Exciting New MS Treatment!

NEWS RELEASE

A new MS drug appears to alter fluid dynamics and repair the blood brain barrier!
In fact, 63% of the patients treated with Perfuza (toxicmuzab) had no new or enhancing MS lesions at 12 months! In light of recent discoveries of the brain's lymphatic vessels and the connection to venous flow, we are thrilled to be able to offer MS patients a drug treatment which may be addressing CNS fluid dynamics.

Here's more on the impressive results of Perfuza from a recent publication in JAMA---

We found a reduction in the mean number of new brain lesions (corresponding to more lesion- free patients) in the toxicumab group compared with the placebo group at 6 to 12 months. The delayed and positive effect on the magnetic resonance biomarker suggests that toxicumab could affect the dynamic of the blood-brain barrier.

Gadolinium enhancement is a marker of damage to the blood-brain barrier, whose time course depends on lymphatic drainage18 and hence on venous drainage from the skull.19 Previous studies have reported that venous pressure is lowered3 and cerebrospinal fluid dynamics is improved20 after taking toxicmuzab, thereby favoring the drainage of cerebro spinal fluid into the dural veins, which depends on a pressure gradient between the subarachnoid spaces and dural veins.21,22

Another study23 reported that white matter lesion load was inversely correlated with reduced cerebrospinal fluid dynamics, as measured by MRI. In addition, flow improvement through the internal jugular veins owing to toxicmuzab has been reported to improve brain perfusion in patients with RRMS.21 It has also been reported that the development of a new MS plaque was preceded by sustained MRI-detected hypoperfusion before the plaque was identified on MRI.24,25

link

Incredible, right???  Finally.  A drug which can potentially affect the blood brain barrier!
Perfuza (toxicmuzab) may be the greatest money-making MS drug in history.
Projections are now at 2-3 billion for 2018 alone.


Only kidding.

The paper I'm quoting from, verbatim, is the recent JAMA review of angioplasty for CCSVI from the Brave Dreams clinical trial. 

Just replace my made up block buster drug Perfuza (toxicmuzab) with angioplasty to restore venous flow.   And then, write a conclusion and snarky editorial that says that we should not pursue this treatment any further, and that CCSVI research is over.

Even though the conclusion of the paper says that over half of patients saw benefit in cerebral blood flow from CCSVI treatment.

The editorial which goes along with this publication is actually incorrect.  The author of the editorial, Dr. Ari Green***, claims that there was absolutely no benefit in those treated for CCSVI, that there was no reduction in new lesions.  Here, read the editorial for yourselves, and read the paper again, and tell me---isn't this incorrect?
https://jamanetwork.com/journals/jamaneurology/fullarticle/2664000

***Dr. Green has received personal compensation for activities with Inception Sciences, Mylan Pharma, Medimmune, and Bionure. Dr. Green has received personal compensation for serving on the board of Inception Sciences. Dr. Green holds stock and/or stock options in Inception Sciences. Dr. Green has received research support from Inception Sciences, Biogen, and Novartis.  link
Dr. Green's Inception Sciences Company owns the patent for an antihistamine-like molecule thought to remyelinate neurons. I wrote about the absurd hype regarding a 1.3% improvement in visual acuity here:  link

To recap---this published paper from the neurologists of the Brave Dreams trial just proved, conclusively-
1. CCSVI is a real condition in people with MS.
2. There are a variety of venous malformations.  There were patients with closed jugular valves, refluxing blood flow, and hypoperfusion.
3. Venoplasty was able to restore normal flow in 54% of the patients.  Not all malformations can be treated with PTA alone.
4.  63% of treated patients had no new MS lesions on MRI at 12 months.
Doesn't this count for something?  At least additional study?

What is real news? What is fake news?
Is this simply spin or is it something darker?

If a room full of neurologists look at the results from CCSVI venoplasty and conclude 
"The delayed effect of venous PTA 6 months after the procedure on the magnetic resonance biomarker suggests a possibility that PTA may produce benefit for a subgroup of patients with MS. This should be further analyzed and investigated." 

yet still write a conclusion and editorial suggesting CCSVI research be stopped--- what is reality?

Please, tell me.  Honestly, I'm flummoxed.

