What is Chronic cerebrospinal venous insufficiency (CCSVI)?

CCSVI Blood Flow Diagram

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.

Further Information

For more on CCSVI please visit the Chronic Cerebrospinal Venous Insufficiency - CCSVI pages.

MSRC Statement on CCSVI and Dr Paolo Zamboni’s work.

"MSRC is very encouraged by the early results of Dr Paolo Zamboni’s work. There is no doubt that this area warrants a great deal more study. This could represent a completely novel approach to MS research which, if proven to be relevant, could be a “sea change” in the understanding of the mechanisms involved in the condition. There has already been a huge amount of interest about this study and MSRC will continue to report on any and all developments in this very important area. MSRC looks forward to the results of the further trials that are taking place and hopes that these studies are able to reproduce the findings of Dr Zamboni.” - Helen Yates MSRC Chief Executive

One of the first clinics in North America devoted to testing for a vascular condition that some experts believe is linked to multiple sclerosis is set to open later this month in Buffalo, just as scientists are to release more findings on the controversial theory.

The Buffalo Neuroimaging Analysis Center (BNAC) has announced that it will begin to offer testing for the newly discovered condition, called chronic cerebrospinal venous insufficiency (CCSVI), in mid-February due to overwhelming demand from MS patients.

Italian scientist Dr. Paolo Zamboni believes that CCSVI causes veins in the neck and upper chest to twist, narrow or become blocked; in some cases, these veins never form at all. The result is poor blood drainage from the brain.

Zamboni has found that more than 90 per cent of patients with MS have these malformed veins, and improper blood flow from the brain.

Due to the overwhelming response to Zamboni's research and to its own study on the condition, the BNAC said it will begin offering diagnostic venous testing to patients beginning in mid-February 2010.

Testing will include:

• An MRI of the brain to measure the level of iron deposits
• An MRI of the neck to study the jugular, vertebral and other collateral veins
• A Doppler exam of the head and neck to determine blood flow
• A follow-up visit with a doctor to discuss the findings
  

News of the findings comes days before scientists from the BNAC release data from their study that includes 500 MS patients who were tested for CCSVI.

"What I can tell you today is that the preliminary results are exciting scientifically and will generate a great deal of discussion among our colleagues, the worldwide press, and individuals like you who are following very closely any developments about CCSVI," Dr. Robert Zivadinov said in the BNAC newsletter.

Zivadinov said the second phase of the study will include another 500 patients and will "pose new and provocative questions about the CCSVI theory."

Scientist welcomes scepticism

Zamboni told CTV's Canada AM Monday that he welcomes skepticism about his findings.

"This is normal when there is a new finding in science," Zamboni said. "I think that this is positive because it stimulates debate."

Zamboni was in Hamilton, Ont., Sunday for a scientific workshop looking into the relationship between MS and CCSVI. Scientists from the United States, Europe and the Middle East reported that they had found CCSVI in more than 95 per cent of MS patients.

"The meeting yesterday was quite successful because we met a lot of colleagues from all over the world that are actually working on our theory," said Zamboni, who is a professor of medicine at the University of Ferrara in Italy.

According to Zamboni, a surgical procedure to restore proper blood flow, which he dubbed the "Liberation treatment," can reduce MS symptoms.

In a study of 65 patients who underwent the procedure, released in the Journal of Vascular Surgery, Zamboni says that 50 per cent of patients with the most common form of MS were relapse-free for at least 18 months.

In a control group of MS patients who did not undergo the procedure, only 27 per cent went 18 months without an MS attack.

Additionally, only 12 per cent of patients in the surgery group had brain lesions -- a sign of active disease -- compared to 50 per cent in the control group.

Research will take time

Dr. Mark Haacke, director of the imaging division in the school of biomedical engineering at McMaster University, organized the weekend conference and said "no one is claiming it's a cure."

"It's a cardiovascular problem first, it may be related to MS, it may cause MS -- but we don't know all those answers yet," he told CTV.ca. "That's going to take time to do very careful research to evaluate those MS patients that do get the operation.

"Do they get better? Do they stay the same? Do their lesions go away? Or do they at least not get worse. (It) may take years and years to really determine the effectiveness of this surgery."

MS societies around the world have responded with funding for research into CCSVI. The Italian Multiple Sclerosis Foundation has allocated up to $4.5 million for research and the MS Society of Canada has called for applications for grants for those studying Zamboni's findings.

Charity Intelligence Canada, a group that provides donors with research and information, called for additional research and funding into Zamboni's findings on Monday.

The group said Canadians donated $62 million to MS-related charities in 2009, and said "supporting CCSVI research presents an opportunity for donors to have high impact in their giving."

"Donors wanting to support CCSVI research in Canada should donate directly to St. Joseph's Healthcare and McMaster University in Hamilton, Ontario and University of British Columbia, designating their donations to CCSVI research," the group said in a statement.

However, experts have warned that the findings are far from being validated and those with MS should continue with their current treatment.

"Although the early data are of great interest, it is important to acknowledge that the concept of CCSVI as a cause of MS and the use of stents or balloons to widen veins as treatments, are ideas that are far from being accepted by most researchers in the field," the MS Society of Canada says on its website.

Experts have expressed concern that the initial excitement over the new procedure was leading some to drop their current treatment.

