Brain dopamine and the syndromes of Parkinson and Huntington Clinical, morphological and neurochemical correlations

Bernheimer, H.; Birkmayer, W; Hornykiewicz, Oleh; Jellinger, K. A.; Seitelberger, F

doi:10.1016/0022-510x(73)90175-5

Cited by 2,404 publications

(1,032 citation statements)

References 72 publications

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“…In this study, PD patients had lower mean PUT:CAU and PUT:SN ratios of 6-[ 18 F]fluorodopa-derived radioactivity than did MSA patients, suggesting that PD involves more severe loss of dopaminergic innervation in the PUT than in other parts of the nigrostriatal system. Postmortem neurochemical studies by Hornykiewicz [35][36][37] showed more severely decreased PUT than CAU DA concentrations in PD; however, Spokes et al also found lower PUT than CAU DA concentrations in MSA patients [38].…”

Section: Discussionmentioning

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

140

103

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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: Discussionmentioning

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

140

103

View full text Add to dashboard Cite

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“…Post-mortem analyses clearly show shrinkage and loss of the pigmented cells of the SN and degeneration in additional brain regions (Braak, 2003). Symptoms do not typically appear until dopamine concentration has decreased by 80%, which corresponds to a loss of approximately 50% -60% of dopaminergic neurons (Hamani & Lozano, 2003;Bernheimer, Birkmayer, Hornykiewicz, Jellinger, & Seitelberger, 1973).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Effect of concurrent walking and interlocutor distance on conversational speech intensity and rate in Parkinson's disease

et al. 2016

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This study examined the effects of concurrent walking tasks and interlocutor distance on conversational speech production in fifteen individuals with idiopathic Parkinson's disease (PD) and fourteen age-equivalent controls. Recent studies of speech in PD have demonstrated that changes in the behavioural conditions and the environmental context can have a powerful effect on the severity of speech symptoms in PD. This investigation focused on changes in speech intensity and speech rate in response to changes in walking speed and interlocutor distance. Results suggest that the introduction of a concurrent walking task significantly increased the conversational speech intensity of both controls and individuals with PD. When compared to sitting and talking or standing and talking, current walking and talking appeared to have an energizing effect on conversational speech intensity. In addition, walking faster was associated with a significant increase in conversational speech intensity relative to normal and slow walking speeds. These results provide important new information about the effect of concurrent walking on speech motor performance and speech symptom severity in PD. The potential energizing effect of concurrent walking conditions on conversational speech intensity may be an important consideration in the assessment and treatment of individuals with low speech intensity in PD.

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“…12,13 PD patients with established disease show a 60-80% loss of specific putamen 18 F-dopa uptake in life, 14,15 in line with the reported loss of ventrolateral nigra compacta cells but less than the 95% loss of putamen dopamine postmortem. 16 These findings suggest that striatal dopamine terminal DDC activity may be relatively upregulated in PD, presumably to boost dopamine turnover by remaining neurons.…”

Section: Imaging the Presynaptic Dopaminergic Systemmentioning

confidence: 96%

Neuroimaging in Parkinson’s disease

Brooks

2004

Neurotherapeutics

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Summary:In this review, the potential role of positron emission tomography and single photon emission computed tomography as biological markers for diagnosing and following the progression of Parkinson's disease (PD) is discussed. Their value for assessing the efficacy of putative neuroprotective agents in PD and for revealing the pharmacological changes underlying the symptomatology and complications of this disorder is also considered. It is concluded that in the future functional imaging will provide a valuable adjunct to clinical assessment when judging the efficacy of putative neuroprotective approaches to PD.

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Brain dopamine and the syndromes of Parkinson and Huntington Clinical, morphological and neurochemical correlations

Cited by 2,404 publications

References 72 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

Effect of concurrent walking and interlocutor distance on conversational speech intensity and rate in Parkinson's disease

Neuroimaging in Parkinson’s disease

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