It is an interesting article from the other side to initiate discussions:
http://medicalmyths.wordpress.com/2009/ ... i-surreal/
The Zamboni Myth: Why “CCSVI” is Surreal
Posted by Colin Rose on November 24, 2009
“Sorcery, astrology, acupuncture, and many other moonshine notions do not require research to be discarded – only clear thinking.”
– Heinz Klatt, prof. emeritus of psychopathology, London, Ont.
Extraordinary claims require extraordinary evidence.
– Carl Sagan
The plural of anecdote is not data.
– Joe Schwarcz
This story has nothing to do with lifestyle diseases but it is valuable in showing the creation of a medical myth in real time. Usually the sort of papers published by Dr. Paolo 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 Brother André, of St. Joseph’s Oratory fame, the miracle worker canonized in 2010, who cured with holy oil, imbued with the healing power of St. Joseph, would have been impressed. The Vatican’s Theological Commission for the Causes of Saints has declared “scientifically unexplainable” at least one of the thousands of healing miracles attributed to Brother André. I hereby nominate Paolo Zamboni for consideration for canonization based on the hundreds scientifically unexplainable miracles attributed to him and his acolytes.
Brother André, canonized on October 17, 2010. The Vatican has determined that two of his miracle cures have no scientific explanation. Has the Vatican heard of Dr. Zamboni?
Dr. Zamboni has also performed miracles with no scientific explanation.
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 as 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.
Dr. Zamboni, a varicose vein surgeon at the University of Ferrara in Italy, was distressed that his wife developed multiple sclerosis, one of the more miserable of chronic, incurable diseases. He was determined to find the cause and the cure. Naturally, he focussed on veins, those vessels he had been operating on for years. As Mark Twain apocryphally said, to a man with a hammer everything looks like a nail.
However, 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. Undeterred by the principles of cardiovascular physiology, Dr. Zamboni hypothesized 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 imagined that some abnormality in the flow patterns of veins draining the brain, he calls “reflux”, caused by possible venous constrictions which somehow causes a leakage of blood from the small veins and an accumulation of iron in the brain, which somehow causes an autoimmune response which somehow damages the myelin sheaths of nerve axons, the basic pathology of MS. But, high venous pressure in the entire brain can only be caused by blockage of the superior vena cava which drains all the blood from the head and arms and not just a blockage in one or both internal jugular veins because of extensive collateral veins (see below). Superior vena cava syndrome causes swelling of the face and arms but has never been associated with MS. Carotid-cavernous sinus fistula can cause localized high venous pressure which is obvious from proptosis and congestion of eyeballs but, also, is never associated with MS.
Proptosis and congestion of the eyeballs caused by a carotid-cavernous sinus fistula. Venous pressure is very high, but patients do not get MS.
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. Dr. Zamboni claims that the same process in the brain is causing MS. But in order to do so ALL of the veins draining the head would have to be obstructed as happens in the superior vena cava syndrome. One or two blocked veins cannot raise venous pressure because of the many collateral veins draining the cranial circulation.
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. Even so, a variety of patterns could be produced in each subject and a selection made after. 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 one’s 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 or in different locations 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 likely look so carefully in the normal subjects. This is not necessarily conscious, fraudulent behaviour, but more often a subconsciously motivated action. Then Dr. Zamboni took these potentially biased venograms and made an unblinded selection of the ultrasound images that seemed to correspond to the “blockages” on the venograms, nullifying whatever randomization he had done initially. Then these patterns were classified in four “abnormal” patterns of flow which Zamboni calls “CCSVI, chronic cerebrospinal venous insufficiency” and which he claims is only present in MS patients are making an unblinded selection of images. “CCSVI” is presumably present from birth but only causes MS after 20 or 30 years. Possible MS causation by venous obstruction would be easy to test in an animal model but Dr Zamboni is not a “mouse doctor”, as he says. Doctors like William Harvey who discovered the circulation of the blood by animal experimentation and gave vascular surgeons, like Zamboni, employment are presumably just inferior “mouse doctors”.
“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. All of these patterns can be perfectly NORMAL, have no effect in raising intracranial pressure and, therefore cannot cause damage to the brain. “CCSVI” is just another name for normal variation in head and neck venous anatomy.
Veins, the capacitors of the circulatory system, are normally tortuous with bulbous dilations which store blood in case of sudden hemorrhage. It’s easy to show relative “obstructions” in normal veins needing “liberation”. Note the connections between the intra- and extra- cranial veins allowing diversion of venous flow in the case of occlusion of a jugular vein. Only blockage of the superior vena cava (the large vein at the bottom, leading directly to the heart) can raise intracranial pressure and potentially damage to brain and would be obvious from swelling of the face and arms.
