Another Study Contradicts Venous Insufficiency in Multiple Sclerosis

From this week's issue of Neurology.

Using MR venography and ultrasound* in 40 patients with MS, German investigators failed to replicate the 100% prevalence of chronic cerebrospinal venous insufficiency (CCSVI) defined famously (and notoriously) by Zamboni et al in 2009 (for background, start here or search Pathophilia for "Zamboni"). This newly published study, by the authors' account, is at least the 13th study** that has failed to validate Zamboni's theory of venous insufficiency in MS and his follow-up idea that the stenting of cerebral veins (ostensibly to improve the egress of iron) could be somehow objectively clinically beneficial.

Here's the parade of negative studies cited by the German authors (Doepp et al); 11 of these studies have been published in English-language peer-reviewed journals (all of which are reasonably well regarded).

Ultrasound studies

• Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol. 2010;68:173-183.
• Baracchini C, Perini P, Calabrese M, Causin F, Rinaldi F, Gallo P. No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset. Ann Neurol. 2011;69:90-99.
• Krogias C, Schroeder A, Wiendl H, Hohlfeld R, Gold R. "Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients. Nervenarzt.
• 2010;81:740-746. (article in German)
  
• Mayer CA, Pfeilschifter W, Lorenz MW, et al. The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry. 2011;82:436-440.
• Centonze D, Floris R, Stefanini M, et al. Proposed CCSVI criteria do not predict MS risk nor MS severity. Ann Neurol. 2011;70:52-59.

MR angiography

• Sundstroem P, Wåhlin A, Ambarki K, Birgander R, Eklund A, Malm J. Venous and cerebrospinal fluid flow in multiple sclerosis: a case control study. Ann Neurol. 2010;68:255-259.
• Wattjes M, van Oosten BW, de Graaf WL, 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.
• Zivadinov R, Lopez-Soriano A, Weinstock-Guttman B, et al. Use of MR venography for characterization of the extracranial venous system in patients with multiple sclerosis and healthy control subjects. Radiology. 2011;258-562-570.
  

Selective venography

• Yamout B, Herlopian A, Issa Z, et al. Extracranial venous stenosis is an unlikely cause of multiple sclerosis. Mult Scler. 2010;16:1341-1348.

Measurement of intraocular venous pressure

• Meyer-Schwickerath R, Haug C, Hacker A, et al. Intracranial venous pressure is normal in patients with multiple sclerosis. Mult Scler. 2011;17:637-638.

Measurement of CSF ferritin levels

• Worthington V, Killestein J, Eikelenboom MJ, et al. Normal CSF ferritin levels in MS suggest against etiologic role of chronic venous insufficiency. Neurology. 2010;75:1617-1622.

* Specifically dynamic extracranial color-coded duplex sonography (ECCS).
** The cited studies do not include the essentially negative ultrasound study from the University of Buffalo, which was recently published in April in Neurology. Consequently the peer-reviewed tally comes to 14 negative studies.

Image of neck veins from Gray's Anatomy (1918).