BACKGROUND AND PURPOSE:We characterized autonomic pilomotor and sudomotor skin function in early Parkinson's disease (PD) longitudinally.METHODS:We enrolled PD patients (Hoehn and Yahr 1-2) and healthy controls from movement disorder centers in Germany, Hungary, and the United States. We evaluated axon-reflex responses in adrenergic sympathetic pilomotor nerves and in cholinergic sudomotor nerves and assessed sympathetic skin response (SSR), predominantly parasympathetic neurocardiac function via heart rate variability, and disease-related symptoms at baseline, after 2 weeks, and after 1 and 2 years.CLINICALTRIALS:gov: NCT03043768.RESULTS:We included 38 participants: 26 PD (60% females, aged 62.4 ± 7.4 years, mean ± SD) and 12 controls (75% females, aged 59.5 ± 5.8 years). Pilomotor function was reduced in PD compared to controls at baseline when quantified via spatial axon-reflex spread (78 [43-143], median [interquartile range] mm2 vs. 175 [68-200] mm2 , p = 0.01) or erect hair follicle count in the axon-reflex region (8 [6-10] vs. 11 [6-16], p = 0.008) and showed reliability absent any changes from baseline to Week 2 (p = not significant [ns]). Between-group differences increased over the course of 2 years (p < 0.05), although no decline was observed within groups (p = ns). Pilomotor impairment in PD correlated with motor symptoms (rho = -0.59, p = 0.017) and was not lateralized (p = ns). Sudomotor axon-reflex and neurocardiac function did not differ between groups (p = ns), but SSR was reduced in PD (p = 0.0001).CONCLUSIONS:Impairment of adrenergic sympathetic pilomotor function and SSR in evolving PD is not paralleled by changes to cholinergic sudomotor function and parasympathetic neurocardiac function, suggesting a sympathetic pathophysiology. A pilomotor axon-reflex test might be useful to monitor PD-related pathology.

Failure to recognize symptoms of orthostatic hypotension (OH) may result in falls, syncope, and injuries. The relationship between orthostatic changes in blood pressure and symptom occurrence and severity is not known. The goal of the present study was to define the relationship between the occurrence and severity of the symptoms of orthostatic hypotension (OH) and (1) the upright systolic blood pressure (SBP) and (2) the fall in SBP after tilting in patients with OH. We prospectively studied 89 patients with OH. Reported BP values include the lowest BP in the first 3 minutes of tilt and the change in blood pressure during tilt. Subjects were queried about symptoms of orthostatic intolerance while supine and during the first 3 minutes of tilt testing using Question 1 of the Orthostatic Hypotension Questionnaire. Mean tilted SBP was 101.6±26.1 mm Hg and mean SBP fall 47.9±18.1 mm Hg. Mean symptom scores when upright were: light-headedness (2.3/10±2.7), dizziness (1.6/10±2.5), and impending blackout (0.8/10±1.9). The majority of patients were asymptomatic or mildly symptomatic and no discrete cutoff for symptoms was observed. The magnitude of the SBP fall (r=−0.07, P=NS) and the lowest upright SBP (r=0.08, P=NS) did not correlate with any reported symptom. These results suggest a poor relationship between the magnitude of the orthostatic BP fall, the upright orthostatic BP, and symptoms. Many patients are asymptomatic despite substantial SBP falls and low orthostatic blood pressures. These findings have implications for clinical care of patients with OH and clinical trials to treat patients with OH.

