About MS  > MS news and research  > ccsviresearch
About MS

What is MS?

MS symptoms

Managing your MS

Effects of MS

MS news and research

Alternative medicine

Amyloids

Bacteria and viruses

Biomarkers and microRNA

Bone marrow transplant

Botox

Brain inflammation & lesions

Brain iron deposits

Cancer and MS

CCSVI

Cognition

Diet

Drugs

Endo-parasites and helpful organisms

Environmental factors

Ethnic groups, geographical regions and MS

Exercise

Gender and MS

Genetics

Hormones

Immune cells

Lipids

Lymphoid tissue inducer (LTI) cells

Medical imaging

Multiple Sclerosis (Etiology)

Myelin

Nerve and brain cells

Neuropsychiatric and psychological

Paediatric MS

Pain

Potential viral causes

Pregnancy

Quality of life

Retroviruses

Sex

Stem cells

Stress

Symptoms

Technology

Thalmus Research

Types of MS

Vaccinations

Vitamin D

News and research archive

Other support

Donate with JustGiving

Latest Tweets

CCSVI

CCSVI Venogram

Chronic cerebrospinal venous insufficiency is described as a chronic problem (ongoing) where blood from the brain and spine has trouble getting back to the heart.

It is caused by a narrowing in the veins (stenosis) that drain the brain and the spine. Blood takes longer to return to the heart, and it can reflux back into the brain and spine or cause oedema and leakage of red blood cells and fluids into the tissues of the brain and spine.

Blood that remains in the brain too long creates a delay in deoxyginated blood leaving the head ("slowed perfusion"). This can cause hypoxia, a lack of oxygen in the brain. Plasma and iron from blood deposited in the brain tissue can also be very damaging leading to iron along with other unwelcome cells crossing the crucial brain-blood barrier.

Researchers urge broad study of venous abnormalities(28/02/14)

Although their oft-cited prior study found no causal relationship between venous abnormalities in the neck and multiple sclerosis (MS), University at Buffalo neurological researchers are strongly advocating more investigation.

Robert Zivadinov, MD, PhD, professor of neurology, and his colleagues cite mounting evidence that the extracranial venous system may play a role in a broad range of central nervous system disorders and aging.

“The full story and consequence of these venous abnormalities that disrupt normal blood flow will require much more research,” says Zivadinov, who also directs UB’s Buffalo Neuroimaging Analysis Center.

New Research Could Explore Risk Factors

Countering calls to abandon related research, Zivadinov has coauthored a debate article, “Potential Involvement of the Extracranial Venous System in Central Nervous System Disorders and Aging,” with Chih-Ping Chung, MD, PhD, of National Yang-Ming University in Taiwan, in BMC Medicine.

Zivadinov also published a related editorial, “Is There a Link Between the Extracranial Venous System and Central Nervous System Pathology?” in the same journal. He and Chung call for research examining the incidence and prevalence of venous abnormalities in relation to developmental and demographic factors, as well as cardiovascular, inflammatory and lifestyle risk factors.

Prior ‘Neurology’ Study Among Most Cited

In their July 2011 study, “Prevalence, Sensitivity and Specificity of Chronic Cerebrospinal Venous Insufficiency in MS,” published in Neurology, Zivadinov’s team found an increased prevalence of extracranial venous abnormalities in MS patients, but no evidence of causation.

Their paper is one of the top 10 articles in neurology and the second-most-cited paper in neurology in the past three years, according to Neuropenews, the news blog of the European Federation of Neurological Societies and the European Neurological Society.

“We have since developed a substantial body of work looking at these abnormalities in relation to Alzheimer’s disease, aging and other neurological diseases,” says Zivadinov.

“We believe our current studies on how these abnormalities impact central nervous system pathology will also prove to be of ongoing interest to the scientific community.”

Abnormalities May Impede Blood Flow From Brain

Extracranial venous abnormalities indicate chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by the narrowing of vessels that drain blood from the cranium.

Paolo Zamboni of the University of Ferrara in Italy was the first to hypothesize that the condition results in changes in blood flow patterns that eventually injure brain tissue and degenerate neurons, leading or contributing to MS.

Compared to Zamboni’s research, the UB study found much lower sensitivity and specificity rates of CCSVI in MS patients.

However, the UB team did find a much higher prevalence of CCSVI in progressive versus non-progressive MS patients, suggesting the condition may be a consequence, rather than a cause, of MS.

The research team included Department of Neurology co-authors Ralph H. Benedict, PhD, professor; Michael G. Dwyer III, PhD, assistant professor; David W. Hojnacki, MD, assistant professor; Bianca Weinstock-Guttman, MD, professor; as well as Murali Ramanathan, PhD, professor of pharmaceutical sciences.

Source: University Of Buffalo © 2014 University at Buffalo (28/02/14)>

MS patients did not benefit from CCSVI intervention - PREMiSe study(22/11/13)

Multiple sclerosis (MS) is a disease of uncertain etiology characterized by demyelinating lesions affecting the central nervous system. In 2009, Dr. Paolo Zamboni et al described an association between MS and extra cranial venous outflow restrictive lesions detected by extra cranial and intracranial venous duplex studies.

They named this venous outflow restriction chronic cerebrospinal venous insufficiency (CCSVI). In addition, they introduced an endovascular interventional treatment for CCSVI in an open-label study that included 65 MS patients with post procedure follow-up of over 18 months. Several subsequent prospective open-label, non-randomized studies investigated safety and efficacy of venous angioplasty in MS. Findings from these studies have generated considerable controversy but remain unproven.

Since 2009, over 30,000 MS patients worldwide have undergone an endovascular procedure. The vast majority of these procedures were done outside a clinical trial raising skepticism.

Dr. Robert Zivadinov, Professor of Neurology, Department of Neurology State University of New York at Buffalo (Buffalo, NY) reported, “The objective of our study, The Prospective Randomized Endovascular Therapy in MS (PREMiSe), was to investigate the safety and efficacy of percutaneous transluminal venous angioplasty (PTVA) for correcting CCSVI in MS in the setting of a prospective, double-blind, sham-controlled, randomized pilot trial.”

PREMiSe is believed to be the first prospective randomized double-blinded, controlled study of balloon angioplasty for MS performed with Institutional Review Board approval in a rigorous fashion in the U.S. with significant safeguards in place to ensure careful determination of risks and benefits. All screening, diagnostic, interventional and follow-up procedures and visits were performed at no cost to the patients.

"The study’s key findings are that while the treatment is safe and was not associated with serious adverse events, it did not provide sustained improvement in MS patients,” explained Zivadinov.

The trial enrolled 30 MS patients. Phase 1 was a safety trial, involving 10 MS patients and Phase II involved a total of 20 MS patients, who were randomized to receive treatment or placebo. Researchers found no difference in clinical symptoms, brain lesions as determined on MRIs or quality of life outcomes between MS patients who underwent balloon angioplasty to correct CCSVI and those who did not receive the treatment.

Zivadinov said, “Based on our findings, our primary message to MS patients and their doctors is that endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) should only be done in the context of randomized, double-blinded, controlled studies like PREMiSe.

About VEITHsymposium: Now in its fourth decade, VEITHsymposium provides vascular surgeons, interventional radiologists, interventional cardiologists and other vascular specialists with a unique and exciting format to learn the most current information about what is new and important in the treatment of vascular disease.

Source: PR Web ©Copyright 1997-2013, Vocus PRW Holdings, LLC (22/11/13)

No link between narrowed veins and MS: Canadian-led study(09/10/13)

A study published in the British medical journal The Lancet finds that narrowing of the veins leading from the brain -- a condition called CCSVI -- is just as prevalent in patients with Multiple Sclerosis as in people without the disease.

The study, funded by the MS Society of Canada and led by Dr. Anthony Traboulsee of the University of British Columbia, calls into question the controversial theory that MS is caused by or associated with CCSVI, or chronic cerebrospinal venous insufficiency.

Four years ago, Italian doctor Paolo Zamboni proposed that MS was linked to constricted veins in the head and neck. He provided research that showed that opening the veins with tiny balloons – a procedure he dubbed the liberation treatment -- could improve symptoms in patients and reduce the number of attacks. Since then, hundreds of patients have sought the procedure and dozens of studies have been presented -- all with conflicting results.

The Lancet study used ultrasound to examine the veins of 79 people with MS, as well as a procedure called catheter venography. They also looked at the veins of 55 people who were siblingsof the patients, as well as 43 unrelated healthy volunteers.

Traboulsee, an associate professor of Neurology at UBC and director of the MS Clinic at UBC Hospital, says that catheter venography is considered the most accurate, "gold standard" technology for revealing the size and shape of veins. The procedure involves injecting a dye into a vein and then examining the vein through an X-ray.

The research team compared the width of veins between the brain and the heart with a normal reference point taken from below the jaw.

They say they found that at least two-thirds of the 79 MS patients and the two groups of healthy volunteers had veins that narrowed by at least 50 per cent. The differences in rates of venous narrowing between the groups were not statistically significant.

In all, vein narrowing was present in:
74 per cent of people with MS
66 per cent of their unaffected siblings
70 per cent of the unrelated volunteers

“It’s certainly clear now that the CCSVI or these narrowings are not the cause of Multiple Sclerosis. They’re just too common to be the cause of Multiple Sclerosis,” Traboulsee said during a news conference Tuesday.

He said the study also showed that the ultrasound criteria usually used to diagnose CCSVI are unreliable. Ultrasound found vein narrowing in fewer than half the cases that were detected by catheter venography.

“We think this is going to be very important information for patients and families, to say look at all the different studies out there when trying to make decisions about their care,” he said.

But MS patient Steve Garvie says the study raises some important questions in his mind – namely, why does he feel so much better after getting the liberation treatment for himself?

“This does work, and it does give people their lives back,” Garvie told CTV News. “I think that every single person should have blood flowing in their body properly, whether they have MS or not.”

Garvie says he worries the study will stop other MS patients from undergoing liberation treatment. “They will dwell in pain and suffer let MS run its course, unfortunately.” Dr. Sandy McDonald, a vascular surgeon based in Barrie, Ont., said the new study hasn’t added any clarity to an important question: Does CCSVI provide any benefit to those with MS?

“We don’t know if the quality of life is better; that trial is yet to be done.”

