrera, NY, Italy, David Hojnacki, Cheryl Kennedy, Ellen Carl, Niels Bergsland, Christopher Magnano, Buffalo, NY, Ilaria Bartolomei, Bologna, Italy, Fabrizio Salvi, Cesena (FC), Italy, Robert Zivadinov, Buffalo, NY

OBJECTIVE:

To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral perfusion in patients with multiple sclerosis (MS).

BACKGROUND:

CCSVI is a vascular condition described in MS patients, characterized by stenoses of the main extracranial veins with hampered cerebral venous outflow. We hypothesized that the impaired venous outflow contributes to hypoperfusion of brain parenchyma.

DESIGN/METHODS:

Sixteen consecutive relapsing-remitting MS patients (mean age 36.1yrs, mean disease duration 7.5yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC), were scanned on a GE 3T scanner using dynamic susceptibility contrast enhanced perfusion-weighted imaging (PWI). Cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM), normal appearing (NA) GM, NAWM, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Diagnosis of CCSVI was established based on the venous hemodynamic (VH) Doppler criteria (Zamboni, JNNP, 2009) and the severity was based on fulfilled VH criteria (score 0-5) and VH insufficiency severity score (VHISS) (score 0-16).

RESULTS:

All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between VH criteria and VHISS, and CBF, CBV and MTT in all examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for lower CBF and higher VHISS in the GM, WM, NAGM and NAWM (r= -0.70 to -0.72, p<0.002), and in the thalamus, caudate, putamen, hippocampus, nucleus accumbens (r= -0.6 to -0.72, p<0.008). The correlation coefficients for CBV and MTT were in a range between r= -0.5 to -0.65. No relationship was observed for NC.

CONCLUSIONS/RELEVANCE:

This study demonstrates that severity of CCSVI is directly associated with hypoperfusion of the brain parenchyma in MS.

Supported by:

Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.

Category - MS and Related Diseases - Clinical Science

Wednesday, April 14, 2010 7:30 AM
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Thu Apr 08, 2010 5:01 pm    Post subject: Study of CCSVI prevalence in MS & related diseases Reply with quote

To be presented at the annual AAN conference being held in Toronto, April 10-17, 2010:

Quote:
Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD Study). Description of the Design and Interim Results of an Epidemiological Study of the Prevalence of Chronic Cerebrospinal Venous Insufficiency in MS and Related Diseases

Robert Zivadinov, Karen Marr, Murali Ramanathan, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Ralph R. H. B. Benedict, Buffalo, NY, Gary Cutter, Birmingham, AL, Cheryl Kennedy, Makki Elfadil, David Hojnacki, Frederick Munschauer, Justine Reuther, Christina Brooks, Kristin Hunt, Michelle Andrews, Bianca Weinstock-Guttman, Buffalo, NY

OBJECTIVE:

To ascertain the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in a large cohort of patients with multiple sclerosis (MS), patients with other neurological diseases (OND) and in normal controls (NC), by using specific proposed Doppler criteria (Zamboni et al, JNNP, 2009).

BACKGROUND:

CCSVI is a complex vascular condition characterized by anomalies of the main extracranial cerebrospinal (CS) venous routes that interfere with the normal CS venous outflow. This condition was previously associated with clinically definite MS.

DESIGN/METHODS:

Cross-sectional study that will enroll consecutive 1700 subjects at one MS center including: 1000 adult patients with possible and definite MS (50 clinically isolated syndrome, 50 radiologically isolated syndrome, 500 relapsing-remitting, 300 secondary-progressive, 50 primary-progressive MS and 50 neuromyelitis optica). A comparative group will include 300 OND patients and 300 adult age- and sex-matched NC. Fifty pediatric patients (<18 yrs) with acquired demyelinating diseases (MS and acute disseminated encephalomyelitis) and 50 pediatric NC will be assessed. All participants will undergo clinical examination and a Doppler scan of the head and neck. All MS patients and a subcohort of NC and OND will undergo an MRI of the brain. A consecutive subgroup (MS, NC and OND) will have also an MRI of the veins of the neck to corroborate the Doppler diagnosis of CCSVI. The Doppler, and MRI evaluators are blinded to the subject status. The prevalence and severity of venous hemodynamic abnormalities identified in the different groups will be analyzed. Data will be unblinded at three predetermined time-points based on the number of subjects enrolled: at 500, 1000 and 1700 subjects respectively.

