Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of the endothelium and heart-brain connection. 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 auto-immune paradigm of MS, and continues the 20 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

Saturday, December 27, 2014

Scientific misconduct?

The negative Canadian CCSVI diagnostic 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

Wednesday, December 10, 2014

You and Your Microbiome

During the past year, there has been a lot in the medical press on the "microbiome."   Researchers continue to explore the connection between the microbiome and neurodegenerative disease.  Articles on the microbiome and MS, Alzheimer's, and dementia as well as cardiovascular disease and stroke, are being published in medical journals and discussed in online communities.

You might say 2014 has been the Year of the Microbiome!

But what is it??  Microbiome literally means the "small living community" inside each of us.  It's the word doctors and researchers use to describe your own, unique ecosystem.  You see, we are not just "ourselves", we are also host to a universe of living organisms.  And most of these guests take up residence in our gut.

We have about two pounds of bacteria living inside us.  These bacteria are broken down into four families: the Actinobactera, Bacteroidetes, Firmicutes and Proteobacteria.  http://www.nature.com/nri/journal/v13/n11/fig_tab/nri3535_F2.html

When these families live in balance, the human body functions better.  When these families get knocked out of balance, diseases can be linked.  "Dysbiosis" is when inflammatory bacteria outnumber beneficial bacteria.  Whether the link to specific diseases is causal, or resultant, is yet to be established.  But there's more and more evidence connecting an imbalanced microbiome to inflammation and diseases of "autoimmunity."

Here are some more specifics on what researchers found, when looking at the fecal bacteria in people with MS, and comparing them to healthy controls.  This is Dr. Sushrit Jangi of Brigham and Women's Hospital discussing results of a recent study:

The preliminary data show that there are at least a couple of different genera of bacteria that are different in the gut of MS patients compared with healthy controls. We found that a bug called Methanobrevibacteriaceae *** is enriched in the gut of MS patients and seems to have immunoproliferative properties that drive inflammation. We also found that the population of Butyricimonas ### bacteria is low in MS patients compared with healthy controls. This is an interesting result because these bacteria produce butyrate, which is thought to be immunosuppressive, but we do need to repeat this study in a larger cohort.
So it seems that our work initially supports the idea that the gut in MS patients contains bugs that drive inflammation and are low in the types of bacteria that control inflammation. This is consistent with work in rheumatoid arthritis and inflammatory bowel disease.
This also mirrors the idea that MS is a disease of the western world. If you go to countries like India and parts of Asia, where diets are far more vegetarian, you don't really see MS. However, when these people come to the United States and adopt a more westernized diet, the incidence of the disease goes up. I think this is an exciting premise but it's still too early to say anything about the causality.
***Methanobrevi bacteria are found to be enriched in those who are constipated.  
### Batyricimonas is also low in RA and inflammatory bowel disease.

I included probiotics and eating more plants in the Endothelial Health Program, because I read a lot of research on the link between bacteria, inflammation and the endothelium.  And I wanted to help Jeff.  He was severely constipated when we started the program (sorry, hon!  Is that TMI?)  His serum numbers were off the charts for inflammation.  His meat and animal protein to plant food ratio was far too high in meats, too low in vegetables and fruits.  His just wasn't eating enough living, plant-based foods with phytonutrients and fiber.  I thought there might be a connection, and found it in the endothelium.  Here is a post from 2011, where I explain:
Probiotics, also know as helpful bacteria, are included in the Endothelial Health program, because they affect the lining of our blood vessels in a positive way, by reducing inflammation and regulating NO. A strong endothelium is less permeable, and will keep plasmic particles out of tissue--in the brain and the gut.  This can modify the reaction of immune cells, and reduce what is called the "autoimmune" reaction.  (Although I believe calling this reaction "autoimmune" is a misnomer.  The immune cells are simply doing their job, by responding to foreign particles which should not be in brain or intestinal wall tissue.)

What to do?  How can we create a more balanced, happier microbiome, and encourage growth of healthy bacteria?   There are a few things scientifically proven that we can do today, while the researchers continue to look for specific answers.

1. Work with your own healthcare provider, and find a probiotic solution that fits your lifestyle and needs.  Some people eat yogurt, others prefer fermented foods like sauerkraut, kimchi or kombucha, or some take a probiotic supplement.  Some folks (like me!) enjoy all three.  Jeff finds his supplement is enough.   Each individual needs to discover what works best for them.

