Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson's disease.

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Use of Valsalva Maneuver to Detect Late-Onset Delayed Orthostatic Hypotension.

BACKGROUND: Standard autonomic testing includes a 10-minute head-up tilt table test to detect orthostatic hypotension. Although this test can detect delayed orthostatic hypotension (dOH) between 3 and 10 minutes of standing, it cannot detect late-onset dOH after 10 minutes of standing. METHODS: To determine whether Valsalva maneuver responses can identify patients who would require prolonged head-up tilt table test to diagnose late-onset dOH; patients with immediate orthostatic hypotension (onset <3 minutes; n=176), early-onset dOH (onset between 3 and 10 minutes; n=68), and late-onset dOH (onset >10 minutes; n=32) were retrospectively compared with controls (n=114) with normal head-up tilt table test and composite autonomic scoring scale score of 0. RESULTS: Changes in baseline systolic blood pressure at late phase 2 (∆SBPVM2), heart rate difference between baseline and phase 3 (∆HRVM3), and Valsalva ratio were lower and pressure recovery time (PRT) at phase 4 was longer in late-onset dOH patients than in controls. Differences in PRT and ∆HRVM3 remained significant after correcting for age. A PRT ≥2.14 s and ∆HRVM3 ≤15 bpm distinguished late-onset dOH from age- and sex-matched controls. Patients with longer PRT (relative risk ratio, 2.189 [1.579-3.036]) and lower ∆HRVM3 (relative risk ratio, 0.897 [0.847-0.951]) were more likely to have late-onset dOH. Patients with longer PRT (relative risk ratio, 1.075 [1.012-1.133]) were more likely to have early-onset than late-onset dOH. CONCLUSIONS: Long PRT and short ∆HRVM3 can help to identify patients who require prolonged head-up tilt table test to diagnose late-onset dOH.

Regional analysis of cerebral hemodynamic changes during the head-up tilt test in Parkinson's disease patients with orthostatic intolerance.

Significance: Cerebral oxygenation changes in the superior, middle, and medial gyri were used to elucidate spatial impairments of autonomic hemodynamic recovery during the head-up tilt table test (HUTT) in Parkinson's disease (PD) patients with orthostatic intolerance (OI) symptoms. Aim: To analyze dynamic oxygenation changes during the HUTT and classify PD patients with OI symptoms using clinical and oxygenation features. Approach: Thirty-nine PD patients with OI symptoms [10: orthostatic hypotension (PD-OH); 29: normal HUTT results (PD-NOR)] and seven healthy controls (HCs) were recruited. Prefrontal oxyhemoglobin (HbO) changes during the HUTT were reconstructed with diffuse optical tomography and segmented using the automated anatomical labeling system. Decision trees were used for classification. Results: HCs and PD-NOR patients with positive rates of HbO change (PD-POS) showed the greatest HbO recovery in the superior frontal gyrus (SFG) during tilt. PD-OH and PD-NOR patients with negative rates of HbO change (PD-NEG) showed asymmetric reoxygenation. The classification accuracy was 89.4% for PD-POS versus PD-NEG, 71% for PD-NOR versus PD-OH, and 55.8% for PD-POS versus PD-NEG versus PD-OH. The oxygenation features were more discriminative than the clinical features. Conclusions: PD-OH showed decreased right SFG function, which may be associated with impaired compensatory autonomic responses to orthostatic stress.

Cerebral hemodynamic monitoring of Parkinson's disease patients with orthostatic intolerance during head-up tilt test.

Significance: Monitoring of cerebral perfusion rather than blood pressure changes during a head-up tilt test (HUTT) is proposed to understand the pathophysiological effect of orthostatic intolerance (OI), including orthostatic hypotension (OH), in Parkinson's disease (PD) patients. Aim: We aim to characterize and distinguish the cerebral perfusion response to a HUTT for healthy controls (HCs) and PD patients with OI symptoms. Approach: Thirty-nine PD patients with OI symptoms [10 PD patients with OH (PD-OH) and 29 PD patients with normal HUTT results (PD-NOR)], along with seven HCs participated. A 108-channel diffuse optical tomography (DOT) system was used to reconstruct prefrontal oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT) changes during dynamic tilt (from supine to 70-deg tilt) and static tilt (remained tilted at 70 deg). Results: HCs showed rapid recovery of cerebral perfusion in the early stages of static tilt. PD-OH patients showed decreasing HbO and HbT during dynamic tilt, continuing into the static tilt period. The rate of HbO change from dynamic tilt to static tilt is the distinguishing feature between HCs and PD-OH patients. Accordingly, PD-NOR patients were subgrouped based on positive-rate and negative-rate of HbO change. PD patients with a negative rate of HbO change were more likely to report severe OI symptoms in the COMPASS questionnaire. Conclusions: Our findings showcase the usability of DOT for sensitive detection and quantification of autonomic dysfunction in PD patients with OI symptoms, even those with normal HUTT results.

Cerebral Perfusion Monitoring Using Near-Infrared Spectroscopy During Head-Up Tilt Table Test in Patients With Orthostatic Intolerance.

The head-up tilt table test (HUT) is one of the primary clinical examinations for evaluating orthostatic intolerance (OI). HUT can be divided into three phases: dynamic tilt phase (supine to tilt up), static tilt phase (remain tilted at 70°), and post tilt phase (tilt down back to supine position). Commonly, blood pressure (BP) and heart rate (HR) are monitored to observe for OI symptoms, but are indirect measurements of cerebral perfusion and can lead to inaccurate HUT evaluation. In this study, we implemented a 108-channel near-infrared spectroscopy (NIRS) probe to characterize HUT performance by monitoring cerebral hemodynamic changes for healthy controls (HCs), OI patients with normal HUT results, and OI patients with positive HUT results: vasovagal syncope (VS), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), and orthostatic hypertension (OHT). By the end of the static tilt phase, OI patients typically did not show a complete recovery back to baseline cerebral oxygenation and total blood volume compared to HCs. We characterized the return to cerebral homeostasis by polynomial fitting total blood volume changes and determining the inflection point. The OI patients with normal HUT results, VS, OH, or OHT showed a delay in the return to cerebral homeostasis compared to the HC group during HUT.

Prefrontal hemodynamic changes measured using near-infrared spectroscopy during the Valsalva maneuver in patients with orthostatic intolerance.

The Valsalva maneuver (VM) with beat-to-beat blood pressure and heart rate monitoring are used to evaluate orthostatic intolerance (OI). However, they lack the ability to detect cerebral hemodynamic changes, which may be a cause of OI symptoms. Therefore, we utilized near-infrared spectroscopy during VM. Patients with OI symptoms and normal healthy subjects were recruited. Patients were subgrouped according to VM results: patients with normal VM (NVM) and abnormal VM (AbVM). Oxyhemoglobin (HbO), deoxyhemoglobin, and total hemoglobin changes were measured at four different source-detector distances (SD) (15, 30, 36, and 45 mm), and latency, amplitude, duration, and integrated total signal were calculated. Those parameters were compared between a normal healthy control (HC) group and the two OI patient subgroups. We found that HbO increment latency at 30-mm SD in the HC, NVM, and AbVM groups was as follows: [Formula: see text], [Formula: see text], and [Formula: see text], respectively ([Formula: see text]). Among the four parameters we evaluated, latency of HbO increment was the best marker for differentiating OI.