RESULTS:

As of 1 Nov 2009, 473 subjects signed informed consent. The initial interim analysis following the first 500 subjects is scheduled for December 2009.

CONCLUSIONS/RELEVANCE:

The interim results of the first 500 enrolled subjects will be presented.

Category - MS and Related Diseases - Clinical Science

Thursday, April 15, 2010 3:00 PM

Poster Session VI: Multiple Sclerosis and Related Diseases: Clinical Trials (3:00 PM-7:30 PM)
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Thu Apr 08, 2010 5:45 pm    Post subject: (Abstract) CCSVI & MS Reply with quote

Among the authors here are at least two big names in the MS research field (Barkhof and Bar-or).

From PubMed, April 8, 2010:

Quote:
Ann Neurol. 2010 Mar;67(3):286-90.

Chronic cerebrospinal venous insufficiency and multiple sclerosis

Khan O, Filippi M, Freedman MS, Barkhof F, Dore-Duffy P, Lassmann H, Trapp B, Bar-Or A, Zak I, Siegel MJ, Lisak R.

Multiple Sclerosis Center, Department of Neurology, Wayne State University School of Medicine, 4201 St Antoine, Detroit, MI 48323, USA. okhan@med.wayne.edu


A chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI), is claimed to be a pathologic phenomenon exclusively seen in multiple sclerosis (MS). This has invigorated the causal debate of MS and generated immense interest in the patient and scientific communities. A potential shift in the treatment paradigm of MS involving endovascular balloon angioplasty or venous stent placement has been proposed as well as conducted in small patient series. In some cases, it may have resulted in serious injury.

In this Point of View, we discuss the recent investigations that led to the description of CCSVI as well as the conceptual and technical shortcomings that challenge the potential relationship of this phenomenon to MS. The need for conducting carefully designed and rigorously controlled studies to investigate CCVSI has been recognized by the scientific bodies engaged in MS research. Several scientific endeavors examining the presence of CCSVI in MS are being undertaken.

At present, invasive and potentially dangerous endovascular procedures as therapy for patients with MS should be discouraged until such studies have been completed, analyzed, and debated in the scientific arena.

PMID: 20373339 [PubMed - in process]






The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Apr 14, 2010 8:56 am    Post subject: (Abstract) CCSVI & MS: Critical analysis... Reply with quote

From PubMed, April 14, 2010:

Quote:
Nervenarzt. 2010 Apr 14. [Epub ahead of print]

["Chronic cerebrospinal venous insufficiency" and multiple sclerosis : Critical analysis and first observation in an unselected cohort of MS patients.]

[Article in German]

Krogias C, Schröder A, Wiendl H, Hohlfeld R, Gold R.

Neurologische Klinik, St. Josef-Hospital, Ruhr-Universität Bochum, Gudrunstrasse 56, 44791, Bochum, Deutschland, christos.krogias@rub.de.


Currently, the hypothesis that altered venous hemodynamics might play a causative role in the pathogenesis of multiple sclerosis (MS) is being controversially discussed. This new "venous hypothesis" postulates that obstructions of the cervical venous system cause an increased pressure of the intracranial venous system and that in turn intracranial congestion disintegrates the blood-brain barrier initiating the inflammatory process in MS.

The "venous hypothesis" is analyzed and evaluated with regard to the following aspects: first concerning the validity of published data, second with regard to the plausibility in view of the currently approved pathogenetic model of MS, and third with regard to the compatibility with preliminary neurosonological findings in a small but unselected cohort of patients at our department.

The authors conclude that the "chronic cerebrospinal venous insufficiency (CCSVI)" cannot represent the exclusive pathogenetic factor in the pathogenesis of MS. In our cohort, only 20% of the patients fulfilled the required neurosonological features of CCSVI.

So far, the pathogenetic relevance of these findings remains speculative. Thus, based on the current scientific position we cannot justify invasive "therapeutic" approaches, especially if they are performed outside of clinical trials.

