Electrochemical Skin Conductance Measurement Research Articles

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study

ObjectiveThe study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. MethodsParticipants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. ResultsParticipants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

Sudoscan as substitute for quantitative sudomotor axon reflex test in composite autonomic scoring scale and its correlation with composite autonomic symptom scale 31 in type 2 diabetes

ObjectiveThis study aims to evaluate the feasibility of substituting electrochemical skin conductance measurement using SUDOSCAN for sudomotor function testing in the Composite Autonomic Scoring Scale (CASS) and to correlate the results with the Composite Autonomic Symptom Scale 31 (COMPASS 31) among patients with type 2 diabetes mellitus (T2DM). MethodsFifty patients with T2DM underwent cardiovascular autonomic function testing and the SUDOSCAN test and completed the COMPASS 31 questionnaire. We developed a SUDOSCAN-based sudomotor subscore as a substitute for the original sudomotor subscore (based on the quantitative sudomotor axon reflex test [QSART]). The modified CASS score (SUDOSCAN-based sudomotor subscore combined with the adrenergic and cardiovagal subscores) and the original CASS score without suomotor assessment (sum of the adrenergic and cardiovagal subscores) were obtained according to the results of the cardiovascular autonomic function and SUDOSCAN tests. ResultsThe total COMPASS 31 score was significantly correlated with the modified CASS score (p = 0.019 and 0.037 for the raw and weighted scores, respectively) but not with the CASS score without sudomotor assessment. After adding the SUDOSCAN-based sudomotor subscore, the number of patients identified as having diabetic autonomic neuropathy (DAN) increased from 24 (48 %, based on the CASS score without sudomotor assessment) to 35 (70 %, based on the modified CASS score). The modified CASS score enhances the accuracy of assessing autonomic function and improves the diagnosis of diabetic autonomic neuropathy (DAN) among patients with T2DM. In medical settings where QSART is not accessible, SUDOSCAN testing offers a practical and efficient alternative.

Validation of the Body Scan®, a new device to detect small fiber neuropathy by assessment of the sudomotor function: agreement with the Sudoscan®.

Sudomotor dysfunction is one of the earliest manifestations of small fiber neuropathy (SFN), reflecting the alteration of sympathetic C fiber innervation of the sweat glands. Among other techniques, such innervation can be assessed by measuring electrochemical skin conductance (ESC) in microsiemens (μS). In this study, ESC was measured at the feet to detect distal SFN. For this objective, the performance of a new device, the Body Scan® (Withings, France), intended for home use, was compared with that of a reference device, the Sudoscan® (Impeto Medical, France), which requires a hospital setting. In patients with diabetes with or without neuropathy or non-diabetic patients with lower-limb neuropathy, the diagnostic performance of the Body Scan® measurement was assessed by calculating its sensitivity (Se) and specificity (Sp) to detect at least moderate SFN (Se70 and Sp70), defined by a value of feet ESC ≤ 70 μS and > 50 μS on the Sudoscan® measure, or severe SFN (Se50 and Sp50), defined by a value of feet ESC ≤ 50 μS on the Sudoscan® measure. The agreement between the two devices was assessed with the analysis of Bland-Altman plots, mean absolute error (MAE), and root mean squared error (RMSE) calculations. The repeatability of the measurements was also compared between the two devices. A total of 147 patients (52% men, mean age 59 years old, 76% diabetic) were included in the analysis. The sensitivity and specificity to detect at least moderate or severe SFN were: Se70 = 0.91 ([0.83, 0.96]), Sp70 = 0.97 ([0.88, 0.99]), Se50 = 0.91 ([0.80, 0.98]), and Sp50 = 0.99 ([0.94, 1]), respectively. The bias and 95% limits of agreement were 1.5 [-5.4, 8.4]. The MAE was 2.9 and the RMSE 3.8. The intra-sample variability was 2.0 for the Body Scan® and 2.3 for the Sudoscan®. The ESC measurements provided by the Body Scan® were in almost perfect agreement with those provided by the reference device, the Sudoscan®, which validates the accuracy of the Body Scan® for the detection of SFN. By enabling simple, rapid, and autonomous use by the patient at home, this new technique will facilitate screening and monitoring of SFN in daily practice. ClinicalTrials.gov, identifier NCT05178459.

Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes.

To explore if novel non-invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross-sectional analysis with optical coherence tomography angiography (OCT-A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC). Seventy-five participants with normoglycaemia (n=20), prediabetes (n=29) and type 2 diabetes (n=26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16-Td·s: 4.05 μV, 95% confidence interval [95% CI] 0.96-7.13) and high (32-Td·s: 5·20 μV, 95% CI 1.54-8.86) retinal illuminance were lower in prediabetes, as were OCT-A parafoveal vessel densities in superficial (0.051 pixels/mm2 , 95% CI 0.005-0.095) and deep (0.048 pixels/mm2 , 95% CI 0.003-0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32-Td·s (r=-0.256, p=0.028), implicit time at 32-Td·s (r=0.422, p < 0.001) and 16-Td·s (r=0.327, p=0.005), OCT parafoveal vessel density in the superficial (r=-0.238, p=0.049) and deep (r=-0.3, p=0.017) retinal layers, corneal nerve fibre length (CNFL) (r=-0.293, p=0.017), and ESC-hands (r=-0.244, p=0.035) were observed. HOMA-IR was a predictor of CNFD (β=-0.94, 95% CI -1.66 to -0.21, p=0.012) and CNBD (β=-5.02, 95% CI -10.01 to -0.05, p=0.048). The glucose threshold for the diagnosis of diabetes is based on emergent retinopathy on fundus examination. We show that both abnormal retinal neurovascular structure (OCT-A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.

777-P: Short-Term Continuous Subcutaneous Insulin Infusion Treatment Improves Peripheral Autonomic Neuropathy in Type 2 Diabetes

Background: Short-term continuous subcutaneous insulin infusion treatment (CSII) in patients with newly diagnosed type 2 diabetes (T2DM) can improve β-cell function and insulin sensitivity, which results in long-term remission. However, the effect of CSII on peripheral neuropathy is rarely studied. Methods: 63 T2DM patients (HbA1c&amp;gt;9%) were hospitalized and treated with CSII for 2 weeks. Peripheral autonomic neuropathy was measured by SUDOSCAN, which provides an age adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤60 indicating sudomotor dysfunction. Blood glucose, HbA1c, C-peptide and SUDOSCAN were measured before and after CSII. HOMA-B was used for assessment of β-cell function. Results: The average HbA1c of included patients was 10.5% with median duration of T2DM was 3.5 years. There were 27 (42.9%) patients who had sudomotor dysfunction at baseline. After 2 weeks of CSII, the proportion of sudomotor dysfunction (42.9% vs. 31.7%, P=0.020) was significantly deceased along with significantly improved HbA1c (10.0±1.9 vs. 8.1±1.0, P&amp;lt;0.001) and HOMA-B [22.0 (IQR 12.1-37.0) vs. 56.9 (IQR 42.4-81.8) , P&amp;lt;0.001]. Correlation analysis revealed that higher ESC composite score was correlated with better HOMA-B after CSII (r=0.445, P=0.015) . Conclusion: Peripheral autonomic neuropathy could be improved by CSII in T2DM. The improvement of β-cell function could be responsible for the amelioration of peripheral nerve function. Keywords: Short-term continuous subcutaneous insulin infusion treatment; peripheral autonomic neuropathy; type 2 diabetes; β-cell function Disclosure J.Jin:None. Funding National Key R&amp;D Program of China (2018YFC1314100) ; the Key-Area Research and Development Program ofGuangdong Province (2019B020230001) ; the China Postdoctoral ScienceFoundation (2018M640871)

Assessment of sympathetic sudomotor function in amyotrophic lateral sclerosis with electrochemical skin conductance

