title: Prospective randomized trial of venous angioplasty in MS (PREMiSe).
abstract: OBJECTIVE
  We report the results of the investigation of safety and efficacy of venous angioplasty in patients with multiple sclerosis (MS) with findings of extracranial venous anomalies, considered hallmarks of chronic cerebrospinal venous insufficiency (CCSVI), in a 2-phase study (ClinicalTrials.gov NCT01450072).
  
  
  METHODS
  Phase 1 was an open-label safety study (10 patients); phase 2 was sham-controlled, randomized, and double-blind (10 sham procedure, 9 treated). All study patients fulfilled venous hemodynamic screening criteria indicative of CCSVI. Assessment was at 1, 3, and 6 months postprocedure with MRI, clinical, and hemodynamic outcomes. Primary endpoints were safety at 24 hours and 1 month, venous outflow restoration >75% at 1 month, and effect of angioplasty on new lesion activity and relapse rate over 6 months. Secondary endpoints included changes in disability, brain volume, cognitive tests, and quality of life.
  
  
  RESULTS
  No perioperative complications were noted; however, one patient with history of syncope was diagnosed with episodic bradycardia requiring placement of a pacemaker before discharge. Doppler evidence-based venous hemodynamic insufficiency severity score (VHISS) was reduced >75% compared to baseline in phase 1 (at 1 month) but not phase 2. In phase 2, higher MRI activity (cumulative number of new contrast-enhancing lesions [19 vs 3, p = 0.062] and new T2 lesions [17 vs 3, p = 0.066]) and relapse activity (4 vs 1, p = 0.389) were identified as nonsignificant trends in the treated vs sham arm over 6 months. Using analysis of covariance, significant cumulative new T2 lesions were related to larger VHISS decrease (p = 0.028) and angioplasty (p = 0.01) over the follow-up. No differences in other endpoints were detected.
  
  
  CONCLUSIONS
  Venous angioplasty is not an effective treatment for MS over the short term and may exacerbate underlying disease activity.
  
  
  METHODS
  This is a Class I study demonstrating that clinical and imaging outcomes are no better or worse in patients with MS identified with venous outflow restriction who receive venous angioplasty compared to sham controls who do not receive angioplasty. This study also includes a Class IV phase 1 study of safety in 10 patients receiving the angioplasty procedure.
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY. asiddiqui@ubns.com rzivadinov@bnac.net.
authors: Adnan H
authors: AH
authors: Siddiqui
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY. asiddiqui@ubns.com rzivadinov@bnac.net.
authors: Robert
authors: R
authors: Zivadinov
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Ralph H B
authors: RH
authors: Benedict
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Yuval
authors: Y
authors: Karmon
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Jihnhee
authors: J
authors: Yu
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Mary L
authors: ML
authors: Hartney
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Karen L
authors: KL
authors: Marr
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Vesela
authors: V
authors: Valnarov
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Cheryl L
authors: CL
authors: Kennedy
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Murali
authors: M
authors: Ramanathan
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Deepa P
authors: DP
authors: Ramasamy
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Kresimir
authors: K
authors: Dolic
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: David W
authors: DW
authors: Hojnacki
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Ellen
authors: E
authors: Carl
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Elad I
authors: EI
authors: Levy
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: L Nelson
authors: LN
authors: Hopkins
authors: From the Departments of Neurosurgery and Radiology, The Jacobs Neurological Institute (A.H.S., Y.K., M.L.H., E.I.L., L.N.H.), and the Departments of Neurology (R.Z., R.H.B.B., D.W.H., B.W.-G.), Biostatistics (J.Y.), and Pharmaceutical Sciences (M.R.), University at Buffalo, State University of New York; and the Buffalo Neuroimaging Analysis Center (R.Z., K.L.M., V.V., C.L.K., D.P.R., K.D., E.C.), NY.
authors: Bianca
authors: B
authors: Weinstock-Guttman
mesh_terms: D000328:Adult; D017130:Angioplasty / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D011446:Prospective Studies; D014689:Venous Insufficiency / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*