Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension

Goldstein, David S.; Holmes, Courtney; Patronas, Nicholas J.; Kopin, Irwin J.

doi:10.1042/cs20020315

Cited by 12 publications

(11 citation statements)

References 31 publications

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“…Six 1-ml aliquots of CSF were obtained and frozen immediately in cryotubes placed in dry ice and stored at )70°C or colder until thawed for assay. The sixth 1-ml aliquot was assayed for catechols in our laboratory [12]. j Postmortem studies…”

Section: Methods J Subjectsmentioning

confidence: 99%

Central dopamine deficiency in pure autonomic failure

et al. 2008

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Surprisingly, PAF and PD entail similarly severe nigral and overall central dopaminergic denervation. There is more severe loss of striatal dopaminergic terminals in PD than in PAF and more severe loss of sympathetic noradrenergic terminals in PAF than in PD. These differences explain the distinctive clinical manifestations of the two Lewy body diseases. Parkinsonism appears to reflect striatal dopamine deficiency rather than loss of nigral dopaminergic neurons per se.

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Section: Methods J Subjectsmentioning

confidence: 99%

Central dopamine deficiency in pure autonomic failure

et al. 2008

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Section: Methodsmentioning

confidence: 99%

“…Six 1-mL aliquots of CSF were obtained and frozen immediately in cryotubes placed in dry ice and stored at -70 °C or colder until thawed for assay. The sixth 1-mL aliquot was assayed for catechols in our laboratory [30].Blood was obtained through an indwelling i.v. catheter, after the subject was supine for at least 15 minutes after catheter insertion.…”

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confidence: 99%

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Goldstein¹,

Holmes²,

Bentho³

et al. 2008

Parkinsonism & Related Disorders

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Objective-Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA).Methods-In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2 hours after 6-[ 18 F]fluorodopa injection, septal myocardial radioactivity measured 8 minutes after 6-[ 18 F] fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities.Results-PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[ 18 F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p<0.0001, p<0.0001, p=0.003 compared to controls), as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p<0.0001 each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p<0.0001). Myocardial 6-[ 18 F]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension (NOH)). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity).Conclusions-PD and MSA feature low PUT:OCC ratios of 6-[ 18 F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:OCC ratios of Corresponding author: David S. Goldstein, MD PhD, Clinical Neurocardiology Section, NINDS, NIH, 10 Center Drive MSC-1620, Building 10 Room 6N252, Bethesda, MD 20892-1620 USA, Phone: 301-496-2103, Fax: 301-402-0180, Blackberry: 301-675-1110 goldsteind@ninds.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Loss of sense of smell in PD has been associated with neuroimaging evidence of both central DA deficiency [22] and cardiac noradrenergic denervation [23]. Decreased olfaction also can occur in MSA [24,25], and it has been unclear how efficiently olfactory testing separates PD from MSA. NIH Public AccessThe main purpose of this study was to identify biomarkers that detect central DA deficiency and distinguish PD from MSA. Because of the impo...

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“…Thus, a bidirectional blood-brain barrier exists for the passage of NE in and out of the CNS. In the dysautonomia of the Shy-Drager syndrome, although plasma NE levels are extremely low, CSF levels are normal or even increased (16).…”

Section: Study Of Arterial Ne-appearance Rate In Mild͞moderate Depresmentioning

confidence: 99%

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia

Gold

Wong

Goldstein

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The mortality of chronic heart failure (CHF) doubles either when CHF patients are depressed or when their plasma norepinephrine (NE) level exceeds those of controls by Ϸ40%. We hypothesized that patients with major depression had centrally driven, sustained, stress-related, and treatment-reversible increases in plasma NE capable of increasing mortality in CHF patients with depression. We studied 23 controls and 22 medication-free patients with melancholic depression. In severely depressed patients before and after electroconvulsive therapy (ECT), we measured cerebrospinal fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic patients, we assessed basal and stress-mediated arterial NE appearance. Severely depressed patients had significant increases in mean around-the-clock levels of CSF NE (P < 0.02), plasma NE (P < 0.02), plasma EPI (P < 0.02), and plasma cortisol (P < 0.02). CSF NE, plasma NE, and cortisol all rose together throughout the night and peaked in the morning. Each fell to control values after ECT. Mildly-to-moderately melancholic patients also had increased basal (P < 0.05) and stress-related (P < 0.03) arterial NE-appearance rates. Severely melancholic depressed, medication-free patients had around-the-clock increases in plasma NE levels capable of increasing mortality in CHF. Twenty-four-hour indices of central noradrenergic, adrenomedullary, and adrenocortical secretion were also elevated. Concurrent diurnal rhythms of these secretions could potentiate their cardiotoxicity. Even mildly-to-moderately depressed melancholic patients had clinically relevant increases in the arterial NE-appearance rate. These findings will not apply to all clinical subtypes of major depression.cerebrospinal fluid ͉ epinephrine ͉ major depression ͉ cardiovascular disease ͉ chronic heart failure T he coexistence of major depression with chronic heart failure (CHF) doubles the mortality of CHF (1-3). CHF patients with asymptomatic left ventricular dysfunction coupled with high plasma norepinephrine (NE) levels also have a doubling in mortality (4). In one study, plasma NE levels equal to 40% or greater than those in their controls also doubled CHF mortality (5). Even a modest (25%) increase in plasma NE levels over 4 months more than doubled mortality in CHF patients (6). Prior studies have shown that elevated NE levels in patients with CHF can be further increased in an additive fashion by the superimposition of complications known to be associated with increased NE levels (7). Thus, substantially increased NE release in depression would result in significant increases in the burden of NE hypersecretion in patients with CHF who become depressed.Evidence of increased NE secretion in major depression could help explain increased mortality in patients with CHF who are depressed. However, results from prior studies of NE secretion in depression have been contradictory (reviewed in ref. 8). This ambiguity is likely to reflect almost exclusive ...

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Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension

Cited by 12 publications

References 31 publications

Central dopamine deficiency in pure autonomic failure

Central dopamine deficiency in pure autonomic failure

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia

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