ObjectiveAmyotrophic lateral sclerosis (ALS) is now recognized as a multisystem neurodegenerative disorder, comprising autonomic dysfunction. We aimed to assess sudomotor function in ALS by measuring the electrochemical skin conductance (ESC). MethodsThirty-one ALS patients [median age of 62 years (1st-3rd interquartile range – IQR, 56–72), male 71%] were prospectively compared with 29 healthy controls, matched for age and sex. We analysed ESC results from hands and feet, bilaterally. ResultsA total of 120 ESC recordings were obtained. Hands and feet ESC measurements were significantly lower in patients compared with controls [64 μS (1st-3rd IQR, 57–58) versus 78 μS (1st-3rd IQR, 70.5–84), p < 0.001 and 76 μS (1st-3rd IQR, 68–83) versus 81 μS (1st-3rd IQR, 78–86), p = 0.008, respectively]. In ALS group, no differences were observed between spinal and bulbar-onset forms for hands and feet results (p > 0.05). Hands and feet ESC measurements did not correlate also with disease duration, total ALSFRS-R scale, or ALSFRS-R progression rate (all p > 0.05). ConclusionESC is a non-invasive, fast and quantitative method suitable for assessing sudomotor function. ALS patients revealed a decreased function in upper and lower extremities. SignificanceSudomotor dysfunction is part of the ALS manifestations.

Prevalence and prognostic value of small fiber neuropathy assessed by Sudoscan ® in transthyretin wild-type cardiac amyloidosis

The prevalence of small-fiber neuropathy (SFN) is high in patients with hereditary transthyretin amyloidosis (ATTRv) but remains unknown in transthyretin wild-type cardiac amyloidosis (ATTRwt-CA). To determine the prevalence of SFN in patients with ATTRwt-CA using Sudoscan®, a non-invasive method used to provide evidence of SFN in clinical practice and based on measurement of electrochemical skin conductance at the hands (hESC) and feet (fESC). A series of 62 non-diabetic patients with ATTRwt-CA was prospectively included over 2 years and compared to healthy elderly subjects, matched on age, gender and body mass index. The presence of SFN was defined as hESC < 60 μS and/or fESC < 70 μS and conductances were analyzed according to clinical, biological, and echocardiographic data. Mean hESC and fESC were significantly lower in patients with ATTRwt-CA than in elderly controls: 61.5 vs. 70.0 μS ( P = 0.006) and 68.3 vs. 76.9 μS respectively ( P < 0.0001). Prevalence of hESC < 60 μS and fESC < 70 μS was higher in patients with ATTRwt-CA than in controls: 33.9% versus 16.7% and 48.4% versus 19.9%, P < 0.05. Univariate analysis showed that fESC, NT-proBNP, creatinine plasma levels, and echocardiographic global longitudinal strain were associated with decompensated cardiac failure and death. Multivariate analysis revealed that fESC was an independent prognostic factor and Kaplan-Meier estimator evidenced a larger occurrence of cardiac decompensation and death in patients with fESC < 70 μS, P = 0.046. A reduced fESC was observed in almost 50% of patients with ATTRwt-CA and was associated with a worse prognosis. Sudoscan® could be used easily to screen ATTRwt-CA patients for the presence of SFN and identify patients at higher risk of outcome.

Multimodal Testing Reveals Subclinical Neurovascular Dysfunction in Prediabetes, Challenging the Diagnostic Threshold of Diabetes

