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

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. 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 FINDINGS: 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 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. 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

Clinical correlates of grey matter pathology in multiple sclerosis

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect

Gray matter imaging in multiple sclerosis: what have we learned?

At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field