Prevalence Of Chronic Cerebrospinal Venous Insufficiency Research Articles

Extracranial Venous Drainage Pattern in Multiple Sclerosis and Healthy Controls: Application of the 2011 Diagnostic Criteria for Chronic Cerebrospinal Venous Insufficiency

The etiology of multiple sclerosis (MS) is still largely unknown and it has been proposed that an impaired venous drainage from the central nervous system, defined as chronic cerebrospinal venous insufficiency (CCSVI), may play a role in this. We investigated the prevalence of extracranial venous drainage pattern alterations in a cohort of MS patients based on the 2011 revised diagnostic criteria for CCSVI. Thirty-nine MS patients and 18 healthy subjects underwent blinded extra-cranial venous echo-color Doppler sonography to reveal the presence of CCSVI. There was no statistically significant difference between MS patients and healthy controls regarding CCSVI prevalence (p value = 0.53). The results challenge the hypothesis that CCSVI plays a primary role in the pathogenesis of MS.

Chronic Cerebrospinal Venous Insufficiency.

Chronic Cerebrospinal Venous Insufficiency.

Italian Chronic Cerebrospinal Venous Insufficiency National Epidemiological Observatory methodology and preliminary data

The aim of our work is to describe the Memnet program’s use and potential and to show the data of Italian Chronic Cerebrospinal Venous Insufficiency (CCSVI)-National Epidemiological Observatory (NEO) activity in the first three years (http://www.osservatorioccsvi. org). From 2011 to 2014, all echo-color- Doppler (ECD) assessments were stored by Mem-net program into CCSVI-NEO web site (http://www.mem-net.it). Mem-net is a tool for multicenter data collection based on the International Society for Neurovascular Disease consensus and position statement, where we can insert patients (pts) history, neurological visits, ECD assessments, different examinations, therapies and surgical procedures. The website provides an epidemiological and statistical program for data analysis in real time. At present, 7 medical centers, affiliated to CCSVI-NEO, input their symptomatic and asymptomatic subjects with CCSVI. Data were storage using the Mem-net program. We analyzed data of only four centers on seven (Rome, Bari, Cagliari and Benevento). Total pts number with multiple sclerosis (MS) was 1109, mean age 46.0±13.4 [male 422 (38.05%); female 687 (61.95%)]. CCSVI positive pts were 937 (84.49%), CCSVI negative pts were 172 (15.51%). The CCSVI type 1 subjects were 530 (56.56%), CCSVI type 2 subjects were 20 (2.13%), CCSVI type 3 subjects were 387 (41.30%). We found 800 (85.38%) pts with criterion 1; 725 (77.37%) with criterion 2; 519 (55.39%) with criterion 3; 483 (51.55%) with criterion 4; 88 (9.39%) with criterion 5. The venous hemodynamic insufficiency severity score mean score was 3.8; the CCSVI mean score was 2.8; the MEM mean score was 34.7; the expanded disability status scale mean score was 4.5; the disease mean duration was 12.5±5.7 years. MS clinical types were divided as follows: relapsing-remitting pts were 449 (47.92%), Secondary progressive pts were 144 (15.37%), primary progressive pts were 72 (7.68%). The CCSVI-NEO database and Memnet software may be useful medical and researching tools for recording, storing, analyzing and studying ECD and vascular data. Preliminary data of NEO show an elevated prevalence of CCSVI in MS.

Chronic cerebrospinal venous insufficiency in Ménière’s disease: diagnosis and treatment