Background: There is growing evidence that small nerve fibre and retinal neurovascular damage occur in prediabetes before the onset of type 2 diabetes. Methods: Participants with normoglycaemia, prediabetes or type 2 diabetes underwent corneal confocal microscopy (CCM), electrochemical skin conductance (ESC), optical coherence tomography angiography (OCT-A), and handheld electroretinography (ERG) measurements. Findings: Seventy-five participants with normoglycaemia (n=20), prediabetes (n=29) and type 2 diabetes (n=26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16 Td·s: 4·05 µV, 95% confidence interval (CI) 0·96-7·13) and high (32 Td·s: 5·20 µV, 95% CI 1·54-8·86) retinal illuminance were lower in prediabetes, as were OCT-A parafoveal vessel densities in superficial (0.051 pixels/mm2, 95% CI 0·005-0·095) and deep (0·048 pixels/mm2, 95% CI 0·003-0·093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32 Td·s (r=-0.256, p=0·028), implicit time at 32 Td·s (r=0·422, p=0·0002) and 16 Td·s (r=0·327, p=0·005), OCT parafoveal vessel density in the superficial (r=-0·238, p=0·049) and deep (r=-0·3, p=0·017) retinal layers, corneal nerve fibre length (CNFL) (r=-0·293, p=0·017), and hand ESC (r=-0·244, p=0·035) were observed. HOMA-IR was a predictor of CNFD (β=-0·94, 95% CI -1·66 to -0·21, p=0·012) and CNBD (β=-5·02, 95% CI -10·01 to -0·05, p=0·048). Interpretation: The diagnosis of diabetes is based on historical data showing emergent retinopathy on fundus examination; newer tests reveal abnormal retinal neurovascular structure (OCT-A) and function (ERG) occurring before retinopathy. Funding: This research received no funding support. Declaration of Interests: None of the authors have any relevant financial disclosures to declare. LKC Technologies Inc. and Impeto Medical Inc. provided free use of the RETeval and SUDOSCAN devices, respectively, for this study. CB is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Ethics Approval Statement: This study adhered to the Declaration of Helsinki (2008) and was approved by an independent National Health Service Research Ethics Committee in November 2018 (REC ID: 18/LO/2126). Written informed consent was obtained from all participants.

Prevalence and prognostic value of autonomic neuropathy assessed by Sudoscan® in transthyretin wild‐type cardiac amyloidosis

AimsThe prevalence of autonomic neuropathy (AN) is high in patients with hereditary transthyretin amyloidosis but remains unknown in transthyretin wild‐type cardiac amyloidosis (ATTRwt‐CA). This study aimed to determine the prevalence of AN in patients with ATTRwt‐CA using Sudoscan®, a non‐invasive method used to provide evidence of AN in clinical practice and based on measurement of electrochemical skin conductance at the hands and feet (fESC).Methods and resultsA series of 62 non‐diabetic patients with ATTRwt‐CA was prospectively included over 2 years and compared with healthy elderly subjects, matched by age, gender, and body mass index. The presence of AN was defined as electrochemical skin conductance at the hands <60 μS and/or fESC <70 μS, and conductances were analysed according to clinical, biological, and echocardiographic data. Mean fESC was significantly lower in patients with ATTRwt‐CA compared with elderly controls: 68.3 (64.1–72.5) vs. 76.9 (75.6–78.1) μS (P < 0.0001), respectively. Prevalence of fESC <70 μS was higher in ATTRwt‐CA patients than in controls: 48.4% vs. 19.9%, P < 0.05. Univariate analysis showed that fESC, N‐terminal pro‐B‐type natriuretic peptide, creatinine plasma levels, and echocardiographic global longitudinal strain were associated with decompensated cardiac failure and death. Multivariate analysis revealed that fESC was an independent prognostic factor, and Kaplan–Meier estimator evidenced a greater occurrence of cardiac decompensation and death in patients with fESC <70 μS, P = 0.046.ConclusionsReduced fESC was observed in almost 50% of patients with ATTRwt‐CA and was associated with a worse prognosis. Sudoscan® could easily be used to screen ATTRwt‐CA patients for the presence of AN and identify patients at higher risk for a poor outcome.

Sudomotor Changes in Hepatitis C Virus Infection with or without Diabetes Mellitus: A Pilot Study in Egyptian Patients.

