Electrochemical Skin Conductance Values Research Articles

Assessment of small fiber neuropathy and distal sensory neuropathy in female patients with fibromyalgia.

We investigated sudomotor dysfunction, small fiber neuropathy (SFN), and their clinical significance in female fibromyalgia patients. Fibromyalgia patients and healthy controls (HCs) were recruited. Clinical and laboratory data were measured. Electrochemical skin conductance (ESC) values of hands and feet were assessed by SUDOSCAN. Additionally, several other methods were employed, including nerve conduction study (NCS), electromyography (EMG), and questionnaires. Spearman correlation coefficient was calculated to identify factors associated with ESC values of SUDOSCAN. Twenty-two female fibromyalgia patients and 22 female HCs were recruited. The fibromyalgia group had lower EQ5D and higher Toronto Clinical Neuropathy scores than the HC group. Most of the EMG/NCS findings of motor and proximal sensory nerves were comparable between the fibromyalgia and HC groups, whereas sensory nerve action potential amplitudes of distal sensory nerves were significantly lower in the fibromyalgia group. Mean ESC values of hands and feet were significantly lower in the fibromyalgia group than in the HC group (57.6 ± 16.2 vs. 68.8 ± 10.3 μS, p = 0.010 for hands, 64.9 ± 11.5 vs. 72.0 ± 8.2 μS, p = 0.025 for feet, respectively). Moderate to severe SFN was more common in the fibromyalgia group (68.2%) than in the HC group (68.2 vs. 50%, p = 0.019). Fibromyalgia disease duration was significantly correlated with the ESC values of hands/feet, and tricyclic antidepressant (TCA) responders had higher ESC values than non-responders. SFN was commonly detected in fibromyalgia patients who had normal EMG/NCS findings and was more severe in fibromyalgia patients with longer disease duration. SUDOSCAN may predict response to TCA therapy.

From Evaluation to Prediction: Analysis of Diabetic Autonomic Neuropathy Using Sudoscan and Artificial Intelligence

A dangerous side effect of diabetes that can significantly lower quality of life and raise the death rate of diabetic individuals is diabetic autonomic neuropathy. It is essential to identify and anticipate this disease early on for prompt intervention and care. This study aims to predict this diabetic complication using Sudoscan and artificial intelligence. In this study, 172 individuals with type 1 or type 2 diabetes mellitus provided clinical and demographic information. Sudoscan was used to evaluate the subjects’ sudomotor dysfunction. Statistical methods were used to link various electrochemical skin conductance values with risk factors for neuropathy such as age, BMI, age of diabetes, or biochemical values such as cholesterol and triglycerides. Different machine-learning algorithms were used to predict the risk of diabetic autonomic neuropathy based on the collected data. The accuracy achieved with Logistic Regression is 92.6%, and with the Random Forest model is 96.3%. Lazzy Classifiers also show that six classifiers have a high performance of 97%. Thus, the use of machine learning algorithms in this field of metabolic diseases offers new perceptions for diagnosis, treatment, and prevention, and improves the quality of life of diabetic patients by reducing the incidence of complications related to this disease.

Validating the usefulness of Sudoscan in ATTRv: a single centre experience.

Variant transthyretin amyloidosis (ATTRv) can cause sensorimotor and autonomic neuropathy. Objective quantification of sudomotor function may be essential for early diagnosis and early initiation of treatment. The aim of this study is to evaluate the diagnostic value of the Sudoscan® in ATTRv. Electrochemical skin conductance (ESC) was measured in V30M ATTRv patients, asymtomatic V30M carriers and healthy controls. Comparisons between the three groups were made using the Kruskal-Wallis test, and ROC curves were used to estimate the discriminatory power of ESC values between groups. ESC was measured in 52 ATTRv patients, 107 asymptomatic carriers and 40 healthy controls. ESC was significantly lower in ATTRv patients compared to asymptomatic carriers and healthy controls in both feet and hands; median values are as follows: 40 µS, 78 µS and 81 µS, respectively (p < 0.001), and 53 µS, 69 µS and 74 µS, respectively (p < 0.001). ESC in feet < 70.5 µS had a sensitivity of 89.7% and specificity of 84.6% to discriminate asymptomatic carriers from patients with ATTRv. The determination of ESC by Sudoscan® is a rapid, noninvasive and easily reproducible technique capable of discriminating patients with ATTRv from asymptomatic carriers and healthy controls with adequate sensitivity and specificity.

Correlation between a commercial electrophysiological test of sudomotor function and intraepidermal nerve fiber density in hereditary transthyretin amyloidosis.

