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

Monday, December 31, 2012

2013--The 150th anniversary of MS as a vascular disease

December 31, 2012 at 9:33am

What's old is new.
2013 is the 150th anniversary of Eduard Rindfleisch's publication describing MS as a vascular disease.  
Rindfleisch, a German pathologist, studied post-mortem brain samples from people with MS.  He noted that inside all of the lesions he could clearly see an enlarged blood vessel.  He believed the inflammatory response seen in the MS brain was created by hypereremia, or engorgement, due to blocked blood flow.
It's now 2013.  150 years is a long time.  Too long.
Here is what Rindfleisch noticed in the MS brain in 1863.

If one looks carefully at freshly altered parts of the white matter ...one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood...All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation. 
Rindfleisch E. - "Histologisches detail zu der grauen degeneration von gehirn und ruckenmark". Archives of Pathological Anatomy and Physiology. 1863;26:474–483.

Unbelievably, in 2012 researchers begin to look at the cerebral veins of people with MS while they are alive, using MRI venograms.  And they notice what Rindfleisch saw---engorged penetrating veins in active, or newly-formed lesions.  
They conclude that the cerebral veins in people with MS are not normal----149 years after Rindfleisch said this.

Here is a timeline which outlines the history of the study of MS as a vascular disease.

When you read this timeline, notice how the researchers asserting the vascular connection used actual autopsied brain tissue from people with MS.  These are not manufactured mouse models of MS. Notice how many times the words perivenous, veins, blood and fibrinogen are mentioned, thoughout the decades of research.  

An inflammatory process is activated whenever there is a break in the blood brain barrier in humans.  The idea that MS is created by a rogue immune system-- crossing the blood brain barrier and attacking myelin-- is STILL only a theory.  The break in the blood brain barrier precedes demyelination in MS.  Why does this happen?

Dr. Zamboni showed how extracranial venous malformations could lead to cerebral hypoperfusion. A process that would lead to a hypoperfusion/reperfusion injury to the brain. 

A process that would explain what Rindfleisch noted 150 years ago and researchers see today.  And despite what some neurologists are claiming, Dr. Zamboni's theory has not been disproven by their research.  Because they are not looking at collateral circulation, hypoperfusion and mean transit time.

When MS specialists claim that "we've investigated the vascular connection to MS, and there's nothing there" they are usually referring to Dr. Tracy Putnam's research and trials of newly discovered blood thinners in people with MS.  This happened in the 1940s, when Dr. Putnam was modeling MS lesions by blocking the venous sinus of dogs.  Dr. Putnam was just beginning to understand the implications of blocked venous flow on the brain, when Thomas Rivers created the EAE model of MS. People wanted a cure for MS, and looked to the creators of the polio vaccine for the answers.  Vascular research was abandoned.  For those interested in more of this history, here is the story of TJ Putnam.

The following paper was published by researchers at the Royal Free Hospital of Medicine in London. It is available online, in toto, for free.  The reason it is important is that researchers examined actual autopsied brains from people with acute MS, and studied the lesions on an immunohistochemical level.  This paper was published in 1994.

Immunohistochemical study of vascular injury in acute multiple sclerosis.

AIMS--To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.

METHODS--Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen.  

RESULTS--Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.

CONCLUSION--It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.


Why is there so much reticence by MS researchers to truly collaborate wih vascular doctors, to understand Dr. Zamboni's discovery of truncular venous malformations in the extracranial veins of pwMS?

Cleveland Clinic/Case Western studied post mortem jugular veins from pwMS and found the presence of a novel venous valve that had not been described in anatomy textbooks.  Just as Dr. Zamboni said, pwMS have truncular venous malformations.  Yet there has been no more investigation into this phenomena.  Why not?  

It is now four years since the first group of patients and caregivers began discussing Dr. Zamboni's research on This is MS.  And so far, only BNAC has collaborated with Dr. Zamboni to study his doppler protocol.  Millions of MS Society dollars are spent on a variety of diagnostics--without looking at the deep cerebral veins, with utilization of valsalva manuever, without consulting phlebologists on the nature of truncular venous malformations.  All of the wasted time and money, in an attempt to quell vascular research, and assert the dominance of immunomodulating drugs.  

Let's celebrate 2013 as the 150th anniversary of Rindfleisch's observation.
We call for collaboration.   It's time.
Happy New Year!!


Monday, December 10, 2012

MS and the Orkney Islands--the BIG picture

December 10, 2012 at 6:57pm

New research shows that the world's highest MS rates are found on Scotland's Orkney Islands.  Researchers are tying this to the environmental factor of sunshine, latitude and vitamin D levels and potential genetic markers, but there's much more to this story.  Because the Orkney Islands population have some serious health issues.  It's not just MS.

Here's more on the MS rates on the Orkney Islands which was announced today:

The Orkney islands in Scotland have the highest incidence of multiple sclerosis in the world, a new study has shown, lending weight to the theory that the absence of strong sunlight may be a factor.
The north of Scotland has been known for some time to have a high prevalence of MS, but the first study of its kind in 40 years has found that the rates in the Orkney Islands, Aberdeen and Shetland are not only very high but have increased since the 1980s.

The prevalence of the condition in Orkney is far higher than has been recorded anywhere else. One woman in 170 in the islands suffers from the degenerative disease – it is more common in women than in men. Shetland has a rate of 295 per 100,000 and the city of Aberdeen has 229 cases per 100,000. The highest reported rates worldwide were previously 350 per 100,000 in Alberta and Nova Scotia in Canada.

