Chronic Cerebrospinal Venous Insufficiency Criteria Research Articles

No association between variations in extracranial venous anatomy and clinical outcomes in multiple sclerosis patients over 5\u2009years

BackgroundNo longitudinal, long-term, follow-up studies have explored the association between presence and severity of variations in extracranial venous anatomy, and clinical outcomes in patients with multiple sclerosis (MS).ObjectiveThis prospective 5-year follow-up study assessed the relationship of variations in extracranial venous anatomy, indicative of chronic cerebrospinal venous insufficiency (CCSVI) on Doppler sonography, according to the International Society for Neurovascular Disease (ISNVD) proposed consensus criteria, with clinical outcomes and disease progression in MS patients.Methods90 MS patients (52 relapsing-remitting, RRMS and 38 secondary-progressive, SPMS) and 38 age- and sex-matched HIs were prospectively followed for 5.5 years. Extracranial and transcranial Doppler-based venous hemodynamic assessment was conducted at baseline and follow-up to determine the extent of variations in extracranial venous anatomy. Change in Expanded Disability Status Scale (∆EDSS), development of disability progression (DP) and annualized relapse rate (ARR) were assessed.ResultsNo significant differences were observed in MS patients, based on their presence of variations in extracranial venous anatomy at baseline or at the follow-up, in ∆EDSS, development of DP or ARR. While more MS patients had ISNVD CCSVI criteria fulfilled at baseline compared to HIs (58% vs. 37%, p = 0.03), no differences were found at the 5-year follow-up (61% vs. 56%, p = 0.486).DiscussionThis is the longest follow-up study assessing the longitudinal relationship between the presence of variations in extracranial venous anatomy and clinical outcomes in MS patients. Conclusion: The presence of variations in extracranial venous anatomy does not influence clinical outcomes over the 5-year follow-up in MS patients.

Centralized and Local Color Doppler Ultrasound Reading Agreement for Diagnosis of the Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis.

Background:An impaired cerebrospinal venous drainage was postulated to be a cofactor in the multifactorial path-ogenesis of multiple sclerosis (MS). Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by abnormalities of the main extracranial cerebrospinal venous outflow routes, which can be detected by color Doppler Ultrasound (CDUS) using 5 venous hemodynamic (VH) criteria. Discrepant results between different investigators were reported in the past, therefore the usefulness and applicability of the CCSVI CDUS-based diagnosis in clinical research and practice has been questioned.The reproducibility of proposed criteria for CCSVI detection depends on the blinding, training level, skills of the operator and interpretation of VH criteria.Objectives:To assess agreement between centralized and local reading of CDUS examination for diagnosis of CCSVI in trained Doppler sonologists.Methods: This study was performed in 78 MS patients and 28 age- and sex-matched healthy controls (HCs). Extracranial and transcranial CDUS venous hemodynamic assessment was conducted, according to International Society of Neurovascu-lar Disease (ISNVD) recommended criteria, by a single CCSVI-trained expert sonologist blinded to the subject disease sta-tus. After the local Doppler sonologist performed the investigation, all images and video clips of the CDUS examination were sent to the centralized reading center, where a second blinded reading was performed by two CCSVI-trained expert sonologists. Statistical analyses were performed comparing accuracy of CCSVI diagnosis (≥2 VH criteria) and each of the 5 individual VH criteria using Cohen kappa statistic, along with positive/negative agreement and Odds ratio (OR) with 95% confidence intervals (95% CI).Results:Diagnosis of CCSVI was obtained in 59.7% of local and 64.3% centralized readers (Kappa, 0.67, p<0.001). Simi-lar Kappa values were obtained for CCSVI diagnosis and individual CCSVI criteria in both MS patients and HCs. The high-est Kappa between local and centralized readers was observed for VH criteria 5 (0.93) followed by VH criteria 4 (0.70), VH criteria 1 (0.66), VH criteria 2 (0.64) and VH criteria 3 (0.58). The positive predictive value (PPV) and negative predictive value (NPV) for CCSVI diagnosis were 82.7% and 86,7%, respectively with an OR of 31.1 (95% CI 11.1-87.5, p<0.001). The highest agreement between local and centralized readers was observed for VH criteria 4 (OR 98.7, 95% CI 17.1-569.9, p<0.001) with 72.7% PPV and 97.3% NPV followed by VH criteria 5 (53, 95% CI 13.4-209.2, p<0.001) with 98.1% PPV and 100% NPV value.Conclusion:Centralized reading of the CDUS examination for the diagnosis of CCSVI is feasible with high accuracy in CCSVI-trained Doppler sonologists. The most reproducible VH criteria between local and centralized readers were VH cri-teria 4 and 5.

