Hypoperfusion (decreased blood flow) in MS

December 31, 2009 at 10:53am

Before 2009 comes to a close, I'd like to share more research on the decrease of blood flow in the MS brain. There are many researchers around the globe using new MRI technology to study slowed perfusion in MS brains.

I would like to break down this one medical research paper for you, to show you how these researchers' findings can be linked what Dr. Zamboni has discovered.  I will quote sections from the paper- and then we will discuss.

Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance

This work was supported by MS Anders (Amsterdam, The Netherlands).

Jacques De Keyser1,2, Christel Steen2, Jop P Mostert2 and Marcus W Koch2

1Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel,Brussels, Belgium

2Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

http://www.nature.com/jcbfm/journal/v28/n10/full/jcbfm200872a.html

from the abstract:

"A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss."

This means that in normal appearing white matter (NAWM) in MS brains, there is a slowing of blood flow which does not appear to be caused by axonal death. Something else is causing the slowed blood flow FIRST-because it shows up before we see lesions.

"The classic teaching is that MS is a T-cell-mediated autoimmune disorder of the central nervous system. However, a number of pathophysiological observations cannot be simply explained on the basis of autoimmune mechanisms. First, the progressive (neurodegenerative) component of the disease continues despite intense immunosuppressive interventions that effectively stop inflammatory disease activity (Coles et al, 1999; Metz et al, 2007; Roccatagliata et al, 2007; Samijn et al, 2006). Second, pathologic studies have shown that some demyelinating lesions develop without a preceding inflammatory reaction (Barnett and Prineas, 2004; Gay, 2007, 2006; Guseo and Jellinger, 1975; Lucchinetti et al, 2000). Third, another intriguing finding difficult to explain by autoimmune phenomena is the finding of a diffuse cerebral white matter hypoperfusion, which is the subject of this review."

The prior thought has been that MS is a t-cell mediated disease, autoimmune..we've all heard this. HOWEVER, the researchers wonder, how can the autoimmune hypothesis explain what we (many other researchers) are observing?

1. Even when suppressing the immune system, damage continues in the MS brain

2. Demyelinating lesions appear BEFORE inflammation

3, There is a slowing down of blood flow in cerebral white matter in MS brains

Vascular white matter lesions are 50-500 times more likely than MS

December 30, 2009 at 2:57pm

Neurologists refer to the "unique" presentation of MS as an autoimmune disease- with oligoclonal banding in CSF showing myelin degradation and perivenous (or around the veins) white matter lesions on MRI.

But these features are not unique to MS. Most of these signs are also found as result of hypoxic injuries to the brain: including (but not limited to) stroke, diffuse cerebral hypoxia, dementia and vascular insufficiency- in which the immune system is similarly activated.  What makes MS unique are the perivenous lesions, shown on MRI.  MS is diagnosed as MS because of the location of the lesions, age of the patient and their symptoms.

Here is research from a radiology web site, authored by Dr. Barkhof, on white matter lesions in MRI.

MS vs. Vascular findings

Consequently, it is not wise to put MS in the differential diagnosis, if the clinician does not suspect the patient of having MS and on the MR incidental white matter lesions (WML) are found.  The odds are against the diagnosis of MS, because vascular WMLs are 50-500 times more likely than MS plaques.

http://www.radiologyassistant.nl/en/p4556dea65db62

MS is a diagnosis of exclusion.  It can be 500 times more likely that someone has a vascular disorder.  Diagnosticians can also exclude those patients who are old, who have had a stroke, who have been poisoned by carbon monoxide, who have high blood pressure- even though these patients may have MRIs that look strikingly similar to an MS patient. When the mode of brain injury is apparent, the diagnosis is easier. MS researchers have here-to-fore not had an explanation for injury, and so the autoimmune theory was employed.  Even though the main issues for these lesions are predominantly vascular.

Dr. Zamboni is now showing us that there is a mode of brain injury in MS patient- chronic cerebrospinal venous insufficiency created by venous stenosis and reflux, which is directly linked to the slowed perfusion and hypoxic-like lesions found in the MS brain-as well as the degradation of gray matter due to iron deposition.

