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

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

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the immune paradigm of MS, and continues the 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

Thursday, November 21, 2013

"Good" Cholesterol and the MS Brain

New research, presented at the annual meeting of the Society of Neuroscience, finds a link to the level of a cholesterol transport protein and MS disease severity.  This research provides us another link to blood and the cardiovascular system, which I'll get into at the end of this note. 

First, let's review the announcement.
http://www.medscape.com/viewarticle/814798

ApoA1 is the main structural protein found in HDL, or what we call "good" cholesterol, and it is found to be low in pwMS.
Blood levels of the reverse cholesterol transport protein apolipoprotein A1 (ApoA1) are low in patients with multiple sclerosis (MS) and correlate with disease severity, new research shows.
ApoA1 is the most abundant component of high-density lipoprotein cholesterol and is known to protect against inflammation.
Dr. Gardner and colleagues investigated ApoA1 levels in 53 patients with relapsing-remitting MS, 50 with secondary progressive MS, 53 with primary progressive MS, and 57 healthy controls. "Remarkably, all MS patients had less ApoA1 than controls," they report in a meeting abstract.
ApoA1 was reduced by approximately 25% in patients with relapsing-remitting MS, 50% in those with secondary progressive MS, and 75% in patients with primary progressive MS, the most severe form of the disease.
I'm always alarmed when neurologists claim a finding like this is "surprising"--especially since lower levels of ApoA1 have been found in other diseases of neurodegeneration.
In Alzheimer's, the connection of more severe AD with low levels of ApoA1 has been established.  Higher levels of ApoA1 are related to sharper mental abilities and memory. 
Low levels of ApoA1 are correlated with more severe Alzheimer's Disease, and high levels of ApoA1 with a lower risk of AD --see Merched et al., 2000Saczynski et al., 2007Bates et al., 2009 
Other studies have hinted at a cognitive effect. High HDL levels associate with sharper mental abilities in the elderly (see ARF related news story on Barzilai et al., 2006), while low HDL levels are a risk factor for memory decline in middle-aged adults (see Singh-Manoux et al., 2008). What might be behind these apparent benefits? ApoA1 is known to have anti-inflammatory effects, and indeed, in a mouse model of brain inflammation, an ApoA1 mimetic improved cognitive deficits (see Buga et al., 2006). http://www.alzforum.org/new/detail.asp?id=2574
In Parkinson's, the connection of ApoA1 as a biomarker for disease risk has been established.  Lower levels of ApoA1 correlated with earlier onset of Parkinson's Disease while higher levels of ApoA1 were shown to be protective.
One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037).
Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.

What does this all mean?  
It means ApoA1 levels are not just important for pwMS, they are important to monitor in all neurodegenerative disease.  It means the heart and brain are connected by our blood flow.  It means you can protect your brain by raising your HDL numbers.
I believe it's important to look at all diseases of neurodegeneration and consider blood flow and serum markers.
This also means that we have to look at the connection between our lives, our hearts and our brain health.  How can we increase our HDL, or good cholesterol--and thereby protect our brains from inflammation and further damage?  While labs work on ways to make drugs to raise our good cholesterol, we can consider how to do this ourselves.

How to raise HDL--or good cholesterol and help your brain.
LIFESTYLE is the most important means to increase HDL.
1. Don't smoke.  Quitting smoking will increase good cholesterol by 10%
2. Lose weight.  Extra weight depletes HDL.
3. Exercise.  Within 2 months of regular exercise, you can increase your HDL by 5%
4. Choose healthier fats for your diet. Avoid transfats, choose omega 3s and monosaturated fats found in nuts, olive oil, and fish

5. Add fiber to your diet--lots of fresh fruits and vegetables, legumes and oats

6. Limit alcohol consumption.
http://www.mayoclinic.com/health/hdl-cholesterol/CL00030/NSECTIONGROUP=2

7. Check your vitamin D, magnesium, calcium and zinc levels--make sure they are in balance.
http://www.ncbi.nlm.nih.gov/pubmed/7608827

Hope this information helps your heart and helps your brain.
Because they are connected,
Joan


Saturday, November 16, 2013

What has Changed?

In the five years since Dr. Zamboni's first publication on the connection of MS to extracranial hemodynamics, there have been many changes in mainstream MS treatment and new discoveries made by researchers around the world.

