Longitudinal Decline in Electrochemical Skin Conductance Reflects Disease Progression in Multiple System Atrophy
Paulo Bastos, Marc Kermorgant, Fabienne Ory‐Magne, Clémence Leung, Margherita Fabbri, Olivier Rascol, Alexandra Foubert‐Samier, David Bendetowicz, Wassilios G. Meissner, Anne Pavy‐le‐TraonABSTRACT
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.