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Zivadinov R. 1,2, Schirda C. 1, Dwyer M. G. 1, Haacke M. E. 3, Weinstock-Guttman B. 2, Menegatti E. 4, Heininen-Brown M. 1, Magnano C. 1, Malagoni A. M. 4, Wack D. S. 1, Hojnacki D. 2, Kennedy C. 1, Carl E. 1, Bergsland N. 1, Hussein S. 1, Poloni G. 1, Bartolomei I. 4, Salvi F. 4, Zamboni P. 4
1 Buffalo Neuroimaging Analysis Center, University at Buffalo, Buffalo, NY, USA;
2 The Jacobs Neurological Institute, University at Buffalo, Buffalo, NY, USA;
3 Wayne State University, MR Research Facility, Department of Radiology, Detroit, MI, USA;
4 Vascular Diseases Center, University of Ferrara-Bellaria Neurosciences, Ferrara and Bologna, Italy
AIM: 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.
CONCLUSION: 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.