More ahead.
Joan

CCSVI included in Oxford Textbook of Vascular Surgery

"The Oxford Textbook series is the foremost international textbook of medicine. Unrivalled in its coverage of the scientific aspects and clinical practice of medicine and its subspecialties, it is a fixture in the offices and wards of physicians around the world."

The new edition of the Oxford Textbook of Vascular Surgery, edited by Matthew M. Thompson, professor of vascular surgery at St. George's Medical School in London, includes articles from "130 global experts."  The new edition features a full chapter on Chronic Cerebrospinal Venous Insufficiency (CCSVI).  Authored by Dr. Paolo Zamboni, Sergio Gianesini and Erica Menegatti from the University of Ferrara, this chapter is included in a section on diseases of veins and lymphatics.  link

While MS specialists and neuroimmunologists have disparaged and intentionally misrepresented Dr. Paolo Zamboni's vascular studies, he has continued to publish, undaunted.  He, along with the International Society of Neurovascular Disease,  have explored how the venous system affects neurodegenerative disease.  He has improved cerebral venous return using open surgery and venoplasty, and has documented benefits in the health of his patients.  He has created a brand new CCSVI diagnostic center at the University of Ferrara, while collaborating with international space organizations, to understand the affects of microgravity on the venous system.  As I have said before, if rocket scientists collaborate with Dr. Zamboni, why can't MS neurologists?  If the Oxford Textbook editors consider his research expert and important enough to include in this new publication, why the continued naysaying from neurology?

Heartfelt thanks to Dr. Paolo Zamboni and the entire vascular department at the University of Ferrara.  Thank you for continuing your research and exploration, even while confronted with unprecedented hysteria and vitriol from the neurological community.

CCSVI exists.  Slowed venous return to the heart harms the central nervous system, just as slowed venous return harms every other major organ in the human body.   This is scientific fact.  Whether or not MS specialists choose to acknowledge the science remains a moot point.  Vascular specialists understand this, and will continue to treat patients and push the research forward.  This is how medical science evolves, one peer-reviewed publication at a time, until the stack becomes undeniable.  Financial incentives, pharmaceutical payouts,  cognitive dissonance, and territorial medical silos cannot stop it.

Share this information with vascular specialists at your local universities and hospitals.  Fund research and support groups like the ISNVD.  Insist that "charities" and organizations who purport to be helping people with MS include vascular specialists on their medical advisory boards.  Question the status quo.

And most importantly, do all you can to improve your own heart and endothelial health.  Because this is real-- the heart and brain are connected-- and there are things you can do today to help yourself.  No prescription necessary.

Be well,
Joan

ISNVD 2014--the big picture

Jeff and I are home from the intense sessions at the fourth annual International Society for Neurovascular Disease (ISNVD) conference.  We both commented that it was like being back in college---the amount of information presented was impressive and challenging, and by the end of the day, our brains were quite literally fried.  We are very thankful to Dr. Michael Dake, the current president of this group, for allowing non-medical folks (I call us the "laity") to sit in on the presentations.  It is very informative for those of us with "skin in the game" to hear where the research is going.

I had a chance to sit down with Dr. Paolo Zamboni and discuss the developments of the past five years.  It was September 2009, when we first met and talked about CCSVI research, at the Bologna conference.  Much has changed since that time, yet one fact remains the same---

We know that the extracranial venous system contributes to neurodegenerative disease, and in many cases, venoplasty to relieve CCSVI can improve neurological symptomology, by increasing cerebral perfusion and cerebrospinal fluid flow.

For those waiting for venoplasty treatment, the progress has been painfully slow, full of delays and frustration.  (The FDA approval of the Hubbard Foundation CCSVI registry is one beacon of good news!)  While many of these delays have seemed like simply a waste of time, some of the delays have helped the researchers understand the larger picture of cerebral hemodynamics--and the skeletal, muscular and truncular venous malformations which may contribute to restricted venous return.

We now know that CCSVI can affect those with Parkinson's and other neurodegenerative diseases.  This is not simply a problem in multiple sclerosis.  The diversity of specialties represented by the conference faculty was indicative of this change.  There were specialists in Alzheimer's research, traumatic brain injury, migraine,  panic attacks, stroke, TIA, and other neurovascular conditions.  All spoke of the vascular connection to their research, and the importance of the venous side of blood flow.  The jugular veins got a lot of attention---something that is a new development, thanks to Dr. Zamboni!