The relationship of the vascular system in MS is being explored, and dealt with in a sideways manner by neurologists.  I do not expect we will ever hear that CCSVI is valid science from neurologists--they will attempt to rename it, requantify slowed venous return and hypoperfusion, and make it their own.  They will call Dr. Zamboni's discovery of CCSVI junk science- while they are working on patenting drugs to address blood flow in pwMS.  This is because neurologists work with pharma and write prescriptions.  They do not deal with the mechanistics of the brain's circulation or with the venous malformations Dr. Zamboni has discovered.  They are not phlebologists or vascular surgeons. For MS specialists, this discovery of hemodynamic alterations goes beyond their practical expertise.

However, one neurologist recently published a paper on the vascular connection to MS, and said this:

"...vascular contributions in MS do appear to support the notion of the vasculature being an initiating target in MS etiology and not simply a bystander presentation of other disease processes. Perhaps the strongest support for this is the number of MS therapies that have been developed, which target leukocyte binding to activated endothelial cells, a central component of the blood-brain barrier (BBB)."
http://www.biomedcentral.com/1741-7015/11/219

Here are drugs being developed by neurologists to address blood flow:
http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html


What have we learned since Dr. Zamboni first began publishing his research on CCSVI?  

1. People with MS (pwMS) have slower cerebral hemodynamics than normal people.  Their blood flow exits the brain at a slower rate. There are hemodynamic differences between normal people and those with MS. Hypoperfusion is real, it opens the blood brain barrier and it damages the brain.  Whether it is a cause or effect of MS will be debated for decades, however vascular researchers have shown better perfusion and cerebral blood flow (CBF) and cerebral spinal fluid (CSF) flow after venoplasty for CCSVI.

2. People with MS do better with exposure to UV rays, which may explain the long-established link of MS rates and northern latitudes. UV ray exposure relieves symptoms in many.  This may be due to increased vitamin D levels, but it might also be due to the way in which UV rays release nitric oxide, change the endothelium and increase blood flow. 

3. People with MS are being advised to consider their nutrition and to eat more fruits, vegetables and whole foods and less saturated fats and processed foods.   When Dr. Swank suggested this 60 years ago, it was called "junk science" and people with MS were told it wouldn't do them an ounce of good.  It is now given as helpful advice by the NMSS and the AAN.   

Same thing with exercise.  Only a few years ago, pwMS were advised not exert themselves, but to rest and conserve their energy.  Now we know that physical exercise and activity delays progression, and reverses gray matter atrophy.  Same thing with smoking cessation, stress reduction, and better sleep.  All of these cardiovascular lifestyle changes can make a difference.

4. Oxidative stress and inflammation are recognized as driving forces in MS progression.  This has lead to exploratons of new modalities of treatment, like the Nrf2 pathway. 

5. Gray matter health has been recognized as a more accurate biomarker of MS progression than white matter lesions.  Gray matter atrophy will become the new target for MS therapies.

6. PwMS have much higher levels of the clotting proteins- fibrin and endothelin-1 in their serum than normals. These are markers of endothelial dysfunction.

7. Upright MRI has allowed us to see how cerebrospinal fluid and blood return to the heart is slowed and impeded in pwMS.

8.  The venous endothelium is being studied, and researchers are noting that there are changes happening to the lining of the veins in people with neurodegenerative disease.
9.  CCSVI is being explored around the globe.  There are literally hundreds of papers published in vascular and neurological journals.  New papers come to press every day.  The connection of blood flow and diseases of neurodegeneration continues, as doctors admit that lifestyle interventions and prevention are staving off Alzheimer's and dementia, while none of the drugs have helped one bit.
http://www.ccsvi.org/index.php/component/search/index.php?option=com_search&task=search

10.  The ISNVD has been established.  There is now an international society of researchers working on understanding the venous connection to neurovascular disease.  Their fourth conference will be held in San Francisco in February, 2014.  The International Society for Neurovascular Disease is convening, publishing, and moving this research forward.
http://isnvdconference.org


All of these connections between MS and the cardiovascular system are new.  And this has happened in just the past five years.  

For those waiting for venoplasty to be accepted as an MS treatment, we have to step back and view the other changes that have happened in MS care.  

The American Academy of Neurologists has several papers featured on their page which connect slowed blood flow and neurodegenerative disease.  They have a patient outreach branch--The American Brain Foundation-- and they have a yearly Brain Fair to discuss diet and lifestyle changes people with neurodegenerative diseases, including MS, should consider.  So much for Dr. Swank's junk science.

Here's a wonderful video Christopher Alkenbrack found on Dr. Roy Swank's work.  It was made in 1989 as part of a Canadian news investigation into the success of Dr. Swank's diet in pwMS as compared to a vastly more expensive and failed chemotherapy trial.  If you haven't seen it, it's a must watch.  

