Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

Abstract

Background: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated. Methods: Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement. Results: CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher. Conclusion: CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.

Concomitant Analysis of Arterial, Venous, and CSF Flows using Phase-Contrast MRI: A Quantitative Comparison Between MS Patients and Healthy Controls

“…The venous hypothesis in MS was revived by the findings of Zamboni et al 2 who highlighted venous flow abnormalities at transcranial color-coded Duplex sonography in 100% of MS patients, with even specific patterns for each phenotype of the disease. Their results were confirmed, although in lower proportion and small populations, in some publications.…”

Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency

“…Jugular vein stenosis was found in some studies to exist in 91% of MS patients with 14% showing bilateral stenosis [26,52]. The cerebral venous outflow in the rat is carried mainly by the external jugular vein with contribution from the vertebral vein, unlike human circulation, the internal jugular vein is almost vestigial in the rat [4].…”

Anomalous Venous Blood Flow and Iron Deposition in Multiple Sclerosis

“…Rather, they were combined in the IJVs, AZ, and lumbar systems, defining four main patterns of distribution (Zamboni et al, 2009b): The CCSVI brings about an overturning of the above-described postural and respiratory mechanisms, rendering abnormal the physiology of cerebral venous return (Zamboni et al, 2007(Zamboni et al, , 2009b. Combined transcranial and extracranial echo-colorDoppler allows for measurement of VH parameters indicative of CCSVI (Zamboni et al, 2009c).…”