But what followed was anything but classic or conventional, and it has thrown open the debate on MS-what it is, what causes it, and how it could be connected to a range of other neurodegenerative diseases, such as Alzheimer's, Parkinson's and dementia.
Elena's husband is Paolo Zamboni, a professor of vascular diseases at the University of Ferrara in northern Italy. Prompted by his wife's diagnosis, he began to explore the disease and its common characteristics, and quickly became convinced that doctors didn't have the whole story.
MS, which afflicts around 2.5 million people worldwide, is believed to be a disease of the central nervous system (CNS)-which includes the brain and spinal cord-and, more specifically, it is described as an 'inflammatory demyelinating' condition. Nerve-cell branches, or axons, in the CNS are protected by a fatty coating-called the 'myelin sheath'-which becomes damaged (de-myelinated) by inflammation, a process that results in scars or sclerosis (hardening similar to that seen in the arteries, or arteriosclerosis). Demyelination tends to occur in the white matter of the brain and spinal cord, although MS symptoms vary, depending on the severity of the damage and the axons that are affected.
Doctors don't know exactly what causes the initial inflam-mation. However, there is some evidence that it could run in families, although this has not been scientifically established. The prevailing theory is that MS is caused by stress or infection.
Iron in the brain
Zamboni found something else. Most of the studies he researched revealed very high levels of iron in the brains of MS patients but, more significantly, the veins that carry blood away from the brain were twisted and obstructed in up to 90 per cent of MS patients. These blockages caused the blood to flow back into the brain, leaving behind iron deposits, which might possibly be a cause of the associated inflammation and auto-immune reactions.
MS may therefore fundamentally be a vascular disease, he argued-which led him to re-name the condition, dubbing it 'chronic cerebrospinal venous insufficiency' (CCSVI). His wife became his first guinea pig, and she underwent pioneering surgery to unblock the veins near her brain.
Astonishingly, her symptoms disappeared immediately-as, indeed, they have for hundreds of other MS patients who have undergone Zamboni's surgical technique, which he now calls 'the Liberation Treatment'.
By 2009, Zamboni had refined the operation, and was using angioplasty-a procedure that uses a catheter-inserted balloon to expand and 'open up' the arteries in heart disease patients-to unblock the cerebral veins.
In one of his earlier 'pilot' studies, involving 65 MS patients, half of them did not suffer a relapse-where the symptoms reappear after a period of relief-whereas only 27 per cent of them had been relapse-free prior to surgery.
The average relapse rate for the group overall, however, was not improved by the procedure, and most of the 'unblocked' veins became restricted again during the 18-month follow-up period (J Vasc Surg, 2009; 50: 1348-58).
The first independent research preliminary results have, so far, been even more ambiguous. In the large-scale, randomized, ongoing Combined Transcranial and Extracranial Venous Doppler Evaluation study, which began in April 2009, researchers at the University at Buffalo Medical Center in New York have been using Doppler ultrasound scanning to look for signs of CCSVI in the first 500 study participants, 280 of whom had MS. However, the researchers have so far found that only around 56 per cent of the MS patients fulfilled the criteria for CCSVI, compared with around 42 per cent of those with some other neurological disorder and 22 per cent of the healthy controls (see www.buffalo.edu/ news/fast-execute.cgi/article-page.html?article=109370009).
The plan now is to recruit a further 500 subjects for the second phase of the clinical study, and to assess them with more advanced diagnostic tools.
A search in vein?
However, other research has been considerably more damning-having found no evidence of any causal link between CCSVI and MS. In one study, headed by Florian Doepp, an expert in venous blood drainage at Humboldt University in Berlin, Germany, the brains of 56 patients with MS (and 20 controls) were examined by colour-coded ultrasound and various blood-flow analyses. However, no evidence whatso-ever of CCSVI could be found (Ann Neurol, 2010; 68: 173-83).