The purpose of this study was to evaluate by the means of Doppler ultrasound and phlebography the relationship between Meniere’s disease (MD) and chronic cerebrospinal venous insufficiency (CCSVI) and to test whether angioplasty is effective in improving symptoms. Phase 1: 50 patients diagnosed with definite MD (American Academy of Otolaryngology 1995) who had gained no benefit from routine therapy, underwent echoenhanced color Doppler sonography using the Zamboni protocol to check for CCSVI. Onehundred healthy subjects matched for age and gender acted as controls. Phase 2: in 20 of echo-color Doppler positive Meniere’s cases we performed a venogram and the diagnosis of associated CCSVI was confirmed. These patients were simultaneously treated by angioplasty of the internal jugular vein, then re-tested respect the baseline scales of MD. Out of a total of 50 patients with MD, an ultrasound diagnosis was made of CCSVI in 45 patients (90%). In the healthy population CCSVI is found in only 3% of cases (P<0.001). Twenty patients were given venograms that confirmed the CCSVI diagnosis. Finally, percutaneous transluminal angioplasty (PTA) proved to be effective in 90% of patients, with significant improvement of several scales of vestibular function at six months follow-up. There is a significant prevalence of CCSVI in patients with MD and treatment with PTA seems useful because of an improvement in symptoms and vestibular function recorded in the majority of patients.

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

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a possible cause ofmultiple sclerosis (MS). Objectives: The CoSMo study evaluated the association between CCSVI and MS. Methods: The primary end-point of this multicentric, case-control study was to compare the prevalence ofCCSVI between patients with MS, patients with other neurodegenerative diseases (ONDs) and healthycontrols (HCs). Color-coded duplex sonography was performed by a sonologist and the images were sentto one of three central sonologists for a second reading. Agreement between local and centralsonologists or, in case of disagreement, the predominant judgment among the three central readers,was required for a diagnosis of CCSVI. All readings, data collection and analysis were blinded. Results: The study involved 35 MS centers across Italy and included 1874 subjects aged 18–55. 1767 (94%)were evaluable: 1165 MS patients, 226 patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%,3.10% and 2.13% for the MS, OND and HC groups, respectively. No significant difference in CCSVIprevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI = 0.72–3.36,p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53–4.11, p = 0.46;MS versus OND, OR = 1.05, 95%CI = 0.47–2.39, p = 0.99). High negative and lowpositive agreement was found between the local and centralized readers. Conclusions: CCSVI is not associated with MS.

The controversy on chronic cerebrospinal venous insufficiency

The objective of this review is to analyze the actual scientific controversy on chronic cerebrospinal venous insufficiency (CCSVI) and its association with both neurodegenerative disorders and multiple sclerosis (MS). We revised all published studies on prevalence of CCSVI in MS patients, including ultrasound and catheter venography series. Furthermore, we take into consideration other publications dealing with the pathophysiologic consequences of CCSVI in the brain, as well as ecent data characterizing the pathology of the venous wall in course of CCSVI. Finally, safety and pilot data on effectiveness of endovascular CCSVI treatment were further updated. Studies of prevalence show a big variability in prevalence of CCSVI in MS patients assessed by established ultrasonographic criteria. This could be related to high operator dependency of ultrasound. However, 12 studies, by the means of more objective catheter venography, show a prevalence &gt;90% of CCSVI in MS. Global hypo-hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Postmortem studies and histology corroborate the 2009 International Union of Phlebology (UIP) Consensus decision to insert CCSVI among venous malformations. Finally, safety of balloon angioplasty of the extracranial veins was certainly demonstrated, while prospective data on the potential effectiveness of endovascular treatment of CCSVI support to increase the level of evidence by proceeding with a randomized control trial (RCT). Taking into account the current epidemiological data, including studies on catheter venography, the autoptic findings, and the relationship between CCSVI and both hypo-perfusion and cerebro-spinal fluid flow, we conclude that CCSVI can be definitively inserted among the medical entities. Research is still inconclusive in elucidating the CCSVI role in the pathogenesis of neurological disorders. The controversy between the vascular and the neurological community is due to the great variability in prevalence of CCSVI in MS patients by the means of venous ultrasound assessment. More reproducible and objective CCSVI assessment is warranted. Finally, current RCT may elucidate the role of CCSVI endovascular treatment.

