Central dopamine deficiency in pure autonomic failure

David S. Goldstein, Courtney Holmes, Takuya Sato, Miya Bernson, Neptune Mizrahi, Richard Imrich, Gilberto Carmona, Yehonatan Sharabi, Alexander O. Vortmeyer

Research output: Contribution to journalArticle

29 Scopus citations


Objective: Pure autonomic failure (PAF) and Parkinson's disease (PD) share several clinical laboratory abnormalities; however, PAF is not associated with parkinsonism. In this study, we tested the hypothesis that preservation of nigrostriatal dopaminergic innervation explains the absence of motor dysfunction in PAF. Methods: Patients with PAF (N = 5) or PD (N = 21) and control subjects (N = 14) had brain 6-[18F]fluorodopa positron emission tomographic scanning and cerebrospinal fluid catechol measurements. A patient with PAF and another with PD had rapid postmortem striatal, nigral, and sympathetic ganglion sampling, with assays of catechols and tyrosine hydroxylase activity. Results: The PAF and PD groups had similarly low mean substantia nigra (SN):occipital (OCC) ratios of 6-[18F]fluorodopa-derived radioactivity and similarly low cerebrospinal fluid dihydroxyphenylacetic acid and DOPA levels. Only the PD group, however, had low PUT:OCC, caudate:OCC, or PUT:SN ratios. The PAF and PD cases had similarly low SN tissue concentrations of dopamine and tyrosine hydroxylase activity, but the PD patient had tenfold lower PUT dopamine and the PAF patient 15-fold lower myocardial norepinephrine concentrations. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalClinical Autonomic Research
Issue number2
StatePublished - Apr 1 2008
Externally publishedYes


  • Dopamine
  • Fluorodopa
  • Parkinson
  • Pure autonomic failure

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology

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    Goldstein, D. S., Holmes, C., Sato, T., Bernson, M., Mizrahi, N., Imrich, R., Carmona, G., Sharabi, Y., & Vortmeyer, A. O. (2008). Central dopamine deficiency in pure autonomic failure. Clinical Autonomic Research, 18(2), 58-65. https://doi.org/10.1007/s10286-008-0457-0