1 / 30

MS as a Vascular Disease: Background and History

MS as a Vascular Disease: Background and History. Marie Rhodes RN. Is MS proven to be a primary autoimmune disease ?. Barnett M, Prineas J. 2004. “Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion.” Ann Neurol . Apr;55(4):458-68. PMID:15048884

leavitt
Download Presentation

MS as a Vascular Disease: Background and History

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MS as a Vascular Disease: Background and History Marie Rhodes RN

  2. Is MS proven to be a primary autoimmune disease?

  3. Barnett M, Prineas J. 2004. “Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion.” Ann Neurol. Apr;55(4):458-68. PMID:15048884 • “The earliest change observed in the lesions examined in this study was widespread oligodendrocyte apoptosis in tissue in which T cells, macrophages, activated microglia, reactive astrocytes, and neurons appeared normal.”

  4. Oligodendrocyte loss and myelin breakdown with microglia scavenging and subsequent immune cell recruitment; the Barnett and Prineas model. Nerve cell with damaged myelin Oligo Microglia Recruited Immune System Cells

  5. Replication • Barnett M, Sutton I. 2006. “The pathology of multiple sclerosis: a paradigm shift.” Curr Opin Neurol. Jun;19:242-47. PMID:16702829 • Barnett M., Henderson A, Prineas J. 2006. "The macrophage in MS: just a scavenger after all?" Mult Scler. Apr;12(2); 121-32. PMID:16622941 • Barnett M, Parratt J, Prineas J. 2009. “Multiple sclerosis: Distribution of inflammatory cells in newly forming MS lesions.” Ann Neur. Dec;66:739-753. PMID:20035511

  6. Barnett M, Parratt J, Pollard J, Prineas J. 2009. “MS: is it one disease?” Int MS J. Jun;16 (2):57-65 PMID: 19671369 • Henderson AP, Barnett MH, Parratt JD, Prineas JW. 2009. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann Neurol Dec;66(6):739-53. PMID:20035511 • These papers have been cited numerous times by other researchers.

  7. Chaudhuri A. 2004. “Multiple sclerosis is not to an auto immune disease." Comment in Arch Neurol. Oct;61(10):1610-12. PMID:15477520 • Behan P, Chaudhuri A. 2002. “The pathogenesis of multiple sclerosis revisited.” J R Coll Physicians Edinb. 32(4):244-265 • Roach E. 2004. “Is multiple sclerosis an autoimmune disorder?” Arch Neurol. Oct;61(10):1615-6. PMID:15477522 • Tsutsui S, Stys P. 2009. “Degeneration versus autoimmunity in MS.” Comment in Ann Neurol. Dec;66(6):712. PMID:20033985

  8. Is MS autoimmune? • MS an inflammatory disease of unknown origin. The inflammation is indisputable, but the cause of the immune system activity is still unproven. • MS standard therapies reduce inflammation, and much of MS damage is caused by inflammation itself regardless of cause. Therefore relapses and inflammatory lesions are reduced with these therapies even though the cause of the inflammation is unknown.

  9. What is known about CVD?

  10. Chronic Venous Disease • Bergan J, Schmid-Schönbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B. 2006. “Chronic venous disease.” N Engl J Med. Aug 3;355(5):488-98. PMID: 16885552 • Review of current understanding in the field of vascular medicine.

  11. Veins become stretched out. • Stretched or vericose veins are under increased pressure. • Pressure inside the vein exceeds normal tissue pressure outside and fluid leaks out— “puffy ankles”. • If this continues red blood cells leak out as well. • The immune system activates in part to remove iron left by RBC’s. • Much of the damage to leg tissue is caused by immune system activity. • If lesions develop venous insufficiency is present. • CVD may be thought of as an inflammatory disease.

  12. CVD Immune Cell Cascade with Reflux Image by Marv Miller from “CCSVI as the Cause of Multiple Sclerosis” iron Iron Immune cells Refluxing blood flow in a varicose vein Red Blood Cells

  13. Paolo Zamboni, MD • Professor of Medicine at University of Ferrara, Italy. • Director of the Vascular Diseases Center. • Graduated in ’82 as a doctor, then completed a general surgery internship through ’87. He then went on to a fellowship at the Vascular Surgery Center at UCSF. • He is a prominent researcher in the vascular field and the recipient of numerous awards for his work. • His wife was diagnosed with MS in 1995

  14. From: Zamboni P. 2006. “The Big Idea: Iron dependent inflammation in venous disease and proposed parallels to MS.” J R Soc Med. 2006 Nov;99(11):589-93. PMID:17082306

  15. Do Zamboni’s ideas have any support in standard MS literature?

  16. The “Father of Neurology” In the 1860’s he documented a case of MS including an autopsy of her brain after death. He noted vascular changes and decided they were a result of her disease process. Jean Martin Charcot

  17. Pathology of MS lesion as noted by Jean Martin Charcot 1863 • “Specific features: in the ventricular wall a massive lesion can be seen to undulate outwards into the cerebral hemisphere; it embeds major venous blood vessels, attended by uneven widening of the perivascular space.” (F A Schelling, 2003)

  18. Dr. E. Rindfleisch 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." Comment in Archives of Pathological Anatomy and Physiology 1863;26:474-483

  19. Tracy J. Putnam MD Dr. Putnam designed many experiments around the idea that MS was a vascular disease. One of 20 founding NMSS neurologists. Because of his work, MS was commonly thought to be vascular in the ’50’s.

