Blood flow matters

If you ever wondered whether blood flow was important to brain health, all you would have to do is read about three new MS drug trials announced in the past month.

All three of these compounds have been shown in EAE mouse trials to reduce symptoms, reduce inflammation and slow progression of MS.  All three have been touted as "neuroprotective."

But all three of these medications have a very similar known method of action (MOA) in humans.  All have been used for years for cardiovascular and stroke patients.  All have an effect on the endothelium and release nitric oxide and lower blood pressure.  All three deal with "hypoperfusion", or reduced blood flow.

They all widen blood vessels, and increase blood flow to and from the brain.

guanabenz-- relaxes blood vessels so that blood may pass through more easily.
http://www.mayoclinic.org/drugs-supplements/guanabenz-oral-route/description/drg-20064106

ibudilast-- increases cerebral blood flow, is a vasodilator
http://www.ncbi.nlm.nih.gov/pubmed/18677969

biotin---decreases blood pressure, increases blood flow, treats ischemia (low O2) after stroke
http://www.ncbi.nlm.nih.gov/pubmed/18179728
http://www.google.com/patents/WO2014016003A1?cl=en



That's right.  MS researchers have learned from Dr. Zamboni's discovery of CCSVI and slowed cerebral blood flow and hypoperfusion in the MS brain.

But they do not want patients to try "alternative treatments"; to have venous malformations treated, or to receive HBOT treatment,  or have atlas adjustments, or to eat better, quit smoking, get UV rays or exercise more.  All of these alternatives have been scientifically shown to increase cerebral blood flow and perfusion.  These alternatives will help people with MS live healthier lives.  But they will not help MS researchers.

MS researchers would prefer it if you would take a pill.  That way, their research labs will remain funded.  That way, they receive finders' fees when you are enrolled in a drug trial.
(Up to $5,000 per patient!)
http://ccsviinms.blogspot.com/2012/04/clinical-trials-and-finders-fees-april.html

That way, they can receive speakers' fees, and have wonderful conferences, and do not have to address the elephant in the room----that the EAE model of MS is not MS.  EAE has been used to create a $20 billion dollar a year drug industry, based on immune modulation and ablation, but has not stopped MS disease progression in humans.

There is most certainly a problem with cerebral blood flow and hypoperfusion in people with MS.  In fact, all diseases of neurodegeneration have hypoperfusion.
http://ccsvi.org/index.php/the-basics/ccsvi-in-other-neurological-diseases

I simply wonder when the MS industry will admit that the new target of "neuroprotection", simply means increasing blood flow to neurons and myelin in the hypoperfused MS brain.

Still waiting,
Joan


This picture on the left is from Dr. Zamboni and Dr. Simka---it illustrates how cerebral blood flow becomes blocked, refluxes up jugular veins and goes to less efficient, collateral veins in CCSVI,  creating hypoperfusion.  I know it's real, because it's what my husband had on MRV (see pic on right)  And there is no pill in the universe that could have restored Jeff's blood flow.  He needed venous repair, and a new lifestyle.  Six years later, no MS progression.  This is real.

MS "breakthrough" research--On/Off Switch!!!

I am sick and tired of reading news stories about some "new MS breakthrough" which uses the EAE mouse model of MS and describes MS as an autoimmune disease.  It is as though the immunology research community believes that if they just keep acting like they are busy discovering things (where they have been looking for 70 years and finding nothing about disease etiology) they can keep getting funding for their labs, and keep people with MS thinking there is momentum.

The latest in a sea of sameness is the Bristol University crap about an "on/off switch" for the immune response to MS.

Here's the full paper, published in Nature---for those who like to read published research, rather than press releases full of hyperbole and BS.

http://www.nature.com/ncomms/2014/140903/ncomms5741/full/ncomms5741.html

In reading the paper, we learn that this new "breakthrough" is remarkebly reminiscent of Copaxone treatment, in which killer T cells are said to be modulated to helpful T cells by means of exposing them to an antigen (in Copaxone's case, that's a mimic of the proteins found in myelin basic protein---glatiramer acetate.)  This particular "new breakthrough hope"  therapy is going after CD4+ T cells, using injected peptide epitopes, rather than intact antigens--which are said to be "more effective."

Again, all of the testing was done on the mouse model, EAE.  Not humans with MS.