PMID: 20386873


The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Jun 05, 2010 10:40 pm    Post subject: Reply with quote

Andrew Wilner, MD, a neurologist, has posted notes on the AAN conference on Medscape, and one of his postings is his impressions of the MS Society-sponsored press conference about CCSVI:

Quote:
Zamboni "Venous Insufficiency" Theory of Multiple Sclerosis-Red Flags Warn of Thin Ice
Andrew Wilner, MD, Apr 14, 2010


Here in Canada, ice hockey is big sport. But everyone knows you don't go skating on the pond when the ice is thin.

At the request of the National Multiple Sclerosis (MS) Society, the AAN hosted a prime time press conference to create a venue where the controversial theory that "chronic cerebrospinal venous insufficiency" (CCSVI) is the etiology of MS could be discussed by its leading proponent, Paolo Zamboni, MD, Director, Vascular Diseases Center, University of Ferrara, Italy, Robert Zivadinov, MD, PhD, Director of the Buffalo Neuroimaging Analysis Center, Buffalo, NY, Andrew Common, MD, Radiologist in Chief, St. Michaels Hospital, University of Toronto, Ontario, CA, and Aaron Miller, MD, Professor of Neurology and Director of the MS Center at Mount Sinai, NY, NY, and Chief Medical Officer of the National MS Society.

Spurred by Dr. Zamboni's 2009 report of 65 patients who had significant improvement in their MS after percutaneous transluminal angioplasty of their jugular or azygous veins to correct CCSVI, over 4,300 people registered to listen in to the press conference. Over 1,000 questions were submitted in advance.

Before I went to the press conference, I was skeptical. A breakthrough in MS by a vascular surgeon seemed unlikely to me, (particularly since my old chief is a neuroimmunologist and pretty smart guy) but, well, who knows?

After the press conference, I was really skeptical.

Dr. Zamboni defined CCSVI as a "syndrome characterized by stenosis of the internal jugular and/or azygous veins with opening of collaterals and insufficient drainage proved by cerebral MRI perfusional study." Why venous stenosis, if it actually exists, should cause MS is unclear-the first red flag. There were at least 2 neuroimmunologists in the room, and I could see that neither one was buying Dr. Zamboni's theory that venous congestion causes leakage of red cells, deposition of iron, break down of the blood brain barrier, and an immunologic response, and Voila! MS. Reversing the venous congestion would, according to Dr. Zamboni, relieve the symptoms.

Apparently, there are neuroimaging criteria for diagnosing CCSVI. These were not explained during the conference, but are critical to the diagnosis. The criteria were defined by Dr. Zamboni, but it is not clear how they were validated, the second red flag.

The third red flag was the hopelessly detailed and confusing presentation by Dr. Zivadinov of the ongoing Combined Transcranial and Extrancranial Venous Doppler Evaluation in Multiple Sclerosis and Related Diseases (CTEVD) Study. The press room was packed with neurologists and journalists, and the conference was specifically designed for lay listeners. I would be amazed if anyone, including the neurologists in attendance, understood much more than the general gist of the three-Phase study, which was to try and identify the prevalence of venous congestion in patients with MS, normals, and patients with other neurologic diseases by various types of imaging. Frankly, I was really frustrated, because I was eager to understand the current research in order to make some assessment about its validity, and I wanted the flags to stop waving.

The fourth red flag was Dr. Zivadinov's insistence that there had to be "scientifically rigorous research alongside respect for patients' rights and needs." I am not sure why he thought this audience needed a lecture on medical ethics, unless it was to imply that somehow this particular research needed to be rushed through. No one, least of all the attendees at AAN, questions the need for better treatment of MS. Indeed, properly controlled randomized clinical trials have spawned several new powerful MS drugs that are likely to be approved in the very near future (see upcoming Medscape post on MS News from AAN).

The fifth red flag was the disclosure that Dr. Zamboni was working on a "proprietery" doppler machine, which would be the only machine that could really detect the problem of CCSVI.

By now, there were so many red flags waving there was turbulence in the room. I had to hang on to my seat to keep from toppling over.

Dr. Common gave a nice, clear, overview for the journalists and laypeople listening in describing interventional radiology and the treatment of venous diseases, but he admitted to no experiencce treating CCSVI.