"To people with MS we say: don't abandon the course of treatment that you have started," Yves Savoie, the president and CEO of the MS Society of Canada told CTV News in November.

"Those treatments have been proven in large trials to be effective in reducing the burden of disability that comes with MS."

Haacke says that since most MS patients have MR scans performed, clinicians should consider performing additional scans for CCSVI.

"It's important for clinicians to begin to realize that they should be taking some time clinically – not on the research side – to scan their patients and find out if this is a problem," he said.

Canada has one of the highest rates of MS in the world, affecting between 44,000 to 78,000 in the country.

Source: CTV News © 2010 CTVGlobeMedia (09/02/10)

Finding a treatment for multiple sclerosis holds as much promise for Hamilton as it does for patients.

St. Joseph's Hospital is one of just two places in Canada testing Italian vascular surgeon Dr. Paolo Zamboni's controversial theory that MS is a vascular disease -- a radical departure from long-held beliefs that it's an autoimmune condition. The University of British Columbia is the other place.

It has brought Hamilton to the attention of the world with about 22,000 MS patients from Asia to Africa to South America to all over the United States and Canada vying to be one of the 100 chosen for the study. It will also recruit 100 healthy people to take part.

"This is a watershed moment," said Dr. Ian Rodger, vice-president of research at St. Joseph's Healthcare. "Opportunities like this don't come along very often."

Hamilton has the chance because of McMaster's affiliation with Detroit imaging expert Dr. Mark Haacke, who met Zamboni in September when the Italian doctor held a conference about his theory.

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 found those veins blocked or malformed in more than 90 per cent of MS patients he studied -- including his wife.

Haacke has long researched the role iron plays in MS and is eager to test Zamboni's theory. His main lab is in Detroit but he's also an adjunct professor at McMaster. With eight other Hamilton doctors, he plans to use St. Joseph's MRI, which is twice as strong as traditional machines, to look at the veins in the brains of MS patients and healthy people to see whether there is a difference.

Haacke says there has been a lot of resistance to Zamboni's theory -- Chronic Cerebrospinal Venous Insufficiency (CCSVI) -- from medical professionals, particularly neurologists.

"It was just so flabbergasting to them," he said.

But the idea can't be ignored.

"We're going to have 10 years of fascinating research."

St. Joseph's, McMaster and Hamilton Health Sciences want to play a big role in that. They don't have funding yet, but are together putting in a proposal to the MS Society of Canada Tuesday for $100,000 a year for two years.

Rodger is leading the research and hoping other funders will come forward so that they can do a much bigger study that would produce results in 12 to 15 months instead of two years or longer. Philanthropists and/or their advisors are expected to be at the workshop Zamboni and Haacke are presenting in Hamilton tomorrow.

The stakes are high for MS patients, as there are few treatment options. Zamboni performs an experimental surgery similar to angioplasty to unclog the veins and improve blood flow. He says it has worked for his wife and others.

Hamilton MS patient Vasilios "Bill" Smyrnios wants to know if that surgery could help him. The 50-year-old who was diagnosed 10 years ago can't walk anymore and has to live in supportive housing.

"This disease is relentless," he said. "It keeps getting worse. It has amazed me. I never expected to get like this."

He has newfound hope since researching Zamboni's theory.

"It was the first thing I've read in a long time that made sense."

While St. Joseph's is studying the theory and hosting the conference, it is a long way from endorsing it.

"There's a great deal of skepticism about the observational study (that Zamboni did)," said Kevin Smith, CEO of St. Joseph's Healthcare. "A lot of the scientific community has already rejected the view. But it resonates profoundly with patients and families so it's our responsibility to determine if this is more than unusual observation."

Source: Thespec.com © Copyright Metroland 2010 (07/02/10)

A medical centre in British Columbia says it wants to become the first in the country to test the controversial theory that multiple sclerosis patients have blocked veins, preventing proper blood flow from the brain.

"There's a large demand for us to look into this," Dr. Anthony Traboulsee told CTV News. "Patients are very excited. We are very interested ourselves, and we want to meet the demand of our patients."

A group of researchers at the University of British Columbia MS Clinic, part of the Vancouver Coastal Health Authority, are planning to study the theory, using a variety of imaging techniques. If it gets approval and funding, it appears to be the most comprehensive examination of this novel theory in the world.

They will be studying the findings of Italian researcher Dr. Paolo Zamboni, who believes that blocked veins in the neck and chest of MS patients lead to blood drainage problems and triggers the immune responses that mark the disease.

Zamboni contends that angioplasty surgery on these blocked veins, a procedure he calls the Liberation Treatment, can then open them. A preliminary study of the treatment in 65 patients showed it improved the quality of life for many patients, and as long as the veins remained open, symptoms of MS were reduced and new attacks were halted.

The BC team envisions a study that begins with MS patients being scanned for abnormalities, likely using the ultrasound test pioneered in Italy. They would also be given MRI scans, to see how the different tests detect possible problems. The prevalence of vein problems would also be assessed in MS patients and in normal healthy control patients. Data would also be blinded to minimize the risk for bias in the research.

Once these non-invasive scans have been done, test patients would proceed to the angiography suite. There they would undergo a venogram. That's where a probe is inserted, from the groin, into the vein system that travels through the chest and into the neck. Doctors inject a dye and watch the blood-flow. This is also, according the University of Ferrara team, the definitive way of seeing blockages in the jugular veins in the neck and the azygos vein in the chest.