As reviewed elsewhere23, 45, peptide epitopes targeting ​CD4+ T cells have distinct advantages over intact antigens, and yet the mechanism by which peptide therapy prevents and treats ongoing autoimmune and allergic diseases is poorly defined. Mucosal routes of administration have proven safe and effective in animal models of allergy and autoimmunity, but have not translated well to the clinic. Here we demonstrate that the s.c. route of administration is more effective than the i.n. route, with a 1,000-fold lower dose of antigen being effective for anergy induction when compared with previous studies17, 18. As noted17, the efficacy of tolerance induction and disease prevention depends on signal strength. In this study, all aspects of inflammatory T-cell function, including proliferation, inflammatory cytokine secretion and encephalitogenicity were suppressed, whereas the ability of cells to secrete ​IL-10 and suppress EAE increased in a dose-dependent manner. ​IL-10 clearly serves as a promising mediator of effective antigen-specific immunotherapy1, 12.

But muting or changing the inflammatory response of CD4 + T Cells isn't really explaining why they are there in the first place, or how come this exact same cellular response shows up in ischemic stroke, slowed cerebral blood flow and reperfusion injury in humans.

That's right!!  CD4+ T cells show up after stroke, ischemia, and reperfusion injury.  These cells are responding to slowed blood flow in the brain, or hypoperfusion.

Here are stroke and vascular researchers discussing CD4+ T cells and the immune reaction to stroke and vascular issues in published research.  Perhaps we should let them know that stroke or reperfusion injury is an autoimmune disease that can be turned on or off!

For instance, lymphocytes from stroke survivors show more activity against myelin than the lymphocytes from patients with multiple sclerosis. In addition, myelin-reactive T cells are found in higher numbers among patients with cerebrovascular disease. These data thus provide evidence that a cellular immune response to brain antigens occurs following stroke.
http://stroke.ahajournals.org/content/41/10_suppl_1/S75.full


These findings indicate that CD4⁺ and CD8⁺ T lymphocytes, but not B lymphocytes, contribute to the inflammatory and thrombogenic responses, brain injury, and neurological deficit associated with experimental stroke
http://circ.ahajournals.org/content/113/17/2105.long

These findings implicate a CD4+ subset of T lymphocytes as key mediators of early inflammatory responses after renal  ischemic reperfusion  injury. 

http://www.scielo.br/pdf/bjmbr/v40n4/6420.pdf


I have a novel suggestion for researchers---why not look at the connection of MS to stroke, the vascular endothelium, CCSVI and reperfusion injury?  Why not understand this cellular response in non "auto-immune" diseases?

Now that would be a REAL breakthrough,
Joan

From Dr. Putnam to Astrocytes--MS as a Vascular Disease

June 22, 2012 at 12:04pm

For those who haven't had a chance to read about the history of the beginnings of the MS Society and the founding neurologist, Dr. Tracy J Putnam---here's a bit of background on the vascular history of MS.
http://ccsviinms.blogspot.com/2012/06/dr.html

The very latest research into multiple sclerosis is discovering what Dr. Putnam hypothesized. MS is created by a response from the vascular system to injury. 

New research, published this month, continues Putnam's thesis, at the cellular level.

Something is signaling the vascular cells in the brain.

Here's how it works.

Astrocytes are beautiful, star-shaped cells that live in the central nervous system. ( I love the fact that our smallest cells look like the largest bodies in our solar system.  There's wonderful symmetry in creation.)

Astrocytes are the most abundant cell in the human brain.  One of the most important things astrocytes do is support the endothelial cells in our brain, and maintain the very important blood brain barrier. The blood brain barrier should have tight junctions, that don't allow blood particles into brain or spinal tissue.  (For those new to the idea of the endothelium, please check out the Endothelial Health program I made for Jeff.  It will explain how MS and our blood supply are connected.)

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

Researchers have recently noted that when the brain is subject to hypoxia, or low levels of oxygen, the blood brain barrier becomes open, or "permeable."  This allows infiltration of blood cells and the immune system, which create damage to the brain.  Please notice that if the blood brain barrier was not open, T and B cells would not have entry.  The immune system isn't just going into the brain, uninvited and without cause.  The gate is wide open.

Blood brain barrier (BBB) permeability is an early and prominent feature of inflammatory CNS conditions, including MS (13), viral encephalitis (14), and traumatic and hypoxic/ischemic injury (15). BBB disruption correlates with neurologic exacerbation, and MS patients with contrast-enhancing plaques are more likely to have irreversible pathology (13, 16). BBB breakdown leads to edema, metabolic imbalance, excitotoxicity, and ingress of factors that potentiate inflammation and inhibit repair (17–20) and facilitates infiltration of T and B lymphocytes, macrophages, and neutrophils (21). In diseases such as MS, current options to restrict relapse severity are limited, and patients may benefit from more selective agents (22).