To their credit, Drs. Zamboni and Zivadinov emphasized that NO PATIENT should have PTA for CCSVI outside a properly controlled clinical trial.

For me, Dr. Miller said it all, "How, when, and indeed whether CCSVI has any role in the treatment of MS remains to be seen."

I look forward to revisiting this topic when there is more high quality, scientific data, and the ice is thick enough to stand on.




You can see the forum posting
here.

About Dr. Wilner: http://www.drwilner.org/
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Wed Jun 16, 2010 11:58 am    Post subject: (AARP) "Liberation" procedure for MS sparks debate Reply with quote

The AARP Bulletin has an article (June 16, 2010) on CCSVI entitled "'Liberation' procedure for multiple sclerosis sparks debate.'" You can read the article
here.
Back to top
View user's profile Send private message
cricket52



Joined: 03 Oct 2006
Posts: 343
Location: northern Ontario

PostPosted: Thu Jun 17, 2010 2:26 pm    Post subject: Reply with quote

Science vs anecdotal evidence. Patients vs doctors.

The anecdotal evidence speaks volumes. If it is as simple as opening a vein then why not? Nothing to lose really. Any surgery is risky and to have function again, if only for a season, would be worth it. Besides, these doctors are not quacks or crackpots, they are scientists too. The only thing that makes them different from their peer detractors is their open minds.
_________________
Cricket
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Thu Jun 17, 2010 5:04 pm    Post subject: Reply with quote

Some people are queasy about having anyone cut into them. No matter how expert the surgeon is, cutting is still cutting. There will be blood shed, there will probably be some scar tissue or other complication down the line.

To make a long story short, I'm a coward. study (That's me, hiding behind a book.)
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Tue Aug 17, 2010 10:07 pm    Post subject: ...severe chronic venous insufficiency in MS patients... Reply with quote

Presented at the AAN Conference in April:


Quote:
[IN7-1.003] Quantitative Venous Vasculature Assessment on Susceptibility-Weighted Imaging Reflects Presence of Severe Chronic Venous Insufficiency in the Brain Parenchyma of Multiple Sclerosis Patients. A Case-Control Study

Guy U. Poloni, Buffalo, NY, Paolo Zamboni, Ferrara, Italy, Mark Haacke, Detroit, MI, Stefano Bastianello, Pavia, Italy, Michael G. Dwyer, Niels Bergsland, Claudiu Schirda, David Wack, Christopher Magnano, Bianca Weinstock-Guttman, Buffalo, NY, Fabrizio Salvi, Ferrara, Italy, David Hojnacki, Robert Zivadinov, Buffalo, NY

OBJECTIVE:

To develop an objective method for quantifying venous vasculature in brain parenchyma on susceptibility-weighted imaging (SWI). To apply this technique in multiple sclerosis (MS) patients and in healthy controls (HC).

BACKGROUND:

SWI is a MRI application that can directly image cerebral veins by exploiting venous blood oxygenation.

DESIGN/METHODS:

Sixty-two (62) MS patients (44 relapsing-remitting and 18 secondary-progressive) and 33 age- and sex-matched HC were imaged on a 3T GE scanner using pre-contrast SWI. A subset of MS patients (50) and HC (7) obtained SWI-post gadolinium contrast sequence (0.1 mMol/Kg Gd-DTPA with 10 min delay). In-house developed segmentation algorithm, based on a 3D multi-scale line filter, was applied for vein segmentation. Absolute volumetric measurement for total vein vasculature was performed in milliliters (ml) and the relative venous intracranial fraction (VIF) was obtained to correct for head size and amount of brain atrophy. The size of individual veins was measured in mm and 4 groups were created according to their mean diameter: <0.3mm, 0.3-0.6mm, 0.6-0.9mm and >0.9 mm. Voxel brain average distance-from-vein maps was also calculated with higher distance indicating fewer veins.

