S9.4 Parkinson disease with orthostatic hypotension: Distinctions from Parkinson disease without orthostatic hypotension and from pure autonomic failure

Abstract

About 40% of patients with Parkinson disease (PD) have orthostatic hypotension (OH). This study reviewed clinical and laboratory data from PD+OH patients compared to PD patients without OH or patients with pure autonomic failure (PAF), a rare Lewy body disease in which OH occurs without parkinsonism. Laboratory assessments used physiologic measures (e.g., baroreflex-cardiovagal gain), neurochemical assays (e.g., concentrations of norepinephrine and its deaminated metabolite, dihydroxyphenylglycol (DHPG), in plasma and skeletal muscle microdialysate), tissue noradrenergic innervation examined by 6-[18F]fluorodopamine positron emission tomographic scanning (PET) of the head, thorax, and abdomen, and striatal dopaminergic innervation by brain 6-[18F]fluorodopa PET. PD+OH patients were older than PD patients without OH, both at the time of testing and at the time of onset of the movement disorder; had worse olfactory dysfunction; and were more likely to have constipation, erectile failure, decreased sweating, dementia, and magnetic resonance imaging evidence of cerebral cortical atrophy. PD+OH patients had higher supine systolic blood pressures, lower baroreflex–cardiovagal slopes, and higher prevalances of abnormal systolic pressure responses to the Valsalva maneuver and of atrial ectopy and sinus bradycardia. Among patients off levodopa, plasma norepinephrine concentrations were lower and increased by less during orthostasis in PD+OH than in PD without OH. Plasma and skeletal muscle microdialysate concentrations of DHPG were lower in PD+OH. PD+OH was associated with lower organ:liver ratios of 6-[18F]fluorodopamine-derived radioactivity, for the interventricular septum and free wall, renal cortex, thyroid, and spleen. Compared to PAF patients, PD+OH patients had higher plasma norepinephrine, DHPG, and epinephrine levels, lower putamen:occipital cortex and caudate:occipital cortex ratios of 6-[18F]fluorodopa-derived radioactivity, and similar substantia nigra:occipital cortex ratios. Taken together, the results indicate that PD+OH differs from PD without OH in terms of age, severity of olfactory dysfunction, baroreflex–cardiovagal failure, supine hypertension, evidence of cortical atrophy, and cardiac and extracardiac noradrenergic denervation. PD+OH differs from PAF in terms of striatal but not nigral dopaminergic deficiency. PAF, PD+OH, and PD without OH therefore seem to be characterized by different relative extents of central and peripheral catecholaminergic denervation.