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