2. Eat more plants, eat less meat and animal products.   And stay away from processed foods. The research shows that the more saturated and trans fats, the less balanced the microbiome.  The more fresh vegetable and fruits, the better the microbiome.

3. Watch your bowel movements!  Are you going at least once a day?  If not, you're not moving waste products through your body efficiently, and that build up of noxious or "bad" bacteria may be enhancing inflammation in your body.  If you are having a couple smooth, not runny, bowel movements a day, chances are, your microbiome is pretty happy.  (sorry, was that TMI again??)

4. Stay at a healthy weight.  Obesity is linked to an unbalanced microbiome.

Let's be good hosts to the universe within us all!

Monday, November 24, 2014

NASA, the Drain Brain and Astro Samantha

Right now, on the International Space Station, the first female Italian astronaut, Samantha Cristoforetti, is settling into her new home.  Over the weekend, Cristoforetti left the earth's orbit from a rocket launch in Kazakhstan.  As she joins other international astronauts as part of Expedition 42/43, Cristoforetti will be conducting a major research experiment, using the technology developed by Dr. Paolo Zamboni.   This study, called Drain Brain, is a collaboration between NASA and the Italian Space Agency.  It will be using strain-gauge plethysmography (a neck collar which measures blood flow) as well as doppler ultrasound technology to analyze cerebral drainage in space.  Here's why, as explained on the NASA site.

On Earth, blood flows down from a person’s brain back toward the heart thanks in part to gravity, but very little is known about how this flow happens without gravity’s effects.  Many crew members report headaches and other neurological symptoms in space, which may be related to the absence of gravity acting on blood flowing through the veins. Drain Brain uses a special neck collar to measure blood flow from the brain, to help researchers understand which physical processes in the body can compensate for the lack of gravity to ensure blood flows properly.

Space Applications
Drain Brain studies how blood returns to the heart from the brain through veins in an astronaut’s neck. This can help scientists better understand the mechanisms that ensure proper blood flow in microgravity. ISS Crewmembers report a variety of neurological symptoms that may be related to changes in this blood flow. The project also studies how blood flow changes in response to crewmember schedules in space, which do not follow the typical day-night schedule of most humans on Earth.
Earth Applications
The instrument developed for Drain Brain, called a strain-gauge plethysmograph, does not require any surgery or special knowledge, which could make it an ideal tool for monitoring patients with a wide range of heart or brain disorders. In previous research, the scientists who developed the instrument identified a possible link between some neurodegenerative disorders, such as multiple sclerosis, and blockage of veins that connect to the brain. Researchers are also interested in studying the connection between these brain-related veins and cognitive disorders, such as Alzheimer’s disease. Drain Brain’s novel system could be a new way to screen for this vein abnormality.  http://www.nasa.gov/mission_pages/station/research/experiments/1278.html
As NASA explains, Dr. Zamboni has been using this neck collar to study people with multiple sclerosis.  And he has found that in people with MS, when compared to healthy controls, there is marked delay in drainage of the brain when patients go from lying down to upright.  Dr. Zamboni, who also discovered Chronic Cerebrospinal Venous Insufficiency (CCSVI) in MS, believes that extracranial obstructions are causing this delay in blood leaving the brain to travel back to the heart.  

What I find particularly ironic in all of this, is the fact that NASA and the smartest rocket scientists on the planet are eager to use Dr. Zamboni's technology, to understand how zero gravity and delayed venous return is affecting the brains and eyes of their astronauts, yet neurologists won't even consider the correlation of slowed venous flow and MS.  
From the abstract of Dr. Zamboni's study:
The rate at which venous blood discharged in the vertical position (EG) was significantly faster in the controls (2.73 mL/second ± 1.63) compared with the patients with CCSVI (1.73 mL/second ± 0.94; P = .001). In addition, respectively, in controls and in patients with CCSVI, the following parameters were highly significantly different: FT 5.81 ± 1.99 seconds vs 4.45 ± 2.16 seconds (P = .003); FG 0.92 ± 0.45 mL/second vs 1.50 ± 0.85 mL/second (P < .001); RV 0.54 ± 1.31 mL vs 1.37 ± 1.34 mL (P = .005); ET 1.84 ± 0.54 seconds vs 2.66 ± 0.95 seconds (P < .001). Mathematical analysis demonstrated a higher variability of the dynamic process of cerebral venous return in CCSVI. Finally, ROC analysis demonstrated a good sensitivity of the proposed test with a percent concordant 83.8, discordant 16.0, tied 0.2 (C = 0.839).


