Cardiac Sympathetic Denervation in Parkinson Disease

Goldstein, David S.; Holmes, Courtney; Li, Sheng-Ting; Bruce, Simon; Metman, Leo Verhagen; Cannon, Richard O.

doi:10.7326/0003-4819-133-5-200009050-00009

Cited by 330 publications

(247 citation statements)

References 33 publications

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“…over 3 minutes. Dynamic data were obtained for 30 minutes, as described previously [29]. Followup 6-[ 18 F]fluorodopamine scans were obtained in 20 PD patients at about 2 years and 11 patients at about 5 years after initial testing.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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

Self Cite

141

110

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“…A second defining feature of PD is the presence of intraneuronal Lewy body inclusions, consisting of predominantly α-synuclein that are found throughout the central, peripheral, and autonomic nervous systems (CNS, PNS and ANS) (Bethlem and Den Hartog Jager 1960;Jellinger 1991;Jellinger 2012). In parallel to the striatal DA denervation (Bedard et al 2011), there is also heterogeneous peripheral denervation (Goldstein et al 1997;Goldstein et al 2000;Kaufmann and Goldstein 2013), with the most common being sympathetic denervation of the left ventricular myocardium leading to orthostatic hypotension (Lucio et al 2013). One of the most promising diseasemodifying therapies for PD involves the delivery of neurotrophic factors to the striatum and/or SNpc to protect DA neurons (Hegarty et al 2014b).…”

Section: Introductionmentioning

confidence: 99%

A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson’s Disease

et al. 2016

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“…In contrast, patients with Parkinson disease and autonomic failure have no detectable 123 I-MIBG-derived (16 -20) or 6-[ 18 F]fluorodopamine-derived (21,22) radioactivity in the left ventricular myocardium and a small or normal decrease in blood pressure in response to trimethaphan (Goldstein DS. Unpublished observations).…”

Section: Chronic Autonomic Failurementioning

confidence: 99%

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

Goldstein

Robertson²,

Esler³

et al. 2002

Ann Intern Med

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The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities. In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after "patchy" autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops. Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with ␤-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology. The notion that the sympathetic nervous system coordinates body functions probably originated with the second-century Greek physician Galen, who taught that nerves were hollow tubes distributing "animal spirits" in the body, thereby fostering concerted action, or "sympathy," of the organs. In 1552, Bartolomeo Eustachius first depicted the sympathetic nerves and the adrenal glands. Winslow reintroduced the sympathetic nervous system in 1732 to describe the chains of ganglia and nerves connected to the thoracic and lumbar spinal cord.The functions of these structures remained unknown until the 19th century, when Bernard and others first reported the effects of sympathetic nerve stimulation. In 1895, Oliver and Schäfer described the potent cardiovascular stimulatory effects of adrenal extracts. Soon afterward-almost exactly a century ago-Abel and Takamine identified epinephrine ("adrenaline" in British and European countries) as the active principle of the adrenal gland.Also in the late 19th century, Langley coined the term autonomic nervous system to denote the portion of the nervous system largely responsible for involuntary, unc...

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Cardiac Sympathetic Denervation in Parkinson Disease

Cited by 330 publications

References 33 publications

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

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

A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson’s Disease

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

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