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

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 (18)F-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 (18)F-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 (18)F-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.

• Authors: David S Goldstein, Irwin J Kopin, Yehonatan Sharabi, Courtney Holmes
• Journal: Clinical autonomic research : official journal of the Clinical Autonomic Research Society (Clin Auton Res) Vol. 25 Issue 1 Pg. 61-7 (Feb 2015) ISSN: 1619-1560 [Electronic] Germany
• PMID: 25638582 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Biomarkers
• Fluorine Radioisotopes
• 3,4-Dihydroxyphenylacetic Acid
• Methoxyhydroxyphenylglycol
• 3,4-dihydroxyphenylglycol
• Dopamine

Topics

• 3,4-Dihydroxyphenylacetic Acid (blood)
• Aged
• Biomarkers (blood)
• Case-Control Studies
• Comorbidity
• Cross-Sectional Studies
• Diagnosis, Differential
• Dopamine (pharmacology)
• Female
• Fluorine Radioisotopes
• Humans
• Hypotension, Orthostatic (blood, diagnosis)
• Male
• Methoxyhydroxyphenylglycol (analogs & derivatives, blood)
• Middle Aged
• Multiple System Atrophy (blood, diagnosis)
• Parkinson Disease (blood, diagnosis)
• Sensitivity and Specificity
• Synaptic Vesicles (drug effects, physiology)