Four-dimensional flow magnetic resonance imaging and ultrasound assessment of cerebrospinal venous flow in multiple sclerosis patients and controls

A possibly causal relationship between multiple sclerosis and chronic cerebrospinal venous insufficiency has recently been hypothesized. Studies investigating chronic cerebrospinal venous insufficiency have reported conflicting results and few have employed multiple diagnostic imaging modalities across a large patient and control population. In this study, three complementary imaging modalities were used to investigate the chronic cerebrospinal venous insufficiency hypothesis in patients with multiple sclerosis and two age- and sex-matched control groups: healthy volunteers and patients with other neurological diseases. Strictly blinded Doppler ultrasound according to the original chronic cerebrospinal venous insufficiency hypothesis; four-dimensional flow magnetic resonance imaging of venous flow in the head, neck, and chest; and contrast-enhanced magnetic resonance venography for neck and chest venous luminography were acquired. An internal jugular vein stenosis evaluation was also performed across modalities. Percentage of subjects meeting ultrasound-based chronic cerebrospinal venous insufficiency criteria was small and similar between groups. In group-wise and pairwise testing, no four-dimensional flow magnetic resonance imaging variables were statistically significantly different, for any measurement location. In contrast-enhanced magnetic resonance venography of the internal jugular and azygos veins, no statistically significant differences were observed in stenosis scores between groups. These results represent compelling evidence against the chronic cerebrospinal venous insufficiency hypothesis in multiple sclerosis.

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: A Failed Concept

Chronic Cerebrospinal Venous Insufficiency: A Failed Concept

Brain Hyperechogenicities are not Associated with Venous Insufficiency in Multiple Sclerosis: A Pilot Neurosonology Study.

The "venous hypothesis" of multiple sclerosis (MS) postulates that intracranial venous congestion disintegrates the blood-brain barrier, resulting in iron accumulation in brain parenchyma triggering the inflammatory process of MS. Transcranial sonography (TCS) reveals brain parenchyma hyperechogenic alterations (BPHA) that are thought to reflect iron accumulation. We sought to investigate potential association of BPHA with chronic cerebrospinal venous insufficiency (CCSVI) in MS. MS patients were evaluated according to established TCS protocol for extrapyramidal disorders examining the presence of hyperechogenicities in different basal ganglia regions. Cerebral and cervical venous system was assessed according to proposed ultrasound protocol for CCSVI detection. In a total of 32 MS patients (age = 40 ± 14 years; male = 41%; EDSS-score = 3.1 ± 2.2) brain parenchyma hyperechogenic alterations were detected in twelve (38%) patients. The two sonographers agreed independently in 28 (87.5%) of the 32 examinations, resulting in a substantial to almost perfect agreement (Cohen's weighted kappa: substantia nigra = 0.904, Lentiform nucleus = 0.871, Thalamus = 0.784, caudate nucleus = 0.651). Two (6%) patients fulfilled the neurosonology criteria of CCSVI, while in 7 patients (22%) one positive criterion was detected. No BPHA were observed in any MS patient fulfilling CCSVI criteria. The prevalence of one positive CCSVI feature did not differ (P = .999) among patients with present (25%) or absent (20%) BPHA. There was no association of BPHA with CCSVI findings. Our findings do not support the "venous hypothesis" resulting in iron accumulation even in the few MS patients fulfilling CCSVI-criteria.

Transvascular autonomic modulation: a modified balloon angioplasty technique for the treatment of autonomic dysfunction in multiple sclerosis patients.

