Sunday January 21st 2018

CCSVI Explained

Chronic cerebro-spinal venous insufficiency (CCSVI) is a syndrome in which the flow of blood in the cervical and thoracic veins, from the central nervous system (CNS) to the heart, is compromised and less efficient. It is proposed that insufficient venous blood flow, in turn, promotes development of brain dysfunction, especially multiple sclerosis.

The reported blood flow compromises involve both reduced and intermittently reversed (reflux) flow velocities in the cerebral veins, changed brain capillary dynamics (altering the blood-brain barrier), and are reportedly associated with stenosis of the jugular and azygos veins. Such a vascular picture was described by Paolo Zamboni in 2008, who also reported an association of CCSVI with multiple sclerosis (MS). The hypothesis has generated optimism, especially from patients, for more effective treatment options for multiple sclerosis. It has also been received with skepticism by some in the medical community, as well as efforts by some institutions to support research into it.

This syndrome was described on 2008 by Paolo Zamboni, one of the main defenders of its relationship with multiple sclerosis. CCSVI had a high sensitivity and specificity differentiating healthy individuals from those with multiple sclerosis. It was soon followed by small open-label study which reported a positive effect of angioplasty in MS patients with CCSVI by the same research group. The first international symposium took place in 2009, at Bologna, Italy. Venous stenosis due to developmental abnormalities was established as the primary cause of CCSVI by the International Union of Phlebology. In 2010 there were conflicting results when evaluating the relationship between MS and CCSVI.

Symptoms and consequences
Potential consequences of the syndrome could be hypoxia, delayed perfusion, reduced drainage of the catabolites and increased transmural pressure, and iron deposits around the cerebral veins.

When MS patients diagnosed with CCSVI in the Zamboni’s studies underwent catheterization of the azygous and IJV veins, the authors claimed that such veins were stenosed in around 90% of the cases. Nevertheless this part of the study was not blinded, reducing its reliability. A vascular component in MS had been cited previously.

It has been theorized by Zamboni and colleagues that the malformed blood vessels caused increased deposition of iron in the brain, which in turn triggers autoimmunity and degeneration of the nerve’s myelin sheath. Nevertheless iron deposition occurs in different neurological diseases such as Alzheimer’s disease or Parkinson’s disease but CCSVI was not seen in their control group with neurological problems.

CCSVI was first found combining extracranial and transcranial doppler sonography. Five parameters of venous drainage have been proposed to be characteristic of the syndrome, although having two of them is enough for diagnosis of CCSVI:

  • reflux in the internal jugular and vertebral veins,
  • reflux in the deep cerebral veins,
  • high-resolution B-mode evidence of stenosis of the internal jugular,
  • flow in the internal jugular or vertebral veins that could not be detected with Doppler, and
  • reverted postural control of the main cerebral venous outflow pathways.

Use of Magnetic resonance venography for the diagnosis of CCSVI in MS patients has limited value, and has been proposed to be used only in combination with other techniques.

While the initial article on CCSVI claimed that abnormal venous function parameters were not seen on healthy people others have noted that this is not the case. In the report by Zamboni none of the healthy participants met criteria for a diagnosis of CCSVI while all patients did. Such outstanding results have raised suspicions on a possible spectrum bias, which originates on a diagnostic test not being used under clinically significant conditions.

While the original results have been replicated in a second study, others have found CCSVI to only occur in 20% of MS patients.

There has been a small pilot study which used balloon angioplasty to treat MS patients who had been diagnosed of CCSVI and had their cerebral veins stenosed. This study reported a clinical benefit, specially in those patients with the relapsing-remitting subtype. In the follow-up of these patients (up to 18 months) there was a very high rate of re-stenosis (around 50%). Improvements in this study are hard to interpret due to the lack of a control group and blindness among the evaluators, small treated sample, and use of approved therapies for the disease among patients.

The high re-stenosing rates led the authors of the pilot study to propose that the use of stents might be a more feasible treatment. Rare but serious adverse events have been reported when using stents. Some US hospitals have banned the surgical procedure outside of clinical trials until more evidence to support its use is available.

Research directions
A larger study is ongoing at Buffalo Neuroimaging Analysis Center to study the relationship between CCSVI and MS with a press release claiming preliminary results supporting the link.

