Ascorbate decreases Fabry cerebral hyperperfusion suggesting a reactive oxygen species abnormality: An arterial spin tagging study

• Published in: Journal of magnetic resonance imaging 2004-10, Vol.20 (4), p.674-683
• Main Authors: Moore, David F., Ye, Frank, Brennan, Marie-Luise, Gupta, Surya, Barshop, Bruce A., Steiner, Robert D., Rhead, William J., Brady, Roscoe O., Hazen, Stanley L., Schiffmann, Raphael
• Format: Article
• Language: English
• Subjects: Adult; Analysis of Variance; ascorbate; Ascorbic Acid - administration & dosage; Ascorbic Acid - pharmacology; Brain - metabolism; Case-Control Studies; cerebral blood flow; Cerebrovascular Circulation - drug effects; Double-Blind Method; Fabry disease; Fabry Disease - drug therapy; Fabry Disease - physiopathology; Humans; Image Processing, Computer-Assisted; Injections, Intravenous; Magnetic Resonance Imaging - methods; Male; Reactive Oxygen Species; Spin Labels; stroke
• ISSN: 1053-1807; 1522-2586
• DOI: 10.1002/jmri.20162

Purpose To test the hypothesis that reactive oxygen species contribute to the cerebral hyperperfusion in Fabry disease. Material and Methods We examined the effect of intravenous injection of ascorbate on cerebral blood flow (CBF) using magnetic resonance arterial spin tagging. Nineteen patients with Fabry disease and 15 control subjects were studied as part of a randomized double‐blind placebo‐controlled trial of enzyme replacement therapy (ERT). Results Vertebro‐basilar hyperperfusion was observed in patients with Fabry disease. A decrease in systemic ascorbate levels relative to healthy controls was found in the patients. CBF decreased after ascorbate infusion in both control subjects and patients treated with ERT. The placebo group had a significantly delayed decrease in the CBF response after ascorbate infusion. Myeloperoxidase levels were elevated in Fabry patients, consistent with ongoing inflammatory processes in these patients. Conclusion Increased CBF in Fabry disease may be related to increased production of reactive oxygen species, while low plasma ascorbate levels suggests a global redox imbalance. These abnormalities were improved by ERT. These observations have implications regarding oxidative processes contributing to accelerated atherosclerosis in Fabry disease. J. Magn. Reson. Imaging 2004;20:674–683. Published 2004 Wiley‐Liss, Inc.