title: Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study.
abstract: BACKGROUND
  Chronic cerebrospinal venous insufficiency has been proposed as a unique combination of extracranial venous blockages and haemodynamic flow abnormalities that occurs only in patients with multiple sclerosis and not in healthy people. Initial reports indicated that all patients with multiple sclerosis had chronic cerebrospinal venous insufficiency. We aimed to establish the prevalence of venous narrowing in people with multiple sclerosis, unaffected full siblings, and unrelated healthy volunteers.
  
  
  METHODS
  We did an assessor-blinded, case-control, multicentre study of people with multiple sclerosis, unaffected siblings, and unrelated healthy volunteers. We enrolled the study participants between January, 2011 and March, 2012, and they comprised 177 adults: 79 with multiple sclerosis, 55 siblings, and 43 unrelated controls, from three centres in Canada. We assessed narrowing of the internal jugular and azygous veins with catheter venography and ultrasound criteria for chronic cerebrospinal venous insufficiency proposed by Zamboni and colleagues. Catheter venography data were available for 149 participants and ultrasound data for 171 participants.
  
  
  RESULTS
  Catheter venography criteria for chronic cerebrospinal venous insufficiency were positive for one of 65 (2%) people with multiple sclerosis, one of 46 (2%) siblings, and one of 32 (3%) unrelated controls (p=1·0 for all comparisons). Greater than 50% narrowing of any major vein was present in 48 of 65 (74%) people with multiple sclerosis, 31 of 47 (66%) siblings (p=0·41 for comparison with patients with multiple sclerosis), and 26 of 37 (70%) unrelated controls (p=0·82). The ultrasound criteria for chronic cerebrospinal venous insufficiency were fulfilled in 35 of 79 (44%) participants with multiple sclerosis, 17 of 54 (31%) siblings (p=0·15 for comparison with patients with multiple sclerosis) and 17 of 38 (45%) unrelated controls (p=0·98). The sensitivity of the ultrasound criteria for detection of greater than 50% narrowing on catheter venography was 0·406 (95% CI 0·311-0·508), and specificity was 0·643 (0·480-0·780).
  
  
  CONCLUSIONS
  This study shows that chronic cerebrospinal venous insufficiency occurs rarely in both patients with multiple sclerosis and in healthy people. Extracranial venous narrowing of greater than 50% is a frequent finding in patients with multiple sclerosis, unaffected siblings, and unrelated controls. The ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography. The significance of venous narrowing to multiple sclerosis symptomatology remains unknown.
  
  
  BACKGROUND
  MS Society of Canada, Saskatoon City Hospital Foundation, Lotte and John Hecht Memorial Foundation, Vancouver Coastal Health Foundation, and the Wolridge Foundation.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: t.traboulsee@ubc.ca.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Traboulsee
authors.affiliation: Department of Physical Medicine and Rehabilitation, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Knox
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Machan
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yinshan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Irene
authors.initials: I
authors.lastname: Yee
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rauscher
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Darren
authors.initials: D
authors.lastname: Klass
authors.affiliation: Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Szkup
authors.affiliation: Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Otani
authors.affiliation: Department of Surgery, University of Saskatchewan, Regina, Saskatchewan, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Kopriva
authors.affiliation: Department of Surgery, University of Saskatchewan, Regina, Saskatchewan, Canada.
authors.forename: Shanti
authors.initials: S
authors.lastname: Lala
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: David K
authors.initials: DK
authors.lastname: Li
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Dessa
authors.initials: D
authors.lastname: Sadovnick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001401:Azygos Vein / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D002908:Chronic Disease; D006801:Humans; D007601:Jugular Veins / Q000000981:diagnostic imaging*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics; D010690:Phlebography; D012680:Sensitivity and Specificity; D035781:Siblings; D014463:Ultrasonography; D062666:Vascular Access Devices; D014689:Venous Insufficiency / Q000000981:diagnostic imaging / Q000209:etiology*