News from Dr. Zamboni- CCSVI lesions classified as congenital

January 26, 2010 at 7:47am

Received an e-mail from Dr. Zamboni this morning-

A Consensus Conference on Venous Malformations - headed by Prof. Byung B Lee from Georgetown - and experts from 47 countries- studied the evidence and unanimously voted in favour of officially including the stenosing lesions found in CCSVI in the new Consensus document and Guidelines. Now published-

http://www.ncbi.nlm.nih.gov/pubmed/20087280?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1

http://www.minervamedica.it/en/journals/international-angiology/article.php?cod=R34Y2009N06A0434

This paper can be brought/linked to interventional radiologists and vascular surgeons. CCSVI lesions are classified as a truncular venous malformations - which means that vascular doctors have now classified this disease, CCSVI, as congenital- and preceding MS lesions.

Vascular doctors have agreed. CCSVI comes first.

Dr. Zamboni has been speaking to medical panels around the world. Yesterday was a "4 hour machine gunning of questions" by the Italian, Canadian and US MS Societies in Milan- Dr. Zamboni said he was able to answer all the questions with scientific evidence, and was quite pleased with the meeting's outcome. He'll be in North American soon. 

New research for 2010- linking "wedge-shaped" lesions to venous drainage

January 11, 2010 at 9:23am

Researchers in Australia and China note lesions that suggest impairment of venous drainage and link it to CCSVI-
http://www.ncbi.nlm.nih.gov/pubmed/20056253?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=5

Wedge-shaped medullary lesions in multiple sclerosis.
Qiu W, Raven S, Wu JS, Carroll WM, Mastaglia FL, Kermode AG.

Centre for Neuromuscular and Neurological disorders, University of Western Australia, Australia;
Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia;
Department of Neurology, the Third Affiliated Hospital of Sun yat-sen University, Guangzhou, China.

Multiple sclerosis (MS) is a heterogeneous disease with variable clinical features and magnetic resonance imaging (MRI) findings. We report four MS cases with unusual wedge-shaped lesions in the paramedian ventral medulla oblongata demonstrated on MRI. The clinical features and MRI characteristics of the medullary lesions suggest an impairment of venous drainage.

We propose that the formation of these wedge-shaped lesions may be related to the pattern of venous drainage in the ventral medulla and raised venous pressure due to chronic cerebrospinal venous insufficiency which has recently been described in MS. Copyright © 2010 Elsevier B.V. All rights reserved.

EAE: How MS became classified as an immune disease

January 9, 2010 at 2:12pm

Let's try to understand how the vascular connection to MS was dismissed, and why.

It's all about EAE (experimental autoimmune encephalomyelitis) and drugs.

Up until the 1930s, the prevailing thought was that MS was initiated by venous congestion. Dr. Tracy Putnam was at the center of this theory, blocking veins in dogs and creating MS-like lesions. Until a new doctor found a new, "simpler" animal model---

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212888/

"In the early 1930s, Thomas Rivers and colleagues provided the first evidence that immune cells can attack the brain. Their simple experiments established what is now the most well-studied model of autoimmunity—the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.

Studies had shown that injection of foreign brain tissues into the brains of rabbits could cause paralysis (2). Intrigued, Rivers—then a virologist at The Rockefeller Institute—set out to duplicate these studies in monkeys. Rivers and his colleagues injected Rhesus macaques with normal brain extracts from rabbits and showed that most of the monkeys developed acute CNS disease with immune cell infiltration and demyelinating lesions. No infectious agent could be cultured from the animals, putting to rest suspicions of an infectious etiology. Rivers' group also noted that the disease-inducing capacity of the brain extracts paralleled their myelin content, providing the first hint that myelin was involved in disease induction. Thus, the experimental allergic (now “autoimmune”) encephalomyelitis (EAE) model was born. The group published these observations in three articles in the Journal of Experimental Medicine (3–5)."

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EAE continues to be the medical model neurologists and immunologists study today, even though this model for MS is deeply flawed. Researchers continue to give mice EAE by injecting them with antigen, and then try to "cure" them with a variety of immune blocking or modulating medicines.