Because today, 25 years later, the NMSS is making these very same dietary and lifestyle recommendations to pwMS.  Yet when asked about dietary changes for pwMS, the neurologist in this video from 1989 says there is "little to no benefit."


When reporters, scientists, neurologists, MS specialists and others say, "Oh, the connection of CCSVI to MS, that's junk science."  We've investigated it, and there's nothing there"---remind them about Dr. Roy Swank.  Remind them how long it took his observations of "capillary fragility", slowed blood flow, increased fibrin and hypercoagulation to be accepted as part of MS.    

He was noting endothelial dysfunction decades before scientists knew about nitric oxide and how environmental factors contributed to blood flow.  And he has never once been credited by mainstream neurology.  You won't see his name or read his research in their journals.  But he was right.

Dr. Zamboni's discovery has revolutionized how we look at cerebral blood flow, by studying the under-researched extracranial venous system, and utilizing doppler ultrasound to understand venous malformations which alter cerebral hemodynamics.  Like Dr. Swank, Dr. T.J.Putnam and others, he is decades ahead of his time.  His discovery of CCSVI may very well be the rest of the equation in understanding the slowed venous return and endothelial dysfunction found in pwMS.   To say that it is junk science, and that there is no connection of venous return in MS, is to negate scientific fact.  


Joan

Saturday, November 2, 2013

A Body in Motion

More research coming in on the importance of execise for people with MS.  This newest study looked at how aerobic exercise can INCREASE the size of the brain, and improve memory.

The hippocampus (literally "sea monster") got its name because of its shape--it resembles a sea horse.  It is the part of the forebrain responsible for memory forming,  mood, organizing and storing.


The hippocampus is much smaller in people who have MS, Alzheimer's, depression and in those who have had some sort of hypoxic, or low oxygen injury to the brain.  And yes, this ties in with Dr. Zamboni's discovery of restricted cerebral outflow and CCSVI.  The hippocampus needs adequate oxygen and blood flow to remain healthy.
http://ccsviinms.blogspot.com/2010/07/study-on-brain-changes-in-ms-and.html

Hippocampal atrophy seen in MS is linked to the memory deficits that affect approximately 50% of individuals with MS. Despite the prevalence of this disabling symptom, there are no effective pharmacological or behavioral treatments. 

"Aerobic exercise may be the first effective treatment for MS patients with memory problems," noted Dr. Leavitt, research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. "Moreover, aerobic exercise has the advantages of being readily available, low cost, self-administered, and lacking in side effects." 

The study's participants were two MS patients with memory deficits who were randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. Baseline and follow-up measurements were recorded before and after the treatment protocol of 30-minute exercise sessions 3 times per week for 3 months. Data were collected by high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Aerobic exercise resulted in a 16.5% increase in hippocampal volume, a 53.7% increase in memory, and increased hippocampal resting-state functional connectivity. Non-aerobic exercise resulted in minimal change in hippocampal volume and no changes in memory or functional connectivity.

Please note that the researchers make some great points.  There are NO MS drugs that can increase your brain size or help with memory.  Exercise, with the consult of your physician, has no side effects, doesn't cost much and you can do it on your own schedule.
Now, here comes the cheerleading part.
Aerobic exercise simply means "with oxygen."  When we engage in aerobic exercise, we get our heart pumping!  Our blood vessels widen, our heart pumps faster and stronger, to deliver oxygen rich blood throughout our body.  This strong flow of blood creates a wonderful effect on the endothelium, called "shear stress."  The forceful flow of blood throughout vessels releases healing and vasodilating nitric oxide.  
I have spoken with Dr. Cooke and Dr. Dake from Stanford about those who have remained stenosis free in the four years since treatment for CCSVI, they have commented that the patients that remained the most aerobically active have done the best.  
If there is any way for you to take 30 minutes, 3x a week, to get your heart pumping, find it!  Suggestions on how to do this include stationary biking, elliptical machines, swimming, jogging, biking, hiking, treadmills, dancing, zumba, jazzercise, boxing, an aerobics or cardio class.   Please consult with a physician or physical therapist to learn which activity might be best suited to your activity abilities.  It may be simply impossible for you to move enough to get your heart pumping, and that's the terrible tragedy of MS progression.  But if there is any way---please try it.  
Jeff started slowly, using an elliptical machine. It wasn't pretty.  He had numbness and balance issues after his MS diagnosis, and this was about all he could handle.  But he kept at it, even with pain and fatigue.  A year later, he was back on his bike, and able to walk the dog and hike a bit.  After venoplasty, his heat intolerance disappeared, and he could work up a real sweat, so he went to mountain biking, hiking and even returned to skiing.  Last week he was showing off, and jogging up the hills on our hike.  And now his brain volume looks normal on MRI.
You can do this!!
Please, share this info in your MS community, and encourage others to join you.
A body in motion, stays in motion--
As the winter approaches and hours of sunshine diminish, fight the impulse to stay in bed or on the couch.  Get up, get moving, and feel the blood moving through your vessels.  The shear stress created heals the endothelium. You are, quite literally, healing your brain.
be well, be active,
Joan

Tuesday, October 22, 2013

Death knells and coffins...

