A blast from the past for ccsvi'rs 1937

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

A blast from the past for ccsvi'rs 1937

Postby Anonymoose » Mon Dec 17, 2012 5:53 pm

I dont know if this has been posted before but i thought that it was kinda funny that they were clued into flow issues in 1937 and its taken this long to do anything about it.
http://archneurpsyc.jamanetwork.com/art ... eid=647231
EVIDENCES OF VASCULAR OCCLUSION IN MULTIPLE SCLEROSIS AND "ENCEPHALOMYELITIS"
TRACY J. PUTNAM, M.D.
Arch NeurPsych. 1937;37(6):1298-1321. doi:10.1001/archneurpsyc.1937.02260180078006. Text Size: A A A
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ABSTRACT
ABSTRACT | REFERENCES
Recent experimental work1 has made it seem probable that the lesions of multiple sclerosis and also those of the forms of "disseminated encephalomyelitis" which seem to represent a more acute stage of the same process2 are produced by a local circulatory disturbance, apparently of the nature of an obstruction on the venous side. According to this point of view, there must be a primary change in the contents of the vessels of the central nervous system, or possibly of the intimal lining, which leads to thrombosis of venules. This produces local passive congestion and a mild degenerative process which affects myelin sheaths more than other structures. The myelin degenerates and is phagocytosed. The "inflammatory" phenomena would then be regarded as secondary or symptomatic and the gliosis as reparative or reactive. This hypothesis obviously must remain largely a speculation as long as it rests on the results of experimentation
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Re: A blast from the past for ccsvi'rs 1937

Postby Anonymoose » Mon Dec 17, 2012 5:59 pm

And another 1942
http://archneurpsyc.jamanetwork.com/art ... eid=649081
VASCULAR PATTERN OF LESIONS OF MULTIPLE SCLEROSIS
ROBERT S. DOW, M.D., Ph.D.; GEORGE BERGLUND, B.S.
Arch NeurPsych. 1942;47(1):1-8. doi:10.1001/archneurpsyc.1942.02290010011001. Text Size: A A A
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ABSTRACT
ABSTRACT | REFERENCES
The theory of a relation between the cerebrovascular system and the lesions of multiple sclerosis has been advanced by many workers. The first of many to assign a primary role to vascular lesions was Rindfleisch.1 Ribbert2 early maintained that the demyelinated areas were related to a primary disseminated thrombosis. He described a congested central vessel in all the sclerotic patches. In two small patches cut in serial section he found white blood cells in the lumen of the vessel, partly adherent to the vessel wall and partly filling the vessel as an embolus. He stated that these changes in the vessel were multiple thrombi and expressed the belief that they had an important causative role in multiple sclerosis. The most recent adherents to the idea that vascular lesions play a primary role in the pathogenesis of the lesions of multiple sclerosis have been Putnam and his collaborators.3
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Re: A blast from the past for ccsvi'rs 1937

Postby cheerleader » Mon Dec 17, 2012 6:54 pm

Thanks, anonymoose. Yes, Putnam has been discussed at length on here, as well as Rindfleisch.
chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic9669.html

For those on Facebook, here's the timeline on the vascular history of MS I wrote up in '10 which is around the web--
https://www.facebook.com/note.php?note_id=234671112210
Here's more on the history of TJ Putnam, the doctor who began the National MS Society -
https://www.facebook.com/notes/ccsvi-in ... 0055457211
the search function is really great on this site (upper right hand corner), and can help you find out if we've ever discussed a topic of interest.
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http://ccsviinms.blogspot.com
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Re: A blast from the past for ccsvi'rs 1937

Postby Anonymoose » Mon Dec 17, 2012 7:09 pm

Nothing has been posted to that thread since 2010 so I guess it's not such a bad thing to be brought up again.

So if its clear that part of the flow issue is in the brain, developing at the site of lesions, why no exploration of reason for and treatment of those occlusions? Unless I have missed that too...(I wouldn't be surprised if I did!)
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Re: A blast from the past for ccsvi'rs 1937

Postby cheerleader » Mon Dec 17, 2012 9:06 pm

Anonymoose---There's been more research into these vascular blockages in the brain--what Putnam saw through a microscope and surmised were emboli, show up on high-powered MRI as microvascular involvement, and are now being studied in MS and aging. So, therapeutic responses are being considered....150 years after Rindfleisch first noted this. Putnam used blood thinners to address what he saw, but he did not cure MS. Which is probably why the vascular theory was discarded for the immune theory.

