What Went Wrong? the Flawed Concept of Cerebrospinal Venous Insufficiency

Abstract

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis (MS), coining the term of chronic cerebrospinal venous insufficiency (‘CCSVI'). The diagnosis of ‘CCSVI' is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration. The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of ‘CCSVI' could alleviate MS. Many investigators tried to replicate Zamboni's results with duplex sonography, magnetic resonance imaging, and catheter angiography. The data obtained here do generally not support the ‘CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the ‘CCSVI' concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment. In our view, there is currently no basis to diagnose or treat ‘CCSVI' in the care of MS patients, outside of the setting of scientific research.

Concomitant Analysis of Arterial, Venous, and CSF Flows using Phase-Contrast MRI: A Quantitative Comparison Between MS Patients and Healthy Controls

“…15 Transcranial color-coded sonography is an imaging method with many advantages (rapid, cheap, realization on patient's bedside), but suffers significantly limiting factors such as operator's skills and experience, head position, respiration, heart rate, external compression, hydration status, as well as factors related to the absence of blinding, and to some technical factors. 16 In turn, PC-MRI, especially using semi-automatic segmentation algorithms, 9 offers operator-independent, rapid, non-invasive; and reproducible quantitative assessment of extracranial and intracranial flows. Moreover, its relevance in venous flow quantification has been demonstrated in healthy subjects in a previous study, 8 and results were validated because they were similar to those of the invasive catheter venography, stated as the gold-standard reference technique.…”

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis

“…20 The definition of venous reflux used by Zamboni and colleagues has been challenged because spectral Doppler measurements of duration were not implemented. 21 Furthermore, the 0.88-second threshold used to identify reflux was adopted from a study that examined internal jugular vein valve insufficiency during the Valsalva manoeuvre and was not based on validated methodology.…”

Modifiable environmental factors in multiple sclerosis

“…In fact, there are reports clearly showing that patients are willing to run the risk of lifeendangering side effects from immunosuppressive drugs for MS in order to continue with the treatment 57,58 . Furthermore, thousands of patients with MS worldwide were found to be willing to submit themselves to a vascular surgical procedure to treat their MS for which there was no scientific basis 59 . The evidence arising from these events therefore begs the following questions: Should modifiable factors be so difficult to modify, given that the methods are inexpensive and safe?…”