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

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

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

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

Tuesday, February 2, 2016

The brain needs immune cells

In 2010, Dr. Alasdair Coles, an academic neurologist at Cambridge University, said to the press:
'We know MS is an auto-immune disease because if you block the immune response with drugs, people get better.'
This now infamous quote from Dr. Coles came when he was asked to comment on Jeff's treatment for CCSVI, as reported in the UK's Daily Mail.

In my mind, linking the cause of MS to how the drugs work (for some) is akin to saying, 
"We know the earth is flat because boats don't sail off the edge of the planet."
The relationship between the brain and immune system is much more complex than ever imagined.

Labeling MS a classic autoimmune disease is a serious misnomer--since we see the same immune cell reaction to myelin after hypoxic injury and stroke.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162361/
There are no antigen specific antibodies in MS. There is no specific immune target in Multiple Sclerosis.  

And, thanks to new research, we now know that immune cells are vital to a functioning brain.  

1.They provide healing after a break of the blood brain barrier, as we see in MS.
2.They aid healing of axons after injury to the central nervous system, via glial scar formation
3.The "autoimmune" t cells often ablated in MS treatment are also responsible for neuroprotection.

At the time of his quote, Dr. Coles was bringing his life's work to market--the chemotherapy drug Alemtuzumab, repackaged for MS as Lemtrada.  Cole's overarching premise in his research is that the immune cells in multiple sclerosis are completely damaging to the brain, and need to be entirely removed.

And his theory then that "people get better" when the immune system is ablated is actually not true.  Yes, inflammation is tamped down in those with RRMS.  But, just like swatting a pesky fly with a sledgehammer, there is a lot of residual damage.   Immune ablation with chemotherapy has a host of horrific side effects, including fatal cancers, fatal viral and bacterial infections, worse autoimmune reactions in other parts of the body including kidney failure, lung tissue swelling, and hypothyroidism.  Not necessarily "all better!"  Which is why this medication has a black box warning, 

Meanwhile, Dr. Coles is busy trying to create an antidote to stop the new autoimmune diseases his drug has caused.  That's right...Lemtrada actually causes autoimmune disease!
The principal adverse effect of alemtuzumab (Lemtrada) is autoimmunity, which arises when reconstitution of the immune repertoire after alemtuzumab occurs by homeostatic expansion of residual lymphocytes. Therefore we are now testing the ability of keratinocyte growth factor to promote thymic lymphopoiesis and so prevent autoimmunity after alemtuzumab, in a MRC-funded clinical trial.

Even worse,  the MS disease process does not stop with Dr. Cole's Lemtrada.  Cerebral atrophy and disability continue, even without any new lesions.

Unfortunately, this did not lead to a clinical improvement in the disability in these patients. In fact, their disability worsened with time at a rate of 0.02 EDSS points for each patient each year. Evidence for continued neurodegeneration in these patients was shown by progressive cerebral atrophy on follow-up MRI scanning. 

In the past decade, a narrative developed in the MS drug industry by MS researchers like Dr. Coles:  the idea that the immune system is at fault, and needs to be halted.   This has led to the creation of a class of drugs which create "lymphocyte sequestration" and "lymphocyte depletion"---meaning they keep the white blood cells walled off in the lymph tissue or deplete them, keeping them out of the body's circulation.  Instead of allowing immune cells protective entry into the body and around the brain, they are held back.  This new class of more powerful disease modifying drugs include Tysabri, Gilenya and Tecfidera.  

Not surprisingly, there is a price to pay when you hold back immune cells, deplete them, and don't let them do their job.  And one of those side effects is the reactivation of latent viruses and bacterial infections, including the John Cunningham virus (JCV).  This virus causes the deadly brain infection, progressive multifocal leukoencephalopathy (PML).  

Neurologists have comforted their patients regarding their PML risk and Tysabri use, telling them that if they were tested as JC virus negative, they would remain that way and not to worry.   But this was simply not true.  

The JC virus is very common in the general population, infecting almost 90% of us in childhood.  It stays under control and latent because our immune system keeps it in check.  This means we have a JC negative status.  The virus is able to cross the blood brain barrier where it attacks myelin and destroys brain tissue.  

New research shows that the risk of JCV reactivation due to Tysabri use is ten times higher than previously estimated.  That not 1%, but 10% of all patients on Tysabri were seen to go from JCV negative status to JCV positive status while taking Tysabri.  The drug is apparently what turns people from JC virus negative to positive.  This makes sense, if you understand that what Tysabri is doing is holding back immune cells, and rendering them unable to stop a virus from reactivating.

It also makes sense as to why Tecfidera and Gilenya have now been linked to PML...and I fear it's only a matter of time until real world reporting comes in.  

Dr. Michal Schwartz has been publishing on the importance of immune cells for brain health for decades.  Both she and Dr. Nedergaard are two of my research heros.  They are brilliant, determined women who have challenged the neurological status quo and are actively publishing their findings.

