Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study

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.