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Here's a paper from 2005

http://www.neuroimmunol.org/papers/16153891.pdf

"Experimental autoimmune encephalomyelitis (EAE) is a useful model for aiding the development of new treatments for MS. All therapies approved for MS ameliorate EAE. Two approved medications, glatiramer acetate and Natalizumab, were developed directly from studies in EAE. Several trials are ongoing in MS after success in EAE, including altered peptide ligands of myelin, DNA vaccines and statins. However, EAE has failed to predict the outcome of certai n approaches. The reasons underlying such failures are discussed here.

Many scientists interested in developing new therapies for MS criticize the EAE model for its poor record of predicting outcomes in the clinic, especially for those instances when promising therapies indicate that they are beneficial in models of EAE, yet then fail in subsequent clinical trials.

Nevertheless, the EAE models are rapid, and can quickly give indications of whether a particular mechanism of action of a specific drug has merit when taken into an in vivo model that recapitulates many aspects of the human disease, MS"

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So, the reason we still use the EAE model for MS is because it is a RAPID proof of DRUGS? 

Because these drugs can cure mice of EAE?

MS researchers continue to use this disease model, to the exclusion of other research, even in light of the fact that these treatments appear to cure mice of EAE...but FAIL IN CLINICAL TRIALS OF HUMANS WITH MS.

Insanity is repeating the same action over and over again and expecting different results. We have had seventy five years of EAE research, and we are not closer to understanding MS.

Perhaps we need to find a new model?

Joan

A History Lesson- from Dr. Mark Haacke

January 9, 2010 at 12:24pm

We've been discussing the importance of knowing the history of MS. As MS patients and caregivers, it is vital that we understand why certain medical paradigms are discarded in preference for others. 

Doctors around the globe are digging into medical vaults and finding more on the venous vascular connection to MS. We will not let this moment pass unnoticed.

From Dr. Haacke:

A Brief History of the Early Venous Vascular Observations in MS

This section will be developing over time as we review the past and sometimes almost ancient literature related to MS. According to Putnam (1) who discussed vascular abnormalities in MS in 1936, the first observations related to abnormal vasculature or effects related to the vasculature appeared in Cruveilhier (2) in 1839, more than 170 years ago who compared areas of sclerosis with the results of embolism. Rindfleisch (3) noted in 1863 an engorged vessel in the center of a plaque and in the same year Charcot (4) described vascular obstruction in MS. These observations would be noted again and again over the next 135 years. What was missing was the advent of imaging as a tool to investigate the vascular system in three dimensions, something that ultrasound takes a step toward as used by Zamboni and more recently the use of magnetic resonance imaging in the study of cerebro-spinal vascular insufficiency or CCSVI.

But Putnam didn't stop there. With an ingenious idea, he proceeded to study the effects of obstructed venous flow in the cerebral veins of dogs. These animals developed a number of abnormalities many of them similar to encephalitis or multiple sclerosis. His comment at the end of his paper was as follows (5): "The later stages (up to ten months) of the lesions consist of plaques of demyelinization with practically complete preservation of the axis-cylinders and with dense fibrous gliosis confined to the white matter. The similarity between such lesions and many of those seen in cases of multiple sclerosis in man is so striking that the conclusion appears almost inevitable that venular obstruction is the essential immediate antecedent fo the formation of typical sclerotic plaques." Despite the wonderful immunological advances in the last 75 years, how can we ignore the early work that so clearly demonstrates the role of the venous system in MS? The precocious work of these early researchers today finds its laurels in the current extracranial obstructions proposed by and seen by Zamboni (6) and now others.

There are more intriguing connections as one reads these old papers. Venous blood is more prone to clot. And these micro-thrombi may rapidly disappear and so become unobservable. An increase in capillary density also seems to develop and this may well describe the "capillary recruitment for venous drainage hypothesis proposed by Haacke". In this hypothesis, the obstructed flow leads to endothelial damage (7) and iron build up (8) and the need to increase the outflow capacity in the venous system. The brain then recruits capillaries to become veins and these in turn are also damaged leading to further iron deposition. If this is the case, then the iron build up should take place backward along the venous drainage system, which appears to be the case (9).