Death knell for CCSVI!---Another nail in the coffin---
Goodbye to all that; a short history of CCSVI---
CCSVI debunked!---The end for CCSVI

If all you read were the headlines, you might think that CCSVI was nothing more than a scourge, a fantasy, a vampiric spector that science has, thankfully, stabbed through the heart and removed forever.
It's over. Move along, people.  Nothing to see here.

But there is much more going on.

This week, a paper published in a neurological journal showed
"severe extracranial venous anomalies that signficantly impaired normal outflow from the brain" occur in some people with MS.
The full paper, in a provisional pdf, can be viewed here for free:
http://www.biomedcentral.com/content/pdf/1471-2377-13-151.pdf

These scientists do not think CCSVI is over.  They're still finding it.

Jeff and I know all about these extracranial venous anomalies that significantly impair the flow of blood from the brain to the heart.

Four and a half years ago, Jeff and I saw that very same problem happening in his body.  We were astounded at the MRV images on the computer screen in his doctor's office, which showed slowed collateral circulation and two malformed, stenotic jugular veins.

I put up an image from his magnetic resonance venography on an MS Forum.

And in doing so, poked a hornet's nest.

You can see in this MRV picture on the left from Stanford, Jeff had no jugular flow on the left side (right on pic), and reduced flow on the right.  This is evidenced by the collateral veins that are lit up like Satan's curly fries.  This is not normal.
What you should see are straight and open jugular veins, that look like drinking straws.  Like the picture on the right.  Can you see the difference???  Well, our doctor saw the difference, and we decided to treat Jeff's venous malformation.



In fact, both of the images were taken at Stanford University, by one of the premiere vascular specialists in the world.  He and his radiology team would later publish a paper on what healthy normal venous MRV looked like, compared to people with MS.  He believes that the kind of collateral circulation and pulsatility found in pwMS could well be damaging to the brain.  Here is one of his papers on this.
http://www.ajnr.org/content/33/8/1615.abstract


When Jeff's jugular veins were opened up, the collaterals went away, his cerebral blood flowed through his jugular veins in a timely manner, no more pulsatility.  And Jeff's brain has healed.  No MS progression.  His gray matter looks normal on MRI.

It's hard not to wonder what would have happened if I had simply taken the research to Stanford, where Jeff was treated, and then gone home to live out our days.  But I was part of an online MS forum, and we'd been sharing information between pwMS and caregivers.  In fact, that was how I first read Dr. Zamboni's published papers.

Maybe the research would have progressed more readily without patient involvement.  Maybe the scientific community would have been more accepting of Dr. Zamboni's research, without the media and patient spotlight.

But I doubt it.
And anyway, there's no going back.
I'm sorry for the way neurologists have used patient advocacy to prevail against the science.... but I'm also not sorry.  Because I got my energetic, brilliant husband back.  And he no longer has heat intolerence, sleep apnea, or crippling fatigue.  No MS progression.  He's still working more than full days, jogging, biking and living.

CCSVI exists.  It impairs blood flow from the brain.  It may not affect everyone with MS, and it may be present in normal people.  It's showing up in other neurological diseases.  There is great debate as to how it should be treated.  Jeff's doctor used stents, others have replaced veins, ballooned, used cutting balloons--others believe lifestyle and exercise may be enough, or antibiotics might help.  There is no agreement on the best course of treatment, and that has created confusion and controversy.

It's also clouded the fact that there are newly discovered and very obvious venous problems related to neurological disease.  

CCSVI exists.
How it is best treated will be debated, but this exploration is not even close to being over.
Joan






Thursday, October 17, 2013

Sleep and the Brain


New research from the University of Rochester, published today, reconfirms the importance of sleep for brain health.

