Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement

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

Research output: Contribution to journalArticle


Background and Purpose - Fabry disease is an X-linked inherited disorder resulting from a deficiency of α-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 α-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.

Original languageEnglish (US)
Pages (from-to)525-531
Number of pages7
Issue number2
StatePublished - Feb 14 2002



  • Blood flow velocity
  • Cerebrovascular accident
  • Cerebrovascular disorders
  • Fabry disease
  • Ultrasonography, Doppler, transcranial

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Moore, D. F., Altarescu, G., Ling, G. S. F., Jeffries, N., Frei, K. P., Weibel, T., Charria-Ortiz, G., Ferri, R., Arai, A. E., Brady, R. O., & Schiffmann, R. (2002). Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement. Stroke, 33(2), 525-531. https://doi.org/10.1161/hs0202.102601