Cerebral venous return characteristics of the patients with CCSVI were markedly different from those of the controls. In addition, our results suggest that cervical plethysmography has great potential as an inexpensive screening device and as a postoperative monitoring tool.http://www.ncbi.nlm.nih.gov/pubmed/22521804?dopt=Abstract

Some of the neurological issues being reported by astronauts living in microgravity include loss of vision, fatigue and headaches,  possibly due to increased intracranial pressure.  One in five astronauts report changes in vision after returning to earth, and many problems involve the optic nerve, also an area of change in multiple sclerosis, which could be related to disturbed venous flow.  After five to six months in zero gravity, 20% of the astronauts are noting vision problems.
21 U.S. astronauts that have flown on the International Space Station for long flights (which tend to be five to six months) face visual problems. These include “hyperopic shift, scotoma, and choroidal folds to cotton wool spots, optic nerve sheath distension, globe flattening and edema of the optic nerve,” states the University of Houston, which is collaborating with NASA on a long-term study of astronauts while they’re in orbit. http://www.universetoday.com/114161/eye-problems-from-space-affect-at-least-21-nasa-astronauts-study/
"What we are seeing is flattening of the globe, swelling of the optic nerve, a far-sighted shift, and choroidal folds," said Dr. C. Robert Gibson, one of authors of the study published in the October 2011 issue of Ophthalmology, the journal of the American Academy of Ophthalmology. "We think it is intracranial pressure related, but we're not sure; it could also be due to an increase in pressure along the optic nerve itself or some kind of localized change to the back of the eyeball."

These black spots, swelling of the optic nerve, and changes to vision are seen in increased intracranial pressure, as well as multiple sclerosis.  My husband had all of these issues, and a loss of peripheral vision, as a child.  It would decades before he would be diagnosed with MS, and after that have a repair of his malformed venous system.

It will be interesting to learn what the Drain Brain study teaches us about venous return and the long terms affects of zero gravity. It is absurd to claim that slowed venous drainage does not matter to brain and eye health.

Here's to rocket scientists!  Here's to Samantha Cristoforetti!  You can follow her on twitter @AstroSamantha   Here's to Dr. Zamboni!  
Here's to answers.


Wednesday, November 19, 2014

How to remyelinate your own brain. New research

New research from the Karolinska Institute shows us, once again, that human and mouse brains are not the same.  Past assumptions about remyelination have been incorrect.  Attempting to model remyelination in the human brain using a mouse model simply does not work.

But there are things humans can do to remyelinate their own brains---and it's all about using the brain, and plasticity.

Here's the new research, which is calling into question all MS specialists thought they knew about myelin.

The brain's plasticity and its adaptability to new situations do not function the way researchers previously thought, according to a new study published in the journal Cell. Earlier theories are based on laboratory animals, but now researchers at Karolinska Institutet in Sweden have studied the human brain. The results show that a type of support cell, the oligodendrocyte, which plays an important role in the cell-cell communication in the nervous system, is more sophisticated in humans than in rats and mice - a fact that may contribute to the superior plasticity of the human brain. 

The learning process takes place partly by nerve cells creating new connections in the brain. Our nerve cells are therefore crucial for how we store new knowledge. But it is also important that nerve impulses travel at high speed and a special material called myelin plays a vital role. Myelin acts as an insulating layer around nerve fibres, the axons, and large quantities of myelin speed up the nerve impulses and improve function. When we learn something new, myelin production increases in the part of the brain where learning occurs. This interplay, where the brain's development is shaped by the demands that are imposed on it, is what we know today as the brain's plasticity. 

Myelin is made by cells known as oligodendrocytes. In the last few years, there has been significant interest in oligodendrocytes and numerous studies have been conducted on mice and rats. These studies have shown that when the nerve cells of laboratory animals need more myelin, the oligodendrocytes are replaced. This is why researchers have assumed that the same also applies in humans. Researchers at Karolinska Institutet and their international collaborators have shown that this is not the case. In humans, oligodendrocyte generation is very low but despite this, myelin production can be modulated and increased if necessary. In other words, the human brain appears to have a preparedness for it, while in mice and rats, increased myelin production relies on the generation of new oligodendrocytes.

