Welcome! This blog contains research, information on lifestyle, nutrition, dietary supplements and health for those with MS, as well as continuing information on the understanding of CCSVI and cerebral hypoperfusion. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the immune paradigm of MS, and continues the 15 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Thursday, January 22, 2015

New blinded study finds CCSVI associated with MS, and NOT found in normals

While CCSVI studies lead by neurologists claim they can't seem to find CCSVI, or conversely, they find it in everyone---

Here are the details of a recent blinded study lead by vascular specialists utilizing correct diagnostic protocols.  It was undertaken at Sapienza Hospital in Rome and lead by Dr. Luciana Tromba.   It's all about specificity and sensitivity of the study, which is reflected in their method and p values.  I'll explain below the abstract.

We enrolled 112 patients with multiple sclerosis and 67 healthy subjects from 20 to 67 years of age. All the patients underwent Duplex and color-Doppler sonography of the neck vessels, transcranial colour duplex sonography, M-mode study of the valve system and of venous abnormalities. Subjects were positive for chronic cerebrospinal venous insufficiency when at least two of five hemodynamic criteria of the Zamboni protocol were fulfilled

No healthy subjects were positive for chronic cerebrospinal venous insufficiency, while in the sample of patients affected by multiple sclerosis the diagnosis was made in 59.8% of cases (p < 0.0001)

I want to point out that very, very small p value number, that number which is smaller than .0001 means these scientists are very sure about their results.  In statistics, the p value is the number which reflects the testing of a hypothesis. The smaller the p value, the larger the significance of results.

What this means is that the study found a significant difference between normals and people with MS, and this is backed up scientifically.  It is not random, or chance.  This was a highly specific, highly detailed study.

The first criterion was the most frequent in patients affected by multiple sclerosis and chronic cerebrospinal venous insufficiency (respectively 54.4% and 76.1%, p < 0.001). The second, third and fourth criteria were never present in healthy subjects but were detected in patients with multiple sclerosis. The positivity of the second criterion was associated with diagnosis of chronic cerebrospinal venous insufficiency in 100% of cases. The third criterion had a prevalence of 52.2% in the subgroup of chronic cerebrospinal venous insufficiency patients. It was positive in 36 multiple sclerosis patients and was associated with chronic cerebrospinal venous insufficiency diagnosis in all cases except one.

This highly detailed study looked at all the CCSVI diagnostic criteria in those with MS and normals and saw very dramatic results.  This leads them to the conclusion---

Chronic cerebrospinal venous insufficiency is a haemodynamic condition strongly associated with multiple sclerosis and is not found in normal controls. The addition of M-mode ultrasound to the diagnostic protocol allows improved observation of venous valve abnormalities.

Again, this study was blinded, followed the correct Zamboni protocol, looked at blood flow (or hemodynamics) using M mode ultrasound.  M mode stands for "motion", and this ultrasound shows problems with delayed blood flow caused by issues inside the veins, like webs or problems with valves.

And the researchers found CCSVI in pwMS, and not in normals.

Dr. Zamboni has always stated that CCSVI is about blood flow, not just how veins look, or measuring stenosis.   As he has said numerous times, "CCSVI is about flow, not architecture."

When scientists work with him, utilize his protocol, they find CCSVI in MS.  That's what scientific replication is about.  It is not about agendas, conflicts of interest, or p values that show no specificity.  It is not about ignoring his protocol, casting aspertions, or creating new measurements for stenosis never before seen in vascular journals, like the Traboulsee study at UBC, which I believe was scientific misconduct.

This exploration of CCSVI is far from over, despite the "death knell" editorials by neurologists.   Thanks to the vascular researchers willing to do the hard work.


Saturday, December 27, 2014

Scientific misconduct?

The most recent negative Canadian CCSVI study, lead by University of British Columbia neurologist Dr. Anthony Traboulsee and published in The Lancet,  did not utilize the original scientific protocol of Dr. Paolo Zamboni.  

This new study displayed even further arrogance and audacity, by deviating from all other published venous and arterial studies, utilizing a false criteria to assess jugular vein stenosis. 

