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MS as a Vascular Disease: Background and History Marie

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MS as a Vascular Disease: Background and History Marie Rhodes RN Second person treated for CCSVI at Stanford & Author: CCSVI as the Cause of Multiple Sclerosis – PowerPoint PPT presentation

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Title: MS as a Vascular Disease: Background and History Marie


1
MS as a Vascular Disease Background and History
  • Marie Rhodes RN
  • Second person treated for CCSVI at Stanford
  • Author CCSVI as the Cause of Multiple Sclerosis
  • Due out April 19, 2011

2
Three Topics Tonight
  • Is MS autoimmune?
  • What is venous disease?
  • Is there historical evidence for venous issues in
    MS?

3
Autoimmune Theory for MS
  • Viruses and genetics combine to program the
    immune system to attack the myelin in the brain.
  • The nerves cannot function without myelin.
  • Immune system cells called T cells are the ones
    that are accidentally programmed to attack the
    myelin, and inflammation from that activity
    damages other brain cells like oligodendrocytes
    and nerves.
  • The best way to cure MS is to suppress the immune
    system so it cant function normally and thus
    stop the attacks.

4
Is MS proven to be a primary autoimmune disease?
5
  • Young MS patient died hours into a relapse.
  • Autopsy showed death of oligodendrocyte followed
    by myelin degeneration.
  • There were no T cells or B cells at the site of
    the dead oligodendrocyte.
  • The immune system was just beginning to respond
    to clean up the dead tissue.
  • Barnett M, Prineas J. 2004. Relapsing and
    remitting multiple sclerosis pathology of the
    newly forming lesion. Ann Neurol.
    Apr55(4)458-68. PMID15048884

6
  • Hypothesis Oligodendrocyte loss and myelin
    breakdown with immune system cleanup.
  • Image by Marv Miller from CCSVI as the Cause of
    Multiple Sclerosis

Nerve cell with damaged myelin
Vein
Oligodendrocyte
Microglia
Recruited Immune System Cells
7
  • The cause of multiple sclerosis (MS) and its
    pathogenesis are unknownWe propose that MS is
    not an autoimmune disease but a genetically
    determined disorder characterized by
    metabolically dependent neuro-degeneration.
  • Behan P, Chaudhuri A. 2004. Multiple sclerosis
    is not an auto immune disease." Comment in Arch
    Neurol. Oct61(10)1610-12. PMID15477520

8
  • Importantly, despite even potent modulation of
    the immune system, which results in profound
    reduction of inflammatory lesions, the effect on
    long-term disability and progression is not as
    robust as we would expect or hope for, and
    treatment of progressive disease has thus far
    been a failure
  • Tsutsui S, Stys P. 2009. Degeneration versus
    autoimmunity in MS. Comment in Ann Neurol.
    Dec66(6)712. PMID20033985

9
Is MS autoimmune?
  • MS an inflammatory disease of unknown origin.
  • Standard MS therapies reduce inflammation, and
    much of MS damage is caused by inflammation
    itself regardless of cause relapses and
    inflammatory lesions are reduced with these
    therapies even though the trigger of the
    inflammation is unknown.
  • Autoimmune or Degenerative both are unproven
    theories. The question is which is first?

10
What is known about Chronic Venous Disease?
11
Current Understanding of CVD
  • Pressure in the vein is increased either by
    reflux or a blockage
  • This alters the endothelium (lining of the vein)
    and it becomes leaky.
  • 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 dying red blood cells, and in part
    because the endothelium is damaged.

12
  • Most of the damage to leg tissue is caused by
    immune system activity.
  • All of these problems combine so that the tissue
    has poor blood flow which worsens the problems.
  • CVD may be thought of as an inflammatory disease
    some researchers are suggesting drugs that
    suppress immune system activity may reduce the
    damage.
  • Repairing the blocked vein often results in
    healing of the lesion, though the area may remain
    very scarred.
  • 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

13
  • CVD Immune Cell Cascade with Reflux
  • Image by Marv Miller from CCSVI as the Cause of
    Multiple Sclerosis

Immune cells
Refluxing blood in stenosed vein
Red Blood Cells
14
Paolo Zamboni, MD
  • Leading venous researcher.
  • His wife got MS in 1995.
  • Noticed that MS has important features in common
    with venous disease, especially fibrin cuffs,
    iron and the way the lesions develop.
  • Investigated the idea and in 2006 presented his
    findings at the Royal Society of Medicine.

15
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
16
Further Zamboni Studies
  • Dr. Zamboni and his team of researchers evaluated
    nearly 700 people over three studies and
    discovered that MS patients had blood flow
    differences when compared to normal people.
  • Recently their landmark study involving 550
    patients and 12 clinical centers was approved.
    Called BRAVE DREAMS, it will perform treatment on
    patients and document outcomes. End point one
    year.
  • Other researchers are trying to design studies
    that help clarify the blood flow issues in MS
    patients.

17
Do Zambonis ideas have any support in standard
MS literature?
18
Jean Martin Charcot, MD 1863
  • The Father of Neurology
  • Documents widened veins and decided they were a
    result of the MS disease process

19
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

20
Tracy J. Putnam, MD
  • Dr. Putnam designed many experiments around the
    idea that MS was a vascular disease.
  • One of 20 original NMSS neurologists.

21
Putnams Experiments
  • Dr Putnam
  • -occluded the brains venous drainage in dogs
    then documented the development of lesions in
    their brains.
  • -experimented with blood thinners which provided
    modest improvement in MS relapse symptoms.
  • -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.

22
Other 50s Vascular Research
  • According to Brickner it was well known that
    vasodilators temporarily improved relapse
    symptoms (perhaps this explains the sudden
    release of symptoms in some patients after
    treatment?)
  • Debate of the 50s centered around exactly how
    these vascular issues manifested and what to do
    about them using available tools.
  • 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
  • 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

23
Immunology
  • is the study of the immune system and its
    related cells.
  • Got started in the late 50s
  • Was the impressive science of the day it was
    thought immunologists would be able to cure or
    manage all inflammatory diseases by managing the
    immune system.
  • Offered a huge advantage in that mice could be
    studied rather than people.
  • Bumped the venous model aside.

24
Newer Venous Findings
  • T. Fog dissected MS lesions and discovered they
    follow the vein closely expanding in successive
    waves countercurrent to blood flow.
  • MRI studies by Tan et al show that MS lesions are
    unique in following the shape of the vein.
  • Adhya et al show that blood flow and tissue
    perfusion is greatly reduced in MS patients.
  • 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
  • Tan et al. 2000. MR Venography of Multiple
    Sclerosis. AJNR 211039-1042
  • 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

25
What does it mean?
  • It is possible that MS is a combination of venous
    and immune abnormalities.
  • Though it is not yet proven that CCSVI causes MS,
    logic suggests that if blood flow can be improved
    this should be helpful to the brain even if MS is
    autoimmune.
  • The plausibility of the theory and the fact that
    current therapies do not stop MS means we must
    investigate this thoroughly NOW.
  • Research is just beginning to evaluate how to
    assess and treat these issues. At this time it
    is best to remember that this model is still
    being investigated and it will be some time
    before anything is proven.

26
For more information
  • Book due out April 19
  • CCSVIbook.com this power point is on the site.
  • 10 of my royalties go to CCSVI Alliance to fund
    research.
  • Digital (ie Kindle) is less expensive but I give
    the same amount to research.
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