Chronic cerebrospinal venous insufficiency (CCSVI or CCVI), a term proposed by Italian neurosurgeon and researcher Dr. Paolo Zamboni, M.D. in 2008 to describe compromised flow of blood in the veins draining the central nervous system and hypothesized as a factor in development of multiple sclerosis (MS), is nothing if not controversial. MS is an unpredictable, progressive, immune-mediated disorder of the brain and spinal cord that affects more than 400,000 people in the United States and 2.1 million in the world.
Dr. Zamboni theorized in published research that CCSVI is a new disorder in which veins draining the central nervous system are abnormal, and that this insufficient venous drainage results in iron accumulation and enhanced central nervous system inflammation. He developed a surgical technique to restore efficient drainage, with some patients who have undergone these endovascular balloon and stent venoplasty procedures anecdotally reporting improvement — sometimes dramatic — in their MS symptoms. However not all researchers have been able to duplicate Dr. Zamboni’s results.
The United States Food and Drug Administration states that studies exploring a link between MS and CCSVI are inconclusive — some suggesting a link exists, while others have found no such connection, and at this time, the FDA believes there is no reliable evidence from controlled clinical trials that this procedure is effective in treating MS and that surgical CCSVI treatments may cause more harm. Dr. Zamboni’s first published research was neither blinded nor did it have a comparison group.
In a new study of CCSVI at The University of Texas Health Science Center at Houston (UT Health), which was published in a recent early online edition of the Annals of Neurology. a UT interdisciplinary team of researchers used several imaging methods that showed CCSVI occurs at a low rate in both people with multiple sclerosis (MS) and non-MS volunteers, contrary to some previous studies.
“Our results in this phase of the study suggest that findings in the major veins that drain the brain consistent with CCSVI are uncommon in individuals with MS and quite similar to those found in our non-MS volunteers,” comments Jerry Wolinsky, M.D., principal investigator and the Bartels Family and Opal C. Rankin Professor of Neurology at The UT Health Medical School in a release. “This makes it very unlikely that CCSVI could be the cause of MS, or contribute in an important manner to how the disease can worsen over time.” Dr. Wolinsky is also a member of the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston and director of the UT Health MS Research Group.
UT Health was one of three institutions in the United States to receive an initial grant to study CCSVI in multiple sclerosis (MS). The grant was part of a $2.3 million joint commitment from the National MS Society and the MS Society of Canada.
The UT Health team tested several imaging methods including ultrasound, magnetic resonance imaging with an intravenous contrast agent, and direct radiologic investigation of the major veins by direct injection of veins with radio-opaque contrast. The goal was to validate a consistent, reliable diagnostic approach for CCSVI, determine whether CCSVI was specific to MS and if CCSVI contributed to disease activity.
The team was blinded to the participant’s diagnosis throughout the study. Doppler ultrasound was used to investigate venous drainage in 276 people — 206 with MS and 70 non-MS. The MS patients were recruited from the MS program of the university neurology clinic and were aged 18 to 65 years, without a history of venoplasty. Non-MS subjects included healthy controls recruited from employees at the university and individuals with other neurological diseases invited from the general and vascular disease specialty programs of the university neurology clinic.
Using the criteria described by Zamboni for the diagnosis of CCVSI, UT Health researchers found less prevalence of CCVSI than in some previous studies and no statistical difference between those with MS and those without MS. The report further notes that CCSVI are much less prevalent than initially reported, and do not distinguish MS from other subjects, and the UT Health researchers’ findings do not support the hypothesis that CCSVI is causally associated with MS. Detailed experience with the other imaging approaches are being readied for publication.
The UT Health team’s findings are certain to stir the CCVSI controversy pot further.