Please consider the following research:

Hypoxia-like tissue injury as a component of multiple sclerosis lesions.

Lassmann H.

http://www.ncbi.nlm.nih.gov/pubmed/12559509

Ischemic Demylination:

Recent studies have looked at lesion load in a fashion analogous to that seen with multiple sclerosis. A particularly relevant clinical model for white matter disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which combines the potential components of small vessel disease, resulting in progressive neurological deficit, with a common association with migraine which can also be associated with white matter lesions. However, the most common pathogenic factor associated with the microangiopathy, which appears to be at the heart of ischemic demyelination, continues to be hypertension. 

http://www.ingentaconnect.com/content/maney/nres/2006/00000028/00000003/art00018

Multiple Sclerosis: The Role of MR Imaging

Y. Ge From Department of Radiology/Center for Biomedical Imaging, New York University Medical Center, New York, NY

http://www.ajnr.org/content/27/6/1165.full

commentary on this research:

Ischemia and Multiple Sclerosis: Perfusion MR Imaging Provides Insight into an Underexplored Pathophysiology

Jack Simon, Guest Editorialist

a University of Colorado Health Sciences Center

http://www.ajnr.org/content/26/6/1306.full

Deep white matter ischemia

http://rad.usuhs.edu/medpix/parent.php3?mode=single&recnum=1503&table&srchstr&search

EGCG (green tea): metal chelator, anti-inflammatory, and super anti-oxidant

December 13, 2009 at 3:54pm

Recent studies on the usage of EGCG (green tea extract) in Multiple Sclerosis patients have shown a benefit as a neuroprotective agent and an effective antioxidant.  

EGCG is also a known chelator of iron and is capable of removing iron and metals from the brain, since it passes through the blood brain barrier, even if taken orally.

Consider this wonderful, natural, inexpensive and non-toxic supplement or just drink the tea.  Something you can do today.

Neuroprotective molecular mechanisms of (-)-epigallocatechin-3-gallate: a reflective outcome of its antioxidant, iron chelating and neuritogenic properties.

Tea, the major source of dietary flavonoids, particularly the epicatechins, signifies the second most frequently consumed beverage worldwide, which varies its status from a simple ancient cultural drink to a nutrient component, endowed possible beneficial neuro-pharmacological actions. Accumulating evidence suggests that oxidative stress, resulting in reactive oxygen species generation, plays a pivotal role in neurodegenerative diseases, supporting the implementation of radical scavengers and metal chelating agents, such as natural tea polyphenols, for therapy. Vast epidemiology data indicate a correlation between occurrence of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, and green tea consumption. In particular, recent literature strengthens the perception that diverse molecular signaling pathways, participating in the neuroprotective activity of the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), renders this natural compound as potential agent to reduce the risk of various neurodegenerative diseases. In the current review, we discuss the studies concerning the mechanisms of action implicated in EGCG-induced neuroprotection and discuss the vision to translate these findings into a lifestyle arena.

http://forschungsberichte.charite.de/FOB_2006-2007/deutsch/PJ/PJ28373.html

Charite University in Berlin is currently conducting a clinical trial of EGCG in MS.  

http://clinicaltrials.gov/ct2/show/NCT00525668

EGCG and neuroprotection --

EGCG, has emerged as a potent neuroprotective agent for treatment of several neuropathological states associated with damaging effects of reactive oxygen species (ROS). EGCG has an inhibitory effect both on inflammation, by influencing T cell proliferation and inhibiting the activation of NF- B, and on neurodegeneration through its antioxidative potency as a free radical scavenger. In the present study we aim to evaluate the safety and neuroprotective effects of orally administered epigallocatechin-gallate in patients with relapsing-remitting MS in a multicentre, double-blind, randomised, stratified, placebo-controlled prospective 2-arm study. As a result of its anti-inflammatory and neuroprotective potency, EGCG should be significantly more effective than placebo in reducing the development of new contrast enhancing and T2 lesions on the one hand, but also in their conversion into T1-hypointense lesions ( black holes ), and in arresting the disease dependent acceleration of brain atrophy, and neuronal loss or dysfunction.

http://forschungsberichte.charite.de/FOB_2006-2007/deutsch/PJ/PJ28373.html

EGCG and metal chelation-

Evidence to link abnormal metal (iron, copper, mercury and zinc) metabolism and handling with Parkinson’s and Alzheimer’s diseases pathology has frequently been reported. The capacity of free iron to enhance and promote the generation of toxic reactive oxygen radicals has been discussed numerous times.

