FDA Issues Safety Warning on Controversial CCSVI Treatment
The US Food and Drug Administration (FDA) has issued a safety alert to warn people living with MS of the risks of serious injury and death associated with the “liberation procedure” used to treat chronic cerebrospinal venous insufficiency (CCSVI).
Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by stenosis (narrowing) of specific veins in the neck (internal jugular veins) and chest (azygos veins) which may impair blood drainage from the brain and upper spinal cord. It is theorized that CCSVI may be a cause of, result of, or in some way associated with multiple sclerosis.
The amount of research studies exploring various aspects of CCSVI testing, associations, and treatment have grown tremendously since Dr. Paulo Zamboni’s original studies first received notice in 2009. Since June 2010, MS Societies in the United States and Canada have devoted $3.4 million to support research into CCSVI.
Recent research presented at the American Academy of Neurology annual meeting in April 2012 did not support the theory that CCSVI is associated with MS. Andrew Barreto, MD, reported that only eight out of 206 MS patients (3.9 percent) participating in ongoing studies met the Zamboni criteria for CCSVI, while five of 59 patients (8.5 percent) with other neurological diseases met criteria.
Zamboni's criteria for CCSVI diagnoses requires that patients have two out of five abnormalities in deep cerebrospinal veins that can be visualized on ultrasound. Of the eight MS patients meeting two criteria abnormalities, three had relapsing-remitting MS, four had secondary progressive disease, and one had primary progressive disease. Another 65 of the MS patients met one of the criteria, or 32 percent of the total (Barreto, 2012).
Nearly as many of the non-MS controls, 24 percent, also met one CCSVI criterion, Barreto told MedPage Today. Another study found no association between CCSVI and pediatric-onset multiple sclerosis (Amato, 2012). Thus CCSVI may not be more common in those who have MS as compared to those who do not have MS.
In a different study published online just yesterday, researchers in Italy have made bold statements regarding the lack of scientific evidence of the CCSVI theory and liberation procedure: “We show that no piece of the CCSVI theory has a solid supportive scientific evidence. The CCSVI appears to be a rather alien condition and its existence should be definitely questioned. Finally, no proven (i.e., based on strict scientific methodology and on the rules of evidence-based medicine) therapeutic effect of the "liberation" procedure (unblocking the extracranial venous obstruction using angioplasty) has been shown up to date.” (Baracchini, 2012)
Patients who believe strongly that the “liberation procedure” would help them with the symptoms of MS have been seeking treatment outside of clinical trials and even outside of the country. For reliable information on CCSVI, please visit CCSVI Alliance.
A prospective pilot study led by Dr. Manish Mehta, vascular surgeon of Albany, NY, does suggest an association between MS and CCSVI which results in slowed emptying of the internal jugular veins (IJV). Of 50 CCSVI-MS patients with IJV stenosis (narrowing) greater than 70% who underwent balloon angioplasty (ie. “liberation” treatment), 78 percent (44/50) experienced successful treatment as defined by less than 20 percent residual stenosis. [There seems to be a discrepancy between the stats of 78% and 44/50.] CCSVI-MS patients who underwent balloon angioplasty had hemodynamic results which were comparable to healthy non-MS subjects who received no treatment (Mehta, 2012).
In February 2012, the FDA issued an additional warning letter to Dr. Mehta regarding the failure to obtain FDA approval prior to conducting a clinical trial involving angioplasty balloon treatment for CCSVI. While the FDA “encourages research to evaluate the relationship between CCSVI and MS and to characterize the safety and effectiveness of treatment procedures,” it also warns of the risk of serious adverse events associated with the use of balloon angioplasty devices or stents in the internal jugular or azygos veins.
“The FDA has received reports of one patient who died from bleeding in the brain and one patient who suffered permanent paralysis from a stroke after CCSVI treatment. Other serious complications of the CCSVI procedure reported primarily as individual incidents or case series in medical journals include: at least one death, stents migrating from their original location to another part of the body (including the heart), venous injury, blood clots forming in the jugular vein or in stents, blood clots in a vein in the brain, cranial nerve damage, and abdominal bleeding. The frequency of these serious complications is not known.” - FDA Safety Communication, May 10, 2012.
For clinical investigators and institutional review boards (IRBs), the FDA emphasizes that investigations of medical devices for use in CCSVI treatment are “significant risk studies” which require approval through an IRB and the FDA’s Investigational Device Exemption (IDE) program. Clinical investigators are encouraged to discuss trial design with the FDA early in the planning process and throughout formal and less formal meetings and conferences. Patients who experience any complication related to CCSVI treatment should report the adverse event to the FDA MedWatch program.
The serious events which the FDA references in their safety alert almost seem like old news to those of us who may have been following the development of CCSVI activism, study, and treatment over the past three years. However, I think that it is a sign of progress that CCSVI has gained enough attention and study that the FDA is publicly discussing the subject with caution.
Here is part of the response (pdf) from the Society of Interventional Radiologists (SIR) to the FDA announcement - “SIR supports and agrees with the FDA’s recommendations to encourage research on CCSVI and the current knowledge regarding the safety and effectiveness of treatment procedures. SIR also agrees that clinical research of CCSVI should be performed through well-designed clinical trials, which should require approval through the FDA investigational device exemption (IDE) program.”
Patients are encouraged to stay in close communication with their doctors and other members of their medical team.
FDA Safety Communication: Chronic Cerebrospinal Venous Insufficiency Treatment in Multiple Sclerosis Patients. Accessed May 10, 2012.
FDA Warning Letter to Dr. Manish Mehta. Accessed May 10, 2012.
“More negative results for vein blockage in MS” by John Gever, MedPage Today. Accessed May 10, 2012.
Amato MP, et al. No association between chronic cerebrospinal venous insufficiency and pediatric-onset MS. Mult Scler 2012 Apr 18. doi: 10.1177/1352458512445943 [Epub ahead of print]
Baracchini C, Atzori M, Gallo P. CCSVI and MS: no meaning, no fact. Neurol Sci. 2012 May 9. [Epub ahead of print]
Barreto A, et al. A study of CCSVI with imaging-blinded assessment: neurosonography update. AAN 2012; Abstract S10.005.
Blinkenberg M, et al. Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis. Acta Neurol Scand. 2012 Apr 25. doi: 10.1111/j.1600-0404.2012.01671.x. [Epub ahead of print]
Kramer L, et al. Prospective, case-control study of CCSVI with imaging-blinded assessment: Progress report correlating magnetic resonance venography with neurosonography. AAN 2012; Abstract S10.006.
Mehta M, et al. The Hemodynamic Impact of Balloon Angioplasty in Multiple Sclerosis Patients with Chronic Cerebrospinal Venous Insufficiency. SVS 2012; Abstract SS29.