Still, two MS experts who reviewed The Lancet study, Dr. Friedemann Paul of Germany and Dr. Mike Wattjes of the Netherlands, write in an accompanying commentary that the results sound a "death knell" for the CCSVI hypothesis.

"If chronic cerebrospinal venous insufficiency actually existed, the ultrasound findings of this study and previous studies would suggest that up to half of the general and otherwise healthy population should be judged to be seriously ill because of venous insufficiency of the cervical veins," they write.

For his part, Traboulsee is still working on a study on the effectiveness of the so-called “liberation therapy."

His team is providing angioplasty to MS patients with narrowed neck veins as well as sham (placebo) treatments. Each group will then "cross over" to the other treatment after a year, so that all patients will receive the angioplasty at some point. Results from that study are expected in late 2015.

Traboulsee says many MS patients want to know if the liberation procedure is beneficial.

"We are committed to evaluating this treatment with robust methods and utilizing patient-focused outcomes," he says.

Source: CTV News © 2013 Bell Media (09/10/13)

CCSVI not a causative factor in pathogenesis of MS - study(30/09/13)

Abstract

Objectives & Methods: We evaluated internal jugular vein and vertebral vein volume flow using ultrasound, in patients with clinically isolated syndrome or mild multiple sclerosis and controls, to determine whether volume flow was different between the two groups.

Results: In patients and controls, internal jugular vein volume flow increased from superior to inferior segments, consistent with recruitment from collateral veins. Internal jugular vein and vertebral vein volume flow were greater on the right in supine and sitting positions. Internal jugular vein volume flow was higher in the supine posture. Vertebral vein volume flow was higher in the sitting posture. Regression analyses of cube root transformed volume flow data, adjusted for supine/sitting, right/left and internal jugular vein/vertebral vein, revealed no significant difference in volume flow in patients compared to controls.

Conclusions: Our findings further refute the concept of venous obstruction as a causal factor in the pathogenesis of multiple sclerosis. Control volume flow data may provide useful normative reference values.

Internal jugular and vertebral vein volume flow in patients with clinically isolated syndrome or mild multiple sclerosis and healthy controls: results from a prospective sonographer-blinded study. - Chambers B, Chambers J, Churilov L, Cameron H, Macdonell R.

Department of Neurology, Austin Health, Melbourne, Australia.

Source: Phlebology. 2013 Sep 24. [Epub ahead of print] & Pubmed PMID: 24065289 (30/09/13)

Chronic cerebrospinal venous insufficiency (CCSVI): early self-reported benefits are not sustained at follow-up interview(24/09/13)

Abstract

Background: Venoplasty with or without intravascular stents (the “liberation” treatment) has been proposed as a treatment for multiple sclerosis (MS) patients with radiologic findings suggestive of Chronic Cerebrospinal Venous Insufficiency (CCSVI). The purpose of the British Columbia (BC) CCSVI Registry is to gather information on safety and efficacy from MS patients in BC, Canada who have received the “liberation” treatment abroad.

Methods: A standardized telephone survey is used to interview volunteer MS patients up to 4 times - initial, 6-month, 12-month and 24-month follow-up. Participants are asked to rate their general health (GH), fatigue level (FL), mobility (M), exercise level (EL) and procedure rating (PR) on a scale of 5 (1= much better, 2= somewhat better, 3= same, 4= somewhat worse and 5= much worse).

Results: As of April 23, 2013, 76 patients completed the first 2 interviews. Patient-reported outcomes at initial interview (average 15.5 months post-treatment) and 6-month follow-up (average 21.5 months post-treatment) will be presented.

Conclusions: The majority of participants’ self-reported benefits in general health, fatigue level, mobility and exercise level following CCSVI “liberation” treatment are short term and decline the longer the time period from treatment. Interestingly, while this self perception of impact of the therapy declines over time, this perception is less true when patients are asked to rate the overall procedure (PR). This may reflect psychosocial and interpersonal issues rather than be a true measure of treatment outcome.

L. Kipp, I. Yee, A. D. Sadovnick, T. Greenwood, M. de Lemos, G. Keyes, L. Machan, A. Traboulsee (Vancouver, CA)

Source: ECTRIMS (24/09/13)

Clinical trial into MS 'liberation treatment' cancelled due to lack of participants(10/09/13)

Canadians who were among multiple sclerosis patients waiting to take part in a clinical trial into the so-called liberation treatment were disappointed on Monday by news that the trial was cancelled.

The Saskatchewan government was told that the Albany Medical Centre in New York has stopped its trial into the effectiveness of angioplasty in treating CCSVI (chronic cerebro-spinal venous insufficiency) and relieving symptoms of multiple sclerosis. The treatment involves opening blocked neck veins.

There were 86 planned participants from Saskatchewan -- a province home to one of the highest rates of M.S. sufferers compared to the rest of Canada. The province had committed up to $2.2 million to have its patients participate in the Albany study.

Clinical trial lead Dr. Gary Siskin told Saskatchewan’s Ministry of Health that he wasn’t able to meet the overall target enrolment needed for the study to meet U.S. government requirements for a clinical trial.

Siskin told CTV News that he’s “very disappointed” the trial had to be cancelled.

He spoke about the difficulty in getting people to enrol in the study, as participants seemed reluctant because of the 50/50 chance that they would receive a placebo treatment instead of the real thing.

Siskin, an interventional radiologist, has treated several hundred patients outside of the trial -- but he stopped in favour of doing formal research into the treatment. His was the only FDA-approved study for CCSVI therapy.

He says despite the setback, his interest in CCSVI is undeterred. "This in no way diminishes my interest in CCSVI," he said.

He told CTV News that in his opinion, narrowed veins in patients with symptoms of MS "is a diagnostic entity” and is “real.”

"I've seen too many people who have responded to treatment to say they are making it up," Siskin said.

Saskatchewan Health Minister Dustin Duncan also expressed disappointment at the news for the approximately 3,500 MS sufferers in his province.

“Our government wants to do everything it can to search for answers and further the science for people with MS,” said Duncan. “That’s why Saskatchewan was supportive of this trial and will continue to be supportive of research that may provide answers for those with MS and their families.”

Source: CTV News © 2013 Bell Media (10/09/13)

Reasearchers split on theory that MS is vascular disease(15/08/13)

Hamilton researchers believe they have debunked a radical new theory that multiple sclerosis is a vascular disease which can be treated by opening up blocked veins.

But a British Columbia researcher says his work has opposite results to the study affiliated with McMaster University, St. Joseph's Healthcare and Hamilton Health Sciences published online Wednesday by the medical journal PLOS ONE.

"I don't think it's the final word," said Dr. Anthony Traboulsee who is also trying to determine if there is any truth to the controversial theory called chronic cerebrospinal venous insufficiency (CCSVI) discovered by Italian vascular surgeon Dr. Paolo Zamboni in 2008.

The much-anticipated Hamilton study found no evidence of abnormalities in the neck and deep cerebral veins of MS patients compared with healthy people with no history of the debilitating autoimmune disease or any neurological condition.

"The results are pretty unequivocal," said Dr. Ian Rodger, principal investigator and professor emeritus at McMaster. "It was quite stunning. The results are black and white. It was pretty compelling to see."

But Traboulsee says similar research being done in Vancouver, Saskatoon and Regina and expected to be published by the end of the year doesn't support the findings.

"It will be different than the Hamilton results," he said. "We have found venous narrowings."

Both studies used ultrasound and magnetic resonance imaging (MRI) to look for narrowed veins. But the BC-led study also used catheter venography to test the blood flow in the veins which is considered the most accurate test to find blockages. The invasive test involves inserting a catheter and injecting dye to get images of the veins.

"They did a great job just not good enough for me," said Traboulsee of the Hamilton study. "They've addressed it can't be determined with MRI and ultrasound but they haven't addressed if it exists because they didn't use the gold standard (test)."

Zamboni believes the veins draining blood from the brain are blocked and leaking in MS patients. This allows iron to leak into brain tissue and he thinks the buildup causes many symptoms of MS.

Zamboni treats it with what he calls the "liberation procedure, " which is inserting stents or balloons to open the malformed and blocked veins.

Source: thespec.com © COPYRIGHT METROLAND 2013 (15/08/13)

CCSVI is not associated with cognitive impairment in multiple sclerosis(18/07/13)

Chronic cerebrospinal venous insufficiency (CCSVI) has been reported in multiple sclerosis (MS) yet its significance in relation to cognitive function is undetermined.This study measured the association between the presence and severity of CCSVI and cognitive impairment in patients with MS.

Methods: CCSVI was assessed using extra-cranial and trans-cranial Doppler sonography in 109 MS patients (79 with relapsing-remitting, 23 with secondary-progressive and 7 with primary-progressive disease subtype). A subject was considered CCSVI-positive if >=2 venous hemodynamic criteria were fulfilled.

The Minimal Assessment of Cognitive Function in MS (MACFIMS) battery was administered assessing the full spectrum of cognitive domains known to be affected by MS. Depression was quantified using the Beck Depression Inventory Fast Screen (BDIFS).

Partial correlations, analysis of variance (or covariance) and linear regression were used to examine the hypothesis that CCSVI status is related to cognition or depression after controlling for education and gender.

Results: There were 64 (58.7%) patients who were considered CCSVI-positive. The regression models predicting venous hemodynamic insufficiency severity score were not statistically significant for any of the MACFIMS predictor variables.

The analysis of variance tests showed a significant effect of CCSVI-positive diagnosis on cognitive ability in only one of the 10 MACFIMS outcomes, and that one was in the opposite direction of the tested hypothesis. There was no correspondence between CCSVI diagnosis and depression, as measured by the BDIFS.

Conclusions: We find no evidence of an association between the presence and severity of CCSVI with cognitive impairment and depression in patients with MS.

Author: Ralph HB BenedictBianca Weinstock-GuttmamKaren MarrVesela ValnarovCheryl KennedyEllen CarlChristina BrooksDavid HojnackiRobert Zivadinov
Credits/Source: BMC Medicine 2013, 11:167

Source: 7thSpace Interactive © 2013 7thSpace Interactive (18/07/13)

Chronic cerebrospinal venous insufficiency: masked multimodal imaging assessment(15/07/13)

Abstract

Background: Chronic cerebrospinal venous insufficiency (CCSVI) was implicated in the pathophysiology of multiple sclerosis (MS).

