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What is CCSVI?

A Basic Definition
The Technical Definition
The Origin and History of CCSVI

A Basic Definition

CCSVI stands for “Chronic Cerebrospinal Venous Insufficiency,” a condition where people have obstructed blood flow in the veins that drain the central nervous system (the brain and spinal cord). Research indicates that CCSVI is significantly correlated with multiple sclerosis.1, 2,3,4

As a result of these venous abnormalities, the blood flow rate through the central nervous system back toward the heart may become slowed, and blood may reflux back toward the brain and spine.1

People with CCSVI have one or more of the following blockages of the veins that drain blood from the central nervous system:

  • Stenosis is an abnormal narrowing of the veins that restricts blood flow. Types of stenoses include the collapse of the vein, twisting of the vein, ring-like narrowings in the vein, and other similar obstructions
  • An abnormal valve, septum, flap, or membrane that blocks or inhibits blood flow through the veins
  • Atresia, hypoplasia, or agenesis are severe venous problems, including veins that are partially closed, underdeveloped, minimally formed, or almost entirely missing

The animation below shows how stenosis in veins draining the central nervous system can cause CCSVI. This animation was provided by Dr. Zamboni.

The Technical Definition

The term CCSVI was coined by Dr. Paolo Zamboni of the University of Ferrara, Italy, in 2008. Dr. Zamboni defines a technical diagnosis of CCSVI based on the presence of two or more of the five indicators of CCSVI as measured by duplex ultrasonography.

  1. Reflux in the Internal Jugular Veins (IJVs); in the vertebral veins (VV); or both, while the head is in any position. (Measurements should be taken when patient is breathing normally and not while coughing or engaged in a Valsalva maneuver);
  2. Reflux in the deep cerebral veins, and/or in other venous segments of the intracranial compartment;
  3. High-resolution B-mode evidence of IJV stenosis; (that is, high-resolution Doppler ultrasound indicates stenosis in an internal jugular vein);
  4. Flow not detected by Doppler in one or both the IJVs or VVs;  
  5. Reverted postural control of the main cerebral venous outflow pathways (That is, when a cross sectional area of the IJV is wider in a sitting position than in the supine posture, a result indicating abnormal venous blood drainage in the sitting/upright position).

Note that researchers and physicians in the United States haven't always applied Dr. Zamboni’s precise diagnostic definitions of CCSVI in their work, typically because U.S. physicians and researchers are not trained in CCSVI diagnosis via the sophisticated duplex ultrasonography used by Dr. Zamboni’s team. In the United States, CCSVI is typically indicated by confirmed blockages or malformations of any/all of the major blood vessels draining the brain and spine (typically, the left and right internal jugular veins, the azygos, lumbar and vertebral veins), and/or by the presence of Reflux.

For detailed information about CCSVI Theory, Diagnosis, and Treatment, please see our Advanced Topics section.

The Origin and History of Today's “CCSVI”

Dr. Zamboni’s basic hypothesis that vascular abnormalities are linked with MS is neither a new nor a radical theory. Rather, it is supported by multiple scientific observers dating back 170 years.

Dr. Zamboni’s personal journey leading to the rediscovery of the vascular link to MS, and his subsequent elaboration of this connection, began more than twenty years ago, when he was a vascular surgeon in Sardinia, Italy. Sardinia is geographically isolated and, for reasons largely unknown, contains very high rates of MS. Studying children in Sardinia, Dr. Zamboni discovered that a great number of them had malformations in their jugular veins. This work lead to one of his earliest professional publications, “The so-called primary venous aneurysms,” published in Phlebology, in 1990.

Dr. Zamboni’s career then included a visiting position at the University of California, San Francisco, followed by a return to the University of Ferrara, Italy, where he published over 30 additional scientific papers on various aspects of the venous system, including diagnosis and treatment for venous abnormalities, and physiologic and neurologic components of venous disease.

In the late 1990s, Dr. Zamboni’s wife was diagnosed with Multiple Sclerosis. As a result, Dr. Zamboni returned his focus to MS, augmenting his early observations in Sardinia with his more recent expertise about the venous system.

To better understand the venous relationship with MS, Dr. Zamboni began using sophisticated imaging equipment (including MRI and Ultrasound) to study the physiologic parameters linked to cerebral blood return in about 500 normal volunteers who were recruited among medical students, residents, and staff of the St. Anna University Hospital in Ferrara, Italy. Subsequently, he began imaging the primary veins responsible for blood flow out of the brain and spinal cord of patients with MS. Reminiscent of what he found in Sardinia, he discovered that they were abnormally narrowed, and even blocked in some places. Because this finding indicated significant differences between the cerebral venous hemodynamics in healthy patients versus MS patients, he began more rigorous investigations into both venous abnormalities in the neck and related veins, and into various MRI and ultrasound methods for studying these issues.

