Diagnostic Accuracy of Electrochemical Skin Conductance in the Detection of Sudomotor Fiber Loss

Abstract

Background: Small fiber neuropathy (SFN) is a common health problem. SFN is associated with loss of small fibers, either sensory, autonomic or both. Reduced autonomic sudomotor sweat gland nerve fiber density (SGNFD) and sensory epidermal nerve fiber density (ENFD) can be seen in SFN. Electrochemical skin conductance (ESC) is a non-invasive test for measurement of sudomotor function. This study evaluated the diagnostic accuracy of ESC to detect abnormal SGNFD and ENFD. Methods: This was a retrospective blinded study of participants referred for evaluation of SFN. The primary outcome measure was the specificity and sensitivity of ESC to diagnose loss of small fibers using SGNFD and ENFD as reference tests. The secondary outcome measures were the correlation between ESC and neuropathy severity, pain, and autonomic clinical scales. Results: Two hundred ten patients were enrolled in the study, age (mean ± sd) 45.5 ± 16.1 years, men/women = 52/158. ESC adjusted for weight (ESC/kg) was reduced in subjects with abnormally low SGNFD (normal/abnormal, ESC/kg = 1.19 ± 0.31/0.94 ± 0.37 µS/kg, p < 0.0001) and abnormally low ENFD (normal/abnormal ESC/kg 1.20 ± 0.37/1.04 ± 0.33 µS/kg, p < 0.0011). ESC/kg correlated with SGNFD (ρ = 0.39, p < 0.0001) and ENFD (ρ = 0.47, p < 0.0001). ESC/kg did not correlate with symptom scales. ESC/kg had 64% sensitivity and 77% specificity (ROC 0.73, p = 0.0001) to predict abnormal SGNFD and 69% sensitivity and 55% specificity (ROC 0.63, p = 0.0017) to predict abnormal ENFD. In comparison, SGNFD had 50.1% sensitivity and 85.1% specificity to predict abnormal ENFD (ROC 0.69, p = 0.0001). Conclusion: ESC/kg has modest accuracy to detect SGNFD loss. ESC may be a useful test in characterization of small fiber neuropathy.

Multisystem Involvement in Post‐Acute Sequelae of Coronavirus Disease 19

“…Inclusion criteria for the study were: (1) adult patients 18 years of age or older; (2) documented diagnosis of COVID‐19 disease by history of positive reverse transcriptase‐polymerase chain reaction (PCR) positive for SARS‐CoV‐2; (3) completion of comprehensive autonomic testing with skin biopsies; (4) availability of electronic health care records; (5) satisfying inclusion criteria for PASC; (6) for the POTS controls, matched by age and sex, satisfying criteria for POTS 10 ; and (7) age and sex matched asymptomatic healthy controls were used from our previous University of Massachusetts (UMASS) study 11 . Testing at the UMASS was identical to the Brigham protocol 12 used in this study except electrochemical skin conductance (ESC) 13 was used instead of quantitative sudomotor axon reflex test (QSART) for sudomotor evaluations. ESC correlates with loss of sweat gland nerve fibers and therefore can be used as a proxy for sudomotor function 13 .…”

“…Testing at the UMASS was identical to the Brigham protocol 12 used in this study except electrochemical skin conductance (ESC) 13 was used instead of quantitative sudomotor axon reflex test (QSART) for sudomotor evaluations. ESC correlates with loss of sweat gland nerve fibers and therefore can be used as a proxy for sudomotor function 13 . In addition, the inflammatory markers were not available for controls.…”

“…SFN is defined as combination of symptoms and signs 20 . The criteria for SFN were SAS or NTSS >1 and abnormal skin biopsies or abnormal sudomotor testing 13,20 …”

Diabetes Distal Peripheral Neuropathy: Subtypes and Diagnostic and Screening Technologies

“…[125][126][127] Since 2015, the literature search identified 14 studies evaluating ESC, namely Sudoscan (Impeto Medical, Paris, France; see Table 6). 51,76,123,[128][129][130][131][132][133][134][135][136][137][138][139] Advancing earlier EZSCAN technology, Sudoscan is a POCD wherein testing requires that the patient place his/her hands and feet, respectively, on 2 stainless steal electrodes. [125][126] While the patient's hands and feet remain on the electrodes for 2 minutes, a computer records ESC values.…”

Hydrogen Peroxide Production by Epidermal Dual Oxidase 1 Regulates Nociceptive Sensory Signals

“…These polymodal sensory nerve fibers penetrate the dermal-epidermal basement membrane and interweave among the very tightly organized epidermal cell layers. Epidermal nerve fiber density (ENFD) is a clinically important histological marker in several neuropathic conditions (Porubcin and Novak, 2020). The close proximity of nerve fibers and keratinocytes renders the latter suitable to function as a secondary sensory cell that can trigger or modulate the activation of the sensory neuron.…”