Objective: We evaluated neurosonography (NS), magnetic resonance venography (MRV), and transluminal venography (TLV) in subsets of MS patients drawn from a single-center, prospective, case-control study of 206 MS and 70 non-MS volunteers.

Methods: As previously reported, findings on high-resolution B-mode NS imaging with color and spectral Doppler of the extracranial and intracranial venous drainage consistent with CCSVI were similar among MS and non-MS volunteers (3.88% vs 7.14%; p = 0.266). Ninety-nine MS participants consented to intravascular contrast-enhanced 3D MRV to assess their major systemic and intracranial venous circulation, and 40 advanced to TLV that included pressure measurements of the superior vena cava, internal jugular, brachiocephalic, and azygous veins.

Results: NS findings and MRV patterns were discrepant for 26/98 evaluable subjects, including four with abnormal findings on NS that had normal venous anatomy by MRV. In no instance were TLV pressure gradients indicative of clinically significant functional stenosis encountered. The three imaging approaches provided generally consistent data with discrepancies referable to inherent technique properties.

Conclusions: Our findings lend no support for altered venous outflow dynamics as common among MS patients, nor do they likely contribute to the disease process.

Staley A Brod1, Larry A Kramer2, Alan M Cohen2, Andrew D Barreto1, Thanh-Tung Bui1, James R Jemelka1, Kelly Ton1, John W Lindsey1, Flavia Nelson1, Ponnada A Narayana2 Jerry S Wolinsky1

1Department of Neurology, University of Texas Health Science Center at Houston, USA

2Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, TX, USA

Source: Multiple Sclerosis Journal Copyright © 2013 by SAGE Publications (15/07/13)

Don't dismiss CCVSI yet, expert says(11/06/13)

Doctors should encourage their patients with multiple sclerosis (MS) who are curious about chronic cerebrospinal venous insufficiency (CCVSI) to "hold off" getting the related procedure until results are in from what some view as a potentially definitive trial on the merits of this intervention, according to Alexander Rae-Grant, MD, neurologist and chair, Neurological Education, Cleveland Clinic, Ohio.

The multicenter trial, led by Anthony Traboulsee, MD, assistant professor, neurology, and medical director, University of British Columbia Hospital MS Clinic, Vancouver, Canada, will compare venous angioplasty with a sham procedure in patients with MS. The theory behind CCSVI is that blocked veins in the head and neck result in excessive iron in the brain and may contribute to the disease process in MS.

"Until you subject this to a well-designed, randomized trial in which it's compared to a sham procedure, and you're sure that you've excluded the possibility that there isn't a therapeutic effect because of small sample size, you really don't know" if it works or not, said Dr. Rae-Grant told Medscape Medical News here during an interview.

He spoke during a symposium on Controversial Unconventional Therapies at the 5th Cooperative Meeting of the Consortium of MS Centers (CMSC) and the Americas Committee for Treatment and Research in MS (ACTRIMS).

Prove Once and for All?

The Canadian trial should "prove the point once and for all" in terms of the effect of treatment, said Dr. Rae-Grant. "One way or the other, the Canadian trial will be the ultimate answer in terms of therapeutics, not in terms of whether there are vascular abnormalities, but in terms of whether this therapeutic intervention is something we should be looking to."

So far, said Dr. Rae-Grant, there have really been only 2 treatment trials: the initial positive trial in 2009, led by Paolo Zamboni, MD, that launched the controversy surrounding the validity of the procedure, and a subsequent negative but "fairly small" trial.

The Prospective Randomized Endovascular Therapy in MS (PREMiSe) enrolled 10 patients in a phase 1 safety trial and 20 patients with active relapsing MS in a phase 2 trial, which randomly assigned patients to treatment or placebo. According to the results released earlier this year at the American Academy of Neurology 65th Annual Meeting, the study looked at whether the procedure was safe or associated with adverse events at 24 hours and 1 month. The primary endpoint was venous outflow restoration at month 1, as well as MRI disease activity and relapse rate.

There were no safety issues at either time point, noted the study's co-principal investigator, Robert Zivadinov, MD, PhD, professor, neurology, University of Buffalo, New York, but for venous outflow restoration, this endpoint was met only in phase 1. In phase 2, venous outflow did not improve with the actual or with the sham procedure.

"The main outcome of the study was very surprising to us," Dr. Zivadinov told Medscape Medical News at that time. Of the 9 patients who underwent venoplasty, 5 had increased disease activity after intervention, with a total of 19 new gadolinium-enhancing lesions and 17 new T2 lesions, vs 3 total new lesions in the sham procedure group. There were 4 relapses in treated patients vs 1 in the sham group. Treatment groups did not differ for quality of life, with all patients reporting improvements.

"So there was a clear-cut increase of disease activity in treated people," he said. "In people with active relapsing MS, I don't think this treatment is appropriate and could lead to potential harm." The researchers will be following these patients for more long-term results.

At the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), results of the COSMO trial, a case-control observational study carried out by Italian researchers, showed the incidence of CCSVI was low and did not differ between groups of patients with MS, those with other neurologic diseases, or healthy controls. Another observational study, also by Italian researchers, looking at the safety of venoplasty to correct CCSVI suggested that the procedure was not without risk, with serious adverse events occurring in about 3% of patients who elected to be treated.

At that time, Giancarlo Comi, MD, director of the Department of Neurology and Institute of Experimental Neurology at the Scientific Institute and University Vita-Salute San Raffaele in Milan, Italy, concluded that given their findings and those in the venoplasty study, further interventional studies were not needed. "I think that because there is no rationale for a trial exploring the efficacy of liberation therapy, I personally think it's absolutely inappropriate that the government finances any type of investigation or research."

However, Dr. Zivadinov said the low incidence of CCVSI as seen in COSMO did not agree with their own experience using a larger variety of imaging modalities, including invasive techniques. The fact that they saw an increase in disease activity argues that venoplasty for CCSVI is having an effect in the brain, even though it was a negative effect.

"I strongly believe we should have further research on CCSVI as a concept, maybe switching from the MS population to more normal populations — aging and healthy people who have this problem, and understand what it means," he said. "It's not unique to MS, and for sure, the endovascular treatment is not an option that should be done on a clinical basis."

Baby With the Bathwater?

Still addressing delegates during the joint CMSC/ACTRIMS meeting, Dr. Rae-Grant emphasized the importance of not dismissing the possibility that CCSVI really does work.

"What if we're missing something? What if there is a vascular piece to this? What if there's a subset in which this means something? What if we're throwing the baby out with the bathwater?" And what if, down the road, it becomes clear that "we missed it," he said.

Neurologists should not be dismissive of a therapy that a good proportion of their patients are interested in and may even want to try, he added. "We can't throw it out; we don't have the data yet to dismiss it."

It's also important to "avoid concerns that there is a conspiracy" of industry and scientists to sabotaging the research, said Dr. Rae-Grant.

Instead, it's important to take "a considered reasonable approach" and find "a place in between," said Dr. Rae-Grant.

After a flurry of interest in what came to be called by some "liberation therapy," anecdotal evidence suggests that the demand for information on this intervention has leveled off in the last 3 years, possibly because of increasing questions surrounding its efficacy, said Dr. Rae-Grant.

The $6 million Canadian trial, a collaborative effort between the Canadian Institutes of Health Research, the MS Society of Canada, and the relevant provinces, will enroll 100 patients with MS at 4 centers (Vancouver, Winnipeg, Montreal, and Quebec City). The patients will be randomly assigned to undergo venoplasty or a sham treatment. Each group will cross over to the other treatment after a year.

Recruitment has not yet begun at her center, said Ruth Ann Marrie, MD, PhD, University of Manitoba, Winnipeg, although she and her colleagues are gathering information on what factors are linked to the decision to have the venoplasty procedure.

Disease Progression Linked to Procedure

At the meeting, she presented results from a survey showing that, contrary to what many expected, patients with MS who have comorbid conditions are less likely to have the procedure.

The study, carried out by the Alberta Multiple Sclerosis Initiative (TAMSI), included 683 participants (77.7% female; 64.2% with relapsing-remitting MS; mean age, 47.9 years). Of these, 20.2% reported having had CCSVI treatment.

Of the sample, 34.1% reported no comorbid conditions, while 28.7% reported 1, 19.5% reported 2, 9.5% reported 3, and 8.2% reported 4 or more. The most commonly reported comorbid conditions were depression (27.7%), hyperlipidemia (15.8%), hypertension (15.7%), and migraine (15.1%).

Individuals with any comorbidity were less likely (odds ratio, 0.68; 95% confidence interval, 0.46 - 0.99) to report undergoing venous angioplasty than those with no comorbidity, and the likelihood of having the procedure decreased with increasing number of comorbid conditions. The type of comorbidity did not seem to matter in the decision to have the operation.

A progressive disease course, greater disability, older age, and male sex were associated with greater frequency of venous angioplasty (all P < .05). Adjusting for these factors did not change the association between venous angioplasty and any comorbidity or number of comorbid conditions.

The researchers now plan to try to find out where patients with MS go to get the procedure, how much they spend on it, and whether they feel it was beneficial, said Dr. Marrie.

In the past year Dr. Rae-Grant has given talks for Biogen and Teva Neurosciences.

Primary Source: 5th Cooperative Meeting of the Consortium of MS Centers (CMSC) and the Americas Committee for Treatment and Research in MS (ACTRIMS). Controversial Unconventional Therapies. Presented May 30, 2013. Abstract #DX45. Presented May 30, 2013.

Source: Medscape News Today Copyright © 1994-2013 by WebMD LLC (11/06/13)

MS patients did not benefit from CCSVI intervention, landmark pilot study of 'liberation treatment' finds(15/03/13)

The first controlled clinical trial to test the safety and efficacy of interventional endovascular therapy on the symptoms and progression of multiple sclerosis has found that the intervention, sometimes called the “liberation treatment,” which has attracted intense interest in the global MS community, does not improve patient outcomes. In a few cases, the treatment made symptoms worse.

University at Buffalo researchers will present their results in an “Emerging Science” poster session March 20 at the annual American Academy of Neurology meeting in San Diego. They discuss the findings in this video: http://youtu.be/94gLM4QlU_A

The Prospective Randomized Endovascular Therapy in MS (PREMiSe) trial is believed to be the first prospective randomized double-blinded, controlled study of balloon angioplasty for MS being performed with Institutional Review Board approval in a rigorous fashion in the U.S. with significant safeguards in place to ensure careful determination of risks and benefits. All screening, diagnostic, interventional and follow-up procedures and visits were performed at no cost to the patients.

