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

Wednesday, December 29, 2010


Raise a glass!
December 29, 2010 at 5:16pm
This year, my New Year's  resolution is going to be to get enough
WATER!
H2O!
agua!

For those who might have missed the note on hypovolemia (loss of blood volume and dehydration) and CCSVI--read the last post on Flow and CCSVI.

Jeff and I have been consciously drinking a bit more water than we normally would, since Dr. Dake recommended hydration after angioplasty.   Nothing crazy, because too much isn't good either.  But we're getting closer to the recommended amount.

Here's a wonderful calculator to help you figure out how much daily water you need.  There are nine questions based on your weight, activity level, climate and more.

According to the calculator, with my body weight, amount of daily exercise and climate, I need 91 ounces of water a day.  That's a lot!  Jeff needs 109 ounces.  We're getting there.

So, will you join us in raising a glass of water to toast the new year?
To your health,  L'chaim!

Joan

Sunday, December 26, 2010

Blood Flow and CCSVI


December 26, 2010 at 2:12pm

We're having a relaxing time in the Sierra Nevada foothills with family.  Lots of good food and company.   Free time allows my mind to wander---and I'm thinking about blood flow and blood volume this week.  Perhaps its from watching the rainwater rush and wend its way down our mountain trails.  Here's what I've been thinking about.

For many women, pregnancy offers a time of blessed relief of MS symptoms.  This has lead to studies of hormones and MS, and a clinical trial of estrogen in MS patients.   But looking at pregnancy from the CCSVI/vascular paradigm, what else can we learn?  

When women are pregnant, their blood volume increases dramatically.  This sends blood pumping throughout the body.

Perhaps the most striking maternal physiologic alteration occurring during pregnancy is the increase in the blood volume. The magnitude of the increases varies according to the size of woman, the number of pregnancies she has had, the number of infants she has delivered, and whether there is one or multiple fetuses.The increases in blood volume progress until term;the average increase in volume at term is 45-50%. The increase is needed for extra blood flow to the uterus, extra metabolic needs of fetus, and increased perfusion of others organs, especially kidneys. Extra volume also compensate for maternal blood loss during delivery. 
link

After delivery is the time during which many women report having exacerbations in their MS, or a return of MS symptoms.  Yes, hormone levels are fluctuating, but so are blood volume levels.  Pondering this fact has lead me to do more reading on blood volume, and I am finding some interesting things to consider.

Hypovolemia means low blood volume.  This condition can be very serious and happens due to blood loss from injury, but it can also be mild and happens in a body that is dehydrated or inactive, or not functioning well. Hypovolemia happens often to the elderly and disabled.   

Low blood volume can cause orthostatic hypotension. This is when there isn't enough blood getting to the brain when a person changes position, from lying down to upright.  This can lead to dizziness, confusion and falls, and often happens in the elderly.  But it can happen in people with MS, too.  Orthostatic hypotension is well-documented in MS and has been a mystery for researchers.  

Thinking about blood volume in terms of CCSVI treatment and restenosis has been very interesting to me.   If angioplasty is returning good, open routes of flow, but the body is not able to compensate by providing adequate blood volume, then these opened vessels will not have the necessary pressure to remain opened.  And the areas of prior stenosis might re-collapse, just like an old garden hose with low flow.

I hope to bring this avenue of discussion to the doctors.  Perhaps aftercare needs to include additional hydration, salt intake, maybe even intravenous fluids--all to keep blood levels adequate.  Inactivity and remaining in the supine position increase hypovolemia--therefore,  movement, exercise and upright activities would encourage blood flow and blood volume.  Something to think about as we move forward with CCSVI research in 2011.

All this talk about dehydration is making me thirsty!  Time for some fresh, mountain water and a walk in the pine trees with Jeff and our dog, Angel.  

With wishes for good flow in the New Year!
Joan 

Thursday, December 16, 2010

Ischemia, MMPs and Myelin loss




December 16, 2010 at 10:47am
Continuing the exploration of the "auto-immune" reaction of the body in situations of slow blood flow, oxidative stress and lowered oxygen levels in the brain--we learn that  myelin breakdown is not unique to MS.  It happens in dementia, Alzheimer's, ischemic stroke, carbon monoxide poisoning and cerebrovascular disease.   

There is recent research on myelin loss in ischemia. 
This paper studies how matrix metalloproteinases (MMPs) are involved in this process--

MMPs:   A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues.   Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis.

In MS---
Multiple MMPs are elevated in human neurologic diseases.  In the setting of MS, it has been shown that serum MMP-9 levels are increased in patients with clinically isolated syndrome (CIS) compared with normal control subjects and are further elevated in patients with clinically definite MS (CDMS) compared with patients with CIS.   In addition, serum MMP levels increase markedly between onset of neurologic symptoms and development of CDMS, whereas levels remain unchanged in subjects with CIS who do not develop CDMS. Other studies have documented elevations of MMP-9 and other MMPs in the serum, CSF, and brain of patients with MS compared with controls.