  20. Putnam’s Experiments • He occluded the neck veins in dogs then documented the development of lesions in their brains. • Experimented with blood thinners which provided modest improvement in symptoms. • Wrote a manual for the NMSS stating MS was vascular. • Was unable with technology of the time to evaluate blood flow in living people but believed until the end of his life that MS was vascular.

  21. Replication of Putnam’s work • Dow and Burglund. 1942. “Vascular pattern of lesions of multiple sclerosis.” Arch Neurol Psychiatry. 1942;47(1):1-18 • Zimmerman, H, Netsky, M. 1950. “The pathology of multiple sclerosis.” Res. Publ. Ass. Nerv. Ment. Dis. New York 28, 271--312 • Confirm vascular issues but suggest clots not as important as Putnam thought.

  22. Related Research in the 50’s: Vasodilators • Brickner R. 1953. “Essential precautions in treatment of new phenomena in multiple sclerosis.” AMA Arch Neuro Psych. Oct;70(4):483-8. PMID:13091497 • Jonez H. 1952. “Management of multiple sclerosis.” Postgrad Med. 1952;2:415-22 • These vasodilators did not change the disease course in spite of temporary improvements.

  23. Why did this model lose stature as the favored model? • Blood thinners and vasodilators were only modestly helpful at best. • Research was severely limited by a lack of technology. • The budding field of immunology seemed to promise to offer a better way of looking at MS by evaluating the obvious inflammation and immune system activity by looking at animals.

  24. Newer Venous Findings • Fog T. 1965. “The topography of plaques in multiple sclerosis.” Acta Neurol Scand. 1965;15:1-161 PMID:5213727 • Fog T. 1963. “On the vessel-plaque relations in the brain in multiple sclerosis.” Acta Psychiat Neurol Scand. 1963; 39, suppl. 4:258 • Dr Fog dissected MS lesions and discovered they follow the vein closely expanding in successive waves countercurrent to blood flow. • Today, the fact that MS lesions surround a vein is well known, but this fact is treated as unimportant to the autoimmune model: it is assumed the changes in the veins are a result of MS not the cause.

  25. F. Alfons Schelling MD • Schelling F.A. 2003. Multiple Sclerosis: The Image and its message. (book available online) • Dr. Schelling follows the history of venous findings in MS from the earliest work in 1838. • He points out that numerous facts about MS cannot be accounted for by the autoimmune model. Example: MS lesions grow on veins of a certain size and expand in successive waves countercurrent to blood flow. EAE lesions do not expand in this way.

  26. Tan et al, 2006 • Because veins and venules are ubiquitous, they traverse most other types of disease processes. We incidentally used this technique in patients with hypoxic ischemic white matter lesions and found that, especially in extensive lesions, veins could be identified within such lesions. However, in contrast to MS lesions, these white matter lesions showed no relationship to the shape and location of the veins. Tan et al. 2000. “MR Venography of Multiple Sclerosis.” AJNR 21:1039-1042

  27. BH Juurlink PhD • Juurlink B. 1998. “The multiple sclerosis lesion: initiated by a localized hypoperfusion in a central nervous system where mechanisms allowing leukocyte infiltration are readily upregulated? Med Hypoth • Speculates that MS is initiated by lack of blood flow which causes death of oligodendrocytes then myelin and a subsequent innate immune response.

  28. Blood Flow is Slow in MS • Adhya S, Johnson G, Herbert J, Jaggi H, Babb JS, Grossman RI, Inglese M. 2006. “Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T.” Neuroimage. Dec;33(4):1029-35. PMID:16996280 • Blood flow in the brains of patients with MS is half the speed that of normal people. • Perfusion and oxygenation in the MS brain is poor.

  29. Venous Revival • Zamboni’s work brings the venous argument back to the forefront. • Today’s technology, used by Zamboni in his research, reveals blood flow issues in MS that were not understood before. • Research is just beginning to evaluate how to assess and treat these issues. It will be some years before best practices are understood even IF this is a treatable issue.

  30. Due out April 19th • 10% of my royalties go to CCSVI Alliance. • Digital (ie Kindle) is less expensive but more goes to CCSVI Alliance.

More Related