Dr Jim Wilson, of the University of Edinburgh's centre for population health sciences and one of the authors of the study published in the Journal of Neurology, Neurosurgery and Psychiatry, said the answer was at least partly genetic. "Our study shows that Orkney has the highest prevalence rate of MS recorded worldwide. 
The figures will also be welcomed by those who believe the high prevalence of MS in northern climes is linked to an absence of strong sunlight, which is needed to make vitamin D in the body. Some scientists and campaigners have lobbied public health authorities for mass dosing of vitamin D in Scotland.
Dr Wilson said this was an ongoing topic of research. "We have 2,300 people in Orkney who are having their vitamin D measured. We will certainly get the answer," he said. "It is probably important but it is not the only factor."

What this press announcement fails to mention is that this MS study is just one part of several major studies being undertaken on the Orkney Islands.  And Dr. Jim WIlson has been involved in these other studies, as well.   The results have shown high rates in cardiovascular disease, diabetes, stroke and other cardiovascular issues for Orkney inhabitants.  Here is some information from 2004 and the ORCADES study.

Tuesday, December 4, 2012

Fibrinogen---found In ALL neurodegenerative diseases, not just MS

December 4, 2012 at 9:29am

The "news" this week was that fibrinogen, an essential clotting protein, crosses over the blood brain barrier in the mouse model of MS and initiates the disease process by destroying nerve cells.  

Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation

But this isn't news.  Researchers have been studying this process in neurodegenerative disease for a decade.  Because this process happens when the blood brain barrier breaks down.

The overall findings from study of Alzheimer's Disease brain tissue and in vivo in Abeta(1-42) and Abeta(1-42) plus fibrinogen stimulated rat hippocampus suggest microglial responses to promote increased extravasation of blood protein as a critical component in amplifying inflammatory reactivity and causing neuronal damage in inflamed AD brain.

Fibrinogen is a pleiotropic blood protein that regulates coagulation, inflammation and tissue repair. Fibrinogen extravasates in the nervous system after injury or disease associated with vascular damage or blood-brain barrier (BBB) disruption. Fibrinogen is not merely a marker of BBB disruption, but plays a causative role in neurologic disease as a potent inducer of inflammation and an inhibitor of neurite outgrowth. Fibrinogen mediates functions in the nervous system as a ligand for cell-specific receptors. In microglia, fibrinogen mediates activation of Akt and Rho via the CD11b/CD18 integrin receptor, while in neurons fibrinogen induces phosphorylation of epidermal growth factor (EGF) receptor via the alphavbeta3 integrin. Pharmacologic targeting of the interactions of fibrinogen with its nervous system receptors could provide novel strategies for therapeutic intervention in neuroinflammatory and neurodegenerative diseases.

Why the race for researchers to understand fibrinogen?
Because pharma wants to monetize a way to block it.
That's right....researchers are not studying WHY fibrinogen is breaking through the blood brain barrier.  No one is looking at causation.
Everyone is studying this to find a pharmacological means of stopping fibrinogen.

But, what if there is an underlying mechanism which begins fibrinogen activation in all neurodegenerative disease?
Wouldn't that be something to study?  Wouldn't that be causation, and lead to potential answers in disease aetiology?

Here's a paper I researched and wrote up for CCSVI Alliance on the discovery of CCSVI in other neurological disease.  It proposes the mechanism found in common with CCSVI in neurodegenerative disease.  Slowed cerebral bloodflow.

HYPOPERFUSION.   A mechanism found in all neurodegenerative disease, which starts fibrin deposition in the brain. This is being studied by stroke researchers.  A decline in cerebral bloodflow initiates fibrin deposition in the brain immediately.

One of the most surprising findings of the present study is that the decline of cerebral blood flow (CBF) in conjunction with hypoxia is sufficient to induce rapid microvascular thrombosis and fibrin deposition within the brain (Figure 9). By analyzing challenged fibrinogen-null mice we have established that fibrin(ogen) plays an important role the reperfusion deficits and brain infarction (Figure 10). These results suggest that if cerebral ischemia is accompanied with hypoxia, this combination can precipitate local coagulation and impede reperfusion after ischemia, similar to the previously described no-reflow phenomenon after cerebral ischemia5 and cardiac arrest.56 It seems likely that fibrin stabilization of platelet thrombi is a major determinant of brain tissue damage. If so, we would predict that a similar, if not more impressive, protection from tissue damage could be realized in mice with a profound defect in platelet function. It is also conceivable that fibrin-mediated inflammatory processes drive secondary tissue damage in the brain. Thus, the modified Levine/Vannucci model described here may be useful for testing new therapies to restore postischemic reperfusion in the face of thrombolytic agents and other approaches to reopened large vessels.
Regarding the mechanism of ischemia/hypoxia-induced thrombosis, it seems likely that hypoxia alters the balance between anti- and procoagulation properties of the endothelial cells in cerebral blood vessels. Although focal ischemia can trigger platelet accumulation and fibrin deposition, these events typically show a late-onset after a transient hyperemia phase.49,53 In contrast, the present study shows that the combination of ischemia and hypoxia precipitates these events almost immediately. 

Please encourage and support the researchers of the International Society for Neurovascular Disease.  

There are only a few groups looking at disease aetiology, or what is causing the disease process.

Blocking fibrinogen won't cure MS.  
Understanding why there is fibrinogen in brain tissue may.