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Prevalence and burden of dysautonomia in advanced Parkinson's disease

We sought to examine the prevalence and burden of dysautonomia in patients with advanced Parkinson’s disease (PD) treated with subthalamic deep brain stimulation (STNDBS) and levodopa-carbidopa intestinal gel infusion (LCIG). Using a standardized battery of autonomic tests, blood pressure measurement protocol, and the Scale for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT), 60 consecutive PD patients treated with STN-DBS (n 5 30) and LCIG (n 5 30) were classified according to the presence or absence of dysautonomia. We evaluated the impairment in activities of daily living/instrumental activities of daily living (ADL/iADL), adjusting for cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), age, and motor severity using the motor subscale of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III). Additional measures included SCOPA-AUT, Orthostatic Hypotension Symptom Assessment, and the PD Quality-of-Life Questionnaire (PDQ-8). Binary logistic regression was used to estimate the impact (odds ratio [OR]) of dysautonomia on ADL/iADL, adjusting for cognitive impairment, age, and motor severity. A multiple linear regression model was used to estimate the correlation between SCOPA-AUT and PDQ-8. In addition, analysis of covariance was used to estimate the extent to which the dependent variables, ADL/iADL, adjusted for MoCA, age, and MDS-UPDRS-III, were influenced by (1) symptomatic state (symptomatic vs asymptomatic orthostatic hypotension); and (2) therapy (STN-DBS vs LCIG). Mann-Whitney and Fisher’s tests were used for comparisons between groups. The overall prevalence of dysautonomia in this unselected population was 48.3% (29 of 60 patients), similar to that in the STN-DBS (50%) and LCIG (46.7%) cohorts (P 5 0.796). Adjusted analysis showed that dysautonomia was independently associated with a threefold impairment in ADL/iADL (OR, 2.850; 95% CI, 1.044-10.326; P 5 0.042). There was a robust correlation between autonomic symptoms (SCOPA-AUT) and quality-of-life impairment (P< 0.001). The strongest correlation was for gastrointestinal (P< 0.001), urinary/sexual (P 5 0.01), and cardiovascular (P 5 0.017) domains. Adjusted ADL/iADL scores differed between patients with and without orthostatic hypotension (P 0.047). In post hoc analyses, symptomatic (15.0%) and asymptomatic (11.7%) orthostatic hypotension worsened ADL/iADL to a similar extent (P 0.045) compared with patients without orthostatic hypotension (Fig. 1). The adjusted ADL/iADL scores was similar in the STN-DBS and LCIG cohorts (P 0.473). Subanalysis of autonomic domains (Fig. 1) revealed worse cardiovascular impairment in the LCIG cohort (P 5 0.039), potentially because of higher dopaminergic dosage (Supplementary Table) and worse pupillomotor impairment in the STN-DBS cohort (P 5 0.026), plausibly associated with electrical spread to the optic tract.