Participants heard research presentations on the cellular level of the endothelium in Alzheimer's disease process, where endothelial dysfunction begins prior to amyloid plaque formation.  Endothelial dysfunction is also implicated in the vascular connection to MS, where an increase of iNOS and a break in the blood brain barrier leads to inflammation and neurodegeneration.

There are still debates as to how to treat CCSVI--whether venoplasty is the best or only way.  I had a few opportunities to discuss the importance of lifestyle with Dr. Paula Grammas.  I first reached out to Dr. Grammas after reading her impressive research on endothelial dysfunction in Alzheimer's Disease.  Dr. Grammas considers the beta amyloid plaques, which have become the only focus of Alzheimer's research, to be a potential symptom of a larger problem--the miscommunication of endothelial cells.  I introduced her to the ISNVD, and was so pleased to hear her give the keynote presentation this year.

Dr. Grammas is a warm and thoughtful woman.  She was a pleasure to talk to. We discussed the anti-angiogenesis drugs that she will be looking at in clinical trials.  But we also discussed "the things we can change" today, in our own lives, without needing a prescription.  There are many known cardiovascular factors which increase our risk for dementia--including smoking, obesity, high cholesterol, inactivity, and stress.  And the best thing we can do for ourselves and our brains is maintain a healthy weight, eat a whole food diet, full of phytonutrients, move every day, not smoke, and reduce stress.  We also talked about the fact that healthy living is not about a "cure" for disease, but a means of prevention of disease progression.  The old adage, "an once of prevention is worth a pound of cure", is being proven in labs around the globe.

It was great to reconnect with friends who are patients and advocates.  The efforts of volunteers like Carol Schumacher and Sharon Richardson cannot be praised enough.  The doctors are always happy to see their patients---Dr. Dake was thrilled to see Jeff doing so well, and to hear him playing his trumpet at the ISNVD Gala.  It was a pleasure to see our Canadian friends--including journalists Avis Favaro and Anne Kingston.

I was thankful to have Jeff with me---for him to see the part of my world and work that has consumed much of my free time during the past five years.  As a friend commented, this research isn't "really his thing."  He is thankful for it, but it hasn't preoccupied him in the same way.  However, Jeff was touched and honored to sit with Dr. Zamboni, to hug and visit with other people with CCSVI, and to meet so many of the doctors who are changing the paradigm in neurovascular research.  I am thankful every day for his renewed energy, health, and our ability to travel together.  As I huffed and puffed, climbing those famous San Francisco hills, struggling to keep up with Jeff on our brisk daily walk...I marvelled at his health, and recommitted myself to helping other people with MS find hope and healing.

Joan

Nicoletta Mantovani-- A Woman Reborn

November 13, 2012 at 8:47am

Today, there are over 50 publications reporting on this story, which is important news in Italy.  I've translated one more link, from Ferrara, where Dr. Zamboni's trial is beginning.  Please note that the reporter states that Dr. Zamboni is going up against powerful opponents--namely the pharmaceutical industry and neurologists in their employ.   Miss Mantovani and Dr. Zamboni and all of us around the world are requesting clinical trials for his procedure. Independent research, without corporate interest.  Joan

http://www.ilfattoquotidiano.it/2012/11/13/metodo-zamboni-nicoletta-mantovani-rinata-dalla-sclerosi-multipla/412488/

Zamboni Method, Nicoletta Mantovani is reborn from multiple sclerosis

The weekly People Pavarotti's widow says her relief from this illness is thanks to the care created by the Professor from Ferrara. But his clinical trial Brave Dreams, operating for just a short time, is already receiving criticism from some medical journals

by Marco Zavagli | Ferrara | 13 November 2012

A woman reborn. Reborn from the disease, multiple sclerosis. Thanks to the care of Dr. Zamboni.  She has always believed and experimented in care for MS, with which she has struggled for years.

She is the honorary president of CCSVI in MS society, a non-profit organization and she is also sick. A president who has been known to be such. Nicoletta Mantovani, the widow of Luciano Pavarotti has been able to get in line and wait her turn. She did not "run away" abroad, as they must do in Canada, where the angioplasty intervention for obstructed neck veins is now on the agenda. She was patient like everyone else. Without utilizing the benefits that the money and fame could provide.

And today, as she confided in an interview published in People, she is "a woman reborn." 

Iron and gray matter - What do we know?