Small internal jugular veins with restricted outflow are associated with severe multiple sclerosis: a sonographer-blinded, case–control ultrasound study

BackgroundRecent evidence has indicated an association between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis. Small internal jugular veins (IJVs) (with a cross-sectional area of less than 0.4 cm2) have been previously described as difficult to catheterize, and their presence may potentially affect cerebrospinal venous drainage. In this blinded extracranial color-Doppler study we had two principal aims: first, to assess prevalence of CCSVI among Serbian MS patients compared to healthy controls; and second, to assess prevalence of small IJVs (with a CSA ≤ 0.4 cm2) among MS patients and controls.MethodsThe sixty seven unrelated patients with clinical isolated syndrome (CIS), relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP) multiple sclerosis and 21 healthy controls were examined by high-resolution color-Doppler.ResultsThe ultrasonographic criteria of CCSVI (according to Zamboni) were positive in 11.9% of the patients and in none of the control subjects. The CCSVI-positive patients had significantly longer disease durations and were significantly more disabled (measured by their Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) scores), but after adjustment for gender and disease duration, CCSVI was not an independent risk factor for multiple sclerosis severity. The small IJVs were found in 28.4% of the patients and 28.6% of the controls. The patients with small IJVs were associated with decreased venous outflow from the brain and presented with longer disease durations and significantly higher EDSS and MSSS scores compared to patients without small IJVs. A multivariate logistic regression analysis adjusted for gender and disease duration showed that small IJV is an independent factor associated with multiple sclerosis severity (EDSS ≥6) (adjusted OR = 8.9, 95% CI: 1.8-45.6, p = 0.007). Among patients with small IJVs the 36.84% were also CCSVI positive.ConclusionsBoth, CCSVI and small IJVs seem to influence or follow MS severity, but only small IJVs turned out to be an independent factor in this study. Thus, small IJVs with restricted outflow, which might be aspects of CCSVI different from the criteria originally described by Zamboni, emerge as a cofactor in the multifactorial pathophysiology of multiple sclerosis.

Evidence against the concept of chronic cerebrospinal venous insufficiency in multiple sclerosis

Aims: Chronic cerebrospinal venous insufficiency (CCSVI) is currently controversially discussed as new disease concept for multiple sclerosis (MS). If an impaired cerebrospinal venous drainage induces the immune response in MS, it ought to be highly abnormal in patients, which manifest with MS during infancy or adolescence. This study aimed to address this question in assessing the prevalence of CCSVI in pediatric MS.

Italian multicentre observational study of the prevalence of CCSVI in multiple sclerosis (CoSMo study): rationale, design, and methodology

Chronic cerebro-spinal venous insufficiency (CCSVI) has been proposed as a “congenital malformation” implicated in the pathogenesis of multiple sclerosis (MS). However, numerous studies failed to confirm its presence in MS patients. This paper presents the rationale, design, and methodology adopted in the CoSMo study, conducted with the aim of verifying whether or not CCSVI is linked to MS. The primary endpoint of the CoSMo study is to compare the prevalence of CCSVI in patients with MS versus patients affected by other neurodegenerative diseases (OND) and healthy volunteers. CoSMo is a multicenter, blinded, prevalence study recruiting 2,000 adult subjects, involving 43 MS centers across Italy. Assessment of the presence or absence of CCSVI is performed by color-coded duplex (CCD) sonography and two out of the five criteria according to Zamboni are necessary for the diagnosis of CCSVI. Local CCD examination carried out by a certified sonologist and the central image readings performed by experts in the field are blinded. An advanced protocol is also described in this paper. The application of a rigorous methodological design will definitively confirm whether an association exists between CCSVI and MS. Should an association be observed, this study also further examines the link between CCSVI and the severity of MS. The addition of subgroups without MS and OND also provides information on whether CCSVI is specific to MS only. Results from the CoSMo study will play a crucial role in the possible studies concerning the potential treatment of CCSVI in MS.

CCSVI is associated with multiple sclerosis

Objectives: To analyze all the arguments against chronic cerebrospinal venous insufficiency (CCSVI) as a medical entity, and its association with multiple sclerosis (MS) and to revise all the findings suggesting a possible connection between these two entities.Methods: We revised the methodology and results of all fourteen published studies on prevalence of CCSVI in MS patients. Furthermore, we take into consideration other work dealing with possible causes and explanations of venous, as well as vascular dysfunctions linked with MS.Results: Studies of prevalence show a great variability in prevalence of CCSVI in MS patients. However, a recent meta-analysis assessed an over 13 times increased prevalence in MS. Global hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Post-mortem studies show a higher prevalence of intraluminal defects in the main extracranial vein in MS patients in respect to controls.Discussion: Taking into account the current epidemiological data, the autoptic findings, and the relationship between CCSVI and both hypoperfusion and cerebrospinal fluid flow, CCSVI can be inserted in the list of multiple factors involved in MS pathogenesis. Our careful data analysis may conclude that great variability in prevalence of CCSVI in MS patients can be a result of different methodologies used in venous ultrasound assessment. Finally, it has been proven that CCSVI share the three main risk factors with MS. On the other hand, smoking is the most important risk factor for endothelial cell damage, vitamin D has a protective role and Epstein–Barr virus passes the blood–brain barrier by invading the endothelial cells, therefore, epidemiologically, linking the imbalance of these three factors to MS through autoimmunity.

Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis

BackgroundChronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the primary veins outside the skull that has been reported to be associated with MS. In the blinded Combined Transcranial (TCD) and Extracranial Venous Doppler Evaluation (CTEVD) study, we found that prevalence of CCSVI was significantly higher in multiple sclerosis (MS) vs. healthy controls (HC) (56.1% vs. 22.7%, p < 0.001).The objective was to evaluate the clinical correlates of venous anomalies indicative of CCSVI in patients with MS.MethodsThe original study enrolled 499 subjects; 163 HC, 289 MS, 21 CIS and 26 subjects with other neurological disorders who underwent a clinical examination and a combined Doppler and TCD scan of the head and neck. This analysis was restricted to adult subjects with MS (RR-MS: n = 181, SP-MS: n = 80 and PP-MS: n = 12). Disability status was evaluated by using the Kurtzke Expanded Disability Status Scale (EDSS) and MS severity scale (MSSS).ResultsDisability was not associated with the presence (≥2 venous hemodynamic criteria) or the severity of CCSVI, as measured with venous hemodynamic insufficiency severity score (VHISS). However, the severity of CCSVI was associated with the increased brainstem functional EDSS sub-score (p = 0.002). In logistic regression analysis, progressive MS (SP-MS or PP-MS) vs. non-progressive status (including RR-MS) was associated with CCSVI diagnosis (p = 0.004, OR = 2.34, CI = 1.3–4.2).ConclusionsThe presence and severity of CCVSI in multiple sclerosis correlate with disease status but has no or very limited association with clinical disability.

Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis

The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology. We investigated cervical and cerebral veins in 24 patients with relapsing-remitting MS (RRMS) and 15 healthy controls, using extracranial high-resolution ultrasound colour Doppler (US-CD) and transcranial colour Doppler sonography (TCDS), as well as magnetic resonance imaging (MRI) and phase-contrast MR blood flow measurements (PC-MR) of the cervical veins. US-CD could not identify the left internal jugular vein (IJV) in one MS patient, other ultrasound examinations were normal in patients with MS. There was no difference in mean cross-sectional area of the IJV in MS patients compared with controls. Only one patient with MS and two healthy controls fulfilled one CCSVI criterion, and none fulfilled more than one CCSVI criterion. MR venography showed insignificant IJV stenosis (1-49%) in two patients with MS, whereas 50-69% IJV stenosis was detected in two healthy controls. There was no difference in PC-MR measurements of mean IJV blood flow between patients with MS and controls. Our results do not corroborate the presence of vascular pathology in RRMS and we found no evidence supporting the CCSVI hypothesis.

