Cardiovascular dysautonomia in Parkinson disease: From pathophysiology to pathogenesis

• Published in: Neurobiology of disease 2012-06, Vol.46 (3), p.572-580
• Main Authors: Jain, Samay, Goldstein, David S
• Format: Article
• Language: English
• Subjects: Atrophy; Autonomic dysfunction; Autonomic nervous system; Autonomic Nervous System - physiopathology; Baroreceptors; Biomarkers; Blood pressure; Cardiovascular Diseases - etiology; Cardiovascular Diseases - pathology; Cardiovascular Diseases - physiopathology; Catecholamine; Catecholamines; Catecholamines - metabolism; Corpus Striatum - physiology; Denervation; Diagnosis, Differential; Dopamine - physiology; Dysautonomia; Heart; Humans; Innervation; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neuroimaging; Neurology; Non-motor features; Norepinephrine; Orthostasis; Parkinson disease; Parkinson Disease - complications; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson's disease; Primary Dysautonomias - etiology; Primary Dysautonomias - pathology; Primary Dysautonomias - physiopathology; Reflexes; Reviews; Sympathectomy; Ventricle; Vesicular amine transporter
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2011.10.025

Abstract Signs or symptoms of impaired autonomic regulation of circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30–40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 min of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD + OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD + OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD + OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a “triple whammy” of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD + OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme-catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain. Parkinson disease (PD) is one of the most common chronic neurodegenerative diseases of the elderly, and it is likely that as populations age PD will become even more prevalent and more of a public health burden. Severe depletion of dopaminergic neurons of the nigrostriatal system cha