In the early stage, hereditary transthyretin (ATTRv) amyloidosis predominantly affects small nerve fibers, resulting in autonomic dysfunction and impaired sensation of pain and temperature. Evaluation of small fiber neuropathy (SFN) is therefore important for early diagnosis and treatment of ATTRv amyloidosis. Herein, we aimed to investigate the accuracy of a quick and non-invasive commercial sudomotor function test (SFT) for the assessment of SFN in ATTRv amyloidosis. We performed the SFT in 39 Japanese adults with ATTRv amyloidosis, and we analyzed the correlations between electrochemical skin conductance (ESC) values obtained via the SFT and the parameters of other neuropathy assessment methods. ESC in the feet demonstrated significant, moderate correlations with intraepidermal nerve fiber density (IENFD) results (Spearman's rank correlation coefficient [rs ], 0.58; p < .002) and other neuropathy assessment methods including the sensory nerve action potential amplitude in the nerve conduction studies (rs , 0.52; p < .001), the Neuropathy Impairment Score (rs , -0.45; p < .01), the heat-pain detection threshold (rs , -0.62; p < .0001), and the autonomic section of the Kumamoto ATTRv clinical score (rs , -0.53; p < .0001). In this study, we found that ESC values in the feet via the SFT demonstrated significant, moderate correlations with IENFD and other SFN assessment methods in patients with ATTRv amyloidosis, suggesting that the SFT appears to be an appropriate method for assessment of SFN in this disease.

Normal values of sudomotor function assessed by electrochemical skin conductance in African population

BackgroundDysfunction of small nerve fibers remains a major public health concern. Subjects suspected of having small nerve fiber damage need to undergo reliable tests to confirm the diagnosis. Sudomotor function test is a reliable noninvasive exploration for detecting peripheral neuropathies. Nevertheless, the normal reference values derived from the sudomotor function test are not known in the African population. The objective of this study was therefore to describe the normal values of Electrochemical Skin Conductance (ESC) measured by the sudomotor function test in healthy African subjects. Materials and methodsBetween December 1st, 2021 and May 31st, 2022, ESC was measured in 475 healthy subjects (median age: 42 [31–53] years, 46% men) using a sudomotor function test, in the hands and feet. Investigators proposed the examination and received participants’ consent; demographic, anthropometric, biological, and clinical data were obtained before the test. Data on 475 healthy study participants who underwent sudomotor function testing was collected and analyzed. The sociodemographic (age, sex), anthropometric (weight, height, waist circumference, body mass index), diastolic blood pressure, systolic blood pressure, heart rate, and electrochemical skin conductances of the hands and feet were assessed. ResultsESC values were statistically higher in men compared to women (right hand ESC: 70 [60–78] versus 63 [53–72], left hand ESC: 72 [61–80] versus 68 [57–75], right foot ESC: 77 [82–99] versus 72 [64–79], ESC left foot: 76 [68–82] versus 72 [62–78] respectively). ESC values were significantly inversely correlated with age (right hand ESC: r=−0.12, P=0.006; left hand ESC: r=−0.11, P=0.01; right foot ESC: r=−0.37, P<0.0001; ESC left foot: r=−0.38, P<0.0001). ESC values measured in feet were significantly inversely correlated with body mass index (right foot r=−0.22, P<0.0001; left foot r=−0.21, P<0.0001). ConclusionThis study reports normal reference values for ESCs according to age and gender in the healthy African population. Progressive decrease in ESC with aging is confirmed by our data. The value of ESC seems lower in the African population than in other reported ethnicities. This finding needs to be further explored in additional studies.

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex

ObjectivesComplex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. Materials and MethodsEleven patients with CRPS at one limb (six women, five men, aged 52.0 ± 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as ≥30% reduction in VNS pain score one month after treatment compared with baseline. ResultsAt baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. ConclusionsThis study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT02817880.

Sympathetic and electrochemical skin responses in the assessment of sudomotor function: a comparative study

