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.

Venous malformations
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.
Chronic cerebrospinal venous insufficiency (CCSVI or CCVI) is a term invented 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 might play a role in the cause or development of multiple sclerosis (MS). Zamboni also devised a surgical procedure which the media nicknamed a liberation procedure or liberation therapy, involving venoplasty or stenting of certain veins. Zambonis ideas about CCSVI are very controversial, with significantly more detractors than supporters, and any treatments based on his ideas are considered experimental.There is no scientific evidence that CCSVI is related to MS, and there is no good evidence that the surgery helps MS patients. Zambonis 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 purported benefits have not been proven. In 2012, 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. In a 2017 study Zamboni et al. stated "Venous PTA cannot be recommended for patients with relapsing-remitting multiple sclerosis."