title: The perfect crime? CCSVI not leaving a trace in MS.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, believed to be triggered by an autoimmune reaction to myelin. Recently, a fundamentally different pathomechanism termed 'chronic cerebrospinal venous insufficiency' (CCSVI) was proposed, provoking significant attention in the media and scientific community.
  
  
  METHODS
  Twenty MS patients (mean age 42.2 ± 13.3 years; median Extended Disability Status Scale 3.0, range 0-6.5) were compared with 20 healthy controls. Extra- and intracranial venous flow direction was assessed by colour-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria. IJV-VCSA ≤ 0.3 cm(2) indicated 'stenosis,' and IJV-VCSA decrease from supine to upright position 'reverted postural control.' The sonographer, data analyser and statistician were blinded to the patient/control status of the participants.
  
  
  RESULTS
  No participant showed retrograde flow of cervical or intracranial veins. IJV-VCSA ≤ 0.3 cm(2) was found in 13 MS patients versus 16 controls (p=0.48). A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding. No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49). Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI.
  
  
  CONCLUSIONS
  This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS.
authors.affiliation: Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany. christoph.mayer@kgu.de
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Mayer
authors.forename: Waltraud
authors.initials: W
authors.lastname: Pfeilschifter
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Lorenz
authors.forename: Max
authors.initials: M
authors.lastname: Nedelmann
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.forename: Helmuth
authors.initials: H
authors.lastname: Steinmetz
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002550:Cerebral Veins / Q000000981:diagnostic imaging / Q000473:pathology; D003251:Constriction, Pathologic / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D007601:Jugular Veins / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000502:physiology; D018615:Ultrasonography, Doppler, Color / Q000379:methods; D014689:Venous Insufficiency / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology