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

被引:140
作者
Moore, DF
Altarescu, G
Ling, GSF
Jeffries, N
Frei, KP
Weibel, T
Charria-Ortiz, G
Ferri, R
Arai, AE
Brady, RO
Schiffmann, R
机构
[1] NINCDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA
[2] NINCDS, Biostat Sect, NIH, Bethesda, MD 20892 USA
[3] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA
[4] Walter Reed Army Med Ctr, Dept Neurol, Washington, DC 20307 USA
关键词
blood flow velocity; cerebrovascular accident; cerebrovascular disorders; Fabry disease; ultrasonography; Doppler; transcranial;
D O I
10.1161/hs0202.102601
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:525 / 531
页数:7
相关论文
共 29 条
[1]   EVALUATION OF CEREBROVASCULAR SPASM WITH TRANSCRANIAL DOPPLER ULTRASOUND [J].
AASLID, R ;
HUBER, P ;
NORNES, H .
JOURNAL OF NEUROSURGERY, 1984, 60 (01) :37-41
[2]   Enhanced endothelium-dependent vasodilation in Fabry disease [J].
Altarescu, G ;
Moore, DF ;
Pursley, R ;
Campia, U ;
Goldstein, S ;
Bryant, M ;
Panza, JA ;
Schiffmann, R .
STROKE, 2001, 32 (07) :1559-1562
[3]   ENZYMATIC DEFECT IN FABRYS DISEASE - CERAMIDETRIHEXOSIDASE DEFICIENCY [J].
BRADY, RO ;
GAL, AE ;
BRADLEY, RM ;
MARTENSS.E ;
WARSHAW, AL ;
LASTER, L .
NEW ENGLAND JOURNAL OF MEDICINE, 1967, 276 (21) :1163-&
[4]   Correlation of transcranial Doppler sonography mean flow velocity with cerebral blood flow in patients with intracranial pathology [J].
Brauer, P ;
Kochs, E ;
Werner, C ;
Bloom, M ;
Policare, R ;
Pentheny, S ;
Yonas, H ;
Kofke, WA ;
Esch, JSA .
JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY, 1998, 10 (02) :80-85
[5]  
Crowder MJ, 1990, ANAL REPEATED MEASUR
[6]   Quantitative analysis of cerebral vasculopathy in patients with Fabry disease [J].
Crutchfield, KE ;
Patronas, NJ ;
Dambrosia, JM ;
Frei, KP ;
Banerjee, TK ;
Barton, NW ;
Schiffmann, R .
NEUROLOGY, 1998, 50 (06) :1746-1749
[7]   CEREBRAL VASOREACTIVITY ASSESSED WITH TRANSCRANIAL DOPPLER AND REGIONAL CEREBRAL BLOOD-FLOW MEASUREMENTS - DOSE, SERUM CONCENTRATION, AND TIME-COURSE OF THE RESPONSE TO ACETAZOLAMIDE [J].
DAHL, A ;
RUSSELL, D ;
ROOTWELT, K ;
NYBERGHANSEN, R ;
KERTY, E .
STROKE, 1995, 26 (12) :2302-2306
[8]  
DeGraba T, 2000, ANN NEUROL, V47, P229, DOI 10.1002/1531-8249(200002)47:2<229::AID-ANA13>3.0.CO
[9]  
2-T
[10]  
DESNICK RJ, 1997, MOL GENETIC BASIS NE, P443