In the study in question, researchers have studied the brains of 55 deceased people in the age range from under 1 to 92 years. They were able to establish that at birth most oligodendrocytes are immature. They subsequently mature at a rapid rate until the age of five, when most reach maturity. After this, the turnover rate is very low. Only one in 300 oligodendrocytes are replaced per year, which means that we keep most of these cells our whole lives. This was apparent when the researchers carbon-dated the deceased people's cells. The levels of carbon-14 isotopes rose sharply in the atmosphere after the nuclear weapons tests during the Cold War, and they provided a date mark in the cells. By studying carbon-14 levels in the oligodendrocytes, researchers have been able to determine their age. 

"We were surprised by this discovery. In humans, the existing oligodendrocytes modulate their myelin production, instead of replacing the cells as in mice. It is probably what enables us to adapt and learn faster. Production of myelin is vital in several neurological diseases such as MS. We now have new basic knowledge to build upon," says Jonas Frisén, PhD, Professor of Stem Cell Research at the Department of Cell and Molecular Biology at Karolinska Institutet.

Human and mice brains do not remyelinate in the same way.

That's right.  By keeping the mind active, learning new skills and firing your neurons, you can potentially remyelinate your own brain.  The problem is, there is no way for pharma to monetize this--so, you probably won't be hearing about this research in the mainstream press.  Because there is nothing to sell you.  No prescription.

After a comment below on how plasticity can't possibly remyelinate the MS brain, because it's "too easy" a solution--I've decided to add recent research that shows how plasticity has been noted in MS recovery.

Cortical plasticity predicts recovery from relapse in multiple sclerosis. http://www.ncbi.nlm.nih.gov/pubmed/24263385
Neuroplasticity and functional recovery in multiple sclerosis

Increasingly sophisticated brain imaging techniques indicate that brain plasticity - the brain's ability to reorganize neural pathways based on new experiences - is the compensatory mechanism largely responsible for the clinical remissions that are typical of early stages of relapsing remitting MS. The adult brain is capable of both functional and structural plasticity - processes that are operational in normal brain development such as learning and memory5.
Interestingly, functional and structural changes can also take place in the brain after injury or damage, and brain plasticity is seen to act as an adaptive mechanism to compensate for a loss of function6. Following tissue damage, the structure and function of undamaged parts of the brain can be remodeled and shaped by the sensorimotor experiences of the individual in the weeks to months following injury7, 8.

Here's more on neuroplasticity from Dr. Norman Doidge on his research and book, "The Brain that Changes Itself."  Learning changes the connection between the neurons in our brain cells.  Activity changes and heals the brain.

Want to remyelinate your brain?  Learn a new language.  Take up a new, challenging hobby.  Paint a picture.  Do a crossword puzzle.  Read books about new topics.  Learn a musical instrument (which is especially helpful for the corpus callosum)   Move as much as you are able, and if you can,  combine a cardiovascular pursuit with learning--like taking a ballroom dancing class, learning a new sport, practicing yoga.  It's all possible.

Don't wait for your neurologist to tell you.
Do this for yourself, your brain.
And please let me know what new skill you're mastering---

be well!

Saturday, November 8, 2014

Genetics and MS

Every few months, there is a news story lauding the fact that researchers have finally verified that MS is autoimmune.  These stories have a similar theme.  MS is most certainly autoimmune, because the connections made between MS and genes are all found in the immune system.  

But that's because it is the only place researchers are looking.  The major histocompatilbility complex (MHC) region remains the area under exploration, now 40 years since its initial discovery.

And they continue to get research grants from pharmaceutical companies to continue to look at the same location, because making this connection to the autoimmune theory advances drug sales.

In fact, the connection to heretability and genetics in MS is rather slim.  In identical twins, genetic risk is less than 1/3 if one twin has MS.  

...there is a 2% to 4% elevated genetic risk in siblings of patients with MS and a 30% greater risk in identical twins.

There was a recent story in the NY Times regarding research into a potential genetic link found in those who die due to Ebola infections.  Researchers Angela L. Rasmussen and Michael G. Katze of the University of Washington  found a problem with blood vessels, which were allowing immune cells open access and an overblown reaction to the virus. That's right.  Death from Ebola happens because of a break down of the endothelium, or the lining of blood vessels.  And there is a potential genetic link.

About two-thirds of people who die from Ebola never develop the terrifying hemorrhages that appear in others a day or two before death, in which eyes turn fiery red, gums bleed, red dots emerge on the skin as blood seeps out of capillaries, and blood appears in vomit and diarrhea. Many mice, too, die of Ebola without hemorrhages.