Hepatitis C virus (HCV) infection can affect the neurological system, and neuropathy is one of these manifestations. Hepatitis C virus infection is associated with diabetes mellitus (DM) type II, and diabetic patients are at higher risk of acquiring HCV infection. Sweat function has been proposed to assess early autonomic neuropathy. This study aimed to evaluate small fiber neuropathy in asymptomatic HCV-related cirrhotic patients with or without DM through sweat function assessment by Sudoscan test. Three groups were involved: 47 healthy controls, 48 HCV-related cirrhotic patients without DM (group 1), and 49 HCV-related cirrhotic patients with DM type II (group 2). All participants were subjected to liver panel tests, renal function tests, cell blood counts, HbA1c, and abdominal ultrasound. Sweat function was assessed in all patients and controls by measuring hand and feet electrochemical skin conductance (ESC, microSiemens [µS]) using Sudoscan. Peripheral neuropathy was detected in none of the controls, 39% of group 1 patients, and 62% of group 2 patients (P < 0.0001). The mean feet ESC (FESC) was 88.3 ± 6.8 µS in controls, 67.2 ± 19.2 µS in group 1, and 57.9 ± 19.4 µS in group 2 (P < 0.0001). A significant correlation was observed between FESC and bilirubin, albumin, creatinine, international normalized ratio, transaminases, and splenic size. Electrochemical skin conductance measurement is a valuable, noninvasive method for early detection of small fiber neuropathy in asymptomatic HCV-related cirrhosis, with or without DM.

Autonomic dysfunction is associated with neuropsychological impairment in Lewy body disease

This study aimed to analyze the association of autonomic dysfunction with cognition, depression, apathy, and fatigue in Lewy body disease (LBD). We included 61 patients [49 with idiopathic Parkinson's disease, 7 with dementia with Lewy bodies, and 5 E46K-SNCA mutation carriers] and 22 healthy controls. All participants underwent a comprehensive battery of neuropsychological and clinical measures, autonomic symptom assessment with the SCOPA-AUT, analysis of non-invasive hemodynamic parameters during deep breathing, the Valsalva maneuver, and a 20-min tilt test, and electrochemical skin conductance measurement at rest (Sudoscan). Student's t tests were used to assess group differences, and bivariate correlations and stepwise linear regressions to explore associations between autonomic function, cognition, depression, apathy, and fatigue. Compared to controls, patients who had significant impairment (p < 0.05) in cognition, higher depression, apathy, and fatigue, more autonomic symptoms and objective autonomic dysfunction, reduced deep breathing heart rate variability [expiratory-to-inspiratory (E/I) ratio], prolonged pressure recovery time, and lower blood pressure in Valsalva late phase II and phase IV, while 24.1% had orthostatic hypotension in the tilt test. Autonomic parameters significantly correlated with cognitive and neuropsychiatric outcomes, systolic blood pressure during the Valsalva maneuver predicting apathy and depression. The E/I ratio was the main predictor of cognitive performance (17.6% for verbal fluency to 32.8% for visual memory). Cardiovascular autonomic dysfunction is associated with cognitive and neuropsychiatric impairment in LBD, heart rate variability during deep breathing and systolic blood pressure changes during the Valsalva procedure are the main predictors of neuropsychological performance and depression/apathy symptoms, respectively.

Early identification of peripheral neuropathy based on sudomotor dysfunction in Mexican patients with type 2 diabetes

BackgroundType 2 Diabetes in Mexico has a high prevalence, 16–87% of patients may experience peripheral neuropathy. Early detection can prevent or halt its progression. The performance of Sudoscan in detecting neuropathy was compared to the Michigan Neuropathy Screening Instrument (MNSI). The aim was to identificate small fibers neuropathy.MethodsPatients type 2 diabetes received both MNSI and sudomotor function assessment through measurement of electrochemical skin conductance (ESC) in the hands and feet.ResultsTwo hundred twenty-one patients with neuropathy according to MNSI B had lower hands and feet ESC, regardless of diabetes duration. Among the 170 patients who had had diabetes for at least 5 years, 76 of them with normal MNSI B had abnormal hands or feet ESC; this was also the case in 28 out of 51 patients with diabetes than 5 or more years. In contrast, only 5 patients in the first group and 1 in the second group had abnormal MNSI B with normal ESC. Using MNSI B as a reference, abnormal hands or feet ESC (< 60 μS and 70 μS respectively) had a sensitivity of 97%, positive predictive value of 87% to detect neuropathy in patients with longer diabetes duration. The group with shorter diabetes duration, the sensitivity of abnormal hands or feet ESC to detect neuropathy was 91% while the positive predictive value was 88%.ConclusionsThe Sudoscan device, which does not require any preparation, is noninvasive, easy and rapid to perform, can be useful in the early diagnosis peripheral neuropathy in type 2 diabetic.

