This story has nothing to do with lifestyle diseases but it is valuable is showing the creation of a medical myth in real time. Usually the sort of papers published by Dr. Zamboni would have been rapidly relegated to the dumpster of science but this myth received a huge boost when two reporters working for CTVglobemedia, André Picard and Avis Favaro, usually quite rational, published a story and did a short documentary on it, calling it a “breakthrough” and related breathless anecdotal stories of dramatic “cures”. Thousands of MS patients and their relatives in Canada became convinced that Zamboni’s “treatment” was the cure they had been waiting for, blogs were full of conspiracy theories and indignation that drug companies had suppressed this surgical cure and many demanded funding from MS charities and government to make the “liberation treatment” available to all MS patients. Even Father André, of St. Joseph’s Oratory fame, would have been impressed.
The Zamboni myth is also a good example of a surgical procedure that is “tested” on a few patients, proclaimed as a cure with no controlled trial, and then gets done on thousands of patients at great cost. Every few years the same thing happens. We have written about coronary bypass, coronary angioplasty and bariatric surgery. Why do surgeons have this power to ignore science? If one wants to sell a drug for treating a disease, one has to test the drug in controlled trials in animals and humans, testing that takes years and many millions of dollars, to prove it is safe and effective. Not for surgical procedures touted to be a cure for whatever disease. As long a new procedure is not obviously killing most of the patients it is used on, surgeons can do as many as they want with no restriction. Why the difference between drug treatments and surgical treatments? Maybe because surgical treatments, like blood-letting of the past that killed thousands of patients, maintain a special mystique, an approach to disease that superficially seems so obvious it couldn’t be wrong. For an extreme example of surgical impunity see the history of Dr. Walter Freeman, the ice pick lobotomist.
Venous circulation of the head
Dr. Zamboni, a cardiovascular surgeon at the University of Ferrara in Italy, was naturally distressed that his wife developed multiple sclerosis, one of the more miserable incurable diseases. He was determined to find the cause and the cure of and for it. Naturally, as a cardiovascular surgeon, he focussed on blood vessels although there has never been any hint that there was any primary vascular problem in MS. As Mark Twain apocryphally said, to a man with a hammer everything looks like a nail. In order for some abnormality in hemodynamics (blood flow and pressure) to cause damage to the brain there must be either or both of an increase in pressure in the small vessels of the brain or a reduction in cerebral blood flow. Neither have ever been shown to be a primary cause of MS. At any rate, Dr. Zamboni thought that MS might be analogous to varicose veins in the leg in which there is very high venous pressure that can lead to red cell leakage and iron deposition in the skin, known as stasis dermatitis. He hypothesized that some abnormality in the flow patterns of veins draining the brain, caused by possible venous constrictions somehow causes a leakage of blood from the small veins and an accumulation of iron in the brain, which somehow caused an autoimmune response which somehow damages the myelin sheaths of nerve axons, the basic pathology of MS. But, if there were enough venous blockages in veins draining the head to cause such a high venous pressure, the heads of MS patients would look like the legs of patients with varicose veins, swollen, and blue with protruding tongue and eyes. Undaunted, Dr. Zamboni set about looking for abnormal venous flow patterns in patients with MS. Download a PDF of his only major publication on his investigation to date.
Stasis dermatitis in a leg caused by high venous pressures secondary to defective venous valves in the large veins of the leg. This is what the head of MS patients would resemble if their disease were caused by obstructions in the veins draining the head. The dark spots are caused by red cell extravasation and iron deposition in the skin. Dr. Zamboni claims that the same process is causing MS.
Colour Doppler imaging is able to visualize structures and direction of blood flow within them. But instantaneous flow patterns in large veins about the heart are highly variable, being dependent upon patient position and breathing pattern, like breath holding or forced expiration. Looking for presumed abnormal patterns of venous flow, Dr. Zamboni used colour Doppler to image the veins in the neck and upper chest of some MS patients and some normal subjects in various positions and breathing status. These studies were blinded as to the diagnosis of the patient, he says. Then Dr. Zamboni made an unblinded selection of the MS patients who had the ”abnormal” flow pattern and did venous angiography to look for obstructions in the large veins. Now, when one is looking for a certain result of an action be it in science or any other field, unless one is extremely careful to isolate your action from the effect, one can even subconsciously alter to action to achieve the effect. Medical studies are particularly prone to this type of manipulation. That is why good journals will only publish rigorously blinded randomized controlled trials of drugs or procedures. In this case, the person injecting the dye knew the diagnosis. The dye can be injected faster or slower to give a picture that one predicts; the MS patients “should” have blockages, so the dye is injected at various places and speeds to find one. But one doesn’t look so carefully in the normal subjects. This is not necessarily conscious, fraudulent behaviour, and more often a subconsciously motivated action. Then Dr. Zamboni took these potentially biased venograms and made a selection of the ultrasound images that seemed to correspond to the “blockages” on the venograms. Then these patterns were classified in four “abnormal” patterns of flow which Zamboni calls “CCSVI, chronic cerebrospinal venous insufficiency”, presumably present from birth but only causing MS after 20 or 30 years.