In Ischemia--

Divergent role for MMP-2 in myelin breakdown and oligodendrocyte death following transient global ischemia.
Walker EJ, Rosenberg GA.
Departments of Neurology, Neurosciences, and Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

Abstract
Transient global ischemia causes delayed white matter injury to the brain with oligodendrocyte (OLG) death and myelin breakdown. There is increasing evidence that hypoxia may be involved in several diseases of the white matter, including multiple sclerosis, vascular dementia, and ischemia.

Matrix metalloproteinases (MMPs) are increased in rat and mouse models of hypoxic hypoperfusion and have been associated with OLG death. However, whether the MMPs act on myelin or OLGs remains unresolved. We hypothesized that delayed expression of MMPs caused OLG death and myelin breakdown. To test the hypothesis, adult mice underwent hypoxic hypoperfusion with transient bilateral occlusion of the carotid arteries. After 3 days of reperfusion, ischemic white matter had increased reactivity of astrocytes and microglia, MMP-2 localization in astrocytes, and increased protein expression and activity of MMP-2. In addition, there was a significant loss of myelin basic protein (MBP) by Western blot and caspase-3- mediated OLG death. Treatment with the broad-spectrum MMP inhibitor, BB-94, significantly decreased astrocyte reactivity and MMP-2 activity. More importantly, it reduced MBP breakdown. However, MMP inhibition had no effect on OLG loss. Our results implicate MMPs released by reactive astrocytes in delayed myelin degradation, while OLG death occurs by an MMP-independent mechanism. We propose that MMP-mediated myelin loss is important in hypoxic injury to the white matter.



Tuesday, December 7, 2010


 Myelin

December 7, 2010 at 12:01pm

Myelin, the insulating sheath around all of our nerves,  is damaged by an auto-immune reaction in stroke, spinal cord injury, neurovascular disease, dementia, and carbon monoxide poisoning.  
This is a fact.
MS is not unique.  The immune system has the same reaction in situations where there is oxidative stress.
Here's some of the research: 

Long term immunologic consequences of experimental stroke and mucosal tolerance
Background
An inflammatory insult following middle cerebral artery occlusion (MCAO) is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP)


The "autoimmune" reaction of t-cells in spinal cord injury ( SCI) 
Previously, we demonstrated that CNS-reactive T cells are activated in SCI [29,30]. Other groups have shown activation of myelin basic protein (MBP)-reactive T cells after experimental and clinical nerve trauma [31,32]. Clinical studies that show increased frequencies of MBP-reactive T cells in SCI and stroke patients provide further evidence of an association between CNS trauma and the activation of CNS-autoreactive T cells.


Myelin basic protein antigens in carbon monoxide poisoning 
We hypothesized that acute CO-mediated oxidative stress causes alterations in MBP and that immune responses to the modified protein precipitate delayed neurological dysfunction.

These findings provide insight into the pathophysiology of brain injury due to CO poisoning. Biochemical and immunological studies indicate that MBP undergoes charge and antigenic alterations. A causal relationship between lipid peroxidation and MBP modifications is supported by colocalization of MDA-adducts.


http://www.pnas.org/content/101/37/13660.full 


In every single one of these instances, antigens (attackers) to myelin basic protein (MBP reactive t-cells) go after the myelin and destroy it. This is considered an "auto-immune" response.
But in stroke, vascular disease, spinal injury, dementia and CO poisoning, the real culprit, ischemia (injury due to low oxygen) and a break in the blood brain barrier is known.  

-No one calls a stroke an "auto immune disease."

Saturday, December 4, 2010

The autoimmune response in stroke



December 4, 2010 at 9:06pm

We are often told that MS is an autoimmune disease, as evidenced by the seemingly unprovoked immune activity against myelin.  But what we are not told is that this same process happens in the brains of those who have strokes and cerebrovascular disease.

In fact, in stroke survivors there is actual more immune response to myelin than there is in people with MS. 

A new paper from 2010--- Post-ischemic immune response to stroke
Here is a link to the full paper.


"To date, there has been little interest in exploring the possibility that autoimmune responses to brain antigens might affect outcome from stroke. There are, however, studies that document the fact immune responses to brain antigens do occur following stroke.

For instance, lymphocytes from stroke survivors show more activity against MBP than the lymphocytes from patients with multiple sclerosis.18,19 

In addition, myelin-reactive T cells are found in higher numbers among patients with cerebrovascular disease.20 These data thus provide evidence that a cellular immune response to brain antigens occurs following stroke.

Furthermore, there are increased titers of antibodies to brain antigens, including neurofilaments and portions of N-methyl-D-aspartate receptor, following stroke, indicating that there is also the development of a humoral response to these antigens.21,22 The immune response to CNS antigens after stroke is likely just an epiphenomena of stroke given that cerebral ischemic injury to the blood–brain barrier allows for the systemic immune system to come into contact with the antigens that are normally sequestered from it. Nonetheless, it is possible that this response leads to "collateral damage"; whether these immune responses affect outcome from stroke is largely an unanswered question."



