Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: results from the CoSMo study

Comi, Giancarlo; Battaglia, Mario Alberto; Bertolotto, Antonio; Sette, Massimo Del; Ghezzi, Angelo; Malferrari, Giovanni; Salvetti, Marco; Sormani, Maria Pia; Tesio, Luigi; Stolz, Erwin; Zaratin, Paola; Mancardi, Gianluigi

doi:10.1177/1352458513501231

Cited by 43 publications

(54 citation statements)

References 33 publications

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“…The most important limitation of the sonographic part of our study is the fact that Doppler sonography is an operator-dependent test [5,24,25]. It is also known that CCSVI is more likely to be diagnosed using ultrasound in a mildly dehydrated patient (for example, after fasting overnight) [26] and that diagnosis of CCSVI given with the use of Doppler sonography is poorly reproducible [24].…”

Section: Discussionmentioning

confidence: 98%

“…Such a unique vascular pathology is not often seen in the venous system, and for the time being no established non-invasive method for the assessment of such a condition exists [3]. Although in most of the published studies a diagnosis of CCSVI was given using Doppler sonography or MR venography, research on the validity of these tests was done primarily in the context of potential association of CCSVI with multiple sclerosis (MS) [1,[4][5][6][7]. However, it seems more accurate to validate a test against the established gold standard, and not against the presence or absence of the disease [8].…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic accuracy of Doppler sonography and magnetic resonance venography for the assessmentv of impaired outflow from the internal jugular vein in patients with multiple sclerosis

Hartel¹,

Kluczewska²,

Simka³

2015

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Objectives: This prospective study was aimed at evaluation of diagnostic value of Doppler sonography and magnetic resonance (MR) venography in the internal jugular vein territory. Material and methods: There were assessed 126 patients (252 internal jugular veins). The patients were initially diagnosed using Doppler sonography and MR venography, and then catheter venography of the veins was performed. For the purpose of this study catheter venography was regarded the reference test. We interpreted sonographic findings in the context of criteria proposed by Zamboni and criteria by International Society for Neurovascular Disease (ISNVD). We applied MR protocols aimed at flow assessment in the scanned veins: fast spin echo-T2-weighted sequences with fat saturation, and axial two-dimensional time-of-flight imaging with saturation band positioned below planned slices. Results: Catheter venography revealed lesions in 171 (67.9%) of the veins studied, primarily stenotic jugular valves (88.0% of abnormal veins). We found that sonographic criteria, using either Zamboni or ISNVD criteria were of poor diagnostic accuracy (Cohen's k coefficient < 0.1). MR venography with the use of our dedicated protocols appeared to be a slightly better diagnostic tool (k about 0.4). Conclusions:The results of our MR imaging protocols for the assessment of abnormalities in internal jugular veins were better if compared to Doppler sonography. Yet, even MR venography was far from being perfect and at the moment neither this examination nor Doppler sonography cannot replace invasive catheter venography and should not be used as a definitive test for diagnosing anatomical and functional abnormalities in the internal jugular veins.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of Doppler sonography and magnetic resonance venography for the assessmentv of impaired outflow from the internal jugular vein in patients with multiple sclerosis

Hartel¹,

Kluczewska²,

Simka³

2015

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“…In fact, the prevalence of CCSVI highlighted in case-control studies has ranged from 0% to 100% in MS patients and from 0% to 36% in controls. 1,3,11,12,26,29,41 Noncontrolled studies have shown a higher prevalence. This fact sharply contrasts with the finding of significant intraluminal (septa, webs, membranes, fixed and rudimental valves, or wall stenosis) or valvular (tricuspid valves, enlarged and malposition valve leaflets, small accessory valve leaflets) abnormalities during post-mortem examinations or surgical procedures.…”