To describe the use of transvascular autonomic modulation (TVAM) to improve cardiovascular autonomic nervous system (ANS) dysfunction in multiple sclerosis (MS) patients, comparing the safety and efficacy of this modified technique with traditional balloon angioplasty. Twenty-one MS patients (11 men; mean age 48.7±13.0 years) who presented with symptoms of cardiovascular ANS dysfunction underwent TVAM. These patients were compared with age/sex-matched MS patients (10 men; 49.3±11.1 years) in the same stages of the disease who presented with chronic cerebrospinal venous insufficiency (CCSVI) and who underwent venous balloon angioplasty. TVAM involved the coupling of balloon angioplasty of the internal jugular veins with the application of external manual compression and dilation of the azygos and renal veins; unlike traditional angioplasty for CCSVI, which treats only abnormal veins (≥50% stenosis or static valve), all targeted vessels were treated with TVAM regardless of the presence of an abnormality. The effect of TVAM on ANS function was indicated by determining heart rate variability based on the electrocardiographic R-R interval lengths using vector analysis to derive the mean circular resultant (MCR) and the expiration/inspiration (E/I) ratio, the Valsalva ratio, and the 30:15 postural ratio at 24 hours after intervention. Left renal vein compression was common among the TVAM patients and resulted in ≥50% luminal compromise in 10 of 21 patients. Azygos vein abnormalities (a static valve) were identified in 5 patients. Overall, 18 patients met the diagnostic criteria for CCSVI with at least one lesion >50%, but only 10 lesions were considered treatable by traditional balloon angioplasty. After intervention, the R-R interval values, including the 30:15 postural ratio (p=0.01), the MCR (p=0.1), and E/I ratio (p=0.1), were higher for the TVAM patients compared to the control group. The safety profile of the TVAM procedure was similar to that of traditional balloon angioplasty. The combination of balloon angioplasty of anatomically normal veins coupled with external compression during dilation of these veins can improve indicators of ANS dysfunction. The safety and efficacy of TVAM in MS patients observed in this pilot study is encouraging, paving the way for the treatment of dysautonomia in pathological states other than MS. Further studies should investigate TVAM in a larger MS cohort.

Hydration status substantially affects chronic cerebrospinal venous insufficiency assessments

We sought to determine the effect of hydration on the criteria for chronic cerebrospinal venous insufficiency (CCSVI), a proposed hypothesis for the etiology of multiple sclerosis (MS). Sixteen subjects (11 MS and 5 controls) were asked to fast overnight. The following morning, 2 CCSVI ultrasound examinations were performed: 1 in the mildly dehydrated state, and another 30-45 minutes after rehydrating with 1.5 L of Gatorade. Seven subjects fulfilled CCSVI criteria in the dehydrated state. Of these, 5 (71%) no longer fulfilled CCSVI criteria after rehydration. One additional subject met CCSVI criteria only after rehydration. Hydration status has a substantial effect on CCSVI criteria, suggesting that the sonographic findings of CCSVI may represent a physiologic rather than pathologic state.

Cerebral arterial and venous blood flow in adolescent multiple sclerosis patients and age‐matched controls using phase contrast MRI

Altered cerebrovascular blood flow has been proposed as a mechanism for multiple sclerosis (MS). The primary objective of this study was to measure arterial and venous blood flow in adolescent MS patients and healthy controls (HC), in whom confounding factors such as age and lifestyle are less influential. Phase-contrast magnetic resonance imaging (MRI) was used to measure flow in 26 MS patients and 26 controls aged 17.7 ± 1.8 and 17.8 ± 2.1 years, respectively. Flow was measured in the left and right internal carotid arteries (ICA), vertebral arteries (VA), internal jugular veins (IJV), and epidural veins (EV). Eighteen MS patients returned for a second MRI examination after 6 months. In all participants, ultrasound criteria for chronic cerebrospinal venous insufficiency (CCSVI) were also evaluated. Flows (mL/min) in the MS group versus HC group were as follows: right ICA = 262 ± 57 vs. 263 ± 32, left ICA = 260 ± 67 vs. 270 ± 36, right VA = 96 ± 50 vs. 103 ± 30, left VA = 104 ± 37 vs. 118 ± 41, right IJV = 342 ± 180 vs. 345 ± 195, left IJV = 190 ± 131 vs. 250 ± 148, right EV = 33 ± 29 vs. 48 ± 43, and left EV = 36 ± 35 vs. 44 ± 28 (P > 0.17 for all comparisons). In MS participants, a nonsignificant trend to lower flow in the left IJV was observed, and the flow pulsatility index in the epidural veins was higher. Two MS participants met ultrasound criteria for CCSVI, but no significant difference in flow was detected. No population difference in flow rate was detected in adolescent MS participants relative to age-matched controls.

