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.

http://www.frontiersin.org/Multiple_Sclerosis_and_Neuroimmunology/10.3389/fneur.2013.00098/full

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.

http://www.ncbi.nlm.nih.gov/pubmed/23436147

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

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http://www.ncbi.nlm.nih.gov/pubmed/23529352

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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?

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.

http://www.ccsvi.org/index.php/helping-myself/endothelial-health

hope this helps a bit!

Joan

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?

http://finance.yahoo.com/news/medicinova-announces-initiation-cooperative-phase-230000864.html

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.

http://med.stanford.edu/ism/2009/august/lisinopril.html

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.

link 

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.