---Why has there been "little interest" in studying the autoimmune response of the body to stroke?   Why have we been told that myelin antigens are found only in the cerebral spinal fluid of those with MS?   These antigens are found in higher levels following a stroke.

"Furthermore, although immunosuppressive strategies might decrease the risk of developing a Th1 (and possibly Th17?) response after stroke, such interventions might increase the risk infection, a risk that is already high in the poststroke period. On the other hand, strategies to enhance the immune response to prevent infection in the poststroke period might increase the risk of developing a detrimental Th1 (and possibly Th17?) immune response to brain, and, as already discussed, these responses might predispose to worse functional outcome from stroke. It is also in the realm of possibility that the development of immune responses to brain antigens, be they cellular or humoral, may have longer-lasting effects. For instance, it is appreciated that stroke is a potent risk factor for dementia, and it could be that autoimmune responses to brain contribute to cognitive decline and even the progression of white matter disease.42 Future clinical studies will need to address the contribution of the postischemic immune response to these long-term outcomes.

In summary, the nature of the postischemic immune response affects outcome from stroke (Figure). Modulation of this response may be a viable approach to improving outcome in stroke, but there are potential dangers associated with immunomodulation. A more complete understanding of the endogenous immune response following stroke is needed to safely manipulate this response in the poststroke period."


Sadly, we know all too well about the potential dangers of brain viruses (like PML) associated with immunomodulation.  Interesting that it is considered too dangerous to give these treatments to those with stroke....but for those with MS, it is an "acceptable risk."  Perhaps we need to understand the disease mechanism of MS first.

Joan


MS as a Cerebrovascular Disease

December 4, 2010 at 5:42pm

Since the beginning of my journey with Jeff's MS diagnosis in 2007, I've been told by neurologists that MS is an auto-immune disease and this can be measured by Myelin Basic Protein (MBP) autoreactive t-cells found in cerebral spinal fluid (CSF) , and that this is exclusive to MS, and this is part of the target for immuno-modulating therapies.  

But what if these MBP auto-reactive T-cells are NOT really exclusive to MS?   Guess what?  They're not.

Here is a study where the CSF of patients with cerebrovascular disease is tested. And those with MS and CVD have the same range of MBP reactive T-cells in the CSF. This leads the researchers to posit that this immune reaction is secondary to damage in the CNS. Which makes me wonder....is the CSF of stroke patients and those with hypoxia or ischemic events regularly tested? And if so, are these people told they have an immune system disease? Why has the research of MS as a cerebrovascular disease been so fraught with controversy? 

Myelin antigen reactive T cells in cerebrovascular diseases
 W.Z.WANG,T.OLSSON,V.KOSTULAS,B.HOJEBERG,H.P.EKRE&H.LINK
Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden 

INTRODUCTION In acute ischaemic cerebrovascular diseases (CVD), mononuclear cells appear in the brain parenchyma within 1-2 days and increase in number over the ensuing 5-30 days[1].Also in cerebrospinal fluid (CSF), elevated numbers of mononuclear cells may be detected. These cells are considered to mainly represent monocytes-macrophages, but there are no detailed studies on their lineage with,e.g.,antibodies to different cell surface markers. Oligoclonal IgG bands are present in the CSF while missing in corresponding serum, in about 10% of patients with CVD [2,3].A local B cell response directed to neurotropic viruses,as in patients with multiple sclerosis, has been reported in those patients with CVD who displayed oligoclonal IgG bands in CSF [4].Taken together,these observations indicate that patients with acute CVD may display an intrathecal immune response. 

The strong increases in numbers of MBP, MBP peptide and PLP reactive T cells in blood, and of MBP reactive T cells in CSF, which we here report in our patients with Cerebro Vascular Disease, are in the same range as we have previously observed in MS [10,11].Thus, both diseases are accompanied by an expanded pool of myelin autoreactive T cells and they may well be secondary to damage to the central nervous system.

Here is the full paper in PDF form.

It's really dense, but it is worth the read.

If these autoreactive t-cells are found in people that have strokes or cerebrovascular disease, and are NOT exclusive to MS,  how on God's green earth can we say that MS is auto-immune?

It's not.  I believe MS is a disease of the vascular system which creates a secondary reaction by the immune system.  I believe Dr. Zamboni discovered the engine in MS---and it is CCSVI.  

more ahead,
Joan

Wednesday, December 1, 2010


Press Release from Fondazione Hilarescere

December 1, 2010 at 1:40pm

Dr. Zamboni has stepped down as lead investigator from the Italian MS Society's (AISM) proposed epidemiological study of CCSVI.  He has stated many times that this group is not following his methodology of testing.

Here is a new press release on this topic---


Who is Responsible for the current problems?

November 20, 2010
The Hilarescere Foundation and its scientific committee chaired by Prof. Paolo Zamboni have always clearly warned that the diagnosis and therapy of CCSVI cannot be improvised. The papers published have underscored the extreme importance of the learning curve required to manage both aspects in an ethically sound manner. 

