. 2022 Jan 7;16(2):295–320. doi: 10.1177/19322968211035375

Table 6.

Electrochemical Skin Conductance (ESC).

Author(s) & Study Aim	Study Population & Design	Study Outcomes & Implications
Ang et al.¹²⁸ - Evaluate ESC as a reliable surrogate for early CAN	N = 77 n = 37 T1D M = 39 ± 8 yrs/age n = 40 HCs M = 38 ± 13 yrs/age Longitudinal	• Using Sudoscan (Impeto Medical, Paris, France) to measure ESC, no significant differences were observed in hands or feet of T1D participants relative to HCs at baseline • In T1D participants, mean ESC, as measured by Sudoscan, declined significantly from baseline to 12 months • While both hands & feet ESC declined over time, the significance of this finding is unclear and warrants further reliability testing
Binns-Hall et al.⁵¹ -Evaluate feasibility one-stop microvascular screening service for early diagnosis of DSPN, painful DSPN, & at-risk diabetic foot Bordier et al.¹²⁹ -Assess repeatability & reproducibility of Sudoscan in HVs & diabetic patients with a range of glycemic control	N = 236 M = 63.5 ± 14.1 yrs/age n = 231 T2D n = 5 T1D n = 84 +DPN n = 69 -DPN n = 83 unclassified N = 32 n = 14 T2D M = 62 ± 9 yrs/age n = 18 HVs M = 37 ± 13 yrs/age Cross-sectional	• Using Sudoscan, AUROC curve was 0.75 with an ESC threshold of ≤58.5 μS; sensitivity was 77.4% & specificity was 68.3% for detecting DSPN • Sudscan may be useful screening device with respectable performance values • On 3 different Sudoscan devices, 2 measurements were performed under usual testing conditions on T2D & HV participants • For hands ESC, in particpants with T2D, the mean repeatability SD was 4.3 μS (mean coefficient of variation was 7.1 ± 5.9%) & mean reproducibility SD was 4.5 μS (mean coefficient of variation was 7.4 ± 6.1%) • For hands ESC, in HVs, the mean repeatability SD was 3.1 μS (mean coefficient of variation was 4.2 ± 2.7%) & mean reproducibility SD was 3.2 μS (mean coefficient of variation was 4.3 ± 2.7%) • For feet ESC, in particpants with T2D, the mean repeatability SD was 4.3 μS (mean coefficient of variation was 6.9 ± 6.3%) & mean reproducibility SD was 4.3 μS (mean coefficient of variation was 6.9 ± 6.3%) • For feet ESC, in HVs, the mean repeatability SD was 2.1 μS (mean coefficient of variation was 2.8 ± 1.6%) & mean reproducibility SD was 2.3 μS (mean coefficient of variation was 3.1 ± 1.5%) • In participants with T2D, ICCs used to compare the 3 devices were 0.95 (0.89–0.98) & 0.88 (0.74–0.96) & for HVs were 0.87 (0.74–0.94) & 0.85 (0.71–0.93) for feet & hands, respectively • Findings establish that repeatability & reproducibility of ESC measurements are respectable in participants with T2D & HVs
Carbajal-Ramírez et al.¹³⁰ -Assess the accuracy of Sudoscan (feet & hands) compared to MNSI in a cross-sectional study of Mexicans with T2D	N = 221, Mexican n = 170 T2D < 5 yrs M = 58.6 ± 12.6 age/yrs n = 51 T2D >5 yrs M = 63.8 ± 11.8 age/yrs Cross-sectional	• Evaluating the diagnostic accuracy of Sudoscan, in participants with T2D >5 years, AUROC curve of hands & feet ESC were 0.84 & 0.78, respectively, with MINSI B as the reference; sensitivity of abnormal hands or feet ESC for detection of neuropathy was 97% • In participants with T2D <5 years, AUROC curve of hands & feet ESC were 0.66 & 0.72 respectively; sensitivity of abnormal hands or feet ESC for detection of neuropathy was 91% • Sudoscan, which does not require any preparation, is noninvasive, easy & rapid to use in detecting P • Sudoscan may be useful in the early diagnosis of PN in T2D
Chae et al.¹³¹ -Determine if Sudoscan can complement NCS & EMG in patients with LSR & PPN	N = 73 LE dysesthesia n = 34 Controls n = 18 LSR n = 21 PPN (57% +DM) M = 63.1 ± 10.8 yrs/age for +DM group Cross-sectional	• AUC was 0.78 for feet ESC; cutoff at 48 µS; sensitivity was 57.1% & specificity was 94.2% to detect PPN • At a 55 µS cutoff, hands ESC had a sensitivity of 71.4% & specificity of 78.8% to detect PPN • Sudoscan was found to have highly acceptable diagnostic accuracy for feet ESC with impressive specificity
