Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: A pilot study in multiple sclerosis patients and healthy controls
Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of primary veins outside the skull that restrict normal outflow of blood from the brain. CCSVI was recently described as highly prevalent in patients with multiple sclerosis (MS), and can be non-invasively diagnosed by Doppler sonography (DS) and invasively by selective venography (SV). The aim of this paper was to investigate the value of neck magnetic resonance venography (MRV) for the diagnosis of CCSVI compared to DS and SV in patients with MS and in healthy controls (HC).
Ten MS patients and 7 HC underwent DS, 2D-Time-Of-Flight venography (TOF) and 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS). MS patients also underwent SV. The internal jugular veins (IJVs) and the vertebral veins (VVs) were assessed by both MRV sequences, and the findings were validated against SV and DS. SV has been considered the diagnostic gold standard for MS patients.
All MS patients and none of the HC presented CCSVI, according to the DS criteria. This was confirmed by SV. For CCSVI diagnosis, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, whereas the figures were 40%, 85%, 58%, 80% and 50% for 3D-TRICKS, and 30%, 85%, 52%, 75% and 46% for 2D-TOF in the IJVs. In MS patients, compared to SV, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100%, 75%, 95%, 94% and 100%, whereas the figures were 31%, 100%, 45%, 100% and 26% for 3D-TRICKS and 25%, 100%, 40%, 100% and 25% for 2D-TOF in the IJVs.
The use of MRV for diagnosis of CCSVI in MS patients has limited value, and the findings should be interpreted with caution and confirmed by other imaging techniques such as DS and SV.
"All subjects were examined on a 3 T GE Signa Excite HD 12.0 scanner (General Electric, Milwaukee, WI). A multi-channel head and neck (HDNV) coil was used to acquire the following sequences: an unenhanced 2D-Time of Flight (TOF) and enhanced 3D-Time Resolved Imaging of Contrast KineticS (TRICKS), as previously described
[6,8,22-24]. The parameters used for TOF were: TR/TE 17/4.3 msec (repetition/echo time), flip angle of 70 degrees, 1.5 mm slice thickness, field of view (FOV) = 220 mm, acquisition matrix 320/192, phase FOV 75%, for an in-plane resolution (IPR) of 0.7 mm × 1.1 mm and acquisition in axial scan plane. "
[Show abstract][Hide abstract] ABSTRACT: There 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 teh 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).
The 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.
The 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.
Noninvasive DS screening for the detection of venous anomalies indicative of CCSVI may be a reliable approach for identifying patients eligible for further multimodal invasive imaging testing of the IJVs. However, the noninvasive screening methods were inadequate to depict the total amount of azygos vein/VVs anomalies identified with invasive testing. This pilot study, with limited sample size, shows that both a non-invasive and invasive multimodal imaging diagnostic approach should be recommended to depict a range of extracranial venous anomalies indicative of CCSVI. However, lack of invasive testing on the study subjects whose results were negative on the DS screening and of healthy controls, limits further generalizibility of our findings. In addition, the findings from the 2 invasive techniques confirmed the existence of severe extracranial venous anomalies that significantly impaired normal blood outflow from the brain in this group of MS patients.
"While the diagnosis of CCSVI can be established using noninvasive and invasive imaging techniques , the validity of DS to establish the diagnosis of CCSVI remains controversial. We showed previously that DS, in properly trained hands, has high sensitivity and specificity for CCSVI diagnosis, when compared to invasive imaging methods [48,49]. This was the same method as used in this study, and thus we are confident in the validity of the CCSVI categorization in our analysis. "
[Show abstract][Hide abstract] ABSTRACT: Chronic cerebrospinal venous insufficiency (CCSVI) has been reported in multiple sclerosis (MS) yet its significance in relation to cognitive function is undetermined.This study measured the association between the presence and severity of CCSVI and cognitive impairment in patients with MS.
CCSVI was assessed using extra-cranial and trans-cranial Doppler sonography in 109 MS patients (79 with relapsing-remitting, 23 with secondary-progressive and 7 with primary-progressive disease subtype). A subject was considered CCSVI-positive if >=2 venous hemodynamic criteria were fulfilled. The Minimal Assessment of Cognitive Function in MS (MACFIMS) battery was administered assessing the full spectrum of cognitive domains known to be affected by MS. Depression was quantified using the Beck Depression Inventory Fast Screen (BDIFS). Partial correlations, analysis of variance (or covariance) and linear regression were used to examine the hypothesis that CCSVI status is related to cognition or depression after controlling for education and gender.
There were 64 (58.7%) patients who were considered CCSVI-positive. The regression models predicting venous hemodynamic insufficiency severity score were not statistically significant for any of the MACFIMS predictor variables. The analysis of variance tests showed a significant effect of CCSVI-positive diagnosis on cognitive ability in only one of the 10 MACFIMS outcomes, and that one was in the opposite direction of the tested hypothesis. There was no correspondence between CCSVI diagnosis and depression, as measured by the BDIFS.
We find no evidence of an association between the presence and severity of CCSVI with cognitive impairment and depression in patients with MS.
BMC Medicine 07/2013; 11(1):167. DOI:10.1186/1741-7015-11-167 · 7.25 Impact Factor
"The dramatic difference in prevalent findings between different studies using non-invasive and invasive imaging techniques (ranging from 0% to 100%) emphasizes the urgent need for the use of a multimodal imaging approach for better understanding of the venous anomalies and developmental variants being considered in CCSVI . In a number of recent studies, noninvasive and invasive imaging techniques were applied and compared [18,27,30,31,34,42,43,47],[50,81,82,102,107,134]. The findings of these studies are extremely important to understand the true prevalence of CCSVI and the comparison of invasive vs. noninvasive imaging findings is especially important in this endeavor. "
[Show abstract][Hide abstract] ABSTRACT: The extra-cranial venous system is complex and not well studied in comparison to the peripheral venous system. A newly proposed vascular condition, named chronic cerebrospinal venous insufficiency (CCSVI), described initially in patients with multiple sclerosis (MS) has triggered intense interest in better understanding of the role of extra-cranial venous anomalies and developmental variants. So far, there is no established diagnostic imaging modality, non-invasive or invasive, that can serve as the "gold standard" for detection of these venous anomalies. However, consensus guidelines and standardized imaging protocols are emerging. Most likely, a multimodal imaging approach will ultimately be the most comprehensive means for screening, diagnostic and monitoring purposes. Further research is needed to determine the spectrum of extra-cranial venous pathology and to compare the imaging findings with pathological examinations. The ability to define and reliably detect noninvasively these anomalies is an essential step toward establishing their incidence and prevalence. The role for these anomalies in causing significant hemodynamic consequences for the intra-cranial venous drainage in MS patients and other neurologic disorders, and in aging, remains unproven.
BMC Medicine 06/2013; 11(1):155. DOI:10.1186/1741-7015-11-155 · 7.25 Impact Factor
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