The mouse studies indicate the animals that hemorrhage and — by implication, humans— die because their immune systems overreact to the virus. The result is an inflammatory response that makes cells leak fluids and white blood cells, and makes tissues and organs deteriorate. Many die at that point. In those mice — or humans — that survive long enough, the researchers propose, blood eventually starts to seep out of vessels.

In fact, researchers found a genetic link to two specific genes, which were allowing for the overblown inflammatory response.

The mouse studies showed that animals that died after bleeding had an overblown inflammatory response to the virus. They also had low activity of two genes, Tie1 and Tek, that made their blood vessels more permeable. The leaky vessels allowed white blood cells to stream out, escalating the inflammatory response and causing a chain reaction of damaging immune system chemicals that destroyed organs. 

She said that “a big take-home lesson from the paper” is that genetics plays a major role in determining the outcome of a mouse’s Ebola infection. By inference, she said, genetics probably plays the same role in humans.

(for those who enjoy learning more, here is a paper on how Tie1 and Tie2 (TEK) are involved in vascular permeability.)

An overblown inflammatory response due to a breakdown of the lining of the blood vessels.  Sounds like something MS researchers might want to investigate, especially considering the recent research of Dr. Yulin Ge of NYU.

At the ISNVD conference in February 2014, Dr. Yulin Ge discussed how 7T MRI technology is allowing us to see tiny hemorrhages in the MS brain which occur before demyelination.  This further elucidates the microvascular connection to MS.
From his abstract at the ISNVD:

Being the most common demyelinating disease of the central nervous system, multiple sclerosis (MS) MS has a significant microvascular pathological component as a consequence of the perivascular inflammation. The role of vascular pathology in MS was suggested long ago. Now there is accumulating evidence of a primary vascular pathogenesis in MS. In vivo studies of vascular and hemodynamic impairment in MS may provide insights into the etiology and pathophysiology of MS and offer the potential metrics for assessment of outcome of the disease. 

The definition of insanity is repeating the same act over and over and expecting different results.  Continually searching in the same place for a genetic link to MS is not bringing us any closer to understanding MS aetiology.  It's making money for research labs and drug companies, but it is not bringing health and healing to people with MS.

Thanks to the ISNVD, for looking beyond the autoimmune paradigm.

Saturday, October 11, 2014

"We have confirmed Dr. Zamboni's results 100%"

It was only five years ago, September 2009, that I attended the very first CCSVI conference in Bologna, Italy.  Dr. Dake and I were invited as guests of Dr. Zamboni---and I was able to sit in on all of the sessions.  I took copious notes, and posted them on the internet.  I re-post the opening event notes  today, as a reminder of what has transpired.  I went to this conference, excited to see the cooperation of neurologists and vascular specialists.  I believed the benefits my husband received from his treatment would excite and encourage medical professionals in all fields.  I was naive.

I believe we have been let down and abandoned by a neurological community, which is intent on maintaining research funding and ties to the pharmaceutical industry.  I do not say this lightly.  I say it with a heavy heart. 
My bolding of the notes below illustrates my point.

The ISNVD will continue, and there are new members, mostly imaging and vascular specialists.  They are intent on understanding how restricted venous flow affects brain health.  They are not giving up on this investigation, despite the best efforts of others to thwart the reseach.  The Australian Alfred Hospital trial and Brave Dreams trials are still continuing.
And we are all older, wiser and most certainly not going away.
stay well,
Monday September 7, 2009
Bologna Italy
CCSVI PreCongress Meeting

Dr. Paolo Zamboni welcomes the gathered doctors and guests to the CCSVI Cenaculum Studiorum.
His topic is CCSVI, How to Move Forward-
He states that there are professionals gathered here from the studies of the blood’s path on the blood brain barrier side to the nervous system and that we all must share opinions and have exchanges. We need to dialogue and to learn from each other.

The origin of Dr. Zamboni’s work in Multiple Sclerosis began when he was a vascular surgeon in Sardinia, Italy. Sardinia is noted for its high level of epidemiology in MS in the general population. During 1987-1992, he noted a high prevalence in children with malformations of the jugular veins. His paper on this topic, “So-Called Primary Venous Aneurysms” was published in 1990. He noted AV fistula and a closed ring stenosis that could not be crossed by their blood in these children, external compression and this vascular anomaly appeared to be congenital. 20 years later, 90% of these children he studied have been diagnosed with MS.

