MS as a Vascular Disease: Background and History - PowerPoint PPT Presentation


PPT – MS as a Vascular Disease: Background and History PowerPoint presentation | free to download - id: 3c6ec9-NDRjM


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation

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 ... – PowerPoint PPT presentation

Number of Views:33
Avg rating:3.0/5.0
Slides: 31
Provided by: ccsvibook
Learn more at:


Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: 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.
    Apr55(4)458-68. PMID15048884
  • The earliest change observed in the lesions
    examined in
  • this study was widespread oligodendrocyte
    apoptosis in
  • tissue in which T cells, macrophages, activated
  • reactive astrocytes, and neurons appeared normal.

  • Oligodendrocyte loss and myelin breakdown with
    microglia scavenging and subsequent immune cell
    recruitment the Barnett and Prineas model.

Nerve cell with damaged myelin
Recruited Immune System Cells
  • Barnett M, Sutton I. 2006. The pathology of
    multiple sclerosis a paradigm shift. Curr Opin
    Neurol. Jun19242-47. PMID16702829
  • Barnett M., Henderson A, Prineas J. 2006. "The
    macrophage in MS just a scavenger after all?"
    Mult Scler. Apr12(2) 121-32. PMID16622941
  • Barnett M, Parratt J, Prineas J. 2009.
    Multiple sclerosis Distribution of inflammatory
    cells in newly forming MS lesions. Ann Neur.
    Dec66739-753. PMID20035511

  • Barnett M, Parratt J, Pollard J, Prineas J. 2009.
    MS is it one disease? Int MS J. Jun16
    (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 Dec66(6)739-53. PMID20035511
  • These papers have been cited numerous times by
    other researchers.

  • Chaudhuri A. 2004. Multiple sclerosis is not
    to an auto immune disease." Comment in Arch
    Neurol. Oct61(10)1610-12. PMID15477520
  • 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.
    Oct61(10)1615-6. PMID15477522
  • Tsutsui S, Stys P. 2009. Degeneration versus
    autoimmunity in MS. Comment in Ann Neurol.
    Dec66(6)712. PMID20033985

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.

What is known about CVD?
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
    3355(5)488-98. PMID 16885552
  • Review of current understanding in the field of
    vascular medicine.

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

  • CVD Immune Cell Cascade with Reflux
  • Image by Marv Miller from CCSVI as the Cause of
    Multiple Sclerosis

Immune cells
Refluxing blood flow in a varicose vein
Red Blood Cells
Paolo Zamboni, MD
  • Professor of Medicine at University of Ferrara,
  • 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

From Zamboni P. 2006. The Big Idea Iron
dependent inflammation in venous disease and
proposed parallels to MS. J R Soc Med. 2006
Nov99(11)589-93. PMID17082306
Do Zambonis ideas have any support in standard
MS literature?
Jean Martin Charcot
  • The Father of Neurology
  • In the 1860s 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.

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)

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 186326474-483

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 50s.

Putnams Experiments
  • He occluded the neck veins in dogs then
    documented the development of lesions in their
  • Experimented with blood thinners which provided
    modest improvement in symptoms.
  • Wrote a manual for the NMSS stating MS was
  • 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.

Replication of Putnams work
  • Dow and Burglund. 1942. Vascular pattern of
    lesions of multiple sclerosis. Arch Neurol
    Psychiatry. 194247(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.

Related Research in the 50s Vasodilators
  • Brickner R. 1953. Essential precautions in
    treatment of new phenomena in multiple
    sclerosis. AMA Arch Neuro Psych.
    Oct70(4)483-8. PMID13091497
  • Jonez H. 1952. Management of multiple
    sclerosis. Postgrad Med. 19522415-22
  • These vasodilators did not change the disease
    course in spite of temporary improvements.

Why did this model lose stature as the favored
  • Blood thinners and vasodilators were only
    modestly helpful at best.
  • Research was severely limited by a lack of
  • 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.

Newer Venous Findings
  • Fog T. 1965. The topography of plaques in
    multiple sclerosis. Acta Neurol Scand.
    1965151-161 PMID5213727
  • Fog T. 1963. On the vessel-plaque relations in
    the brain in multiple sclerosis. Acta Psychiat
    Neurol Scand. 1963 39, suppl. 4258
  • 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.

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.

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 211039-1042

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.

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.
    Dec33(4)1029-35. PMID16996280
  • 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.

Venous Revival
  • Zambonis work brings the venous argument back to
    the forefront.
  • Todays 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.

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