Metal chelation has the potential to prevent iron-induced oxidative stress and aggregation of alpha-synuclein and beta-amyloid peptides. The efficacy of iron chelators depends on their ability to penetrate the subcellular compartments and cellular membranes where iron dependent free radicals are generated. Thus, natural, non-toxic, brain permeable neuroprotective drugs, are preferentially advocated for “ironing out iron” from those brain areas where it preferentially accumulates in neurodegenerative diseases. This review will discuss the most recent findings from in vivo and in vitro studies concerning the transitional metal (iron and copper) chelating property of green tea and its major polyphenol, (−)-epigallocatechin-3-gallate with respect to their potential for the treatment of neurodegenerative diseases.

http://www.ncbi.nlm.nih.gov/pubmed/17447435

Jeff's been doing well with EGCG, going on five years now.  Ask your doctor or naturopath if it might be good for you, too.  Remember, I'm not a doctor, but I want to bring you the recent studies in MS.

Joan

Some common sense things you can do today

November 25, 2009 at 11:06pm

There are many small things you can do to help your vascular health while waiting to be tested or treated for CCSVI. While these actions won't get rid of any congenital venous obstruction, they can help your whole body and maybe improve cerebral blood flow and endothelial health.  I'm not a doctor- these are just some common sense steps you can take right away.  Always speak to your own physicians before beginning any new health program.

1. Eat a heart healthy diet! Lots of leafy greens, fruits and veggies. 

Limit saturated fats (like red meat) and stick to lean, white meat protein. Fish is a terrific choice. Stay clear of man made fats, transfats and anything the has too many ingredients (like overly processed foods.) Limit glucose and simple sugars.  Eat a good, whole food diet- like the Best Bet Diet or Dr. Swank's MS 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.  It also creates "shear stress" in your blood vessels and increases a healthy, strong endothelium.

3. Try to limit stress. Cortisol, the hormone released when we stress out, creates vasoconstriction and closes down blood vessels. Prayer, meditation and deep breathing can really help. Laughter actually opens blood vessels up! Try to find joy everyday--with your children, friends,  pets, funny movies, good books.

4. Alcohol only small amounts. A glass of wine opens up blood vessels a bit, and provides some phytonutrients, but any more than one drink becomes vasoconstrictive.

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

6. No more smoking. Sorry. Cigarettes are vasoconstrictors- they close up blood vessels. That's why we've seen so much about smoking and MS in the news lately. Cigarettes actually mute the immune system---so 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.


For more information, and to read the science and research behind all this, check out my Endothelial Health program I made up for Jeff.  It's the first post on this blog.  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

Iron in the Brain or the Immune System

September 17, 2009 at 9:36am

Many disease modifying treatments use the reduction of immune activated lesions as shown on MRI as proof a treatment is "working" in MS. This has baffled me, since we know that the number of lesions does not correlate to level of disease progression. Someone like my husband can have 20 brain lesions and function quite well. Someone else can have one or two lesions and be wheelchair-bound. Also, at a certain point, lesion progression stops when MS turns progressive. There must be another mechanism of injury, along with the immune system, at work in the MS brain.

In Bologna, Dr. Mark Haacke addressed another means of measuring brain tissue injury in MS. Susceptibility Weighted MRI. What SWI MRI shows us, is that iron deposited in the brain is a bio marker for MS progression.

What is different in SWI-MRI, according to Dr. Haacke, is that brain damage shown due to iron deposition actually CORRESPONDS to disability in MS.

The more iron deposed in the brain, the more disability, the more progressive MS is. This is different than the usual measuring of hyperintense lesions on MRI, which have no specific correlation to disease severity.