RESULTS:

A significantly lower absolute venous volume was detected in MS patients compared to HC, both in pre-contrast (67.5 vs. 82.7ml, -18.3%, p<0.001) and post-contrast (70.4 vs. 87.1ml, -19.1%, p<0.011) images. The VIF was significantly lower in MS patients (p<0.001). The highest mean diameter difference was found for the smallest veins (<0.3 mm), both on pre- (p<0.001) and post-contrast (p<0.018) images. The distance-from-veins was also significantly higher in MS patients (p<0.001).

CONCLUSIONS/RELEVANCE:

We developed and validated a quantitative vein segmentation method that showed altered visibility of venous vasculature on SWI pre- and post-contrast images in MS patients. These findings suggest severely compromised brain venous system in MS patients.

Category - MS and Related Diseases - Clinical Science



Platform Session: Integrated Neuroscience: Multiple Sclerosis Imaging

Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Aug 28, 2010 7:08 pm    Post subject: NMSS Reply with quote

The National MS Society has produced this video interview with Dr. Jerry Wolinsky, a neurologist at the University of Texas and Chairperson of the National Clinical Advisory Board of the NMSS. The interview is 13 minutes long and is called "CCSVI and MS." It is part of the MS Learn Online series. The interview can be seen here.

If others have been following discussions elsewhere about CCSVI, maybe you'll agree with me that the tone of the discussions is often shrill and even fierce.

It was refreshing to watch this interview because it appears to be objective. I'm not one who always favors everything the MS Society does or stands for, but in this instances they just might have something to say that needs to be said.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Oct 25, 2010 5:14 pm    Post subject: (ECTRIMS) Clinical correlates of CCSVI in MS Reply with quote

Presented as a poster session at the annual ECTRIMS conference in Sweden, October 15, 2010:

Quote:
Clinical assessment tools 2

Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis

B. Weinstock-Guttman, G. Cutter, K. Marr, D. Hojnacki, M. Ramanathan, R.H.B. Benedict, C. Morgan, E.A. Yeh, E. Carl, C. Kennedy, J. Reuther, C. Brooks, M. Elfadil, M. Andrews, R. Zivadinov (Buffalo, Birmingham, US)

Objectives:

To evaluate the clinical correlates of chronic cerebrospinal venous insufficiency (CCSVI) in a large cohort of patients with multiple sclerosis (MS).

Background:

CCSVI is a complex vascular condition characterized by anomalies of the primary veins outside the skull (Zamboni et al, JNNP, 2009). We previously showed in a pre-planned Combined Transcranial (TCD) and Extracranial Venous Doppler Evaluation (CTEVD) blinded study that the prevalence of CCSVI was significantly higher in the MS cohort vs. healthy controls (HC) (56.1% vs. 22.7%, p< 0.001).

Results:

This study enrolled 499 subjects; 163 HC, 289 MS patients, 21 CIS patients, 26 subjects with other neurological disorders underwent a clinical examination and a combined Doppler and TCD scan of the head and neck. Thirty patients that were defined as borderline (technical limitation for criteria 2 and not meeting definition of CCSVI) were considered negative for this analysis.

CCSVI prevalence was significantly higher in more advanced MS disease subtypes: 89.5% in relapsing secondary-progressive (SP), 67.2% in non-relapsing SP, 54.5% in primary-progressive (PP), 49.2% in relapsing-remitting (RR) and 38.1% in CIS (p = 0.033). The mean venous haemodynamic insufficiency severity score (VHISS) was higher for subjects diagnosed with CCSVI (mean VHISS ± SD: 4.05 ± 1.4, n = 218) than for subjects without CCSVI (1.20 ± 1.0, n = 281; p < .001). Criteria 2, 4 and 5 showed significant associations with an EDSS >=4.0 (Criteria 2: OR of 2.25, p=0.005; criteria 4: OR: 3.28, p=0.004 and Criteria 5 OR: 2.67, p=0.008). MS subjects with CCSVI had significantly higher Pyramidal (p = 0.020), Cerebellar (p = 0.049), and Brain Stem (p = 0.010) EDSS sub-scale score than subjects without CCSVI. Subjects with CCSVI were significantly older than subjects without CCSVI (p = 0.04). However, the mean Multiple Sclerosis Severity Score (MSSS) trended higher for subjects with CCSVI (4.22 ± 2.6, n = 160) than for subjects without CCSVI (3.63 ± 2.4, n =127), but this difference was not significant (p = .073).