This very seriousness that must be guaranteed to patients both scientifically and in terms of the methodology adopted has led Prof. Zamboni and Dr. Salvi to make painful choices, among which the decision to resign from the FISM/AISM study after having devoted time to it and made a series of proposals that have gone unheeded because said study has proven to be inadequate to achieve the set goal. It is a study that is all but a comparison with the "Zamboni method", since its basic principles have been neglected. All too often and misleadingly the FISM/AISM epidemiological study is referred to as a study promoted by Prof. Zamboni. However, for the aforementioned reasons he has clearly and consistently kept a due distance from it. 

Great concern has been clearly expressed in the Foundation's website and it has been stressed in every interview that CCSVI interventions are spreading and that these do not follow approved protocols that ethically ensure patient safety. The Foundation rejects clinical activities that prey on the desperation of patients to generate forms of medical tourism that offer absolutely no guarantee of quality to patients. Unfortunately, it is obvious that all this leads to extremely painful situations. We cannot offend people's suffering by exploiting it. It is absolutely shameful. This is still the time of studies and research; diagnosis and treatment must be managed within this framework with all the necessary guarantees. When carried out correctly, the treatment is mini-invasive and has an excellent level of safety as proven by many international experiences and articles.

Anything outside of this framework is wrong. But it must also serve as a stern warning for all those who do not heed the legitimate expectations of patients frustrating them with slow, all too slow studies that are blatantly inadequate. 



 Press Office
Francesca Rossini - Laboratorio delle Parole
Tel. 051-273861 – mobile 331-6752354 and 335-5411331  notizie@laboratoriodelleparole.it

Friday, November 19, 2010

Dr. Michael Dake on CCSVI


November 19, 2010 at 11:26am

from the V-Aware November issue.

Dr. Dake is the cardio-thoracic specialist I contacted with Dr. Zamboni's research in January 2009.  He was our local doctor at Stanford University.  The damage that Dr. Dake saw in Jeff's brain on MRI, and the damage he found in Jeff's jugular veins on MRV made sense to him.  As a vascular doctor, he understands the correlation of venous drainage and disease.

Important Points to note in this article:
1. CCSVI resembles a known venous disease, superior vena cava syndrome.  Symptoms related to this condition are similar to those in CCSVI.  Relieving CCSVI via angioplasty produces similar results in angioplasty for superior vena cava occlusion.

2. CCSVI might account for the low flow states (hypoperfusion) found in pwMS.

3. Slowed blood flow changes the endothelial layer of blood vessels, allowing for a break in the blood brain barrier and immune cell penetration 

4. Inflammation created by disturbed blood flow in CCSVI continues to damage the vein lining.  Thus, CCSVI will progress with age of patient and length of disease.
++++++++++++++++++++++

Here is Dr. Dake on CCSVI---


Evidence presented recently in the medical literature proposes that patients with multiple sclerosis (MS) have a coexisting high frequency of obstruction to veins that drain the brain and spinal cord.

These data suggest that MS is associated with blockages in veins located in the neck or chest that alter cerebral venous hemodynamics, causing alterations in venous pressure and flow patterns. This venous obstruction is called chronic cerebrospinal venous insufficiency (CCSVI).

Wednesday, November 10, 2010


Dr. Zamboni's published letter in response to the Doepp study

November 10, 2010 at 2:00pm

Published in the Annals of Neurology-

Regarding ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis. Intraluminal Jugular Septation’’ Paolo Zamboni, MD

I read with interest the article titled ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis’’ by Doepp and coworkers.1   Contrary to their conclusions, I believe that the authors’ results are a further validation of venous flow irregularities in multiple sclerosis (MS) patients.

One of the major regulators of cerebral venous outflow is posture, due to the gravitational gradient between the cerebral parenchymal veins and the base of the neck (␣30mmHg).2   The authors demonstrate a much larger change in blood flow volume in normal subjects compared to MS patients when the subjects go from a supine to an upright position. They find a change of 128ml/min and 56ml/min for the right and left sides, respectively, for MS patients. But they find a much larger change of 266ml/min and 105ml/min for their normal subjects. This result actually suggests the presence of chronic cerebrospinal venous insufficiency (CCSVI). Possible causes include intra-luminal septum, membrane, and immobile valve affecting the hydrostatic pressure gradient in the upright position. The presence of such blockages in the extracranial and extravertebral cerebral veins has been proven also by using catheter venography, the unquestionable gold standard in medicine.3,4

There was a trend toward significance (0.06) when comparing the mean global cerebral blood flow (CBF) in MS patients with that in controls. However, the level of significance is under- estimated by the low control sample, 20 versus 56 patients. The reduction in CBF in MS, meaning in practical terms stasis, might become significant by simply increasing the control sample.


Tuesday, October 19, 2010


Two new papers from Dr. Chung

October 19, 2010 at 8:11am

For those who have been following this page for a bit, you may remember my references to Dr. Chung in Taiwan who has been studying the jugular veins in relationship to transient global amnesia (TGA) and other neurological disorders.  