Here's the rub:
Pharma companies use the lesions shown on MRI as "proof" that their particular drug is working. Look! We've reduced hyperintensities on MRI! Our amaze-a-bub is slowing MS! Stock prices go up, investors are happy, and MS patients continue to decline.

If we look at the TRUE cause of disability- the only measurement in the brain that correlates to disability is iron deposition and brain atrophy.

This is why my husband had 20 lesions at his diagnosis and could mountain bike, and someone with one lesion is in a wheelchair. It's not just about the white matter lesions.

If we understand that the macrophages and immune system are activated as janitors to clean up the cellular death in the brain, we understand that the lesions we see on standard MRI may be secondary--just as they are a stroke patient, or someone with an ischemic brain ijury.

Thank goodness for Dr. Haacke, and other scientists who are speaking out.  It is not simply about the lesions on MRI. We will be told it is, because we can be sold drugs that halt these lesions---but that has not stopped MS progression.  There is no drug to stop reflux, iron deposition and hypoxic injury in the brain, and this is why it has not been explored since TJ Putnam in the 1940s, and will be fought.

Notes from CCSVI conference, 

Bologna, Italy --September 8, 2009

September 9, 2009 at 7:37pm

Notes from the CCSVI presentation
September 8, 2009


Dr. Ellliot Frohman, University of Texas Southwestern Medical Center Neurology, Dallas, Texas and Robert Zivadinov, Jacobs Neurological Institute, Buffalo, NY are chairs for the morning session:

Dr. Frohman makes the introduction. CCSVI is removed from how we think about MS or any other immune mediated diseases. Could other diseases we currently classify as autoimmune be related to venous disease? Autoimmune diseases share in common molecular adhesion molecules. Perhaps Crohn’s could be venous? Validating CCSVI in MS may affect the classification of other autoimmune disorders. This venous model has been overlooked.

Micrographs, histopath proficles, periventricular cuffs, red cells we see in post capillary venules. This is not new. In 1863 -before Charcot.- G.E. Rindfleisch writes of venous congestion in MS.

Could the immune system go anywhere blood goes? Is this why there is an inappropriate immune response? He notes the large crowd in the room (it’s packed) and says he hopes people will speak out. (they will!)

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

Dr. Paolo Zamboni- Universita degli Studi di Ferrara, Italy director of vascular studies

The drama of CCSVI and MS is that of severe stenosis of the extracranial pathways. Everyone in this room can return home and establish a cooperation between vascular and neurology departments. A simple demonstration - he shows a video demonstration of doppler protocol to aid diagnosis. There is a blocked outflow of blood.

In the normal control groups, there is a monodirectional flow of blood. In MS the periventricular vein has a bidirectional flow. Substitute circles avoid intracranial hypertension. Mean transit time is increased.

Dr. Zamboni proposes a “Menu” for the day-

1. Entree- what is the origin of venous stenosis?
2. Pasta- May we assess consequences of CCSVI in the brain. Perhaps microbleeding is the source of lesions.  Just like CVI in other parts of the body- there is microcirculation
Cerebral spinal fluid ultrafiltration and reabsorption depends on transmural pressure.
TMP = IVP-EVP
In venography, there is much higher pressure in MS patients then controls.
Histology- research cited:
-red blood cell extravastion during relapse
-fibrin cuffs in venous hypertension
-iron laden macrophages
are ALL found in MS patients.

3. Main Course- Is CCSVI treatable?
measuring pressure before and after Liberation procedure is significantly changed.

4. Dessert- What are the effects of CCSVI treatment?

and for Today’s Special---Chronic fatigue as a symptom of CCSVI
(you have to love the Italians and their food analogies.)

Endothelial Health Program

August 26, 2009 at 7:51am

Here is the original program I wrote up for Jeff in 2008 and shared on ThisIsMS.  This was before we'd read Dr. Zamboni's research.  I sent it to Dr. John Cooke at Stanford University. Dr. Cooke's endothelial research and his book, The Cardiovascular Cure, were highly inspirational to me, and I wanted to get his thoughts on MS as a disease of endothelial dysfunction.  It is suggested for healthy vascular living for MS patients.  I knew that there was a connection between Jeff's hypercoagulated blood, high liver enzymes, c-reactive protein, petechiae and inflammation--and thought maybe the program might help others with MS.