What is going on?  What signals the astrocytes to open the gate?  Researchers are looking specifically at VEGF--vascular endothelial growth factor.

Studies have identified astrocytes as regulators of BBB induction and maintenance (9–11) and have implicated astrogliosis, particularly induced by IL-1, as a driver of both BBB breakdown and repair (10, 12, 48). The mediators producing the effects of reactive astrocytes are incompletely characterized, and our data revealed VEGF-A as an important astrocyte-derived inducer of BBB disruption and pathology in vivo. Although VEGF-A–induced vascular permeability has previously been implicated in pathogenesis of disorders, including myocardial infarction, CNS hypoxia/reperfusion injury, and tumor growth and metastasis (49), and we and others have previously speculated on its role in BBB breakdown (12, 26), this study is the first to our knowledge to show the significance of astrocyte-derived VEGF-A in lesion pathogenesis and generation of clinical deficit in models of CNS inflammatory disease.

http://www.jci.org/articles/view/60842

This is the first study that has noted the importance of astrocyte derived VEGF in the formation of lesions and brain damage in a model of MS.

Please note the other diseases that have VEGF created "vascular permeability"--hypoxia and myocardial infarction--are vascular diseases.  VEGF-a is activated in situations where there is low oxygen, and the organ begins to suffer the effects of low O2.

So, what is VEGF and why does it matter in MS?  

Vascular endothelial growth factor (VEGF) is a chemical signal produced by cells that stimulates the growth of new blood vessels, called "angiogenesis."  This is part of a system which restores the oxygen supply to tissues when blood circulation is inadequate.

VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, and new vessels (collateral circulation) to bypass blocked vessels.

Here is a rather pejorative look at the vascular connection, written in a condescending tone by a group of German Neurologists-- 

Vascular pathology in multiple sclerosis: mind boosting or myth busting?

The idea of MS being a vascular disease is not new. In the 1930s T.J. Putnam proposed venous obstruction as the primary alteration in MS [7]. Given the venotopic localization of MS plaques, this hypothesis has been discussed on and off ever since. In 2007 an Italian group headed by P. Zamboni added new fuel to the fire by demonstrating that venous blood flow alterations can be found at a high frequency in MS patients [5]. 

While the concept of CCSVI has gained much attention in the field of MS research and in particular among MS patients, there is increasing evidence that the relation of venous changes to the pathophysiology of MS may not be as simple as initially described. Most importantly, new MR imaging techniques add to the notion of vascular changes in MS, yet again raise doubts whether these alterations are cause or rather consequence of the disease process.

(At the end of the article, the authors state they have nothing to disclose, yet all of them have participated in many MS drug trials. Drugs which are based on the EAE immune model of MS-  Dr. Linker has received personal compensation for activities with Bayer Health Care, BiogenIdec, Merck Serono, Novartis and TEVA Pharma. Dr. Linker has received research support from BiogenIdec, Novartis and TEVA Pharma.)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156723/?tool=pubmed

Why is it only neurologists who believe some "mystery mechanism" disease process is behind VEGF activation, blood brain barrier disruption and inflammation---when we have other models of vascular disease in vivo, such as stroke, which illustrate how hypoxic injury creates this scenario? 

If MS specialists want to continue to pretend there is no vascular involvement in MS, and that MS is a disease of a mysterious and crazed immune system,  they can keep saying it-- and creating, testing and selling the drugs.  But the truth is, all of the research continues to point to the importance of the endothelium and the vascular response of the body to injury of the brain.  

What's causing the injury?  Slowed flow through the brain, hypoperfusion, low O2 and glucose levels from collateral venous return?   Makes sense to me.   More to come.

Joan

Why mouse models of stroke and MS don't work

April 22, 2012 at 8:51am

MS is not the only neurological disorder which has a flawed rodent model.  Turns out, stroke researchers just aren't happy with their mouse model, either.  Why?  Because the immune response after stroke is different in mice and people.

EAE is not MS in humans.  

Believe it or not, the current MS drugs cure mice of EAE.  But they sure do not cure people of MS.  

What's the problem?   There are many problems with the EAE model.    

