2016 Research Roundup

2016 proved to be a banner year for break through Multiple Sclerosis research.  And it showed us that what is old, is also new.

We now understand the brain has a vital and circulating immune system, reliant on draining veins and newly discovered lymphatic vessels.  New modes of technology are allowing scientists to study microbleeds, plasmic particles in brain tissue and the central vein sign (CVS) found only in MS lesions, which was first described in 1863.   Researchers are discovering how plasmic proteins initiate inflammation and contribute to brain atrophy in the MS brain.

Many of these discoveries are being made inside independently funded labs--like the Gladstone Lab and the Kipnis Lab--innovative labs outside the traditional autoimmune theory of MS.  These researchers are breaking down neuron-centric walls in hopes of understanding the etiology of MS.

And yes, these are vascular connections to the disease.  The brain is connected to the rest of the body via 60,000 miles of blood and lymphatic vessels.  

Neuroimmunologists who continue to ignore and ridicule the vascular connection to MS are still wrong.  History will not be kind to those who turned a blind eye, or purposefully denegrated this research.


1.  From the Kipnis Lab--brand new research finds a special immune cell in the brain which protects against injury and disease. Immune cells were found outside lymph vessels in the dural sinus, near the draining veins of the brain. These rare lymphocytes are also found in the gut, and may be the gut-brain connection researchers have been searching for. The brain needs these immune cells.  We do not understand the implications of how lymphocyte sequestering drugs may be inhibiting their work.  Dr. Kipnis is working specifically on Multiple Sclerosis right now--and he is very hopeful.

The cells, known as “type 2 innate lymphocytes,” previously have been found in the gut, lung and skin – the body’s barriers to disease. Their discovery in the meninges, the membranes surrounding the brain, comes as a surprise. They were found as UVA researcher Jonathan Kipnis, PhD, explored the implications of his lab’s game-changing discovery last year that the brain and the immune system are directly connected via vessels long thought not to exist.

“This all comes down to immune system and brain interaction,” said Kipnis, chairman of UVA’s Department of Neuroscience. “The two were believed to be completely not communicating, but now we’re slowly, slowly filling in this puzzle. Not only are these [immune] cells present in the areas near the brain, they are integral to its function. When the brain is injured, when the spinal cord is injured, without them, the recovery is much, much worse.”

Curiously, the immune cells were found along the vessels discovered by Kipnis’ team. “They’re right on the lymphatics, which is really weird,” noted researcher Sachin Gadani. “You have the lymphatics and they’re stacked right on top. They’re not inside of them – they’re around them.”

link

2. Imperial College in London, UK has discovered how a leaking blood protein called hemoglobin is associated with brain atrophy in those with progressive MS.  Hemoglobin is responsible for delivering oxygen and iron to brain cells, but when red blood cells break down inside blood vessels---from endothelial dysfunction or disturbed blood flow--the blood cells fall apart and release hemoglobin, causing inflammation and neuronal destruction inside brain tissue.  

An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease.

link

In English----- inside blood vessels there is a chronic break down of red blood cells, which releases the protein hemoglobin into the blood stream.   This freed hemoglobin is found inside MS plaques and inside the brains of those with MS and is linked directly to brain tissue loss.   Dr. Zamboni first described this process in 2006 .  He noted how venous disease of the legs looked like MS in his ground-breaking paper "The Big Idea"   link


3.  Hypercoagulation has been shown, yet again, to be a factor in the inflammatory phase of MS.  Elevated levels of prothrombin and factor x, which are blood coagulation proteins, were found to be linked to disease progression in those with RRMS and SPMS.  link

This discovery confirms continuing work by the Gladstone Lab, which has honed in on fibrinogen as the initiating factor in MS lesions.   link

All of these leaked blood proteins (hemoglobin, fibrinogen, prothrombin, factor x) are supposed to remain inside red blood cells, inside healthy blood vessels.  They are inflammatory once freed from vessels and behind the blood brain barrier.  This was my thesis in The Endothelial Health Program.

If the endothelium becomes damaged and the NO levels become imbalanced, cells which should remain in the blood can leak through blood vessels and into adjacent body tissue. Some of the leaked cells can include proteins, such as the C-Reactive protein, which is produced by the liver and causes inflammation⁸.   link

It was Jeff's sky high hypercoagulation numbers which first brought me to endothelial research and the vascular connection to MS almost 10 years ago.
The blood matters.    link


4.   The central vein seen inside an MS lesion is now recognized as a biomarker for MS,   according to a consensus statement from the North American Imaging in MS Cooperative (NAIMSC)  Multiple Sclerosis is unique, in that there is an enlarged vein at the center of each lesion.  Not an artery (which delivers blood)---but a VEIN, or a draining vessel,  which has become engorged and leaky.   Rindfleisch first noticed this phenomena with his microscope in 1863.  And the central vein is still there.  Finally, MS imaging specialists acknowledge this is a biomarker for MS.
link

A group of scientists asked this cooperative why they chose not to cite Dr. Paolo Zamboni's prior research, as he has published on the central vein sign and the link to venous disease.   Their query was published in Nature.  Again, it is Dr. Zamboni's ground-breaking paper, The Big Idea from 2006.

Re: The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

Bernhard HJ. Juurlink MD, Dario Alpini MD, Attilio Guazzoni MD, Laura Mendozzi MD, Raffaello Pagani MD, PierluigI Stimamiglio MD, Pietro Maria Bavera MD

We read with interest the consensus statement titled "The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative" (1).
We wonder why the authors haven't cited in the notes any paper of Dr. Paolo Zamboni from University of Ferrara, Italy.
Particulary, his oldest paper titled "The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis" published in November 2006 (2).
In that paper he readily showed the histology of the CVS, and explicitly reported the possibility to image it by the means of MR, as well.
Regards.
Disclosures: none
References:
1) Sati, Pascal, et al. "The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative." Nature Reviews Neurology (2016).
2) Zamboni, Paolo. "The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis." Journal of the Royal Society of Medicine 99.11 (2006): 589-593.

5.  Dr. Paolo Zamboni presented an update on his Brave Dreams placebo controlled CCSVI trial at the 2016 Veith Conference in New York City.  This is the first placebo controlled multi-center trial which is utilizing neurologists, MS specialists and vascular specialists, all working together and collaborating.  All are independently reviewing the results from the study.  Dr. Zamboni spoke with Sharon Richardson of CCSVI Alliance, to give a breakdown of the study.

link

This was a six center study throughout Italy.  200 subjects started the year long study, 125 people completed it.  They were mostly RRMS and some SPMS  (under 5.5 EDSS) who were investigated, treated (or not if they were in the sham control) and followed a year through completion of this study.  There were primary endpoints, which Dr. Zamboni explained were OBJECTIVE.  This means that these changes were not subjective, or based on patient's feelings, but were measurable by approved medical instrumentation.  These objective measurements included volume of bladder, visual acuity, timed walking and manual dexterity, as well as MRI lesion consideration.  All of these measurements were looked and compared during 3, 6, 9, and year intervals.  The first paper will report on these primary endpoints after treatment, and will hopefully be available next June.