In 2002, Dr. Zamboni noted that positive urine hemosiderin- a disease marker used to assess the severity of chronic venous disease- was administered to MS patients while they were in the midst of relapse. All of the MS patients tested positive. After he published a paper on this, he received an e-mail from Dr. FA Schelling- which referred him to Dr. Torben Fog’s paper- “Topography of Plaques in MS” The note from Dr. Schelling stated that perhaps Dr. Zamboni would now find what he was looking for...that the lesions of MS spread counter current from normal venous flow, and that there was where he should begin to study.

Dr. Zamboni then began to dedicate his work to develop a system of diagnosis of venous flow in the brain. He has found 100% correspondence with CCSVI and MS. He believes an international training program in Echo-Color doppler needs to be developed. and that there needs to be cooperation of neurologists and vascular surgeons. He mentioned endothelial disrupters such as smoking, cpn, EBV, and intracellular iron deposition as all being means of exacerbating this mechanism of disease. He spoke of his collaboration with neurologist Dr. Fabrizio Salvi of Bologna and the Jacobs Neurological Dept of SUNY Buffalo as being an example of such a collaboration.

Dr. Robert Zivadinov, Assistant professor of Neurology at Jacobs Neurological Institute at SUNY, Buffalo and Buffalo Neuroimaging and Analysis spoke next as to the Aim of the Meeting. He stated that we need to synthesize the current concepts about evaluation, pathogenesis and clinical relevance of CCSVI in MS. Individual variability in MS makes identifying the causative process very difficult.
He stated that the Journal of Vascular Surgery will soon be publishing the open label EVT intervention results of Zamboni, and that the current study at Jacobs, which will be completed in October ‘09 with the original 8 patients from America- has confirmed Dr. Zamboni’s results 100%. Dr. Zivadinov said that Jacobs is now recruiting and training new centers to test, diagnose and treat CCSVI in America.

He stated that he believes the next ten years will see 20,000 papers on CCSVI in vitro, vivo and animal studies. He reiterated that we need cooperation of various practices to find the solution. We need both the neurological and vascular perspective. He will be presenting at ECTRIMS after the Bologna conference.

Dr. Claude Franceschi- Director of the Paris Hospital Vascular lab spoke next on the Hemodynamic Factors of CCSVI.
The venous system is responsible for draining tissue, and the central parameter of drainage, transmural pressure, is changed when venous drainage is impaired. If TMP is too high, tissue suffers, edema and inflammation and vein dilation results.

Extra pressure on the nervous system comes from cerebral spinal fluid. Hydrostatic pressure is posture related- changing when the patient is supine or standing. The residual pressure- in which arterial blood surges into the venous system- is reduced in micro circulation. There is an increase in DR (downstream resistance) which is blocked by an obstacle. Obstacles can cause collateral veins to open as vicarious shunts and CSF will be excessive, causing edema and plaques. Cerebrospinal tissue is more sensitive to this. He believes the answer to CCSVI may lie in postural therapy, or a direct change in pressure via the Liberation technique or stenting.

Dr. Fabrizio Salvi- Head neurologist at the University of Bologna spoke of his clinical observations as a neurologist working with the CCSVI paradigm for three years. He told us that in 500 MS patients he has tested now, 100% have CCSVI. He stated the doppler is a wonderful tool of diagnosis and their needs to be training in the technique. He has a hypothesis as to why there are different varieties of screening in high risk subjects- because prognosis is related to the type of malformation. He wants to answer the question if the Liberation procedure is a disease modifying treatment in MS. He will give proof tomorrow that there is plasticity and remyelination in the CNS and the Liberation procedure have proven to activate remyelination in the CNS as shown by MRI.
“Yes!!!” stated Dr. Salvi...”no one is lost!!”

Dr. Patricia Coyle of Stony Brook University asks a question-
“How do we diagnose CCSVI?” 
The first answer comes from Dr. Zivadinov-
Doppler investigation is the beginning. If there is non-direction of flow in any body condition, or continual flow in the opposite direction- CCSVI is implicated. Transcranial doppler in the deep cerebral veins shows reflux. And then it is necessary to locate the stenosis. In MS, the jugular/Vertebral veins flow is consistently subverted. Dr. Zivadinov states that they had tested a 25 year old girl who had come into Jacobs as a control. A healthy girl, who presented with bilateral jugular occlusion. Months later, she had her first CIS attack of MS, and an MRI was done to show two lesions. She also has a familial history of MS. He reiterated that all of the doppler testing was blinded, yet it corraborated CCSVI in MS 100%.