Risk Factors for Chronic Cerebrospinal Venous Insufficiency (CCSVI) (P05.127)

Objective: To investigate the association between presence of a newly proposed vascular condition called chronic cerebrospinal venous insufficiency (CCSVI) and environmental factors in a large volunteer control group without a known central nervous system pathology. Background The role of intra- and extra-cranial venous system impairment in the pathogenesis of various vascular, inflammatory and neurodegenerative neurological disorders, as well as in aging, has not been studied in detail. Design/Methods: The data were collected in a prospective study from 252 subjects who were screened for medical history as part of the entry criteria and participated in the case-control study of CCSVI prevalence in multiple sclerosis (MS) patients and were analyzed post hoc. All participants underwent physical and Doppler sonography examinations, and were assessed with a structured environmental questionnaire. Fullfilment of ≥ 2 positive venous hemodynamic (VH) criteria on Doppler sonography was considered indicative of CCSVI diagnosis. Risk and protective factors associated with CCSVI were analyzed using logistic regression analysis. Results: Seventy (27.8%) subjects presented with CCSVI diagnosis and 153 (60.7%) presented with one or more VH criteria. The presence of heart disease (p=.001), especially heart murmurs (p=.007), a history of infectious mononucleosis (p=.002), and irritable bowel syndrome (p=.005) were associated with more frequent CCSVI diagnosis. Current or previous smoking (p=.029) showed a trend for association with more frequent CCSVI diagnosis, while use of dietary supplements (p=.018) showed a trend for association with less frequent CCSVI diagnosis. Conclusions: Risk factors for CCSVI differ from established risk factors for peripheral venous diseases. Vascular, infectious and inflammatory factors were associated with higher CCSVI frequency. Supported by: Funded with internal resources of the Buffalo Neuroimaging Analysis Center and Baird MS Center, the Jacobs Neurological Institute, University of Buffalo. In addition, we received support from the Direct MS Foundation and the Jacquemin Foundation. Disclosure: Dr. Dolic has nothing to disclose. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals. Dr. Marr has nothing to disclose. Dr. Valnarov has nothing to disclose. Dr. Carl has nothing to disclose. Dr. Hagemeier has nothing to disclose. Dr. Brooks has nothing to disclose. Dr. Kilanowski has nothing to disclose. Dr. Ramanathan has received personal compensation for activities with EMD Serono, Biogen Idec, Allergan, Netezza, Pfizer, Novartis, The National Multiple Sclerosis Society, The Department of Defense, Jog for the Jake Foundation, and The National Institutes of H as a consultant.Dr. Ramanathan has received personal compensation in an editorial capacity for The American Association of Pharmaceutical Scientists.Dr. Ramanathan has received research support from EMD Serono, Biogen Idec, Allergan, Netezza, Pfizer, Novartis, The National Multiple Sclerosis Society, The Department of Defense, Jog for the Jake Foundation, and The National Institutes of H. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corporation, Bracco, Questcor Pharmaceuticals and EMD Serono.

Multiple Sclerosis: Cerebral Circulation Time

To assess cerebral circulation times (CCTs) in patients with multiple sclerosis (MS) and control subjects by using contrast material-enhanced ultrasonography (US) to determine whether vascular abnormalities can be detected in this disease. This study was approved by the local ethics committee, and informed consent was obtained from all subjects. One hundred three patients with MS and 42 control subjects underwent extracranial and transcranial venous echo-color Doppler ultrasonography (US) and contrast-enhanced US. CCT was defined as the difference in arrival time of the US contrast agent bolus between the carotid artery and the internal jugular vein. The presence of chronic cerebrospinal venous insufficiency (CCSVI) was defined according to previously reported criteria for the extracranial and transcranial US techniques. Nonparametric statistics, including the Mann-Whitney U test and the Kruskal-Wallis analysis of variance, were used to compare contrast-enhanced US parameters between groups. The longest and average CCTs were substantially prolonged in patients with MS compared with those in control subjects (median longest CCT in patients with MS, 6.47 seconds [range, 3.29-29.24 seconds]; that in control subjects, 5.54 seconds [range, 2.57-7.63 seconds]; P < .001; median average CCT in patients with MS, 5.76 seconds [range, 2.64-17.51 seconds]; that in control subjects, 5.01 seconds [range, 2.57-7.06 seconds]; P < .002). No correlation was found between CCTs and clinical parameters. The prevalence of CCSVI was higher in patients with MS than in control subjects (77% vs 28%, P < .0001). CCT was not significantly different between patients with MS who had CCSVI and patients with MS who did not (P = .182). These results suggest that contrast-enhanced US with CCT assessment may have a role in the evaluation of cerebral blood flow in patients with MS and that a vascular impairment could be associated with MS. The finding of a prolonged CCT at contrast-enhanced US does not result from outflow impairment. Further studies are required to verify these observations and to clarify if CCT and CCSVI have any physiologic and clinical relevance in MS.

