Objective: Previous studies in Parkinson's disease (PD) patients have demonstrated a high prevalence of polyneuropathy (PNP) and pronounced alpha-Synuclein pathology in dermal nerve fibers already at early disease stages. The aim of this study was to analyze associations between the prevalence and severity of PNP with nonmotor and motor symptoms in PD patients. Methods: Fifty PD patients were characterized comprehensively for the presence of clinical symptoms (nonmotor and motor), electrophysiologic alterations andfor the first timeusing high-resolution ultrasound of peripheral nerves. Results: Sixty-two percent of PD patients showed electrophysiological pathology of PNP. The prevalence of patient-reported PNP symptoms was 86% and was particularly present in patients with longer disease duration, compromised scores of nonmotor and motor symptoms as well as with a negative evaluation of quality of life. Seventy-five percent of patients showed morphologic alterations similar to axonal PNP in high-resolution ultrasound compared to healthy controls. Interpretation: The study demonstrates the high burden of peripheral nervous system disease in Parkinson's disease. It advocates further studies to delineate the underlying pathophysiological mechanisms in order to optimize treatment approaches for PD, including the associated PNP.

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The aim of this prospective study was to investigate autonomic function in Parkinson’s disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively in 80 patients with Parkinson´s disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n=40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n= 76). The cross-sectional area of right/left vagus nerve of Parkinson´s patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn & Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n=11, chronotropic incompetence n=31, postural orthostatic tachycardia syndrome n=1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson’s Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional-area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity (high frequency power of the distance between two consecutive R waves in electrocardiogram (RR-Interval)) at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson´s patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson´s disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.