In 2018 a study in Neurology concluded "Our data do not support the continued use of venoplasty of extracranial jugular and/or azygous venous narrowing to improve patient-reported outcomes, chronic MS symptoms, or the disease course of MS."Research on CCSVI was fast-tracked, but researchers have been unable to find a connection between CCSVI and 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. Hypothesis
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. Pathophysiology
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 nerves 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.
The study, a phase II clinical trial designed to evaluate safety and efficacy of endovascular treatment, enrolled initially 10 patients that received the treatment and 20 more afterwards that were either allocated to receive angioplasty or a placebo intervention.Kuwait became the first country in the world where treatment of CCSVI, as of 2010, was explicitly allowed by the medical authorities and paid by the state health system. As of 2010, the procedure was performed privately in 40 countries, and, despite existing recommendations, as of 2013 it is believed that over 30,000 patients have undergone the procedure. Procedures
Balloon angioplasty and stenting have been proposed as treatment options for CCSVI in MS. The proposed treatment has been termed "liberation therapy" though the name has been criticized for suggesting unrealistic results.Balloon angioplasty in a preliminary, uncontrolled, unblinded study by Zamboni improved symptoms in MS in a minority of treated people. Although the procedure pushes the vein open temporarily, the effect does not persist, supporters advise against using stents.Venous percutaneous transluminal angioplasty (PTA) has proven to be safe but due to its ineffectiveness is not recommended. Adverse effects
While the procedure has been reported to be generally safe for MS patients, severe complications related to the angioplasty and stenting that have been reported include intracranial hemorrhage, stent migration into a renal vein, thrombosis and nerve compression syndrome of cranial nerves XI and XII. One death case appeared in the scientific literature, while 3 other deaths have been related to CCSVI treatment in the media.