As Dr. Zamboni stressed---this type of trial is unique and should become the gold standard for MS treatments.   NO drug trial has ever been weighted and measured in such a precise, objective way.
To the patients, Dr. Zamboni asked us all to "be patient".  There will be more coming on how CCSVI treatment improves perfusion and cerebrospinal flow, as well as how it helps with depression, memory, fatigue, and cognition.  This research is more "like an opera"--it is going to take cross-disciplinary collaboration and cooperation.  Across disciplines and countries.



2017 will only further our understanding of the connection of the brain to the rest of the body, and how the vasculature is implicated in the MS disease process.

Until we know more, live your best, vascularly healthy life.
Move as much as you can, as often as you can.  Eat organic whole, colorful foods full of phytonutrients.  Get your UV rays and Vitamin D.  Get good sleep and manage your stress levels.  Don't smoke or eat junk food.  Stay hopeful.
There are better days ahead.

Promise,
Joan

Dr. Zamboni interview on Brave Dreams Trial

Dr. Paolo Zamboni is presenting at the Veith Symposium in New York City today.  He sat down for a live Facebook chat with CCSVI Alliance President, Sharon Richardson.   Here are some of the main talking points I jotted down while watching from my kitchen in California.  The video is available to all here:  https://www.facebook.com/CCSVI-Alliance-125892427429118/

It was good to hear and see these two, and their conversation was wonderful.  Sharon has become a well-versed advocate for those with MS.  The fact that she has MS and understands all of the medical terminology and scientific talk-- and takes it upon herself to travel and document this research--is so helpful for all of the laypeople around the world who wish to understand more about CCSVI research.  Thank you, Sharon!!!  You are a dynamo and we all appreciate you!!!  Thanks also to Florence D'Eon for all of her technological and photographic support.  She also has MS and travels on her own to document the science.  Thank you!!

The Brave Dreams trial is a scientifically robust, double-blinded, placebo controlled trial.  It is currently embargoed--meaning we will not know specific results until it is published in a peer-reviewed journal.  Because it is an interdisciplinary study involving neurologists, interventionalists, vascular and imaging specialists, it is going to take a lot of work to get the results vetted by all, and written up in a manuscript everyone agrees to.  Dr. Zamboni stressed that this is essential, in order to have the science taken seriously and published.

What we do know--this was a six center study throughout Italy.  200 subjects started the year long study, 125 people completed it.  They were mostly RRMS and some SPMS  (under 5.5 EDSS) who were investigated, treated (or not if they were in the sham control) and followed a year through completion of this study.  There were primary endpoints, which Dr. Zamboni explained were OBJECTIVE.  This means that these changes were not subjective, or based on patient's feelings, but were measurable by approved medical instrumentation.  These objective measurements included volume of bladder, visual acuity, timed walking and manual dexterity, as well as MRI lesion consideration.  All of these measurements were looked and compared during 3, 6, 9, and year intervals.  The first paper will report on these primary endpoints after treatment, and will hopefully be available next June.

As Dr. Zamboni stressed---this type of trial is unique and should become the gold standard for MS treatments.   NO drug trial has ever been weighted and measured in such a precise, objective way.

To the patients, Dr. Zamboni asked us all to "be patient".  There will be more coming on how CCSVI treatment improves perfusion and cerebrospinal flow, as well as how it helps with depression, memory, fatigue, and cognition.  This research is more "like an opera"--it is going to take cross-disciplinary collaboration and cooperation.  Across disciplines and countries.

For those who are out of wait---this news is frustrating.  For many of us, the time it is taking to gain scientific acceptance is far too long.  And as many have stated--how can having slowed venous drainage be good for the brain?  Shouldn't CCSVI be repaired?

There are other CCSVI treatment trials happening now or planned for the future at Alfred Hospital in Australia, in Canada, and through the ISNVD.   As to the comment that CCSVI science is "dead"-- many scientists agree that the study is just beginning.  To claim that vascular MS research is over, simply because this is taking time and hard work, is absurd.

The 2017 ISNVD conference will be in Taormina, Italy in May.  It will focus on the microbleeds and inflammation in the brain,  neurodegenrative disease, stroke, the heart brain connection and vascular interventions.  It will bring together international imaging specialists, neurologists and vascular specialists.  This will be a meeting of hearts and brains.  Patients, caregivers and laypeople are invited to attend.
link to ISNVD 2017

Onward,
Joan

Lipoic Acid improves MS and Endothelial Health

An inexpensive over the counter supplement, Lipoic Acid, has been shown to decrease brain atrophy and increase walking speed in people with secondary progressive MS.

Participants took 1200mg. of lipoic acid daily, while others took placebo.  And there were improvements shown in the pwMS--so much so, that neurologists are talking about it at ECTRIMS, in a recent oral presentation at the conference.

Link to news release 

"There is a great unmet need to find a disease-modifying therapy for progressive MS. We wanted to look at lipoic acid as possibly filling this role since it's a small-molecule agent that, because of its low cost, could be readily available to anybody who needed it," said Dr Spain.

As I've written many times on this page, it is MUCH easier to test one supplement at a time against placebo, rather than having a trial for an entire lifestyle program.   This is why "gold standard" drug or supplement trials get all of the research dollars and attention.  So, it's at least nice to see a trial of a supplement which has no harmful side effects.

What is Lipoic Acid (LA), also known as a-lipoic acid (ALA) and how does it help people with MS? 

Lipoic Acid (LA) is found in almost all foods. Highest levels are found in organ meats, broccoli and spinach.  Tomatoes, peas and brussel sprouts also have higher levels of LA.

LA is an anti-oxidant, and prevents damage due to oxidative stress. 

It has been tested and found to be helpful for people with metabolic syndrome and diabetes---because it improves endothelial function. 

link

link

That's right.  LA helps the vasculature and blood flow.  It increases nitic oxide availabilty and allows for vasodilation.  You won't be reading that in any neurology press releases any time soon, but this is a fact.  LA increases blood flow, via dilation of vessels through endothelial health.  And this could account from the maintenance of gray matter and improved walking times in people with MS.  

But you know what is even better than simply taking LA or biotin or any other supplement?  Using an entire lifestyle program-- including nutrition, exercise, stress reduction, UV ray exposure-- which is shown to reduce oxidative stress, increase endothelial health and protect your brain.

The Endothelial Health Program

It's not a pill,  it's a lifestyle.

Joan

Eating Food

I love food.  And because of this love, I've dealt with weight issues my entire life.  By the time I was 12 years old, I weighed in at 180.  A good weight for a "light heavyweight" prize fighter, but for a young girl in middle school, not so much.  As a result of this enthusiasm for food, I've tried a variety of ways to keep myself slim.  Liking boys and in turn wanting them to like me was the first motivator to join Weight Watchers.  It took almost two years, but I dropped 60 pounds.  By the time I was 14, I'd lost my baby fat, but had discovered the confusing world of dieting.

Diets do not work.  By that I mean, deprivation and punishment are no way to live.  Because as soon as you end the diet and return to "normal" life, the weight will return.  Trust me, I've yo yo'd enough to know.  That's why I always use the word "lifestyle."  Living in a particular way, with certain habits, is the only way to maintain health.

Food matters.  It is our means of taking in nutrition.  Our bodies rely on a good intake of antioxidants, which come from colorful plants and spices.  Envision blueberries' deep color or the vivid orange of curcumin.  The staining red of fresh beets and the deep green of kale.   These colors signify levels of phytonutrients (simply, nutrients from plants)---the darker the color, the more plentiful the essential nutritional value.

We now know that our microbiome, the 2 pounds of bacteria which live in our guts, are responsible for the health of our brain.  The microbiome maintains our neuronal network, our neurotransmitters and hormone production. link to science  If we do not provide enough good prebiotic food for the good bacteria by means of colorful fruits and vegetables, we starve the good bacteria, and allow the bad to overtake the territory.  link  The survival of our microbiome, and in turn our brains, means choosing the right foods.

In 431 B.C., Hippocrates knew that food was the best medicine.

And there is a reason why researchers, like Dr. Terry Wahls, are honing in on the right diet to maintain the health and integrity of our bodies.  It's not because they are some sort of passionless creatures, attempting to take all of the fun out of eating, to make us suffer longer lives in healthy boredom.   It's because they understand the science behind nutrition, and they want to help us feel better.

There is a lot of confusing information out there.  We all read the news stories and click bait articles--DON'T eat bananas if you want to lose belly fat, ONLY drink lemon water with maple syrup, mix a protein and a carb, coconut oil is the way to beat Alzheimer's or the worst thing in the world.  Should I try paleo or vegan??? Wait, do coffee drinkers have less strokes or more cancer?  What the heck is gluten, anyway?  It's difficult to know what to believe.  And if you're like me, you don't want to take all the fun out of having a meal.  Sitting down with loved ones over a delicious meal is one of the true joys of being human.  We're not science experiments in a lab.

When I started changing up our family's meal plans almost ten years ago, I got a ton of pushback.  Let's just say that Jeff was not thrilled I stopped buying processed meats and cheese.  He loved both of these food groups so much, that he could have happily lived on sausage, cubes of cheddar, with a frosty diet Dr. Pepper to wash it all down. Suddenly, dinner was a piece of fish with a big leafy salad.  His "snacks" were now almonds and dried blueberries, or an apple.  Really???  What happened to the steaks and pasta with cheese?  And where was the mayonnaise?  Why, exactly,  couldn't he have a diet soda?  It's diet!!!  Let's just say, he was not happy, and I heard about it.  But I carried on, trying out new recipes and buying only organic and no prepared foods.  This meant more work for me, but I knew it would be worth it.

After about a year of this new lifestyle, we felt better.  We both lost our middle age love handles, our energy was better, we were sleeping well, we were staying active with less joint pain and better mobility. Less constipation, no heartburn, and our blood tests were coming back with astounding numbers.  No high CrP, low cholesterol, no inflammation, great liver enzymes, great vitamin D, perfect red and white blood cell counts.  Our doctor joked with us that if she just saw our serum markers, she'd think we were in our twenties. The truth is, we didn't feel deprived at all,  because we had found healthy substitutions for all of the foods we were missing.

Here's a few of our lifestyle hacks---the reason we still love to eat, and don't feel deprived.

Instead of:                     We have:

Crackers n'cheese    carrots, jicama sticks,
                                 pea pods w/salsa/guacomole

Potato Chips             home roasted
                                  sweet potato fries or home roasted kale chips

Ice Cream                 Yonanas
                                  frozen fruit dessert   http://yonanas.com

Pasta Alfredo           Eggplant moussaka
                                 w/garbanzo beans

Mayonaise               Hummus

Cold cuts                home roasted
                               organic chicken

Milk                     almond milk

Candy                   dried blueberries,
                              fresh strawberries, grapes

Bread/buns          corn tortillas
                            or lettuce wraps


You might notice that our substitutions look an awful lot like a Mediterranean Diet--and indeed, that's what we've grown to love.  (You can, too!!  link )  Tons of fresh fruits and veggies, less animal products, olives and olive oil, nuts and beans, LOTS of spices, and no more processed food.

I like to think of this lifestyle as Foods Made in Sunshine.  All of the ingredients we consume need sunshine in order to be produced.  Nothing originates inside a factory.  All of our food comes from the great outdoors.

I also like to think of this way of eating as "Yes, you can" rather than "No, don't have that!"  By replacing the mindset of deprivation with one of plenty and gratitude, we can enjoy what we eat, and not suffer with iceberg lettuce and a sad tomato slice, wishing it was something else.

Hope this is an inspiration for those of you wanting to try a new lifestyle.  Shaming never worked for me when I wanted to lose weight or feel better.  Deprivation wasn't the way for me or my family.  But finding positive and healthy ways to think about food has been the key.

Wishing you and yours health and wholeness.  And lots of happy eating.
xo
Joan

MS Mi$diagnosis

Most people assume that diagnosing multiple sclerosis is easy, but nothing could be further from the truth.  Diagnosing MS is a challenge, as there is no specific biomarker or blood test for the disease.  Other diagnoses, mostly caused by vascular issues like migraine or TIA, also show white matter lesions on MRI.  In fact, white matter lesions are up to 500 times more likely to be related to a vascular condition than MS! link  Even oligoclonal banding tests are non-specific for MS, as people with ischemic stroke have similar markers in CSF.   link

It's far too easy to misdiagnose MS;  a disease named for its symptom (many scars) and diagnosed by neurologists.  Neurologists have supposed eminence in MS diagnosis, which I believe has created a huge blind spot towards vascular evidence.  More on eminence vs. evidence based medicine
Maslow's theory also comes to mind:  "If all you have is a hammer,  everything looks like a nail."

Dr. Andrew J. Solomon, neurologist from the University of Vermont College of Medicine, has been publishing on this problem for many years.  He is lead investigator in a new study on MS misdiagnosis, presented at the recent AAN conference in Vancouver. link

Dr. Solomon's latest study was just published online in Neurology. Twenty four American MS specialists reviewed the cases of 110 patients who were misdiagnosed with MS, gave them correct diagnoses and then published their results.

The time for carrying a misdiagnosis was 3 to 9 years in 29% of patients and 10 to 20 years in 26% of patients.  31% of the patients experienced "unnecessary morbidity", which means they suffered for no reason.  How did that happen?  They were given drugs with dangerous side effects, which they did not need.

According to the study findings, 72% of the misdiagnosed patients (Edit: that's 79 people!) took medication to treat a disease they didn't have, some took these medications for many years. Four of the patients misdiagnosed with MS had participated in clinical trials for experimental MS therapies.

"This study suggests significant and long-term unnecessary risk for these patients," Solomon says.

Some of the treatments for MS carry serious side effects. One drug, taken by 13 percent of the misdiagnosed patients, can cause a potentially fatal brain infection, Solomon says. (Edit: 14 misdiagnosed patients were given Tysabri!) Other patients suffered from the discomfort and inconvenience of daily injections, others experienced side effects from medications, and finally, they lacked treatment for their actual correct diagnoses.
link

Other misdiagnosed patients were given mitoxantrone and cyclophosphamide.  This is absolutely unconscionable. I hope these patients find legal representation and are compensated for their pain, morbidity and suffering.  They deserve it!

Here's a recent news story, where two women took the neurologist who misdiagnosed them with MS to federal court.  These two women filed separate negligence law suits against Dr. Gary M. Weiss, a former Vail Colorado based neurologist, who misdiagnosed them with MS using his own MRI lab, and them put them on MS drugs.   One woman was wrongly given over 100 infusions of Tysabri.   Over 20 of Dr. Weiss' MS patients now claim they were misdiagnosed.  link to news story Shockingly,  Dr. Weiss is still treating patients, as a practicing neurologist in Florida.

The problem highlighted in this lawsuit is that many neurologists see dollar signs when they diagnose M$.  An MS diagnosis means ongoing care, high fees for infusion centers or MRI centers, lots of prescriptions, and a patient for life.  Many neurologists receive kickbacks from pharmaceutical companies, in the form of honorariums, speaking fees and fees for enrolling patients in clinical trials.

Maran Wolfston, an MS patient and doctoral student, investigated her neurologist when she felt he was pushing her use specific MS drugs.  She later published her revelations.  Her neurologist first encouraged her to enroll in a clinical trial, and after she declined he told her she would need to begin Tysabri infusions.   Sure enough,  using the Dollars for Docs site sponsored by Propublica and thanks to the Affordable Care Act, she could search her neurologist's payments from pharmaceutical companies.  (You can, too! Link to Dollars for Docs )  She discovered her neurologist was receiving major payments from Biogen--the sponsor of the clinical trial he had recommended and maker of Tysabri.  She has published a paper on the result of her "loss of trust."

I knew that I had felt pressured to take medications by my neurologist. When I found that he had been paid large sums of money—six times my yearly salary—to work for the manufacturers of those same drugs, my loss of faith was complete. I never returned to his neurology clinic again.   link to paper

There is no similar monetary incentive for the diagnosis of vascular disease.  Neurologists only consider their particular "hammer" of immune modulating drugs and then they assert their eminence. And patients are too intimidated, sick and overwhelmed to ask questions.

Here's more from the lead neurologist, who also published in 2012 Link to "Undiagnosing" MS.  Dr. Solomon half-heartedly tries to rationalize the hair-trigger response in prescribing drugs:

In patients diagnosed with MS, prompt initiation of treatment with immune modulating therapies is often appropriate, so, notes Solomon, "There is pressure to make the diagnosis of MS early, and to start patients on MS therapies quickly. But in some patients who do not meet rigorous standards for diagnosis, waiting longer and close follow-up may determine the correct diagnosis."

Making sure the diagnosis is correct and waiting seems like the best idea.  Many studies now show that starting patients early on MS drugs might decrease relapses, but makes no difference in long term disability or MRI results, so why not wait to prescribe Tysabri or mitoxantrone??

Better still, why not first address the more common cardiovascular causes of white matter lesions, and truly make MS a diagnosis of exclusion?

White matter lesions on MRI, a supposed "hallmark" of MS, appear most often in vascular conditions.  These conditions include antiphospholipid syndrome (Hughes Syndrome), migraine, stroke, and transient ischemic attacks.  Any of these vascular conditions---which all involve a disturbance of cerebral circulation and hypoperfusion--can exhibit white matter lesions on MRI.  

White matter lesions on MRI are up to 500 times more likely to be related to vascular disease than MS.   link  The idea of MS lesions being related to the vasculature and slowed cerebral blood flow is not new. link  People with MS have cerebral circulation 2X slower than healthy controls.  link

If you know someone who has recently been diagnosed with MS and questions their diagnosis, or if you have questions regarding your own diagnosis---please--go through the list of differential diagnoses with your doctor or get a second opinion, especially before taking any disease modifying drug.  link

And if you have any vascular issues, like hypercoagulation, blood clots, migraine, high blood pressure, obesity, TIAs, stroke, high inflammation (C reactive protein) or venous disease---please, talk to your doctor about addressing these issues.  If there are vascular commorbities, there is a chance that in addressing vascular problems you may never require disease modifying medication.

Be a patient like Maran Wolfston---be knowledgable, ask questions, do your research.
Be that patient (or caregiver) almost every neurologist dreads.
Make them roll their eyes.
Trust me, the momentary embarrassment is worth it.

be well,

Joan

ECTRIMS '16

The European Committee for Treatment and Research in MS (ECTRIMS) is gathering for their yearly conference in London this September.link I thought it might be interesting to see if any researchers are going outside the EAE autoimmune model of MS, to discuss the connection of MS to the vascular system, as there have been many breakthroughs in this area during the past year, thanks to 7 Tesla MRI and published research on the heart brain connection, endothelial dysfunction, coagulation cascade activation, microbleeds and hypoperfusion in MS.  

Using the search term "vascular",  I found one reference.

Under the Teaching Course heading of "MS Brain Health", which is being chaired by Dr. Giovannoni of London (oh, the irony!), Dr. Ruth Ann Marrie from Canada will be presenting on her research regarding vascular commorbidities in MS.  link  Dr. John Saxton from Newcastle, UK, will also be discussing "Lifestyle Modifications" in MS.  

This area of discussion is new to ECTRIMS.  MS researchers are loath to acknowledge any connection of the MS disease process to vascular health.  The language they use to broach this subject shows just how reticent they are to give up any ground to vascular specialists--just notice the wording of the paragraph below.  But they have to talk about this now, as the science is in, and the elephant in the room must be addressed.  The heart and brain are connected.