The Multiple Sclerosis Society of Canada has committed to funding further experimental trials on the hypothesis, though the head of the organization noted that the results “merit serious and robust studies” but also “pleaded with patients to not do anything drastic until the theory is tested and proven”.

The hypothesis has generated optimism, especially from patients, for more effective treatment options for multiple sclerosis. It has been received with caution or skepticism by some experts, who found it to rely on too limited data to support at least some of the following claims: (a) that the syndrome actually exists; (b) that it could be causative of (or a co-factor in) multiple sclerosis; (c) that vascular treatments for the syndrome would prevent or reduce the incidence of multiple sclerosis.

Both the neurology community and some MS organizations such as the National Multiple Sclerosis Society of the USA recommend not to use the proposed treatment until its effectiveness is confirmed by controlled studies

4 Comments for “CCSVI Explained”

  • joe longo says:

    Hello kind folks: Great site. I can’t see where I can sign up to your site. Just a log in feature but not a new member button. Unless I missed it.

    I know at least 10 people that would enjoy going to your site.
    Plese send me the needed info. Thanks Joe

  • Deana Grenier says:

    First this is my understanding of what has been thought to be Multiple Sclerosis (MS)

    The theory is that MS is an “auto immune disease” which basically means the immune system attacks the brain and central nervous system for some unknown reason. The treatment for this disease has been to use immune system suppressants to prevent the immune system from attacking.
    It has recently been pointed out that this theory has never actually been proven.

    Some time in 2009 an Italian Doctor, Paulo Zamboni came out with some research he had been doing. This Doctor was vested in finding the cause of MS because his wife had gotten the disease. He had found some old research that had tried to make the link between the blood flow to and from the brain and MS and he thought that they might have been onto something. So he tested this theory out on his wife. In the mean time the study of the vascular system has greatly advanced in the years since the original connection had been made and Dr. Zamboni was able to have a colleague of his who specialized in venous disease check his wife more thoroughly then had ever been done before. Much to their surprise and amazement they found narrowing in the tiny veins leading to and from the brain. Years before, these veins may not have been visible to humans, as the technology did not exist.

    They opened these veins up using a procedure called angioplasty, most commonly used to open clogged arteries in the heart. Mrs. Zamboni’s symptoms were greatly lessoned by having her veins opened.

    Thus the new theory had been proposed. The immune system was not attacking the brain for “no reason”. The lessened flow of blood to and from the brain and central nervous system was causing a build up of iron deposits and whatever else the blood flow is supposed to clean up and the immune system is actually attacking these things.

    So if you open up the blood flow, restoring the bodies’ natural cleansing process, the immune system will no longer have anything to attack. This has been dubbed the “Liberation Treatment”, because people who have had this procedure feel as though they have been liberated from their symptoms of ms.

    They are testing this theory and so far it looks like it could be the case. Many of people suffering with MS do not want to wait for this theory to be proven. They have seen enough and are allowing themselves to have this procedure before the theory is scientifically proven. The reality is weather or not this is a “cure” or cause of MS doesn’t really matter. For people suffering with MS any lessening of symptoms is a welcome course of treatment!

    We believe in Liberation!

  • Steve says:

    This a hopefull breakthough for MS patients. Anyone with MS or has family with MS needs to demand the Canadian government accept this as treatment. The problem is that the interests of the BIG PHARMACEUTICAL companies control the Healthcare System in North America. Do you think big PHARMA wants a cure ? The answer is NO They want everyone with MS and other chronic diseases to be at the mercy of them and their profit hungry agenda.Time to rise up and defeat the greedy interests of BIG PHARMA and have this therapy available to anyone that needs in in Canada !! It is a disgrace for anyone in an advanced country such as Canada have to go to places like India to get this done !!

  • Lynne Davidson says:

    I strongly agree that the liberation technique should be an available option for all MS sufferers in Canada.

    There is another aspect that should be concurrently investigated in MS patients: the presence of a persistent viral infection in the CNS caused by the Bornavirus, an emerging zoonotic virus that neurologists are currenly ignoring. MS sufferers should have access in Canada to the European blood test procedure to determine if they suffer from Bornavirus infection.


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