Eur J Neurol. 2026 Jun;33(6):e70620. doi: 10.1111/ene.70620.
ABSTRACT
BACKGROUND: Multiple system atrophy (MSA) is characterized by progressive autonomic/motor dysfunction, but robust biomarkers do not exist. Electrochemical skin conductance (ESC) provides a noninvasive measure of sudomotor function, but its longitudinal predictive value and prognostic relevance in MSA remain insufficiently studied. We aimed to comprehensively evaluate ESC in a large longitudinal cohort.
METHODS: We analyzed 175 patients with MSA followed for a mean of 4.2 ± 2.1 years. Disease severity was assessed using UMSARS Parts 1 and 2, COMPASS31, SCOPA-AUT, and orthostatic blood pressure (BP) measurements. Hand and foot ESC were measured using Sudoscan. Cross-sectional and longitudinal associations were examined using linear mixed-effects models, repeated-measures correlations, and grouped 10-fold cross-validation. Mortality predictors were assessed with time-varying Cox proportional hazards models.
RESULTS: ESC was strongly inversely associated with UMSARS 1 and 2 (β = -0.58 to -0.65; r = -0.67 to -0.75; all p < 0.0001), whereas associations with orthostatic BP, autonomic symptom scales, and disease duration were weaker or inconsistent. ESC declined significantly over time (feet -6.88 ± 0.60 μS/year; hands -5.41 ± 0.46 μS/year; both p < 0.001), paralleling UMSARS progression. ESC outperformed orthostatic BP drops in predicting UMSARS scores in mixed-effects models and cross-validation. Higher ESC independently predicted lower mortality, while higher UMSARS scores and greater orthostatic BP drops predicted increased risk. Median survival was 46.2 months.
CONCLUSIONS: ESC is a sensitive biomarker of disease severity, progression, and survival in MSA, substantially outperforming orthostatic BP measures. Its simplicity and prognostic value support incorporation into routine monitoring and clinical trials.
PMID:42318805 | DOI:10.1111/ene.70620