By enhancing diagnostic accuracy with high resolution Doppler-based ultrasound and color-coded data displays (together, called Duplex Ultrasonography), Dr. Zamboni was able to view the actual blood flow inside the main cerebral outflow routes from the head and neck. There, he discovered that, in some cases, blood was actually flowing backwards, or refluxing, into the central nervous system of some of his patients.

Dr. Zamboni and his colleagues imaged the veins of several dozen additional MS patients. They found virtually all of them had venous abnormalities (a finding not seen in healthy control subjects), and many of those abnormalities appeared to be congenital.

After extensively detailing a range of venous obstructions, including abnormal webs of tissue obstructing blood flow, abnormal flaps and septums, frozen or malformed valves, and membranous obstructions, Dr. Zamboni and his colleagues’ work was recognized by the International Union of Plebologists (IUP).  The IUP formally designated CCSVI-related venous obstructions as recognized “truncular” venous malformations in their 2009 Consensus document.6 The IUP is the world’s largest scientific society dedicated to study of venous disease.

Dr. Zamboni and his team continued to find that many of the venous malformations, including agenesis and atresia, appeared developmental in origin. While additional pathological study on the origins of venous obstructions is ongoing, evidence currently suggests that, because many of these obstructions are likely developmental, CCSVI obstructions may precede the onset of MS. Dr. Zamboni’s current hypothesis is that congenitally or developmentally malformed veins causing a chronic insufficient CNS drainage could be a contributing cause of inflammation, which in turn could eventually lead to an immune response.

Specifically, Dr. Zamboni hypothesized that CCSVI could damage CNS tissue in a variety of ways, notably by breaching the blood brain barrier of stressed, dilated, and inflamed blood vessels, and leaking iron and other antigens into nearby tissues. This, after all, would explain an ages-old observed characteristic of MS that has been confirmed and reconfirmed over the years but never explained: MS lesions are “venocentric” – that is, they occur around veins in the brain and spinal cord. 

Finally, given these findings, and based on his theory connecting MS and venous obstruction, Dr. Zamboni theorized that if venous obstructions could be removed, perhaps some relief of MS symptoms could be achieved. Thus, together with a group of neurologists and physicians, his team began treating MS patients with a technique known as Percutaneous Balloon Angioplasty (PTA).

Today, based on Dr. Zamboni’s findings and his theory of CCSVI, doctors in the United States, Europe, South Asia, and the Middle East have begun treating venous obstructions by using either PTA, stents, or  both. Further, independent research is currently underway attempting to confirm, or refute, the link between CCSVI and MS as well as the efficacy of CCSVI Treatment.

Lastly, it should be noted that while Dr. Zamboni has received substantial attention for his efforts, he has not been working alone: a team of dedicated research physicians have played a pivotal role in the development, testing, and reporting of all aspects of CCSVI. The Italian team of Drs. Galeotti, Menegatti, Salvi, Gianesini, Bartolomei, Mascoli, and Malagoni, has made significant contributions to CCSVI.

In the United States, the first case of CCSVI treatment and the first formal treatment protocols were pioneered by Dr. Michael Dake of Stanford University.  Dr. E. Mark Haacke of Wayne State University, McMaster University, the Brain Body Institute, and the MRI Institute for Biomedical Research, is at the forefront of developing CCSVI imaging protocols, and, particularly iron quantification.  Dr. Robert Zivadinov of the Buffalo Neuroimaging Analysis Center at the University of Buffalo is leading clinical trials testing the relationship between CCSVI and MS, and the efficacy of CCSVI treatment.  Dr. Salvatore Sclafani of Kings County Hospital Center and SUNY Downstate College of Medicine was one of the first U.S. physicians to reach out directly to the MS community, making CCSVI information and treatment more widely available. Since these physicians began their CCSVI work, many others have followed. 


  1. Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry. 2009; 80: 392-399
  2. Al-Omari MH,  Rousan, LA. Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. International Angiology.  April, 2010; 29(2):115-120
  3. Simka M, Kestecki J, Zaniewski M, Majewski E, Hartel M. Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis. International Angiology.  April, 2010; 29(2): 109-114
  4. Zivadinov, R. Preliminary Result
  5. Bartolomei I, Salvi F, Galeotti R, Salviato E, Alcanterini M, Menegatti E, Mascalchi M, Zamboni P.  Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis. Correlation with symptoms at onset and clinical course. International Angiology. 2010 Apr;29(2):183-8.
  6. Lee BB, Bergan J, Gloviczki P, Laredo J, Loose DA, Mattassi R, Parsi K, Villavicencio JL, Zamboni P. Diagnosis and treatment of venous malformations Consensus Document of the International Union of Phlebology (IUP)-2009. International Angiology. 2009 Dec;28(6):434-51.)

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