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

Tuesday, July 4, 2017

Interferon β almost doubles the risk of stroke and migraine in MS. Why?

An important observational study on long term use of interferon β and increased risk of stroke and migraine in MS was just published by one of my favorite MS researchers, Professor Helen Tremlett at the University of British Columbia.  Current interferon beta drugs prescribed for MS are Avonex, Betaseron, and Rebif.  

The complete paper is available here:
Evaluating the Safety of B Interferons in MS

Dr. Tremlett does not represent any drug company or MS treatment.  Dr. Tremlett simply studies people with MS, to understand disease progression and environmental factors, like gut microbia, vascular commorbidities, liver enzymes, Vitamin D, sun exposure, fatigue and pregnancy.  link

She has been studying the adverse affects of MS drugs and documenting many things pharmaceutical trials marginalize, or completely ignore.  In her publications, she highlights MS DMDs' modest efficacy, and the fact that clinical trials are of short duration and in a highly selected patient group, and do not give us a complete picture of long-term adverse events.

The IFN-βs are modestly effective, reducing relapse rates by about one-third and having a beneficial effect on imaging outcomes,2 but findings regarding longer-term effects on disability have been mixed.3,4The IFN-βs are generally considered safe, especially compared to newer agents for MS.5 However, few studies have systematically assessed their safety in real-world clinical practice (appendix e-1 at Neurology.org).5 A meta-analysis of 9 clinical trials estimated that patients treated with IFN-β had a 2.8-fold increased risk of discontinuing drug because of an adverse event compared to the placebo group. The most common adverse events were flu-like symptoms, injection-site reactions, leukopenia, lymphopenia, and elevated liver enzymes.6 However, because of their short duration and relatively small sample sizes, clinical trials cannot identify all potential adverse effects of a drug treatment or predict the safety of the drug in clinical practice. Furthermore, participants in clinical trials are highly selected in terms of comorbidities and concomitant medications and often differ substantially from patients who use the drug once it reaches the market. We identified signals of potential adverse events related to IFN-β treatment in a large population-based cohort of patients with RRMS.

This new study looked at patients with RRMS, registered at the UBC MS Clinic from 1995-2004, who were treated with interferons.  2,485 eligible patients were followed up until death, until they left BC, or until they stopped taking interferons.  After compiling the data, the study showed that patients who had taken interferons, there was a 1.8 fold increase (almost double risk at 180%) of stroke or migraine.  There was also a 1.3 fold increase in depression and hematologic abnormalities.

I realize this might be an obvious observation to many of my readers, but I feel like it will be overlooked by neurologists.  All of these adverse affects are vascular.  Stroke, migraine, blood issues --and yes, even depression---are related to blood flow, cerebral perfusion, coagulation and endothelial health.  Interferon B changes platelet adhesion to the endothelium and appears to raise blood pressure.

Here's more on this from the paper:

Our study is a comprehensive assessment of the potential risks for a broad range of adverse events related to IFN-β in the real-world clinical setting. Several of the adverse events that we observed to be associated with IFN-β exposure such as migraine, hematologic abnormalities, and depression are included in the known safety profile of the IFN-βs. Stroke, on the other hand, is not well recognized as a potential adverse event, being limited to a few case reports.19,20 Nonetheless, it is biologically plausible that this event is associated with IFN-β because this drug may alter wall competence or enhance the major histocompatibility complex-1 molecule expression of platelets and other cells,21,22 resulting in enhanced platelet adhesion to the endothelium.22,23 
Hypertension can also increase the risk of both migraine35 and stroke, and we observed a higher risk for hypertension among current users of IFN-β, which might point to a common pathway.

Other researchers are also studying the long term vascular side effects caused by interferons---
including thrombotic microangiopathy, which is a disease of endothelial injury resulting in thrombosis.  These clots can cause stroke, chronic kidney disease and renal failure.  