January 3, 2012 at 8:52am

As more and more MS reseachers come forward and explain how MS appears to be a disease of the gray matter first---before white matter lesions appear---it is vital that we look at gray matter structures in the MS brain, to see what is different in the MS brain when compared to normal brains.

This post will be long, but I believe it's important to understand MS research as it stands today, the beginning of 2012.

Last month, University of Texas researchers published in the Journal of Neuroscience--reporting that the thalamus, the deep gray matter of the brain, is smaller and atrophied in people with MS when compared to normal brains, and that this loss of deep gray matter tissue happens at the beginning of the disease, early on and before any white matter lesions are detected.

http://health.usnews.com/health-news/family-health/brain-and-behavior/articles/2011/12/30/multiple-sclerosis-may-cause-changes-in-thalamus-study

+++++++++++++++++++++++++++++++++

A recent paper from Hubbard, Haacke, et al shows how stenotic veins creates slowed jugular return of blood in pwMS.  Blood flow thru the brains of pwMS is much less than those with non-stenotic veins.  This may be an indication of hypoperfusion and decreased oxygenation, and we'll be hearing more about that from the Hubbard Foundation later this year.

Dr. E. Haacke has also noted an early change in the gray matter of MS brains--abnormally high iron content.

Dr. E. Mark Haacke has been looking at the gray matter in MS brains for almost a decade.  He is one of the inventors of SWI technology, an imagery system that can visualize iron deposed into brain tissue.

This is from his new paper is published in the American Journal of Neuroradiology--

Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and thalamas (THA) structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep gray matter (GM) structures.

RESULTS: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor.

The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content.

Currently, there is an increased interest in studying how GM is affected and particularly deep GM involvement in MS when iron deposition has been observed.  

Brain iron accumulation in neurodegenerative diseases, including MS, is not new and has been shown histologically in the past.  In MS, its source is likely due to myelin or oligodendrocyte debris, concentrated iron in the macrophages, or as a product of local microhemorrhages following venule wall damage.  As the wall breaks down, free iron may escape outside the vessel. This process has typically been seen in the basal ganglia, neurons, oligodendrocytes, macrophages, and microglia.6 Generally, free iron is known to lead to the formation of highly reactive hydroxyl radicals that can trigger cell membrane dysfunction and chronic microglial activation. Thus, iron from any of the above-mentioned sources could lead to inflammation and a further buildup of iron, causing the system to be self-sustainable.  

+++++++++++++++++++++++++

What Dr. Haacke is explaining is that we've known about iron in gray matter tissue in MS brains and other neurodegenerative diseases for awhile.   This is not new information.   Dr. Haacke explains that there are three possible causes of this iron in the MS brain.  The iron could come from one, two, or all three of these sources.

From Dr. Zamboni on new published research

August 12, 2011 at 1:22pm

An important message from Dr. Zamboni regarding the newly published study placed online today.  This is the 2nd  CCSVI endovascular treatment study undertaken in Ferrara, Italy.  The patients were Italian and American, in cooperation with BNAC.   There were two groups, an immediate treatment group, and a delayed treatment group,  The MRI technicians were blinded as to who was in which group.  All patients were on disease modifying drugs before, during and after, for consistancy in treatment.   This is very important to understand.  Angioplasty for CCSVI reduced lesions, improved MS symtoms and reduced relapses, when compared to those in the delayed group on the drugs alone.  Here's the note from Dr. Zamboni-

_______________________________________________________

Here attached for you, from the site of the European Journal of Vascular Endovascular Surgery, the second treatment study.  This study is also known as MS-EVT treatment of American and Italian patients who have traveled from across the Atlantic to be treated.
http://www.ejves.com/article/S1078-5884%2811%2900201-2/abstract

The study design is unique in the history of medicine. The patients were operated on in Ferrara, but the results were audited in Buffalo. Patients were divided into two mixed groups of Italians and Americans. The first ITG  (immediate treatment group) was operated on immediately, while the second group DTG (delayed treatment group) was treated six months later, allowing us to compare the ITG with DTG. Finally, we compared patients in the second six months, when both groups were operated on.  Then, all patients were compared with their original state during the previous year, prior to PTA.