Section: Discussionmentioning

confidence: 99%

New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study

Farina¹,

Novelli²,

Pagani³

2017

Neuro – Open Journal

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Background: The pathophysiological mechanism defined "chronic cerebrospinal venous insufficiency" (CCSVI) diagnosed using Zamboni criteria has raised a heated debate about possible correlations with several neurological disorders, but also on subjectivity of these ultrasonographic criteria used for its diagnosis. Although in 2011 new criteria have been introduced to reduce the high inter-observer variability only two studies were conducted according to the new investigation protocol. Therefore, we wanted to verify the impact of the revised protocol and its ability to meet the demand for reduction of the high heterogeneity in inter-observer agreement. Patients and Methods: Between June 2010 and June 2014, 1020 subjects (693 MS patients and 327 HCs) were prospectively screened for CCSVI by two investigators, blinded regarding the observed subject. After exclusion of discordant cases between the two examiners, 630 patients with clinically defined MS and 10 patients with CIS (clinically isolated syndrome) were matched by gender (male 38.7%, male/female 248/392) and age (mean age 44.0 years, range 18.5-77.0 years) with 315 HCs (male 43.2%, male/female 136/179-mean age 46.5 years, range 19.8-79.9 years). Results: The prevalence of CCSVI in MS subjects before the introduction of the new ECD criteria (94.3%) was observed to be significantly reduced (83.4%) after their introduction (p<0.001). In MS patients, the strength of inter-observer agreement changed from moderate (k=0.532) to good (k=0.761) before/after the revision. B-mode analysis detected only 65.7% of valvular defects. Its diagnostic accuracy was 88.6% (95% CI: 84.0%-93.2%), with a sensitivity of 83.5% (95% CI: 75.2%-89.9%), a specificity of 96.0% (95% CI: 88.8%-99.2%), a positive predictive value of 96.8% (95% CI: 91.0%-99.3%) and a negative predictive value of 80.0% (95% CI: 70.3%-87.7%). Conclusions:The new ECD criteria introduced by the revised protocol ensure, at this time, a substantial reduction of the inter-observer variability. Under this perspective, M-mode analysis is essential for its ability to identify the valvular abnormalities frequently not detectable by Bmode analysis.

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“…This generated a considerable scientific controversy, mainly linked with the initially proposed Doppler ultrasound protocol apparently affected by low reproducibility [8,13].…”

Section: Introductionmentioning

confidence: 99%

The Pathology of the Internal Jugular Vein Wall in Multiple Sclerosis

Pedriali¹,

Zamboni²

2015

J Mult Scler

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In the last years it has been described a condition named Chronic Cerebrospinal Venous Insufficiency (CCSVI), frequently but not exclusively associated to Multiple Sclerosis (MS), which generated a strong scientific controversy about the epidemiological prevalence and the possible role in the complex, multi-factorial MS ethio-pathogenesis.However, CCSVI description also stimulated a considerable research activity on the extracranial veins. Among the fields of interest, the pathology of the Internal Jugular Veins (IJVs) was deeply investigated by some groups, so improving our knowledge in an underestimated field of MS research. Currently, the available papers clearly show the presence of abnormalities in the IJV wall of MS patient's respect to control tissue. In the tunica intima a significant derangement and loss of the endothelial cells have been described. Interestingly scanning electronic microscopy showed absence of endothelium in the defective jugular valves. In the adventitia it has been described an inverted ratio between type I and type III collagen, with prevalence of the latter. Finally, in the adventitia layer it has been found the presence of calcifications arranged around the vena venarum. Assessment of immune cells in the three IJV layers did not demonstrate increased infiltration. Current studies do not clarify the origin of the pathology of the IJV in patients with MS. Congenital, infectious, or even post thrombotic ethiology have been advocated. Finally, the review summarizes studies which link the CCSVI pathophysiology to the complex MS pathogenesis, and particularly to the impact of restricted brain outflow on the cerebral spinal fluid dynamics and cerebral perfusion.

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Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: results from the CoSMo study

Cited by 43 publications

References 33 publications

Diagnostic accuracy of Doppler sonography and magnetic resonance venography for the assessmentv of impaired outflow from the internal jugular vein in patients with multiple sclerosis

Diagnostic accuracy of Doppler sonography and magnetic resonance venography for the assessmentv of impaired outflow from the internal jugular vein in patients with multiple sclerosis

New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study

The Pathology of the Internal Jugular Vein Wall in Multiple Sclerosis

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