Multimodal noninvasive and invasive imaging of extracranial venous abnormalities indicative of CCSVI: Results of the PREMiSe pilot study

Abstract

BackgroundThere is no established noninvasive or invasive diagnostic imaging modality at present that can serve as a ‘gold standard’ or “benchmark” for the detection of the venous anomalies, indicative of chronic cerebrospinal venous insufficiency (CCSVI). We investigated the sensitivity and specificity of 2 invasive vs. 2 noninvasive imaging techniques for the detection of extracranial venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral veins (VVs) in patients with multiple sclerosis (MS).MethodsThe data for this multimodal imaging comparison pilot study was collected in phase 2 of the “Prospective Randomized Endovascular therapy in Multiple Sclerosis” (PREMiSe) study using standardized imaging techniques. Thirty MS subjects were screened initially with Doppler sonography (DS), out of which 10 did not fulfill noninvasive screening procedure requirements on DS that consisted of ≥2 venous hemodynamic extracranial criteria. Accordingly, 20 MS patients with relapsing MS were enrolled into the multimodal diagnostic imaging study. For magnetic resonance venography (MRV), IJVs abnormal findings were considered absent or pinpoint flow, whereas abnormal VVs flow was classified as absent. Abnormalities of the VVs were determined only using non-invasive testing. Catheter venography (CV) was considered abnormal when ≥50% lumen restriction was detected, while intravascular ultrasound (IVUS) was considered abnormal when ≥50% restriction of the lumen or intra-luminal defects or reduced pulsatility was found. Non-invasive and invasive imaging modality comparisons between left, right and total IJVs and between the VVs and azygos vein were performed. Because there is no reliable way of non-invasively assessing the azygos vein, the VVs abnormalities detected by the non-invasive testing were compared to the azygos abnormalities detected by the invasive testing. All image modalities were analyzed in a blinded manner by more than one viewer, upon which consensus was reached. The sensitivity and specificity were calculated using contingency tables denoting the presence or absence of vein-specific abnormality findings between all imaging modalities used individually as the benchmark.ResultsThe sensitivity of CV + IVUS was 68.4% for the right and 90% for the left IJV and 85.7% for the azygos vein/VVs, compared to venous anomalies detected on DS. Compared to the venous anomalies detected on MRV, the sensitivity of CV + IVUS was 71.4% in right and 100% in left IJVs and 100% in the azygos vein/VVs; however, the specificity was 38.5%, 38.9% and 11.8%, respectively. The sensitivity between the two invasive imaging techniques, used as benchmarks, ranged from 72.7% for the right IJV to 90% for the azygos vein but the IVUS showed a higher rate of venous anomalies than the CV. There was excellent correspondence between identifying collateral veins on MRV and CV.ConclusionsNoninvasive DS screening for the detection of venous anomalies indicative of CCSVI may be a reliable approach for identifying patients eligible for ...

Chronic cerebrospinal venous insufficiency: current perspectives

“…IVUS has revealed even more lesions than catheter venography, since CCSVI seems to be principally an endoluminal disease. 21,[28][29][30][31] This is probably the reason why investigators who utilized nondiluted contrast found less frequent (55%-70%) pathology in patients with multiple sclerosis. 32,33 Also, it should be remembered that catheter venography is inadequate to demonstrate external compression of the IJVs by aberrant muscles, because radiologic contrast injected into the vein, even under low pressure, can easily reopen a compressed vein.…”

“…30,32,36,37,39,40,44,46 Compression of the upper IJV was also found by MRV studies in 15%-50% of healthy individuals. 30,32,37,40,46 Further, a similar prevalence and localization of IJV stenoses in healthy controls were revealed by computed tomography angiographic studies. 47,48 Nonetheless, a pathological role of flattening of the upper IJV remains elusive.…”

“…49 The other abnormality that could be revealed by means of MRV was the presence of enlarged venous collaterals in the neck. 30,37,39,40,49 Such collaterals were found more often in patients with multiple sclerosis than in healthy controls. 37,40 However, such an increased collateral outflow has also been seen in patients with migraine, 41 and is probably an anomalous collateral outflow pattern that is not specific for multiple sclerosis.…”

“…41 and magnetic resonance techniques evaluating both morphology and flow. 30,[42][43][44] Further, current magnetic resonance imaging is not very good at demonstrating pathology of the jugular valves (catheter venography studies tell us that this is the most common CCSVI abnormality). 25,[27][28][29]45 These valves are tiny structures, which are not easily visible on standard magnetic resonance images.…”

“…In addition, the majority of authors did not verify the results of Doppler sonography against a more reliable diagnostic test, such as catheter angiography 26 or IVUS. 30,31 The researchers assessed the IJVs at different levels, used different definitions of normal and abnormal veins, used different sonographic machines, and the sonographers had very different experience in studying the IJVs (it is obvious that some of them evaluated these veins in a manner similar to that used for examination of the carotid arteries). Some of these studies were blinded, ie, the authors did not know whether they were evaluating a patient with multiple sclerosis or a healthy control, 33 test.…”