The study’s key findings are that while the treatment is safe and was not associated with serious adverse events, it did not provide sustained improvement in MS patients.

Based on their findings, the UB researchers’ primary message to MS patients and their doctors is that endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) should only be done in the context of randomized, double-blinded, controlled studies like PREMiSe.

“Our strong recommendation to patients and to practitioners, who have, in earnest, been seeking betterment for their disease and a cure for MS is that they should instead consider enrolling in trials, rather than undergoing these procedures on a fee-for-service basis,” said Adnan Siddiqui, MD, associate professor of neurosurgery, UB School of Medicine and Biomedical Sciences and PREMiSe principal investigator.

Since 2009, approximately 30,000 MS patients worldwide have undergone the endovascular procedure that opens blockages in veins that drain blood from the brain. The vast majority of these procedures were done on a fee-for-service basis, and not as part of clinical trials.

The idea for PREMiSe took shape as a collaboration between the UB Department of Neurosurgery and the UB Department of Neurology at the suggestion of L. Nelson Hopkins, MD, SUNY Distinguished Professor and chair of neurosurgery, who is co-principal investigator.

The researchers at the UB School of Medicine and Biomedical Sciences were “uniquely situated” to study this important question, Siddiqui said. “Here at UB, some of the world’s leaders in stroke intervention, in the Department of Neurosurgery, are located right next door to some of the world leaders in multiple sclerosis in the UB Department of Neurology and in imaging at the Buffalo Neuroimaging Analysis Center (BNAC),” he said.

Researchers at UB’s BNAC have published or presented more than 25 studies on CCSVI and its relationship to neurological diseases including MS.

“Our findings over the last three years have indicated that CCSVI is more prevalent in MS patients than in healthy controls but the cause or consequence of these venous abnormalities has not been established,” said Robert Zivadinov, MD, PhD, FAAN, UB professor of neurology, director of the BNAC and co-principal investigator on the study.

The endovascular intervention is based on the hypothesis that the narrowing in the large veins in the neck and chest might cause improper drainage of blood from the brain, resulting in eventual injury to brain tissue, Zivadinov explained. It was thought that angioplasty -- treatment commonly used by cardiologists and other endovascular surgeons to treat atherosclerosis -- may remedy the blockages.

“The whole idea of PREMiSe was to find out if opening up the veins that drain blood from the brain and the spinal cord would improve outcomes for MS patients,” said Bianca Weinstock-Guttman, MD, UB professor of neurology and director of UB’s MS Center.

“What we found was rather surprising and unexpected,” Siddiqui said. “It was quite the opposite of what we originally expected to find. The study showed that endovascular treatment of stenosed veins had no effect in MS patients.”

A total of 30 MS patients, most of whom were from Western New York, were studied in the PREMiSe trial. Phase 1 was a safety trial, involving 10 MS patients and Phase II involved a total of 20 MS patients, who were randomized to receive treatment or placebo.

The UB researchers found no difference in clinical symptoms, brain lesions as determined on MRIs or quality of life outcomes between MS patients who underwent balloon angioplasty to correct CCSVI and those who did not receive the treatment.

The researchers stressed that the UB study was small and that larger studies should be undertaken and should be conducted in a rigorous fashion with IRB approval, as was PREMiSe.

“This is not the last word on this endovascular treatment for MS,” Siddiqui concluded. “This is the first word because this was the first double-blinded, randomized sham-controlled trial on the subject. However, these findings lead us to caution strongly against the general acceptance of this invasive procedure for MS patients.”

In addition to Siddiqui, Zivadinov, Weinstock-Guttman and Hopkins, Ralph H.B. Benedict, PhD, UB professor of neurology and Elad Levy, MD, UB associate professor of neurosurgery contributed significantly to the study design and interpretation of the findings. Other UB co-investigators are Yuval Karmon, Jihnhee Yu, Karen Marr, Vesela Valnarov, Murali Ramanathan, Deepa P. Ramasmamy, Kresimir Dolic, David Hojnacki, Ellen Carl and Cheryl Kennedy.

The study was funded by Kaleida Health, UB, the Direct MS Foundation (Canada), Volcano Corp, ev3 Corp and many individuals who have a personal stake in MS research.

Source: University Of Buffalo © 2013 University at Buffalo (15/03/13)

First Published Results from National MS Society-Funded CCSVI Study(05/03/12)

Researchers at the University of Texas Health Science Center at Houston have published their first results from a National MS Society-supported study investigating CCSVI (chronic cerebrospinal venous insufficiency) using several different imaging techniques to examine blood outflow from the brain. For the first portion of the study, the team, purposefully unaware of any participant’s diagnosis, used Doppler ultrasound to investigate venous drainage in 276 people with and without MS. They report much less prevalence than previously reported by other groups and no statistical difference between those with MS and those without MS. The study, by Andrew D. Barreto, MD, Jerry S. Wolinsky, MD, and colleagues, was published early online in the Annals of Neurology.

Background: In June 2010, the National MS Society (USA) and the MS Society of Canada committed over $2.4 million to support seven new research projects on the role of CCSVI in MS, a postulated abnormality of blood drainage from the brain and spinal cord in MS originally reported by Paolo Zamboni, MD (University of Ferrara, Italy). In the interim since the Society-funded studies began, there have been conflicting results reported on the prevalence of CCSVI in MS, and the emergence of reports of CCSVI in people who do not have MS. There has also been variability in the methods used to study this phenomenon, including by Dr. Zamboni.

The Society-supported projects examine the structure and function of veins draining the brain and spinal cord in people representing a spectrum of MS types, severities and durations, and compare them to structure and function of veins in people with other diseases and healthy volunteers. The studies incorporate high standards of experimental blinding and controls designed to provide objective results.

One of the seven teams has now published first results from a portion of its comprehensive study at the University of Texas Health Science Center at Houston. Dr. Wolinsky assembled an expert team with diverse specialties to increase understanding of CCSVI. They tested several imaging methods including ultrasound, the relatively noninvasive imaging techniques using an MRI machine and intravenous contrast agent, and direct radiologic investigation of the major veins by direct injection of veins with radio-opaque contrast. The goal was to validate a reliable diagnostic approach and to demonstrate that CCSVI is specific to MS and contributes to disease activity.

The collaborators in this project, all from University of Texas Health Science Center at Houston, include the Chief of Vascular Interventional Radiology (Alan M. Cohen, MD) the director of the neurosonography laboratory (Dr. Barreto), the Chief of Cardiovascular MRI (Larry A. Kramer, MD), and expert MS neurologists (Drs. Wolinsky, Staley A. Brod, John W. Lindsey and Flavia Nelson).

The study: This was a single-center study that enrolled MS and non-MS volunteers at the University of Texas Health Science Center at Houston. MS participants were 18 to 65 years. Of 206 recruited, 128 had relapsing-remitting MS, 48 had secondary-progressive MS, 15 had primary-progressive MS, 12 had clinically isolated syndrome, and 3 had progressive relapsing MS. There were 70 non-MS volunteers, including 37 with other neurological diseases, 22 with cerebrovascular diseases, and 11 healthy controls.

For the first portion of this comprehensive study, the team focused on using Doppler ultrasound to evaluate venous drainage in a blinded fashion (meaning neither the technician performing the scan, nor the professional reading the scan, knew the disease status of the participant). The team utilized a standard Doppler ultrasound machine rather than purchasing the specific machine used by Dr. Zamboni’s team. The protocol used to evaluate extracranial and intracranial vessels using criteria consistent with those originally published by Dr. Zamboni (J Neurol Sci 2009;282:21-27) is described in detail in the published paper.

They report that 82 out of 276 (29.7%) participants fulfilled at least one of five criteria for anomalous venous outflow proposed by Dr. Zamboni; 13/276 (4.7%) fulfilled two criteria consistent with CCSVI; none fulfilled more than 2 criteria. CCSVI was found in 7.14% of non-MS participants and in 3.88% of MS participants, a difference that was not statistically different. There was no significant difference between MS subgroups, and also no significant differences between MS and non-MS subjects for measures of cross-sectional areas of the internal jugular veins or for venous flow rates.

The team concludes that they find less CCSVI than previously reported by other groups, and that their findings do not support the idea that CCSVI is causally related to MS. They are now focusing on whether ultrasound can be complemented or supplanted by MRV and/or transluminal venography. The authors describe some of this study’s limitations. First, it is from a single center, and they did not use multiple trained sonographers and image interpreters. However, they point out that they also obtained alternative neuroimaging results which were blinded to the results reported from ultrasound, and these results will be published in a future paper. The team did not test whether the neurosonologist remained blinded to the diagnostic status of participants, but note that all subjects were instructed not to discuss medical history. They also did not assess venous anomalies such as dysfunctional valves, which were not described in the original CCSVI articles but were added to consensus protocols after this study began. Finally, they did not have participants repeat testing, so it is not known whether abnormal findings would be reproduced at a later point.

Comment: This thorough study adds to a growing body of evidence exploring the phenomenon of CCSVI. Additional results expected from this and other teams in coming months should shed further light on CCSVI and its implications for people who live with MS and for advocacy organizations such as the National MS Society, whose research focuses on speeding research toward stopping MS, restoring function, and ending MS forever.

Source: Multiple Sclerosis Copyright © 2013 Multiple Sclerosis (05/03/13)

What went wrong? The flawed concept of cerebrospinal venous insufficiency(04/03/13)

Abstract

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis (MS), coining the term of chronic cerebrospinal venous insufficiency (‘CCSVI’).

The diagnosis of ‘CCSVI’ is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration.

The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of ‘CCSVI’ could alleviate MS. Many investigators tried to replicate Zamboni’s results with duplex sonography, magnetic resonance imaging, and catheter angiography.

The data obtained here do generally not support the ‘CCSVI’ concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the ‘CCSVI’ concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment.

In our view, there is currently no basis to diagnose or treat ‘CCSVI’ in the care of MS patients, outside of the setting of scientific research.

This work was supported by the German Research Council (DFG Exc 257 to FP). The MS Center Amsterdam is funded by the Stichting MS Research, Voorschoten, The Netherlands.