Non-invasive evaluation of sudomotor function in patients with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease associated with antibodies against the nicotinic muscle acetylcholine receptor (AChR) at the neuromuscular junction. Dysautonomia has been previously described in MG. Electrochemical skin conductance (ESC), assessed by Sudoscan®, is a non-invasive method that allows evaluation of sudomotor function. Since sweat glands are innervated by sudomotor, postganglionic, cholinergic sympathetic C-fibers, we hypothesized that ESC could be a reliable method for assessing autonomic dysfunction in MG. ESC measurements were prospectively assessed in patients with generalized MG and in healthy controls. Patients with diabetes mellitus, anticholinergic medication or electrophysiological findings of peripheral neuropathy were excluded. Data regarding demographic and disease features were collected. Presence of autonomic symptoms in patients with MG was assessed by Compass-31. For statistical analysis we performed student t-test and Chi2 test for comparison between both groups. We included 24 patients (mean age of 46.4±10.6, 75% women, mean disease duration 12.5 years, 62.5% positive for AChR antibodies) and 37 controls. We found no difference in either foot (P=0.13) or hand (P=0.83) ESC measurements between patients and controls, even after correcting for age. We could not prove the presence of autonomic sympathetic dysfunction in our cohort of MG patients when assessed by Sudoscan®. In addition, Compass-31 was not a useful questionnaire in this clinical context.

How to explore automic dysfunction on clinical practice?

Objectives Various validated clinical scales and questionnaires are available and many neurophysiological and functional tests have been developed to evaluate dysautonomia. This work aims to review the neurophysiological tools that can be used to characterize distal autonomic dysfunction, particularly in the context of peripheral neuropathies. Methods Neurophysiological tests exploring autonomic vasomotor and sudomotor function have been reviewed. The accuracy of each technique for the diagnosis of small-fiber autonomic neuropathy has been assessed. Results Sudomotor innervation can be investigated by many tests including sympathetic skin reflex recording (SSR), quantitative sudomotor axon reflex testing (QSART), electrochemical skin conductance measurement (ESC) by Sudoscan®, and the Neuropad® colorimetric test. Both the Neuropad® test and ESC measurement by Sudoscan®, provide early markers of neuropathy in context of familial amyloid polyneuropathy as well as in diabetic polyneuropathy. The Neuropad® test could be used as a screening tool, requiring confirmation by ESC measurement by Sudoscan®, which is more convenient for follow-up assessment. Unlike the SSR, QSART is also a sensitive test for detecting sudomotor dysfunction. However, its test-retest reliability is really moderate. For vasomotor aspects, investigation includes the stimulated skin wrinkling (SSW) test, laser Doppler flowmetry (LDF) and laser Doppler imaging (LDI-flare). The SSW test appears valuable when applied to the fingers, but not to the toes. The LDF and LDI-flare tests were found to be sensitive in various clinical contexts (e.g., Parkinson's disease, diabetes, and HIV infection), but they lack standardization and have poor test-retest reliability, especially LDF. Conclusion Sudomotor tests and notably ESC measurement by Sudoscan® appear to be relevant to assess distal autonomic dysfunction in the context of peripheral neuropathy, while the reliability of vasomotor tests should still be improved. Finally, various autonomic tests that are not performed at limb extremities can also be very informative and sensitive in this clinical context, such as heart rate variability measurement at deep breathing.

