Related Experiment Videos
Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement
David F Moore1, Gheona Altarescu, Geoffrey S F Ling
1Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda Md 20892-1260, USA.
Insights
Patients with Fabry disease exhibit elevated cerebral blood flow velocities. Enzyme replacement therapy significantly improved these velocities, indicating a potential treatment benefit for cerebrovascular complications.
Area of Science:
- Neurology
- Genetics
- Vascular Medicine
Background:
- Fabry disease is an X-linked genetic disorder caused by alpha-galactosidase A deficiency.
- Cerebrovascular complications in Fabry disease include small-vessel disease and large-vessel ectasia.
- Abnormal cerebral blood flow is a key feature of Fabry disease.
Purpose of the Study:
- To assess cerebral blood flow velocities in Fabry disease patients using transcranial Doppler (TCD).
- To evaluate the impact of enzyme replacement therapy (ERT) on cerebral hemodynamics.
- To examine cerebrovascular reactivity through CO2 challenge tests.
Main Methods:
- Noninvasive TCD measurements of cerebral blood flow velocities.
- Enrollment of 26 Fabry disease patients in a 6-month double-blind, placebo-controlled ERT trial.
- 18-month open-label follow-up with statistical analysis using mixed-effects ANOVA.
Main Results:
- Fabry patients showed significantly higher peak, mean, pulsatility, and resistance indices compared to controls.
- Elevated flow velocities were observed in the middle cerebral artery (M1) and posterior cerebral artery.
- ERT significantly reduced peak, mean, and end-diastolic velocities and flow acceleration at 18 months.
Conclusions:
- Fabry disease is associated with elevated cerebral blood flow velocities.
- Enzyme replacement therapy demonstrates significant improvement in cerebral blood flow parameters.
Background And Purpose:
Fabry disease is an X-linked inherited disorder resulting from a deficiency of alpha-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 alpha-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.