Stenosis is routinely measured by comparing the narrowed segment to the adjacent normal section of vein or artery and expressing this as a percentage.  This is the accepted way to measure stenosis.  All international vascular researchers use this method.  It is published in vascular textbooks, which is where I found this diagram.  This is how Dr. Zamboni quantified stenotic jugular veins in CCSVI.

But the Canadian neurology study did not do this.  Instead, UBC researchers created a brand new measurement to quantify stenosis using the full length of the jugular vein.  This method has never before been utilized in published vascular studies. And when Dr. Zamboni pointed this problem out, the Lancet refused to publish his response.

The very first step in the scientific method is replication of results.   When a scientist comes forward with a new discovery, other scientists are asked to look at the evidence.  In order to do this, the original scientific protocol must be followed.

This means that scientists collaborate with each other.  They enter a dialogue with the discoverer of new information. They talk to each other, discuss diagnostic and treatment protocols.  They are open, they do not have agendas.  This step in the scientific method is recognized the world over.  It is part of the critical process used to further evidence-based research.

When this doesn't happen, the scientific method does not work.  Fraud and deception are the result.  This is called scientific misconduct.

"Deviations from the planned protocol can affect the validity or relevance of a study.
The most important component of critical appraisal is careful assessment of the study design; however, other steps, such as evaluation of the statistical methods used, interpretation of the findings and potential conflicts of interest are also essential." 

Not only did the Traboulsee et al CCSVI study not utilize the original protocol by Dr. Zamboni, the investigators refused to speak with the protocol designer.  They would not respond to his requests for input, and they did not respond to his comments on the erroneous study.  They went ahead with a poorly designed study, and published their results as the "final word" in CCSVI.  This is an egregious betrayal of the scientific method.

The medical journal, The Lancet, refused to publish the response of the original protocol designer. However,  Dr. Zamboni's response is now linked on pub med in the comments section.

Here is the truth.  Dr. Zamboni responds to the errors of the Traboulsee et al study, "Prevelance of Extracranial Venous Narrowing" which is now published in a venous journal.  My comments will be in parentheses.

Last January The Lancet published the article by Traboulsee et alPrevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case control study

These Authors confirmed the presence of chronic cerebrospinal venous insufficiency with a high prevalence of about 70% in the Canadian population, but without significant differences between patients and healthy controls, yet. 

However, they used a criterion never published to assess stenosis, in alternative to the classic measurement of the diameter in the segment immediately preceding the narrowest point. 

Traboulsee et al. measure the stenosis along the entire length of the internal jugular vein, by comparing the maximum diameter with the narrowest point. It has been demonstrated, from normal anatomy findings, how the jugular bulb diameter normally exceeds 50% of the minimum diameter of the internal jugular vein, clearly showing the reason why Traboulsee et al. did not find significant differences between people with multiple sclerosis, their sibilings, and unrelated healthy controls. 

(In other words, using this new, not gold standard method, Traboulsee and team make it seem like most people have CCSVI.  If you compare the maximum diameter of the vein at the jugular bulb to the minimum location and call that result a "stenosis"-- well, heck!  Everyone has CCSVI!  But that's not science.  That's fraud.  It is scientific misconduct. Stenosis is classically measured in both veins and arteries by comparing the closed off area to the normal, open part right next to it.)

Furthermore, as the outcome measure of Traboulsee et al., wall stenosis is a neglected part of primary venous obstruction, because in the majority of cases obstruction is the consequence of intraluminal obstacles, as a considerable part of truncular venous malformations, and/or compression; rarely of external hypoplasia. 

(Dr. Zamboni has been saying this since 2009.  You need to look at obstacles inside the vein, as well as compression from the outside.  This study considered none of this.)

Finally, several recently published methods can be adopted for objective assessment of restricted jugular flow in course of chronic cerebrospinal venous insufficiency, by the means of non invasive magnetic resonance imaging, ultrasound and plethysmography. This may help us in improving the assessment of cerebral venous return in the near future.

(Why didn't the researchers work with Dr. Zamboni, a venous specialist?  NASA is using his technology, yet Traboulsee would not give him the courtesy of a phone call?  An e-mail?  Perhaps the honor of publishing his response?)