Here's what's happening today:

Seven-Tesla magnetic resonance imaging: new vision of microvascular abnormalities in multiple sclerosis.

We demonstrated markedly enhanced detection of unique microvascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the venous wall on 7-T compared with 3-T MRI.

These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo but also have important implications for monitoring lesion activity and therapeutic response.


http://www.ncbi.nlm.nih.gov/pubmed/18541803

Here's a thread where this was discussed--
post175059.html?hilit=microvascular%20rush%20university#p175059

Research regarding fibrinogen as the first blood protein to cross the blood brain barrier in MS was first posited by Dr. Zamboni in his "Big Idea" paper of 2008, where he compared venous disease/ulcers of the legs with MS lesions, and showed the correlation between fibrin cuffs (or emboli), iron deposition and venous reflux. New research from Gladstone Labs confirms Dr. Zamboni's observation regarding fibrinogen.
http://www.nih.gov/news/health/nov2012/ninds-27.htm

Here's the history of Putnam, the vascular theory and MS. I'll copy what I wrote over from Facebook. It is a long read, but I hope worth it. Since you seem really interested, I hope this answers some questions about where we've been, and hopefully, where we may be going.
best,
cheer/Joan

The history of the National Multiple Sclerosis Society in the United States, first called the Society for the Advancement of Multiple Sclerosis Research, is told in one very specific way, in a brochure published on the NMMS page. Their focus is on the immunology of MS.

With remarkable foresight, the very first research grant from what was then called The Society for the Advancement of Multiple Sclerosis Research was awarded to study the immunology of MS—the relationship between the body’s immune system and the central nervous system (the brain and spinal cord). This 1947 grant went to Dr. Elvin Kabat at Columbia University. He subsequently identifi ed abnormal immunologic proteins in the spinal fluid of people with MS. These proteins appeared in patterns known as oligoclonal bands.

But this is only part of the history. The founding neurologist and first honorary chairman of The Society for the Advancement of Multiple Sclerosis Research is never mentioned by the National MS Society. In fact, this neurologist was responsible for bringing immunology into MS research. He invited Dr. Elvin Kabat to work on MS research with him at Columbia University, and hired this young researcher in 1940. He was responsible for helping select him for the first research grant made by the MS Society.
http://www.annualreviews.org/doi/pdf/10 ... 183.000245

Who was this neurologist? His name was Dr. Tracy J. Putnam, and he created an animal model of multiple sclerosis by occluding the venous sinus in dogs. He believed MS was a disease of blocked venous blood flow, which created the immune response in the central nervous system.

Dr. Tracy Putnam, American neurologist and chair of the medical advisory board for the National MS Society, experimented by obstructing venous outflow in dogs, only to find that the dogs quickly developed brain plaques similar to those found in MS patients. Putnam wrote about his observation, “The similarity between such lesions [in dogs] and many of those seen in cases of multiple sclerosis in man is so striking that the conclusion appears almost inevitable that venular obstruction is the essential immediate antecedent to the formation of typical sclerotic plaques.”

He is absent from the NMMS history. But we need to remember his name.

Here is a story about the founding of the National MS Society, printed in Time Magazine in 1946---

Time Magazine, 1946 "The Mystery Crippler"

The patient first notices a pins-&-needles sensation in his legs. After a time his head and shoulders may twitch, his eyeballs roll wildly, he sees double, reels when walking, stumbles in his speech, from time to time is seized by uncontrollable laughing or crying jags. In advanced stages he may be paralyzed.

The patient is not drunk. These are symptoms of a mysterious, widespread disease known as multiple sclerosis, a disorder of the nervous system. Doctors have recognized it for nearly 100 years (the German poet Heinrich Heine is believed to have died of it), but they have never discovered its cause or cure.

Last week the first concerted attack on the disease was launched by a new organization started by multiple sclerosis sufferers. Based in Manhattan, the Association for Advancement of Research on Multiple Sclerosis has enlisted some of the top U.S. neurologists (honorary chairman: Dr. Tracy J. Putnam, director of Columbia University's Neurological Institute).