Their results, published in Science, show that during sleep a plumbing system called the glymphatic system may open, letting fluid flow rapidly through the brain. Dr. Nedergaard's lab recently discovered the glymphatic system helps control the flow of cerebrospinal fluid (CSF), a clear liquid surrounding the brain and spinal cord."It's as if Dr. Nedergaard and her colleagues have uncovered a network of hidden caves and these exciting results highlight the potential importance of the network in normal brain function," said Roderick Corriveau, Ph.D., a program director at NINDS.


A few years ago, I first wrote about REM sleep and brain oxygenation. After venoplasty and restoration of jugular, rather than collateral venous flow,  my husband Jeff had a return of dreaming and restful sleep.  Now that his jugular veins had been repaired, they were the major route of venous return for his brain while he slept, and the changes for him were immense and immediate.  After coming home from his procedure at Stanford, he no longer had night time spasms or fits of apnea, when he would literally wake up, gasping for air.  He now slept through the night, and woke refreshed.  He could now recount his very vivid dreams to me.   This was all new for him.

When I attended the first CCSVI conference in Bologna in 2009, I heard Dr. Salvi talk about the restoration of REM sleep and dreaming in Italian patients that had been treated for CCSVI.  It was the first intimation that something vital was happening to Jeff's brain while he was in deep sleep.  Here is my post on this topic, with research on oxygenation of the brain during sleep--
http://ccsviinms.blogspot.com/2010/09/to-sleep-perchance-to-oxygenate.html#more

Earlier this year, a new study from the University of Wisconsin showed us why sleep is essential for remyelination of the brain and synthesis of oligodendrocyte precursor cells.

They found that during sleep, hundreds of transcripts that govern the synthesis of cells called oligodendrocyte precursor cells (OPCs) are up-regulated during sleep, while genes involved in cell death, cell stress response and cell differentiation are up-regulated during wake. An assay of living cells confirmed that OPC proliferation doubles during sleep, especially during rapid eye movement phase (REM sleep) associated with dreaming.
http://www.med.wisc.edu/news-events/sleep-produces-cells-that-grow-and-repair-nerve-cell-insulation-/41696
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And today, a new study from the University of Rochester helps us understand the different functions the brain performs during sleep and wake, and why sleep is essential.  
http://www.eurekalert.org/pub_releases/2013-10/nion-bmf101713.php

In findings that give fresh meaning to the old adage that a good night's sleep clears the mind, a new study shows that a recently discovered system that flushes waste from the brain is primarily active during sleep. This revelation could transform scientists' understanding of the biological purpose of sleep and point to new ways to treat neurological disorders.

The University of Rochester researchers have been studying how the brain cleans waste during sleep, and they have named this process the "glymphatic system", because it combines the lymph process of cleansing and glial cells.  This system is like "a plumbing system that piggybacks on the brain's blood vessels and pumps cerebral spinal fluid (CSF) through the brain's tissue, flushing waste back into the circulatory system where it eventually makes its way to the general blood circulation system and, ultimately, the liver."


Time for the BIG picture. When we lie down, our cerebral circulation changes.  This is, due in large part, to the fact that gravity allows the jugular venous system to become the main outflow.  The collateral venous system, which is activated when we are upright, gives way to the larger jugular veins.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665206/


In normal people-- who do not have jugular venous malformations, or CCSVI-- this allows for effective flow while supine.  Why is this important?  Because it appears that this flow is essential for removal of waste from the brain.  Here's more from the U of R--

Tuesday, October 8, 2013

Venous Hemodynamics


Understanding venous hemodynamics is of the utmost importance when studying CCSVI.
"CCSVI is not about architecture, it's about flow."
Dr. Paolo Zamboni said this to me when we first met at his international CCSVI conference in Bologna, Italy in September 2009.
He explained that it was not enough to scan the veins, or use MRV technology, or just look for stenosis.  It was essential to understand hemodynamics.

Which is why the knowledge of scientists like Clive Beggs is so important.  As an engineer and Professor of Medical Technology, Professor Beggs has insight into the physics of blood flow.

Highly Recommended Reading----


Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis  
Clive B Beggs
Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.
CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.
Despite conflicting studies, there is increasing evidence that CCSVI is a real physiological phenomenon, and that it is in some way associated with MS. The evidence from CSF-related studies in patients with MS, and the hydrodynamic analysis presented here, suggests that CCSVI causes venous hypertension in the dural sinuses. However, the role that CCSVI might play in the pathophysiology of MS remains unclear, and more work is urgently needed to understand the clinical relevance of this condition.

http://www.biomedcentral.com/1741-7015/11/142

Monday, October 7, 2013

The FDA and Multiple Sclerosis treatments


Who gets to advise the FDA on multiple sclerosis drugs and treatments?

