Dr. Rafael Moguel, the Director of the Clinic of the Heart at the Amerimed Hospitals in Los Cabos is conducting CCSVI clinical trials for MS sufferers. If interested in participating in the trial contact:
Dr. Rafael Moguel at cathboss@gmail.com

Written by Ashton Embry PhD for New Pathways Magazine. Nº 57. September/October 2009 Since then, clinical testing is being performed by Dr. Rafael Moguel and his team of specialists at the Clinic of the Heart in the Amerimed Hospital in Los Cabos, Mexico

In August, I received a message asking me what I thought about CCSVI in multiple sclerosis. I had the same reaction most of you did when you read the title of this article – “What the hell is CCSVI?” A Google search told me it stood for “chronic cerebrospinal venous insufficiency” and a PubMed search led me to a handful of papers on CCSVI, all authored by an Italian vascular researcher/surgeon named Paolo Zamboni.

The papers provided solid and mind-expanding evidence that an entirely new disease process was part of MS. It soon became clear that the concept of CCVSI had the potential to completely change how we saw MS and how to treat it.

The Italian researchers discovered that, in persons with multiple sclerosis, the veins which acted as the main drainage pathways for blood flowing from the brain back to the heart were substantially narrowed and even blocked. These included the jugular veins, veins along the spinal column, and other veins I had not heard of before such as the azygous vein.

The researchers had never seen these problems in anyone before. Their equipment allowed them to study the blood flow in the veins and to also take pictures of the veins. They found that all the persons with MS they examined had impaired venous drainage from the brain and that such a problem caused the phenomenon of “reflux”. This means the venous blood would flow back toward the brain as it established new pathways around the blocked and narrowed veins. They labeled this compromised venous drainage as CCSVI.

Improper venous drainage is well known in the lower torso of many people (e.g. varicose veins, etc). In some cases, it has been demonstrated that poor venous flow in the lower body can result in iron deposition and associated inflammation. Furthermore, sclerosis and degenerative lesions can occur with the inflammation.

Knowing the problems that poor venous drainage can cause in the lower torso, Zamboni and his co-authors offered the reasonable interpretation that the reflux action of the blood flow into the veins of the brain resulted in iron deposition and inflammation of the blood-brain barrier (BBB). Notably iron deposits have long been documented in MS lesions and it is well known that every MS lesion forms symmetrically around a vein. Such characteristics of MS lesions have never been satisfactorily explained before the Zamboni discoveries.

In the MS literature, there are two opposing hypotheses for how MS autoimmunity begins. The most popular one is that myelin-sensitive T cells are activated through molecular mimicry by a childhood virus such as EBV. The myelin-sensitive T cells then cross the BBB and lead an autoimmune attack on myelin.

The other hypothesis is that the initial event in the MS disease process is a breech of the BBB and the consequent exposure of the central nervous system to the immune system. This uncovering of previously hidden antigens not seen before by the immune system leads to an autoimmune attack on myelin.

With the work of Dr Zamboni, it now appears that the second hypothesis, the breech of the BBB due to impaired venous drainage, is the best explanation for the initiation of MS autoimmunity. In support of this, the researchers found that, of the 109 persons with MS studied, every last one of them had impaired venous drainage. Furthermore, of the 177 control subjects, a group that included persons with other neurological diseases and healthy people of various ages, not a single one had impaired venous drainage from the brain. Such a 100% separation of persons with MS from controls on the basis of impaired venous drainage leaves little doubt that such a phenomenon is very important in the MS disease process.

Another important observation made by Zamboni’s team is that the pattern of reflux, that is, the specific pathway the blood uses to flow back to the brain, showed a strong correlation to the type of MS. Persons with PPMS had a different reflux pattern that those with RRMS and SPMS. Furthermore, the PPMS reflux pattern provided a good explanation why this form of MS is more aggressive and problematic.

The other convincing data that demonstrates that CCSVI is a key part of MS are the results from the use of a treatment which relieves the venous drainage problems. This treatment is called „the liberation procedure”. The problematic veins are first identified by venography. Then, balloon angioplasty is used to open up the problematic veins and, in some cases, stents are inserted in non- responding sections. The procedure is relatively non-invasive and is done in day hospital under local anesthesia. Access to the veins is through the left femoral vein in the thigh. Total time in the hospital is usually less than 6 hours and the subject has a compression dressing on for 24 hours.

