Vascular pathology in multiple sclerosis: mind boosting or myth busting?

Chronic cerebrospinal venous insufficiency (CCSVI) describes a vascular condition characterized by anomalies of the main extra-cranial cerebrospinal veins that interfere with normal cerebrospinal outflow [1]. These anomalies i.e. stenoses may affect the internal jugular veins, the vertebral veins or the azygous vein and can be detected by venous echo-color Doppler and invasive venography [1-4]. CCSVI has recently been reported at a high prevalence in multiple sclerosis (MS) patients and proposed as a pathogenic factor challenging the autoimmune hypothesis of the disease [1,5,6].The idea of MS being a vascular disease is not new. In the 1930s T.J. Putnam proposed venous obstruction as the primary alteration in MS [7]. Given the venotopic localization of MS plaques, this hypothesis has been discussed on and off ever since. In 2007 an Italian group headed by P. Zamboni added new fuel to the fire by demonstrating that venous blood flow alterations can be found at a high frequency in MS patients [5]. The initial study on 89 MS patients and 60 control subjects was soon followed by a second one by the same investigators addressing venous hemodynamics in 65 patients with clinically definite MS and 235 controls [1]. Using high resolution echocolor Doppler sonography (ECD) and transcranial color Doppler sonography (TCCS). Zamboni et al. defined five parameters that-if at least two are present-allow diagnosis of CCSVI i.e. (1) reflux in the internal jugular and/or vertebral veins; (2) reflux in the deep cerebral veins; (3) B-mode evidence of internal jugular vein stenosis; (4) flow not Doppler-detectable in the internal jugular and/or vertebral veins; (5) reverted postural control of the main cerebral venous outflow pathways. He reported that the presence of venous outflow anomalies was dramatically associated with the diagnosis of MS [1]. This finding was confirmed by another study of the same group who detected CCSVI in all of 109 MS subjects but none of the 177 controls (se