In multiple system atrophy (MSA) and pure autonomic failure (PAF), orthostatic hypotension (OH) results from deficient noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with OH due to MSA or PAF. A total of 28 patients with OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with Alzheimer's disease, 18 patients with dysautonomia (postural tachycardia syndrome or neurocardiogenic syncope) and six patients with MSA in the absence of OH. Patients with OH had lower cerebrospinal fluid concentrations of noradrenaline (0.53±0.07 nmol/l) and dihydroxyphenylglycol (6.52±0.46 nmol/l) than did control subjects (0.90±0.09 and 9.64±0.46 nmol/l respectively; P=0.0001). The MSA + OH group had higher plasma levels of both catechols (noradrenaline, 1.31±0.16 nmol/l; dihydroxyphenylglycol, 5.08±0.43 nmol/l) than did the PAF group (noradrenaline, 0.38±0.08 nmol/l; dihydroxyphenylglycol, 2.53±0.30 nmol/l; P<0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with OH had lower cerebrospinal fluid levels of noradrenaline and dihydroxyphenylglycol than those without OH (noradrenaline, 1.71±0.64 nmol/l; dihydroxyphenylglycol, 10.41±1.77 nmol/l respectively; P=0.006). The findings are consistent with central noradrenergic deficiency in both MSA + OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to OH.
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June 01 2003
Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension
David S. GOLDSTEIN;
*Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 6N252, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620, U.S.A.
Correspondence: Dr David S. Goldstein (e-mail [email protected]).
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Courtney HOLMES;
Courtney HOLMES
*Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 6N252, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620, U.S.A.
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Nicholas PATRONAS;
Nicholas PATRONAS
†Department of Radiology, NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Irwin J. KOPIN
Irwin J. KOPIN
*Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 6N252, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620, U.S.A.
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Publisher: Portland Press Ltd
Received:
November 06 2002
Revision Received:
November 29 2002
Accepted:
January 22 2003
Accepted Manuscript online:
January 22 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 104 (6): 649–654.
Article history
Received:
November 06 2002
Revision Received:
November 29 2002
Accepted:
January 22 2003
Accepted Manuscript online:
January 22 2003
Citation
David S. GOLDSTEIN, Courtney HOLMES, Nicholas PATRONAS, Irwin J. KOPIN; Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension. Clin Sci (Lond) 1 June 2003; 104 (6): 649–654. doi: https://doi.org/10.1042/CS20020315
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