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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.

CCSVI trial reports no benefit with venous angioplasty(02/07/14)

Prospective randomized trial of venous angioplasty in MS (PREMiSe).

Siddiqui AH, Zivadinov R, Benedict RH, Karmon Y, Yu J, Hartney ML, Marr KL, Valnarov V, Kennedy CL, Ramanathan M, Ramasamy DP, Dolic K, Hojnacki DW, Carl E, Levy EI, Hopkins LN, Weinstock-Guttman B.

Abstract

OBJECTIVE: We report the results of the investigation of safety and efficacy of venous angioplasty in patients with multiple sclerosis (MS) with findings of extracranial venous anomalies, considered hallmarks of chronic cerebrospinal venous insufficiency (CCSVI), in a 2-phase study (ClinicalTrials.gov NCT01450072).

METHODS: Phase 1 was an open-label safety study (10 patients); phase 2 was sham-controlled, randomized, and double-blind (10 sham procedure, 9 treated). All study patients fulfilled venous hemodynamic screening criteria indicative of CCSVI. Assessment was at 1, 3, and 6 months postprocedure with MRI, clinical, and hemodynamic outcomes. Primary endpoints were safety at 24 hours and 1 month, venous outflow restoration >75% at 1 month, and effect of angioplasty on new lesion activity and relapse rate over 6 months. Secondary endpoints included changes in disability, brain volume, cognitive tests, and quality of life.

RESULTS: No perioperative complications were noted; however, one patient with history of syncope was diagnosed with episodic bradycardia requiring placement of a pacemaker before discharge. Doppler evidence-based venous hemodynamic insufficiency severity score (VHISS) was reduced >75% compared to baseline in phase 1 (at 1 month) but not phase 2. In phase 2, higher MRI activity (cumulative number of new contrast-enhancing lesions [19 vs 3, p = 0.062] and new T2 lesions [17 vs 3, p = 0.066]) and relapse activity (4 vs 1, p = 0.389) were identified as nonsignificant trends in the treated vs sham arm over 6 months. Using analysis of covariance, significant cumulative new T2 lesions were related to larger VHISS decrease (p = 0.028) and angioplasty (p = 0.01) over the follow-up. No differences in other endpoints were detected.

CONCLUSION: Venous angioplasty is not an effective treatment for MS over the short term and may exacerbate underlying disease activity.

CLASSIFICATION OF EVIDENCE: This is a Class I study demonstrating that clinical and imaging outcomes are no better or worse in patients with MS identified with venous outflow restriction who receive venous angioplasty compared to sham controls who do not receive angioplasty. This study also includes a Class IV phase 1 study of safety in 10 patients receiving the angioplasty procedure.

© 2014 American Academy of Neurology.

Source: Neurology. 2014 Jun 27. pii: 10.1212/WNL.0000000000000638. [Epub ahead of print] & Pubmed PMID: 24975855 (02/07/14)

Modified approach to the treatment of autonomic dysfunction in MS patients(13/06/14)

A new study sheds light on the positive effect of a venous procedure upon the sympathetic nervous system. Researchers were able to pinpoint how the procedure improved the abnormal sympathetic function found in patients with many chronic conditions including Multiple Sclerosis. Additionally, the study may offer insight on the beneficial effects of Chronic Cerebrospinal Venous Insufficiency (CCSVI) treatment.

Newport Beach Interventional Radiologist, Michael Arata, MD, has co-authored the study, which will be published in the June 2014 issue of Journal of Endovascular Therapy. The study, performed by Dr. Arata and his research associate, Zohara Sternberg, PhD, found that using an angioplasty balloon to stimulate vein-associated nerves increased sympathetic activity. This treatment for autonomic dysfunction shows promise for patients who suffer from Multiple Sclerosis, an inflammatory disease that causes damage to the central nervous system and can lead to paralysis.