D’Amato et al.¹³² -Determine diagnostic value of the combined scores of composite autonomic symptom score 31, validated questionnaire for autonomic symptoms, CAN, & ESC	N = 102 DM; 65% T2D M = 57.1 ± 13.7 yrs/age Cross-sectional	• In assessing the diagnostic accuracy of Sudoscan, AUC of ESC feet was 0.69 for DPN diagnosis • Among participants with DPN, ESC had a sensitivity of 62% specificity of 67%, & positive predictive value of 67% • Findings reveal fair Sudoscan test performance
Fabry et al.⁷⁶ -Compare several methods of evaluating small sensory & autonomic nerve fibers	N = 245 M = 50.4 ± 15.0 yrs/age n = 24 +DM n = 6 +IGT n = 102 “Definite SFN” n = 90 “No SFN” Retrospective study	• Diagnostic performance of ESC (Sudoscan) & IENFD was evaluated by studying the normality or abnormality of each test according to the diagnosis of “Definite SFN” or “No SFN,” respectively • ESC sensitivity was 60%, specificity was 89%, & positive predictive value was 86% for detecting SFN • IENFD sensitivity was 58%, specificity was 91%, & positive predictive value was 88% for detecting SFN • ESC or Sudoscan revealed significant differences between the “Definite SFN” & “No SFN” groups both in hands (60.2 ± 16.7 vs. 75.0 ± 8.9 μS) & feet (70.2 ± 16.5 vs. 81.6 ± 7.0 μS) • ESC & IENFD had comparable sensitivity, specificity, & positive predictive values
Gandecka et al.¹³³ -Evaluate sudomotor function & its relationship to metabolic control & diabetic complications	N = 485 Median = 41 yrs/age, IQR = 32–51 n = 404 T1D n = 84 Controls Case Control Study	• Participants with T1D had a significantly lower ESC (as measured by Sudoscan+) relative to controls • Discriminative value of feet ESC to identify patients with PN was slightly better than that of ESC in the hands: AUC 0.77 vs. AUC 0.72 • With a cutoff point of 79 μS or less for feet ESC (optimal Youden index), sensitivity was 72%, specificity was 68%, & Youden index was 0.4 • Reproducibility of Sudoscan (feet & hands ESC) was confirmed with a cutoff value ratio not significantly different from 0 & slope ratio close to unity
Goel et al.¹³⁴ -Determine efficacy of ECS in diagnosing early DPN when compared to VPT & DNS score	N = 523 T2D n = 110 +DPN M = 54.4 ± 11.9 yrs/age n = 413 -DPN M = 48.1 ± 11.4 yrs/age Cross-sectional	• AUC of the ROC plot for feet ESC (Sudoscan) was 0.88 & for VPT was 0.84 • Feet ESC, with a cutoff of <60 μS, had a sensitivity of 85% & specificity of 85% for classifying DPN • VPT, with a cut-off of >15 V, had a sensitivity of sensitivity of 72% & specificity of 90% for classifying DPN • Feet ESC measurement was superior to VPT testing for identifying patients with early DPN
Jin et al.¹³⁵ -Evaluate whether SUDOSCAN has good diagnostic ability in DSPN & CAN	N = 180 T2D, Chinese n = 60 -DSPN M = 54.4 ± 11.3 yrs/age n = 120 +DSPN M = 59.8 ± 8.0 yrs/age Cross-sectional	• AUROC was 0.61, sensitivity was 89.8% & specificity was 41.2% to diagnose DSPN • Sudoscan is a sensitive test to detect DSPN in China & may be an effective screening tool in primary health care settings
Krieger et al.¹²³ -Evaluate performance of Sudoscan against QSART in diagnosing DPN	N = 63 n = 27 T2D, +DPN M = 69 ± 4.8 yrs/age n = 20 T2D, -DPN M = 66 ± 5.8 yrs/age n = 16 MCs M = 64 ± 5.1 yrs/age Cross-sectional	• For feet ESC (Sudoscan), AUROC curve was 0.71; cutoff ≤ 80.0 μS (optimal Youden index) with a sensitivity of 70% & specificity of 53% • For hand ECS, AUROC curve was 0.71; cutoff of ≤ 75.0 μS (optimal Youden index) with a sensitivity of 85% & specificity of 50% • Feet & hand ESC significantly lower in patients with +DPN as compared to MCs • Patients with +DPN also had lower hand ESC than patients with -DPN • Sudoscan shows poor to good performance in detecting DPN • Sudoscan has high potential as a DPN screening tool in patients with T2D