The story continues with a reference to Borst who founded a theory on the occurrence of vascular obstruction where he mentions the process of significant narrowing to the point of complete obliteration, hyaline transformation, etc. Perivacular hemorrhages were also frequently described by many authors. Borst (10) also mentions the presence of pigments. Others describe the combination of all three: congestion, perivascular hemorrhage and pigments (possibly hemosiderin or iron related) in encephalitis post measles (11). Many noticed venous engorgement and one study showed that thrombi were visualized in nine of seventeen MS cases and all three encephalomyelitis cases.

(1) Putnam (1939). Evidences of vascular occlusion in multiple sclerosis and encephalomyelitis.
(2) Cruveilhier (1839).
(3) Rindfleisch (1863). Histologisches detail zu der grauen degeneration von gehirn und rueckenmark. Arch. Path. Anat. Physiol. Klin. Med. 26: 474.
(4) Charcot (1863).
(5) Putnam (1935). Studies in multiple sclerosis: encephalitis and sclerotic plaques produced by venular obstruction. Archives of Neurology and Psychiatry. 33: 929-940.
(6) Zamboni (2009). Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 80:392-399.
(7) Adams 1987. Periventricular lesions in MS. Neuropathol Appl Neurobiol. 13: 141.
(8) Singh and Zamboni (2009). Anomalous venous blood flow and iron deposition in multiple sclerosis Anomalous venous blood flow and iron deposition. JCBF 1-12.
(9) Haacke et al. Evidence of an increase in basal ganglia and thalamic iron content in multiple sclerosis and its vascular implications: An initial analysis with susceptibility weighted imaging. Submitted to Intern. Angiology.
(10) Borst Anatomica 9, 67, 1903 Die multiple sklerose des zentranervovensystems.
(11) F. Wohlwill. Ueber encephalomyelitis. Neurol and Psychiat, 112: 20, 1928.

The venous connection to MS- a timeline

January 3, 2010 at 6:09pm

To those doctors who insist the venous connection to MS is an unproven theory, I offer a timeline of doctors who might beg to differ.

1863 Rindfleisch

Dr. E. Rindfleisch noticed that, consistently in all the autopsy specimens of MS brains he viewed with his microscope, a vein engorged with blood was present at the centre of each lesion.

Rindfleisch wrote:

"If one looks carefully at freshly altered parts of the white matter ... one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood ... All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation."

Rindfleisch E. - "Histologisches detail zu der grauen degeneration von gehirn und ruckenmark". Archives of Pathological Anatomy and Physiology. 1863;26:474–483.

1930s Putnam

Dr. T. J. Putnam researched lesions and noted that thrombosis of small veins could be the underlying mechanism of plaque formation-  He later created MS-like lesions in dogs by blocking their dural sinuses.

Putnam, T.J. (1937) Evidence of vascular occlusion in multiple sclerosis

1940s Dow and Berglund

Dr. Robert Dow and Dr. George Berglund continue on with Dr. Putnam's research and finding venous connections to MS lesions.

VASCULAR PATTERN OF LESIONS OF MULTIPLE SCLEROSIS Arch Neurol Psychiatry. 1942;47(1):1-18.

1950s  Zimmermann and Netsky

Dr. Zimmerman and Netsky carry on with Dow and Berglund's research, and note that the lesions are indeed venous in nature, but not caused by small thrombosis as Putnam surmised.

Zimmerman, H. M., Netsky, M. G.: The pathology of multiple sclerosis. Res. Publ. Ass. Nerv. Ment. Dis. New York 28, 271--312 (1950)

1960s Fog

Dr. Torben Fog, a Danish professor – noted that MS lesions are predominantly around the small veins. His subsequent study of 51 plaques from two cases of typical MS, making thin sections of the plaques and following their shape and course with direct drawings of each section, showed that most were prolongations of periventricular plaques, and that the plaques did follow the course of the venous system.

Fog Torben, The topography of plaques in multiple sclerosis, with special reference to cerebral plaques. Acta Neurol Scand, 41,Suppl. 15:1, 1965)

Fog T. On the vessel-plaque relations in the brain in multiple sclerosis. Acta Psychiat Neurol Scand. 1963; 39, suppl. 4:258

1980s Schelling

The story began in 1973, at the University of Innsbruck, when F. Alfons Schelling, M.D. began investigations into the causes and consequences of the enormous individual differences in the widths of the venous outlets of the human skull. The results of this study appeared, in 1978, in the official organ of the German-speaking Anatomical Societies, the "Anatomischer Anzeiger".