Dr. Chung found that in those with internal jugular vein valve problems, or valves that didn't close properly,  there was reflux of blood in their jugulars when they used a "valsalva maneuver"--that means pushing air up against a closed airway, or straining.  The valves opened and this sent blood back up into the brain, and created temporary ischemic (low oxygen) events.  Dr. Chung postulated this is what causes temporary amnesia.   Some activities that create valsalva manuever are coughing, straining, opening up plugged up ears, lifting, and stressful responses. 

Dr. Chung has two new papers out on aging and the jugular veins.  I thought these were important to discuss after the ECTRIMS conference-- in which a researcher from the American University in Beirut stated that CCSVI could not be important in MS, because he only found CCSVI in older or more progressed MS patients.  He and his team found CCSVI in 92% of what he called "late MS" patients---those who had MS 10 years or more.  To anyone who knows MS, 10 years is not "late MS." 

I know many people who have had MS 30 years and more, but let's get on with what Dr. Chung discovered.  Dr. Chung is now measuring venous return in the jugular veins of the "healthy"  elderly.

Wednesday, October 6, 2010

Snake oil?

October 6, 2010 at 8:33am

We're seeing many neurologists and MS specialists responding to CCSVI research reflexively.  The common attack is
"This CCSVI angioplasty is no different than bee stings!  It is simply snake oil."

I think it's important for patients and caregivers to understand history when trying to respond to this claim.  You know me and history (Rindfliesch, Putnam, Swank)  I LOVE history.

The term snake oil comes from the late 19th and early 20th century in the US, when you could actually purchase real snake oil to help your health.  Snake oil was claimed to have many healing properties and was sold by traveling salesmen, who put on shows with feverish sales pitches, hysterical claims, and miraculous healings which rivaled religious revival meetings.  But these products didn't really do much for one's health, and soon the public caught on to the quackery and the term snake oil became associated with false medical claims.

When Dr. Zamboni discovered Chronic Cerebrospinal Venous Insufficiency (CCSVI)  he actually discovered a new disease.  
Other international researchers, like Dr. Chung in Taiwan, were noting how internal jugular vein valve incompetence (IJVVI) affected by valsalva manuevers was related to transient global amnesia and hypoxic events.   Dr. Zamboni, while utilizing ultrasound equipment and scanning the neck of an MS patient-- noted venous reflux.  Something that was not normal, and had not been detected before--reflux in the absence of valsalva, independent of body position.   He spent the next five years conducting blinded doppler studies, writing research, bringing other doctors on board and learning all he could about this disease mechanism. He tried to address the truncular venous malformations he found in MS patients' veins with angioplasty.  It helped his patients.  And then he published his research, and I read it--along with patients, caretakers and doctors around the globe.

Venoplasty to relieve CCSVI is not a product.  It is not sold as a cure.  
It is not quackery.  Angioplasty is used to relieve venous congestion and stenosis in many known diseases, including Budd-Chiari, heart disease, kidney disease, and jugular insufficiency in dialysis patients. Sometimes, the organ with venous congestion is too damaged to have much healing after venoplasty (as in Budd Chiari, when a liver transplant is necessary.)  But, if caught early, treated venous malformations can lead to symptom relief and stop disease progression in the affected organ.

Thursday, September 30, 2010

To sleep, perchance to oxygenate


September 30, 2010 at 9:12am

One of the most profound, although seemingly minor, changes for my husband, now 18 months since his venoplasty for jugular and dural sinus stenosis--has been the return of dreaming.  After his procedure, he would wake up in the morning and recount for me his vivid dream from the night before.  It was so strange to us...he realized that for several years, he couldn't remember his dreams. 

He was now sleeping soundly, no longer spasming or waking up gasping for air.  And in this deep sleep, his dreams had returned. 

When I went to the CCSVI international symposium in Bologna last year, Dr. Salvi got up and spoke about the changes in his patients after angioplasty.  And one of the global differences his patients noted was deeper, more restful sleep, and the return of dreams.  He had a wonderful illustration that came on the screen during his power-point-- a cartoon of a person deeply sleeping, smiling, with a colorful dream bubble over their head.  I almost leapt out of my seat.  "That's happened to Jeff!"  I whisper/exclaimed to Dr. Dake, seated on my left.  "He's dreaming again."
Now, I read time and time again from patients and their caregivers about the return of deep, restful sleep and dreaming.  I realize that dreaming might not seem important in the grand scheme of recovery from MS....but I believe it is.  I believe it is proof of a brain that is healing.  A brain that does not have REM (rapid eye movement) sleep, does not dream.   There is research that links dreams, REM sleep and oxygenation.

"REM sleep time is strongly reduced by hypoxic and increased by hyperoxic atmosphere, in accordance with the existence of an O2 diffusion limitation. Any pathological decrease in arterial PO2 and/or O2 delivery creates a specific risk in REM sleep."