Another study from Germany, this one carried out by researchers at Goethe-University Frankfurt, came to a similar conclusion. In a report ironically titled "The perfect crime? CCSVI not leaving a trace in MS", the researchers again found no evidence of venous obstruction or retrograde flow on examining the brains of 20 MS patients and 20 healthy controls using extra- and transcranial sonogrphy (J Neurol Neurosurg Psychiatry, 2011, February 4; doi: 10.1136/jnnp.2010.231613).
Likewise, researchers at University Hospital in Padova, Italy, also could find no evidence of a cause and effect relationship between CCSVI and the inflammatory lesions indicative of possible MS when they examined 50 such patients together with a further 50 age- and gender-matched healthy controls (Ann Neurol, 2011; 69: 90-9).
However, despite these negative results, there is still the elephant in the room that needs to be addressed: why have so many MS sufferers dramatically improved after undergoing Zamboni's so-called Liberation Treatment?
Robert Zivadinov, who is heading up the research team at Buffalo, believes he has found the answer in the initial findings he has already assembled.
"CCSVI is not the cause of MS, but might be a consequence or a contributing factor to progression, and I think that has to be studied," he says. "What Professor Zamboni discovered in terms of veins is something much bigger than MS. We need to understand the role of the venous system in the pathology of central nervous diseases and aging."
The Alzheimer's connection
If constrictions and obstructions in the venous system are a characteristic of the neuro-degenerative diseases in general, and not just of MS, this would suggest that there might be a common bond between other autoimmune and/or inflammatory conditions, such as Parkinson's and Alzheimer's diseases, which are usually associated with ageing.
Researchers at the University of South Florida in Tampa have pointed out that inflammation and degeneration are both present at certain time points in many chronic neurological disorders. Alzheimer's starts with degeneration and is follow-ed by inflammation, whereas the opposite occurs in MS, they say (Aging Dis, 2010; 1: 169-72).
MS is also similar to stroke, Alzheimer's and schizophrenia in that these are all conditions characterized by damage to the axons, or nerve cell branches, in the brain's white matter (Neurology, 2011; 76: 397-404).
Indeed, post-mortem examination of the brains of both MS and Alzheimer's victims, using histochemical techniques, have shown similar damage (Immunol Invest, 2011; 40: 197-205), thereby leading to breakthroughs in our understanding of inflammation and neurodegenerative diseases that are nothing less than a "paradigm shift" in neuro-pathology, say researchers at the Cecilie Vogt Clinic for Neurology in Berlin (J Mol Med, 2008; 86: 975-85).
Nevertheless, if MS is not an isolated disease entity, but a member of a subset of inflam-matory conditions that includes Alzheimer's, Parkinson's, stroke and schizophrenia, then the $64,000 question remains: what is causing them?
While everything from family history and viral infection (Med Hypotheses, 2010; 75: 204-13) to artificial sweeteners (AAOHN J, 2008; 56: 251-9) and power lines (Am J Epidemiol, 2009; 169: 167-75) have been mooted as causes, the most compelling evidence was amassed over 60 years ago-and has been systematically ignored ever since.
The Swank hypothesis
There's one further feature shared among the conditions that are known as neurodegenerative diseases, researchers at Duke University have discovered.
In a study of 770 Parkinson's patients, they found these patients' vitamin D receptors had been damaged, which means they were unable to process vitamin D, the main source of which is sunlight (Ann Hum Genet, 2011; 75: 201-10).
In addition, George Ebers and colleagues at the University of Oxford Wellcome Trust Centre for Human Genetics found a close relationship between MS and exposure to sunlight when they assessed the prevalence of the disease in Scotland. The rate of the disease rose significantly among populations in the more northerly latitudes, where sun exposure was minimal (PLoS One, 2011; 6: e14606).
A similar close association was found when researchers explored rates of MS in various regions of France. Indeed, the prevalence of MS was sometimes almost twice as high in regions that had low levels of sunlight, as determined by ultraviolet (UVB) radiation levels (Neurology, 2011; 76: 425-31).
