Effects of Venous Angioplasty on Cerebral Lesions in Multiple Sclerosis: Expanded Analysis of the Brave Dreams Double-Blind, Sham-Controlled Randomized Trial

Abstract

Purpose: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI). Materials and Methods: The Brave Dreams trial ( ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a post hoc assessment, venograms of patients who underwent venous angioplasty were graded as “favorable” (n=38) or “unfavorable” (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared. Results: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005). Conclusion: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Post hoc analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

Internal Jugular Vein Thrombosis: Etiology, Symptomatology, Diagnosis and Current Treatment

“…IJVthr in medical literature has been associated to a variety of different conditions, generally described in anecdotal case reports and in safety endovascular studies: effort thrombosis of the axillary/subclavian venous trunk extended to the IJV [ 2 ]; the combination of congenital IJV hypoplasia with inherited coagulation deficit [ 50 ]; in microgravity condition, during space flight on the International Space Station, for the combination of dehydration status with the lack of gravitational gradient [ 76 , 77 ]; rarely following balloon venoplasty but more frequently after stenting of the IJV for chronic cerebrospinal venous insufficiency (CCSVI) treatment [ 66 , 67 , 86 , 87 ]; an elongated styloid process [ 24 , 88 , 89 ] and associated to Behçet disease [ 26 ].…”

An overview of randomized controlled trials on endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis patients

“…This analysis, which involved also secondary progressive MS patients who participated in this study, utilized the venographic classification of CCSVI lesions suggested by Giaquinta [20] and focused at MRI findings after 12-month follow-up, demonstrated significantly less new MS plaques revealed by MRI in the treatment arm of the study. Moreover, patients with favorable morphology of CCSVI lesions, such as focal or segmental defects were significantly more likely to be free from new MS lesions in comparison with patients presenting with less favorable morphology of venous abnormalities, such as long intraluminal defects, hypoplasia of the internal jugular vein or external compression of this vein by adjacent muscles [28,29].…”

Vascular Biomarkers: Physics Parameters and Circulating Molecules Can Be Two Faces of the Same Coin

“…The latter, being the most common chronic neurological disease in young adults, attracted other authors who explored the vascular aspects of MS [ 6 , 7 ]. Unconventional brain magnetic resonance techniques make it possible to transform such diagnostic tools into a sort of noninvasive external laboratory.…”