Chronic cerebrospinal venous insufficiency (CCSVI)

What is CCSVI?

CCSVI is a syndrome characterised by poor removal of oxygen-depleted blood from the central nervous system. This is thought to be caused by a constriction of blood vessels in the brain and neck which affects brain blood flow and drainage.

It has been suggested that a reduction in blood flow can lead to blood leakage into surrounding tissue. This could result in a build-up of iron deposits in the central nervous system (CNS), which was hypothesised to trigger an immune response associated with MS.

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Why has CCSVI been linked to MS?

An early-stage study published in 2009 looked at the prevalence of CCSVI in people with MS, and found that CCSVI was present in 90 per cent of people with MS. Since then this has been contradicted by larger studies that have shown no difference in the rate of CCSVI amongst people with and without MS, there is still however an enormous amount of interest in the potential link between CCSVI and MS.

Numerous small studies into CCSVI diagnosis rates and treatment have been carried out and reported, all with varying results. This is due to great differences in the techniques used to diagnose CCSVI and the fact that the interpretation of results from these techniques is highly subjective, meaning diagnosis or treatment effect can be biased by the clinician or scientist reviewing the information.

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CCSVI and MS - what do we know?

In order to understand more about the prevalence of CCSVI in people with MS, the National Society in the US and the MS Society of Canada announced $2.4m of funding to support seven research projects in June 2010. The results of these studies, along with other large studies carried out in Europe, are highlighted below.

These studies:

  • Used large numbers of people both with and without MS
  • Used a range of different techniques. These included neurosonogaphy, a type of ultrasound carried out on the brain that can identify how blood flows in the nervous system. Other techniques used include MRI and the Doppler ultrasound technique, which is the technique used in the original study proposing a link between CCSVI and MS.
  • In these studies, diagnosis was carried out by experts who were ‘blinded’. This means they were not told if the images they assessed were from people with or without MS so the study results were not biased.


A large study  was carried out in Italy and involved 1,165 people with MS, 226 people with other neurodegenerative conditions (like Parkinson’s Disease) and 376 people without MS. They found that the number of people with CCSVI was extremely low (just over 3 per cent), and there was no significant difference in the rate of CCSVI between the 3 groups.

The first NMSS funded study was carried out by researchers in Texas and involved over 200 people with, and 70 people without MS. In this study, researchers found that the rate of CCSVI was much lower in general than previous reports, and that diagnosis was in fact higher in people without MS (7 per cent) than people with MS (under 4 per cent). The study also showed that there were no significant differences in blood flow rates between people with MS and people without.

Comparing techniques for diagnosis

Researchers in Canada investigated CCSVI using a number of different techniques, including ultrasound and catheter venography. The study involved 177 people – 79 people with MS, 55 of their siblings and 43 unrelated people who didn’t have MS. They found that the technique used made a big difference to the number of people diagnosed with CCSVI, which could explain why results differ from trial to trial. Whichever technique they used however, they found that there was no difference in the prevalence of CCSVI in people with MS compared to those without.

Another study was carried out in Cleveland. The study involved 90 people with MS and 80 people without MS, and used ultrasound and MRI techniques to investigate the prevalence of CCSVI. As with the Canadian study above, they found that the prevalence of CCSVI differed depending on the technique and the criteria used to diagnose CCSVI. They did not however find any difference in the prevalence of CCSVI in people with MS compared to those without.

Researchers in Alberta compared vein drainage between 120 people with MS and 60 people without MS using ultrasound and MRI techniques. The study revealed no differences in the proportion of vein flow abnormalities between people with and without MS. Researchers also revealed concerns about the proposed criteria for diagnosis of CCSVI, finding that there was a large, natural variance in the anatomy of the veins in the head and neck and that vein drainage can be affected by as little as how the person is lying or siting during the test.

A study in Ottawa used an extremely powerful MRI machine to look not only at the veins in the neck, but also to assess for the presence of iron deposits in the brain (which has been linked to CCSVI). The study involved 100 people without MS, and the researchers found that variations in the anatomy of the veins in the neck and chest were quite common in the people in the trial. They therefore concluded that these variations are not unique to people with MS.

CCSVI and childhood MS

A study in Toronto focused on CCSVI in relation to MS in children. The study involved 26 children with MS, 26 age-matched controls who did not have MS, and 13 young adults with paediatric-onset MS. They found that CCSVI was not associated with an increased risk of paediatric MS.

CCSVI research - next steps

Taken together, these large studies provide evidence that there is no link between CCSVI and the risk of developing MS. There is still one ongoing study at the University of Wisconsin. Researchers are investigating the rate of vein drainage in 112 people with MS, 56 people without MS and 56 people with other neurological conditions - we look forward to seeing the results.

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Clinical trials investigating the effect of treating CCSVI on MS

In addition to studies on prevalence, there have also been a few small scale clinical trials looking at the safety and effectiveness of treating CCSVI for people with MS.

The proposed treatment for CCSVI involves opening blocked or narrowed veins by inflating a small balloon or inserting a stent to allow for better blood flow and improve drainage of blood from the brain.

These early studies focused mainly on the safety of the treatment. They also looked at the effect of the surgery on relapse rate and disability. All of these studies were open labelled, meaning that placebo effects were not accounted for. It remains difficult to draw firm conclusions on the potential risks and benefits of CCSVI treatment in people with MS without larger and better controlled studies.

There are a number of studies that have looked at the risk of the surgery for treating CCSVI. Some complications that have been described are:

  • Developing clots in the vein
  • Arrhythmias (disruptions to the heart beat and rhythm)
  • Vein dissection (separation of the vein)
  • In-stent thrombosis (bleeding at the site of the stent placement)
  • Vein rupture
  • Groin hematoma (collection of blood outside the blood vessel).

In May 2012 the US Food and Drug Administration (FDA) issued a safety communication on CCSVI, which outlines reports of adverse events associated with treatment for CCSVI.

Some people with MS have had treatment for CCSVI privately. The MS Society recommends against seeking an unproven treatment, like CCSVI, outside of a properly regulated clinical trial, due to the potential risk of undergoing such unknown therapies.

The PREMiSe Trial

In 2014, researchers in the USA reported the results of a Phase 2 (mid-stage) trial into treating CCSVI as a means of therapy for people with both relapsing remitting and progressive MS. Nineteen people were involved in the trial, nine of whom underwent a procedure to widen the veins in the neck called venous angioplasty. Compared to the group who didn’t undergo the surgery, there was a trend among the angioplasty group to have a higher relapse rate and a higher number of new lesions.

The results of this trial shows that treating CCSVI does not effectively prevent the progression of MS, and may in fact exacerbate some aspects of the condition, like number of lesions and relapses.

Canadian Interventional CCSVI Trial

In 2011, the Canadian government and the MS Society of Canada announced that they would fund a phase 1/2 clinical trial of CCSVI treatment and MS. The trial will involve approximately 100 people with relapsing remitting or secondary progressive MS, and will look at the safety and impact of the treatment on MS. This trial is estimated to finish in May 2017.

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