Here's my favorite description of what's wrong with EAE, from Dr. Michael Dake--

"There's an animal model, but it's not really, unfortunately, like most animal models, it's not really a human model.  Basically, you take like a mish of ground up spinal cord and brain from some other species, you mix it with some oily substance, some TB bacilli, and some bordatella pertussis, some whooping cough toxin, and inject it into peridium,  and what you get is this whopping inflammatory response, and that's good because you get the accelerated disease process, but obviously in humans, it's a much more chronic and progressive thing."

People with MS haven't had this cocktail of viruses injected into their brains.  (Good thing!)

But there's much more. The immune system of rodents and humans are very different, too.

Stroke researchers understand that their rodent models are not working.  

This is because the immune reaction after ischemia is very different in rodents when compared to humans. 

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

Here is a recent paper on the problem with the rodent model of stroke--and the difference in the immune response in mice and men.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085747/

Important to note---the immune system responds after stroke, just as it does in MS.  Ischemic injury, or lack of oxygen to brain tissue, calls in the immune system to clean up dead cells.  This happens in all mammals.

The rodent immune cell composition is remarkably different from that of humans.

Specifically, rodents have a lymphocyte predominance with a 1:5 ratio of neutrophils to lymphocytes.

Humans have a 2:1 ratio of neutrophils to lymphocytes.

What does this mean?  Time for some explaining.

Neutrophils and lymphocytes are both types of white blood cells that make up the innate immune system of all mammals.

Vascular aspects of multiple sclerosis

June 21, 2011 at 1:35pm

I have the complete review paper from Lancet Neurology.  It is a review of recent research in MS and is a compilation of the many studies we've linked on this page.  The endothelium, hypoperfusion, ischemia , CCSVI and the many terms we've learned over the past two years are all mentioned.  I do not want to violate copyright laws,  and can't copy and paste the full paper, but I'll give a brief breakdown.  You'll see text from the paper in italics, and then my comments.  

Note the word "might" is used extensively.  They review the research connecting the vascular system to MS.  While this is not earth-shattering to those of us who know CCSVI, up close and personal--it is encouraging to see this review in a neurological journal.  

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(11)70105-3/abstract

Abstract:

Vascular aspects of multiple sclerosis

Miguel D’haeseleer, Melissa Cambron, Ludo Vanopdenbosch, Jacques De Keyser

Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial dysfunction secondary to inflammatory disease activity and increased plasma homocysteine concentrations. Second, patients with MS have global cerebral hypoperfusion, which might predispose them to the development of ischaemic stroke. The widespread decrease in perfusion in normal-appearing white matter and grey matter in MS seems not to be secondary to axonal degeneration, but might be a result of reduced axonal activity, reduced astrocyte energy metabolism, and perhaps increased blood concentrations of endothelin-1. Data suggest that a subtype of focal MS lesions might have an ischaemic origin, and there seems to be a link between reduced white matter perfusion and cognitive dysfunction in MS. Third, the pathology of MS might be the consequence of a chronic state of impaired venous drainage from the CNS, for which the term chronic cerebrospinal venous insufficiency (CCSVI) has been coined. A number of recent vascular studies do not support the CCSVI theory, but some elements of CCSVI might be explained by slower cerebral venous blood flow secondary to the reduced cerebral perfusion in patients with MS compared with healthy individuals.

#1   People with MS have ischemic stroke more often than healthy people.

Inflammation is widely accepted to play an integral part in the pathogenesis of atherosclerosis.18,19 Endothelial dysfunction is an early step towards overt atherosclerosis and the immune system seems to be highly involved in both processes.20 Endothelial dysfunction has been described in the very early stage of rheumatoid arthritis, probably as a result of inflammatory disease activity.21 Rheumatoid arthritis is an autoimmune disease22 in which increased cardiovascular morbidity and mortality has been noted.23 Alterations in endothelial function, as well as platelet activation and thrombophilia, have been reported in MS.24–26 Moreover, oxidative stress contributes to the development of endothelial dysfunction.27 Higher amounts of systemic and CNS oxidative stress have been reported in patients with MS than in healthy controls.28–30

The concentration of plasma homocysteine, which is believed to be an independent cardiovascular risk factor,31 is also raised in patients with MS.32,33 The cause of the increase in homocysteine concentration is unknown, but it occurs independently of serum concentrations of vitamin B12, vitamin B6, or folate.34 There is evidence that hyperhomocysteinaemia can cause endothelial dysfunction, even at moderately increased concentrations of homocysteine.35,36

The above evidence suggests that the increased frequency of ischaemic stroke in MS might be mediated through converging inflammatory pathways, oxidative stress, and raised homocysteine concentrations leading to endothelial dysfunction.

