title: Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control study.
abstract: OBJECTIVE
  Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. Aim of this study was to investigate the relationship between CCSVI and iron deposition in the brain of MS patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter structures and lesions, as measured by susceptibility-weighted imaging (SWI), and to preliminarily define the relationship between iron measures and clinical and other magnetic resonance imaging (MRI) outcomes.
  
  
  METHODS
  Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI.
  
  
  RESULTS
  All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume.
  
  
  CONCLUSIONS
  The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS.
authors.affiliation: Buffalo Neuroimaging Analysis Center, University at Buffalo, Buffalo, NY, USA. rzivadinov@bnac.net
authors.forename: R
authors.initials: R
authors.lastname: Zivadinov
authors.forename: C
authors.initials: C
authors.lastname: Schirda
authors.forename: M G
authors.initials: MG
authors.lastname: Dwyer
authors.forename: M E
authors.initials: ME
authors.lastname: Haacke
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: E
authors.initials: E
authors.lastname: Menegatti
authors.forename: M
authors.initials: M
authors.lastname: Heininen-Brown
authors.forename: C
authors.initials: C
authors.lastname: Magnano
authors.forename: A M
authors.initials: AM
authors.lastname: Malagoni
authors.forename: D S
authors.initials: DS
authors.lastname: Wack
authors.forename: D
authors.initials: D
authors.lastname: Hojnacki
authors.forename: C
authors.initials: C
authors.lastname: Kennedy
authors.forename: E
authors.initials: E
authors.lastname: Carl
authors.forename: N
authors.initials: N
authors.lastname: Bergsland
authors.forename: S
authors.initials: S
authors.lastname: Hussein
authors.forename: G
authors.initials: G
authors.lastname: Poloni
authors.forename: I
authors.initials: I
authors.lastname: Bartolomei
authors.forename: F
authors.initials: F
authors.lastname: Salvi
authors.forename: P
authors.initials: P
authors.lastname: Zamboni
mesh_terms: D000328:Adult; D001284:Atrophy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation; D002908:Chronic Disease; D003251:Constriction, Pathologic; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007501:Iron / Q000032:analysis*; D007558:Italy; D007601:Jugular Veins / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009518:New York; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012039:Regional Blood Flow; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000098:blood supply*; D014689:Venous Insufficiency / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D007501:Iron