Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease

Abstract

Background and Objectives:Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P) with the latter been characterized by diffuse anhidrosis in prospective study including patients in late stage of disease.We aimed to evaluate morphological and functional postganglionic sudomotor involvement in patients with new diagnosis MSA-P and PD to identify possible biomarkers that might be of help in differentiating the two conditions in early stage.Methods:One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At time of recruitment, questionnaires to assess non-motor, autonomic and small fiber symptoms were administered and patients underwent post-ganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor and pilomotor nerve fibers was measured on confocal images using dedicated software. A follow-up visit twelve months after recruitment was performed to confirm the diagnosis.Results:We recruited 57 patients with PD (M/F=36/21; age 63.5±9.4years) and 43 patients with MSA-P (M/F=27/16; age 62.3±9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in MSA-P compared to PD patients. Sweating output and intraepidermal, pilomotor and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in MSA-P patients. Pilomotor and sudomotor nerve density correlated with sweating function and with non-motor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers, efficiently separated the two populations, the receiver operating characteristics showing an area under the curve of 0.83.Discussion:Dynamic sweat test and the quantification of cutaneous autonomic nerves provided to be a sensitive morpho-functional approach to assess postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to early differentiate the two conditions.Classification of Evidence:This study provides Class II evidence that post ganglionic sudomotor morpho-functional assessment accurately distinguish PD from MSA-P patients.

Two‐Year observational study of autonomic skin function in patients with Parkinson's disease compared to healthy individuals

“…A predominantly central mechanism of sympathetic sudomotor dysfunction might also be consistent with the results of a study in 35 patients with early‐to‐intermediate PD, which revealed neither peripheral sympathetic nerve fiber impairment nor changes in adrenoreceptor sensitivity but attenuated muscle sympathetic nerve activity [24]. A recent study in patients with PD and multiple system atrophy–parkinsonian type (MSA‐P) using quantification of local sweat response to pilocarpine iontophoresis showed distinct differences in the postganglionic component of sudomotor dysfunction between both disorders, with more pronounced impairment in MSA‐P [25]. Another study was able to show that PD patients with higher disease stage tended to have impaired sudomotor axon‐reflex function [24].…”

“…Our observation of increasing differences in pilomotor function between PD patients and healthy controls in our PD cohort could indicate a possible value of QPART in monitoring response to disease‐modifying treatment noninvasively. Many investigational disease‐modifying strategies target alpha‐synuclein directly, including for instance blocking of alpha‐synuclein receptors to inhibit alpha‐synuclein spread, reduction of alpha‐synuclein amounts using gene‐silencing mechanisms to target alpha‐synuclein mRNA levels, and immunization against alpha‐synuclein using a humanized IgG1 monoclonal antibody [25–29]. Emerging research on these disease‐modifying interventions substantiates an urgent need for assessment tools that are easy to use and have the capability to detect and monitor progression of pathology.…”

“…A recent study in patients with PD and multiple system atrophyparkinsonian type (MSA-P) using quantification of local sweat response to pilocarpine iontophoresis showed distinct differences in the postganglionic component of sudomotor dysfunction between both disorders, with more pronounced impairment in MSA-P [25].…”

Multiple system atrophy

“…► Heat intolerance or flushing due to progressive hypohidrosis, which is more severe in MSA than in Parkinson's disease. 48 ► Impaired peripheral vasomotor function/ circulation leading to 'reddish-blue' discolouration of the extremities, often associated with the 'cold hand' or 'cold foot' sign. 49…”

Unraveling Autonomic Dysfunction in GBA‐Related Parkinson's Disease

“…Sudomotor function was investigated using the Dynamic Sweat Test (DST), which measures post-ganglionic sudomotor function by stimulating the skin via iontophoresis at 2 mA for 5 0 using pilocarpine. 40,41 Progressive sweating was recorded for 3 min with high resolution digital camera (Toshiba Camileo X150) and analyzed, through ImageJ software [Rasband, W.S. (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) ImageJ.…”