Chronic cerebrospinal venous insufficiency

Chronic cerebrospinal venous insufficiency (CCSVI or CCVI) is a term developed by Italian researcher Paolo Zamboni in 2008 to describe compromised flow of blood in the veins draining the central nervous system. Zamboni hypothesized that it played a role in the cause or development of multiple sclerosis (MS). Zamboni also devised a procedure which was termed by the media as 'liberation procedure' or 'liberation therapy', involving venoplasty (or stenting) of certain veins in an attempt to improve blood flow. Chronic cerebrospinal venous insufficiency (CCSVI or CCVI) is a term developed by Italian researcher Paolo Zamboni in 2008 to describe compromised flow of blood in the veins draining the central nervous system. Zamboni hypothesized that it played a role in the cause or development of multiple sclerosis (MS). Zamboni also devised a procedure which was termed by the media as 'liberation procedure' or 'liberation therapy', involving venoplasty (or stenting) of certain veins in an attempt to improve blood flow. Within the medical community, both the procedure and CCSVI have been met with skepticism. Zamboni's first published research was neither blinded nor did it have a comparison group. Zamboni also did not disclose his financial ties to Esaote, the manufacturer of the ultrasound specifically used in CCSVI diagnosis. The 'liberation procedure' has been criticized for possibly resulting in serious complications and deaths while its benefits have not been proven. The United States Food and Drug Administration states that it is not clear if CCSVI exists as a clinical entity and that these treatments may cause more harm. In 2017 they emphasized that this use of balloon angioplasty is not an approved use. Research on CCSVI has been fast tracked but researchers have been unable to confirm whether CCSVI has a role in causing MS. This has raised serious objections to the hypothesis of CCSVI originating multiple sclerosis. Additional research investigating the CCSVI hypothesis is underway. A 2013 study found that CCSVI is equally rare in people with and without MS, while narrowing of the cervical veins is equally common. Proposed consequences of CCSVI syndrome include intracranial hypoxia, delayed perfusion, reduced drainage of catabolites, increased transpulmonary pressure, and iron deposits around the cerebral veins. Multiple sclerosis has been proposed as a possible outcome of CCSVI. Zamboni and colleagues claimed that in MS patients diagnosed with CCSVI, the azygos and IJV veins are stenotic (abnormally narrowed) in around 90% of cases. Zamboni theorized that malformed blood vessels cause increased deposition of iron in the brain, which in turn triggers autoimmunity and degeneration of the nerve's myelin sheath. While the initial article on CCSVI claimed that abnormal venous function parameters were not seen in healthy people, others have noted that this is not the case. In the report by Zamboni none of the healthy participants met criteria for a diagnosis of CCSVI while all patients did. Such outstanding results have raised suspicions of a possible spectrum bias, which originates on a diagnostic test not being used under clinically significant conditions. Further studies of the relationship between CCSVI and MS have had variable results, with many failing to reproduce the association between MS and CCSVI. Moreover, the greatest predictor of positive results is researchers' involvement in the administration of the 'liberation procedure'. This effect goes to the extent that, when only fully independent studies are considered, no association at all is found. The poor reproducibility across studies and diagnostic modalities has led some authors to conclude that CCVSI might be nothing more than a clinically irrelevant sonographic construct. Already by 2010, there were 'a growing number of papers that raise serious questions about its (CCSVI) validity', although evidence had been 'both for and against the controversial hypothesis'. It was agreed that it was urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS, although existing data did not support CCSVI as the cause of MS. Most of the venous problems in MS patients have been reported to be truncular venous malformations, including azygous stenosis, defective jugular valves and jugular vein aneurysms. Problems with the innominate vein and superior vena cava have also been reported to contribute to CCSVI. A vascular component in MS had been cited previously. Several characteristics of venous diseases make it difficult to include MS in this group. In its current form, CCSVI cannot explain some of the epidemiological findings in MS. These include risk factors such as Epstein-Barr infection, parental ancestry, date of birth and geographic location. MS is also more common in women, while venous diseases are more common in men. Venous pathology is commonly associated with hypertension, infarcts, edema and transient ischemia, and occurs more often with age, however these conditions are hardly ever seen in MS and the disease seldom appears after age 50. Finally, an organ-specific immune response is not seen in any other kind of venous disease.