"Abnormal" patterns of flow and obstructions in veins draining the head in patients with MS as divined by Dr. Zamboni from ultrasound images and venography. We are particularly intrigued by patterns B and C in which venous blood in the internal jugular veins (IJV) is flowing upwards towards the head. If this ever happened for more than a second one's eyes would pop out of one's head.
Then Dr. Zamboni had the idea to open the “blockages” with a catheter-tipped balloon and insert a stent to keep them open in the same manner as is done in coronary angioplasty. He has done a small non-blinded, non-radomized, non-controlled trial of what he calls the “liberation procedure” on his wife and a group of patients who all claim immediate relief of symptoms like fatigue, “brain fog” and heat sensitivity , highly non-specific symptom, notoriously susceptible to the placebo effect. The “liberation procedure” is the modern equivalent of faith healing; the name evokes the same emotion, one is liberated from evil spirits. With the waning of organized religion, instead of prayer to a divinity, modern, sophisticated but desperate people now put their faith in technology. Self-promoting surgeons wielding high-tech tools are modern shamans; no disease should be resistant to their power.
The MS Society of Canada has now been intimidated by desperate patients into funding a trial of the Zamboni procedure.
Zamboni’s myth is not science; it’s an artistic creation in that this process can never be reproduced by other investigators. But all this is really irrelevant anyway because such flow patterns can never damage the brain without causing an increase in cerebral capillary pressure. Any MS patient with a large enough increase in venous pressure to cause red cells to leak out of small veins would have a head that looked like a leg with severe varicose veins; his eyes and tongue would protrude and his face would be very swollen and blue. So, there is no point in even funding a trial of the “liberation treatment” because it is impossible to know what Zamboni actually did and the basic science says that there no point in even trying to figure out what he did. When one doesn’t even know how to reproduce a test, how can one do a clinical trial of it? No more money should be wasted on the Zamboni myth.
We will keep our readers updated on the expansion of the Zamboni myth and it’s inevitable implosion. When it implodes I would hope Dr. Zamboni will visit all those MS patients to whom he gave false hope and personally apologize.
Nov. 25, 2009
A patient has reported that Dr. Michael Dake a professor of cardiothoracic surgery at Stanford University, is performing the Zamboni procedure in MS patients who ask for it. How he determines where the venous “blockages” are is a mystery. At any rate, it is unethical and contrary to the Hippocratic Oath, to perform a procedure, not yet proven to be safe or effective, outside of a blinded, randomized controlled trial of that procedure. Modern medicine is supposed to be evidence-based and there is no scientific evidence that the Zamboni procedure, however one wants to interpret it, has any utility in MS patients.
Here are venograms of the internal jugular vein of an MS patient done in Poland before and after presumed cure of a stenosis which is presumably causing the MS. There is no way that slight indentation of the vein, which may even be just an artifact of how the dye was injected or catheter placement in a very thin-walled vessel, could cause a significant increase in upstream pressure enough to cause damage to the brain and cause MS. It is highly unethical to insert such a stent without hemodynamic proof of the importance of the “obstruction” by measuring a significant pressure gradient across it.
Left: a presumed stenosis in the IJV. Right; presumed cure of the stenosis with a stent
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Here is the original report in the Globe and Mail
November 20, 2009
Researcher’s labour of love leads to MS breakthrough
By André Picard and Avis Favaro
From Saturday’s Globe and Mail
Elena Ravalli was a seemingly healthy 37-year-old when she began to experience strange attacks of vertigo, numbness, temporary vision loss and crushing fatigue. They were classic signs of multiple sclerosis, a potentially debilitating neurological disease.
It was 1995 and her husband, Paolo Zamboni, a professor of medicine at the University of Ferrara in Italy, set out to help. He was determined to solve the mystery of MS – an illness that strikes people in the prime of their lives but whose causes are unknown and whose effective treatments are few.
What he learned in his medical detective work, scouring dusty old books and using ultra-modern imaging techniques, could well turn what we know about MS on its head: Dr. Zamboni’s research suggests that MS is not, as widely believed, an autoimmune condition, but a vascular disease.
Share your stories Tell us what this potential breakthrough in multiple sclerosis treatment means to you
More radical still, the experimental surgery he performed on his wife offers hope that MS, which afflicts 2.5 million people worldwide, can be cured and even largely prevented.