Meta-Analysis of the Correlation Between Chronic Cerebrospinal Venous Insufficiency and Multiple Sclerosis

To determine whether a correlation exists between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis (MS). A meta-analysis of the current literature was performed to evaluate the frequency of CCSVI, diagnosed by echo color Doppler criteria, in patients with MS and in normal controls. In all, 19 studies were identified from January 2005 through February 2013; however, 3 studies were excluded due to duplicate data and 3 additional studies because 0 patients fulfilled CCSVI criteria in both MS and control groups. In order to improve homogeneity, 4 outlier studies were also removed from the analysis. Analysis of the remaining 9 studies demonstrated a significant correlation between CCSVI and MS (odds ratio 1.885, P < .0001) with no significant heterogeneity of the studies (I (2) = 18, P = .279). The meta-analysis demonstrated a correlation between CCSVI and MS. However, there was no evidence that CCSVI has a causative role in MS.

Evidence against the Involvement of Chronic Cerebrospinal Venous Abnormalities in Multiple Sclerosis. A Case-Control Study

ObjectiveMultiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS. Recently a controversial vascular hypothesis for MS, termed chronic cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of this study was to evaluate the relative prevalence of the venous abnormalities that define CCSVI.MethodsA case-control study was conducted in which 100 MS patients aged between 18–65 y meeting the revised McDonald criteria were randomly selected and stratified into one of four MS subtypes: relapsing/remitting, secondary progressive, primary progressive and benign. Control subjects (16–70 y) with no known history of MS or other neurological condition were matched with the MS cases. All cases and controls underwent ultrasound imaging of the veins of the neck plus the deep cerebral veins, and magnetic resonance imaging of the neck veins and brain. These procedures were performed on each participant on the same day.ResultsOn ultrasound we found no evidence of reflux, stenosis or blockage in the internal jugular veins (IJV) or vertebral veins (VV) in any study participant. Similarly, there was no evidence of either reflux or cessation of flow in the deep cerebral veins in any subject. Flow was detected in the IJV and VV in all study participants. Amongst 199 participants there was one MS subject who fulfilled the minimum two ultrasound criteria for CCSVI. Using MRI we found no significant differences in either the intra- or extra-cranial venous flow velocity or venous architecture between cases and controls.ConclusionThis case-control study provides compelling evidence against the involvement of CCSVI in multiple sclerosis.

Feasibility and safety of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

Chronic cerebrospinal venous insufficiency (CCSVI) is a recently discovered syndrome mainly due to stenoses of internal jugular (IJV) and/or azygos (AZ) veins. The present study retrospectively evaluates the feasibility and safety of endovascular treatment for CCSVI in a cohort of patients with multiple sclerosis (MS). From September 2010 to October 2012, 1202 consecutive patients were admitted to undergo phlebograpy± endovascular treatment for CCSVI. All the patients had previously been found positive at color Doppler sonography (CDS) for at least two Zamboni criteria for CCSVI and had a neurologist-confirmed diagnosis of MS. Only symptomatic MS were considered for treatment. Percutaneous transluminal angioplasty was carried out as an outpatient procedure at two different institutes. Primary procedures, regarded as the first balloon angioplasty ever performed for CCSVI, and secondary (reintervention) procedures, regarded as interventions performed after venous disease recurrence, were carried out in 86.5% (1037 of 1199) and 13.5% (162 of 1199) of patients, respectively. Procedural success and complications within 30 days were recorded. Phlebography followed by endovascular recanalization was carried out in 1999 patients consisting of 1219 interventions. Balloon angioplasty alone was performed in 1205 out of 1219 (98.9%) procedures, whereas additional stent placement was required in the remaining 14 procedures (1.1%) following unsuccessful attempts at AZ dilatation. No stents were ever implanted in the IJV. The feasibility rate was as high as 99.2% (1209 interventions). Major complications included one (0.1%) AZ rupture occurring during balloon dilatation and requiring blood transfusion, one (0.1%) severe bleeding in the groin requiring open surgery, two (0.2%) surgical openings of the common femoral vein to remove balloon fragments, and three (0.2%) left IJV thromboses. The overall major and minor complication rates at 30 days were 0.6% and 2.5%, respectively. Endovascular treatment for CCSVI appears feasible and safe. However, a proper learning curve can dramatically lower the rate of adverse events. In our experience, the vast majority of complications occurred in the first 400 cases performed.