And if there are blocked or narrowed veins, the UBC researchers want to open them up to see what happens.

"Not only do we want to see if we can detect these abnormalities, we also want to see, if we change them, does it improve peoples' lives?" said Traboulsee.

The B.C. researchers, who include radiologists, vascular specialists, and physicists working on new imaging technologies, say they had heard about the theory before CTV's W5 aired a story describing the theory, and were investigating the possibility of a study.

But interest in the theory in Canada has exploded since the episode aired.

A professor of neurosurgery at the University of Buffalo, Dr. Robert Zivadinov, who worked on an early study with Zamboni, says his office was contacted by 8,000 MS patients in the three weeks after the W5 episode aired.

The Vancouver researchers want to determine the prevalence of the vein abnormality, which Zamboni has dubbed CCSVI -- or chronic cerebrospinal venous insufficiency. They also want to know how easily it can be detected with ultrasound and MRI testing.

Joining the study will be Alex Rauscher, a physicist. He hopes to look at MRI scans of patients to search for evidence of iron deposits in the brain, since some research has suggested that iron in the brain may contribute to the inflammation and the immune system attacks that mark MS.

"It is our duty to find the answers," said Rauscher.

The Vancouver Coastal Health researchers say they have applied for funding from the MS Society of Canada to fund research to determine the most practical and reliable test for CCSVI. But because of the size and scope of the study -- and their desire to begin quickly -- they are also accepting funding from other agencies and private donations.

Donations should be directed to: VGH and UBC Hospital Foundation , UBC Faculty of Medicine (funds can be specified for CCSVI research)

The researchers note that their study is not accepting patients yet and likely won't for a few months until they acquire funding, obtain ethical approval, and develop an MRI and ultrasound testing protocol.

Patients are asked to refrain from contacting the clinics until they are ready to proceed with the study.

Meanwhile in Italy, one of the companies that manufactures the ultrasound machines used in the testing for CCSVI, is beginning to hold training sessions for doctors and technicians who want to learn the novel technique for scanning the neck and head.

One training program is being held this week at the University of Ferrara with technicians who developed the tests, and with Zamboni. A second session is planned for March.

Contact information for the course is available through: Claudio.Buffagni@esaote.com

Source: CTV News © 2010 CTV Globe Media (30/01/10)

Investigators at the University of Sydney have published a study suggesting that the earliest activity seen in the brain in MS is the destruction of cells that make myelin (oligodendrocytes), occurring before the onset of immune activity usually blamed for triggering the disease.

This provocative study, co-funded by many sources including the National MS Society, opens up new possibilities for finding the cause of the disease and developing new treatments. The study is authored by Drs. John W. Prineas, Andrew P.D. Henderson and colleagues, and is published in the December issue of Annals of Neurology (2009;66:739–753).

Background: Multiple sclerosis has long been thought to be triggered by immune attacks in the brain and spinal cord, causing a spectrum of neurological symptoms. Extensive research has been underway to better understand what triggers the immune attacks and which immune cells are involved, and to better understand the damage to the central nervous system that occurs during the course of MS. In addition to studies of immune activity underlying what has been considered an autoimmune process, another important approach has centered on pathology studies involving microscopic explorations of MS lesions (damaged areas, also called plaques) in the brains of people with MS.

The lead author of the current study, John W. Prineas, MB, BS, FRCP, was the 2001 winner of the John Dystel Prize for MS Research, an award given jointly by the National MS Society and the American Academy of Neurology. He was recognized for being the investigator who first described how myelin, the substance that insulates nerve fibers, is broken down in MS, and he was the first to demonstrate that myelin repair occurs during the course of MS through the body’s natural repair processes.

Current Study: For this study, the team used brain specimens from 11 people who had died early in the course of their MS, and the team also used comparison specimens from people with other disorders including stroke. Some of the tests focused on subsets of specimens from seven people who had lesions showing active myelin destruction. To get a sense of immune cell activity in the brain and at what stage it was occurring, the team examined newly active and resolved lesions, as well as nearby blood vessels, surrounding areas showing some disease activity and surrounding areas that appeared normal, and areas that were farther away from the lesions of interest.

Results: In tissues surrounding newly forming lesions, the investigators found evidence of the loss of oligodendrocytes with an absence of immune T or B cells that would normally be held responsible for launching the immune attack against oligodendrocytes and the myelin they produce. These and other immune cells, including scavenger cells (macrophages and microglia), were more numerous in lesions and surrounding tissues at apparently later stages of destruction and sometimes in lesions that were in the process of repair. In specimens from two very early cases of clinical onset of disease, they found few immune cells within the lesions and no evidence of activation of scavenger cells.

These and other unexpected findings from this study led the investigators to propose that the early immune activity seen in active lesions is that of macrophages and microglia, whose job it is to clean up and remove damaged myelin. They propose that lesion formation is caused by something other than destructive immune activity led by inflammatory cells against a component of myelin or oligodendrocytes.

Comment: This study is a significant addition to a small but growing body of evidence that highlights the question of what triggers MS and whether there is something other than, or in addition to, the immune attacks that lead to tissue damage in the brain and spinal cord of people with MS. Further research, which is ongoing by investigators around the world, should shed further light on this question and may offer novel treatment approaches.

