Chronic cerebrospinal venous insufficiency in multiple sclerosis: diagnostic, pathogenetic, clinical and treatment perspectives

Abstract

Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in multiple sclerosis patients. CCSVI is characterized by impaired brain venous drainage due to outflow obstruction in the extracranial venous system, mostly related to anomalies in the internal jugular and azygos veins. The current CCSVI diagnosis is based on Doppler sonography of extracranial and transcranial venous hemodynamics criteria. To date, prevalence estimates of CCSVI, provided by different groups using various imaging methods of assessment, vary widely from none to 100%. There is an urgent need to define and validate the spectrum of cranial/extracranial venous anomalies and to establish reliable, diagnostic gold-standard test(s). The potential usefulness of endovascular treatment for CCSVI in multiple sclerosis patients is still unknown.

Keywords::

• association
• causality
• chronic cerebrospinal venous insufficiency
• diagnosis
• multiple sclerosis
• pathogenesis
• prevalence
• treatment

Acknowledgement

We thank Eve Salczynski for technical assistance in the preparation of this manuscript.

Disclosure

The results from the Combined Transcranial and Extracranial Venous Doppler study led to the organization of the institutional review board-approved, unblinded, open-label, descriptive, fee-for-service registry study that included patients with either possible or definite multiple sclerosis who sought information on their chronic cerebrospinal venous insufficiency status. This study completed enrollment. The Buffalo Neuroimaging Analysis Center organized a 5-day Cerebral Venous Function and Anomaly Program for Continuing Medical Education (CME) Credit. The University of Buffalo School of Medicine & Biomedical Sciences designated this educational activity for a maximum of 30.75 AMA PRA Category 1 Credit(s)™. The Society of Diagnostic Medical Sonographers has approved this educational activity for a maximum of 25 CME Credits. The Esaote North America provided logistical support for this CME course.

Financial & competing interests disclosure

The authors of this review article declare that their chronic cerebrospinal venous insufficiency studies were funded with internal resources of the Buffalo Neuroimaging Analysis Center, Baird MS Center and the Jacobs Neurological Institute, University of Buffalo (NY, USA). In addition, they received support from the Direct MS Foundation, Kaleida-Health, Volcano, Ev3, Codman, the Jacquemin Foundation, the Bronfman Foundation and from smaller donors.

Robert Zivadinov received personal compensation from Teva Neuroscience, Biogen Idec, EMD Serono and Questcor Pharmaceuticals for speaking and consultancy fees. He received financial support for research activities from Biogen Idec, Teva Neuroscience, Genzyme, Bracco, Questcor Pharmaceuticals and EMD Serono.

Murali Ramanathan received research funding or consulting fees from EMD Serono, Biogen Idec, Allergan, Netezza, Pfizer, Novartis, the National Multiple Sclerosis Society, the Department of Defense, Jog for the Jake Foundation, the National Institutes of Health and National Science Foundation. He received compensation for serving as an Editor from the American Association of Pharmaceutical Scientists. These are unrelated to the research presented in this article.

Adnan H Siddiqui has received research grants from the NIH and the University at Buffalo (Research Development Award); holds financial interests in Hotspur, Intratech Medical, StimSox, and Valor Medical; serves as a consultant to Codman & Shurtleff, Inc., Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting, and Penumbra; and belongs to the speakers’ bureaus of Codman & Shurtleff, Inc. and Genentech. He serves on an advisory board for Codman & Shurtleff; and has received honoraria from Abbott Vascular, American Association of Neurological Surgeons’ courses, an emergency medicine conference, Genentech and Neocure Group LLC.

Ralph HB Benedict received personal compensation for consulting, speaking and serving on a scientific advisory board for Bayer, Biogen Idec and EMD Serono. He received financial support for research activities from Biogen Idec, Shire, Accorda, NIH and NMSS.

Bianca Weinstock-Guttman received personal compensation for consulting, speaking and serving on a scientific advisory board for Biogen Idec, Teva Neuroscience and EMD Serono. She also received financial support for research activities from NMSS, NIH, ITN, Teva Neuroscience, Biogen Idec, EMD Serono, and Aspreva.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.