Comparison of Different Methods for Carbohydrate Disorder Detection

Measurement of fasting glucose and prandial glucose, as well as glycated haemoglobin (HbA1c) and oral glucose tolerance test (OGTT) could confirm diabetes or impaired glucose tolerance but they are invasive and time consuming methods. Some new technologies assessing dermal changes in perspiration like EZscan are used for defining carbohydrate state. We compare common methods used for detecting carbohydrate disorders with EZscan methodology assessing their potency to reveal diabetic and prediabetic patients. We studied 124 patients (64 males, 60 females, mean age 43.4±8.9years) with very high risk for diabetes. In these patients we measured HbA1c and performed OGTT and diagnosis diabetes or prediabetes was based on general recommendations. In addition patients underwent EZscan test in which diagnosis is based on measurement of electrochemical skin conductance. Only in 37 patients (29.8%) HbA1c was above 6.5% and in another 38 patients (30.6%) HbA1c was between 6.0-6.49%. After performing OGTT 22 patients (17.7%) were defined with increased fasting glucose (IFG) and 37 patients (29.8%) were with impaired glucose tolerance (IGT), 58 patients (46.7%) were with diabetes. Results from EZscan test show that 65 patients (52.4%) are with IFG/IGT and 55 patients (44.3%) are with diabetes. Age and gender did not have influence on the results. We conclude that EZscan could be used as test with similar to OGTT power for diagnosis of diabetes. HbA1c shows least potency for diagnosis. EZscan presents with some additional advantages being noninvasive method, taking no more than five minutes, with no need of special condition. Disclosure I. Daskalova: None. T. Totomirova: None. N. Petrov: None.

Sudomotor dysfunction independently predicts incident cardiovascular-renal events and all-cause death in type 2 diabetes: the Joint Asia Diabetes Evaluation register.

BackgroundEarly detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular–renal events in type 2 diabetes (T2D).MethodsSUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012–13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular–renal events until 2015.ResultsIn this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0–13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01–1.04], 1.04 (1.00–1.07) and 1.04 (1.00–1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09–2.23) for CKD and 3.11 (95% CI 1.27–7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk.ConclusionsA low ESC composite score independently predicts incident cardiovascular–renal events and death in T2D, which may improve the screening strategy for early intervention.

The value of electrochemical skin conductance measurement using Sudoscan® in the assessment of patients with familial amyloid polyneuropathy

ObjectiveTo reappraise the value of electrochemical skin conductance (ESC) measurement by Sudoscan® to assess the distal involvement of small autonomic fibers in familial amyloid polyneuropathy (FAP) due to various transthyretin (TTR) mutations. MethodsESC was measured at both hands and feet in 126 patients with either Val30Met (n = 65) or non-Val30Met (n = 61) TTR mutation. This series included clinically asymptomatic (n = 21) and paucisymptomatic (n = 30) patients, as well as patients with moderate (n = 37) or advanced (n = 38) TTR-FAP. ResultsESC measures did not differ between patients according to the type of TTR variant and were reduced in 24% of clinically asymptomatic patients, 40% of paucisymptomatic patients, 65% of patients with moderate TTR-FAP, and 92% of patients with advanced TTR-FAP. ESC measures were found to correlate with patients' clinical status, especially assessed by the Neuropathy Impairment Score and Karnofsky Performance Status. ConclusionESC measures well correlate with the severity of TTR-FAP and could provide early marker of the disease. SignificanceESC measures appear to be relevant to evaluate distal autonomic involvement in the context of amyloidosis.

Assessment of sudomotor function.

