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Research ArticlePractice

Vascular intervention for multiple sclerosis

Michael Kolber, Ken Makus, G. Michael Allan and Noah Ivers
Canadian Family Physician June 2011, 57 (6) 676;
Michael Kolber
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Ken Makus
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G. Michael Allan
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Noah Ivers
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Clinical question

In patients with multiple sclerosis (MS), is angioplasty of obstructed extracranial venous lesions safe and does it improve MS symptoms?

Evidence

In a cohort study, 65 MS patients with chronic cerebrospinal venous insufficiency (CCSVI) underwent angioplasty for obstructed azygous or internal jugular venous lesions.1

  • Participants: mean age 41 years, 46% male, minimal to moderate disability (not in wheelchair), taking MS disease-modifying agents.

  • Vascular outcomes: no serious operative or immediate postoperative complications.

    • -Restenosis at 1 year was about 50% for internal jugular.

  • Neurologic outcomes at 18 months, compared with baseline (no control or placebo group):

    • -No benefit in primary or secondary progressive subtypes.

    • -Significant improvements in relapsing-remitting MS subtype: fewer patients relapsing during 1-year period (50% vs 73%, P = .0014); fewer patients with lesions seen on magnetic resonance imaging (12% vs 50%, P < .0001); and improved MS functional composite and quality-of-life scores.

  • All relapsing-remitting patients with patency after their procedures were relapse free.

  • Concerns: single study site, not randomized, no control group, and unblinded.

    • -Remission is a hallmark of relapsing-remitting MS: untreated patients can have reductions (even prolonged) in clinical symptoms2,3 or lesions.4 A control group and long-term follow-up are essential.

Context

  • Hypothesis of CCSVI and MS: chronic insufficient cerebral venous drainage → cerebral iron deposits → engender the immune response underlying MS. Angioplasty improves cerebral blood outflow → decreases iron deposits → improves MS symptoms.5

  • Many patients are attempting this unproven procedure, and complications are being observed.6

  • Multiple subsequent studies question the relationship between CCSVI and MS.7–10

Bottom line

The initial study seems promising, but it is critically flawed for assessing benefit, and subsequent studies are not supportive. It is premature to recommend endovascular angioplasty for MS. The fluctuating nature of relapsing-remitting MS absolutely necessitates a long-term, multicentre, blinded RCT to determine if endovascular angioplasty is beneficial.

Implementation

Remind patients that all provider organizations and patient advocacy groups consider vascular surgery for MS purely experimental.11 While awaiting results of ongoing research, FPs can help manage MS symptoms, including depression.12 Decision aids can help patients weigh risks and benefits and make informed decisions.13,14 For those considering approved treatments, 2 decision aids exist.15,16 For those pursuing this experimental treatment, some information is available from the MS Society of Canada.17

Notes

Tools for Practice articles in Canadian Family Physician are adapted from articles published twice monthly on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician. Feedback is welcome and can be sent to toolsforpractice{at}cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

  • The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

  • Copyright© the College of Family Physicians of Canada

References

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    1. Zamboni P,
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    . A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009;50(6):1348-58.e1–3.
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    1. Martínez-Yélamos S,
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    . Regression to the mean in multiple sclerosis. Mult Scler 2006;12(6):826-9.
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    1. Ebers GC,
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    4. Kappos L,
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    6. Palace J,
    7. et al
    . Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998;352(9139):1498-504. Erratum in: Lancet 1999;353(9153):678.
    OpenUrlCrossRefPubMed
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    1. Zhao Y,
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    . Regression of new gadolinium enhancing lesion activity in relapsing-remitting multiple sclerosis. Neurology 2008;70(13 Pt 2):1092-7.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Singh AV,
    2. Zamboni P
    . Anomalous venous blood flow and iron deposition in multiple sclerosis. J Cereb Blood Flow Metab 2009;29(12):1867-78.
    OpenUrlCrossRefPubMed
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    1. Samson K
    . Experimental multiple sclerosis vascular shunting procedure halted at Stanford. Ann Neurol 2010;67(1):A13-5.
    OpenUrlPubMed
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    1. Doepp F,
    2. Paul F,
    3. Valdueza JM,
    4. Schmierer K,
    5. Schreiber SJ
    . No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010;68(2):173-83.
    OpenUrlPubMed
    1. Sundström P,
    2. Wåhlin A,
    3. Ambarki K,
    4. Birgander R,
    5. Eklund A,
    6. Malm J
    . Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol 2010;68(2):255-9.
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    1. Baracchini C,
    2. Perini P,
    3. Calabrese M,
    4. Causin F,
    5. Rinaldi F,
    6. Gallo P
    . No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset. Ann Neurol 2011;69(1):90-9.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Zivadinov R,
    2. Marr K,
    3. Cutter G,
    4. Ramanathan M,
    5. Benedict RHB,
    6. Kennedy C,
    7. et al
    . Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Ann Neurol 2011 Apr 13. Epub ahead of print.
  9. ↵
    MS Society of Canada [website]. Position statements. Toronto, ON: MS Society of Canada; 2011. Available from: http://ccsvi.ca/ccsvi/position.html. Accessed 2011 Apr 12.
  10. ↵
    1. Sollom AC,
    2. Kneebone II
    . Treatment of depression in people who have multiple sclerosis. Mult Scler 2007;13(5):632-5.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Trevena LJ,
    2. Davey HM,
    3. Barratt A,
    4. Butow P,
    5. Caldwell P
    . A systematic review on communicating with patients about evidence. J Eval Clin Pract 2006;12(1):13-23.
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  12. ↵
    1. O’Connor AM,
    2. Bennett CL,
    3. Stacey D,
    4. Barry M,
    5. Col NF,
    6. Eden KB,
    7. et al
    . Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2009;(3):CD001431.
  13. ↵
    Multiple sclerosis: should I start taking medicines for MS? Boise, ID: Healthwise; 2010. Available from: www.healthwise.net/cochranedecisionaid/Content/StdDocument.aspx?DOCHWID=tf2571. Accessed 2011 Apr 12.
  14. ↵
    Multiple sclerosis decisions. London, Engl: UCLH NHS Trust; 2010. Available from: www.msdecisions.org.uk. Accessed 2011 Apr 12.
  15. ↵
    Considering CCSVI-related procedures. Toronto, ON: MS Society of Canada; 2011. Available from: http://ccsvi.ca/procedure.html. Accessed 2011 Apr 12.
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Canadian Family Physician: 57 (6)
Canadian Family Physician
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1 Jun 2011
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Vascular intervention for multiple sclerosis
Michael Kolber, Ken Makus, G. Michael Allan, Noah Ivers
Canadian Family Physician Jun 2011, 57 (6) 676;

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