Top

BMC Neurology

Published in:

Open Access 01-12-2002 | Research article

Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease

Authors: David F Moore, Gheona Altarescu, Peter Herscovitch, Raphael Schiffmann

Published in: BMC Neurology | Issue 1/2002

Abstract

Background

Fabry disease is a lysosomal X-linked enzyme deficiency of α-galactosidase A associated with an increased mortality and morbidity due to renal failure, cardiac disease and early onset stroke.

Methods

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.

Results

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.

Conclusions

Enzyme replacement therapy reverses the exaggerated cerebrovascular response in Fabry disease.

Available only for authorised users

Brady R, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L: Enzymatic defect in Fabry disease: ceramide trihexosidase deficiency. N Engl J Med. 1967, 276: 1163-1167.CrossRefPubMed

Kint J: Alpha-galactosidase deficiency. Science. 1970, 167: 1268-CrossRefPubMed

Kanda A, Nakao S, Tsuyama S, Murata F, Kanzaki T: Fabry disease: ultrastructural lectin histochemical analyses of lysosomal deposits. Virchows Arch. 2000, 436: 36-42.CrossRefPubMed

Desnick R, Ioannou YA, Eng CM: α-Galactosidase A Deficiency: Fabry Disease. Valle. Edited by: R Charles, Scriver, Arthur L, Beaudet William, S Sly David. 2001, New York, McGraw-Hill, 3733-3774.

Moore DF, Scott LJC, Gladwin MT, Altarescu G, Kaneski C, Suzuki K, Pease-Fye M, Ferri R, Brady RO, Herscovitch P, Schiffmann R: Regional Cerebral Hyper-Perfusion and Nitric Oxide Pathway Dysregulation in Fabry Disease: Reversal by Enzyme Replacement Therapy. Circulation. 2001, 104: 1506-1512.CrossRefPubMed

Schiffmann R, Kopp J, Austin H, Sabnis S, Moore DF, Weibel T, Balow J, Brady RO: A randomized double-blind, placebo-controlled trial of enzyme replacement therapy in Fabry disease. JAMA. 2001, 285: 2743-2749. 10.1001/jama.285.21.2743.CrossRefPubMed

Mitsias P, Levine SR: Cerebrovascular complications of Fabry's disease. Ann Neurol. 1996, 40: 8-17.CrossRefPubMed

Evans O, Parker CC, Haas RH, Naidu S, Moser H, Bock HGO: " Inborn errors of metabolism of the nervous system. Chapter 68, Neurology in Clinical Practice.,". Butterworth-Heinemann, Woburn, MA, ed. Third Edition,. 2000

Altarescu G, Moore DF, Pursley R, Campia U, Goldstein S, Bryant M, Panza JA, Schiffmann R: Enhanced endothelium-dependent vasodilation in Fabry disease. Stroke. 2001, 32: 1559-1562.CrossRefPubMedPubMedCentral

10.

Moore DF, Herscovitch P, Schiffmann R: Selective arterial distribution of cerebral hyper-perfusion in Fabry disease. J. Neuroimaging. 2001, 11: 303-307.CrossRefPubMed

11.

Crutchfield K, Patronas NJ, Dambrosia JM, Frei KP, Banerjee TK, Barton NW, Schiffmann R: Quantitative analysis of cerebral vasculopathy in patients with Fabry disease. Neurology. 1998, 50: 1746-1749.CrossRefPubMed

12.

Fox P, Raichle ME: Stimulus rate determines regional brain blood flow in the striate cortex. Ann Neurol. 1985, 17: 303-305.CrossRefPubMed

13.

Herscovitch P, Markham J, Raichle ME: Brain blood flow measured with intravenous O-15 water. Theory and error analysis. J Nucl Med. 1983, 24: 782-789.PubMed

14.

Koeppe R, Holden JE, Polcyn RE, Nickles RJ, Hutchins GD, Weese JL: Performance comparison of parameter estimation techniques for the quantitation of local cerebral blood flow by dynamic positron computed tomography. J Cereb Blood Flow Metab. 1985, 5: 214-223.CrossRefPubMed

15.