Note: The availability of donor brain specimens was crucial to this and other studies focusing on disease pathology

Source: US National Multiple Sclerosis Society (30/01/10)

The Italian Multiple Sclerosis Foundation today announced it will allocate up to $4.5 million to fund ongoing research into CCSVI -- a condition linked to Multiple Sclerosis.

The foundation says it is accepting research proposals until March 8 from scientists interested in studying CCSVI -- a condition discovered by a team at the University of Ferrara in Italy and lead scientist Dr. Paolo Zamboni.

“We await proposals from groups of Italian researchers, in particular by the research groups that are already active with Prof. Zamboni,” said in a press release.

The condition causes veins in the neck and upper chest to twist, narrow or become blocked. In some cases these veins never form at all. The result is poor blood drainage from the brain. Dr. Zamboni has found that more than 90 per cent of patients with MS have these malformed veins, and improper blood flow from the brain.

Roberta Amaedo, President of the Italian Association for Multiple Sclerosis, said in the release: "We need certainty about the relationship between MS and CCSVI and on the clinical course that this can cause, and on that clinical trials will make an important contribution.”

The association also cautioned patients against seeking endovascular or surgical procedures to open these blocked veins outside of controlled research studies.

In another development, an international group of doctors who specialize in disorders of the veins has issued a consensus document, on the diagnosis and treatment of these problems, including CCSVI.

The international Union of Phlebology officially classified CCSVI as a congenital vascular malformation, outlining official guidelines for diagnosis and treatment.

Dr. James Laredo, a vascular surgeon at Georgetown University Hospital, and one of the authors of the statement, said the members of the group voted unanimously in favour of including CCSVI as a venous malformation.

The statement also says the origins of this novel condition appear to take root during development in the uterus, before birth. Dr. Zamboni, who first identified the condition, is also part of this group.

Dr. Laredo told CTV News that his hospital is now planning to begin a study in a month with neurologists to screen MS patients for these abnormal veins and determine if there is a link between CCSVI and multiple sclerosis. They will be treating MS patients who are found to have CCSVI.

"In Dr. Zamboni's group of MS patients, I feel that he has demonstrated proof of concept. Furthermore, I feel that his findings are significant enough that it requires further investigation and that is why we at Georgetown University Medical Center have begun our investigation into CCSVI," said Dr. Laredo.

Source: CTV News © 2010 CTVGlobeMedia (28/01/10)

A Consensus Conference on Venous Malformations - headed by Prof. Byung B Lee from Georgetown - and experts from 47 countries studied the evidence and unanimously voted in favour of officially including the stenosing lesions found in CCSVI in the new
Consensus document and Guidelines. Now published- http://tinyurl.com/yh8qgq3

This paper can be brought to interventional radiologists and vascular surgeons. CCSVI lesions are classified as a truncular
venous malformations - which means that vascular doctors have now classified this disease, CCSVI, as congenital- and
preceding MS lesions.

Vascular doctors have agreed. CCSVI comes first.

Dr. Zamboni has been speaking to medical panels around the world. Yesterday was a "4 hour machine gunning of questions"
by the Italian, Canadian and US MS Societies in Milan- Dr. Zamboni said he was able to answer all the questions with scientific
evidence, and was quite pleased with the meeting's outcome. He'll be in North American soon.

Source: ThisisMS CCSVI Forum (26/01/10)

Multiple sclerosis (MS) is a heterogeneous disease with variable clinical features and magnetic resonance imaging (MRI) findings.

We report four MS cases with unusual wedge-shaped lesions in the paramedian ventral medulla oblongata demonstrated on MRI.

The clinical features and MRI characteristics of the medullary lesions suggest an impairment of venous drainage.

We propose that the formation of these wedge-shaped lesions may be related to the pattern of venous drainage in the ventral medulla and raised venous pressure due to chronic cerebrospinal venous insufficiency which has recently been described in MS.

Qiu W, Raven S, Wu JS, Carroll WM, Mastaglia FL, Kermode AG.

Centre for Neuromuscular and Neurological disorders, University of Western Australia, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia; Department of Neurology, the Third Affiliated Hospital of Sun yat-sen University, Guangzhou, China.

Copyright © 2010 Elsevier B.V. All rights reserved.

Source: PubmedPMID: 20056253 (11/01/10)

Possible connection to Chronic Cerebrospinal Venous Insufficiency - CCSVI explained.

Re: Epstein–Barr virus is associated with grey matter atrophy in multiple sclerosis
R Zivadinov, M Zorzon, B Weinstock-Guttman, M Serafin, A Bosco, A Bratina, C Maggiore, A Grop, M A Tommasi, B Srinivasaraghavan, M Ramanathan
J Neurol Neurosurg Psychiatry 2009;80:620-625 Published Online First: 23 January 2009 doi:10.1136/jnnp.2008.154906

Dear Editor,

I read the article by Zivadinov ⁽¹⁾ with reference to the association of Epstein-Barr virus (EBV) to gray matter atrophy in multiple sclerosis (MS) patients.

Accumulation of EBV infected B cells in meninges and perivascular regions of MS lesions in 21 or 22 patients with MS ⁽²⁾ was noted as well, indicating direct involvement of the brain and perivascular spaces by EBV in MS patients..

A recent study has indicated chronic cerebrospinal venous insufficiency with multiple extracranial venous strictures in MS patients ⁽³⁾.