Also being studied is how interferons affect blood clotting and cause hypertension

There have been case studies where people with MS who were treated with interferon B had subsequent strokes.

Previous studies have shown that people with MS already have a two fold increase in risk of venous clots, independent of drug treatment.

Perhaps long-term use of Interferon β-- which further increases the risks of clotting, hypertension,  stroke and endothelial dysfunction, while only reducing relapse risk by 1/3-- isn't the best approach for people with MS.

The vascular connection to MS is real.
Endothelial health is essential.


Friday, June 9, 2017

Caution and concern: minocycline and antibiotics for MS

There are new reports and publications advocating for use of minocycline as a "safe and inexpensive treatment for MS"--as well as a new publication on combined antibiotic treatment for CCSVI.

There is no doubt that antibiotics have been helpful for many with MS.

However, I have serious concerns about using antiobiotics as an MS treatment, due to a side effect which can go undetected, causing damage to the brain and vision.

First, a bit of history.  When Jeff was diagnosed with MS in 2007, I found a publication which considered use of minocycline as a low-risk MS treatment.  Yes, this antibiotic has been touted before.  What's old is new.  link

I brought in the research in and asked his neurologist if she would prescribe the antiobiotic for him, and she agreed.

Jeff took minocycline for a couple of days, and developed serious pressure headaches.  He kept on with it, even though he was in agony,  as we had read some articles about "herxing" and bacterial "die-off" and thought maybe that might be the issue.  But the headaches got worse.  After consulting with his neurologist, we learned that Jeff's headaches were most likely due to a KNOWN side-effect of minocycline.

Minocycline is believed to hamper reabsorption of cerebrospinal fluid in the brain,  potentially creating intracranial hypertension and vision loss.  In fact, doctors know about this side effect, and it has been well documented.   For someone with already slowed venous flow and build-up of CSF (as a patient with CCSVI),  this side effect could be even more harmful.

As intracranial hypertension does not always manifest in vision loss or headache, it might be difficult to know if this antibiotic is hampering CSF flow in the brain.   link
For those who wish to learn more about how all tetracyclines, like minocycline, create intracranial hypertension. link

Jeff's neurologist advised him to stop taking minocycline, and the headaches went away.  He was lucky, he had a very obvious side effect, and knew to stop.  But not everyone gets headaches.

So, please be careful.  Something which seems "benign" as a treatment for MS, may actually have side effects that we still do not understand.

We also do not clearly know the impact of antibiotics on the gut's microbiome.  And this is another area of concern for me.

The study, recently published in mBio, found that just one weeklong course of antibiotics changed participants' gut microbiomes, with the effects sometimes lasting as long as a year. After all, antibiotics don’t discriminate—as they attack the bad bacteria, the good ones are vulnerable too.

For people who have benefitted from antiobiotic protocols, I'm truly happy for you!  MS is indeed a snowflake disease, and chronic infections are known endothelial disrupters.   This post is for the folks who have not had benefit, or had damage, or who want to know more.

Because people with MS do not always get the complete story,

Tuesday, May 30, 2017

Jugular anomalies and collateral flow in multiple sclerosis

There is a new paper recently published in the American Journal of Radiology from Dr. Haacke's superb radiology team at Wayne State University in Detroit, called Jugular Anomalies in Multiple Sclerosis are Associated with Increased Collateral Venous Flow

The complete paper is here:  link

As many of my readers know, there has been very little study of the outgoing venous system, especially when compared to the ingoing arterial side of blood flow.  We have a well-documented understanding of how problems with carotid arteries, the main inflowing blood vessels to the brain, can cause disease.  link  There are many papers on carotid arterial stenosis and stroke, dementia, Alzheimer's and other diseases of neurodegeneration.  And carotid artery scans are quite commonplace.  Angioplasty treatment for carotid arterial disease is an accepted and even routine practice today.