Doppler Ultrasound Examination of Multiple Sclerosis Patients and Control Participants: Inter-observer Agreement and Association with Disease

Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a major risk factor for multiple sclerosis (MS). The aim of this study was to assess inter-observer agreement between two ultrasound examiners and to compare findings in MS patients and control participants. A prospective, blinded, controlled study of MS patients diagnosed within 2 years (MS ≤ 2, n = 39), patients diagnosed more than 10 years ago (MS > 10, n = 43) and age- and sex-matched control participants (n = 40). Ultrasound examinations were performed by two independent examiners. CCSVI criteria 1, 3, 4 and 5 as proposed by Zamboni were explored: (1) reflux in the internal jugular (IJV) and vertebral veins (VV), (3) IJV cross-sectional area (CSA) ≤0.3 cm(2), (4) absence of flow in IJV and VV, and (5) reverted postural control of venous outflow. Criteria 1, 4 and 5 were met in less than 10% of the MS patients and control participants as studied by both examiners. The level of inter-observer agreement was poor for all parameters except assessment of the CSA of IJV at the thyroid level. Findings meeting CCSVI criterion 3 (CSA ≤ 0.3 cm(2)) were observed in 18/40 (45%) of the control participants, in 24/37 (65%) of MS ≤ 2 patients (p = 0.09 vs. control participants) and in 30/43 (70%) of the MS > 10 patients (p = 0.022 vs. control participants). The feasibility of the CCSVI criteria for common use is questionable because of low inter-observer agreement. Small-calibre IJVs meeting the CCSVI criterion 3 appear common in both Finnish control participants and MS patients, but the clinical significance of this finding is questionable.

No Evidence for Impairment of Venous Hemodynamics in Children or Young Adults with Pediatric-Onset Multiple Sclerosis

Chronic cerebrospinal venous insufficiency is a postulated etiologic factor for multiple sclerosis, but the higher frequency with longer disease duration and progressive disability suggests that chronic cerebrospinal venous insufficiency is secondary to chronic disease. We evaluated the presence of chronic cerebrospinal venous insufficiency in pediatric-onset MS. Twenty-six pediatric patients with MS (18 years of age or younger), 26 age-matched healthy controls, and 13 young adults with pediatric-onset MS underwent sonography of the internal jugular, vertebral, and deep cerebral veins. Five venous hemodynamic criteria were assessed, with 2 criteria required for chronic cerebrospinal venous insufficiency. MR imaging studies, performed in the pediatric patients with MS and healthy control groups, included intracranial 2D time-of-flight MR venography and velocity-sensitive phase-contrast sequences. Contrast-enhanced brain MR images were obtained in pediatric patients with MS to further evaluate venous patency. We used paired t tests, Wilcoxon matched pairs, McNemar tests, and exact conditional logistic regression to estimate the association of chronic cerebrospinal venous insufficiency with MS. Fifty participants (73.5%) had normal ultrasound findings, 15 (23.1%) met 1 venous hemodynamic criterion, and 2 pediatric patients with MS and 1 young adult with pediatric-onset MS met chronic cerebrospinal venous insufficiency criteria. Chronic cerebrospinal venous insufficiency was not associated with MS (odds ratio, 2.41; 95% CI, 0.19-infinity). Demographic and disease characteristics did not differ between the patients with MS meeting chronic cerebrospinal venous insufficiency criteria (n = 3) and those who did not (n = 36; all, P > .05). The mean (SD) MR imaging measures of intracerebral flow did not differ between the 2 pediatric patients with MS meeting chronic cerebrospinal venous insufficiency criteria (0.85 ± 0.11) and healthy controls (0.87 ± 0.16, P = .50); no child demonstrated venous obstruction. Chronic cerebrospinal venous insufficiency is rarely observed in children or young adults with pediatric-onset MS. Venous anatomy and flow rates indicate that venous outflow is intact in pediatric patients with MS. Our findings argue against chronic cerebrospinal venous insufficiency as a component of MS etiology.

