link to abstract
Ajay Vikram Singh1 and Paolo Zamboni2
1Department of Physics, European School of Molecular Medicine (SEMM), IFOM-IEO Campus, Centro Interdisciplinare Materiali e Interfacce Nanostrutturati (CIMAINA), University of Milan, Milan, Italy
2Vascular Diseases Center, University of Ferrara, Ferrara, Italy
Correspondence: Professor P Zamboni, Director Vascular Diseases Center, University of Ferrara, Milan, Italy. E-mail: firstname.lastname@example.org
Received 27 April 2009; Revised 27 July 2009; Accepted 29 July 2009; Published online 2 September 2009.
Multiple sclerosis (MS) is primarily an autoimmune disorder of unknown origin. This review focuses iron overload and oxidative stress as surrounding cause that leads to immunomodulation in chronic MS. Iron overload has been demonstrated in MS lesions, as a feature common with other neurodegenerative disorders. However, the recent description of chronic cerebrospinal venous insufficiency (CCSVI) associated to MS, with significant anomalies in cerebral venous outflow hemodynamics, permit to propose a parallel with chronic venous disorders (CVDs) in the mechanism of iron deposition. Abnormal cerebral venous reflux is peculiar to MS, and was not found in a miscellaneous of patients affected by other neurodegenerative disorders characterized by iron stores, such as Parkinson's, Alzheimer's, amyotrophic lateral sclerosis. Several recently published studies support the hypothesis that MS progresses along the venous vasculature. The peculiarity of CCSVI-related cerebral venous blood flow disturbances, together with the histology of the perivenous spaces and recent findings from advanced magnetic resonance imaging techniques, support the hypothesis that iron deposits in MS are a consequence of altered cerebral venous return and chronic insufficient venous drainage.
This was the focus of Dr Haacke's presentation as well...he showed SWI MRI images of severe iron deposition and hypoxia (lack of oxygen) and loss of gray matter in the MS brain as measured by new technologies he has developed. Read his presentation again from my notes for further detail. Looks like Dr. Zamboni is sticking to this as the mechanism of injury in brain tissue, and after seeing Dr. Haacke's presentation, I understand why. And as we've been discussing for awhile here, this kind of injury can set the immune system off...but the reflux comes first.