______________________________________________________

During REM sleep, there is an increase in blood flow to the limbic system and the brain stem, with circulation to these structures decreasing during non-REM sleep.  As brain activity increases during REM sleep, the cerebral requirements for glucose and oxygen both increase....
Fundamentals of Sleep Technology--Butkov, Lee-Choing  2007

_______________________________________________________


Tuesday, September 28, 2010


Harvard professor visits Dr. Zamboni in Italy--
The More Iron, The More Severe the Disease

September 28, 2010 at 7:30am

From the Italian press---Professor Rohit Bakshi of Harvard University came to Ferrara University to discuss how his decade long study of iron deposition in MS brains has now intertwined with Dr. Zamboni's research:

Here is a Google translation of the press release:

Too much iron, more severe disease
New Ferrara - September 24, 2010 page 19 Section: Commentary

"It 's another piece of the puzzle that is made," says the researcher Paolo Zamboni.To place a new tile on the mosaic of research on multiple sclerosis was yesterday Professor Rohit Bakshi, Harvard University, came to Ferrara to explain the outcome of a decade of study during which he analyzed the role of iron as a contributory cause of the disease. His line of research was independent from that beaten by Ferrara Zamboni, but its conclusions have been come to intertwine with the results of tests carried out by the researcher and neurologist Bologna Ferrara Fabrizio Salvi on Ccsvi, which have established a hypothetical link between stenosis of the venous vessels in the brain iron accumulation and the onset of multiple sclerosis.

"The current therapies - said the scientist in the main hall of the university - are not effective in stopping the neurodegeneration. Bakshi was able, with a common magnetic resonance imaging to measure the actual concentration of iron in the brain, an operation in the past only run during the autopsy. Plaques and iron stores were associated, but especially "the greater the presence of iron - Bakshi said - the more you exacerbate the effects of the disease." Studies have revealed that the abnormal presence of iron affects the white matter and gray and tends to cause atrophy of certain areas of the brain.


Please note that Dr. Bakshi is confirming that current pharmaceuticals DO NOT stop the neurodegeneration of the MS disease process.

Here is an article on Dr. Bakshi's studies of MS and iron deposition from 2003:






Monday, September 6, 2010


Venous Malformations

September 6, 2010 at 7:46pm

Dr. Zamboni--the vascular researcher who discovered CCSVI and has spent years developing a diagnostic and treatment protocol), has found many different types of venous malformations in those with MS.    It is very important to understand that CCSVI can be caused by several issues.  The doctors researching CCSVI are finding many defects.  And each individual has unique issues.

Dr. Zamboni has described CCSVI as created by truncular venous malformations, mostly "intraluminal defects", meaning problems inside the walls of the jugular and azygos veins.  

The types of malformations found by Dr. Zamboni and included in his published research are:
  • Annulus --refers to significant circumferential stenosis of the whole venous wall; 
  • Septum/valve malformation --refers to anomalous valve apparatuscausing significant flow obstacles at the level of the junction of the IJVs with the brachiocephalic/anonymous trunk; 
  • Hypoplasia --refers to under-developed long venous segments; 
  • Twisting-- refers to severe stenosies in consequence of a twisted venous segment; 
  • Membranous obstruction--  (web) refers to a membrane almost occluding a vein; 
  • Agenesis-- refers to the complete anatomical absence of a venous segment. 
Annulus, septum, membranous obstruction, hypoplasia and agenesis are truncular malformations previously described in other venous segments (cava, iliac, deep veins of the lower limbs).13 In Figure 7 there are some examples of venous stenosing lesions morphologically quite similar to those described in the IJVs/AZ in course of CCSVI. In contrast, twisting of the AZ is a truncular malformation never been described so far (Figure 8). In Table 1the distribution of the different truncular lesions in the extracranial and extravertebral cerebrospinal veins aregiven, and the more typical malformations are shown in the figures.

Here is the full paper:

This research is very important to understand, because there is no one size-fits all approach to treating CCSVI.  And the IRs are working hard to develop a standard protocol.  That's what the convening meetings and conferences are all about.    

It is very understandable to want to believe that your doctor knows everything about CCSVI....it's a natural response, especially before undergoing a medical treatment, and perhaps paying for it.    But we need to be honest and upfront.  We are at the beginning stages.  Read Dr. Zamboni's paper, and note that there are many underlying issues creating Chronic Cerebrospinal Venous Insufficiency.  It's different in everyone.

Joan




Saturday, August 28, 2010


Treating Neurodegenerative Diseases--a new approach

August 28, 2010 at 5:27pm

Here's a wonderful piece on a new way of treating brain diseases---a preventative/diagnostic approach rather than a search for a specific pharmaceutical cure--although this piece focuses on Alzheimer’s, I believe the logic behind preventative measures for brain health apply to all neurological diseases.  

"While the search for a pharmaceutical cure plays front and center, quietly in the background countless neuroscientists worldwide have concluded that Alzheimer's, as well as memory decline and other age-related dementias are actually slow-developing chronic diseases, like heart disease and cancer, partly dependent on lifestyle and other treatable diseases.

De la Torre, for example, is convinced that Alzheimer's and dementia are particularly tied to cardiovascular factors, notably, constricted blood flow to brain cells, and that midlife screening to detect and correct such heart-related deficits would help prevent much brain degeneration during aging. 