Dr. Dake then stated that he had also tested a relative of a confirmed MS patient. A woman who had not been diagnosed with MS, but who presented at Stanford with jugular occlusion and a variety of neurological deficits, yet no MS diagnosis. She also showed lesion activity on an MRI, and he stented he occlusion the day before he flew to Bologna.

Dr. Zamboni makes the final statement to this question...he wants to articulate again that flow is more important than stenosis- especially as a preliminary diagnostic tool.
We are dismissed and all walk to a lovely formal dinner at the beautiful estate, Circolo della Caccia.

link to original post on Facebook September 7, 2009

How research has been manipulated:

Thursday, October 2, 2014

Systems Approach to healing-- Alzheimer's reversal!

Published in the September issue of Aging, "Reversal of cognitive decline: A novel therapeutic program", a new study at UCLA shows exactly how a personalized "Systems Approach" helped Alzheimer's patients recover memory and health.

Dr. Dale Bredesen, Professor of Neurology at UCLA, authored the new paper.  Dr. Bredesen is one of many researchers who has questioned the pharmaceutical model of inhibiting beta amyloid plaques in Alzheimer's.  

In the case of Alzheimer's disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease's progression, and drugs have only had modest effects on symptoms. "In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer's at an aggregate cost of over a billion dollars, without success," he said.

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer's is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain -- as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer's disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.


Dr. Bredesen believed that using a multiple target lifestyle therapy with his Alzheimer's patients might improve brain signaling.  Here are the main features of the program he created, which was adjusted for each individual patient.

(1) eliminating all simple carbohydrates (breads, pastas, baked goods)
(2) eliminating gluten and processed food, with increased vegetables, fruits, and non-farmed fish
(3) reducing stress with yoga
(4) as a second measure to reduce the stress, meditation for 20 minutes twice per day
(5) melatonin each night
(6) increasing sleep from 4-5 hours per night to 7-8 hours per night
(7) methylcobalamin (vitamin B12)
(8) vitamin D3
(9) omega 3 fish oil
(10) CoQ10
(11) Exercising for a minimum of 30 minutes, 4-6 days per week.

(Long time readers of this blog will notice that this program shares a lot with the Endothelial Health Program)

The results for 9 patients was better overall health, better body mass index, and a reversal of memory loss.   That's Alzheimer's Disease reversal!   Something no one drug has been able to achieve.

I've written about the difficulty in conducting double-blind, placebo control trials for lifestyle.   As Dr. Roy Swank, Dr. George Jelinek and Dr. Terry Wahls could all attest,  the "gold standard" trial approach works best for drugs. But that doesn't mean a holistic approach to healing is invalid, or cannot be trialled.  It just means it takes more work for both patient and researcher.  

There is no way to patent or monetize a new lifestyle, so drug companies won't be paying for these studies.   However, a holistic approach addresses many different aspects of health.

Yes, this is a small study, and yes, it is still anecdotal evidence.  But this program can be used in clinical trials.  It will be costly, and take time---but it may save brains.

What does this Alzheimer's research have to do with MS?  When we consider the link of the heart to the brain and the importance of cardiovascular health to cerebral perfusion, we can understand the need for endothelial health.  An oxygenated, perfused, cleansed and fed brain is a happy and healthy brain.

All diseases of neurodegeneration share hypoperfusion, or simply, reduced cerebral blood flow.  

There are lifestyle changes that can be made to aid healing.  Please note that I did not use the word "cure."  For more on how the "cure mentality" can hamper our efforts to heal--read 

The era of a "brain in isolation" research is ending.  More and more researchers, like Dr. Bredesen, are considering the body as a whole unit, and addressing cardiovascular function in brain health.

Thanks to Dr. Bredesen and UCLA for going up against the pharmaceutical companies, and bringing hope and healing to his Alzheimer's patients.

Where are the MS specialists ready to take on this challenge?
We're waiting,

Tuesday, September 30, 2014

REAL breakthroughs in MS research

It's been a busy month for MS research.  I wanted to give a brief overview of the new publications coming out in vascular journals, linking CCSVI and MS to slowed cerebral blood flow, changes in cerebrospinal fluid flow and coagulation factors.

