title: Efficacy and safety of venous angioplasty of the extracranial veins for multiple sclerosis. Brave dreams study (brain venous drainage exploited against multiple sclerosis): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a disabling progressive course. Chronic cerebrospinal venous insufficiency (CCSVI) has recently been described as a vascular condition characterized by restricted venous outflow from the brain, mainly due to blockages of the internal jugular and azygos veins. Despite a wide variability among studies, it has been found to be associated with MS. Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins.
  
  
  METHODS
  This is a multicenter, randomized, parallel group, blinded, sham-controlled trial to assess the efficacy and safety of PTA. Participants with relapsing remitting MS or secondary progressive MS and a sonographic diagnosis of CCSVI will be enrolled after providing their informed consent. Each participant will be centrally randomized to receive catheter venography and PTA or catheter venography and sham PTA. Two primary end points with respect to efficacy at 12 months are (1) a combined end point obtained through the integration of five functional indicators, walking, balance, manual dexterity, bladder control, and visual acuity, objectively measured by instruments; and (2) number of new brain lesions measured by T2-weighted MRI sequences. Secondary end points include annual relapse rate, change in Expanded Disability Status Scale score, proportion of patients with zero, one or two, or more than two relapses; fatigue; anxiety and depression; general cognitive state; memory/attention/calculus; impact of bladder incontinence; and adverse events. Six hundred seventy-nine patients will be recruited. The follow-up is scheduled at 12 months. Patients, treating neurologists, trained outcome assessors, and the statistician in charge of data analysis will be masked to the assigned treatment.
  
  
  CONCLUSIONS
  The study will provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01371760.
authors.affiliation: Vascular Diseases Center, University of Ferrara, C.so Giovecca 203, 44100 Ferrara, Italy. zmp@unife.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Zamboni
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
authors.forename: Paolo
authors.initials: P
authors.lastname: Boldrini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cenni
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Alessandro
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: Massimo
authors.initials: M
authors.lastname: Del Sette
authors.forename: Roberto
authors.initials: R
authors.lastname: Galeotti
authors.forename: Stefania
authors.initials: S
authors.lastname: Galimberti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Liberati
authors.forename: Luca
authors.initials: L
authors.lastname: Massacesi
authors.forename: Donato
authors.initials: D
authors.lastname: Papini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.forename: Silvana
authors.initials: S
authors.lastname: Simi
authors.forename: Andrea
authors.initials: A
authors.lastname: Stella
authors.forename: Luigi
authors.initials: L
authors.lastname: Tesio
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Graziella
authors.initials: G
authors.lastname: Filippini
mesh_terms: D000328:Adult; D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000379:methods*; D001401:Azygos Vein / Q000000981:diagnostic imaging / Q000601:surgery*; D001921:Brain / Q000098:blood supply; D002908:Chronic Disease; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007601:Jugular Veins / Q000000981:diagnostic imaging / Q000601:surgery*; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000601:surgery*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000601:surgery*; D010690:Phlebography; D012107:Research Design; D014463:Ultrasonography; D014689:Venous Insufficiency / Q000000981:diagnostic imaging / Q000601:surgery*