F.A. Schelling's 1981 discovery, at the Hospital for Nervous Diseases in Salzburg, of a striking widening of the main venous passageways through the skulls in victims of multiple sclerosis were to occupy the author's thoughts through the following decades of his quite diversified medical career. And in putting together, bit by bit, all the observations on the venous involvement in the emergence of the specific, and, in particular, cerebral lesions of multiple sclerosis, he was able to recognize their causes.

"Unequal propagation of central venous excess pressure into the different cerebral and spinal venous drainage systems is the rule rather than the exception. The intensity of the forces thus to be exerted on vulnerable cerebrospinal structures by the resulting pressure-gradients in the craniovertebral space is unknown. There is a need to consider the various conditions which may cause individual proneness to heavier reflux into particular cerebral as well as epi- and subdural spinal venous compartments. An attempt is made to indicate eventual consequences of excessive retrograde dilatation especially of internal cerebral veins. The importance of elucidating the neuropathological and clinical implications of undue reflux into the skull or spine is deduced from the probability of relations between localized backflow into the craniovertebral space and unexplicated cerebrospinal diseases. In this regard the features of multiple sclerosis are discussed."

Damaging venous reflux into the skull or spine: relevance to multiple sclerosis, Schelling F.

Here is Dr. Schelling's website for more information. His book (available for free on his site) outlines the history of the connection of MS to the venous system. Dr. Schelling is a brilliant, kind and generous man. When he came public with his research, he was dismissed, ridiculed and mocked. I am so happy that he is able to now witness Dr. Zamboni's technological corroboration of his findings. It was my pleasure and honor to meet him in Bologna, and to share his research with you.

link to Dr. Schelling's site

The "Alternative" Connection

January 2, 2010 at 3:37pm

Many, many MS patients have found symptom relief and stabilization by utilizing "alternative" treatments. I thought it might be interesting to go thru these and connect the dots to Dr. Zamboni's findings of impaired endothelial health and venous outflow in MS.

1. Diet- Back in 1948, Dr. Roy Swank came forward with a way to help MS patients using his specialized low fat diet. From Dr. Swank's site:

"60 years ago Dr. Roy Swank discovered that a low-fat diet, very low in saturated fats and polyunsaturated oils, helps MS patients live healthy and productive lives. Also low in red and other fatty meats, high in grains, fruits and vegetables, it is simple to follow and in many cases alleviates chronic symptoms. Some of his very first patients are still ambulatory and leading independent lives thanks to following Dr. Swank's regimen for the last half-century."

http://www.swankmsdiet.org/Home%20Page

Other researchers, such as Dr. Ashton Embry, Dr. George Jelinek and Dr. Terry Wahls encourage MS patients to eat a variety of whole food diets high in antioxidants and vitamins. I won't go through each program, but I believe they all have great merit, and advise MS patients and caregivers to look at each program. Why? Because they promote cardiovascular and endothelial (lining of blood vessels) health.

2. Exercise- many MS patients are able to keep moving-through varieties of vigorous exercise, or swimming, yoga or seated exercise. Most patients find that any motion seems to help symptoms and keep progression at bay. Why? Because exercise promotes cardiovascular and endothelial health.

3. Lifestyle changes- Here are a few that seem to help many MS patients:

a. reducing stress, limiting cortisol release

b. quitting smoking

c. getting more sunshine and Vitamin D

d. finding time for meditation, prayer, quiet reflection

Why? Because each of these changes promotes cardiovascular and endothelial health.

4. Other treatments:

Here are a list of some common alternative treatments and supplements that help MS patients- and links to Dr. Zamboni's findings.

a. prokarin- combines histamine and caffeine. Both are known vasodilators (open the blood vessels)

b. LDN- low dose naltrexone. One of the effects of LDN is angiognesis, the creation of new blood vessels

c. Bee stings- increase histamine in the system, which creates vasodilation (opening of blood vessels)

d. EGCG- green tea extract- chelates iron from brain tissue and is an anti-oxidant

e. HBO- hyperbaric oxygen treatments- increases oxygen delivery to the brain

Some of these alternative treatments make no sense when looked at from the autoimmune paradigm. 