Dr Roy Swank, a neurologist at the Oregon Health & Sciences University in Portland, anticipated this discovery around 60 years ago.
Swank, who died in 2008 at the age of 99, was one of the first to identify a link between geographical location-where we live and the amount of sunshine we are exposed to-and poor diet and MS. As the Duke University researchers were to discover much later, it wasn't just about our exposure to vitamin D, but also our ability to process it.
In 1948, Western Europe was a ready-made laboratory for Swank's research. It was just three years after a devastating war, and diets had changed dramatically across the conti-nent. His first researches took place in Norway, where he discovered that MS was rare in coastal regions, and nine times more commonplace in the mountains. Not surprisingly, those living along the coast ate a diet that was rich in seafood, while people living in isolated mountain areas tended to eat more meat, milk, eggs and cheese (Trans Am Neurol Assoc, 1950; 51: 274-5).
From this and other studies, Swank surmised that MS might be reversed by eating a low-fat diet, a theory that was proven over the years in a group of 150 MS sufferers who agreed to follow such a dietary regime.
Astonishingly, Swank stayed in touch with them right up until the year 2000. They were contacted every three months and, once a year, Swank and his team would examine them. Some of the MS patients were unable to stick to the low-fat diet; nevertheless, by 1991, 21 per cent of those eating only 17 g/day of fat had died compared with 75 per cent of those eating 30 g/day, and 81 per cent of those eating 42 g of fat every day (Nutrition, 1991; 7: 368-76).
Swank had also noted the phenomenon that Zamboni had observed and which had become the basis of the Italian's CCSVI theory: MS sufferers have poor blood flow around the brain, and one that progressively worsens. However, Swank had already taken Zamboni's theory one step further by maintaining that the cause of the poor cerebral blood flow was the modern diet that is high in saturated fats (Swank RL, Dugan BB. The Multiple Sclerosis Diet Book. New York, NY: Doubleday, 1977).
If Swank was right and MS is primarily caused by our modern high-fat diet, it follows that it's a disease that should be increasing in prevalence-and, in fact, the history of MS appears to bear this out. One of the very first recorded instances of the disease was found only as recently as the mid-1800s, but it had already become a recognized disease by the turn of the 20th century, just 50 years or so later. Even by 1922, researchers had noted that MS incidences had increased over the previous 20 years (Arch Neurol Psychiatry, 1922; 8: 59-75).
Swank himself noted a 50-per-cent increase from 1935 to 1958 in Montreal, Quebec, while a more recent study in the highly genetically stable population of Sardinia showed that the disease had increased fivefold over the nearly 35 years prior to 1999 (Neuroepidemiology 2005; 25: 129-34).
Researchers at the Wellcome Trust Centre for Human Genetics in Oxford, working with the Canadian Collaborative Study Group, uncovered further clues that pointed to MS being a lifestyle and environmental disease. In a study of around 27,000 MS patients, they discovered that the prevalences of the disease in the two genders had shifted dramatically over the previous 50 years. MS used to affect men and women almost equally, but the scientists found that, by 2006, there were 3.2 women for every man who had the disease (Lancet Neurol, 2006; 5: 932-6).
The missing piece
Nevertheless, MS is still a relatively rare disease. The overall risk of developing the disease is just one in 700 compared with, for example, the one in three risk for cancer and the one in 22 risk for chronic heart disease.
If Swank is right and given the large numbers people in the West who consume a high-fat diet, you might expect that more people should be suffering from MS (although the rate does rise dramatically when MS is viewed as a subset within a wide range of neurodegenerative diseases).
Charles Poser, a neurologist at Harvard Medical School, believes that he may have the missing piece of the jigsaw puzzle. He was tantalized by the MS rates in Hawaii, which vary wildly among the various ethnic groups living there. Caucasians who were born in California, but who now live in the Islands, have three times the rate of MS compared with Caucasians born and raised there. On the other hand, Hawaii-born Japanese have triple the rate of MS compared with Japanese people born and raised in Japan, but who now live in Hawaii (Neurology, 1971; 21: 122-30).