Neurologists estimate that multiple sclerosis is more prevalent than infantile paralysis. The disease is characterized by sclerosis (hardening) of scattered patches of nerves in the central nervous system. It has been attributed variously to 1) clots in the small blood vessels of the nervous system; 2) spasmic contractions of the blood vessels 3) a spirochete (not the syphilis variety). But treatments based on these theories (e.g., anti-clotting and blood-vessel dilating drugs) do not cure the disease. It usually strikes between the ages of 20 and 35. It is seldom painful, and rarely fatal, but often cripples its victims.

Prime aims of AARMS: 1) raise funds for a full-dress research program; 2) determine the scope and prevalence of the disease.
http://www.time.com/time/magazine/artic ... z0cF87aQQF


Dr. Tracy J. Putnam was the Director of Columbia University's Neurological Institute and the leading expert on Multiple Sclerosis in early 1946, when the Time Magazine article was published. Putnam was a neurosurgeon and a neurologist. He was the first major researcher to go public with a theory for MS. But by mid 1947, he was forced to resign from Columbia and left New York and his academic career in disgrace. Why? One reason is because Dr. Putnam did not cure MS.

Senator Charles W. Tobey of New Hampshire sponsored the National Multiple Sclerosis Act, which began hearings before the Senate Subcommittee on Health of the Committee on Labor and Public Welfare on May 10, 1949. Senator Tobey's own daughter had multiple sclerosis, and he sought the advice of the National Multiple Sclerosis Society in composing the legislation. When the proposal for a National MS Research Institute was included in hearings on a National Health Plan in the House of Representatives in 1949, Ralph I Straus, the president of the NMMS, gave testimony, as did Senator Tobey, Mrs. Lou Gehrig and Dr. Tracy Putnam, as well as a number of other doctors, family members and patients.

They were not entirely in agreement. Most of the laypeople present stated that no progress whatsoever had been made in the "fight" against MS and demanded the kind of government interventions that had made possible the mass production of penicillin, which in turn was credited tor the sustained health of Allied troops invading Nazi Europe. Putnam, who had been an active participant in MS research for the last two decades, was confronted by a discontented public who did not seem to know about the progress he and others had achieved since Cruveilhier and Carswell.

Putnam was the first major researcher to go public with a theory of MS cause and the prospect of a treatment in 1942, but in 1949 he could not claim great success for this treatment. Though he described further research into other medications, he was facing people who wanted results, no hypotheses.
From Multiple Sclerosis through history and human life by Richard M. Swiderski page 159 (google books)

Dr. Putnam only had his hypothesis of blocked veins, but he did not have success in treating MS with newly discovered anticoagulants. The public wanted results. They wanted a penicillin for MS. They wanted a vaccine, like the polio vaccine. They wanted a cure.

All Putnam had were theories, his published research, and a trial in pwMS using the drug dicoumarin. This drug had just been discovered in 1941; created from spoiled clover. It was found to be useful in dissolving blood clots. Dicoumarin was helpful for relieving symptoms in people with MS. But it was not a cure. The disease continued to progress. http://archneurpsyc.jamanetwork.com/art ... amp;page=1


It is important to state that this is why neurologists say, "We've already been down the vascular path in MS research. It was a dead end." Because Tracy Putnam did not cure MS with a newly discovered blood thinner. He had a decade for his vascular research, and it was dismissed. The EAE autoimmune model has had over six decades, and there is still no cure for MS.

Who was this brilliant man, and why has he been removed from the story of multiple sclerosis research? Why has his work been categorized as failure?

Dr. Putnam assumed the Directorship of Neurological Unit at the Boston City Hospital in 1934 as Professor of Neurology at Harvard. His intellect, scientific bent, and exceptional teaching and writing skills, all developed to the fullest in the exceptional period of Harvard’s eminence in the neurosciences, soon catapulted him into the international prominence.

During his research years at Harvard, he developed novel fields of study and surgical approaches to neurological disorders, he developed novel ideas about subdural hematoma, hydrocephalus, motor disorders and epilepsy, and participated in the early studies with Houston Merritt and others, eventually developing the drug Dilantin as he described in his book in 1970 “The Demonstration of the Specific Anticonvulsant Action of Diphenylhydantoin and Related Compounds.” He was appointed Professor of Neurology, Professor of Neurological Surgery, and Director of the Neurological Institute of New York in 1939, just before the onset of World War II and the departure of a number of the talented younger people who he brought as supporting staff to New York.

Dr. Putnam’s years at the Neurological Institute of New York were not happy ones for him, since World War II decimated the younger and potentially helpful members of his staff, and his gentility and generosity of spirit were commonly misunderstood as weakness and vulnerability.

