Orthostatic hypotension from sympathetic denervation in Parkinson's disease.
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.
Goldstein
D S
DS
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov
Holmes
C S
CS
Dendi
R
R
Bruce
S R
SR
Li
S-T
ST
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging; D002395:Catecholamines / Q000097:blood; D003891:Desipramine / Q000494:pharmacology; D003937:Diagnosis, Differential; D005260:Female; D006321:Heart / Q000294:innervation / Q000503:physiopathology; D006801:Humans; D007024:Hypotension, Orthostatic / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010300:Parkinson Disease / Q000150:complications* / Q000503:physiopathology; D016683:Supine Position; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014055:Tomography, Emission-Computed; D014636:Valsalva Maneuver
D018759:Adrenergic Uptake Inhibitors; D002395:Catecholamines; D003891:Desipramine; D009638:Norepinephrine