Poser explains these contradictory data with his multiple sclerosis trait (MST) theory. He believes that some people are genetically susceptible to MS-they have the MST-but do not necessarily ever develop the disease. Only when a certain environmental 'event' occurs will they then manifest MS-and such an event could be anything from infection, vaccination, a high-fat diet or inadequate exposure to sunshine (Clin Neurol Neurosurg, 2005; 108: 227-33).
This theory is supported by a research project that involved carrying out magnetic resonance imaging (MRI) of 296 healthy people, around half of whom were directly related to an MS sufferer, whereas the rest had no such familial connection to the disease. None of the participants had been diagnosed with MS.
However, the researchers discovered that 10 per cent of those with familial connections to MS had brain lesions that were identical to those found in MS sufferers-and yet, they had no symptoms-while 4 per cent of the non-familial participants also had similar lesions. This suggests that those with the lesions were all carriers of the MST, but nothing in their life had so far triggered the disease to manifest itself (Ann Neurol, 2006; 59: 11a-2a).
A response, not a disease
So, what exactly is MS? Poser and Swank have established that it's not an autoimmune disease, as doctors have maintained, but an autoimmune response. Such a response-which may include poor blood circulation-is likely to be triggered by a viral infection such as shingles or chickenpox, a high-fat diet, a food intolerance, a nutritional deficiency of, especially, vitamin D or parasites.
This means that MS is not a progressive and incurable dis-ease, but a response that may be stopped, once the cause has been identified and reversed. Poser has also demonstrated that, on its own, simply having a genetic proclivity is not enough to trigger MS.
Doctors are not trained to ask the 'why' question and, yet, that's the one that patients most want to have answered: why do I have X? If medical professionals were so trained, they might be closer to reversing the so-called 'autoimmune diseases', such as MS, Alzheimer's and Parkinson's, instead of merely treating the symptoms.
Factfile: The Kingsley approach
Dr Patrick Kingsley treated more than 9000 multiple sclerosis (MS) patients from his surgery in a tiny village in Leicestershire, in the UK, until he retired several years ago. In almost every case, he achieved a dramatic improvement and, often, complete remission (he is reluctant to use the word 'cure').
He found that MS usually manifested in one of two possible ways: as functional MS, where the muscles do not perform properly; and as sensory MS, where the patient feels numbness and 'pins-and-needles'. However, some of his patients suffered from both types of symptoms.
As treatment, Kingsley used two main approaches-dietary and lifestyle-along with intravenous infusions of high-dose vitamins. He also manipulated his patients' jaws on occasions with remarkable success. Sensory MS appeared to respond better to the infusions, and to the removal of amalgam fillings, than to dietary changes.
He believes that MS may be caused by a range of factors, including food intolerances, toxic metals (including amalgam fillings), pesticides and food additives, nutritional deficiencies-especially vitamins B12 and D, and magnesium-as well as infections, stress and hormonal imbalances.
The dietary approach involved some detective work, as the patient would attempt to determine which foods had caused the MS. His patients were told to avoid dairy, caffeine, alcohol, refined and white-flour products, sugar, all foods and drinks with chemical additives and possibly all red meat. Instead, an MS patient should eat lots of vegetables, salads, nuts and seeds, whole grains, fish-especially oily types such as tuna and salmon-chicken, bottled mineral water and herbal teas.
Sensory types also responded well to infusions and especially to high doses (30,000 mcg) of vitamin B12, while functional types fared better on infusions of magnesium and lower doses (5000 mcg) of B12.
(Dr Kingsley is currently preparing his book, The New Medicine, which outlines his entire approach and his treatment protocols across a range of illnesses).
Factfile: The amalgam connection
Amalgam dental fillings could be a cause of multiple sclerosis, and they certainly contribute to a worsening of MS symptoms. These fillings-which include mercury, the most toxic metal known to man-can change MS patients' mental health, making them more depressed, hostile, psychotic and obsessive-compulsive.