To review the currently available literature on clinical autonomic tests of sudomotor function. We searched PubMED/MEDLINE for articles on technical principles and clinical applications of sudomotor tests with a focus on their drawbacks and perspectives in order to provide a narrative review. The quantitative sudomotor axon reflex sweat test (QSART) is the most widely used test of sudomotor function. The technique captures pathology with low intra- and inter-subject variability but is limited by technical demands. The thermoregulatory sweat test comprises topographic sweat pattern analysis of the ventral skin surface and allows differentiating preganglionic from postganglionic sudomotor damage when combined with a small fiber test such as QSART. The sympathetic skin response also belongs to the more established techniques and is used in lie detection systems due to its high sensitivity for sudomotor responses to emotional stimuli. However, its clinical utility is limited by high variability of measurements, both within and between subjects. Newer and, therefore, less widely established techniques include silicone impressions, quantitative direct and indirect axon reflex testing, sensitive sweat test, and measurement of electrochemical skin conductance. The spoon test does not allow a quantitative assessment of the sweat response but can be used as bedside-screening tool of sudomotor dysfunction. While new autonomic sudomotor function testings have been developed and studied over the past decades, the most were well-studied and established techniques QSART and TST remain the gold standard of sudomotor assessment. Combining these techniques allows for sophisticated analysis of neurally mediated sudomotor impairment. However, newer techniques display potential to complement gold standard techniques to further improve their precision and diagnostic value.

Assessing sudomotor impairment in patients with peripheral neuropathy: Comparison between electrochemical skin conductance and skin biopsy

ObjectiveSudoscan provides a rapid assessment of sudomotor function based on the measurement of electrochemical skin conductance (ESC), which is thought to be proportional to small nerve fibres innervating the sweat glands. However, the relationship between ESC and small nerve fibre density on skin biopsy remains unclear. MethodsIn a retrospective single-centre study, we compared ESC measurements with autonomic sweat gland nerve fibre density (SGNFD) and somatic intraepidermal nerve fibre density (IENFD) in patients with polyneuropathy. Results63 patients were included (mean age: 60.6 ± 13.3 years). ESC was more strongly correlated with SGNFD (r = 0.49; p = 0.0005) than with IENFD (r = 0.42; p = 0.0005). Foot ESC was lower in patients with abnormal SGNFD (1.0 ± 0.3 µS/kg versus 0.7 ± 0.4 µS/kg; p = 0.0419) or abnormal IENFD (1.1 ± 0.3 µS/kg versus 0.8 ± 0.3 µS/kg; p = 0.0425). ConclusionESC measurement is a novel method of potential value for assessing sudomotor function. More studies are required to define its place beside ancient well-established techniques. SignificanceThe weak correlation of ESC with skin biopsy results suggests that mechanisms other than the loss of innervating fibres may be responsible for sweat gland dysfunction in polyneuropathies.

Clinical correlates of sudomotor dysfunction in patients with type 2 diabetes and peripheral neuropathy

AimsTo investigate the factors associated with abnormal electrochemical skin conductance (ESC) in patients with type 2 diabetes mellitus (T2D) and early diabetic peripheral neuropathy (DPN). MethodsWe recruited 523 consecutive patients with T2D (median age: 50 [interquartile range: 16] years; median T2D duration: 4 [5] years). Sudomotor dysfunction was defined as an ESC <60 µS, and DPN as a neuropathy disability score (NDS) ≥6. Logistic regression was performed to determine the predictors of sudomotor dysfunction in patients with DPN. ResultsThe prevalence of sudomotor dysfunction was 29% for all patients and 84.5% for patients with DPN. A significant negative correlation was observed between the NDS and ESC measurements (r = −0.52, p < 0.0001). In the univariate analysis, abnormal ESC measures were associated with age, diabetes duration, glycated hemoglobin, diabetic retinopathy, insulin therapy, and foot abnormalities. In the multivariate analysis, ESC abnormalities were associated with age, diabetes duration, glycated hemoglobin levels, insulin therapy, and foot deformities. There was a robust association between foot deformities and abnormal ESC (p = 0.049; odds ratio = 16.02) in patients with DPN. ConclusionSudomotor dysfunction is highly prevalent in patients with T2D, especially in those with DPN. Various diabetes-related factors were linked to lower ESC values, indicating an association between chronic hyperglycemia and sudomotor function. We also observed a strong relationship between foot deformities and ESC abnormalities. We conclude that the factors associated with DPN are also relevant to sudomotor dysfunction.