EBV appears to infect endothelial cells ⁽⁴⁾, and may be important in the pathology of EBV virus.

EBV virus has been found to cause deep venous thrombosis in a patient with hereditary thrombophilia ⁽⁵⁾.

EBV may infect the venous endothelium causing venous thromboses and strictures in the cranial and spinal venous drainage system and perivascular regions of MS lesions in patients with MS.

Such venous involvement may be implicated in MS disease involvement.

Chronic EBV infection may involve the venous system with secondary effects on the brain and spinal cord in MS.

References

^1.Zivadinov R, Zorzon M, Weinstock-Guttman B, Serafin M, Bosco A, Bratina A, et al.
Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis
J Neurol Neurosurg Psychiatry 2009; 80: 620 -625.

^2.Serafani B, Rosicarelli B, Franciotta D, et al.
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain.
J Exp Med 2007; 204:2899-2912.

^3. Zamboni P, Galeotti P, Menegatti E, Malagoni AM, Tacconi G, et al.
Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.
J Neurol Neurosurg Psychiatry 2009: 80: 392-398.

^4. Jones K, Rivera C, Sgadari C, Franklin J, Max EE, et al.
Infection of human endothelial cells with Epstein-Barr virus.
J Exp Med. 1995; 182: 1213-1221.

^5. Mashav N, Saar N, Chundadze T, Steinvil.
Epstein-Barr virus associated thromboembolism: A case report and review of the literature.
Thromb Res. 2008; 122: 570-571.

No conflict of interest.

Steven R Brenner, Neurologist
St. Louis VA Medical Center and Dept Neurology and Psychiatry at St. Louis University

Source: J Neurol Neurosurg Psychiatry © 2009 by the BMJ Publishing Group Ltd

The University of British Columbia has announced plans to begin patient trials to test a potentially groundbreaking method of diagnosing and treating multiple sclerosis, a disease that afflicts up to 75,000 Canadians.

Researchers have proposed launching a study involving 100 patients to test a theory that MS is a vascular disease that can be treated with surgery. It's the first research proposal in Canada to suggest evaluating the findings of an Italian doctor whose early studies indicate that multiple sclerosis might be caused by vein blockages that lead to a buildup of iron in the brain.

The findings of Paolo Zamboni have generated a great deal of interest among researchers and those with MS. Earlier this year, the Multiple Sclerosis Society of Canada appealed to scientists to follow up Dr. Zamboni's theories.

The proposed UBC trial, which would be done in collaboration with researchers at the University of Saskatchewan, is an answer to that appeal, said Anthony Traboulsee, medical director of the UBC MS Clinic.

Dr. Traboulsee said Dr. Zamboni's studies have caused both hope and anxiety among people with MS. They are hungry for a breakthrough, but realize the Italian doctor's findings are preliminary.

“They are very anxious about this,” Dr. Traboulsee said Tuesday in an interview. “MS is a lifelong disease. Young people are hungry for hope.” Because of the intense interest in the new findings, Dr. Traboulsee said the proposed patient trials must “take a careful” approach.

Unlike Dr. Zamboni's earlier studies, the UBC research plan will include a control group – which gives more heft to a study's findings – and will take place over a longer period.

In Dr. Taboulsee's proposed trial, researchers would closely examine participants' neck and stomach veins. The study group will include people with and without MS. Each participant will undergo three tests, including an ultrasound, a magnetic resonance imaging test and the insertion of a catheter. In that test, dye is injected to give researchers a closer look at the veins.

Only MS participants with blocked or narrowed veins will move on to the second stage of the trials.

Half that group will undergo a vein dilation procedure – similar to an angioplasty – to expand the vein, the other half won't.

The purpose of UBC's proposed research trial is to build on the knowledge uncovered by Dr. Zamboni, a professor of medicine at the University of Ferrara in Italy. His theory is that a condition that he dubbed chronic cerebrospinal venous insufficiency causes MS. The current thinking is that MS is an autoimmune condition in which the immune system attacks myelin, a fatty substance that coats nerve cells.

Dr. Zamboni found that, in about 90 per cent of people with multiple sclerosis, the veins draining blood from the brain were malformed or blocked, which led to a buildup of iron in the brain, which he theorized causes the neurological symptoms of MS.

Dr. Zamboni had 65 of his patients undergo an angioplasty to clear the blockage. Of those, 50 per cent reported no attacks in the next 18 months. In a group that did not have surgery, that rate was 27 per cent.

Multiple sclerosis is a degenerative condition that can cause loss of balance, heat sensitivity, impaired speech, double vision and paralysis.

UBC's trial still needs funding and approval from an ethics committee. The researchers will apply for funds from the MS Society of Canada, private donors and the Canadian Institutes of Health Research. Dr. Taboulsee said the study will cost nearly $1-million for equipment and staff.

Researchers including some at UBC have already been studying links between MS and iron in the brain, Dr. Taboulsee said. He said the latest findings are like another piece to a jigsaw puzzle. Previous studies have linked MS to, among other things, a Vitamin D deficiency and cold climates.

Source: The Globe And Mail © 2009 CTVglobemedia Publishing Inc. (16/12/09)

New data from a pilot open-label study suggest that endovascular treatment of strictures in extracranial cerebrospinal veins is safe in patients with multiple sclerosis (MS) and may provide some neurological benefit for these patients, researchers conclude.