Researchers at the Rocky Mountain Research Institute in Colorado assessed the mental health of 47 MS patients with amalgam fillings, and compared them with 50 patients who had had their fillings removed. Overall, those with amalgam fillings had 43-per-cent more symptoms compared with those who no longer had such fillings (Psychol Rep, 1992; 70: 1139-51).
As a possible cause of MS, when researchers did a systematic search through the literature and pooled a range of the relevant studies published between 1966 and 2006, they found a consistent association between amalgam fillings and MS (J Public Health Dent, 2007; 67: 64-6).
Factfile: Is it Lyme disease?
Multiple sclerosis is a difficult disease to diagnose accurately. A diagnosis is based on clinical criteria, such as scarring within the central nervous system, which can be detected by an MRI scan. However, other diseases can also cause scarring. Lyme disease-caught from a tick bite-not only causes similar scarring, but also mimics the exact same symptoms as MS.
In an analysis of 55 patients diagnosed with MS, three were found to have Lyme disease instead, which suggests that up to 6 per cent of all MS patients might be wrongly diagnosed (Med Clin, 1990; 94: 685-8).
In a separate case study of a Brazilian woman 45 years of age, she had been treated for MS for 15 years before doctors found evidence of Lyme disease in a blood sample. An MRI scan of her brain revealed MS-like lesions (Arq Neuropsiquiatr, 1994; 52: 566-71).
Researchers from the International Lyme and Associated Diseases Society (ILADS) point out that Lyme disease has now become a common infection, and one that mimics the symptoms of MS. For this reason, they say that it's very likely that many MS patients have been misdiagnosed (Clin Neurol Neurosurg, Dec 17, 2010; epublished ahead of publication).
Factfile: The Swank diet
Dr Roy Swank was among the first to associate multiple sclerosis with a high-fat diet. For this reason, he put hundreds of his patients on a low-fat diet, including limiting saturated fats and polyunsaturated oils. Red and fatty meats were also banned in the first year of the diet, while grains, fruits, vegetables and oily fish were eaten instead.
Swank never claimed that his diet was a cure, but said that it made MS manageable. Indeed, many of his patients lived with MS for years-some for as long as 50 years-without suffering some of the worst of its debilitating symptoms.
u Dairy products: These must all be non-fat. You must also avoid margarine, butter, shortening, lard, cocoa butter, coconut oil, palm oil and hydrogenated oil.
u Eggs: Eat only the white of the egg.
u Grains and cereals: Eat only wholegrain products, and avoid muffins, pastry, cakes, pies and biscuits that contain hydrogenated oils.
u Pasta and rice: Wholegrain pasta is preferred, but refined pasta and rice are permissible under the Swank diet.
u Processed foods: Most foods in a packet contain processed, or hydrogenated, oil, which must be avoided.
u Condiments: Only mayonnaise is banned.
u Drinks: Caffeine increases nervousness and insomnia, and is best avoided. If you're not overly affected by caffeine, restrict your intake to three cups a day.
u Alcohol: MS patients are usually sensitive to alcohol. If not, a glass of wine a day is allowed.
u Nuts and seeds: Walnuts, sunflower seeds and pumpkin seeds are a good snack food.
u Fruits and vegetables: Eat as many fruit and vegetables as you like, but avoid avocados and olives as they contain unsaturated fatty acids.
u Poultry: Eat skinless white chicken or turkey meats, and avoid all processed meats.
u Fish: Eat white fish, including cod, halibut and sole. Shellfish, including crabs, oysters and scallops, are also allowed, but restrict the amount of fatty fish, such as tuna and salmon.
u Red meats: These are not allowed-especially in the first year of the diet. After that, a small amount of low-fat meat is allowed, and this includes lamb, liver and kidney.
u Vitamins: Daily supplements of cod liver oil, 1000 mg of vitamin C and 400 IU of vitamin E are recommended.
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