It is a dark time for science.  While neurological journals and researchers rule the MS dialogue, the science of the endothelium, venous function and cerebral blood flow are relegated to "death knells", "closed caskets" and "final words" in neurological publications.  Researchers refuse to speak to specialists in other fields.  Comments from the scientist who discovered CCSVI are not published.  False diagnostic criteria are created.  The death knell rings, not for CCSVI, but for the public's' trust.

And yes, there are serious conflicts of interest.  Here are Dr. Traboulsee's funding diclosures.
Anthony Traboulsee, MD, has received honoraria from EMD Serono, Teva Neurosciences, Bayer, Biogen Idec, Chugai Pharmaceuticals and Roche.  Traboulsee reported relationships with Bayer, Roche, Biogen Idec, Merck Serono, and Chugai. http://www.medpagetoday.com/Neurology/MultipleSclerosis/42151

Here are three new studies---published just this past month, two from Canada, ALL finding a connection to the vasculature and multiple sclerosis. This comes from cellular biologists, who are looking for real answers into disease etiology. And their research is being sponsored by universities and governmental agencies, not pharmaceutical companies.

Hoping for brighter days in the coming new year,

Monday, December 22, 2014

From cells to space stations--vascular research continues

While astronaut Samantha Cristoforetti works high above our planet on the International Space Station---studying venous return in microgravity and utilizing Dr. Paolo Zamboni's technologies----cellular biologists are looking at the MS brain. The macrocosm and the microcosm of MS vascular research is happening right now!

New technologies are allowing researchers to view the MS brain at a cellular level, before formation of lesions.  I wanted to share three of these new papers, all published in the last month.

Please note that the researchers are cellular biologists---they are looking at the MS brain on the most basic level, and they all see the vascular links to the disease.  They are not studying MS to find out how immune modulating drugs work, they are trying to solve the mystery of what causes MS.  And they are all seeing a connection to blood flow and the blood brain barrier.

When neurologists tell you CCSVI research is over, please point them to the continuing, confirming research which is further elucidating the vascular connection to MS. 

If NASA can work directly with Dr. Paolo Zamboni, why won't neurologists?
NASA wants to understand why 20% of their astronauts are coming back to earth with neurological and visual issues, and how it's related to blood flow.  So, they went to the expert.

Here are the brand new papers, all finding a link to MS and blood flow.

1.  The Role of Angiogenesis in the Pathology of MS

Cell biologists from the University of Irvine have noted how the loss of endothelial tight junctions in the blood brain barrier contributes to inflammation and angiogenesis (the growth of new blood vessels) in the MS brain,  and how this process is initiated by hypoxia.  This low oxygen state and resultant angiogenesis occurs prior to formation of demyelinating lesions.

This cellular research is further defining the hypothesis of cellular biologist Dr. Bernhard Juurlink, made in the 1990s.

It also fits in with my hypothesis of MS as a disease of hypoperfusion/reperfusion injury.

2. In vitro study of the direct effect of extracellular hemoglobin on myelin components.

The cellular biologists from the University of Guelph are looking at how blood particles damage myelin.  They are seeing microscopic deposits of hemoglobin in the MS brain, around the veins.  This blood contains iron, which when deposited into delicate brain tissue, begins a process of oxidative stress.
"This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease."
This work confirms the theory of Dr. Zamboni from 2006, called his "Big Idea" theory, which saw the similarities of venous disease to MS, by noting how blood particles caused damage to tissue via the iron found in our red blood cells.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/

3.  Focal disturbances in the blood brain barrier are associated with formation of neuroinflammatory lesions

Neurobiologists from the University of Montreal are seeing changes to the blood brain barrier which happen before immune cells enter the MS brain. There are changes to the tight junctions of endothelial cells. 
 Our findings suggest that BBB breach occurs before significant immune cell infiltration and demyelination.

I wanted to briefly highlight these new studies, and encourage all readers to pursue cardiovascular and endothelial health in 2015.  

The discoveries of endothelial dysfunction and the link to the breakdown of the blood brain barrier in MS are being made.  While we wait for the venoplasty and pharmaceutical solutions, there is much that can be accomplished with lifestyle changes.

Happiest of holidays to all.  Here's to a healthy 2015.

Here is Samantha's view                                               Here is a microbiologist's view