Patients with isolated systolic hypertension (ISH) are thought to show a diminished blood pressure (BP)–lowering effect after renal sympathetic denervation (RDN). This conclusion is mostly derived from unipolar radiofrequency catheter ablation studies. Limited data for newer RDN technologies exist. We used data from the RADIOSOUND-HTN (Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension) comparing 3 different RDN approaches to investigate a possible interaction between ISH and RDN response. One hundred twenty patients were stratified by having ISH or combined systolic-diastolic hypertension (CH). Of these, 39 underwent radiofrequency ablation of the renal main arteries, 39 combined radiofrequency ablation of the main and branch arteries, and 42 were treated with ultrasound-based ablation of the main renal artery. Patients with ISH (n=61) were older and had lower systolic and diastolic BP on ambulatory measurement (ambulatory BP measurement) at baseline in comparison to CH (n=59). At 3 months, patients with ISH showed a less pronounced BP-lowering effect of RDN as compared to patients with CH (daytime average −5.9±11.8 versus −13.3±11.7 mm Hg, P =0.001). This difference was significant for radiofrequency ablation of the renal main arteries and ultrasound-based ablation of the main renal artery treatment but did not reach significance in the radiofrequency ablation of the main and branch arteries group. After adjustment for baseline BP values and age, there was no significant difference in BP reduction between ISH and CH. Using unadjusted BP values, RDN seems to be more effective in CH than in ISH. However, adjusting for baseline BP values revealed similar BP reduction in ISH and CH patients, irrespective of the RDN treatment used. The value of ISH as predictor for successful RDN might have been overestimated in the past. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02920034.

Objective: To define the relationship between changes in BP on orthostatic symptom development in patients with OH. Background: Orthostatic hypotension (OH) is a common feature of many neurological disorders, including the alpha-synucleinopathies. Patients with OH can present with a wide range of symptoms, although often without clear link to blood pressure (BP). Design/Methods: In this retrospective study we reviewed 1037 charts of patients for autonomic testing from January 2016 to March 2018. Systolic, diastolic and mean arterial pressures were recorded continuously and each minute of testing. Change in blood pressures was compared to baseline values after supine rest, prior to testing. BP measures included the lowest BP in the first 3 minutes of tilt, the absolute BP value on tilt vs the lowest and the orthostatic BP-drop. Subjects were questioned about symptoms of orthostatic intolerance at baseline and two times during the first ten minutes of tilt. Results: Eighty-nine patients (57% male, mean age 69 years) with OH were included in the final analysis. All patients completed the symptom questionnaires during tilt table testing. Supine hypertension was present in 59%. The majority (78/89) of patients had OH related to neurodegenerative disease or peripheral neuropathy, with lightheadedness and dizziness the most common symptoms. There was no relationship between magnitude of blood pressure fall and maximum symptoms (R2=0.0, P=NS) or total symptoms (R2=0.04, P=NS). There was no relationship between absolute lowest blood pressure and maximum symptoms (R2=0.02, P=NS) or total symptoms (R2=0.05, P=NS). Conclusions: These results suggest a poor relationship between the magnitude of the orthostatic blood pressure fall, the absolute orthostatic blood pressure and symptoms. Many patients are asymptomatic despite substantial BP falls and low orthostatic blood pressures. These findings have implications for clinical care of patients with OH and clinical trials to treat patients with OH. Disclosure: Dr. Freeman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abide, Astellas, Aptinyx, Biogen, Chromocell, Dong-A, Ironwood, Lundbeck, MundiPharma, NeuroBo, Novartis, Pfizer, Regenacy, Toray and Theravance. Dr. Freeman has received personal compensation in an editorial capacity for Autonomic Neuroscience: Basic and Clinical. Dr. Freeman has received compensation for serving on the Board of Directors of NeuroBo. Dr. Freeman holds stock and/or stock options in NeuroBo. Dr. Freeman has received research support from Pfizer. Dr. Gibbons has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck Inc. Dr. Gibbons has received personal compensation in an editorial capacity for Autonomic Neuroscience: Basic and Clinical. Dr. Gibbons has received research support from Grifols Inc. Dr. Lapusca has nothing to disclose. Dr. Illigens has nothing to disclose. Dr. Campagnolo has nothing to disclose. Dr. Abuzinadah has nothing to disclose. Dr. Sinn has nothing to disclose.