LF power reflects baroreflex function, not cardiac sympathetic innervation.

Abstract-Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-͓ 18 F͔fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (Ϫ52Ϯ6 ͓SEM͔ versus Ϫ49Ϯ5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84Ϯ0.23 versus 1.33Ϯ0.35 ms/mm Hg during Valsalva; 0.43Ϯ0.09 versus 0.27Ϯ0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97Ϯ29 versus 71Ϯ23 pg/mL during orthostasis; Ϫ82Ϯ10 versus Ϫ73Ϯ8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193Ϯ19 pg/mL) than without (348Ϯ46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment. Key Words: hypotension Ⅲ sympathetic nervous system Ⅲ norepinephrine Ⅲ baroreflex P rimary chronic autonomic failure syndromes have been classified clinically in 3 forms: pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure. 1 All 3 forms feature neurogenic orthostatic hypotension (OH), supine hypertension, 2,3 and attenuation of the orthostatic increase in the plasma level of norepinephrine (NE), the sympathetic neurotransmitter. 4,5 Levodopa is a precursor of dopamine and therefore of NE. In the treatment of PD, levodopa is usually combined with an inhibitor of L-aromatic-acid-decarboxylase, such as carbidopa, which does not penetrate the blood-brain barrier. Combined levodopa/carbidopa treatment therefore augments delivery of levodopa to the brain and mitigates nausea and vomiting thought to result from occupation of dopamine receptors outside the blood-brain barrier. Combined levodopa/carbidopa treatment attenuates but does not prevent catecholamine synthesis from levodopa outside the brain. 6,7 Reflexive cardiovagal gain has been reported to be variably decreased in PD 8,9 and markedly decreased in PDϩOH. 10 Levodopa treatment of PD can affect reflexive cardiov...

There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[ 18 F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.In Parkinson disease (PD), by the time the movement disorder develops, most of the nigrostriatal dopamine terminals have been lost. Identification of biomarkers of PD should improve early diagnosis and spur development of effective treatments.Correspondence: David S. Goldstein, MD, PhD, Clinical Neurocardiology Section, NINDS, NIH, 10 Center Drive MSC-1620, Building 10, Room 6N252, Bethesda, MD 20892-1620; goldsteind@ninds.nih.gov. No author conflicts of interest were reported in the original publication of this article. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptBraak has proposed a pathogenetic sequence beginning outside the brain, with invasion of peripheral, vulnerable autonomic neurons, followed by alpha-synucleinopathy in lower brainstem nuclei and then by alpha-synucleinopathy in the midbrain substantia nigra and then finally in the cerebral cortex. 3,4 Consistent with early involvement of peripheral autonomic or lower brainstem centers, several studies of de novo PD have reported evidence of cardiac noradrenergic denervation 5,8,14,22 or of decreased baroreflex-cardiovagal function. 1,2,6,14,18 Whether these abnormalities can actually precede symptomatic PD has been unknown. Here we report the case of a patient who had cardiac noradrenergic denervation, detected by 6-[ 18 F]fluorodopamine positron emission tomography, and decreased baroreflex-cardiovagal gain, detected by abnormal beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver, 4 years before the clinical onset of PD. CASE REPORTA 56-year-old man was referred for possible pheochromocytoma, based on episodic hypertensive episodes and symptoms suggesting excessive catecholamine effects.He had no serious health problems until about 1998, when he began to experience malaise and exercise intolerance and episodes of hypertension or hypotension, palpitations, and chest tightness. He also had a long history of constipation and dyspepsia, a tendency to urinary retention, and complained of a sense of fullness in the left neck. The patient's career was in marketing and business development, until he quit work due to his symptoms. His mother had died of PD. Cardiac catheterization showed normal coronary arteries. Gastrointestinal endoscopy was unrevealing. Biochemical testing showed elevated plasma levels and urinary excretion of epin...