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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.

Prevalence of CCSVI in multiple sclerosis: a blinded sonographic evaluation(23/01/15)

L Tromba, S Blasi, A Vestri, D Kiltzanidi, F Tartaglia, A Redler


Objectives: To verify the prevalence of chronic cerebrospinal venous insufficiency in patients affected by different clinical forms of multiple sclerosis and in healthy subjects using the Zamboni ultrasound protocol combined with M-mode ultrasound examination.

Materials and methods: We enrolled 112 patients with multiple sclerosis and 67 healthy subjects from 20 to 67 years of age. All the patients underwent Duplex and color-Doppler sonography of the neck vessels, transcranial colour duplex sonography, M-mode study of the valve system and of venous abnormalities. Subjects were positive for chronic cerebrospinal venous insufficiency when at least two of five hemodynamic criteria of the Zamboni protocol were fulfilled. Chronic cerebrospinal venous insufficiency condition was further analyzed by a multivariate analysis including age, sex, disease duration, subtypes of multiple sclerosis and expanded disability status scale score as independent variables.

Results: No healthy subjects was positive for chronic cerebrospinal venous insufficiency, while in the sample of patients affected by multiple sclerosis the diagnosis was made in 59.8% of cases (p < 0.0001). The first criterion was the most frequent in patients affected by multiple sclerosis and chronic cerebrospinal venous insufficiency (respectively 54.4% and 76.1%, p < 0.001). The second, third and fourth criteria were never present in healthy subjects but were detected in patients with multiple sclerosis. The positivity of the second criterion was associated with diagnosis of chronic cerebrospinal venous insufficiency in 100% of cases. The third criterion had a prevalence of 52.2% in the subgroup of chronic cerebrospinal venous insufficiency patients. It was positive in 36 multiple sclerosis patients and was associated with chronic cerebrospinal venous insufficiency diagnosis in all cases except one. The multivariate analysis showed that age, disease duration, sex, subtypes of multiple sclerosis and expanded disability status scale score were not considered predictors of this haemodynamic condition.

Conclusion: Chronic cerebrospinal venous insufficiency is a haemodynamic condition strongly associated with multiple sclerosis and is not found in normal controls. The addition of M-mode ultrasound to the diagnostic protocol allows improved observation of venous valve abnormalities.

Full Article 

Source: Phlebology: The Journal of Venous Disease © 2015 by SAGE Publications (23/01/15)

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.


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)