Although multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system numerous systemic and lifestyle factors affect MS outcomes. In summary Brain Health refers to a holistic approach to the management of multiple sclerosis that focuses on MS-specific, and MS non-specific, factors that are modifiable. An important aspect of brain health is the empowerment of people with the disease to make them understand that there is a lot they can do themselves to self-manage their own disease. The course will review the philosophical underpinnings of brain health and the shift to treating MS more actively and to a target. To optimise outcomes for people with MS we have to actively monitor the disease. An important part of brain health is the screening for, and the active management of, comorbidities, or other diseases, which have been shown to have a negative impact on MS disease outcomes. Examples include smoking, hypertension, metabolic syndrome and obesity. As part of managing MS, and comorbidities, people with the disease need to adopt a healthy lifestyle, including regular exercise, a healthy diet and good sleep hygiene. The lifestyle issues not only have the potential to improve MS outcomes, but may improve wellness of people with MS. At the end of the teaching course attendees will know about brain health and how to optimise MS outcomes. They will know how to screen for, diagnose and treat the common comorbidities and will know how important it is to address lifestyle issues when treating people with MS.

link

There was an interesting poster on coagulation factors elevated in both RRMS and SPMS by Kerstin Gobel  link 

But sadly, this is all there is on the ECTRIMS site regarding the connection of MS to vascular health. Using the following search terms, I found nothing on the endothelium, cerebral microbleeds, venous hypertension, fibrinogen, aerobic exercise, nitric oxide, epigenetics, environmental factors.  There were a few scant mentions of Vitamin D or cardiovascular lifestyle factors.  And CCSVI is gone.  

I'm not sure how ECTRIMS can continue to call itself a research organization, when all of the presentations are focused on disease modifying drug studies and the EAE animal model of MS, but there you have it.  MS is now a 20 billion dollar a year industry, and the gate keepers want to keep it that way.  Afterall, it's pharma that throws this party every year.   

In the meantime, do all you can to help yourself by optimizing vascular health with exercise, whole food nutrition, smoking cessation, Vitamin D optimization, and good sleep.  All part of the Endothelial Health Program.

When this gang goes to the trouble of mentioning it, you have to figure there's probably something there.

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

Russia? сюрприз!

I recently found these new publications on PubMed.  Only the abstracts are available, as the articles are in Russian.


Multiple sclerosis and endothelial dysfunction (a review).
[Article in Russian]
Spirina NN, Spirin NN, Fadeeva OA, Shipova EG, Boĭko AN.
The endothelium plays an important role in the maintenance of vascular homeostasis, the tone and anatomical structure of the vascular wall. It is an essential component of the blood-brain barrier. In adverse conditions, damaged endothelium initiates many pathological processes in the human organism and plays a key role in the pathogenesis of a number of systemic diseases including multiple sclerosis. In this review, we discussed in detail the concepts of structural and functional features of a healthy endothelium and endothelial dysfunction, and present the basic theory of the damage mechanism of the blood-brain barrier and the role of endothelial cells, adhesion molecules, cerebral hypoperfusion in multiple sclerosis.


von Willebrand factor and adhesion molecules in patients with multiple sclerosis.
[Article in Russian]
Spirin NN1, Spirina NN, Boĭko AN
Based on a role of certain adhesion molecules and vascular endothelial damage in multiple sclerosis (MS), we explored C-reactive protein, von Willebrand factor, matrix metalloproteinase-9, sICAM-1, sPECAM-1, E-selectin and P-selectin in the blood of patients. One group of the patients received pathogenic therapy. There was the increase in the level of the von Willebrand factor in patients who did not receive the therapy. The levels MMP-9 and sE-selectin were correlated with the high activity of the disease. The authors suggest the presence of the endothelial dysfunction in some patients. MMP9 and sE-selectin may be considered as potential markers of the activity of multiple sclerosis.

I searched pubmed for Russian publications because this blog has been receiving an inordinate amount of traffic from Russia.  In the past several months, there have been hundreds of thousands of hits. I've now have more readers from Russia than the US or Canada.   I'm honestly not sure what this is all about, and whether these might be bots, or another variety of nefarious internet activity.

But I'm hoping it's more about actual Russians wanting to understand the vascular connection to MS, and being sent here by internet search engines.

So, if any of my Russian readers would like to pop on and say hi (or Здравствуйте) in the comments---I'd be honored. I first noticed endothelial dysfunction, high SED rate, C-reactive protein and hypercoagulation in my husband's serum results back in 2007, and created a lifestyle program to help address it.  link I keep writing all these years later, and my tracking results show that people all over the world are reading this blog.

Both sides of my father's family emigrated to America from Russia in the early 1900s.  They were escaping the pogroms and seeking religious tolerance and work opportunities.  I hope to visit their homeland under better circumstances, to honor my family's hard work and courage.  The world is much smaller today, thanks to our internet access.

I'd suggest that any interested researchers who visit this blog contact the ISNVD  www.isnvd.org  and submit your studies.  We're together in wanting to understand the vascular connection to MS--a disease which affects people all over the world.  Especially those of us in developed countries above and below the 40th parallel.

всего хорошего,

Joan

7T MRI shows MS vascular connection

High powered MRI is allowing us to see the vascular connection to MS.  A recently published study used 7T MRI to compare the lesions of people with MS and those with Neuromyelitis Optica (NMO).  link

21 patients with MS and 21 patients with NMO were imaged.  There was one important difference between the two groups.  Only the patients with MS showed signs of "iron laden lesions" which contained a central vein.  None of the people with NMO showed this.

NMO is a truly autoimmune disease, in which immune cells attack the optic nerve and spine.   In contrast to MS,  NMO has a known antigen, called Aquaporin 4.  In NMO, the immune cells attack this antigen and cause demyelination.  However, there has never been a specific antigen discovered for MS.  In fact, MS lesions are very different from NMO lesions, as high powered MRI is showing us that inside MS lesions, there is a central vein which is allowing blood products, like iron, into brain tissue.

Here is how the researchers describe the difference:

Distinguishing MS from NMO lesions. 
Axial T2-weighted image from a representative patient with MS demonstrating a hyperintense lesion (black arrow) traversed by an ill-defined central venule adjacent to the inferior horn of the lateral ventricles. The lesion appears hypointense on a corresponding T1-weighted MPRAGE image. The lesion shows a hypointense peripheral rim and an iso- to hypointense central core traversed by a well-defined venule on GRE-T2*-weighted image. This lesion is hyperintense on QSM. Hypointense signal intensity within the lesion on GRE-T2*-weighted image and hyperintensity on QSM suggest iron accumulation (upper row). An axial T2-weighted image from a representative NMO lesion reveals 2 round hyperintense lesions (white arrows) in the subcortical WM region. The lesions appear hypointense on T1-weighted and hyperintense on GRE-T2*-weighted images. However, these lesions are isointense and therefore inconspicuous on QSM (lower row). The scale bar is for the QSM image with units of parts per billion.