Dr. Schwartz explains her decades long search in understanding the importance of the immune system for the brain in her new book,  Neuroimmunity: A New Science That Will Revolutionize How We Keep Our Bodies Healthy and Young.

This book is simply wonderful!  It is written clearly and simply, so that lay people might understand her research.  But it is also in-depth enough to appeal to researchers.  All of her publications are cited.

Scientists long believed that there was no communication between the brain and the immune system; in fact, it was thought that any infiltration of immune cells into the brain was a major threat to our health. Based on this assumption, the standard treatment for inflammation associated with neurodegenerative diseases, such as Alzheimer’s, was to totally suppress the body’s immune system.

Prof. Schwartz turned this theory on its head by proving that the immune system and the brain do “speak” to each other – and that, in fact, neurodegenerative diseases are the result of a communication breakdown between the brain and the immune system. Instead of suppressing the immune system, she argues that the most effective way to treat Alzheimer’s and other chronic neurodegenerative diseases is to do the opposite: boosting targeted immune cells in the brain. 

The brain needs immune cells.

Please, if you have MS--- until we understand more about the immune system and brain health, make sure to discuss this new research with your neurologist, especially if they are putting pressure on you to try these new immune ablating and lymphocyte depleting drugs for MS.  New research is coming in every single day, showing that this method might not be the best approach for long-term brain health.

Be well, be curious.
The earth is not flat.

Sunday, January 24, 2016

Jugular Veins are Important

Recently published in the Journal of Mutiple Sclerosis, a review paper co-authored by Dr. Paolo Zamboni and Dr. Massimo Pedriali on the "Pathology of the Internal Jugular Vein in Multiple Sclerosis".   The complete paper is available on line for free---and I'd recommend it to all.  It is a very thorough review.


As this review outlines, there are observable and documented differences between the jugular veins of healthy controls, when compared to people with Multiple Sclerosis.  These pathological differences involve the endothelial cells which comprise the veins' lining.  Endothelial cell aptosis (death) and derangement, as seen in MS, changes the ability of the jugular veins to drain.  Valvular and intraluminal abnormalities in the jugular veins of people with MS have hemodynamic implications.  There is a shift in collagen in the jugular veins of people with MS which affects venous compliance.

Veins have received little attention and research, when compared to the study and understanding of arteries.  Certainly, in terms of brain health, the carotid arteries are scanned and studied, and neurology and stroke researchers know that blockages, clots, and impairment in flow can be disastrous to the brain.  There are treatment modalities developed to deal with carotid artery issues---from medications to open surgery, to interventional proceedures.  No one questions the importance of healthy blood flow to the brain.

But the venous system and the removal of fluids from the brain is even more important than previously imagined.

During the past two years, international researchers have described a newly discovered lymphatic drainage system, which has actual draining vessels, and relies on the brain's draining veins.  These vessels take lymph fluid, carrying metabolites, proteins and toxins, out of the brain.  This process is aided by sleep.  This science is brand new.   It has reversed what we once believed was the brain's "immune privilege."

This "stunning discovery" of a lymphatic drainage system relies on the jugular veins.

"Instead of asking, 'How do we study the  of the brain?' 'Why do  patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral  through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). 

The brain is like every other organ in our body---it needs drainage.  Jugular veins are responsible for the exit of blood, cerebrospinal fluid (CSF) and lymph.  Any delays can cause changes to the brain's immune functioning, oxygenation, glucose metabolism and health.  Delays cause neuronal death and inflammation.  Or, what we see in multiple sclerosis.

Dr. Jonathan Kipnis, the discoverer of these lymphatic vessels, will be the keynote speaker at the International Society for Neurovascular Disease.  He will be presenting his research and proposals for studies in MS, alongside Dr. Zamboni and the other members of the ISNVD.

Here's the program.   “How the Extracranial Venous System Influences Neurological Diseases.”

This is not going away.
jugular veins are important,


Notice the difference between the top panel---healthy endothelial cells lining the jugular veins in normal controls, compared to the endothelial cells of a person with MS (bottom)

Figure 5: Scanning electronic microscopy. Top panel: regular disposition of the endothelial cells in IJVs of healthy controls, respectively at 800x (right) and 1500x (left). Bottom panel: irregular arrangement of the endothelial cells in the IJV of a MS patient, respectively at 800x (left) and 1500x (right). The cells appear lifted with craters.

Thursday, January 21, 2016

HSCT-- Facts behind the Headlines

Whenever there is a news story on autologous hematopoietic stem cell transplants (HSCT), I hear about it.  Perhaps this also happens to you, MS patients and caregivers?  Well-meaning friends, family, and acquaintances forward you links to glowing miracle cure stories.  And I reply with sincere thanks--and also inform them that Jeff's doing really well, with no MS disability, inflammation, new lesions or disease progression, now 9 years past his diagnosis with MS.  So, HSCT is really not for him.  Believe me--I know how fortunate we are to be able to report that!