Full article 

José M Valdueza, Florian Doepp, Stephan J Schreiber, Bob W van Oosten, Klaus Schmierer, Friedemann Paul and Mike P Wattjes

Source: Journal of Cerebral Blood Flow And Metabolism © 2013 International Society for Cerebral Blood Flow & Metabolism (04/03/13)

Chronic cerebrospinal venous insufficiency in multiple sclerosis: a highly prevalent age-dependent phenomenon(14/02/13)

Abstract (provisional)

Background
This study aimed to investigate the prevalence and clinical relevance of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients and healthy controls using extra- and intracranial colour Doppler sonography.

Methods
We examined 146 MS patients, presenting with a clinically isolated syndrome, relapsing-remitting, secondary progressive, or primary progressive MS, and 38 healthy controls. Sonographic examination was performed according to Zamboni's protocol and was performed by three independent sonographers. The results of sonographic examination were compared with clinical and demographic characteristics of the patients.

Results
CCSVI, defined as the presence of at least two positive Zamboni's criteria, was found in 76% of MS patients and 16% of control subjects. B-mode anomalies of internal jugular veins, such as stenosis, malformed valves, annuli, and septa were the most common lesions detected in MS patients (80.8%) and controls (47.4%). We observed a positive correlation between sonographic diagnosis of CCSVI and the patients' age (p=0.003). However, such a correlation was not found in controls (p=0.635). Notably, no significant correlations were found between sonographic signs of CCSVI and clinical characteristics of MS, except for absent flow in the jugular veins, which was found more often in primary (p<0.005) and secondary (p<0.05) progressive patients compared with non-progressive patients. Absent flow in jugular veins was significantly correlated with patients' age (p<0.0001).

Conclusions
Sonographically defined CCSVI is common in MS patients. However, CCSVI appears to be primarily associated with the patient's age, and poorly correlated with the clinical course of the disease.

The complete article is available as a provisional PDF The complete article is available as a provisional PDF.

Roberta Lanzillo, Marcello Mancini, Raffaele Liuzzi, Orlando Di Donato, Elena Salvatore, Valentina Maglio, Giovanni Vacca, Luca Amato, Gennaro D¿Anna, Arturo Brunetti and Vincenzo Brescia Morra

Source: BMC Neurology © 2013 BioMed Central Ltd (14/02/13)

Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of 462 cases(25/01/13)

Abstract

Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI.

The objective of the study is to evaluate the outcome and safety of ET in Italian MS patients.

Italian MS centers that are part of the Italian MS Study Group were all invited to participate to this retrospective study.

A structured questionnaire was used to collect detailed clinical data before and after the ET.

Data from 462 patients were collected in 33 centers.

ET consisted of balloon dilatation (93 % of cases) or stent application.

The mean follow-up duration after ET was 31 weeks. Mean EDSS remained unchanged after ET (5.2 vs. 4.9), 144 relapses occurred in 98/462 cases (21 %), mainly in RR-MS patients. Fifteen severe adverse events were recorded in 3.2 % of cases.

Given the risk of severe adverse events and the lack of objective beneficial effects, our findings confirm that at present ET should not be recommended to patients with MS.

Ghezzi A, Annovazzi P, Cocco E, Coarelli G, Lugaresi A, Rovaris M, Patti F, Capello E, Rodegher ME, Moiola L, Malucchi S, Salemi G, De Rossi N, Provinciali L, Perini P, Bergamaschi R, Scarpini E, Lus G, Gallo A, Tola MR, Amato MP, Rottoli MR, Bianchi A, Comi G; The MS Study Group-Italian Society of Neurology.

Source: Neurol Sci. 2013 Jan 25. & Pubmed PMID: 23354606(25/01/13)

Percutaneous transluminal angioplasty for treatment of CCSVI in MS patients(14/12/12)

The more popularly known 'Liberation procedure' for treatment of venous stenoses (CCSVI) in the brain of MS sufferers

Multiple sclerosis (MS) is an inflammatory disease of the nervous system and the most frequent cause of neurological disability in young adults. Myelin, the material that wraps around and protects the nerves becomes damaged and this results in scarring and the formation of scar-like plaques.

MS is considered to be an immune-mediated disease in which the person's own immune system attacks the nervous system and most of the current drug therapies are based on this hypothesis.

However, a new theory has been recently proposed with a suggestion that impaired blood flow in the veins draining the central nervous system, so called chronic cerebrospinal venous insufficiency (CCSVI), may play a role in the cause of MS. CCSVI is thought to be congenital and it may result in iron deposits which in turn trigger the immune system to attack the central nervous system thus damaging the myelin. The proposed treatment for CCSVI is balloon angioplasty which entails the widening of narrowed (stenosed) veins, the commonly named 'liberation procedure'. This theory has gained a lot of attention via the Internet, mainly among the patients' community, and the increased interest by the media has further enhanced the expectations of people suffering with MS. We searched the relevant literature but found no studies that matched the criteria of methodological quality necessary for their inclusion in this review.

There is currently no evidence to support or refute the efficacy and the safety of angioplasty for CCSVI in people with MS. Well-designed and robust studies are warranted.

Abstract

Background

Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. The most widely accepted hypothesis regarding its pathogenesis is that it is an immune- mediated disease. It has been hypothesised more recently that chronic venous congestion may be an important factor in the pathogenesis of MS. This concept has been named 'chronic cerebrospinal venous insufficiency' (CCSVI) and is characterised by stenoses of either the internal jugular or azygos veins, or both. It is suggested that these stenoses restrict the normal blood flow from the brain, causing the deposition of iron in the brain and the eventual triggering of an auto-immune response. The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain thereby alleviating some of the symptoms of MS.

Objectives

To assess the effects of percutaneous transluminal angioplasty for the treatment of CCSVI in people with MS.

Search methods

We searched the following databases up to June 2012: The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register, CENTRAL in The Cochrane Library 2012, Issue 5, MEDLINE (from 1946), EMBASE (from 1974), and reference lists of articles. We also searched several online trials registries for ongoing trials.

Selection criteria

Randomised controlled trials assessing the effects of percutaneous transluminal angioplasty in adults with multiple sclerosis, that have been diagnosed to have CCSVI.

Data collection and analysis

Our searches retrieved 159 references, six of which were to ongoing trials. Based on assessment of the title or abstract, or both, we excluded all of the studies, with the exception of one which was evaluated following examination of the full text report. However, this study also did not meet our inclusion criteria and was subsequently excluded.

Main results

No randomised controlled trials met our inclusion criteria.

Authors' conclusions

There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. Clinical practice should be guided by evidence supported by well-designed randomised controlled trials: closure of some of the gaps in the evidence may be feasible at the time of completion of the six ongoing clinical trials.

Esther J van Zuuren, Zbys Fedorowicz, Eugenio Pucci, Vanitha A Jagannath, Edward W Robak

Source: The Cochrane Library Copyright © 1999–2012 John Wiley & Sons, Inc (14/12/12)

Largest CCSVI study fails to support MS theory(15/10/12)

Largest CCSVI study fails to support MS theory The largest study to date testing the venous-obstruction theory of multiple sclerosis failed to support it, leading the Italian Multiple Sclerosis Society to declare the theory dead.

Reported here by leaders of the group, known by its Italian abbreviation AISM, the study of nearly 2,000 individuals with blinded central imaging analysis found the condition in only about 3% of MS patients and in only slightly fewer healthy controls or patients with other neurological conditions.

Key data were released at a press briefing by principal investigator Giancarlo Comi, MD, of the University of Milan, and other study leaders in advance of Comi's formal presentation, scheduled for Saturday at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.

They characterized the study as the largest yet conducted on the so-called chronic cerebrospinal venous insufficiency theory (CCSVI), advanced in 2009 by Paolo Zamboni, MD, of the University of Ferrara in Italy.

The CCSVI theory quickly took the MS community by storm, leading many patients to seek venous angioplasty and stenting procedures in hope of obtaining relief or even a cure, as Zamboni and some other vascular surgeons claimed was possible.

But the theory also drew substantial criticism, especially after numerous other researchers were unable to reproduce Zamboni's original findings of 100% presence of CCSVI in MS patients and 0% in non-MS controls. Some groups were unable to detect CCSVI in more than a small fraction of patients, while others found that it was relatively common but without specificity for MS.

In the new study, sponsored by AISM and called CoSMo, ultrasound analyses were performed on 1,874 individuals at 35 clinics throughout Italy. A total of 107 were subsequently excluded because of technical problems with the images or because participants were found not to meet the specified inclusion criteria (such as age or disease duration).

The analysis included 1,165 patients with MS (including 104 with clinically isolated syndrome), 376 healthy controls, and 226 patients with other neurological diseases.

All participants were evaluated for MS under standard diagnostic criteria.

Initial diagnoses of CCSVI or its absence were made by the sonographers at each clinic, who had received special training in cerebral venous imaging. Some of them had previously trained in Zamboni's clinic. The local sonographers were blinded to participants' diagnoses.

The local clinic diagnoses were then reviewed by one of three blinded central imaging experts: Erwin Stolz, MD, of Justus-Liebig University in Giessen, Germany; Massimo Del Sette, MD, chairman of the Italian Society of Neurosonology and Cerebral Hemodynamics; and Giovanni Malferrari, MD, chairman of the Italian Interdisciplinary Neurovascular Society.

When there was disagreement between the local and central readers, all three of the central readers reviewed the images, with the opinion shared by two counted as the final diagnosis. Analyses in the two-year study were completed last month.

The prevalence of CCSVI as determined under this process was as follows in the three groups of participants:

MS patients: 3.26% (95% CI 2.38% to 4.45%)
Healthy controls: 2.13% (95% CI 1.10% to 4.14%)
Other neurological disorders: 3.10% (95% CI 1.58% to 6.44%)
On the basis of these small values, and the lack of significant (P<0.05) differences between them, the AISM issued a statement declaring that "CCSVI is not a disease connected to multiple sclerosis."

Moreover, it continued, "for people affected by MS, there is no need to carry out additional tests to diagnose CCSVI, nor is vein surgery required."

The AISM is the first national MS society to make such a conclusive determination. In the U.S. and Canada, research on CCSVI commissioned by the major organizations in those countries is still under way, and no similar declaration is likely until those studies are completed.

Comi said that Zamboni had been invited to participate in CoSMo, and did for a time. But he quit before all the sonographers had been trained, objecting to multiple aspects of the study design that he believed would bias the results against finding a relationship between CCSVI and MS.