Looking at the images, we can see the arrows pointing to the MS and NMO lesions.  All the images (on the top for MS and bottom for NMO) are of the same area of brain tissue.   It is the GRE-T2 image which clearly shows the MS lesion has a very small, yet well-defined vein (venule) going through the center.  The NMO lesion does not.  The QSM image shows that around this vein, in the MS patient, there is iron.  The researchers do not say that this is from blood leaking into tissue.  But this is the very obvious inference.  Blood, or heme, contains iron.  Microbleeds into brain tissue have been documented in MS. link   And here, once again, we have more proof.

For those of us who know our history, we remember that Rindfleisch saw the EXACT SAME THING through his microscope in 1863.

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

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

link

CW Adams published on damaged cerebral veins and the deposition of iron from blood in MS brains in 1988.
Yet, even after all the historical evidence, when Dr. Zamboni published on the link between venous disease, iron deposition into tissue, inflammation and MS lesions in his "Big Idea" paper in 2008---he was resoundingly ignored (or worse, mocked) by MS researchers. Here's the history of this research into the central vein sign, iron deposition and MS lesions-- link

Once again, we see the evidence of the vascular connection, in clear, high-powered MRI images. Iron deposited into brain tissue, creating inflammatory lesions, all around a small, central vein.

At a certain point, you simply have to say---
WAKE UP!

My family reached that point almost a decade ago, and because of this, my husband remains healthy. The evidence continues. There is a vascular connection to MS.
Whether or not MS specialists and immunologists will ever acknowledge this fact and help patients is moot. It is up to all of us to educate, inform, encourage, and move the research forward.


Be well,
Joan

Cerebral Microbleeds and MS

Readers of this blog will know I began writing about the vascular connection to MS after finding a link between Jeff's hypercoagulated serum test results, the small dots of blood seen on his legs called petechiae, and the realization that if he had pinpoint drops of blood escaping vessels on his legs, this could be happening in his brain, as well.  Blood in brain tissue creates oxidative stress, causes demyelination and initiates the coagulation cascade.  Dr. Roy Swank had noted the same thing in the 1950s, and had termed the leaky vessels "fragile capillaries."  I brought this research into the 21st century, by linking this blood vessel fragility to endothelial dysfunction and issues with nitric oxide.
Link

Finally, neurological researchers are noting the importance of cerebral microbleeds in the brains of those with MS, and exploring the cardiovascular connection to MS progression.

Published online today in Radiology, BNAC at the Jacobs School of Medicine in Buffalo reports on the link of cerebral microbleeds to disability in patients with MS.  link

The researchers found that the more cerebral microbleeds a patient had, the more severe were their physical and cognitive outcomes. In particular, MS patients who had more cerebral microbleeds had more physical disability after adjusting for age, hypertension and whole-brain volume.

"This is significant because it suggests that cerebral microbleeds are associated with increased physical disability in MS patients, independent from these additional risk factors for cerebral microbleeds," said Zivadinov.

In terms of cognitive disability, the researchers found that in the subgroup of MS patients who underwent neuropsychological testing, those with more cerebral microbleeds had higher disability on verbal and other cognitive function tests.

"Those MS patients who have cerebral microbleeds are subject to developing more physical and cognitive disabilities earlier in their disease, and therefore monitoring them more closely might be appropriate," Zivadinov noted. 

Significant research is now being done on ways to combat cerebral microbleeds, Zivadinov said, adding that currently, prevention of cardiovascular risk factors was seen as the best way to prevent their formation since there are no currently available target therapies.

This is exactly why taking care of heart health is so vitally important.  There are NO DRUGS to prevent cerebral microbleeds.  It is why I created the Endothelial Health Program to combat all of the environmental factors which contribute to the weakening of the endothelial cells.  A strong endothelium keeps blood inside vessels and stops micro bleeds.  It's not a pill, it's a lifestyle.

Link to Complete Program

The heart and brain are connected, and the research keeps coming in to prove this.  I look forward to the day when cardiovascular and endothelial preserving therapies are the FIRST LINE treatment recommended to MS patients.

Joan

Gene implicated in progressive MS related to vascular disease

New research published in Neuron by the University of British Columbia finds an inherited genetic mutation related to rapidly progressing MS (PPMS).  link Variants of the mutation are also seen in inflammatory vascular diseases.   This research was first presented at ECTRIMS in 2015 link

The mutation of gene NR1H3 was found in seven of 2,000+ people with MS,  and 70% of the people with this mutation went on to develop MS.   Blood samples with this mutation were taken from two Canadian families who have members with primary progressive MS.  Although this mutation is rare,  it could an important marker for those diagnosed with PPMS, and help scientists understand the disease process behind PPMS.

This discovery relates to inflammation, lipids, and vascular health, as the NR1H3 gene encodes liver receptor protein A (LXRA)  If there is a mutation,  liver receptor proteins are dysregulated, lipids cannot be processed and inflammation occurs. But the UBC press release doesn't even mention this.

Cardiovascular researchers have found an NR1H3 mutation related to vascular inflammation, coronary artery disease, diabetes, metabolic disease, and serum lipid processing.

link  link 

Alzheimer's researchers have found an NR1H3 mutation related to AD disease severity.

link

And stroke researchers are studying how this is related to ischemic vascular disease. 

link

How does this genetic mutation affect the vascular system in all of these different diseases?  It's all about inflammation and fats.

Liver X receptor  (LXR) proteins are mainly found in the liver and adipose, or fat tissue.  They help the body process fats and cholesterol.  link  

In obese patients, there is an increased release of free fatty acids, and this can lead to liver disease, inflammation, metabolic diseases and diabetes due to LXR protein dysregulation. 

link  link  link
LXR proteins are expressed on endothelial cells and in adipose (fat) tissue, and affect the inflammatory response.

Cardiovascular exercise creates laminar flow and shear stress over endothelial cells, and this regulates LXR proteins, decreasing inflammation.  link

Now, understanding this information,   here is Dr. Traboulsee on this discovery of an NR1H3 mutation in MS-

“If you have this gene, chances are you will develop MS and rapidly deteriorate,” said co-author Dr. Anthony Traboulsee, the MS Society of Canada Research Chair at UBC and Director of Vancouver Coastal Health’s MS and Neuromyelitis Optica Clinic. “This could give us a critical early window of opportunity to throw everything at the disease, to try to stop it or slow it. Until now, we didn’t have much basis for doing that.”   link

What would part of this critical early window,  "throw everything" treatment be?