The study is small (we had no money to do more), however, is very strong, certainly stronger than that of 2009 JVS, as it eliminates many of the criticisms of the latter. Particularly--

1. There is a control group for comparison, in practice it as a randomized as possible for use in surgery

2. MRI measures are rigorous, high-standard 3-tesla, comparable and indisputable as completely blind

3. Patients were evaluated by neurologists and neuroradiologists of two centers

4. Statistical analysis was done by an independent statisticians and blinded.

What does it prove

1. Both groups after the PTA had a significant improvement in the MSFC score compared to previous year, with substantial maintenance of EDSS (no disease progression)

2. In the ITG during the first 6 months there were fewer relapses. The percentage has been on an annual basis of 0.16 against 0.66 of the DTG. In fact the DTG in the first six months received only drugs. After surgery, the DTG no longer had more relapses than the ITG, confirming the protective effect of PTA on relapses.

3. ITG  T2 lesion load decreased while the DTG increased. After the PTA in the DTG lesion load stabilized during the second six months.

4. Complications were zero, zero thrombosis

5. 27% restenosis

6. ITG had one patient- despite the PTA, who had a recurrence and worsening on the MRI, confirming that the MS-CCSVI can not be handled alone by only interventionist. This article suggests the causes of deterioration after PTA on which new studies are needed.

More results

1. Ahead Zivadinov and all 17 consecutive patients had venography confirmed CCSVI

2. the ITG had an effect more pronounced in brain volume reduction than that of the DTG, a likely anti-edema and anti-inflammatory effect of the PTA.

Key messages

* CCSVI is associated with MS --as the first treatment of the condition changes the clinical parameters of the second

* The modification of parameters in a blinded MRI is totally immune from the placebo effect, then measured the improvements are real

* The treatment is safe in safe hands and can be beneficial

* To say after these two pilot studies, positive treatment studies, epidemiological studies have to wait is not sustainable

Paolo Zamboni, MD

Director, Vascular Diseases Center

University of Ferrara

Dr. Zamboni's published letter in response to the Doepp study

November 10, 2010 at 2:00pm

Published in the Annals of Neurology-

http://www.ncbi.nlm.nih.gov/pubmed/21061390

Regarding ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis. Intraluminal Jugular Septation’’ Paolo Zamboni, MD

I read with interest the article titled ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis’’ by Doepp and coworkers.1   Contrary to their conclusions, I believe that the authors’ results are a further validation of venous flow irregularities in multiple sclerosis (MS) patients.

One of the major regulators of cerebral venous outflow is posture, due to the gravitational gradient between the cerebral parenchymal veins and the base of the neck (␣30mmHg).2   The authors demonstrate a much larger change in blood flow volume in normal subjects compared to MS patients when the subjects go from a supine to an upright position. They find a change of 128ml/min and 56ml/min for the right and left sides, respectively, for MS patients. But they find a much larger change of 266ml/min and 105ml/min for their normal subjects. This result actually suggests the presence of chronic cerebrospinal venous insufficiency (CCSVI). Possible causes include intra-luminal septum, membrane, and immobile valve affecting the hydrostatic pressure gradient in the upright position. The presence of such blockages in the extracranial and extravertebral cerebral veins has been proven also by using catheter venography, the unquestionable gold standard in medicine.3,4

There was a trend toward significance (0.06) when comparing the mean global cerebral blood flow (CBF) in MS patients with that in controls. However, the level of significance is under- estimated by the low control sample, 20 versus 56 patients. The reduction in CBF in MS, meaning in practical terms stasis, might become significant by simply increasing the control sample.

Harvard professor visits Dr. Zamboni in Italy-- The More Iron, The More Severe the Disease

September 28, 2010 at 7:30am

From the Italian press---Professor Rohit Bakshi of Harvard University came to Ferrara University to discuss how his decade long study of iron deposition in MS brains has now intertwined with Dr. Zamboni's research:

Here is a Google translation of the press release:

Too much iron, more severe disease

New Ferrara - September 24, 2010 page 19 Section: Commentary

"It 's another piece of the puzzle that is made," says the researcher Paolo Zamboni.To place a new tile on the mosaic of research on multiple sclerosis was yesterday Professor Rohit Bakshi, Harvard University, came to Ferrara to explain the outcome of a decade of study during which he analyzed the role of iron as a contributory cause of the disease. His line of research was independent from that beaten by Ferrara Zamboni, but its conclusions have been come to intertwine with the results of tests carried out by the researcher and neurologist Bologna Ferrara Fabrizio Salvi on Ccsvi, which have established a hypothetical link between stenosis of the venous vessels in the brain iron accumulation and the onset of multiple sclerosis.

