Elevated cerebral blood flow velocities in Fabry disease with reversal after enzyme replacement.
OBJECTIVE
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.
Moore
David F
DF
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda Md 20892-1260, USA.
Altarescu
Gheona
G
Ling
Geoffrey S F
GS
Jeffries
Neal
N
Frei
Karen P
KP
Weibel
Thais
T
Charria-Ortiz
Gustavo
G
Ferri
Raymond
R
Arai
Andrew E
AE
Brady
Roscoe O
RO
Schiffmann
Raphael
R
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015331:Cohort Studies; D004311:Double-Blind Method; D000795:Fabry Disease / Q000188:drug therapy* / Q000503:physiopathology*; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow / Q000187:drug effects; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D002245:Carbon Dioxide; D000519:alpha-Galactosidase