Stolz said that the sonographers were not trained specifically in Zamboni's method, but that he and others who had conducted the training had extensive experience in cerebrovascular ultrasound imaging.

He noted that this had also been the case with other groups that failed to replicate Zamboni's findings, despite having been trained in his clinic. Stolz added that a diagnostic procedure is only meaningful if it can be taught and used reliably by other experienced practitioners.

"If it is not repeatable, it has no value," he said.

Comi said that other researchers would be permitted to conduct their own evaluations of sonograms collected during the study, as long as the blinding to clinical diagnosis was maintained.

Initial diagnosis of CCSVI in the individual clinics in fact varied widely, Comi said. At one clinic, the condition was found in 60% of participants; in two others, the prevalence was 0%.

Overall, the detection rate at the initial step was considerably higher than after central review: 15.9% among MS patients, 12% in healthy controls, and 15% in patients with non-MS neurological disorders. Comi noted that even at these higher prevalences, there was still no meaningful difference between MS patients and other participants.

He also indicated that central reviewers rarely overruled the local clinic sonographers on negative diagnoses. In only 3% of cases in which the local sonographer found no CCSVI did the central reviewers say it was present.

Agreement was poorer for positive diagnoses. Central reviewers overturned 89% of the CCSVI diagnoses made by local sonographers.

Stolz attributed the lack of concordance on positive findings to the fact that "local sonographers are not on the moon." He suggested that seeing participants, and noting any physical or mental impairments, could have biased them toward diagnosing CCSVI.

Gianluigi Mancardi, MD, head of the AISM's scientific committee and co-principal investigator on the study with Comi, said he hoped the study would put the CCSVI theory permanently to rest.

"In our opinion, this is the final answer," he said.

Noting that the AISM had spent some $2 million to conduct the CoSMo study, he said the group now hoped to direct its attention to more fruitful areas of research in MS and its treatments.

The study was funded by the Italian Multiple Sclerosis Society.

Comi reported consulting fees for participating on advisory boards from Novartis, Teva, sanofi-aventis, Merck Serono, and Bayer Schering; lecture fees from Novartis, Teva, sanofi-aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation. Mancardi reported honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Schering, Biogen Idec, sanofi-aventis, Novartis, and Merck Serono.

Stolz declared that he had no relevant financial interests.

Primary source: European Committee for Treatment and Research in Multiple Sclerosis

Source reference: Comi G, et al "Chronic cerebro-spinal venous insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo study" ECTRIMS 2012; Abstract 167.

Source: Medpage Today © 2012 MedPage Today, LLC (15/10/12)

Largest CCSVI study fails to support MS theory(15/10/12)

The largest study to date testing the venous-obstruction theory of multiple sclerosis failed to support it, leading the Italian Multiple Sclerosis Society to declare the theory dead.

Reported here by leaders of the group, known by its Italian abbreviation AISM, the study of nearly 2,000 individuals with blinded central imaging analysis found the condition in only about 3% of MS patients and in only slightly fewer healthy controls or patients with other neurological conditions.

Key data were released at a press briefing by principal investigator Giancarlo Comi, MD, of the University of Milan, and other study leaders in advance of Comi's formal presentation, scheduled for Saturday at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.

They characterized the study as the largest yet conducted on the so-called chronic cerebrospinal venous insufficiency theory (CCSVI), advanced in 2009 by Paolo Zamboni, MD, of the University of Ferrara in Italy.

The CCSVI theory quickly took the MS community by storm, leading many patients to seek venous angioplasty and stenting procedures in hope of obtaining relief or even a cure, as Zamboni and some other vascular surgeons claimed was possible.

But the theory also drew substantial criticism, especially after numerous other researchers were unable to reproduce Zamboni's original findings of 100% presence of CCSVI in MS patients and 0% in non-MS controls. Some groups were unable to detect CCSVI in more than a small fraction of patients, while others found that it was relatively common but without specificity for MS.

In the new study, sponsored by AISM and called CoSMo, ultrasound analyses were performed on 1,874 individuals at 35 clinics throughout Italy. A total of 107 were subsequently excluded because of technical problems with the images or because participants were found not to meet the specified inclusion criteria (such as age or disease duration).

The analysis included 1,165 patients with MS (including 104 with clinically isolated syndrome), 376 healthy controls, and 226 patients with other neurological diseases.

All participants were evaluated for MS under standard diagnostic criteria.

Initial diagnoses of CCSVI or its absence were made by the sonographers at each clinic, who had received special training in cerebral venous imaging. Some of them had previously trained in Zamboni's clinic. The local sonographers were blinded to participants' diagnoses.

The local clinic diagnoses were then reviewed by one of three blinded central imaging experts: Erwin Stolz, MD, of Justus-Liebig University in Giessen, Germany; Massimo Del Sette, MD, chairman of the Italian Society of Neurosonology and Cerebral Hemodynamics; and Giovanni Malferrari, MD, chairman of the Italian Interdisciplinary Neurovascular Society.

When there was disagreement between the local and central readers, all three of the central readers reviewed the images, with the opinion shared by two counted as the final diagnosis. Analyses in the two-year study were completed last month.

The prevalence of CCSVI as determined under this process was as follows in the three groups of participants:

MS patients: 3.26% (95% CI 2.38% to 4.45%)
Healthy controls: 2.13% (95% CI 1.10% to 4.14%)
Other neurological disorders: 3.10% (95% CI 1.58% to 6.44%)
On the basis of these small values, and the lack of significant (P<0.05) differences between them, the AISM issued a statement declaring that "CCSVI is not a disease connected to multiple sclerosis."

Moreover, it continued, "for people affected by MS, there is no need to carry out additional tests to diagnose CCSVI, nor is vein surgery required."

The AISM is the first national MS society to make such a conclusive determination. In the U.S. and Canada, research on CCSVI commissioned by the major organizations in those countries is still under way, and no similar declaration is likely until those studies are completed.

Comi said that Zamboni had been invited to participate in CoSMo, and did for a time. But he quit before all the sonographers had been trained, objecting to multiple aspects of the study design that he believed would bias the results against finding a relationship between CCSVI and MS.

Stolz said that the sonographers were not trained specifically in Zamboni's method, but that he and others who had conducted the training had extensive experience in cerebrovascular ultrasound imaging.

He noted that this had also been the case with other groups that failed to replicate Zamboni's findings, despite having been trained in his clinic. Stolz added that a diagnostic procedure is only meaningful if it can be taught and used reliably by other experienced practitioners.

"If it is not repeatable, it has no value," he said.

Comi said that other researchers would be permitted to conduct their own evaluations of sonograms collected during the study, as long as the blinding to clinical diagnosis was maintained.

Initial diagnosis of CCSVI in the individual clinics in fact varied widely, Comi said. At one clinic, the condition was found in 60% of participants; in two others, the prevalence was 0%.

Overall, the detection rate at the initial step was considerably higher than after central review: 15.9% among MS patients, 12% in healthy controls, and 15% in patients with non-MS neurological disorders. Comi noted that even at these higher prevalences, there was still no meaningful difference between MS patients and other participants.

He also indicated that central reviewers rarely overruled the local clinic sonographers on negative diagnoses. In only 3% of cases in which the local sonographer found no CCSVI did the central reviewers say it was present.

Agreement was poorer for positive diagnoses. Central reviewers overturned 89% of the CCSVI diagnoses made by local sonographers.

Stolz attributed the lack of concordance on positive findings to the fact that "local sonographers are not on the moon." He suggested that seeing participants, and noting any physical or mental impairments, could have biased them toward diagnosing CCSVI.

Gianluigi Mancardi, MD, head of the AISM's scientific committee and co-principal investigator on the study with Comi, said he hoped the study would put the CCSVI theory permanently to rest.

"In our opinion, this is the final answer," he said.

Noting that the AISM had spent some $2 million to conduct the CoSMo study, he said the group now hoped to direct its attention to more fruitful areas of research in MS and its treatments.

The study was funded by the Italian Multiple Sclerosis Society.

Comi reported consulting fees for participating on advisory boards from Novartis, Teva, sanofi-aventis, Merck Serono, and Bayer Schering; lecture fees from Novartis, Teva, sanofi-aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation. Mancardi reported honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Schering, Biogen Idec, sanofi-aventis, Novartis, and Merck Serono.

Stolz declared that he had no relevant financial interests.

Primary source: European Committee for Treatment and Research in Multiple Sclerosis

Source reference: Comi G, et al "Chronic cerebro-spinal venous insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo study" ECTRIMS 2012; Abstract 167.

Source: Medpage Today © 2012 MedPage Today, LLC (15/10/12)

Canadian study tracks MS patients after ‘liberation treatment’(10/10/12)

A Canadian study that tracked 80 multiple sclerosis patients who underwent the controversial “liberation treatment” outside of the country suggests that about half of them saw their symptoms improve after the procedure.

Researchers in British Columbia surveyed 80 people over the phone one year after they received the controversial treatment, which involves opening up blocked veins to improve blood flow from the brain.

“The picture that seems to be coming out is that about half of the patients feel some improvements in MS symptoms. The degree of improvements ranges from mild to significant,” Dr. Anthony Traboulsee, medical director of the UBC Hospital MS Clinic, told CTV News.

“And about half the patients feel exactly the same as before the procedure or worse.”

About 11 per cent of surveyed patients reported complications around the time they received the liberation treatment. Another 13.8 per cent experienced troubles up to one month afterward.

Pain and bleeding were among the complications experienced. One patient suffered a stroke after the procedure while another one reported symptoms similar to those of a heart attack.

Nine patients had difficulties related to the procedure itself. One reported insufficient anesthetic and said they woke up near the end of the procedure.

Lori Batchelor was among those who found the treatment beneficial. She travelled to a U.S. clinic for the procedure after living with MS for over two decades. Before the treatment, she had difficulty walking and standing.

“I felt very strongly that because my results were so good, I wanted it on record that this is a really important procedure to finally have some sort of treatment available for someone like me who was left to just get worse over the years with absolutely nothing available,” she told CTV News.

Fifty-eight women and 22 men were involved in the study. For the respondents, the average age of MS diagnosis was 39 years of age.

The treatment results relayed in the survey are according to reports from the patients themselves, and are not confirmed by a medical assessment.

Traboulsee said the results of the telephone survey underline the need for a formal study of the treatment’s effect on MS patients.

“We have so many unanswered questions, and no shortage of opinion about this situation and a treatment trial is an efficient way to address those concerns," he said.

That’s why Traboulsee and his team will soon begin recruiting people for a broader study in which 100 MS patients will receive the liberation treatment, similar to angioplasty.

The team has received ethics approvals from institutions in B.C. and Québec for the clinical trial.

The controlled study will monitor MS patients over a two-year period to observe any changes in their symptoms. It is a collaborative effort of the Canadian Institutes of Health Research, the MS Society of Canada and the provinces of B.C. and Quebec.

The liberation treatment was developed by Italian doctor Paolo Zamboni, who theorized that MS has vascular symptoms. He posited that narrowed veins in the neck cause a condition he termed Chronic Cerebrospinal Venous Insufficiency, or CCSVI.

Zamboni’s findings have been highly controversial and some experts have dismissed his claims.

Several studies currently underway in North America are looking at whether vein abnormalities and MS are linked.

A recent observational study of people in Newfoundland and Labrador who travelled abroad for the treatment found no measurable benefit from liberation treatment.

Source: CTV News © 2012 (10/10/12)

Patient trial of proposed MS treatment announced by Canadian government(01/10/12)

A long-awaited national trial of a controversial experimental treatment for multiple sclerosis has been given the go-ahead and will soon begin recruiting patients, federal Health Minister Leona Aglukkaq announced Friday.

Aglukkaq, in Halifax for a meeting with provincial and territorial health ministers, said about 100 MS patients will be enrolled in the Phase I and II trial to assess the safety of the procedure to unblock narrowed neck veins and its efficacy in improving MS symptoms.

The condition — dubbed chronic cerebrospinal venous insufficiency, or CCSVI — has been proposed as a possible cause of MS by Italian vascular surgeon Paolo Zamboni.

More than three years ago, Zamboni hypothesized that narrowed and twisted veins in the neck and chest create a backup of blood in the brain, resulting in iron deposits that could cause the brain lesions typical of MS.

The disease causes the destruction of myelin, the protective sheath around nerves throughout the body, leading to progressive physical and cognitive disability. An estimated 55,000 to 75,000 Canadians have MS, and the country has one of the highest rates of the incurable disease in the world.

"We've always said that we needed the science behind the actual procedure," Aglukkaq told reporters. "This area of MS clinical trials is very important to many of our constituents and today is huge progress."

Dr. Anthony Traboulsee, medical director of UBC Hospital's MS Clinic, will lead the $6-million study, which will be conducted initially in Vancouver and Montreal. Medical and ethical approval is also being sought for parts of the trial to be conducted in Quebec City and Winnipeg.

"It's going to be a randomized-control study where patients who have the presence of CCSVI will be randomly selected to either have the venoplasty, which is dilation of the vein, or a sham treatment, which is not an actual dilation, just a pretend dilation," Traboulsee said from Vancouver.

"And after a year, the groups will switch so that everybody eventually gets the dilation of the vein."

A venoplasty to widen veins is the same technique as an angioplasty used to expand coronary arteries; a tiny balloon is fed into the blood vessel, then expanded.

None of the participants will know which treatment they received or during which half of the study, Traboulsee said.

"The patients won't know when they're getting the dilation, the first time or the second time, so it doesn't bias their interpretation of benefit," he said.

Despite criticisms of Zamboni's theory — some neurologists question or even outright dismiss the notion of blocked veins contributing to MS — many patients desperate for relief have embraced the treatment.

Thousands of Canadians with MS have reportedly travelled to clinics outside the country, paying thousands of dollars for the vein-widening procedure since Zamboni's theory first made headlines in late 2009.

Many patients — but by no means all — reported their symptoms had improved following CCSVI treatment, fuelling insistent calls by many MS patients and their advocates to allow doctors to perform the procedure in Canada.

But with several deaths and complications attributed to the surgery, and studies on CCSVI around the world showing mixed results at best, an expert medical panel advised Ottawa to first mount a clinical trial to test Zamboni's theory.

Traboulsee's group, whose study design was chosen from among three proposals, said "safety is really important."

"We've been surveying patients who have gone out of the country for the treatment and we found a complication rate of 11 to 12 per cent. That's what patients are reporting," he said.

"My impression is it's mostly related to stents, and we're not going to be using stents in our study. We don't think the stents are the best idea at this point."

Stents are small mesh cylinders inserted into blood vessels to keep them propped open. Their use in veins is controversial, as the stents can cause blood clots or migrate from their original site. Even Zamboni does not advocate their use in his CCSVI treatment.

"There has been a lot of controversy around it," Traboulsee said of the procedure. "That's why I think it's important to move this forward and get some final answers to it.

"Because so many Canadians are going out of the country to have this procedure done, if we don't bring some resolution to it soon, we won't be able to give people the information they need to make safe, informed decisions."

A spokesman for the CCSVI Coalition, a patient advocacy group that's been pushing to have the treatment performed in Canada, welcomed the announcement of the study.

"It's long overdue," said Dr. Michael Shannon, chair of the group's scientific advisory board. "If the results from this trial come out unequivocally in favour of CCSVI or the other way, either way it's good news — if and only if the trial has been designed properly.

"If it is flawed in any way, you'll be right back to the drawing board and you'll never be able to convince everyone. So this thing has to be so rigorous."

Dr. Alain Beaudet, president of the Canadian Institutes of Health Research (CIHR), said trial subjects will be drawn from the three provinces where the research is being conducted.

Beaudet said the study is among only a handful worldwide that are blinded, randomized-control trials, the gold standard of medical research.

"Which is critical here, because we're wondering if it's a true effect. Is it a placebo effect? Is there really an effect?" he said from Halifax.

Saskatchewan has set aside $5 million for clinical trials of the so-called liberation therapy; $2.2 million of that is funding a trial of the procedure involving 86 patients from the province, being conducted at a clinic in Albany, N.Y.

Provincial Health Minister Dustin Duncan said the rest of the money could go toward a pan-Canadian trial.

"What has been announced today is just the beginnings, I think, of what the federal government is doing," Duncan told The Canadian Press. "We certainly want to be a part of whether it's in trials or whether it's in monitoring ... we want to be a part of trying to answer that question of whether CCSVI is an effective treatment for people with MS."

The national study is funded by the federal government through CIHR, the three provinces where it is taking place, and the MS Society of Canada.

Traboulsee said researchers will use not only standard yardsticks to evaluate patients during the study period, but also some patient-focused measures.

"We've had a lot of patient input into the study, so it's a nice balance of what we consider a classic standard MS clinical trial, with a lot of patient input into the outcome,"

he said. "So it's in a sense validated by the patient support groups in that it's addressing questions that they think are important to them as well as to the clinicians."

Source: The Province © 2012 Postmedia Network Inc (01/10/12)

Australian results published on prevalence of CCSVI in early MS(25/09/12)

Australian researcher, A/Prof Brian Chambers of the Austin Hospital, Melbourne, has published the results of his MSRA-funded study into the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in early MS (view the abstract here).

CCSVI is a condition where drainage of blood from the brain and spinal cord is impeded. It is thought CCSVI may contribute to the development or symptoms of MS and was originally described by Dr Zamboni of Italy in 2009. In his sample, all people with MS had CCSVI whereas healthy individuals showed no evidence of CCSVI. Subsequent studies have been unable to replicate this marked difference in CCSVI prevalence. Some studies have found an increased prevalence of CCSVI in MS, but have also shown that it is present in healthy individuals and in people with other neurological diseases (OND). For earlier round-ups of CCSVI news, please type ‘CCSVI’ into the search box of this website.

Australian results A/Prof Chamber’s study tested whether CCSVI was more prevalent in people with CIS or mild MS, which would imply a role for CCSVI in the development of MS. The study examined 70 people, made up of 94% with relapsing remitting MS with an expanded disability score (EDSS) of 2 or less and 6% with clinically isolated syndrome (CIS – a first attack of MS-like symptoms) and compared them to 70 healthy individuals. Controls were unrelated to the people with MS and were matched for age and sex.

All subjects were examined by ultrasound using the criteria published by Dr Zamboni, with CCSVI defined as the presence of two or more Zamboni criteria. A/Prof Chambers communicated closely with Dr Zamboni to ensure he was interpreting the criteria according to Dr Zamboni’s descriptions. The Australian team also derived their own criteria for venous abnormalities, which were closely related to the Zamboni criteria, but with defined parameters in relation to flow alterations and internal jugular vein narrowing.

The venous flow parameters were studied with subjects lying down on their backs (supine position) and sitting postures. Careful measures were taken to ensure that the sonographer did not know whether participants had MS, including no discussion of clinical status with the subject and the sonographer being absent from the room while subjects were positioned on, and removed from, the couch. A questionnaire conducted with the sonographer after each subject confirmed that blinding was successful.

Only one individual, a person without MS, satisfied the Zamboni definition of CCSVI. However, 19 MS subjects and 13 controls had Zamboni criteria abnormalities, this difference was explained by an increased prevalence of internal jugular vein narrowing, defined as cross-sectional area 0.3cm2 or less. Using the teams’ more clearly defined measure of stenosis, the difference disappeared. This more rigorous method was designed to avoid potential errors introduced by vein compression or normal side to side variation in vein diameter. Further analysis revealed an abnormal internal jugular vein valve in 7 people with MS and one control.

The team concluded that CCSVI does not have a causal role in MS. However, an apparent increase in internal jugular vein abnormalities in people with MS warrants further investigation.

Source: Multiple Sclerosis Research Australia © 2012 Multiple Sclerosis Research Australia (25/09/12)

Researchers continue with their progress in the seven funded CCSVI studies in MS(05/09/12)

Seven research projects investigating CCSVI (Chronic Cerebrospinal Venous Insufficiency) and MS — launched with a $2.4 million investment by the National MS Society and the MS Society of Canada — have reached the two-year milepost.

The funded multi-disciplined researchers have been reporting significant progress in their two-year study goals. As of July 2012, most of the investigators are in the process of completing their projects and expect to do so within the next year. Although the work continues for several of the teams, some are already presenting preliminary results at medical meetings, and all have shared technical advice so that the projects can move forward as smoothly and quickly as possible.