He was beset by administrative and wartime personnel problems while at the same time maintaining a major editorship in Neurology and important governmental responsibilities.

Because of the various pressures and other factors, he moved to California in June 1946 to become Director of Neurology at the Cedars of Lebanon Hospital. As Dr. Edward Schlesinger* has written, “Rarely has an individual brought so many talents to neurology and neurosurgery, or pointed out so many directions of ground-breaking research. Unfortunately, coincidences of time and place exacted a catastrophic toll on his career and he died on March 29, 1975.”
http://neurosurgery.org/society/bio.aspx?MemberID=2839

There were rumblings about Dr. Putnam. He had hired many "non-Aryan" neurologists on the Columbia staff. He had brought in Jewish researchers, like Elvin Kabat, to help him understand MS. Putnam did not care about racial or religious divides. He only wanted to work with the best and brightest. For those of us who were not living during this time, it may be hard to comprehend, but anti-semitism in the US was very prevalent. Here is more on this part of the history---

Dr. Putnam was forced to resign in 1947, ending his career at Columbia. Colleagues at the time suspected several reasons, including a lack of administrative skills, enemies on the staff and the conflicts that arose from having a neurosurgeon running a neurological institute.

But Dr. Rowland unearthed another explanation. A New York newspaper of the era, called PM, reported in 1947 that Dr. Putnam had been told to fire all of the “non-Aryan” neurologists, something he was unwilling to do.

Dr. Rowland corroborated this story when he discovered a 1961 letter written by Dr. Putnam to a fellow physician. Dr. Putnam reported that Charles Cooper, then head of Columbia’s affiliated hospital, Presbyterian, had told him in 1945 “that I should get rid of all the Jews in my department or resign.”

Quotas for Jewish medical students and physicians disappeared fairly rapidly after World War II, partly in response to Nazi atrocities against the Jews. But Dr.Putnam’s quiet advocacy on behalf of Jewish physicians when such a stance was unpopular should not be forgotten.
http://www.nytimes.com/2009/05/26/health/26quot.html

Another one of the Jewish MS researchers Dr. Putnam worked with and supported was Alexandra Adler-

Adler also contributed to the understanding of the neurological basis of multiple sclerosis. Adler and the Harvard neurosurgeon Tracy Jackson Putnam (Putnam & Adler, 1937) conducted a post-mortem study of the brain of a woman diagnosed with multiple sclerosis, demonstrating that cerebral plaques characteristically spread in a rather odd, specific relationship to large epiventricular veins and bizarrely altered the affluents of these veins. Illustrations from this article are routinely reproduced in the medical literature on multiple sclerosis.
http://www.apadivisions.org/division-35 ... raphy.aspx

Dr. Tracy Putnam left Columbia University and academia behind. He moved to Beverly Hills, CA, and became Director of Neurology at the Cedars of Lebanon Hospital. and also began a private practice as a neurosurgeon and neurologist. He continued to treat MS patients with anticoagulants. But he was a broken man. He was bitter over his treatment at Columbia, he was disheartened that his research had been dismissed. He kept very detailed records on the MS patients he treated with anticoagulation therapy. He cared deeply about his patients, and wanted to be able to offer them more help and hope.
http://www.oac.cdlib.org/findaid/ark:/13030/tf1n39n78s/

I've thought about Dr. Putnam many times during the past four years, wondering how he would respond to Dr. Schelling's book or the new doppler ultrasound technology and Dr. Zamboni's discovery of intraluminal venous malformations in people with MS.

We can see the parallels --the tossing aside of Dr. Putnam's research after a lack of a "cure" and the discontent with Dr. Zamboni's CCSVI research and the lack of an immediate cure. I worry that the immunological side of MS is given all of the research money and time, while the vascular connection remains underexplored and underfunded. I worry that the focus on a "cure" is put before the understanding of MS pathogenesis. How can we cure what we do not understand? It bothers me that there is not more curiosity in the neurological world regarding truncular venous malformations. As regular people, we can see the direct connection from Dr. Putnam's studies on veins in dogs, to Dr. Zamboni's discovery of intraluminal malformations in jugular veins, and the hemodynamic changes in blood flow in people with MS. Why is there not more curiosity in MS specialists? Where are the Tracy J. Putnams?

