Cardiovascular Autonomic Dysfunction in Parkinson’s Disease

Abstract

Patients with Parkinson’s disease (PD) often have signs or symptoms of impaired reflexive regulation of the circulation, including orthostatic intolerance from orthostatic hypotension (OH). Regardless of levodopa treatment, patients with PD + OH have abnormal blood pressure responses to the Valsalva maneuver and markedly decreased baroreflex–cardiovagal gain. In contrast, only a minority of patients without OH have abnormal Valsalva responses, and baroreflex–cardiovagal gain is often within normal limits. All patients with PD + OH have reduced sympathetic noradrenergic innervation of the left ventricular myocardium, and most of those without OH also have diffuse or localized loss of cardiac sympathetic innervation. In PD patients with localized denervation, denervation is earlier or more prominent in the inferolateral wall or apex than in the anterobasal septum, consistent with a retrograde, centripetal pathogenetic process. Plasma levels of the sympathetic neurotransmitter, norepinephrine and its main neuronal metabolite, dihydroxyphenylglycol, are lower in PD + OH than in PD without OH, indicating a smaller complement of sympathetic nerves in PD + OH; however, patients with pure autonomic failure (PAF) have even lower norepinephrine and dihydroxyphenylglycol levels, suggesting more extensive noradrenergic denervation in PAF than in PD + OH. These findings contrast with those in multiple system atrophy (MSA), which can be difficult to distinguish clinically from PD + OH, because most MSA patients have intact cardiac and overall noradrenergic innervation. Therefore, PD involves not only loss of nigrostriatal dopaminergic neurons but also a peripheral catecholaminergic lesion with loss of postganglionic sympathetic noradrenergic neurons. Recent studies have reported a lack of association of cardiac noradrenergic with striatal dopaminergic denervation across individual patients and a closer association of loss of sense of smell with the peripheral noradrenergic than nigrostriatal dopaminergic lesions. Bases for cardioselectivity of sympathetic denervation in PD and for the seeming independence of central dopaminergic and peripheral noradrenergic denervation are subjects of current research.