Extra- and Transcranial Echo Colour Doppler in the Diagnosis of Chronic Cerebrospinal Venous Insufficiency

A new venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis (MS). It is a vascular condition characterized by an impaired cerebrospinal venous drainage due to obstructions in the main extracranial cerebrovenous outflow routes (i.e. internal jugular veins [IJV] and/or azygos veins). In this review, the studies which assessed the prevalence of CCSVI in MS by echo colour Doppler (ECD) will be discussed. The technical aspects of determination of the five CCSVI criteria: (1) reflux in the IJV and/or vertebral veins in supine and upright position, (2) reflux in the deep cerebral veins, (3) high-resolution B-mode proximal IJV stenosis, (4) flow not Doppler detectable in IJVs and/or vertebral veins (VVs) and (5) reverted postural control of the main cerebrovenous outflow pathway are described in detail. We conclude that so far there are many studies with contradictory results, and as yet a strong scientific base to support the evidence for a causative relationship of CCSVI and MS is lacking. Recent studies call into question the validity of using ECD as a proper and reliable test for the diagnosis of CCSVI. One explanation for the variety in interpretation of the individual CCSVI criteria, with the wide-ranging percentages CCSVI, could be the different methods by using ECD to determine various criteria.

Prevalence study of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: preliminary data

This study aimed to evaluate the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). From November 2009 to February 2010, 74 participants (40 MS patients and 34 healthy controls) were enrolled in a randomised singleblind prospective study. All participants underwent ultrasonography (US) to detect signs of CCSVI. CCSVI was detected in 55% of patients in the MS group and 35% in the control group; the difference was not statistically significant (p=0.089). In our experience, a slight difference exists in the prevalence of CCSVI between MS and healthy controls, but it is not as yet clear which parameters may be most significant. This preliminary study failed to show a statistically significant difference in the prevalence of CCSVI among patients affected by MS. It did, however, reveal a tendency that requires a larger number of patients to achieve statistically significant results.

Risk Factors for Chronic Cerebrospinal Venous Insufficiency (CCSVI) in a Large Cohort of Volunteers

BackgroundThe role of intra- and extra-cranial venous system impairment in the pathogenesis of various vascular, inflammatory and neurodegenerative neurological disorders, as well as in aging, has not been studied in detail. Nor have risk factors been determined for increased susceptibility of venous pathology in the intra-cranial and extra-cranial veins. The aim of this study was to investigate the association between presence of a newly proposed vascular condition called chronic cerebrospinal venous insufficiency (CCSVI) and environmental factors in a large volunteer control group without known central nervous system pathology.Methods and FindingsThe data were collected in a prospective study from 252 subjects who were screened for medical history as part of the entry criteria and participated in the case-control study of CCSVI prevalence in multiple sclerosis (MS) patients, and then were analyzed post-hoc. All participants underwent physical and Doppler sonography examinations, and were assessed with a structured environmental questionnaire. Fullfilment of ≥2 positive venous hemodynamic (VH) criteria on Doppler sonography was considered indicative of CCSVI diagnosis. Risk and protective factors associated with CCSVI were analyzed using logistic regression analysis. Seventy (27.8%) subjects presented with CCSVI diagnosis and 153 (60.7%) presented with one or more VH criteria. The presence of heart disease (p = .001), especially heart murmurs (p = .007), a history of infectious mononucleosis (p = .002), and irritable bowel syndrome (p = .005) were associated with more frequent CCSVI diagnosis. Current or previous smoking (p = .029) showed a trend for association with more frequent CCSVI diagnosis, while use of dietary supplements (p = .018) showed a trend for association with less frequent CCSVI diagnosis.ConclusionsRisk factors for CCSVI differ from established risk factors for peripheral venous diseases. Vascular, infectious and inflammatory factors were associated with higher CCSVI frequency.

Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS

Background: Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). A subject is considered CCSVI positive if ≥2 venous hemodynamic (VH) criteria are fulfilled. Objective: To determine prevalence of CCSVI in a large cohort of patients with MS, clinically isolated syndrome (CIS), other neurologic diseases (OND), and healthy controls (HC), using specific proposed echo-color Doppler (ECD) criteria. Methods: Transcranial and extracranial ECD were carried out in 499 enrolled subjects (289 MS, 163 HC, 26 OND, 21 CIS). Prevalence rates for CCSVI were calculated in 3 ways: first, using only the subjects for whom diagnosis was certain (i.e., borderline subjects were excluded); secondly, including the borderline subjects in the “no CCSVI” group; and finally, taking into account subjects who presented any of the VH criteria. Results: CCSVI prevalence with borderline cases included in the “no CCSVI” group was 56.1% in MS, 42.3% in OND, 38.1% in CIS, and 22.7% in HC ( p p p p = 0.004). Conclusions: Our findings are consistent with an increased prevalence of CCSVI in MS but with modest sensitivity/specificity. Our findings point against CCSVI having a primary causative role in the development of MS.

Systematic review of sonographic chronic cerebrospinal venous insufficiency findings in multiple sclerosis

The sonographic findings of chronic cerebrospinal venous insufficiency (CCSVI) are used by some as selection criteria for venography. We performed a systematic review to establish the prevalence and strength of association between sonographic CCSVI and multiple sclerosis (MS). Two reviewers searched PubMed and EMBASE from 1948 to date using the keywords 'chronic cerebrospinal venous insufficiency' according to PRISMA guidelines. Four cross-sectional studies met the criteria for inclusion. The prevalence of CCSVI ranged from 7% to 100% in MS patients and from 2% to 36% in healthy controls. Diagnostic odds ratios for MS varied between 2 and 26, 499 (I(2) = 94%). Sensitivities of CCSVI for MS varied between 7% and 100% (I(2) = 98%). Specificities varied between 64% and 100% (I(2) = 95%). There is substantial variation in the strength of association between CCSVI and MS beyond that explained by demographic differences or sonographer training. Reliable evidence on which to base decisions requires sonographic consensus and assessment of the reproducibility of individual criteria between trained sonographers.

Progressive multiple sclerosis is not associated with chronic cerebrospinal venous insufficiency

Chronic cerebrospinal venous insufficiency (CCSVI) had been suggested to play a major pathogenetic role in multiple sclerosis (MS), but recent data on early stages of MS have not confirmed this theory. Nonetheless, CCSVI could represent a late phenomenon of MS or be associated with progression of disability. Thus, we studied CCSVI prevalence in primary progressive (PP) and secondary progressive (SP) MS, to clarify whether CCSVI characterizes the progressive forms of this disease. A total of 35 patients with SPMS, 25 patients with PPMS, and 60 age- and gender-matched normal controls (NC) were enrolled into a cross-sectional study. Extracranial and transcranial high-resolution venous echo color Doppler sonography (ECDS-TCDS) was performed in all patients and NC. Those patients having any abnormal ultrasound finding were asked to undergo selective venography (VGF). Patients with PPMS (11 women, 14 men; mean age 47 ± 11 years) had a disease duration of 11 ± 7 years and Expanded Disability Status Scale (EDSS) score of 6.0 ± 0.5. Patients with SPMS (22 women, 13 men; mean age 45 ± 14.5 years) had a disease duration of 18 ± 14 years and EDSS score of 6.0 ± 0.8. TCDS was normal in all patients. ECDS showed one or more abnormal findings in 9/60 (15.0%) patients (7/35 [20.0%] SPMS, 2/25 [8.0%] PPMS) and in 14/60 (23.3%) NC (p not significant for all comparisons). CCSVI criteria were fulfilled in 0 NC and 4 (6.7%) patients with MS: 3 SPMS and 1 PPMS. VGF, performed in 6/9 patients, was abnormal only in one case who had bilateral internal jugular vein stenosis. Our findings indicate that CCSVI is not a late secondary phenomenon of MS and is not associated with disability.