“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.
André Picard is the public health reporter at The Globe and Mail. Avis Favaro is the medical correspondent at CTV News.
With reports from Elizabeth St. Philip, CTV News
W5 DOCUMENTARY
Watch W5’s documentary on the groundbreaking new treatment for multiple sclerosis, which includes the first time the “liberation” surgery was filmed.
It is available on the Web at www.W5.ctv.ca, and will be replayed Sunday on CTV Newschannel.
MS IN CANADA
An estimated 55,000-75,000 Canadians have multiple sclerosis, and every day three more people in Canada are diagnosed with the disease. Canada has one of the highest rates of MS in the world. MS is the most common neurological disease affecting young adults in Canada.
- Women are more than three times as likely as men to develop MS.
- MS can cause loss of balance, heat sensitivity, impaired speech, extreme fatigue, double vision and paralysis. The disease is characterized by lesions on the brain, a result of the breakdown of myelin, the protective covering wrapped around the nerves of the central nervous system.
- The most common treatment for MS is corticosteroids. Steroids reduce inflammation at the site of new demyelination, lessening symptoms.
- MS was first identified and described by French neurologist Jean-Martin Charcot in 1868.
- MS is widely believed to be an autoimmune disorder, but the cause or causes are unknown. There are a number of theories about what might trigger the disease, including exposure to a virus in childhood; exposure to tobacco smoke; lack of the female sex hormone prolactin, which plays a role in the development of myelin; and vitamin D deficiency. Vitamin D may play a role in MS because it helps to construct the interior layer of blood vessels.
- Despite the long-held assumption that MS is an autoimmune disorder, new research suggests it is actually a vascular disease triggered by a buildup of iron in the brain due to problems in blood flow.
Source: MS Society of Canada
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Here is an example of the someone caring for an MS patient enthralled by the Zamboni myth. Sad.
Hi everyone-
It’s just one person. Joan Beal, wife of MS patient Jeff Beal. We were the American family featured in the CTV documentary in part 2. There’s been alot of comments and some anger expressed as to “who set us this page???”. I just want folks to know that I started this page over the summer. Because I wanted to get the word out. I’ve been writing about CCSVI research on ThisIsMS.com since last December. That’s where Ashton Embry found me as “Cheerleader.” Lots of folks have been discussing this treatment over the last year at ThisIsMS…we have an amazing online community. And that’s how Avis Favaro found me. Come visit us and learn more.
I’ve been searching for the vascular connection to my husband’s MS since his diagnosis. And I have worked many months, reading medical journals online and learning all I could about the history of MS. When a friend on ThisIsMS.com posted Dr. Zamboni’s CCSVI research, it made sense with everything I had noticed in my husband’s MS- his first flare occurred after an hypoxic event (lack of oxygen to the brain) at high altitude, and he had many abnormal blood numbers, high liver enzymes, high SED rate, and overwhelming fatigue. These appeared to me to be signs of hypoxic injury to his brain. And in Dr. Zamboni’s research he found iron deposition, slowed perfusion and hypoxic injury to gray matter were the real insult to MS brains. And this was caused by closed veins. The blood heading back to the heart couldn’t get there in a timely matter, and it injured brain tissue. The demyelination happened AFTER the gray matter injury. By allowing oxygen to flow and stopping iron deposition with the Liberation procedure, Dr. Zamboni found a way to halt the demyelinating lesions and slow MS progression. And to relieve many of the worst symptoms of MS, including fatigue, depression, spasms, sleep issues and more.
I am not a doctor. I was trained as an opera singer. But I can write like a doctor now, because I wanted to learn all I could. There is no ulterior motive to this page. I just wanted to help other MS patients. Once I saw my husband’s twisted jugular veins on MRV technology, and his improvement after having them corrected- I knew this was real.
I promise I will never write and sell and e-book. Really. The supplement/diet/lifestyle program I made up for Jeff is on here for free. Look for Endothelial Health program in the notes section.
We all need to be our OWN ADVOCATES. No one will do the heavy lifting for us. If you want someone to learn about CCSVI, print out the research, print out the press and mail or bring the packet of information to the doctors you hope to reach. That’s all I did. Really. I tell you how to do it. Read the notes for “dubious doctors.” Read all the notes I wrote up…I tried to explain all of this in plain english.
So, go start your own Facebook or web page!! Please!!! Lots of folks are organizing around the globe. There’s no trademark on CCSVI, and Dr. Zamboni would be thrilled to have his research tested by other doctors. He’s wanted to get the word of CCSVI out….and thanks to Avis Favaro and Elizabeth St. Philip, now it is!
I’m just one gal who loves someone with MS. Really.
My best to everyone fighting to cure this horrific disease,
Joan