The controversial approach, which has recently been making headlines in consumer media outlets, proposes that narrowing in the veins draining the brain, called chronic cerebrospinal venous insufficiency (CCVI), may be an early step in the disease process causing MS, and further, this narrowing may respond to simple angioplasty.

Lead author Paolo Zamboni, MD, director of the Vascular Diseases Center at the University of Ferrara, Italy, emphasized that the current report should be viewed as an interesting finding that urgently requires replication by other groups.

"What we know is that MS is very complex and multifactorial," Dr. Zamboni told Medscape Neurology. "We have identified an unknown factor and possible treatment for this factor."

The study is published as an online article in the December issue of the Journal of Vascular Surgery.

CCVI and MS

In a previous study published online in December 2008, Dr. Zamboni and colleagues assessed venous outflow routes in 65 patients with clinically definite MS (CDMS) and 235 control patients using a combined transcranial and extracranial color Doppler high-resolution examination. They reported that CDMS and venous outflow abnormalities were "dramatically" associated, with an odds ratio of 43 (95% confidence interval, 29 - 65; P < .0001).

Venography showed the presence of multiple severe extracranial stenoses affecting the principal venous segments in the patients with MS but not the control patients. "This provides a picture of chronic cerebrospinal venous insufficiency with 4 different patterns of distribution of stenosis and substitute circle," the authors write. "Moreover, relapsing-remitting and secondary progressive courses were associated with CCVI patterns significantly different from those of primary progressive (P < .0001)" (Zamboni P, et al. J Neurol Neurosurg Psychiatry 2009;80:392-399).

In an editorial accompanying that publication, Claude Franceschi, MD, from Saint Joseph and Pitié-Salpétrière Hospitals in Paris wrote that, "in light of the association between such a previously overlooked vascular picture and MS, a further stimulating research field is opened by this article. This should be addressed in understanding the contribution of venous drainage to the different aspects of inflammation, autoimmunity and neurodegeneration characterising the intriguing puzzle of MS" (Franceschi C. J Neurol Neurosurg Psychiatry 2009;80:358).

Dr. Zamboni stressed that this association between venous stenoses in main extracranial veins and MS is not contradictory to what is already known about the disease. "What I've found is a previously unknown factor, widely diffuse in my MS population, which could trigger or facilitate both immune reaction and inflammation," he told Medscape Neurology. "If you have elevated pressure and difficulty of drainage in the brain, you have the possibility of extravasation of blood components crossing the blood–brain barrier, and this could trigger inflammation and also immune reaction."

Restenosis a Problem

In the current report, the researchers describe the safety and early outcomes in these same patients after endovascular treatment of stenoses in the internal jugular vein and the azygous vein.

Of the 65 patients, 35 had relapsing-remitting disease, 20 had secondary-progressive disease, and 10 had primary progressive MS. All underwent percutaneous transluminal angioplasty to address strictures in these veins. All procedures were done as day surgery under local anesthesia, and no operative or postoperative complications were seen, including vessel rupture, thrombosis, or adverse effects from contrast.

Postoperative headache was reported in 6 patients, which resolved spontaneously, and minor hemorrhages with hematoma occurred at vascular access sites "occasionally," the authors report.

After the procedure, venous pressure was significantly lower in the internal jugular and azygous veins (P < .001). Stenoses in these venous pathways "were never found to be isolated," the researchers note, but always combined in the internal jugular, azygous veins, or lumbar system in 4 main patterns of distribution.

At a mean follow-up of 18 months, the risk for restenosis after intervention was higher in the internal jugular vein, Dr. Zamboni noted, with a patency rate of 53% compared with 96% in azygous veins (95% confidence interval, 3.5 - 72.5; P < .0001).

Patency at follow-up depended on the type of obstruction faced, including membranous obstructions, twisting, and hypoplasia. A stent was placed in 1 patient to resolve a twisted vein, but a second case not treated with a stent retwisted, the authors note.

Using the patients as their own control, the researchers found improvement with treatment on some clinical outcome measures after the intervention, particularly for the relapsing-remitting patients. In this group, 27% were relapse-free before surgery and 50% were so after treatment (P < .001). Gadolinium-enhancing lesions on magnetic resonance imaging (MRI) fell from 50% to 12% on a blinded assessment (P < .001).

Significant improvement over the preoperative assessment was seen at 1 year on the Multiple Sclerosis Functional Composite again for relapsing-remitting patients (P < .008), but not among those with a secondary or primary progressive course.

Physical quality-of-life measures also improved significantly in relapsing-remitting MS patients and in primary-progressive patients, with a positive trend among those with secondary progressive disease. Mental quality of life also was significantly improved for the relapsing-remitting and primary progressive groups, but not for those with secondary progressive MS.

The authors conclude that although improved endovascular techniques are needed to approach the internal jugular vein, "the results of this pilot study warrant a subsequent randomized control study."

It is possible that the addition of stents to this endovascular approach that he calls the "liberation procedure" may improve outcomes, Dr. Zamboni noted. "However, the results are really interesting, if you think that all treated patients were already under the best treatment for MS and had adjunctive neurological benefits from the liberation procedure compared to the previous 2 years."

Mixed Response From Neurology Community

Asked for comment on these findings, Lily Jung, MD, from the Swedish Neuroscience Institute, Seattle, Washington, speaking on behalf of the American Academy of Neurology, was cautious in her assessment. She feels some of the strong claims in the current report are not supported by the data.

