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(Stroke. 2002;33:525.)
© 2002 American Heart Association, Inc.

Original Contributions

Elevated Cerebral Blood Flow Velocities in Fabry Disease With Reversal After Enzyme Replacement

David F. Moore, MD, PhD, DIC; Gheona Altarescu, MD; Geoffrey S.F. Ling, MD, PhD; Neal Jeffries, PhD; Karen P. Frei, MD; Thais Weibel, MD; Gustavo Charria-Ortiz, MD; Raymond Ferri, MD, PhD; Andrew E. Arai, MD; Roscoe O. Brady, MD; Raphael Schiffmann, MD

From the Developmental and Metabolic Neurology Branch (D.F.M., G.A., K.P.F., R.O.B., T.W., G.C.-O., R.F., R.S.) and Biostatistics Section (N.J.), National Institute of Neurological Disorders and Stroke, and Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute (A.E.A.), National Institutes of Health, Bethesda Md; and Department of Neurology, Walter Reed Army Medical Center, Washington, DC (G.S.F.L.).

Correspondence to Dr Raphael Schiffmann, National Institutes of Health, Bldg 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892-1260. E-mail rs4e{at}nih.gov

Background and Purpose— Fabry disease is an X-linked inherited disorder resulting from a deficiency of -galactosidase A. Cerebrovascular disease in Fabry disease includes small-vessel disease and larger-vessel ectasia in a predominantly posterior distribution. We assessed transcranial Doppler (TCD) blood flow velocities in naive and enzyme-treated Fabry patients.

Methods— TCD was used to noninvasively examine patients with Fabry disease for abnormal cerebral blood flow velocities. TCD measurements were also made during CO₂ retention by breathholding to examine cerebrovascular vessel reactivity. Twenty-six patients were enrolled in a 6-month, double-blind, placebo-controlled trial of enzyme replacement therapy consisting of biweekly intravenous -galactosidase A infusions, with a subsequent 18-month follow-up in an open-label trial. Statistical analysis consisted of applying a mixed-effects ANOVA model for correlated outcomes.

Results— Peak velocity, mean velocity, pulsatility index, and resistance index were found to be significantly higher in patients compared with control subjects. When the individual vessels were considered, elevated flow velocities were found in the middle cerebral M1 branch and the posterior cerebral artery. Enzyme replacement therapy significantly decreased peak, mean, and end-diastolic velocities and flow acceleration at the 18-month follow-up time point.

Conclusions— Patients with Fabry disease have elevated cerebral blood flow velocities. These velocities significantly improved with enzyme replacement therapy.

Key Words: blood flow velocity • cerebrovascular accident • cerebrovascular disorders • Fabry disease • ultrasonography, Doppler, transcranial

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