The need for continued work beyond the two-year grant funding period is not uncommon, as practical and logistical issues begin impacting on projected timelines, including such items as:

- Getting proper protocols in place;

- Applying for and gaining approvals from the required Institutional Review Boards in the U.S. or the Research Ethics Board in Canada, a requirement established by regulatory authorities to protect humans involved in research projects;

- Getting technicians and other team members trained on how to conduct appropriate screenings; and

- Recruiting study participants.

After the research projects are completed, the data collected in these studies will be analyzed and submitted for publication in one or more scientific journals so that other scientists can evaluate and comment on the findings. Currently it is not known when the full data and results will be available, though updates will continue as appropriate to reflect the ongoing transparency of the work being supported by the MS Society of Canada. Results from the seven projects, as well as other studies underway around the globe, will help guide our planning for future investments in this area of research.

Research project highlights and progress

The teams include an integration of experts drawn from all key relevant disciplines including neuroradiology, neurovascular imaging, MS imaging, vascular surgery, biostatistics, interventional radiology, interventional neuroradiology and MS clinical neurology. Bringing together experts across these areas will help to facilitate understanding of CCSVI in MS as quickly as possible.

The research teams have recruited and scanned a broad spectrum of people with MS and others to build understanding of who may be affected by CCSVI. In addition they are refining CCSVI imaging methods for accuracy and consistency to reliably validate the occurrence of CCSVI and understand its implications in the MS disease process.

Already more than 900 people have undergone scanning with various imaging technologies being used by the studies, including the Doppler ultrasound technology used by Dr. Paolo Zamboni and his collaborators, as well as magnetic resonance studies of the veins (MR venography), catheter venography, MRI scans of the brain, and clinical measures.

Some of the teams have been trained in, and are using, the ultrasound technique originally published by Dr. Zamboni. Others are using the same methods but are utilizing standard Doppler ultrasound machines rather than purchasing the specific machine used by Dr. Zamboni’s team.

Future Steps – Clinical Trial

Grantee results will help guide future steps, including the development of a clinical trial to test whether treating vein blockages is a safe and effective therapy for people with MS. The Canadian Institutes of Health Research (CIHR) announced in April 2012 that a research team had been chosen to conduct a phase I/II clinical trial to determine the safety of venous angioplasty and obtain evidence on patient outcomes in people with MS. The location of the study has not yet been announced. The clinical trial is a collaborative initiative between the CIHR and the MS Society of Canada.

At this point, no connection has been confirmed between CCSVI and MS, in fact, CCSVI appears to occur in many people who do not have MS. Although some individuals who have MS have undergone surgical procedures for CCSVI, there has not yet been a controlled trial to determine its effectiveness in treating the symptoms or course of the disease. In addition, the U.S. FDA has issued a safety communication about potential risks associated with procedures and devices used to treat CCSVI, encouraging additional research.

The MS Society shares in the public urgency to advance the understanding of CCSVI as quickly as possible, and is urging researchers to complete their studies and to analyze and publish their results as soon as possible.

All Canadians living with MS urgently require answers about the potential risks and benefits of CCSVI treatment. The MS Society honours and respects the decisions Canadians living with MS make for the benefit of their own health. We acknowledge and respect that some Canadians living with MS have travelled abroad to seek CCSVI related procedures and others have decided to wait for more research.

Source: The Multiple Sclerosis Society of Canada (05/09/12)

Clinical improvement after extracranial venoplasty in Multiple Sclerosis(30/08/12)

Purpose
This study proposed to prospectively evaluate safety and clinical changes in outpatient endovascular treatment in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI).

Materials and Methods
Two hundred fifty-nine patients with MS were followed with the Multiple Sclerosis Impact Scale (MSIS-29) before and for 1and 6 months after treatment of extracranial internal jugular vein and azygos vein stenoses and occlusions using venous angioplasty, as well as stent placement in 2.5% of patients. Before treatment, the patients were tested with magnetic resonance (MR) venography and flow quantification.

Results
We found statistically significant improvements in the MSIS-29 scores (P < .01) at both 1 and 6 months. At 1 and 6 months, 67.9% and 53.6% were improved on the physical scale, respectively, and 53.0% and 44.4% were improved on the psychological scale, respectively. Women showed greater improvement than did men on the physical scale at 6 months (P = .01). Patients with primary progressive MS (PPMS) showed less improvement than did those with relapsing-remitting MS (RRMS) on the psychological scale at 1 month, and venoplasty treatment of more vein sites versus fewer vein sites showed greater improvement on the physical scale at both 1 and 6 months. Fifteen patients (6.3%) reported recurrent symptoms after clinical improvement and were treated again. There was one serious adverse event, a deep venous thrombosis at the catheter insertion site, which resolved with treatment.

Conclusions
Endovascular treatment of CCSVI in patients with MS appears to be a safe procedure resulting in significant clinical improvement.

David Hubbard, MD, Donald Ponec, MD, Justin Gooding, MD, Richard Saxon, MD, Heidi Sauder, PhD, Mark Haacke, PhD

Source: JVIR © 2012 SIR. Published by Elsevier Inc (30/08/12)

MRI findings shed light on Multiple Sclerosis(21/08/12)

New MRI research shows that changes in brain blood flow associated with vein abnormalities are not specific for multiple sclerosis and do not contribute to its severity, despite what some researchers have speculated. Results of the study were published online, August 21, by the Radiological Society of North America in the journal Radiology.

New magnetic resonance imaging (MRI) research shows that changes in brain blood flow associated with vein abnormalities are not specific for multiple sclerosis (MS) and do not contribute to its severity, despite what some researchers have speculated. Results of the research are published online in the journal Radiology.

“MRI allowed an accurate evaluation of cerebral blood flow that was crucial for our results,” said Simone Marziali, M.D., from the Department of Diagnostic Imaging at the University of Rome Tor Vergata in Rome.

MS is a disease of the central nervous system in which the body’s immune system attacks the nerves. There are different types of MS, and symptoms and severity vary widely. Recent reports suggest a highly significant association between MS and chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by compromised blood flow in the veins that drain blood from the brain. This strong correlation has generated substantial attention from the scientific community and the media in recent years, raising the possibility that MS can be treated with endovascular procedures like stent placement. However, the role of brain blood flow alterations on MS patients is still unclear.

To investigate this further, Italian researchers compared brain blood flow in 39 MS patients and 26 healthy control participants. Twenty-five of the MS patients and 14 of the healthy controls were positive for CCSVI, based on Color-Doppler-Ultrasound (CDU) findings. The researchers used dynamic susceptibility contrast-enhanced (DSC) MRI to assess blood flow in the brains of the study groups. DSC MR imaging offers more accurate assessment of brain blood flow than that of CDU. MRI and CDU were used to assess two different anatomical structures.

While CCSVI-positive patients showed decreased cerebral blood flow and volume compared with their CCSVI-negative counterparts, there was no significant interaction between MS and CCSVI for any of the blood flow parameters. Furthermore, the researchers did not find any correlation between the cerebral blood flow and volume in the brain’s white matter and the severity of disability in MS patients.

The results suggest that CCSVI is not a pathological condition correlated with MS, according to Dr. Marziali, but probably just an epiphenomenon—an accessory process occurring in the course of a disease that is not necessarily related to the disease. This determination is important because, to date, studies of the prevalence of CCSVI in MS patients have provided inconclusive results.

“This study clearly demonstrates the important role of MRI in defining and understanding the causes of MS,” Dr. Marziali said. “I believe that, in the future, it will be necessary to use powerful and advanced diagnostic tools to obtain a better understanding of this and other diseases still under study.”

“Brain Hemodynamic Changes Associated with Chronic Cerebrospinal Venous Insufficiency (CCSVI) Are Not Specific for Multiple Sclerosis (MS) and Do Not Contribute to Its Severity.” Collaborating with Dr. Marziali were Francesco G. Garaci, M.D., Alessandro Meschini, M.D., Maria Fornari, M.D., Silvia Rossi, M.D., Milena Melis, M.D., Sebastiano Fabiano, M.D., Matteo Stefanini, M.D., Giovanni Simonetti, M.D., Diego Centonze, M.D., and Roberto Floris, M.D.

Source: redOrbit © 2002-2012 redOrbit.com (21/08/12)

Saskatchewan selects first person for MS CCSVI trial(17/08/12)

A Saskatoon man with multiple sclerosis will be the first person sent by the province to the United States to see if he can participate in neck vein therapy clinical trials.

Andrew Dahlen will fly to Albany, N.Y., Monday for a final assessment in order to join a two-year study of the so-called liberation therapy for MS.

The therapy involves using tiny balloons, surgically inserted, to open up constricted veins.

MS is a neurological disease that can seriously affect mobility, vision, speech and bladder function.

Hundreds of people from Canada have gone to the U.S. or overseas for the treatment, and many say it has given them relief from their symptoms.

However, neck vein therapy is controversial, with a number of medical experts saying it doesn't work, or that the relief it provides is temporary or can be explained by the placebo effect.

No Canadian province pays for the procedure for Chronic Cerebrospinal Venous Insufficiency (CCSVI) , which costs thousands of dollars per treatment, so people who leave the country for it must pay out of their own pockets.

Saskatchewan doesn't pay for the procedure either, but it has set aside $2.2 million to have 86 Saskatchewan patients participate in the Albany trials.

Half of the participants will receive the procedure, while the other half will receive a "placebo" operation.

Dahlen, a 28-year-old Saskatoon cook who was diagnosed with MS six years ago, said he's excited to be part of the Saskatchewan effort. He will have to go through a final assessment before he can undergo the procedure, and even then, may not be in the group that receives the real treatment.

After the Albany treatments are complete, a Saskatchewan neurologist will work with the U.S. team with assessments, referrals and ongoing monitoring of Saskatchewan participants, the province says.

Source: CBC.ca Copyright © CBC 2012 (17/08/12)

MS and CCSVI: A population-based case control study(16/08/12)

Abstract

Background
Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS).

Objective
To evaluate the possible association between CCSVI and MS, using a population-based control design.

Methods
A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if =2 venous hemodynamic criteria were fulfilled.

Results
CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p=0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p=0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR=4.7; 95% CI 1.83–12.0, p=0.001); the association was weaker with the RR patients (age adjusted OR=2.58; 95%CI 1.12–5.92; p=0.02) or not significant in CIS group (age adjusted OR=2.04; 95%CI 0.40–10.3; p=0.4).

Conclusions
A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.

Source: PLoS One v.7(8); 2012 PMC3411668 (16/08/12)