Then Dr. Zamboni had the idea to open the “blockages”, to “liberate” them, with a balloon-tipped catheter 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-randomized, 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”, heat sensitivity, cold feet, and facial colour, highly non-specific symptom, very 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. If he had called it the “jugular vein stenting” would it have had the same placebo effect? 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. Because of the long duration and intermittent nature of their disease, MS patients are particularly prone to the siren song of con artists of all sorts.
Another diagram of "abnormal" venous flows in the head as imagined by Dr. Marian Simka, a Polish acolyte of Dr. Zamboni. Those nasty looking red chevrons are supposed to indicate high pressures damaging the brain. But even total occlusion of both internal jugular veins does not raise intracranial pressure because venous flow is directed through the extensive perivertebral venous plexus.
Intra- (grey) and extra- (black) cranial veins. Emissary veins allow communication between intra- and extra-cranial veins. The transient rise in venous pressure with occlusion of an internal jugular vein is rapidly relieved by diversion of venous flow into the other extra-cranial veins.
Venous adaption after occlusion of the internal jugular vein so that there is no increase in intracranial pressure and no damage to the brain including MS.
Digital subtraction angiography of the cranial circulation (venous phase) after removal of both internal jugular veins for cancer showing diversion of intracranial venous flow through the emissary veins at the base of the skull into the extracranial veins so that intracranial pressure is not increased. So, even total occlusion of both internal jugular veins cannot cause brain pathology including MS.
Why “CCSVI” is surreal:
1. Perhaps the most potent physiological argument against the Zamboni myth is that if, for whatever reason, brain blood flow were reduced, the first cells that would be affect are the high-oxygen consumption neurones in the grey matter, not the low oxygen-consuming, myelin-producing glial cells in the white matter, dysfunction of which is responsible for MS. Normally, blood flow to the white matter is very small compared to that to the grey matter. So, any theory of MS causation that invokes some aspect of blood flow is absurd. With any cause of reduced cerebral blood flow, one would lose consciousness long before there was any damage to glial cells in the white matter.
2. Chronically high central venous pressure (high pressure in all cerebral veins) does not cause MS. There are a number of cardiac conditions, such as tricuspid insufficiency and constrictive pericarditis, in which central venous pressure and jugular pressure are markedly elevated over long periods. Never has MS been described as a complication of these diseases.
I note that Pacific Interventionalists of Southern California who consider themselves experts in treating diseases of the veins and say they are doing treatment for “CCSVI” initially had the following on their patient info page:
“Currently the relationship between Multiple Sclerosis (MS) and CCSVI is still being defined and is debated among leading MS experts. However, many of the symptoms of central venous occlusion and stenosis seen in CCSVI are well understood and have been treated for many years. Central venous occlusion and stenosis may cause a variety of symptoms including swelling of the head, face, or neck, skin color changes within the head, face, or neck, swelling, heaviness, and throbbing of the arms, and occasionally light headedness.”
Note that they confound CENTRAL venous occlusion, (superior vena cava syndrome) with “CCSVI” (presumed or real blockage of jugular veins) which does not raise distal venous pressure because of collateral venous drainage. Central venous occlusion has never been associated with MS.
3. Chronic occlusion of one or both internal jugular veins does not increase intracranial venous pressure and, therefore cannot cause brain pathology. Intracranial pressure is increased transiently after internal jugular vein occlusion but quickly returns to normal as collateral veins open. Collateral perivertebral veins are adequate to handle venous drainage from the brain.
4. Zamboni’s paper says there was NO INCREASE in jugular venous pressure, the only parameter that matters if “CCSVI” is to damage the brain. The small gradients observed across presumed “stenoses” are not pathologically significant. So there is no way that whatever Zamboni is seeing could possible cause pathology. If “CCSVI” is causing brain pathology, it must do so via some mysterious, unmeasurable, un-disprovable “reflux”, not amenable to the scientific method.
5. 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. This is a perfectly normal IJV. Inserting rigid stents into large, thin-walled veins is potentially disastrous. Rupture of a large vein in the chest would be very hard to repair. Pressure cannot be applied to stop bleeding and patients could bleed to death internally before repair could even be attempted.
Here is a video from the same Polish lab doing “liberation”. Note the streaming of the dye along the wall giving the appearance of a severe stenosis. Injecting dye slowly into a large volume vein with laminar flow will result in streaming along the lamina. This internal jugular vein is perfectly normal. As one can see in the reconstruction above there is a normal relative constriction in the normal IJV as it enter the larger innominate vein. It appears that these doctors are doing stenting of normal veins and telling MS patients they have been “liberated.” High tech, dangerous snake oil.