Role of Venoplasty for Treatment of Multiple Sclerosis: Value of Open-label Studies and Surrogate Treatment Outcomes

Multiple sclerosis (MS) is considered an autoimmune disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration ( 1 Frohman E.M. Racke M.K. Raine C.S. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med. 2006; 354: 942-955 Crossref PubMed Scopus (1346) Google Scholar ). The underlying cause of MS is still unknown. The concept of a vascular link to the etiology of MS was pursued from the early years of initial MS descriptions ( 2 Charcot J. Histologie de la sclerose en plaques. Gaz Hopit Civils Milit. 1868; 41: 554-566 Google Scholar , 3 Putnam T. The pathogenesis of multiple sclerosis, a possible vascular factor. N Engl J Med. 1933; 209: 786-790 Crossref Google Scholar ). Recently, the venous vascular hypothesis returned to the forefront of MS research following a report that chronic cerebrospinal venous insufficiency (CCSVI) is unique to patients with MS ( 4 Zamboni P. Galeotti R. Menegatti E. et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009; 80: 392-399 Crossref PubMed Scopus (577) Google Scholar ). CCSVI is a vascular condition defined as impaired blood outflow from the central nervous system to the periphery, secondary to anatomic and functional abnormalities of the major extracranial veins ( 4 Zamboni P. Galeotti R. Menegatti E. et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009; 80: 392-399 Crossref PubMed Scopus (577) Google Scholar , 5 Zamboni P. Galeotti R. Menegatti E. et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009; 50 (e1–e3): 1348-1358 Abstract Full Text Full Text PDF PubMed Scopus (329) Google Scholar , 6 Zivadinov R. Marr K. Cutter G. et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology. 2011; 77: 138-144 Crossref PubMed Scopus (184) Google Scholar , 7 Dolic K. Marr K. Valnarov V. et al. Intra- and extraluminal structural and functional venous anomalies in multiple sclerosis, as evidenced by 2 noninvasive imaging techniques. AJNR Am J Neuroradiol. 2012; 33: 16-23 Crossref PubMed Scopus (32) Google Scholar , 8 Bastianello S. Romani A. Viselner G. et al. Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study. BMC Neurol. 2011; 11: 132 Crossref PubMed Scopus (38) Google Scholar , 9 Ludyga T. Kazibudzki M. Simka M. et al. Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe?. Phlebology. 2010; 25: 286-295 Crossref PubMed Scopus (79) Google Scholar , 10 Mandato K.D. Hegener P.F. Siskin G.P. et al. Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients with multiple sclerosis. J Vasc Interv Radiol. 2012; 23: 55-59 Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar ). However, recent studies have demonstrated that venous-related abnormalities are not exclusive to patients with MS, and that healthy individuals or patients with other neurologic diseases can also present with these anomalies ( 6 Zivadinov R. Marr K. Cutter G. et al. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology. 2011; 77: 138-144 Crossref PubMed Scopus (184) Google Scholar , 7 Dolic K. Marr K. Valnarov V. et al. Intra- and extraluminal structural and functional venous anomalies in multiple sclerosis, as evidenced by 2 noninvasive imaging techniques. AJNR Am J Neuroradiol. 2012; 33: 16-23 Crossref PubMed Scopus (32) Google Scholar , 11 Wattjes M.P. van Oosten B.W. de Graaf W.L. et al. No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study. J Neurol Neurosurg Psychiatry. 2011; 82: 429-435 Crossref PubMed Scopus (121) Google Scholar , 12 Centonze D. Floris R. Stefanini M. et al. Proposed chronic cerebrospinal venous insufficiency criteria do not predict multiple sclerosis risk or severity. Ann Neurol. 2011; 70: 51-58 Crossref PubMed Scopus (86) Google Scholar ). Likewise, the clinical correlates of these findings are still unknown. Clinical Improvement after Extracranial Venoplasty in Multiple SclerosisJournal of Vascular and Interventional RadiologyVol. 23Issue 10PreviewThis study proposed to prospectively evaluate safety and clinical changes in outpatient endovascular treatment in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI). Full-Text PDF