Dr. Arata has spent more than a decade performing angioplasty and has been at the forefront of research for CCSVI, a venous condition in which blood flow from the brain is restricted. "There is a possibility that improved autonomic function may diminish symptoms and have an impact on the course of the disease," explained Dr. Arata, who serves as Medical Director at Synergy Health Concepts in Newport Beach and has performed more than 2000 procedures on patients with autonomic-associated disease, maintaining a high clinical (patient response) success rate in excess of 90% in a recent study group.

"The current study demonstrates the procedure's effect on autonomic function, offering an explanation for why patients may see symptom improvement with venous ballooning even though separate studies have failed to show a relationship between venous obstruction and Multiple Sclerosis. The mechanism of symptom improvement is improved autonomic tone rather than relief of flow obstruction," he said.

About Michael Arata, M.D.

A graduate of UCSF School of Medicine, Dr. Arata completed his four year residency at Duke University Medical Center. Dr. Arata is certified by the American Board of Venous and Lymphatic Medicine. He has been caring for patients with autonomic dysfunction for four years, and he established the first endovascular treatment center focused on treating autonomic dysfunction, located in Newport Beach, CA.

Source: Digital Journal copyright © 2014 digitaljournal.com (13/06/14)

Canadian study finds no link between blocked veins, MS(03/06/14)

A new Canadian study is casting doubt on the link between blocked neck veins and multiple sclerosis, after finding no difference in the proportion of abnormalities in the veins of MS patients and healthy controls.

The study, published Monday in The Canadian Medical Association Journal, found no link between chronic cerebrospinal venous insufficiency (CCSVI) and MS.

Using ultrasound and MRI technology, University of Calgary neurologist Dr. Fiona Costello and her colleagues tested the criteria used to diagnose a patient with CCSVI on a group of MS patients and healthy controls.

They compared the ultrasound results of 120 patients and 60 controls and found a "high" proportion of both groups met one or more of the criteria required for a CCSVI diagnosis. Their results showed that 58 per cent of MS patients and 63 per cent of the healthy controls met one or more of the proposed criteria. "We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls," the study's authors conclude. "Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity."

Dr. Paolo Zamboni first put forth his theory that constricted veins in the head and neck were linked to MS in 2009. Zamboni also postulated that a vein-widening procedure, which he called the "liberation treatment," could improve the symptoms of MS patients.

Since that time, hundreds of MS patients have sought the treatment, often paying to have it done overseas. As well, several studies have examined Zamboni's theory, with many poking holes in his work.

A recent study published last October in The Lancet also found that a narrowing of the veins leading from the brain was just as prevalent in healthy individuals as it was in patients with MS.

Meanwhile, a separate survey found that a group of Canadian MS patients who left the country to get the controversial "liberation treatment" were relatively satisfied with the results, despite receiving sub-optimal care.

Of the 124 participants, nearly 60 per cent said they received no follow-up investigations at the centre where they had received the procedure. More than 40 per cent said they had no follow-up care of any kind.

Jamie Greenfield, a data analyst at the University of Calgary's MS Research Program, said only 6 per cent of the survey respondents reported that they had not been told of potential adverse side effects. Some potential risks, such as stent migration or kidney damage resulting from the dyes used to help locate blocked veins, were rarely raised, she said.

Despite these findings, 50 per cent of the patients rated their overall satisfaction with the procedure as good or better. As well, 122 of the 124 participants said their procedure was successful, with 79 per cent reporting no complications and 19 per cent saying it was "successful with some trouble."

Greenfield presented the results of the survey at the joint meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis in Dallas over the weekend. The results of her presentation were published in MedPage Today.

Barrie, Ont. resident Steve Garvie opted to have the liberation treatment in 2010. He told CTV News that it was only because of the procedure that he was able to attend his daughter's recent wedding in Boston.

"I walked her down the aisle and had the father and daughter dance with her," he said. "I feel truly blessed. Without the procedure I would be either cheering her on from my wheelchair in government housing, or I would not be on this earth to have this joy."

Source: CTV © 2014 Bell Media (03/06/14)

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)