As much as neurologists and immunologists continue to claim this exploration is dead, finito, over---there are still dozens of publications in press or being published which elucidate the vascular connection of CCSVI to neurological disease.  This exploration is far from over, as more and more international investigators join in the exploration.

1.  The International Society for Neurovascular Disease (ISNVD)--a multi-disciplinary group of researchers, has published their position statement on recommendations for multimodal noninvasive and invasive screening for detection of extracranial venous abnormalities indicative of CCSVI.

The full text is available here:

This position paper is extremely important, because it addresses the variablity of findings made by other researchers examining impaired venous flow in people with MS---and gives the first ever standardized imaging and evaluation recommendations.  It is written by some of the leading venous and imaging experts in the world.

The ISNVD recommends the use of a multimodal noninvasive and invasive imaging approach to optimally identify extracranial venous structural/morphologic and hemodynamic/functional abnormalities indicative of CCSVI. Creation of more quantitative imaging criteria are needed for further characterization of these venous abnormalities. Screening and monitoring of these venous abnormalities with the use of a combined noninvasive and invasive imaging approach should help establish the actual incidences and prevalence of extracranial venous abnormalities indicative of CCSVI in various populations. In addition, a multimodal imaging approach will address whether these abnormalities can cause significant hemodynamic consequences for intracranial venous drainage. The proposed noninvasive and invasive imaging protocols represent a first step toward establishing and validating the criteria for detection and monitoring of extracranial venous abnormalities indicative of CCSVI in open-label or double-blinded randomized controlled studies. The ISNVD recognizes that the rapidly evolving science and growing interest in this field will facilitate a refinement of these protocols in the near future.

2.  Another international collaborative effort looks at cerebrospinal fluid (CSF) dynamics in MS, using phase contrast MRI.  At the helm of this research is internationally recognized imaging expert, Dr. E. Mark Haacke.

This research separated pwMS into two groups, those with stenotic internal jugular veins (ST), and those without stenotic IJVs (NST) Changes in outflow was noted in those with stenotic veins.

The delay between the beginning of beginning of systole and the CSF outflow was higher in ST compared to NST MS. Less IJV flow was observed in ST vs NST MS. None of the measures was different between the different MS phenotypes. These results suggest that alterations of IJV morphology affect both IJV flow and CSF flow timing but not CSF flow amplitude

3.  Tying into this impairment of CSF outflow dynamics, another recent publication found that the third ventricle in the brains of those with CCSVI was much larger than in healthy controls on MRI.   The third ventricle is one of four ventricles in the brain, and is filled with cerebrospinal fluid (CSF).  In normal brains it is a narrow cavity and CSF flows freely through in a timely manner.  In those with hydrocephalus or normal pressure hydrocephalus, this ventricle expands.  

This buildup of fluid can damage the brain.  And the third ventricle is enlarged in those with CCSVI, indicating a lack of timely venous flow is impacting CSF flow.

In the MS–CCSVI group, the third ventricle diameter was 6.2±1.7 mm (from a minimum of 2.5 mm to a maximum of 9.2 mm, with a median of 6.3 mm, and a mode of 6.0 mm). Our data showed that 29 patients (88%) had an increase in third ventricle diameter, whereas only four patients (12%) had physiological size (less than 4 mm) comparable to all healthy control group subjects (27.28%). These results show that the increase in the third ventricle diameter could represent a criterion of positivity of neurological disease in patients with CCSVI.

4.  Finally, a group of vascular researchers look at how successful endovascular treatment of CCSVI changes the blood.  The fact that MS is related to higher levels of fibrin, ET1 and other markers of hypercoagulation and endothelial dysfunction has already been firmly established.

This group wanted to see if these blood markers changed, once normal venous flow was established.  They were.  In fact, lower coagulation activation status was associated with a better clinical outcome.  Another connection to the blood and endothelium.

Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

There is much movement in the study of how impaired venous return affects the brain for those with CCSVI/MS, and how treating this impairment improves clinical outcomes.  I live with anecdotal proof.  Jeff is now almost six years past his endovascular treatment and repair of malformed jugular veins and dural sinus.  He is jogging, traveling the world, working more than full-time, with a reversal of gray matter atrophy.  His third ventricle looks normal on MRI, he has had no further MS progression.  His coagulation numbers went from severe hypercoagulation, to normal.

There is a connection.  We will not let this research slip through the cracks.
stay tuned,