For example, the number of patients in the report is small, "and to make the correlation between the patterns of venous obstruction and the categories of MS is a real stretch," Dr. Jung said. Assessment was done by unblinded neurologists, which is "not ideal." She also noted that the MRI results used different techniques, different protocols, and different study intervals.

"The bottom line is that my colleagues and I have been flooded by calls and emails from patients who have been led by the publicity around this article to believe that there is a cure for MS, and to make such a claim with such preliminary results is premature," Dr. Jung said. "We would welcome some randomized, controlled, double-blinded studies to look at the issue, but before then would not be encouraging our patients to jump in with both feet to do this procedure, which has significant risks and has not been proven to be safe."

As a vascular interventionalist, Dr. Zamboni says he is keen to collaborate with neurologists in the setting of MS, but acknowledged that his work has had a mixed response from the neurology community. Some, he says, have been excited and at least curious, which in his view is important in research. Researchers from institutions including Stanford, Harvard, SUNY Buffalo, and others have asked to discuss the technique so that they may attempt to reproduce these findings in their own populations.

"To the contrary, of course, I've also found big opposition, but I think that probably it is a prejudgement, and they have not read the paper carefully," he said. "But it's not important. What is important is to have other people interested in doing the research and understanding more."

The first step will be to understand how widespread the presence of CCVI is among patients with MS, he said. "We need to test patients very rapidly to have the epidemiological data, which are very important."

Already, Dr. Zamboni is collaborating with Robert Zivadinov, MD, and colleagues at Buffalo General Hospital in New York on an open-label, MRI-blinded study of 16 relapsing-remitting patients with MS with confirmed strictures in the cerebrospinal venous outflow routes. Half — 4 randomly selected patients in Italy and 4 in New York — will undergo early intervention to address the blockages at 3 months, and 8 patients will have a delayed procedure at 6 months of follow-up.

Safety and preliminary efficacy will be monitored using MRI and clinical examination, and outcomes will be compared at 1 year. Dr. Zamboni and Dr. Zivadinov presented their protocol at the 25th Congress of the European Committee for the Treatment and Research in Multiple Sclerosis earlier this year in Düsseldorf, Germany.

In Buffalo, Dr. Zivadinov is also conducting a larger epidemiological study aimed at determining the prevalence of CCVI among their MS patients.

Dizzying Excitement, Desperate Hope

Although Dr. Zamboni has published previously on this procedure, a news report by a national Canadian news organization with an associated documentary on the same network recently profiled this work, generating a dizzying excitement for many patients in Canada, where MS rates are among the highest in the world. Their subsequent comments on various Internet news and patient sites reflect a desperate hope that this new approach may provide those with MS a possible alternative to lifelong drug therapy and the steady encroachment of disability.

In a public statement issued December 1, the National Multiple Sclerosis Society cautioned that the findings are preliminary. "Many questions remain about how and when this phenomenon [CCVI] might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to prove that this phenomenon is the cause of MS."

However, the society also notes that it is very interested in seeing more data on this procedure and is prepared to put its money where its mouth is, calling for research proposals to generate that data.

"If confirmed, these findings may open up new research avenues into the underlying pathology of MS, as well as potential new approaches to therapy," the statement notes. "The National MS Society has invited research proposals to investigate this lead, and is in active discussions with the MS Society of Canada about the possibility of collaborative funding of [CCVI] research."

The authors have disclosed no relevant financial relationships.

Source: Medscape Today © 1994-2009 by Medscape (07/12/09)

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

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

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

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

This work was presented at the Thirty-first Charing Cross Symposium, London, United Kingdom, Apr 3-7, 2009.

Paolo Zamboni, MDa, Roberto Galeotti, MDa, Erica Menegatti, RVTa, Anna Maria Malagoni, MDa, Sergio Gianesini, MDa, Ilaria Bartolomei, MDb, Francesco Mascoli, MDa, Fabrizio Salvi, MDb

^a Vascular Diseases Center, University of Ferrara, Ferrara, Italy

^b Department of Neurology, Bellaria Hospital, Bologna, Italy

Source: Journal Of Vascular Surgery © 2009 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.(02/12/09)

Multiple sclerosis (MS) is primarily an autoimmune disorder of unknown origin.

 This review focuses iron overload and oxidative stress as surrounding cause that leads to immunomodulation in chronic MS. Iron overload has been demonstrated in MS lesions, as a feature common with other neurodegenerative disorders.

However, the recent description of chronic cerebrospinal venous insufficiency (CCSVI) associated to MS, with significant anomalies in cerebral venous outflow hemodynamics, permit to propose a parallel with chronic venous disorders (CVDs) in the mechanism of iron deposition.

Abnormal cerebral venous reflux is peculiar to MS, and was not found in a miscellaneous of patients affected by other neurodegenerative disorders characterized by iron stores, such as Parkinson's, Alzheimer's, amyotrophic lateral sclerosis. Several recently published studies support the hypothesis that MS progresses along the venous vasculature.

The peculiarity of CCSVI-related cerebral venous blood flow disturbances, together with the histology of the perivenous spaces and recent findings from advanced magnetic resonance imaging techniques, support the hypothesis that iron deposits in MS are a consequence of altered cerebral venous return and chronic insufficient venous drainage.

