Dataset Information

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis.

ABSTRACT:

Background

The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis.

Methods

We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls using extracranial Doppler ultrasonography and gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were blinded to the clinical status of participants.

Results

We enrolled 120 patients with multiple sclerosis and 60 healthy controls. High proportions of both patients (67/115 [58%]) and controls (38/60 [63%]) met 1 or more of the proposed ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency (p = 0.6). A minority of patients (23/115 [20%]) and controls (6/60 [10%]) fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences between patients and controls in the prevalence of each individual ultrasound criterion. Similarly, there were no differences in intracranial or extracranial venous patency between groups, as measured by magnetic resonance venography.

Interpretation

We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls. Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity.

SUBMITTER: Costello F

PROVIDER: S-EPMC4119167 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis.

Costello Fiona F Modi Jayesh J Lautner David D Bhayana Deepak D Scott James N JN Davenport W Jeptha WJ Trufyn Jessie J Frayne Richard R Ciura Viesha A VA Goyal Mayank M Mah Jean J Hill Michael D MD

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20140602 11

<h4>Background</h4>The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis.<h4>Methods</h4>We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy control ...[more]

PMID: 24890104

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Project description:BACKGROUND: It has been proposed by Zamboni and colleagues that multiple sclerosis is caused by chronic cerebrospinal venous insufficiency, a term used to describe ultrasound-detectable abnormalities in the anatomy and flow of intra- and extracerebral veins. We conducted a meta-analysis of studies that reported the frequency of chronic cerebrospinal venous insufficiency among patients with and those without multiple sclerosis. METHODS: We searched MEDLINE and EMBASE as well as bibliographies of relevant articles for eligible studies. We included studies if they used ultrasound to diagnose chronic cerebrospinal venous insufficiency and compared the frequency of the venous abnormalities among patients with and those without multiple sclerosis. RESULTS: We identified eight eligible studies: all included healthy controls, and four of them also included a control group of patients with neurologic diseases other than multiple sclerosis. Chronic cerebrospinal venous insufficiency was more frequent among patients with multiple sclerosis than among the healthy controls (odds ratio [OR] 13.5, 95% confidence interval [CI] 2.6-71.4), but there was extensive unexplained heterogeneity among the studies. The association remained significant in the most conservative sensitivity analysis (OR 3.7, 95% CI 1.2-11.0), in which we removed the initial study by Zamboni and colleagues and added a study that did not find chronic cerebrospinal venous insufficiency in any patient. Although chronic cerebrospinal venous insufficiency was also more frequent among patients with multiple sclerosis than among controls with other neurologic diseases (OR 32.5, 95% CI 0.6-1775.7), the association was not statistically significant, the 95% CI was wide, and the OR was less extreme after removal of the study by Zamboni and colleagues (OR 3.5, 95% 0.8-15.8). INTERPRETATION: Our findings showed a positive association between chronic cerebrospinal venous insufficiency and multiple sclerosis. However, poor reporting of the success of blinding and marked heterogeneity among the studies included in our review precluded definitive conclusions.

Project description:BackgroundNormally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs).MethodsThe IJVs of 313 MS patients with CCSVI (male 43.8%, male/female 137/176; mean age 45 years old, range 19-77 years) and 298 HCs, matched by gender (male 43.6%, male/female 130/168) and age (mean age 46 years old, range 20-79 years), were compared using ECD. Their CSAs were evaluated with the subjects seated in a tiltable chair, first in the supine position at the level of the cricoid cartilage, with the head in a neutral position, and then after contralateral rotation to 90° from midline.ResultsSignificant differences between the jugular CSAs before and after head rotation were observed only in the MS patients for the IJVs with wall collapse (F[6,1215]?=?6414.57, p?<?0.001), showing on longitudinal scans a typical "hourglass" aspect that we defined as "miopragic". No significant difference was found in the distribution of these miopragic veins with regard to MS duration. There was a strong association between the CCSVI scores and the complexity of jugular morphological types (?2 [9, N?=?313]?=?75.183, p?<?0.001). Wall miopragia was mainly observed in MS patients with SP (59.3%) and PP (70.0%) clinical forms, compared to RR (48.3%) forms (p?=?0.015).ConclusionA dynamic ECD approach allowed us to detect IJVs with a significant increase in their CSAs during head rotation, but only in MS subjects. This feature, most likely the expression of congenital wall miopragia, could be secondary to dysregulation of collagen synthesis, but further histochemical studies will be needed to confirm this hypothesis.

Project description: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.

Dataset Information

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis.

Background

Methods

Results

Interpretation

Publications

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis.

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