"The current therapies - said the scientist in the main hall of the university - are not effective in stopping the neurodegeneration. Bakshi was able, with a common magnetic resonance imaging to measure the actual concentration of iron in the brain, an operation in the past only run during the autopsy. Plaques and iron stores were associated, but especially "the greater the presence of iron - Bakshi said - the more you exacerbate the effects of the disease." Studies have revealed that the abnormal presence of iron affects the white matter and gray and tends to cause atrophy of certain areas of the brain.

http://ricerca.gelocal.it/lanuovaferrara/archivio/lanuovaferrara/2010/09/24/UCNPO_UCN06.html?ref=search

http://lanuovaferrara.gelocal.it/cronaca/2010/09/23/news/sclerosi-multipla-oggi-la-lezione-di-bakshi-2406157

Please note that Dr. Bakshi is confirming that current pharmaceuticals DO NOT stop the neurodegeneration of the MS disease process.

Here is an article on Dr. Bakshi's studies of MS and iron deposition from 2003:

http://www.webmd.com/multiple-sclerosis/news/20031022/multiple-sclerosis-tied-to-iron-in-brain

Venous Malformations

September 6, 2010 at 7:46pm

Dr. Zamboni--the vascular researcher who discovered CCSVI and has spent years developing a diagnostic and treatment protocol), has found many different types of venous malformations in those with MS.    It is very important to understand that CCSVI can be caused by several issues.  The doctors researching CCSVI are finding many defects.  And each individual has unique issues.

Dr. Zamboni has described CCSVI as created by truncular venous malformations, mostly "intraluminal defects", meaning problems inside the walls of the jugular and azygos veins.  

The types of malformations found by Dr. Zamboni and included in his published research are:

• Annulus --refers to significant circumferential stenosis of the whole venous wall; 
• Septum/valve malformation --refers to anomalous valve apparatuscausing significant flow obstacles at the level of the junction of the IJVs with the brachiocephalic/anonymous trunk; 
• Hypoplasia --refers to under-developed long venous segments; 
• Twisting-- refers to severe stenosies in consequence of a twisted venous segment; 
• Membranous obstruction--  (web) refers to a membrane almost occluding a vein; 
• Agenesis-- refers to the complete anatomical absence of a venous segment. 

Annulus, septum, membranous obstruction, hypoplasia and agenesis are truncular malformations previously described in other venous segments (cava, iliac, deep veins of the lower limbs).13 In Figure 7 there are some examples of venous stenosing lesions morphologically quite similar to those described in the IJVs/AZ in course of CCSVI. In contrast, twisting of the AZ is a truncular malformation never been described so far (Figure 8). In Table 1the distribution of the different truncular lesions in the extracranial and extravertebral cerebrospinal veins aregiven, and the more typical malformations are shown in the figures.

Here is the full paper:

http://phleb.rsmjournals.com/cgi/content/full/25/6/269

This research is very important to understand, because there is no one size-fits all approach to treating CCSVI.  And the IRs are working hard to develop a standard protocol.  That's what the convening meetings and conferences are all about.    

It is very understandable to want to believe that your doctor knows everything about CCSVI....it's a natural response, especially before undergoing a medical treatment, and perhaps paying for it.    But we need to be honest and upfront.  We are at the beginning stages.  Read Dr. Zamboni's paper, and note that there are many underlying issues creating Chronic Cerebrospinal Venous Insufficiency.  It's different in everyone.

Joan

CCSVI Facts--

April 9, 2010 at 2:21pm

1. Dr. Paolo Zamboni found a new medical condition when he noted that MS patients have stenotic veins draining the brain and spine. Through his blinded research, he found a condition he called Chronic Cerebrospinal Venous Insufficiency. It was new technology--doppler ultrasound--that showed him the blood was refluxing and slowed in MS patients brains. Although the connection of MS to the venous system has been made for over 100 years, Dr. Zamboni was the first to see a direct correlation. Many doctors around the world have now confirmed what he saw.

