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Plasma biomarkers of decreased vesicular storage distinguish Parkinson disease with orthostatic hypotension from the parkinsonian form of multiple system atrophy

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Abstract

Background

Parkinson disease with orthostatic hypotension (PD + OH) and the parkinsonian form of multiple system atrophy (MSA-P) can be difficult to distinguish clinically. Recent studies indicate that PD entails a vesicular storage defect in catecholaminergic neurons. Although cardiac sympathetic neuroimaging by 18F-dopamine positron emission tomography can identify decreased vesicular storage, this testing is not generally available. We assessed whether plasma biomarkers of a vesicular storage defect can separate PD + OH from MSA-P.

Methods

We conceptualized that after F-dopamine injection, augmented production of F-dihydroxyphenylacetic acid (F-DOPAC) indicates decreased vesicular storage, and we therefore predicted that arterial plasma F-DOPAC would be elevated in PD + OH but not in MSA-P. We measured arterial plasma F-DOPAC after 18F-dopamine administration (infused i.v. over 3 min) in patients with PD + OH (N = 12) or MSA-P (N = 21) and in healthy control subjects (N = 26). Peak F-DOPAC:dihydroxyphenylglycol (DHPG) was also calculated to adjust for effects of denervation on F-DOPAC production.

Results

Plasma F-DOPAC accumulated rapidly after initiation of 18F-dopamine infusion. Peak F-DOPAC (5–10 min) in PD + OH averaged three times that in MSA-P (P < 0.0001). Among MSA-P patients, none had peak F-DOPAC > 300 nCi-kg/cc-mCi, in contrast with 7 of 12 PD + OH patients (χ 2 = 16.6, P < 0.0001). DHPG was lower in PD + OH (3.83 ± 0.36 nmol/L) than in MSA-P (5.20 ± 0.29 nmol/L, P = 0.007). All MSA-P patients had peak F-DOPAC:DHPG < 60, in contrast with 9 of 12 PD + OH patients (χ 2 = 17.5, P < 0.0001). Adjustment of peak F-DOPAC for DHPG increased test sensitivity from 58 to 81 % at similar high specificity.

Interpretation

After F-dopamine injection, plasma F-DOPAC and F-DOPAC:DHPG distinguish PD + OH from MSA-P.

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Abbreviations

6F-DOPAC:

6-Fluorodihydroxyphenylacetic acid

DHPG:

3,4-Dihydroxyphenylglycol

MAO:

Monoamine oxidase

OH:

Orthostatic hypotension

MSA:

Multiple system atrophy

PAF:

Pure autonomic failure

PD:

Parkinson disease

ROC:

Receiver operating characteristic

VMAT2:

Type 2 vesicular monoamine transporter

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Acknowledgments

Authors acknowledge the support of the intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS, NIH), 10 Center Drive MSC-1620, Building 10 Room 5N220, Bethesda, MD, 20892-1620, USA

    David S. Goldstein, Irwin J. Kopin & Courtney Holmes

  2. Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel

    Yehonatan Sharabi

Authors
  1. David S. Goldstein
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  2. Irwin J. Kopin
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  3. Yehonatan Sharabi
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  4. Courtney Holmes
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Correspondence to David S. Goldstein.

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Goldstein, D.S., Kopin, I.J., Sharabi, Y. et al. Plasma biomarkers of decreased vesicular storage distinguish Parkinson disease with orthostatic hypotension from the parkinsonian form of multiple system atrophy. Clin Auton Res 25, 61–67 (2015). https://doi.org/10.1007/s10286-015-0268-z

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  • DOI: https://doi.org/10.1007/s10286-015-0268-z

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