CCSVI and MS: a statement from the European Society of neurosonology and cerebral hemodynamics

To systematically review the ultrasonographic criteria proposed for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI). The authors analyzed the five ultrasonographic criteria, four extracranial and one intracranial, suggested for the diagnosis of CCSVI in multiple sclerosis (MS), together with the references from which these criteria were derived and the main studies that explored the physiology of cerebrospinal drainage. The proposed CCSVI criteria are questionable due to both methodological and technical errors: criteria 1 and 3 are based on a scientifically incorrect application of data obtained in a different setting; criteria 2 and 4 have never been validated before; criterion 2 is technically incorrect; criteria 3 and 5 are susceptible to so many external factors that it is difficult to state whether the data collected are pathological or a variation from the normal. It is also unclear how it was decided that two or more of these five ultrasound criteria may be used to diagnose CCSVI, since no validation of these criteria was performed by different and independent observers nor were they blindly compared with a validated gold-standard investigation. The European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) has considerable concerns regarding the accuracy of the proposed criteria for CCSVI in MS. Therefore, any potentially harmful interventional treatment such as transluminal angioplasty and/or stenting should be strongly discouraged.

Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: A case-control study from Iran

Chronic cerebrospinal venous insufficiency (CCSVI) is a newly suggested cause for multiple sclerosis (MS) detected by color-coded Doppler sonography. Our aim was to evaluate the relationship between CCSVI and MS compared to the control group. The study was performed on 84 MS patients and 115 healthy subjects. The presence of at least two of the extra- and/or intra-cranial Zamboni's criteria was considered positive for evidence of CCSVI. Although the total number of MS patients with any detectable CCSVI criterion was significantly higher than the controls (22.6% vs. 10.4%, P = 0.019), only one out of 84 patients fulfilled the Zamboni's criteria (1.2% vs. none, P = 0.422). Our results do not support the presence of a relationship between MS and CCSVI criteria defined by Zamboni.

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.

Abstract No. 43: The diagnostic utility of ultrasound for chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis

To evaluate the ability of ultrasound (US) to diagnose venous disease in patients with MS undergoing treatment for CCSVI. A retrospective analysis of all MS patients treated for CCSVI during an 8-month period was performed. The study population consisted of patients undergoing US of the internal jugular veins (IJV) within 24 hours of venography (CV). US was performed utilizing the protocol described by Zamboni, et al. A positive US met 2/5 criteria for CCSVI. A positive unilateral US met 2/4 criteria (without the transcranial evaluation of the deep cerebral veins). A positive CV was defined as one identifying a ≥50% stenosis in at least one vein, including the azygos vein. The US and CV findings were then compared. 416 patients were treated during the study period; the study population consisted of 310 patients (mean age 49 years; 30% male and 70% female). 224/310 patients (72%) had a positive US, and 155 (69%) of these patients had a positive CV; 86/310 patients (28%) had a negative US, and 66 (77%) of these patients had a positive CV (p=0.240). An ROC curve was generated (AUC=0.463). 300/310 (97%) patients underwent PTA of at least one vessel (215/224 with a positive US and 85/86 with a negative US) because venography showed either a ≥50% stenosis or a flow abnormality in association with a <50% stenosis; US therefore had a false negative rate of 99%. On the left side, 87/310 (28%) patients had a positive US, and 41 (47%) of these patients had a positive CV; 223/310 (72%) had a negative US, and 117 (52%) of these patients had a positive CV (p=0.472). On the right side, 63/310 (20%) patients had a positive US, and 28 (44%) of these patients had a positive CV; 247/310 (80%) had a negative US, and 130 (53%) of these patients had a positive CV (p=0.308). Findings on a Zamboni-protocol US are not associated with findings on contrast venography in light of the high false negative rate; 99% of the patients with a negative US had a significant stenosis and/or flow abnormality treated with angioplasty. A prospective study is needed to define the role of US and other modalities in the non-invasive diagnosis of CCSVI.

Proposed Chronic Cerebrospinal Venous Insufficiency Criteria Do Not Predict Multiple Sclerosis Risk or Severity

Proposed Chronic Cerebrospinal Venous Insufficiency Criteria Do Not Predict Multiple Sclerosis Risk or Severity