Full Paper - http://www.nature.com/jcbfm/journal/v29/n12/full/jcbfm2009180a.html

Ajay Vikram Singh¹ and Paolo Zamboni²

¹Department of Physics, European School of Molecular Medicine (SEMM), IFOM-IEO Campus, Centro Interdisciplinare Materiali e Interfacce Nanostrutturati (CIMAINA), University of Milan, Milan, Italy
²Vascular Diseases Center, University of Ferrara, Ferrara, Italy

Source: Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1867–1878; doi:10.1038/jcbfm.2009.180 (30/11/09)

US scientists are testing a radical new theory that multiple sclerosis (MS) is caused by blockages in the veins that drain the brain.

The University of Buffalo team were intrigued by the work of Italian researcher Dr Paolo Zamboni who claims 90% of MS is caused by narrowed veins.

He says the restricted drainage, visible on scans, injures the brain leading to MS.

He has already widened the blockages in a handful of patients.

The US team want to replicate his earlier work before treating patients.

Experts welcomed the research saying it was important to confirm the basic science before evaluating any therapy.

MS is a long-term inflammatory condition of the central nervous system which affects the transfer of messages from the nervous system to the rest of the body.

The Buffalo team, led by Dr Robert Zivadinov, plan to recruit 1,100 patients with MS and 600 other volunteers as controls who are either healthy or have neurological diseases other than MS.

Using Doppler ultrasound, they will scan the patients to see if they can find any blockages within the veins of the neck and brain.

If they can prove Dr Zamboni's theory of " chronic cerebrospinal venous insufficiency", they say it will change our understanding of MS.

Rewriting science

Margaret Paroski, who is chief medical officer at Kaleida Health, where the Buffalo researchers are based, said the work could overturn prevailing wisdom that the damage in MS is predominantly the result of abnormal immune responses.

"When I was in medical school, we thought peptic ulcer disease was due to stress. We now know that 80% of cases are due to a bacterial infection.

"Dr Zivadinov's work may lead to a whole different way of thinking about MS."

Dr Zamboni, of the University of Ferrara, believes the blockages are the cause rather than the consequence of MS and that they allow iron from the blood to leak into the brain tissue, where it causes damage.

He has performed procedures similar to angioplasty to unblock the veins and get the blood flowing normally again.

He claims this "liberation procedure" can alleviate many of the symptoms of MS and is due to publish his findings in the Journal of Vascular Surgery.

In an interview with CTV News in Canada he said: "I found the evidence of narrowing - narrowing of the veins just in MS patients.

"I'm fully convinced that this is very, very important for people."

Early days

Kevin Lipp, an MS patient from the US, has been symptom-free since being treated by Dr Zamboni.

He said: "It's only been 10 months. If nothing happens in the next two to three years, we'll know it's working."

The BBC has heard anecdotally of other surgeons in Europe testing out the same treatment.

The MS Society said more research was needed to see if this was an avenue that should be explored further.

"This is not something patients can expect as a treatment now. This is experimental work and is being tested. We need to know more about its safety and effectiveness."

Helen Yates, of the MS Resource Centre (MSRC), said: "There is no doubt that this area warrants a great deal more study.

"This could represent a completely novel approach to MS research which, if proven to be relevant, could be a "sea change" in the understanding of the mechanisms involved in the condition."

Source: BBC News © British Broadcasting Corporation 2009 (27/11/09)

The Multiple Sclerosis Society of Canada announced it will request research operating grants related to chronic cerebrospinal venous insufficiency (CCSVI) and MS.

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

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

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

The competition will open on December 9, 2009, and the deadline for applications will be January 22, 2010.

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

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

Source: Multiple Sclerosis Society of Canada (24/11/09)

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

The researchers will test the possibility that the symptoms of MS result from narrowing of the primary veins outside the skull, a condition called "chronic cerebrospinal venous insufficiency," or CCSVI.

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

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

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

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

Margaret Paroski, M.D., executive vice president and chief medical officer of Kaleida Health, parent of Buffalo General Hospital where the BNAC is located, commented: "Will Rogers once said, 'It isn't what we don't know that gives us trouble, it's what we do know that ain't so'. Challenging basic assumptions about diseases has lead to some very important discoveries.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Commenting on the study, Helen Yates, Multiple Sclerosis Resource Centre Chief Executive said, “CCSVI is a very recent “discovery” in the field of MS and any work that can further Paolo Zamboni’s research and hypothesis is very welcome indeed.  As Robert Zivadinov,MD says, if CCSVI is proven to be the underlying cause of MS this would be a major sea change in the understanding of the disease, its cause and will open up new areas of research towards a potential cure”

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

Source: University at Buffalo © 2009 University at Buffalo. All rights reserved and MSRC (15/10/09)

Background:
The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated.

Methods:
Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement.

Results:
CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher.

Conclusion:
CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.

P Zamboni,¹ R Galeotti,¹ E Menegatti,¹ A M Malagoni,¹ G Tacconi,¹ S Dall’Ara,¹ I Bartolomei,² and F Salvi^2
1 Vascular Diseases Center, University of Ferrara, Ferrara, Italy
² Department of Neurology, Bellaria Hospital, Bologna, Italy

Source: J Neurol Neurosurg Psychiatry. 2009 April; 80(4): 392–399. (03/07/09)

© Multiple Sclerosis Resource Centre