ABSTRACT
In PD, orthostatic hypotension reflects sympathetic noradrenergic denervation. The authors assessed sympathetic cholinergic innervation by the quantitative sudomotor axon reflex test (QSART) in 12 patients who had sympathetic neurocirculatory failure, markedly decreased cardiac 6-[18F] fluorodopamine-derived radioactivity, and subnormal plasma norepinephrine increments during standing. All 12 had normal QSART results. The sympathetic nervous system lesion in PD involves loss of postganglionic catecholaminergic but not cholinergic nerves.
Subject(s)
Acetylcholine/physiology , Dihydroxyphenylalanine/analogs & derivatives , Norepinephrine/physiology , Parkinson Disease/physiopathology , Sympathectomy , Autonomic Fibers, Postganglionic/physiopathology , Cholinergic Fibers/physiology , Fluorine Radioisotopes , Heart Ventricles/diagnostic imaging , Hemodynamics , Humans , Hypohidrosis/physiopathology , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Norepinephrine/blood , Parkinson Disease/complications , Radiopharmaceuticals , Tomography, Emission-Computed , Valsalva ManeuverABSTRACT
BACKGROUND: Patients with PD often have signs or symptoms of autonomic failure, including orthostatic hypotension. Cardiac sympathetic denervation occurs frequently in PD, but this has been thought to occur independently of autonomic failure. METHODS: Forty-one patients with PD (18 with and 23 without orthostatic hypotension) and 16 age-matched healthy volunteers underwent PET scanning to visualize sympathetic innervation after injection of 6-[(18)F]fluorodopamine. Beat-to-beat blood pressure responses to the Valsalva maneuver were used to identify sympathetic neurocirculatory failure and plasma norepinephrine to indicate overall sympathetic innervation. RESULTS: All patients with PD and orthostatic hypotension had abnormal blood pressure responses to the Valsalva maneuver and septal and lateral ventricular myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity >2 SD below the normal mean. In contrast, only 6 of the 23 patients without orthostatic hypotension had abnormal Valsalva responses (p < 0.0001 compared with patients with orthostatic hypotension), and only 11 had diffusely decreased 6-[(18)F]fluorodopamine-derived radioactivity in the left ventricular myocardium (p = 0.0004). Of the 12 remaining patients without orthostatic hypotension, 7 had locally decreased myocardial radioactivity. Supine plasma norepinephrine was lower in patients with than in those without orthostatic hypotension (1.40 +/- 0.15 vs 2.32 +/- 0.26 nmol/L, p = 0.005). 6-[(18)F]fluorodopamine-derived radioactivity was less not only in the myocardium but also in the thyroid and renal cortex of patients with PD than in healthy control subjects. CONCLUSIONS: In PD, orthostatic hypotension reflects sympathetic neurocirculatory failure from generalized sympathetic denervation.
