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.
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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.
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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!!
Joan