There have been several new MS drugs brought to market in the five years since CCSVI research was first discussed in medical journals.  We have to wonder whether the process of hastening these new drugs to market was aided by the influence of phamaceutical companies.

In the news today, e-mails are released that show pharmaceutical companies pay to attend FDA advisory meetings and submit their own recommendations on drugs to be marketed,   http://www.washingtonpost.com/business/economy/pharmaceutical-firms-paid-to-attend-meetings-of-panel-that-advises-fda-e-mails-show/2013/10/06/a02a2548-2b80-11e3-b139-029811dbb57f_story.html?hpid=z1

I thought it might be a good idea to see what information is available to the public regarding who is recommending MS treatments to the FDA, and how they do this.

The group that looks at evidence for the MS community and advises on drug approval is the 
"Peripheral and Central Nervous System Drugs Advisory Committee"
There are many reports prepared by pharmaceutical companies to be submitted to this group, which are available for public disclosure without redaction on the FDA.gov site.

Here is one for Fingolimod, now marketed as Gilenya-- prepared by Novartis- and submitted to the advisory committee for their June 10th, 2010 meeting.

The authors are free-lance biotechnicians who specialize in "bringing pharmaceuticals to market."

The FDA advisory committee decided that day to approve Fingolimod/Gilenya and made the announcement to the press.  They were giddy with the fact that this drug was the first FDA approved oral medication for people with MS.

What is important to note is that by the time 2012 came around, the FDA had to issue a formal warning on Gilenya, due to several deaths and cardiac events reported after the drug was marketed to pwMS.  These cardiac deaths and side-effects were not flagged by the FDA, or Novartis---but reported by a non profit watchdog group, the Institute for Safe Medication Practices.

Recently, the Institute for Safe Medication Practices, a nonprofit watchdog group, has urged the FDA to put more restrictions on the use of Gilenya. The group reviewed the number of side effects of the drug reported to the FDA MedWatch program in the second quarter of 2011, and it concluded that "the FDA and manufacturer should consider substantial restrictions on its use and enhanced monitoring."

Here is the strongly worded comment from the ISMP--
It was a significant gamble for the FDA to allow unrestricted marketing of powerful but novel immunosuppressant drug before determining the optimal dose and learning more about its long term risks.  Only about 300 people were exposed to fingolimod for a period of two years prior to approval.

Friday, October 4, 2013

Moving forward



For the many people with MS who were first treated for CCSVI in 2009 and 2010, It is more than insulting to be told that your benefits are “short-lived” or “not measurable” or “placebo.”  Especially when there is documentation that contradicts this claim.
As many of you know, my husband Jeff had difficulty walking at his diagnosis in 2007, but six years later, he is downhill skiing and mountain biking.  Yes, MS is a variable and relapsing-remitting disease, but I would like to propose something.

Jeff has had many tangible and quantifiable benefits from venoplasty. 

1. His cerebral blood flow and venous return were measurably increased. 
2 His gray matter atrophy reversed, and his gray matter now looks “normal” on MRI.  This includes his third ventricle width, thalamus and brain stem.
3. He has had no further white matter lesions, nor has he had another MS relapse.
4. He has EDSS improvement from 1.5 to .5
5. As a 50 year old man who was told he would progress quickly, due to the number of enhancing lesions he had at presentation, these quantifiable measurements, (which would be heralded as great victories for Tysabri or Rituxan, had he taken these drugs) matter.


And we are keeping Jeff’s medical records and his disease process is being followed, now 4.5 years past venoplasty.

Kathleen Lynch made a wonderful suggestion at the NCS conference---I had been asked by an audience member how I believed we could continue to move this research forward, and not let it be tossed into the trash bin-- as the MS Societies, MS specialists and pharmaceutical companies are currently recommending.

Kathleen stood up and suggested that patients needed to keep their medical records and documentation as a scientific proof of their disease process.

If you have documented proof of improvement in EDSS or on MRI, or disease cessation, I encourage you to document this,  and keep all of your records on file.  I think we may want to make a concerted, international effort, to begin a data registry--which includes this documentation.  And we will need to make a formal presentation of this evidence to the MS Societies and scientific councils who are in charge of research funding.  I would like them to meet Jeff, see his MRI and assess him.


At the NCS Sherbrooke conference, which was not attended by any of the invited MS Societies or MS specialists, Sean Sethi from MR Innovations presented many clear MRV examples of the difference between stenotic jugular veins in people with MS and the open and flowing images of normal jugular veins.  The visuals were striking.

His comment was that he wants this evidence to “be the hammer that takes the nail out of the CCSVI coffin.”