One glaring example is smoking cessation. Smoking is linked to MS progression, yet cigarette smoking hinders immune system functioning. In the autoimmune paradigm, smoking might actually be good for MS patients!

None of these alternative treatments can "cure" MS; but each of them has offered individuals a means to better health and symptom relief. Isn't it funny how quickly most doctors will discount these alternatives, without even questioning WHY they help so many MS patients? 

I believe Dr. Zamboni's discovery of CCSVI provides us with a link to understanding the affect of alternative treatments in MS.

For more info on the Endothelial Health program I put together for my husband:

http://www.ccsvi.org/index.php/helping-myself/endothelial-health

Joan

Let's talk about iron....

January 1, 2010 at 5:41pm

Now, let's talk about the iron issue. This has been Dr. Zamboni's "smoking gun." He wrote a paper on iron called "The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis"- in which he explicitly outlines the parallels between chronic venous insufficiency in the legs and iron deposition and what we see in MS brains. If you haven't read it yet, it's a must read-

http://jrsm.rsmjournals.com/cgi/content/full/99/11/589?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=zamboni&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

So, how long have doctors known about this connection of iron and the MS brain? 

Here is a paper from 1988- yes, that is over 20 years ago- discussing the cerebral vein walls and iron deposition in multiple sclerosis-

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1031540/pdf/jnnpsyc00537-0096.pdf

"C W M ADAMS
From the Division of Histopathology, United Medical and Dental Schools of Guy's and St Thomas's Hospitals, University of London, UK

SUMMARY Evidence of damage to cerebral vein walls was sought in 70 cases of multiple sclerosis. Seventy control cases were also examined. The multiple sclerosis cases showed venous intramural fibrinoid deposition (7 %), recent haemorrhages (17%), old haemorrhages revealed by haemosiderin deposition (30%), thrombosis (6%) and thickened veins (19%). In all, 41% of all multiple sclerosis cases showed some evidence of vein damage. Occasional control cases showed haemosiderin deposition in the brain but, unlike the multiple sclerosis cases, these were diffuse and almost entirely related to coexistent cardiovascular or cerebrovascular disease. Haemosiderin deposition was common in the substantia nigra and other pigmented nuclei in all cases. It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis."

Here we have a study in 1988 showing vein damage in almost half of the MS patients- and the researchers note hemorrhage, hemosiderin (iron storage) deposition, thickened vein walls and call it a form of "vasculitis."

"The results reported here reinforce the view that damage to the vein wall is an important aspect of the pathology of the multiple sclerosis plaque. The vasculitis caused is different from and of a more modest nature than that, for example, in systemic lupus or polyarteritis nodosa but is, nevertheless, enough to cause haemorrhage, and structural and permeability changes in the vessel wall. The term proposed by Lendrum for a wide range of vasculitic disorders is plasmatic vasculosis, and the damage to the vein wall in multiple sclerosis could be regarded as causing a minor degree of such plasmatic vasculosis. Inflammatory and reparative changes in the vein wall might be exacerbated by pulsations or surges in intracranial venous pressure and may result in increased permeability of the multiple sclerosis plaque, as shown at necropsy, by immunohistochemistry and by brain scan."

So, the researchers note that this is different than vasculitis- it's really about damage to the VEIN wall. They even posit that this damage may be caused by PULSATIONS or SURGES of intracranial venous pressure (like from venous reflux, perhaps?)
Let's just move ahead 20 years, thru the vast miasma of autoimmune research-

Here is Dr. Haacke's paper from earlier this year. This is research completed BEFORE he read Dr. Zamboni's research. After attending the first CCSVI symposium in Bologna in 2009, Dr. Haacke has since became so convinced that Dr. Zamboni's research provided the missing link, he is now covering the globe, opening research centers to diagnose venous stenosis and reflux.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650739/

Iron deposition in the MS brain is real, and we need to understand how it gets there, and what we can do to stop this injurious process.

Joan