Dr Zamboni has described the results of the use of the liberation procedure on 51 patients with relapsing-remitting MS. Eighteen of the subjects were treated in emergency with an acute attack and all of them had their symptoms completely resolved within a few hours to a few days. The other subjects had a greatly reduced yearly attack rate and, notably, the only ones experiencing an attack following the procedure were those who had a recurrence of the impaired venous drainage problems. The subjects also reported a dramatic improvement in chronic fatigue. In summary, it would appear that the relief of venous drainage problems results in major improvements of MS symptoms. This is further evidence of the major role that CCSVI plays in MS.

Finally the researchers noted that there was no difference in the severity of venous drainage problems between those using an MS drug and those not on a drug.

Given that CCSVI explains why PPMS differs from RRMS, as well as the occurrence of previously inexplicable features of MS lesions (e.g. venocentricity, iron deposits), CCSVI becomes a very compelling explanation for the initiation of CNS autoimmunity which drives MS. Further research is needed to confirm this.

Perhaps the most important question that remains is “what is the ultimate cause of the venous drainage problems?” Zamboni and colleagues did not offer any explanations/speculations on this. Hopefully, this question will be the subject of an intensive research effort. It is worth noting that, given adequate vitamin D in childhood prevents MS in most cases, vitamin D supply must have a substantial effect on the venous drainage system.

This new understanding of the MS disease process makes the use of the recommended nutritional strategies even more imperative. These strategies enhance blood flow, strengthen the BBB, counteract autoimmune reactions and quite possibly improve venous drainage from the brain. Overall, the Zamboni work provides further insight into why nutritional strategies work so well for many people.

In answer to the question in the title of this article, I am convinced that CCSVI is a huge breakthrough for MS. Correction of this problem with a relatively simple procedure may well turn out to be a very effective, long lasting, drug- free treatment for MS at the time of diagnosis. However, a great deal of research and clinical testing will have to happen before CCSVI is widely accepted as a key part of MS and the liberation procedure becomes standard procedure. In the past, non-drug treatments for MS have been marginalized, mainly for financial reasons. I predict it will be a long, hard fight to get the treatment of CCSVI from the laboratory to the clinic.