Conclusions:

The presence of CCSVI in MS patients was associated with more advanced MS disease subtypes and more severe motor, cerebellar and brainstem involvement.



The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Mon Oct 25, 2010 5:24 pm    Post subject: (ECTRIMS) CCSVI an unlikely cause of MS Reply with quote

Presented as a poster session at the ECTRIMS conference in Sweden, October 15, 2010:

Quote:
Pathology 2

Chronic cerebrospinal venous insufficiency is an unlikely cause of multiple sclerosis

B. Yamout, A. Herlopian, Z. Issa, R.H. Habib, A. Fawaz, J. Salameh, H. Wadih, H. Awdeh, N. Muallem, R. Raad, A. Al-Kutoubi (Beirut, LB)

Introduction:

A state of chronic cerebrospinal venous insufficiency (CCSVI) secondary to extracranial venous stenosis (EVS) was suggested as a possible cause of multiple sclerosis (MS).

Methods:

In this study we performed selective extracranial venous angiography (SV) on 42 patents with early MS (EMS): clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) of less than 5 years duration, and late MS (LMS): RRMS of more than 10 years duration. We also reviewed available MRI and clinical relapse data in patients with documented EVS.

Results:

EVS was present in 7/29 (24%) patients with EMS and 12/13(92%) patients with LMS, a highly significant statistical difference (p<0.0001). Only 3/42 (7%) patients (all in the LMS group) had 2 vessel stenosis, while the rest had only 1 vessel involved. The incidence of EVS in CIS was 9% compared to 33% in RRMS of less than 5 years duration. The most important factor in determining presence of EVS was disease duration: mean=9.4±6.8 years in 19 patients with EVS compared to 3.2±4.1 years in patients without (p<0.005), which stayed significant after controlling for age at disease onset and gender (p<0.002). Within the EMS group, patients with (n=7) and without (n=22) EVS had similar EDSS (1.43±2.13 and 0.8±0.008, p=0.85) and disease duration (mean =2.1 and 2.4 years, p=0.521), suggesting similar disease severity. The 7 EMS patients with stenosis had a total of 14 relapses since disease onset. No clear correlation could be found between site of EVS and relapse anatomical localization. A total of 97 spine and brain MRIs available since disease onset on all 19 patients with stenosis were reviewed. Again no clear correlation could be seen between the location of gadolinium-enhancing (Gd+) lesions and site of EVS.

Conclusion:

CCSVI is an unlikely cause of MS since it is not present in most cases early in the disease, and in only a minority of MS patients affects more than 1 extracranial vein. It is likely to be a late secondary phenomenon, possibly related to chronic central nervous system (CNS) disease and atrophy.




The abstract can be seen here.
Back to top
View user's profile Send private message
agate
Site Admin


Joined: 17 May 2006
Posts: 5694
Location: Oregon

PostPosted: Sat Nov 06, 2010 5:44 pm    Post subject: Video interview with Dr. David Hubbard Reply with quote

An e-mail was sent to me with a link to this video:

http://www.komonews.com/home/video/106175483.html?tab=video

It is an interview with David Hubbard, MD, who has a Website:

http://hubbardfoundation.org/david_hubbard_md.html

In the video he discusses CCSVI, focusing on the procedure as it affected his son, who has MS.

His point is that since no placebo-controlled trial of the CCSVI procedure is likely to be done, the procedure won't be legitimized in the opinions of those neurologists who have cast doubt on it.

However, he believes in going ahead with the procedure for those who are shown to have MS and the kind of venous obstruction that would be cleared by the CCSVI process.
Back to top
View user's profile Send private message
Display posts from previous:   
Post new topic   Reply to topic    msspeaks Forum Index -> MS - RESEARCH, ARTICLES, ABSTRACTS, DISCUSSION All times are GMT - 7 Hours
Page 1 of 1

 
Jump to:  
You can post new topics in this forum
You can reply to topics in this forum
You can edit your posts in this forum
You can delete your posts in this forum
You cannot vote in polls in this forum
Create your own free forum now!
Terms of Service Purchase Ad Removal Forum Archive Report Abuse