A treatment program for someone with an NR1H3 genetic mutation--as we understand it in currently modeled studies of variants (link and link) 

  

1. stop eating a high fat/high glucose/low nutrient "western style diet"  

2. regulate fat intake by avoiding known inflammatory fats and increasing anti- inflammatory omega 3 fats,  

3. increase anti-oxidants and fiber from fruits and vegetables,  

4. eliminate excess sugar and processed foods,  

5. maintain a healthy body weight through optimal nutrition and exercise.  

All of the above lifestyle interventions help counteract the influence of dysregulated LXR proteins by limiting damaging fats, decreasing inflammation, and strengthening the vascular endothelium; giving  the heart, liver and brain their healthiest environment.   It will not change the genetic mutation, but it can help modify and calm the body's inflammatory response.  Today.   link

Sounds a lot like what Dr. Roy Swank was publishing sixty years ago.      link

Do you truly want to "throw everything" at this disease, and stop and slow MS progression, Dr. Traboulsee?  Really?
Because there has been an incredible amount of research recently pointing to food and MS progression.  The western diet harms the microbiome and increases inflammation link  link
and fasting reduces inflammation. link
In fact, your own colleague at UBC, Dr. Helen Tremlett,  recently published on the inflammatory gut microbiota associated with children with MS.  link

Let's get this information out and help people now.

Joan

Ocrevus and "wrapping up MS"

While Dr. Stephen Hauser is proclaiming the "spectacular" results of the latest immune cell suppressing therapy, Ocrevus (ocrelizumab),  other MS researchers are not as impressed.

"While anti-CD20+ treatment for relapsing-remitting disease looked like a home run, these data in primary progressive disease are not nearly as impressive," David Hafler, MD, of Yale University in New Haven, Conn., who was not involved in the study, told MedPage Today.

Dennis Bourdette, MD, of Oregon Health & Science University in Portland, said the 24% reduction in confirmed progression "is not great."

"This is a younger group with shorter duration than in previous trials in PPMS," Bourdette told MedPage Today. "It is also not representative of most PPMS patients that neurologists are seeing today."

link

Not impressive results, in a younger healthier population of patients doesn't seem like something to get excited about, expecially with dangerous and deadly side effects.   But that doesn't stop the hyperbole.

In a press release full of bravado ---"Wrapping up multiple sclerosis at UCSF"--  link  Dr. Hauser humble brags about his discovery.

“My hope is that, with these wonderful results against relapsing MS and finally a treatment that works at least partially for PPMS, there will be new octane in academia and industry to make even more meaningful advances,” says Hauser. “MS is no longer a black box. There is so much more that can be accomplished, and we need to build upon this important success.”

Hauser's wording could not be more ironic----as there will most likely be an FDA black box warning for ocrelizumab, due to the risk of deadly infections, malignancies, and patient deaths.

Dr. Thrower predicted that the FDA may approve ocrelizumab with a black box warning for progressive multifocal leukoencephalopathy (PML)

link

But Montalban noted that there were numerically more malignancies among those in the drug group. There were 11 cancers among those on ocrelizumab compared with only two in the placebo group, something that deserves further monitoring, he said.  There was also a numerical imbalance in deaths, with four in the drug group and one in the placebo group.

link

Ocrelizumab is a CD20 monoclonal antibody,  which was originally developed as a lymphoma treatment.  It targets and binds mature B lymphocytes and suppresses them.   It is a humanized version of the chimeric Rituxan, (which was a the end of its patent and had to be altered and re-patented for MS, to continue making money.)  So, the idea that this is a new discovery could not be further from the truth.

In fact, ocrelizumab has been around for many years, and trials of this drug in rheumatoid arthritis and lupus were halted, after serious infections and deaths were reported at 52 and 48 weeks.

There were 6 deaths associated with serious infections in the RA phase III trial.
link
There were 5 deaths associated with serious infections in the Lupus phase III trial.
link

The financial press didn't think ocrelizumab would ever get this far. The Wall Street Journal commented on the dangers of the drug back in 2010, when Roche ended its RA drug trial.

"Roche said Tuesday that ocrelizumab's phase II trials in treating patients with relapsing remitting multiple sclerosis are continuing. But some analysts doubt the drug will come to market as the recent safety issues are likely to put the U.S. Food and Drug Administration on alert.

The recent trial failures have curbed the drug's sales potential and some analysts now expect that if ocrelizumab's multiple sclerosis indication passes all regulatory hurdles, it will generate less than $1 billion in annual sales."

link

Another problem is that autoreactive B cells return after treatment termination, as this study of rituxan in type 1 diabetes illustrated.  Autoreactive B cells would create a rebound or relapse after the immune system is reconstituted, similar to what we see with Tysabri immune reconstitution inflammatory syndrome (IRIS), which occurs after termination of treatment.

We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.

http://www.ncbi.nlm.nih.gov/pubmed/26642366

If MS researchers truly want to make breakthrough discoveries, they will have to expand past the EAE mouse model and their narrative of an out of control immune system.  They could begin by looking at the newly discovered lymphatic vessels of the CNS, cerebral endothelial cell permeability,  fibrinogen, microbleeds in the MS brain, neurodegeneration and hypoperfusion. If plasmic particles, like viruses, are indeed entering the MS brain through a permeable blood brain barrier, than blocking B cells may not be the best idea.  Time will tell.

So much for "wrapping up" MS.....in a billion dollar black box. 

Joan  

The Endothelial Health Program

The neuroprotective lifestyle program I created for Jeff in 2008, and would share with university researchers, grew out of a year of in-depth study; plowing through pubmed, and reading every book on the history and etiology of MS I could find at my public library or on the internet.

I call it The Endothelial Health Program, and it changed our lives. 

I am happy to see there are many more published papers on PubMed years later.  Finally, the discussion of endothelial health is becoming mainstream, and the Nobel Prize winning science of Nitric Oxide (EDRF) is reaching doctors' offices.

Highly regarded MS and Alzheimer's researchers are now actively looking at the endothelium, nitric oxide and hypoperfusion in neurodegeneration, and encouraging other researchers to do the same.  This gives me great hope.