Let's keep Dr. Putnam's research and humanity alive. He may not be included in the National MS Society pages as a hero, but we can honor him in our own ways. By telling his story, by encouraging multi-disciplinary collaboration in MS research, by caring about those with MS, and by believing that the best and brightest- no matter their heritage, background or medical training-should be allowed to explore and understand this disease. (and maybe you can give to CCSVI Alliance, and help us carry on this work http://www.ccsvi.org

Thank you, Dr. Putnam.
Joan

Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: A blast from the past for ccsvi'rs 1937

Postby Anonymoose » Tue Dec 18, 2012 8:06 am

Thank you so much for putting that together and sharing it. Wow. I can't believe anti-semitism has interfered with our progress towards understanding and curing MS. Bizarre and sad for so many reasons.

So the thought that was niggling at my brain all night (sleep thinking is overrated) is in the cases that angioplasty of the jugulars and azygous results in marked/immediate deterioration, is it possible that the removal of those obstructions results in greater BBB failure? I'm imagining a flexible hose with a lump (plaque) on the inside at one point and further down the line a narrowing of the hose creating back pressure. As blood flows by the lump, the lump doesn't move much because the back pressure balances out the force being exerted upon it by incoming bloodflow. If you remove the back flow/narrowing, the lump moves more erratically, weakening the hose, creating leaks. In the human body I imagine this would create inflammation at that point, attracting immune response leading to further BBB failure.

Has that been discussed already too?
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Re: A blast from the past for ccsvi'rs 1937

Postby cheerleader » Tue Dec 18, 2012 9:09 am

Anonymoose wrote:So the thought that was niggling at my brain all night (sleep thinking is overrated) is in the cases that angioplasty of the jugulars and azygous results in marked/immediate deterioration, is it possible that the removal of those obstructions results in greater BBB failure?


sadly, the few individuals who have had strokes (due to warfarin treatment after venoplasty) may be examples of this breakdown of the BBB.. And for those who have deterioration after treatment...we don't know enough yet. That's why randomized trial procedures are warranted. Dr. Zamboni kept all of his patients on their disease modifying drugs before and after venoplasty, because of this concern. And Marie and I wrote about that (a lot) and she and Jeff remained on copaxone after treatment. BNAC has kept patients on their DMDs during their study, too. Jeff had also changed his diet and lifestyle, prior to and after venoplasty---like a stroke or heart patient. And this may have helped strengthen his cerebral endothelium, too. We just don't know.
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Re: A blast from the past for ccsvi'rs 1937

Postby Cece » Tue Dec 18, 2012 11:04 am

Yes! They were clued into flow issues back in Putnam's time but then he pursued anticoagulation that didn't work and politics led to him dropping from favor and another neurologist rising in favor. But I think the advances in imaging are why this discovery was made now and not then. MRV, doppler ultrasound, IVUS. Not to mention the advances in communication that led to people reading somewhat obscure research from Italy and acting on it.

For deterioration after treatment, we first need to know that the treatment was successful (all blockages opened and stay open), which would be possible to know in a trial. But wasn't there a study that captured MRI improvements neurologically some months after the procedure in 15 out of 16 patients, but in 1 patient, there was deterioration and new lesions. European study, can't remember who was involved, about a year ago.

What are the rates of stroke after angioplasty and in conjunction with anticoagulants? It's an estimate that there have been two such situations in CCSVI treatment. If that is 2 out of 40,000 (also estimated, possibly badly estimated), then it might be no more than what is normally seen in angioplasty plus anticoagulation treatments.
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Re: A blast from the past for ccsvi'rs 1937

Postby Anonymoose » Tue Dec 18, 2012 11:09 am

Edited to delete careless remarks made without understanding.

You didn't happen to get a good picture of Jeff's brain veins before and after he altered his diet and lifestyle, did you? Those would be interesting to see!

(Cece, you posted while I was writing so what you have said hasn't been taken into consideration...yet)
Last edited by Anonymoose on Thu Jan 31, 2013 4:16 pm, edited 1 time in total.
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Re: A blast from the past for ccsvi'rs 1937

Postby Anonymoose » Tue Dec 18, 2012 11:38 am

Cece,

That just makes me wish for a great big spread sheet documenting the pre/post angioplasty MRIs, vein pictures (lol, ultrasound??), symptoms, medications, diet, lifestyle, etc over a period of 20 years (hasn't been nearly 20 years since first ccsvi angioplasty, I know) I hope they do some better tracking in the future. For now, I'll just have to browse the CCSVI section.

Thanks for the info!
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