May 17, 2012
Dr. William Maisel
Deputy Director, Center for Devices and Radiological Health, FDA
Dear Dr. Maisel,
We are writing to you regarding the alert that the FDA issued on May 10, 2012, on chronic cerebrospinal venous insufficiency or CCSVI. Like Health Canada, the FDA’s mandate is to ensure the safety of patients undergoing treatments or following drug therapy for medical conditions. The work that these two organizations perform in Canada and in the United States is essential to the health of the citizens of both countries.
Consequently, we were dismayed to read the CCSVI alert since it seems to be based on out-of-date information and a particular way of thinking that has led, in Canada, to a medical turf war between MS neurologists and vascular specialists with patients caught in the middle.
First, CCSVI is a vascular condition characterized by the stenosis of the veins responsible for draining blood from the brain. In December 2009, the International Union of Phlebology issued a consensus document confirming the view of this organization’s members, who are the world’s vein experts, that CCSVI lesions are truncular venous malformations and that CCSVI is congenital and preceding MS lesions ( HYPERLINK "http://csvi-ms.net/en/content/consensus-document-international-union-phlebology-iup-2009" http://csvi-ms.net/en/content/consensus-document-international-union-phlebology-iup-2009.
Second, the treatment for CCSVI is a treatment to correct venous malformations; it is not a treatment exclusively for Multiple Sclerosis and should not be characterized as such. Consequently, whether or not it is effective in relieving some of the symptoms of MS is irrelevant. Proper blood flow is essential to good health as we are sure you know. People who wish to be tested and treated for CCSVI should be encouraged to discuss the treatment with vascular specialists who can give expert advice and counsel based on experience and knowledge.
Third, some of the world’s leading vascular specialists (including those in the United States) have no doubt that CCSVI exists and have been treating patients for this condition since early 2010. Indeed, a prominent neurologist, Dr. Zivadinov, who heads one of the largest CCSVI research programme in the world in Buffalo, told an audience in Florida earlier this year – at the International Society for Neurovascular Disease – that there is no doubt that CCSVI exists and his research and the research of others prove it.
Fourth, it is unclear how many serious events – death and stroke – prompted the FDA’s alert. To date, over 30,000 treatments for CCSVI have been performed in 60 countries. We know of three deaths, one of which was the result of a brain aneurysm, one a result of follow-up care being denied in Canada, and one whose cause of death remains unknown at least to us. These deaths are tragic and we extend our heartfelt sympathies to the families of these people. We also extend our sympathies to the 232 people (88 in the United States) who have developed permanent brain infection linked to Tysabri and to the 49 who have died (data as of 5 April, 2012). Our sympathies also go to the families of the 11 people whose deaths have been linked to Gilenya. Tysabri and Gilenya, MS disease modifying drugs, have been approved by Health Canada and FDA and aside from “reviewing” these drugs and changing the label for Tysabri, no alert similar to the one just issued for CCSVI has been forthcoming regarding these drugs.
Fifth, the FDA alert does not acknowledge three safety studies that have been done on CCSVI treatment and that have been published in peer reviewed journals:
Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe?
Ludyga, T. et al. Phlebology. 2010 Dec;25(6): 286-96
Safety profile of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.
Petrov, I. et al. J Endovasc Ther. 2011 Jun;18(3): 314-23
Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients with multiple sclerosis.
Mandato, KD. et al. J. Vasc Interv Radiol. 2012 Jan;23(1): 55-9 Epub 2011 Nov 15
Together these three studies involved 1,261 people with CCSVI and MS and none of them found the major complications cited in the FDA alert.
Sixth, the criteria for diagnosing CCSVI using Doppler ultrasound has been well established by
Dr. Paolo Zamboni and conflicting results seem to materialize when researchers do not use the ultrasound techniques established by Dr. Zamboni. People who have been properly trained do not seem to have a problem detecting CCSVI. Obviously, some of the veins that are responsible for draining blood from the brain cannot be tested using ultrasound so a venogram is required to determine, for example, if the azygous vein in the chest is stenosed, but that poses less risk than an angiogram and both are performed every day in hospitals around the world. We could argue that a lumbar puncture to diagnose MS is far more dangerous than the diagnostic methods used to detect CCSVI (possible complications of a lumbar puncture include headache, intracranial bleeding, cardiac arrest, seizures, infection, and damage to the spinal cord or spinal nerve roots resulting in weakness or loss of sensation or even paraplegia - HYPERLINK "http://www.mult-sclerosis.org/news/May2000/ComplicationsofLumbarPunctureandTheirPrevention.html" http://www.mult-sclerosis.org/news/May2000/ComplicationsofLumbarPunctureandTheirPrevention.html).
Seventh, while the cause of MS is not known it is clear that MS has a vascular component and an autoimmune component. Whether or not CCSVI causes MS is irrelevant, however, CCSVI is the only “explanation” that has been offered to date to explain why the autoimmune system is activated so that nerve damage occurs. The idea of a vascular component for MS is not new; a French anatomist first noticed in 1839 that plaque in the brains of people with MS occurs around the veins in the brain.
Finally, people with MS and healthcare professionals need to know as much as possible to make informed decisions. The FDA alert falls short of providing the balanced information that is required.
Linda Hume-Sastre
President, CCSVI Ontario (526 members)
http://www.facebook.com/notes/ccsvi-ontario/ccsvi-ontario-challenges-the-fda-warning/333825723355005