Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of the endothelium and heart-brain connection. 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 auto-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. 



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