What this section is saying is that oxidative stress, endothelial dysfunction, endothelin-1 levels and homocysteine levels are higher in pwMS, and may contribute to higher stroke levels.  (We've talked about this on here for awhile, it's why I created the endothelial health program for Jeff--I noted this connection in his serum numbers, and tried to help him thru diet, supplements, exercise and lifestyle.)

The researchers are positing that this is all due to inflammation and the immune system in MS. They believe it all begins there.   But they have no proof of this.  It's just their theory--their way of looking at the evidence thru their prism of MS as immune.  But what we've discussed on here is that all of these factors are also found in diffuse cerebral hypoxia, or low levels of O2 in the brain.   We don't need to involve the immune system in this theory if we look at it thru the prism of reduced oxygenation in the brain due to slowed blood flow.

Searching for a cure

March 31, 2011 at 7:49pm

Let's talk about the word cure.  This is a very, very powerful word.  We use it when we talk about solving the worst of our mystery diseases, like cancer, diabetes, Alzheimers and multiple sclerosis.  But the truth is, doctors are now admitting there may not be an actual cure for these diseases.  They are beginning to write and speak out and say that prevention and lifestyle changes early in life may stop these diseases from happening later.   Here's a highly recommended paper on "the best cure for disease"

link

Let me explain further.

We understand that there is no cure for a stroke, right?  Someone develops a blood clot over time.  Maybe they smoked, maybe they didn't get enough exercise and liked to eat fatty foods, or maybe it was just a predisposition they inherited. One day WHAM!  The clot breaks off and heads up the carotid artery and goes into the brain.  The clot blocks blood flow and brain tissue doesn't get oxygen and it dies.  The stroke patient is given clot busting medicine, blood flow is restored, but there's been damage.

Well, it looks like the damage from CCSVI could be somewhat like a stroke.  It may be affected by epigenetics and environment. Lifestyle matters. It is a chronic process due to a venous malformation which creates slowed cerebral blood flow and possible venous hypertension.   

My husband lost his peripheral vision as a kid due to a swollen optic discs--but it wasn't until 30 years later he got an MS diagnosis.  We now know he had venous hypertension his whole life.  That's a long time!   Eventually the brain is not able to reroute around the damaged parts and there is MS progression.  This leads to an MRI, a lumbar puncture, an eventual diagnosis of MS.    But the part of the brain or spine or optic nerve that has been damaged is not going to come back completely, even if we get blood flow going correctly.  Dead axons are dead.  My husband won't get his vision back.  

There is hope through rehabilitation and recovery.  A stroke victim works hard to learn how to walk again, to speak normally, to take care of themselves.  Perhaps, via plasticity,  the brain can reroute around the damage.  But there is no "cure" for a stroke.  A stroke victim doesn't go back to the way he was before the stroke.  And that also happens in MS.

We need to stop speaking about venoplasty to relieve CCSVI as a cure, or a return to complete health.   It just gives false hope to pwMS, and leads to high expectations and later disappointment.  The truth is, the brain and spine may be damaged due to years of insufficient blood flow.  That doesn't mean there is no hope.  There may be symptom relief for many.  Often the relief comes in a lifting of fatigue or heat intolerance, a reduction in spasms, a return of better vision, clearer thinking, and yes, even return of mobility in some.  This allows for physical therapy, brain plasticity and rerouting,  retraining the body, adopting a new, healthier lifestyle and hopefully, an end to disease progression.  Just like a stroke patient--it is all about rehabilitation and a new life.

To make venoplasty the "cure" for MS is to expect too much.  Dr. Zamboni says so himself--this is not a cure.   As a community, we have to be honest with those who are looking at this treatment.  We need to be honest with each other.  And we need to realize that venoplasty is not a one time magical answer to ending MS.  It is a commitment to an ongoing lifestyle, a relationship with a vascular doctor, hopefully covered by insurance,  and a new life.  That may be hard to read and harder to comprehend on a gut level, but it has to be said; because too many are mortgaging the house, using their IRAs, going into debt--to buy a "lottery ticket" for a cure.  And they're getting hurt.

Don't get me wrong, I believe in miracles.  I've seen them in my own life and in others' lives, and I know God is bigger than any one of us--but I also believe in honesty and full disclosure.  Please understand that no one, including the doctors, is calling this a cure.  

Joan

 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)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816867/

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.

http://recovery.tamu.edu/journal%20club%20articles/Popovich03.pdf

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."

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.

http://stroke.ahajournals.org/content/41/10_suppl_1/S75.full

"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