It is far too early for any organization to be proclaiming CCSVI research as over.

How can any group which purports to be looking after people with multiple sclerosis deny the very clear evidence of venous abnormalities in MS, and the documented improvements in many who have been treated to repair these malformations? 

To not pursue this research, to dismiss those who have MRI evidence of disease cessation and healing of brain tissue, is purely evil, and should not be tolerated.

For those who have this evidence, now is the time to get your files in order.  This goes beyond YouTube videos and anecdotal reporting.  This will be scientifically valid proof.

And we have it.
Joan

Friday, September 20, 2013

The Central Vein Sign and New Research


September 20, 2013

It was 150 years ago, in 1863, when Eduard von Rindfleisch first peered through his microscope at an MS lesion and noted a vein inside the cerebral MS lesion.

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.

We've known for over a century that MS lesions are perivenous, meaning lesions form around a vein.  There is a vein in the center of almost every cerebral MS lesion, and this makes the MS lesion unique.

So, it was interesting to see THREE brand new papers on this topic in 2013, coming from neurological research. 

Here's one from July 2013, published in "Frontiers of Neurology"--suggesting that these central veins and perivenous lesions, which are now very clear on 7Tesla MRI, might be helpful in making an MS diagnosis.

Venocentric Lesions: an MRI marker in MS?
In the past decade, numerous studies have explored a promising biomarker for MS: MRI-detectable veins within lesions. This biomarker is well established as detectable at 3 and 7T and efforts should be made to identify/optimize clinically practical methods for its evaluation. Prospective studies have shown that the presence of venocentric lesions at an early but ambiguous clinical presentation is highly predictive of future MS diagnosis. Work remains to be done to confirm or exclude lesions of common MS mimics as venocentric. Common imaging practice and lesion-rating paradigms should be adopted by scientists working in this field.

Here's another paper entitled "The Central Vein Sign: is there a place for susceptibility weighted imaging in possible multiple sclerosis." (Readers of this page know that CCSVI investigator, Dr. Mark Haacke, is the inventor of SWI.  He has noted these central veins and iron deposition in the MS brain for almost a decade now, and linked their presence to CCSVI.)

Susceptibility weighted imaging (SWI) may have the potential to depict the perivenous extent of white matter lesions (WMLs) in multiple sclerosis (MS). We aimed to assess the discriminatory value of the "central vein sign" (CVS).

The "central vein sign" was predominantly seen in MS lesions. The "central vein sign" helps discriminate between MS and non-MS lesions.

Here's yet another study published in the Journal of Neuroimmunology in May 2013 which notes the central veins visible in MS lesion.

Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions.
In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms
.

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

These papers are no surprise--researchers have been noting these veins inside MS lesions for over a century.  But what continues to shock me is that researchers aren't asking WHY?

Sunday, September 1, 2013

Things you can do today to help your health


September 1, 2013

There are many things you can do to improve your health whether or not you are considering venoplasty for CCSVI.  Each of these lifestyle factors has been scientifically shown to help reduce symptoms in people with MS.   These actions can help your whole body and potentially increase cerebral blood flow.  I'm not a doctor- these ideas are based on the endothelial research of Dr. John Cooke of Stanford University and his book,  The Cardiovascular Cure.

People with CCSVI and MS need to consider their cardiovascular systems, and do all they can to help encourage healthy blood flow.  Always discuss any new health programs with your physician.  Here are some tips:

1. Eat a heart healthy diet! Lots of good leafy greens, fruits and veggies.  Stay clear of man made fats and anything the has too many ingredients (like overly processed foods.) Limit fructose corn syrup or transfats.  Many find going gluten free is very helpful.   Eat a good, nutritious whole food diet- like the Best Bet Diet, Dr. Swank's MS Diet, or Dr. Terry Wahls' Diet.

2. Move as much as you are able. Exercise- whether it is a stationary bike, seated exercise, water aerobics or yoga- is good for your circulatory system and will keep blood flowing.  If you have trouble exercising, practice deep, diaphragmatic breathing.  Taking deep breaths into the belly and releasing slowly will help blood flow.

3. Try to limit stress. Cortisol, the hormone released when we stress out, closes down blood vessels (this is called vasoconstriction)  Prayer, deep breathing and meditation can really help.

4. Limit alcohol... only small amounts. A glass of wine opens up blood vessels a bit, but any more than one drink becomes constrictive.

5. Get some sun on your face. Vitamin D and UV rays help the body utilize oxygen and are a vasodilator. If you have no sun in your area, try a sun lamp and take a vitamin D supplement.  Have your D3 levels tested regularly.