2. We know about Chronic Venous Insufficiency in other parts of the body. This is a recognized condition. Vascular doctors have studied this and treated it with angioplasty for many years. Surprisingly, the jugular and azygos veins had never been studied in depth before. Vascular doctors have studied the veins draining the legs, kidneys, liver and heart, yet not the brain. This is why CCSVI is new; however treating veins is not new. When veins do not work, there is harm to the organ they are supposed to drain.

3. The autoimmune theory for MS is a theory. It has never been proven. Dr. Thomas Rivers created EAE in the 1930s, when he discovered that he could mimic the demyelinating lesions seen in the MS brain. He created these CNS lesions by injecting rhesus monkeys brains with rabbit brain extract. He called this experimental allergic encephalomyelitis--EAE. (now the "a" is for autoimmune.)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212888/

We have never- in all of these years of research-- found out exactly why the immune system is activated in MS. Dr. Zamboni's research provides a very plausible reason: slowed venous drainage and reflux causes a break in the blood brain barrier which leads to deposition of foreign particles (including iron) which activates the immune system. He undeerstands this, because this is exactly what happens in venous stasis ulcers formed on the legs in Chronic Venous Disease.

4. People do not like new ideas, especially when they counter the status quo.

5. Doctors do not like patients reading on the internet and telling them what to do.

6. Time is brain...this expression is used for stroke treatment, but is applicable for MS, as well.

7. If MS is re-categorized as a venous disease with neurological complications, many people who make their living treating MS will be affected--researchers, professors, doctors, pharmaceutical reps and CEOS, nurses, and neurologists. Not all of them are happy about this. Many want this to just "go away."

8. Vascular doctors understand the importance of venous return....but not all want to or are able to treat CCSVI.

9. A knowledgeable, informed patient or caregiver is an asset to any doctor. But see #5. We need to read the research and understand the facts. 

Speak softly and carry a large stack of research papers. 

Joan

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. 

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

Notes from CCSVI conference, 

Bologna, Italy --September 8, 2009

September 9, 2009 at 7:37pm

Notes from the CCSVI presentation
September 8, 2009


Dr. Ellliot Frohman, University of Texas Southwestern Medical Center Neurology, Dallas, Texas and Robert Zivadinov, Jacobs Neurological Institute, Buffalo, NY are chairs for the morning session:

Dr. Frohman makes the introduction. CCSVI is removed from how we think about MS or any other immune mediated diseases. Could other diseases we currently classify as autoimmune be related to venous disease? Autoimmune diseases share in common molecular adhesion molecules. Perhaps Crohn’s could be venous? Validating CCSVI in MS may affect the classification of other autoimmune disorders. This venous model has been overlooked.

Micrographs, histopath proficles, periventricular cuffs, red cells we see in post capillary venules. This is not new. In 1863 -before Charcot.- G.E. Rindfleisch writes of venous congestion in MS.

Could the immune system go anywhere blood goes? Is this why there is an inappropriate immune response? He notes the large crowd in the room (it’s packed) and says he hopes people will speak out. (they will!)

+++++++++++++++++++++++++++++++++

Dr. Paolo Zamboni- Universita degli Studi di Ferrara, Italy director of vascular studies

The drama of CCSVI and MS is that of severe stenosis of the extracranial pathways. Everyone in this room can return home and establish a cooperation between vascular and neurology departments. A simple demonstration - he shows a video demonstration of doppler protocol to aid diagnosis. There is a blocked outflow of blood.

In the normal control groups, there is a monodirectional flow of blood. In MS the periventricular vein has a bidirectional flow. Substitute circles avoid intracranial hypertension. Mean transit time is increased.

Dr. Zamboni proposes a “Menu” for the day-

1. Entree- what is the origin of venous stenosis?
2. Pasta- May we assess consequences of CCSVI in the brain. Perhaps microbleeding is the source of lesions.  Just like CVI in other parts of the body- there is microcirculation
Cerebral spinal fluid ultrafiltration and reabsorption depends on transmural pressure.
TMP = IVP-EVP
In venography, there is much higher pressure in MS patients then controls.
Histology- research cited:
-red blood cell extravastion during relapse
-fibrin cuffs in venous hypertension
-iron laden macrophages
are ALL found in MS patients.

3. Main Course- Is CCSVI treatable?
measuring pressure before and after Liberation procedure is significantly changed.

4. Dessert- What are the effects of CCSVI treatment?

and for Today’s Special---Chronic fatigue as a symptom of CCSVI
(you have to love the Italians and their food analogies.)