Moore David F, Altarescu Gheona, Herscovitch Peter, Schiffmann Raphael
Developmental and Metabolic Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
BMC Neurol. 2002 Jun 18;2:4. doi: 10.1186/1471-2377-2-4.
Fabry disease is a lysosomal X-linked enzyme deficiency of alpha-galactosidase A associated with an increased mortality and morbidity due to renal failure, cardiac disease and early onset stroke.
We examined the functional blood flow response of the brain after visual stimulation (reversing checkerboard pattern), and cerebral vasoreactivity following acetazolamide (15 mg/kg) with [15O]H2O and positron emission tomography (PET) in Fabry disease. Twenty-six hemizygous patients (age range 19-47 years) were enrolled in a randomized double-blind placebo-controlled 6-month trial of enzyme replacement therapy administered by intravenous infusion every two weeks. Regional cerebral blood flow (rCBF) was measured with PET at the beginning and end of the trial.
Fabry patients had a significantly greater increase in rCBF following visual stimulation and acetazolamide challenge compared to controls. Visual reactivity was normal. The time for recovery of the cerebral vasculature following acetazolamide was prolonged in Fabry patients compared to controls. The abnormal rCBF response induced by visual stimulation and acetazolamide decreased significantly following enzyme replacement therapy, as did the prolonged recovery of the cerebral vasculature.
Enzyme replacement therapy reverses the exaggerated cerebrovascular response in Fabry disease.
法布里病是一种溶酶体X连锁的α-半乳糖苷酶A缺乏症，因肾衰竭、心脏病和早发性中风导致死亡率和发病率增加。
我们在法布里病患者中，使用[15O]H2O和正电子发射断层扫描（PET）检查了视觉刺激（反转棋盘图案）后脑的功能性血流反应，以及乙酰唑胺（15mg/kg）后的脑血管反应性。26名半合子患者（年龄范围19 - 47岁）参加了一项随机双盲安慰剂对照的6个月试验，每两周静脉输注一次酶替代疗法。在试验开始和结束时用PET测量局部脑血流量（rCBF）。
与对照组相比，法布里病患者在视觉刺激和乙酰唑胺激发后rCBF的增加明显更大。视觉反应性正常。与对照组相比，法布里病患者乙酰唑胺后脑血管系统的恢复时间延长。酶替代治疗后，视觉刺激和乙酰唑胺诱导的异常rCBF反应以及脑血管系统延长的恢复均显著降低。
酶替代疗法可逆转法布里病中过度的脑血管反应。