Novak¹³⁶ -Determine the relationship between ECS measurements & loss of small fibers in the skin	N = 81 +SFN M = 53.3 ± 17.3 yrs/age n = 48 SFN-I n = 33 SFN-AD n = 9 DM n = 2 IGT Prospective, blinded	• ESC (Sudoscan) of feet (M = 0.88 ± 0.35 μS/kg), among participants with abnormal IENFD, was significantly reduced relative to participants with normal IENFD (M = 1.17 ± 0.27 μS/kg) • ESC significantly correlated with IENFD but not symptom scores • AUROC ESC feet was 0.74, with IENFD as reference, while adjusting for weight • ESC shows acceptable performance with the gold standard as the reference, revealing it may be useful in detecting SFN
Porubcin et al.¹³⁷ - Evaluate diagnostic accuracy of ESC to detect abnormal SGNFD & IENFD	N = 210 M = 45.5 ± 16.1 yrs/age n = 132 SFN-I n = 78 SFN-AD n = 2 IGT Retrospective, blinded	• ESC (Sudoscan), adjusted for weight (ESC/kg), was significantly reduced in participants with abnormally low IENFD (normal/abnormal ESC/kg 1.20 ± 0.37/1.04 ± 0.33 μS/kg) • AUROC curve was 0.63 for ESC/kg in predicting abnormal IENFD; sensitivity was 69% & specificity was 55% • ESC/kg showed modest performance & accuracy to detect SFN in the diverse sample
Selvarajah et al.¹³⁸ -Assess if Sudoscan is a reliable screen for DPN in clinics	N = 70 n = 24 T1D, +DPN M = 52.1 ± 9.7 yrs/age n = 21 T1D, -DPN M = 40.6 ± 9.8 yrs/age n = 25 HVs M = 48.1 ± 16.4 yrs/age Cross-sectional	• Foot ESC (Sudoscan) was significantly lower in participants with +DPN compared to those with -DPN & HVs • AUROC curve for foot ESC was 0.85; foot ESC cutoff point ≤ 77.0 μS (optimal Youden index); sensitivity & specificity were 88% & 76%, respectively, for classifying DPN • Sudoscan, a non-invasive & quick test, may be used as an objective screening test for DPN in busy diabetic clinics
Sheshah et al.¹³⁹ -Evaluate if ESC at foot can detect DPN & risk of foot ulceration as compared to traditional methods	N = 296, Saudi Arabians M = 46.7 ± 11.2 age/yrs n = 272 T2D n = 24 T1D Cross-sectional	• Feet ESC (Sudoscan; threshold <50 μS for severe SMD) AUC was 0.73 & 0.73 to detect severe DPN & FU, respectively, with NDS as the reference; sensitivity (61%, 64%) & specificity (85%, 82%) for DPN & FU, respectively • Feet ESC (Sudoscan; threshold <70 μS) AUC was 0.66 & 0.65 to detect DPN & FU, respectively, with NDS as the reference; sensitivity 81% & 81% & specificity 51% & 49% for DPN & FU, respectively • Sudoscan, a simple & objective tool, may be used to detect DPN & risk of FU in patients with DM

Abbreviations: AUC, area under the curve; AUROC, area under receiver operator characteristic; CAN, cardiovascular autonomic neuropathy; DM, diabetes mellitus; DNS, Diabetic Neuropathy Symptom Scale; DPN, diabetic peripheral neuropathy or diabetic polyneuropathy; DSPN, diabetic distal symmetric peripheral neuropathy or distal symmetrical polyneuropathy; EMG, electromyography; ESC, electrochemical skin conductance; FU, foot ulceration; HC, healthy control; HVs, healthy volunteers; IENFD, intraepidermal nerve fiber density; IGT, impaired glucose tolerance; IQR, interquartile range; kg, kilogram; LE, lower extremity; LSR, lumbosacral radiculopathy; M, mean; MC, matched controls; MNSI B, Michigan Neuropathy Screening Instrument B; NCS, nerve conduction study; NDS, Neuropathy Disability Score; PN, peripheral neuropathy; PPN, peripheral polyneuropathy; QSART, quantitative sudomotor axon reflex testing; ROC, receiver operator characteristic; SFN, small fiber neuropathy; SFN-AD, small fiber neuropathy classified according to associated disorders; SFN-I, small fiber neuropathy classified as idiopathic; SGNFD, sweat gland nerve fiber density; T1D, type 1 diabetes; T2D, type 2 diabetes; VPT, vibration perception threshold; yrs, years; μS, microSiemens.