6. No smoking. Sorry. Cigarettes are vasoconstrictors- they close up blood vessels and can make stenosis worse. That's why we've seen so much about smoking and MS in the news. Cigarettes actually mute the immune system; you'd think they'd be good for MS, if MS was autoimmune! But cigarettes are linked to MS progression. In the CCSVI paradigm, that's because they inhibit good blood flow.

7. Hydrate.  Drinking adequate amounts of fresh water will keep blood flowing and limit risks from hypovolemia, or low blood volume due to inadequate fluid intake.

8.  Supplements.  Look into adding supplements to your whole food diet.  Vitamin D and omega 3 oils are essential.   EGCG, quercetin, bromelain are all good anti-inflammatories, anti-oxidants and great for blood flow.  Proteolytic enzymes, like serrapeptase and nattokinase, naturally break down fibrin and thin the blood.

9.  Laughter, joy, community, sharing....all of these have been actually proven to encourage better blood flow!  Watching funny movies, spending time with good friends (who really care, are positive and don't stress us out!) actually changes the level of nitric oxide in our bodies.

For more information, and to read the science and research behind all this, check out the Endothelial Health program I put together for my husband  Jeff- link below. 

Lots of these things are common sense and part of an overall healthy lifestyle, but it's always good to understand the science behind it.


hope this helps a bit!
Joan




Thursday, August 22, 2013

Medications for MS: addressing blood flow


August 22, 2013 at 12:16pm

With the growth of research into the connection of MS to cerebral blood flow,  we've seen an interest in exploring new ways to address hypoperfusion (slowed blood flow), endothelial dysfunction (damaged blood vessels) and  brain atrophy (loss of brain tissue).

Why is this?  Because MS specialists, neurologists and advocacy groups are much more comfortable designing, testing and recommending a drug for MS, rather than encouraging healthy lifestyles and treating venous malformations.  You cannot monetize or patent a diet, exercise and angioplasty.  It's impossible to have a placebo-controlled clinical trial for lifestyle.  But you can develop a drug and make a lot of money selling it to a population with a chronic and degenerative disease.  

Please note that I am not recommending these specific drugs at all, I'm just pointing out how MS research is slowly shifting.  

We saw this paradigm change happen with the Vitamin D.  Six years ago, Jeff's neuro chuckled when I asked to have his D3 levels tested. But slowly, with independent research funded by patient advocacy groups like Direct MS,  the research paradigm has changed. And now, neurologists are testing their new patients' vitamin D levels, and adding supplementation accordingly. I believe we will see this shift continue with drug approaches to reducing hypoperfusion. 

This is tacet proof that blood flow matters in MS.  But you will not hear that from neurologists-yet.   They will discuss cerebral blood flow with their patients when they have a prescription they can write.  




Here's some info on a few of these new medications which target blood flow, currently in clinical trials.

Ibudilast (MN-166)
Clinical trials in progressive MS patients to be lead by Dr. Robert Fox and the Cleveland Clinic with the NMSS.  Dr. Fox received NMSS money to study CCSVI, and after finding new venous malformations in the jugular veins of people with MS, he has moved on to a clinical trial using a vasodilating and neuroprotective drug.  Is this coincidental?


MN-166 has been marketed in Japan and Korea since 1989 to treat cerebrovascular disorders, including post-stroke complications, and bronchial asthma. MediciNova licensed MN-166 (ibudilast), from Kyorin Pharmaceutical for potential utility in MS.


Lisinopril 
An inexpensive blood pressure medication and ACE inhibitor which modulates angiotensin.  This drug opens up blood vessels and allows blood to flow more easily. This older drug is being developed to treat MS by Dr. Lawrence Steinman of Stanford University School of Medicine.  (Dr. Steinman is also one of the inventors of Tysabri--which he has since spoken out against as a first line treatment for MS.) 

... angiotensin immediately causes blood vessels to constrict. “That raises your blood pressure so when you stand up to get out of a chair, you don’t fall down and faint,” said Steinman, who is also the George A. Zimmerman Professor in the medical school. But angiotensin overactivity causes chronic hypertension. Lisinopril controls blood pressure by blocking an enzyme that converts angiotensin’s precursor into the active hormone. The drug also appears to have certain anti-inflammatory properties.

Here is info on the current study:

 In these studies, lisinopril reduced molecular measures of inflammation that accompany MS, yet it did not inhibit overall immune function.


Statins
Although these cholesterol-lowering drugs failed in earlier trials for RRMS, they are now being brought back to life to address brain atrophy in progressive MS.