There is a shortened version hosted on the CCSVI Alliance site-

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

For those who want to read more, here's the full paper:

Overwhelmed:

Reversing Endothelial Dysfunction 

By Joan Beal

I am not a doctor. Not even close. I took chemistry in high school, but I didnʼt like my teacher and chatted my way through labs. That was the end of my science career. I majored in music in college, and have spent my adult life pursuing the creative arts. Although math and science were never to be my forté, I do enjoy puzzles. I cannot walk away from an unfinished Sudoku, and much to my husbandʼs frustration, I always shout out “I know who did it!” before the first act of a mystery is completed. I guess Iʼm a “big picture” gal- I like to step back and find the connections between seemingly disparate things. You could also call me a “holistic” person, because I enjoy finding commonalities and patterns. Just like the nine digits in the Sudoku box.

Multiple Sclerosis is not a puzzle I was prepared for. By the time my husband finally went to the doctor, after a month of my pleading and cajoling, he was really sick. He was numb on his left side and his feet were burning. He went in for an MRI and the technician added the contrast dye to his veins. We knew he was in trouble.   When we went to meet with the neurologist, I noticed under the harsh fluorescent lights his skin had a jaundiced pallor. And what were those strange red dots up and down his shins? I hadnʼt seen him in shorts recently...what were those?

His neurologist said that had nothing to do with his illness. He had multiple sclerosis.  It was an autoimmune disease. My husbandʼs t- cells were attacking the myelin on his brain and spine, and he had 20 cerebral lesions to show for it. His blood labs had come back with some irregularities;  he had extremely high liver enzymes, high coagulation numbers and high c-reactive protein,  and once again the neuro said, “But that has nothing to do with his MS.” She recommended a disease modifying treatment- a daily shot called glatiramer acetate or Copaxone,  to retrain his t-cells- She also gave us a list of some nutritional supplements that she said “might help”, and sent us on our way.

I was incredulous. How could my healthy husband one day just wake up with an immune system in attack mode? And why werenʼt things like those spots (Iʼd later learn they were called petechiae) and his liver enzymes and jaundice related to this new illness?

So I went to work deciphering this new code. I read medical journals on line, and the more I read, the more questions I had. Because MS is incurable and no one really knows what causes it, it is open to more theories and less concrete evidence than almost any other disease. And it can be a variable illness, causing disability and paralysis in some, while remaining relatively benign in others. It has been almost two years since my husbandʼs diagnosis, and he is still stable and in remission from his first flare. We thank God everyday for his health and ability to carry on with his life.   Jeff has radically changed his diet, maintains a healthy weight through exercise, and takes supplements. He has also worked on lessening the stress in his life and finding ways to deal with neuropathic pain and fatigue, the nasty reminders of his disease. He is fortunate, and he is determined. But we realize that nothing is guaranteed.

I am not writing about curing MS. I do not believe I have the abilities or knowledge to cure anyone. I am only addressing ways to minimize the affects of disease and to help people feel better and perhaps remain in remission. For now, my husbandʼs MS is not progressing, but I do not know how to stop his MS for good. Right now, it appears that only God can do that. Let me be clear, I am also not about blaming people for becoming sick. There is a genetic component to each of these diseases that no one would ever ask for or bring upon themselves. The reasons why people develop specific diseases goes beyond my limited understanding. But there is hope and relief through lessening the external factors which contribute to disease.

24 million Americans suffer from some form of autoimmune disease. These diseases, in which the immune system appears to turn on the self, include diabetes, MS, rheumatoid arthritis, and lupus. The number of afflicted is growing at an astounding rate. I believe all autoimmune diseases are related. Inflammation, vascular problems, coagulation issues, neuropathic pain and suffering are common to each affliction, although the specific area that is affected is different. In MS, itʼs a breech in the blood brain barrier of the central nervous system. In rheumatoid arthritis, itʼs the joints. If we step back far enough from the names of individual diseases and all the various specialists who treat them, we can begin to see the big picture; and I believe it all begins inside each and every one of us with our blood.