A to Z of MS
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A to Z of MS CCSVI (Chronic cerebro-spinal venous insufficiency)
Chronic cerebro-spinal venous insufficiency (CCSVI) is a theory proposed by Professor Paolo Zamboni, a vascular surgeon at the University of Ferrara in Italy. He suggests that in people with multiple sclerosis an abnormal narrowing in veins taking blood from the brain causes a build up of iron which crosses the blood-brain barrier damaging cells in the central nervous system.
Prevalence
Prof Zamboni's study found CCSVI in 95% of the 65 participants with MS, but not in a control group of healthy people and people with other neurological conditions.
The first study to test this theory, based at the University of Buffalo, released results in February 2010. Scans of 500 people, including 280 with MS, showed CCSVI in 56.4% of the people with MS but also in 22.4% of the healthy controls. Results were reported at the American Academy of Neurology meeting in April and further phases are ongoing.
Whilst the prevalence of CCSVI is not as clear cut as in the original findings, the implications of the higher prevalence in people with MS requires further exploration and is the subject of ongoing research. An international panel of neurologists, vascular surgeons and radiologists has been formed to review applications for funding for further studies.
Published research into the prevalence of CCSVI
A number of trials are ongoing around the world. Those below have been published.
- Zamboni P, et al.
Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.
Journal of Neurology, Neurosurgery and Psychiatry 2009;80:392-399.
read online - First blinded study of venous insufficiency prevalence in MS shows promising results
University of Buffalo press release - 10 February 2010.
Presented at the American Academy of Neurology (AAN) meeting in April 2010.
read online - Simka M, et al.
Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis.
International Angiology 2010;29(2):109-114.
abstract - Al-Omari MH, Rousan LA.
Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. International Angiology 2010;29(2):115-120.
abstract - Krogias C, et al.
Chronische zerebrospinale venöse Insuffizienz und Multiple Sklerose.
[in German - Chronic cerebrospinal venous insufficiency and multiple sclerosis]
Der Nervenarzt June 2010;81(6):740-746.
abstract (in German and English) - Doepp F, et al.
No cerebro-cervical venous congestion in patients with multiple sclerosis.
Annals of Neurology 2010;68(2):173-183.
abstract - Sundström P, et al.
Venous and cerebrospinal fluid flow in multiple sclerosis - a case-control study.
Annals of Neurology 2010;68(2):255-259.
abstract - Simka P, et al.
Correlation of localization and severity of extracranial venous lesions with clinical status of multiple sclerosis.
Poster presentation submitted to the ECTRIMS/RIMS meeting in October 2010. - Wattjes MP, et al.
No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study.
Journal of Neurology, Neurosurgery and Psychiatry 2011 Apr;82(4):429-435.
abstract - Baracchini C, et al.
No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset.
Annals of Neurology 2011 Jan;69(1):90-99.
abstract - Mayer CA, et al.
The perfect crime? CCSVI not leaving a trace in MS.
Journal of Neurology Neurosurgery and Psychiatry 2011;82(4):436-440.
full article - Zivadinov R, et al.
Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS.
Neurology 2011;77(2):138-144
full article - Marder E, et al.
No cerebral or cervical venous insufficiency in US veterans with multiple sclerosis.
Archives of Neurology 2011 Aug 8. [Epub ahead of print]
full article
Found CCSVI in 91% of people with MS (n=65), but not in people who didn't have MS (n=235)
CCSVI in 55-62.5% of people with MS (n=280) and in 25.9% of controls without MS (n=220). These results were published in April 2011
CCSVI in 90.0% of people with MS (n=70). Open label study, no control group.
CCSVI in 84% of people with MS (n=25) and 0% of controls without MS (n=25)
Abnormal ultrasound findings in 92% of people with MS and 24% of controls
CCSVI in 20% of people with MS (no numbers given or control group mentioned)
CCSVI in 0% of people with MS (n=56) and 0% of controls (n=20)
No significant differences between the MS group (n=21) and control group (n=20) relating to total internal jugular vein blood flow.
Venous blockages were found in 97.1% of the people with MS (n=381). Dr Simka leads the team offering scanning and surgery for CCSVI in Poland.
