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

Abstract

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 CO 2 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

White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up

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Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach

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“…One consequence of NO pathway dysregulation may be cerebral hyperperfusion resulting in altered vascular reactivity and elongation of cerebral blood vessels predominantly in the vertebrobasilar circulation (5). Evidence for excess formation of superoxide or reactive oxygen species (ROS) was provided recently by a magnetic resonance imaging and arterial spin labeling study (7).…”

Cerebral hemorrhage in Fabry's disease

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