The special journal issue produced by de la Torre, called "Basics of Alzheimer's Disease Prevention," also included new research on the relationship between Alzheimer's and diabetes, high blood pressure, triglycerides, cholesterol and cholesterol- lowering drugs, (statins), a Mediterranean diet, exercise, fish oil, B vitamins and antioxidants.



Friday, August 27, 2010

Blood Flow and white matter lesions


August 27, 2010 at 10:58pm

The idea that MS is related to hypoperfusion, or slowed blood flow, is not new.
Here's is Dr. Juurlink's proposal from 12 years ago--


Hypoperfusion in the MS brain explained:

"Hypo"; meaning under or sub-par and "perfusion"- meaning the delivery of blood to the capillary bed.

In MS brains, there is a below normal delivery of blood into brain tissue.  Neurologists have never given a good explanation as to why this happens.  Here's a great paper that looks at this phenomena.

(terms to know -NAWM  is normal appearing white matter, or healthy myelin.  
Ischemia means a lack of oxygen or hypoxia.)


"Accumulating evidence indicates that there is a decreased perfusion throughout the NAWM (normal appearing white matter) in patients with MS. It occurs in both relapsing–remitting and primary progressive MS, strongly suggesting that it represents an integral part of the disease process. Ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions). There appears to be a relationship between reduced white matter perfusion and cognitive dysfunction in patients with MS.

Ge et al (2005) interpreted the hypoperfusion in NAWM as a vasculopathy in the context of the perivascular inflammations that occur in focal MS lesions. However, although inflammatory infiltrates in MS are typically located around small- or medium-sized veins (Adams, 1989) and in the perivascular spaces surrounding arterioles (Gay, 2006; Gay et al, 1997), microvessel thrombosis is only exceptionally being observed within these lesions (Aboul-Enein and Lassmann, 2005; Wakefield et al, 1994)."

So, this paper comes pretty close to saying that this slowed perfusion and white matter lesions could be created by slowed blood flow and a lack of oxygen in the brain.  This is exactly what Dr. Juurlink was proposing.

Here's a study that shows that white matter lesions in rats were formed when cerebral hypoperfusion was created in their brains.

"Cerebrovascular white matter lesions represent an age-related neurodegenerative condition that appears as a hyperintense signal on magnetic resonance images. These lesions are frequently observed in aging, hypertension and cerebrovascular disease, and are responsible for cognitive decline and gait disorders in the elderly population. In humans, cerebrovascular white matter lesions are accompanied by apoptosis of oligodendroglia, and have been thought to be caused by chronic cerebral ischemia. In the present study, we tested whether chronic cerebral hypoperfusion induces white matter lesions and apoptosis of oligodendroglia in the rat. Doppler flow meter analysis revealed an immediate reduction of cerebral blood flow ranging from 30% to 40% of that before operation; this remained at 52–64% between 7 and 30 days after operation. Transferrin-immunoreactive oligodendroglia decreased in number and the myelin became degenerated in the medial corpus callosum at 7 days and thereafter."

There is NO NEED for any auto- immune system activation to create white matter lesions or myelin destruction.  NONE.  Dr. Juurlink knew this.  Many doctors who study stroke know this.   All that is needed is slowed blood flow.  

Did you know that most elderly people have white matter lesions in their brains?  We don't see them, because they are not routinely given MRIs.  But it's a known fact that the aging brain has slower perfusion, slower circulation and decreased blood flow, resulting in less oxygenation.  Why has the correlation of circulation in MS and other neurodegenerative diseases been ignored?  This chaps my hide.

Here's a paper where they created white matter lesions in rats' brains by clamping their carotid arteries closed.  Remember, the arteries bring the blood in, the veins take it out.  Slowed perfusion can be created by slowed delivery of blood, or slowed removal.  It works both ways.

Notice in this study, the first areas of white matter lesions were on the optic nerve after only THREE DAYS of ligation.  This mimics the order of problems we see in pwMS. RRMS patients typically present with vision problems first and show white matter lesions.

"Cerebral white matter (WM) lesions are observed frequently in human ischemic cerebrovascular disease and have been thought to contribute to cognitive impairment. This type of lesion can be experimentally induced in rat brains under chronic cerebral hypoperfusion by the permanent occlusion of both common carotid arteries. However, it remains uncertain whether chronic ischemia can damage both the gray and white matter, and whether it can induce demyelination with or without axonal damage. Therefore, we examined axonal damage using immunohistochemistry for the amyloid β/A4 precursor protein (APP), chromogranin A (CgA) and demyelination using immunohistochemistry for the encephalitogenic peptide (EP) in this model. Severe WM lesions such as vacuolation and the loss of nerve fibers appeared in the optic nerve and optic tract after 3 days of ligation, and less intense changes were observed in the corpus callosum, internal capsule, and fiber bundles of the caudoputamen after 7 days with Klüver–Barrera and Bielschowsky staining. These WM lesions persisted even after 30 days. The APP, CgA, and EP-immunopositive fibers increased in number from 1 to 30 days after the ligation in the following WM regions: the optic nerve, optic tract, corpus callosum, internal capsule, and fiber bundles of the caudoputamen. "

When neurologists say that Dr. Zamboni's research is not based on fact....give them a lecture on hypoperfusion and white matter lesions.  This is science, this is fact, this is real.