Anomalies of the venous system (venous stenosis/occlusions) in 50% of people with MS (n=20) and 40% of healthy control group (n=20). No venous backflow in any person with MS or control.
Extracranial Doppler sonography abnormalities in 52.0% of people with possible MS (n=50), in 68.3% of people with transient global amnesia (n=60) and in 31·8% of healthy controls (n=110). Eight (16%) of people with possible MS fulfilled the diagnosis of CCSVI. Selective phlebography in 7 of these people did not show venous anomalies.
One healthy control (n=20) and no people with MS (n=20) fulfilled at least two of the five criteria for CCSVI.
Peer reviewed publication of the Buffalo results. Results quote prevalence both without and including borderline cases (the latter shown in brackets). CCSVI was found in 56.1% (62.5%) in MS (n=289), 38.1% (42.1%) in CIS (n=21), 42.3% (45.8%) in other neurological conditions (n=26) and 22.7% (25.5%) in healthy controls (n=163). Amonst the people with MS, CCSVI prevalence was higher in people with progressive MS.
Four people with MS (n=18) and four controls (n=11) met one definition for CCSVI proposed by Zamboni.
Surgery
Prof Zamboni has proposed that CCSVI can be treated with surgery. His review of 35 people with relapsing remitting multiple sclerosis found that 50% had no relapses in the year following surgery, compared to 27% in the period before undergoing the procedure. Results from 30 people with progressive forms of MS showed no significant change in cognitive and motor function.1
Some centres have begun to offer scanning and surgical treatment for CCSVI. Anecdotally, there are indications of initial improvements although in a number of cases symptoms and CCSVI seem to return and some people have had further operations.
Although the surgical treatment is similar to procedures used in other conditions, there is a small risk of complications. There have been a handful of reports of problems, particularly where treatment has involved inserting a stent - a mesh tube - to support the vein. Two deaths have been reported following treatment.
A retrospective study of people attending a clinic in America reported at the Society of Interventional Radiology's Meeting in March 2011, reported that treatment - both with and without a stent - had proven safe. 231 people with MS underwent surgery with "97 percent treated without incident." Complications included abnormal heart rhythm in three people and four instances of the veins immediately re-narrowing2.
A small study of venous angioplasty with a one year follow up was published in August 20113. This reported that people in the early treatment group (n=8) had experienced two relpases compared to five in a group whose treatment was delayed for six months (n=7). 27% of particpants showed a re-narrowing of veins during the follow up period.
Prof Zamboni himself, whilst advocating scanning and treatment, suggests that surgery should be carried out within a research setting4, an opinion repeated at the 2010 ECTRIMS meeting5. This view is echoed by Dr Robert Zivadinov, who led the study at the University of Buffalo6.
In August 2011, NICE (the National Institute for Health and Clinical Excellence) issued draft guidance to the NHS on percutaneous venoplasty as treatment for CCSVI. In the consultation document, NICE is proposing that the procedure should only be used in the context of research so that further evidence on its safety and clinical efficacy can be developed7. Final guidance expected in winter 2011.
CCSVI needs further research and treatment is as yet based on incomplete evidence. However, undergoing any treatment has to be a matter of personal choice, having weighed up the benefits and risks. If considering surgery, ask key questions such as, what will the surgery achieve and how can this be demonstrated; what is the experience of the surgeon; will more operations be necessary; and what level of support is available should there be complications?
References
- Zamboni P, et al.
A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency.
Journal of Vascular Surgery 2009;50:1348-1358.
abstract - Minimally invasive treatment options for those with multiple sclerosis.
Medical News Today - 28 March 2011.
read news item - Start opening veins for MS patients, MDs say.
CBC News - 15 June 2010.
read news item - Zamboni P, et al.
Venous angioplasty in patients with multiple sclerosis: results of a pilot study.
European Journal of Vascular and Endovascular Surgery 2011 Aug 10. [Epub ahead of print]
abstract - CCSVI in focus at ECTRIMS: New data but still little clarity.
Medscape Today - 17 November 2010.
read news item - Zivadinov's update on chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis.
Question and answer item on Masters of MS website. - Percutaneous venoplasty for chronic cerebrospinal venous insuffciency (CCSVI) in multiple sclerosis.
NICE - August 2011
read on the NICE website