Collins D, Zijdenbos AP, Kollokian JG, Kabani NJ, Holmes CJ, Evans AC: Design and construction of a realistic digital brain phantom. IEEE Transactions on Medical Imaging. 1998, 17: 463-469. 10.1109/42.712135.CrossRefPubMed

16.

Friston K, Ashburner J, Frith CD, Poline JB, Heather JD, Frackowiak RSJ: Spatial registration and normalization of images. Human Brain Mapping. 1995, 2: 165-189.CrossRef

17.

Nowinski W, Bryan RN, Raghavan R: The Electronic Clinical Brain Atlas. New YorK, Thieme. 1999

18.

Faraci F, Heistad DD: Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels. Physiological Reviews. 1998, 78: 53-97.PubMed

19.

Szabo C: Physiological and pathophysiological roles of nitric oxide in the central nervous system. Brain Research Bulletin. 1996, 41: 131-141. 10.1016/S0361-9230(96)00159-1.CrossRefPubMed

20.

Inao S, Tadokoro M, Nishino M, Mizutani N, Terada K, Bundo M, Kuchiwaki H, Yoshida J: Neural Activation of the Brain with Hemodynamic Insufficiency. J Cereb Blood Flow Metab. 1998, 18: 960-967. 10.1097/00004647-199809000-00005.CrossRefPubMed

21.

Dahl A, Russell D, Rootwell K, Nyber-Hansen R, Kerty E: Cerebral vasoreactivity assessed with transcranial Doppler and regional cerebral blood flow measurements. Dose, serum concentration, and time course of the response to acetazolamide. Stroke. 1995, 26: 2302-2306.CrossRefPubMed

22.

Hayashida K, Tanaka Y, Hirose Y, Kume N, Iwama T, Mikyake Y, Ishida Y, Matsuura H, Miyake Y, Nishimura T: Vasoreactive effect of acetazolamide as a function of time with sequential PET ¹⁵O-water measurements. Nuclear Medicine Communications. 1996, 17: 1047-1051.CrossRefPubMed

23.

Kiss B, Dallinger S, Findl O, Rainer G, Eichler HG, Schmetterer L: Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide. Am. J. Physiol. 1999, 276: R1661-R1667.PubMed

24.

White R, Deane C, Vallance P, Markus HS: Nitric Oxide Synthase Inhibition in Humans Reduces Cerebral Blood Flow but Not the Hyperemic Response to Hypercapnia. Stroke. 1998, 29: 467-472.CrossRefPubMed

25.

Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou H, Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP: Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. Journal of Biological Chemistry. 2001, 276: 38121-38138. 10.1074/jbc.M008340200.CrossRefPubMed

26.

Razani B, Lisanti MP: Caveolin-deficient mice: insights into caveolar function and human disease. Journal of Clinical Investigation. 2001, 108: 1553-1561. 10.1172/JCI200114611.CrossRefPubMedPubMedCentral

27.

Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000, 87: 840-844.CrossRefPubMed

28.

Wei E, Christman CW, Kontos HA, Povlishock JT: Effects of oxygen radicals on cerebral arterioles. Am J Physiol. 1985, 248: H157-H162.PubMed

29.

Etchevers H, Vincent C, Le Dourarin NM, Couly GF: The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain. Development. 2001, 128: 1059-1068.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/2/4/prepub

Title: Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease
Authors: David F Moore
Gheona Altarescu
Peter Herscovitch
Raphael Schiffmann
Publication date: 01-12-2002
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2002
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/1471-2377-2-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2002

To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?

P-ANCA vasculitic neuropathy with 12-year latency between onset of neuropathy and systemic symptoms

An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis

Confounding factors in diagnosing brain death: a case report

Chromosome 4q;10q translocations; Comparison with different ethnic populations and FSHD patients

Delayed minocycline but not delayed mild hypothermia protects against embolic stroke