Although multiple sclerosis (MS) has traditionally been viewed and researched as an immune-mediated demyelinating and neurodegenerative disease of the human central nervous system (CNS), its highly complex pathogenesis clearly includes a significant vascular inflammatory component and many therapeutic approaches achieve benefit by direct or indirect effects on cerebrovascular endothelial cells.
link to research

Substantial evidence suggests that the neurodegenerative process is initiated by chronic cerebral hypoperfusion (CCH) caused by ageing and cardiovascular conditions. CCH causes reduced oxygen, glucose and other nutrient supply to the brain, with direct damage not only to the parenchymal cells, but also to the blood-brain barrier (BBB), a key mediator of cerebral homeostasis. BBB dysfunction mediates the indirect neurotoxic effects of CCH by promoting oxidative stress, inflammation, paracellular permeability, and dysregulation of nitric oxide, a key regulator of regional blood flow
link to research

The Endothelial Health Program is not a diet,  or a "don't do this" approach.  It's not about following specific rules.   It's proactive.   It's about living in a way which reverses damage and protects the six trillion endothelial cells inside every human body.
Why?   Because these cells maintain the health of all your organs and your immune system.

The endothelium is actually your largest organ.  It is the lining of 60,000 miles of blood and lymph vessels, and it communicates with all of your other organs.  It is also the interface between your immune system and your vascular system, and is what controls the blood brain barrier and keeps harmful plasmic particles out of delicate brain tissue.  It controls how much blood, oxygen and nutrition your neurons receive. Maintaining endothelial health is neuroprotective.  link to recent pub science from Columbia University

This communicative lining is made up of trillions of endothelial cells, and if these cells become damaged or die, this vital, protective network disintigrates.   This is a problem in ALL diseases of neurodegeneration, such as Alzheimer's, Parkinson's,  and dementia.   PubMed now has hundreds of scientific papers on endothelial dysfunction and each these diseases.   But endothelial cell death and dysfunction can be reversed.

I had been hugely inspired by Dr. John Cooke's book, The Cardiovascular Cure,  Link to book  and reached out to him.  That's how Jeff and I originally connected with Stanford University.   The information was out there,  I was just compiling and connecting the heart to brain health.    This is a complete lifestyle, a new way of looking at rising rates of neurodegenerative disease as a result of our westernized, industrialized lives.  It was an attempt to reverse cell-damaging practices that had become part of our modern routines, and to return to our inherent nature, to allow for balance and healing.

It was an attempt to connect the heart and brain, to understand the vascular connection to MS.  And I did it for Jeff.



The basic tenets of the lifestyle program are:

1.  Movement.  Daily cardiovascular pursuits are essential and healing. Shear stress, created by an active heart pumping flowing blood over endothelial cells, maintains their integrity by increasing nitric oxide release.  Inactivity allows endothelial cells to die.

2.  Stress reduction. The acts of deep breathing, the practice of meditation, yoga, prayer, all reduce endothelial cell damaging cortisol and increase healing, vasodilating nitric oxide.

3.  Liver health. Decreasing liver damaging toxins--like alcohol, plastics exposure, chemicals, pesticides, heavy metals, drugs--and increasing liver protecting flavonolignans (like silymarin) and antioxidants found in fruits and vegetables, maintains endothelial cell health.

4.  Vitamin D/UV ray increase. Skin makes vitamin D when exposed to ultraviolet B (UVB) rays from the sun. Because of sunscreen and our indoor lives, many people are not receiving enough of this potent hormone.  And our circadian rhythm is affected.  Vitamin D creates endothelial cell health by increasing nitric oxide.  UV rays release nitrates from the skin, creating vasodilation. 

5.  Sleep.  Sleep deprivation creates endothelial dysfunction and cell death.

6.  Eating whole, organic foods.  Eating a diet of whole foods (unprocessed foods; foods that retain the natural state) provide ample levels of nutrition, vitamins and antioxidants. Antioxidants bind with free radicals to minimize the damage they cause to the endothelium.  Vitamins B and C are hugely protective of endothelial cells.  A lack of B vitamins increases homocysteine, which kills endothelial cells.

7.  Eating healthy fats   Increasing omega 3 (DHA) fats found in fish, olives, flax seed, avocados, walnuts, etc.  and decreasing transfats and highly saturated animal fats improves endothelial cell health. 

8.  Probiotics and gut health.  The endothelial cells of the gut's lining communicate with the rest of the body and rely on "good" bacteria.  

9.  Essential minerals.  Magnesium, calcium and zinc are all important in the preservation of endothelial cells.

10. Anti-inflammatory food sources, spices and herbs. Curcumin, Salvia, Ginko, and Garlic are all shown to decrease inflammation and regulate blood viscosity, preventing hypercoagulation, allowing for better shear stress.  Proteolytic Enzymes, both serrapeptase and nattokinase, are enzymes which reduce inflammation and pain and help blood viscosity by regulating clotting. Bromelain, found in pineapple, is one of the best anti-inflammatory substances known.

11.  Reducing glucose and gluten.  Sugary baked goods, simple breads, pastas and snack foods are damaging to endothelial cells. 

12.  Smoking cessation.  Please quit...smoking kills endothelial cells.

13.  Laughter, joy, community, purpose, loving relationships.  All of these things increase nitric oxide and improve endothelial health.

That's it.  Simple, right?  Yes and No.  It took our family a couple of years to utilize all of the strategies.  Jeff was NOT thrilled that I changed our meal plans.  He was resistant at first, but after the first several months of MS disease stability, he embraced his new life.  

And then he went even further.  Jeff has added his own twist on endothelial health by incorporating neuroplasticity.  He has become an expert in the dictum of "use it or lose it."  He got back on his bike, back on skis, back to composing, conducting, performing and public speaking.  The things that had become challenging, like balancing or staying up all day, became an activity to face head on and in doing so, rewire his brain.   Receiving his venoplasty treatment at Stanford allowed for increased perfusion of his brain and healing.  But he kept that shear stress going by remaining active and engaged.   His grey matter looks normal on MRI, and he's had remyelination of MS lesions.  He is my hero.

This model for health is called "a systems approach." as opposed to a mono-therapeutic approach utilized by pharmaceutical companies.  It is much more expensive and difficult to clinical trial a lifestyle when compared to a singular drug or supplement,  but it can be done.  UCLA recently published on a systems approach in disease reversal in Alzheimer's.   https://www.aging-us.com/article/100690/text    My dream would be to fund a gold standard clinical trial of this program.  Maybe someday.

What's ahead?  God willing, more of this.   We have no idea of what tomorrow may bring, but we consider the gift of this lifestyle program to be our message of hope. 

So please, share the program.  Try it out, let me know how you're doing.  Always work with your own physician, to modify the program to suit your individualized needs.  I don't have a book to hand you, but I think that's OK.  I was given this direction as an answer to prayer, and will continue to share it for free.

Be encouraged, 

Joan

bounty from our organic garden---full of colorful phytonutrients (nutrients from plants!)

hiking provides UV ray exposure, calming nature, and exercise