Since the initial paper, a number of CCSVI studies of various designs have been undertaken, with contradictory results. Following are some of the investigations reported within the past year:
• Researchers at the University of Buffalo found that up to 62% of the 280 patients with MS enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation study – the first randomized clinical trial to evaluate MS patients for CCSVI – had the characteristic narrowing of the extracranial veins compared with approximately 22% of 220 healthy controls. While the results, which were reported at the annual meeting of the American Academy of Neurology, did not establish causation, they showed "that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis," principal investigator Dr. Robert Zivadinov said in a statement. He acknowledged that the finding of vascular narrowing in nearly a quarter of the healthy controls warranted additional investigation.
• In an open-label study of extracranial Doppler criteria of CCSVI in 70 MS patients in Poland – 49 with relapsing-remitting MS, 5 with primary progressive MS, and 16 with secondary progressive MS – investigators detected at least two of four extracranial criteria in 90% of the patients. They concluded that, while the extracranial abnormalities could exist in various combinations, "the most common pathology in our patients was the presence of an inverted valve or another pathologic structure [like membranaceous or netlike septum] in the area of junction of the [internal jugular vein] with the brachiocephalic vein (Int. Angiol. 2010;29:109-14).
• A comparison of the internal jugular vein hemodynamics and morphology in 25 patients with MS and 25 controls identified abnormal findings in 92% of the MS patients and 24% of the controls, and evidence of CCSVI in 84% of the MS patients and none of the controls, leading the investigators to conclude that both hemodynamic abnormalities and morphologic changes in the internal jugular vein "are strongly associated with MS" (Int. Angiol. 2010;29:115-20).
• An extended extra- and transcranial color-coded sonography study in 56 MS patients and 20 controls detected no internal jugular vein stenosis and normal blood flow direction in all but 1 patient. There were no between-group differences in intracranial veins and during Valsalva maneuver, and none of the patients fulfilled more than one CCSVI criterion, according to the authors. They concluded that their findings "challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS" (Ann. Neurol. 2010;68:173-83).
• Swedish investigators used phase-contrast MRI to study 21 relapsing-remitting MS patients and 20 healthy controls and found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux between the two groups. Although contrast-enhanced MR angiography showed internal jugular vein stenosis in 3 of the 21 MS patients, the authors stated they found no evidence "confirming the suggested vascular multiple sclerosis hypothesis" (Ann. Neurol. 2010;68:255-9).
• The authors of an MR venography and flow quantification study in The Netherlands compared the intracranial and extracranial venous anatomy and the intracerebral venous flow profiles of 20 MS patients and 20 age- and gender-matched controls, with image analysis performed by blinded interventional neuroradiologists. They identified venous system anomalies in 50% of the MS patients and 40% of the healthy controls and no venous backflow in either group. "Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions," the authors wrote (J. Neurol. Neurosurg. Psychiatry 2010 Oct. 27 [doi: 10.1136/jnnp.2010.223479]).
• Italian researchers investigating the occurrence of CCSVI in 50 consecutive patients with clinically isolated syndromes suggestive of MS reviewed the patients’ extracranial and transcranial venous echo-color Doppler sonographs and compared the findings to those of 50 age- and gender matched healthy controls as well as those of 60 patients with transient global amnesia (TGA) and 60 healthy controls matched to the TGA patients. They found extracranial Doppler sonographic abnormalities in 52% of patients with possible MS, 68.3% of patients with TGA, and 31.8% of the healthy controls. While eight of the patients with possible MS fulfilled the CCSVI criteria, selective phlebography showed no venous anomalies in seven of them. The authors concluded that there was no evidence of CCSVI at MS onset but recommended further studies to "clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS" (Ann. Neurol. 2011;69:90-99).
Not only do the findings of this study challenge the hypothesis that CCSVI plays a role in the pathogenesis of MS, they suggest that some patients may be getting unnecessary surgery, according to lead author Dr. Claudio Baracchini of the University of Padua, Italy. "The few patients [in this study] with venous anomalies suggesting a CCSVI pattern had normal cerebral venous hemodynamics and all of the patients who underwent selective venography had predominantly normal findings," he said in an interview. For such patients, the surgery is "unjustified and associated with unnecessary risk," he stressed.