Joan

Monday, August 16, 2010

Breathe


August 16, 2010 at 11:32am

Lots of people have commented on how the stresses of life have caused MS exacerbations and flare ups for them.  My husband Jeff has noted this; he'd be in a stressful situation at work, and his left foot would tingle and then go numb.  Many of you have written about how stress brought about your MS diagnosis.  So, what's up with this?  How does it fit in with what we know about CCSVI?  I've got a theory I wanted to share it with you, in case it might help someone.  It's helped Jeff a lot.

There's new research out about internal jugular vein valve incompetence and people who have transient global amnesia. This is different than CCSVI, but related. These people have been shown to have reflux of blood in their jugular veins, which creates an ischemic (low oxygen) event in the brain.  

"A high prevalence of internal jugular vein (IJV) valve insufficiency appears to be present in patients with a clinical diagnosis of transient global amnesia (TGA), suggesting that venous congestion in areas of the brain associated with memory may partially explain episodes of benign TGA. Claudia Cejas, MD, and colleagues at the Institute for Neurological Research, FLENI, in Buenos Aires, Argentina, found that IJV valve insufficiency was present on at least 1 side in almost 80% of patients with TGA, compared with only 25% of control subjects. There was also a trend toward a predominance of right-sided IJV valve insufficiency."

There are many papers about the connection of venous return and TGA.

The researchers tested the reflux in the jugular veins using doppler ultrasound and having the patients do a "valsalva maneuver".  A valsalva manuever is when you force air up from your lungs, but keep your mouth and nose closed.  Some people do this to relieve pressure in the ears when flying, some people do this when breath holding, or straining with lifting heavy objects,  having sex or going to the bathroom.  This is not something you want to do with any regularity.  Many people do this when they are under stress, and do not even realize it!  Valsalva manuevers create reflux of blood.

(It's important to note that Dr. Zamboni found a reflux of blood from blocked jugulars in people with  CCSVI---he did NOT use valsalva manuever to see refluxing blood.  That means pwMS are at a disadvantage, because your blood  could be refluxing without performing these breath holding manuevers.)
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Another link to transient global amnesia is severe emotional stress.  Read the next case history.

A healthy 61-year-old man was brought to the emergency department by his wife after she noticed that he was forgetful of the previous evening's activities and was unable to form new memories during the subsequent day. The patient repeated the same questions and could not remember events minutes after their occurrence. There was no history of intoxication, drug use, head trauma, or obvious physical or emotional stress. He had no medical history other than seasonal allergies and took no regular medications. The physical and neurologic examinations were otherwise normal.

On hospital day 2, the patient had a normal mental status and was able to form anterograde memories. He remembered that just before his amnestic episode, he had fallen asleep and dreamed about his son joining the Marines and being killed in combat in Iraq. He vividly saw his son in a casket draped with an American flag. At this point, he screamed and woke up with amnesia. The patient was especially distraught because his son was contemplating joining the military at the time the dream occurred. The episode of transient global amnesia was considered to be due to the stress of the dream, and the patient was discharged."

Stress can create this retrograde blood flow.  It can be so severe, it can starve the brain of oxygen.

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So, what can pwMS do to prevent this exacerbation of reflux?  How can we avoid this kind of emotional turmoil, and keep blood flowing back to the heart?  

I believe the answer begins with our breathing.

When we are stressed, we tend to hold our breath, use valsalva manuever, or breathe too shallowly.

Try this experiment.
Breathe on your fingers like you just burned your hand.  Make your breath cool, and do it quickly.
This is called "clavicular breathing", it is from the top of your lungs, and is shallow.  
Your throat is tight.  This is what I call "stressed out breathing."

Now, breathe on your hands like you are outdoors at winter time and want to warm your fingers.  
Make your breath warm, do this slowly.
This is called "diaphragmatic breathing." It comes from deep in your belly, below your lungs.  Your throat is open.

This low, warm breath is what we want to find when we start to get stressed.  This type of breathing is practiced in yoga and the ancient traditions of meditation and breath counting.  It is this low and slow,  conscious breath that can slow our heart rate, open our blood vessels, relieve valsalva pressure, calm our spirits.  

Take a deep, low breath.  Open your mouth, open your throat.   Lower your shoulders, fill your lungs. Let your belly release.
Now, let this breath slowly escape thru your nose.  Think "warm air" at the back of your throat.
This is conscious breathing.

Feel the sense of calm.  Try to do this when the world gets too noisy or insane.
I do this is the car during traffic jams, when LA traffic is driving me crazy.
Jeff does it when work becomes overwhelming, and his feet don't tingle any more.

I hope this connection of jugular vein reflux, valsalva manuever and stress makes some sense to you, and that learning how to counteract life's stresses and strains with your own breath will help you--

don't forget to breathe,
Joan