Here's the latest miracle cure HSCT story out of Sheffield Teaching Hospital in the UK, which was picked up on British television and the press.  It's received a lot of coverage after the BBC aired a report:

For those who have had MS awhile now, these repeated stories on HSCT are heartening, but at the same time discouraging.  Because HSCT is certainly not for everyone, and many can't even consider this treatment.  It is good to know that some people are getting relief from MS and recovering their abilities, even if only temporarily.   It's also very important to understand that these stories are anecdotal.  They are heart warming, for sure, I'm not trying to be a downer.  But there is a dark side to this "cure narrative" I'd like to explore:  the premise that a "faulty immune system" in MS which needs to be ablated and completely removed is keeping us from understanding true disease progression.  

The general public, press, and politicians get a false sense of progress when they read these news stories.  They think, "well, at least we've got multiple sclerosis cured"....when nothing could be farther from the truth.  And new and recently diagnosed MS patients, who have yet to have gone through a decade of these kinds of stories, may mistakenly believe this is a cure.

HSCT was developed for pediatric cancer, and has been a blessing for the children and their families who have seem mortality rates decrease and life expectancy increase.  In this instance, carpet bombing the body and killing off cancer cells and then rebuilding the immune system with harvested and purified stem cells has saved lives. http://emedicine.medscape.com/article/989518-overview

In MS, HSCT use was first promoted by Dr. Richard Burt in the 1990s and has been used to treat thousands with MS.  However, there have been no randomized, double-blind placebo controlled trials, so even after all this time, results are still not considered "gold standard."  In fact, some of the results may be placebo.  The stronger or more invasive the proposed treatment, the more powerful the placebo effect.   https://www.psychologytoday.com/blog/sideways-view/201502/the-placebo-effect

Here are the facts:

1.  HSCT is only appropriate for those with highly inflammatory relapsing remitting MS, who have not responded to other drug therapies, and who have new lesions and relapses within the past year.  Trial participants cannot have had MS for longer than 10 years.  This is a very specific group of people with MS.

2.  HSCT uses chemotherapy to wipe out the existing immune system.  Many researchers urge caution regarding this approach, because chemotherapy--on its own-- is known to have many deadly side effects, causing up to 5% mortality in some trials.  Chemotherapy also causes demyelination and brain atrophy.  I've written extensively on the long term neurological effects of chemotherapy here:  http://ccsviinms.blogspot.com/2014/03/chemotherapy-causes-brain-atrophy.html

3.  Long-term success rates show that MS disability is not halted.  HSCT is not a cure.  It may be a very helpful treatment for some with highly inflammatory MS, however the disease continues to progress in most patients.  And autoreactive T cells to myelin targets return.

Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation.http://www.ncbi.nlm.nih.gov/pubmed/17293360

Demyelinating and inflammatory activities of MS persisted after allo-HSCT in all of the patients with MS. Active and chronic active MS lesions exhibited significantly higher numbers of CD3+ T cells and CD8+ cytotoxic T cells and significantly higher scores of CD68+ microglia/macrophages than did chronic inactive lesions or normal-appearing white matter.http://www.ncbi.nlm.nih.gov/pubmed/20558390

Re-emergence as well as in vivo expansion of autoreactive T cells to multiple myelin targets was evident in all patients studied. The reconstituted myelin-specific T cells exhibited the same Th1 and Th2 responses as preablation myelin-reactive T cells. In contrast, the post-therapy T-cell repertoire exhibited a significantly diminished capacity for Th17 responses.http://www.ncbi.nlm.nih.gov/pubmed/23463494

And now, the big question.  Why do autoreactive T cells return even after they've been blasted to kingdom come and replaced with a new immune system?  Why does MS continue to progress?
Could it be that the underlying cause of the activation of these t cells is not a faulty immune system---but rather a continuing process of neurodegeneration?

The kind of neurodegenerative process we see happening in the gray matter structures of the MS brain?  The type of neurodegeneration that shows continued atrophy of the thalamus in all people with MS---from CIS to PPMS?  http://ccsviinms.blogspot.com/2016/01/thalamic-atrophy-and-ms-progression.html

There is a huge difference between finding MS treatments which give patients relief from their symptoms and reduction in disability-----and understanding the underlying disease mechanism which allows for continued MS progression.  Temporarily tamping down inflammation is not the same as halting MS disease progression.  

Keep getting the correct info out there.  Push for researchers and policy makers to examine the underlying cause of MS disease progression.  
That's the only way forward,


This is about the use of bone marrow stem cells to to replace the immune system and is the most extreme form of "induction therapy" aimed at rebooting the immune system. This study has been reported by us and it is clear that the majority of people are not leaping out of their wheel chairs. This is just the type of poor reporting that the media specialise in ...media hype 

PICTURE CREDIT:  TOM SCOTT---Journalism Warning Labels