“I am confident that this could be a revolution for the research and diagnosis of multiple sclerosis,” Dr. Zamboni said in an interview.
Not everyone is so bullish: Skeptics warn the evidence is too scant and speculative to start rewriting medical textbooks. Even those intrigued by the theory caution that MS sufferers should not rush off to get the surgery – nicknamed the “liberation procedure” – until more research is done.
U.S. and Canadian researchers are trying to test Dr. Zamboni’s premise.
For the Italian professor, however, the quest was both personal and professional and the results were stunning.
Fighting for his wife’s health, Dr. Zamboni looked for answers in the medical literature. He found repeated references, dating back a century, to excess iron as a possible cause of MS. The heavy metal can cause inflammation and cell death, hallmarks of the disease. The vascular surgeon was intrigued – coincidentally, he had been researching how iron buildup damages blood vessels in the legs, and wondered if there could be a similar problem in the blood vessels of the brain.
Using ultrasound to examine the vessels leading in and out of the brain, Dr. Zamboni made a startling find: In more than 90 per cent of people with multiple sclerosis, including his spouse, the veins draining blood from the brain were malformed or blocked. In people without MS, they were not.
He hypothesized that iron was damaging the blood vessels and allowing the heavy metal, along with other unwelcome cells, to cross the crucial brain-blood barrier. (The barrier keeps blood and cerebrospinal fluid separate. In MS, immune cells cross the blood-brain barrier, where they destroy myelin, a crucial sheathing on nerves.)
More striking still was that, when Dr. Zamboni performed a simple operation to unclog veins and get blood flowing normally again, many of the symptoms of MS disappeared. The procedure is similar to angioplasty, in which a catheter is threaded into the groin and up into the arteries, where a balloon is inflated to clear the blockages. His wife, who had the surgery three years ago, has not had an attack since.
The researcher’s theory is simple: that the underlying cause of MS is a condition he has dubbed “chronic cerebrospinal venous insufficiency.” If you tackle CCSVI by repairing the drainage problems from the brain, you can successfully treat, or better still prevent, the disease.
“If this is proven correct, it will be a very, very big discovery because we’ll completely change the way we think about MS, and how we’ll treat it,” said Bianca Weinstock-Guttman, an associate professor of neurology at the State University of New York at Buffalo.
The initial studies done in Italy were small but the outcomes were dramatic. In a group of 65 patients with relapsing-remitting MS (the most common form) who underwent surgery, the number of active lesions in the brain fell sharply, to 12 per cent from 50 per cent; in the two years after surgery, 73 per cent of patients had no symptoms.
“ I am confident that this could be a revolution for the research and diagnosis of multiple sclerosis ”— Dr. Paolo Zamboni
Augusto Zeppi, a 40-year-old resident of the northern Italian city of Ferrara, was one of those patients. Diagnosed with MS nine years ago, he suffered severe attacks every four months that lasted weeks at a time – leaving him unable to use his arms and legs and with debilitating fatigue. “Everything I was dreaming for my future adult life, it was game over,” he said.
Scans showed that his two jugular veins were blocked, 60 and 80 per cent respectively. In 2007, he was one of the first to undergo the experimental surgery to unblock the veins. He had a second operation a year later, when one of his jugular veins was blocked anew.
After the procedures, Mr. Zeppi said he was reborn. “I don’t remember what it’s like to have MS,” he said. “It gave me a second life.”
Buffalo researchers are now recruiting 1,700 adults and children from the United States and Canada. They plan to test MS sufferers and non-sufferers alike and, using ultrasound and magnetic resonance imaging, do detailed analyses of blood flow in and out of the brain and examine iron deposits.
Another researcher, Mark Haacke, an adjunct professor at McMaster University in Hamilton, is urging patients to send him MRI scans of their heads and necks so he can probe the Zamboni theory further. Dr. Haacke is a world-renowned expert in imaging who has developed a method of measuring iron buildup in the brain.
“Patients need to speak up and say they want something like this investigated … to see if there’s credence to the theory,” he said.
MS societies in Canada and the United States, however, have reacted far more cautiously to Dr. Zamboni’s conclusion. “Many questions remain about how and when this phenomenon might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to suggest that this phenomenon is the cause of MS,” said the Multiple Sclerosis Society of Canada.
The U.S. society goes further, discouraging patients from getting tested or seeking surgical treatment. Rather, it continues to promote drug treatments used to alleviate symptoms, which include corticosteroids, chemotherapy agents and pain medication.
Many people with multiple sclerosis, though, are impatient for results. Chatter about CCSVI is frequent in online MS support groups, and patients are scrambling to be part of the research, particularly when they hear the testimonials.
Kevin Lipp, a 49-year-old resident of Buffalo, was diagnosed with MS a decade ago and has suffered increasingly severe attacks, especially in the heat. (Heat sensitivity is a common symptom of MS.) His symptoms were so bad that he was unable to work and closed his ice-cream shop.
Mr. Lipp was tested and doctors discovered blockages in both his jugular and azygos veins. In January of this year, he travelled to Italy for surgery, which cleared five blockages, and he began to feel better almost immediately.
“I felt good. I felt totally normal. I felt like I did years ago,” he said. He has not had an attack since.
As part of the research project, Mr. Lipp’s siblings have also been tested. His two sisters, both of whom have MS, have significant blockages and iron deposits, while his brother, who does not have MS, has neither iron buildup nor blocked arteries.
While it has long been known that there is a genetic component to multiple sclerosis, the new theory is that it is CCSVI that is hereditary – that people are born with malformed valves and strictures in the large veins of the neck and brain. These problems lead to poor blood drainage and even reversal of blood flow direction that can cause inflammation, iron buildup and the brain lesions characteristic of multiple sclerosis.
It is well-established that the symptoms of MS are caused by a breakdown of myelin, a fatty substance that coats nerve cells and plays a crucial role in transmitting messages to the central nervous system. When those messages are blurred, nerves malfunction, causing all manner of woes, including blurred eyesight, loss of sensation in the limbs and even paralysis.
However, it is unclear what triggers the breakdown of myelin. There are various theories, including exposure to a virus in childhood, vitamin D deficiency, hormones – and now, buildup of iron in the brain because of poor blood flow.
While he is convinced of the significance of his discovery, Dr. Zamboni recognizes that medicine is slow to accept new theories and even slower to act on them. Regardless, he can take satisfaction in knowing that the woman who inspired the quest, and perhaps a dramatic breakthrough, has benefited tremendously.
Dr. Zamboni’s wife, Elena, has undergone a battery of scans and neurological tests and her multiple sclerosis is, for all intents and purposes, gone.
“This is probably the best prize of the research,” he said.