But in contrast, the venous system, specifically the internal jugular veins which are the main drainage route for the brain, has been under-researched and is not well understood.  A common thought from doctors has been that the brain can utilize collateral veins to drain, and that when the jugular veins are blocked, it's no big deal, since there are other veins to take up the flow.  This paper is one of the first which is looking specifically at how blockage of the IJV changes venous flow patterns.

Research on venous abnormalities in MS thus far has been limited to the IJV, and little is known about extracranial venous collateralization. The extrajugular drainage system consists of the vertebral venous system; the deep cervical veins, which anatomically are paraspinal toward the heart; and the anterior and external jugular veins, which receive blood from facial and superficial areas.8 Although the presence and structure of collateral veins have been assessed by using time-resolved imaging of contrast kinetics venography, flow values were not quantitatively evaluated.9-11 The purpose of this work was to examine the relation of extracranial venous anatomy and flow in a large cohort of patients with MS and healthy controls (HCs) taken from our neuroimaging data base.12 Because of the complexity of the extracranial venous system, we have classified these vessels into 3 groups based on anatomic MR information and their drainage path: primary (ie, IJV), paraspinal, and superficial. We hypothesized that increased venous paraspinal and superficial flow will also be observed for cases that evidence abnormal IJV structure and flow. In contrast, a subset of patients with MS may have a distinct collateral venous flow pattern compared with patients with MS and HCs without structural venous anomalies. 

In a study of 153 people with MS, 55% of the MS group exhibited jugular venous stenosis.  In the healthy control group of 105 people, 20% had stenotic veins.  Both of these groups had collateral venous flow, either through the vertebral or paraspinal veins.   The anatomic assessment of these vessels really isn't the complete picture.  Remember Dr. Zamboni's quote--"It's not the architecture, it's the flow."

Collateral flow has hemodynamic consequences.   This collateral system is like taking a winding country road when the main highway is blocked.  It is slower, less direct and has consequences for the brain, including venous hypertension and venous insufficiency.  There will be further research on the hemodynamic consequences of collateral venous flow.

One of the leading researchers publishing on this link is ISNVD member Professor Clive Beggs.

Professor Beggs has been able to show that MS is associated with changes in the dynamics of the CSF pulse in the cranium, and that the normal relationship between this and the jugular veins is profoundly altered in MS patients. He has also found that venous drainage anomalies in patients with Alzheimer's disease are associated with blood retention in the cerebral veins, suggesting that constricted venous outflow might be a generic phenomenon implicated in the pathophysiology of other neurological diseases.   Professor Beggs said: “My work suggests that vascular anomalies can profoundly alter the biomechanics of the intracranial space. This is important because there is a growing body of evidence that altered haemodynamics in the cranium are associated with a wide range of neurological conditions.  link
I know it has been frustrating for those waiting for CCSVI science to come in.  In the ten years since Dr. Zamboni first published his initial papers on CCSVI, we have seen an unprecedented pushback from the neurological community to even consider venous flow and the brain.

But we have also seen new publications like this one from radiologists,  and contributions from groups like the Nedergaard Lab, the Kipnis Lab, the Gladstone Lab and the ISNVD.  These groups are publishing on the newly discovered lymphatic system, which relies on the venous system of the brain.  We are now seeing how absolutely vital the brain's veins are--and how problems in venous flow are linked to all diseases of neurodegeneration.  This is real, and the science is coming in.  link

For those who are "out of wait" and frustrated by the pace of this research--it is best to consider the vascular connection to MS and live your most  endothelially healthy life today.  Talk to your own doctor about eating whole, colorful natural foods, exercising or physical therapy, getting UV ray exposure,  increasing quality sleep, reducing stress,  and finding joy and community.  Maybe consider NUCCA or atlas orthogonal treatments, having your venous system scanned for irregularities and getting treatment from a respected IR.

Be hopeful, and be well.

My husband's MRV from Stanford University, April 2009
Showing 99% and 70% obstructed IJVs and collateral flow (those curly, small veins) before his venoplasty treatment