ObjectivesThe sympathetic skin response (SSR) is a well-established test, whereas the electrochemical skin conductance (ESC) is still under evaluation. Our aim was therefore to assess the diagnostic accuracy of ESC to detect abnormal sudomotor function, using SSR as a reference test. MethodsA cross sectional observational study was performed of 61 neurological patients assessed for possible sudomotor dysfunction and 50 age-matched healthy controls (HC). Patients with diagnoses of vasovagal syncope (VVS, n=25), Parkinson's disease (PD, n=15), multiple system atrophy (MSA, n=11) and peripheral neuropathies (PN, n=10) were included. Sudomotor function was assessed with SSR and ESC tests in all participants. The absence of SSR in the palms or soles indicates abnormal sudomotor function. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of the ESC. Cardiovascular autonomic (CV-Aut) function was evaluated through the Ewing score, based on the following tests: Heart rate change with deep breathing, Valsalva ratio, 30:15 ratio, blood pressure changes on standing and during isometric exercise. A Ewing score ≥ 2 indicates the presence of CV-Aut dysfunction. ResultsMean SSR amplitudes and ESC values showed differences between HC and patients with MSA or PN (p < 0.05), but not in patients with VVS or PD. Absence of SSR was associated with abnormal ESC (p < 0.05). Patients with abnormal CV-Aut dysfunction had lower ESC (p< 0.05). Palm ESC (P-ESC) and sole ESC (S-ESC) assessment had a sensitivity of 0.91 and 0.95 to predict sudomotor dysfunction, with a specificity of 0.78 and 0.85, respectively. The area under ROC curve was 0.905 and 0.98, respectively. ConclusionsESC in palms and soles has a high diagnostic accuracy for sudomotor dysfunction as detected by absent SSR in patients with MSA and PN.

Electrochemical skin conductance and heart rate variability in patients with non-dialysis chronic kidney disease

BackgroundChronic kidney disease (CKD) is very common now and associates with high overall and cardiovascular mortality. Numerous studies have reported that Heart rate variability (HRV) could also be used to detect cardiovascular autonomic dysfunction (CAD). We investigated the association of electrochemical skin conductance (ESC) of EZSCAN results with HRV in non-dialysis CKD patients. MethodsIn a cross-sectional study, we enrolled 248 prevalent non-dialysis CKD patients. Patients underwent a 24-h Holter (CB-2302-A, Bio Instrument, China). A time domain analysis of HRV was performed, and the following parameters were obtained: SDNN, SDANN, rMSSD, pNN50. EZSCAN device (Impeto Medical, Paris, France) measures ESC values of each participants. Mean global skin conductance computed as 0.5 * (reflecting (right + left hand)/2 + (right and left foot)/2). Log transforms data into a normal distribution for statistical analysis. ResultsThere were 142 males and 106 females included in the present study. Patients' age was 56.6±17.08 years. Logarithm(Log) (global ESC) was independently predicted by age (P<0.01), hypertension history, estimated Glomerular filtration rate (eGFR) and log SDNN (P<0.05). While log SDANN, rMSSD and pNN50 were not independent predictors for log (global ESC). ConclusionIncreased global ESC significantly associated with elevated HRV, specifically SDNN in non-dialysis CKD patients. This suggested that global ESC may appear to be an important predictor of CAD, and even could be used as a cardiovascular risk factor in non-dialysis CKD patients.

Central Sensitization and Small-fiber Neuropathy Are Associated in Patients With Fibromyalgia

To study the prevalence of small-fiber neuropathy (SFN) in a large cohort of patients with fibromyalgia (FM) and to better characterize the subset of patients with both FM and SFN. This 1-year, retrospective, observational cohort study included 265 patients with FM. They all performed electrochemical skin conductance (ESC) using the Sudoscan device, 1 of the simplest and most reliable technique to assess the distal autonomic nerve fibers. They completed 4 self-assessment questionnaires: (1) the Central Sensitization Inventory (CSI), (2) the Neuropathic Pain Symptom Inventory (NPSI), and (3) the Hospital Anxiety and Depression Scale (HADS), the Fibromyalgia Impact Questionnaire (FIQ). Fifty-three patients (20%) had reduced ESC values. These patients had higher CSI and HADS scores, and a larger intake of analgesic drugs compared with patients with no ESC abnormalities. Central sensitization, which was extreme in 69% of the patients (CSI score ≥60), was 1 of the main determinants of ESC abnormalities and was associated with a higher NPSI score, even though these 2 factors were not correlated. Over the past 10 years, studies have shown that a significant proportion of patients with FM have signs of small nerve fiber impairment. The possible involvement of SFN, in the occurrence and presentation of clinical symptoms in FM patients, remains however unclear. This is the first study that showed an association between central sensitization and both small nerve fiber impairment and neuropathic pain features in FM patients, rather than a direct association between SFN and neuropathic pain.

Association of electrochemical skin conductance with neuropathy in chemotherapy-treated patients

PurposeChemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of cancer treatment that can affect sensory, motor, or autonomic nerves. Assessment of autonomic neuropathy is challenging, with limited available tools. Accordingly, it is not routinely assessed in chemotherapy-treated patients. In this study, we aimed to examine whether electrochemical skin conductance (ESC) via Sudoscan, a potential measure of autonomic function, associates with subjective and objective measures of CIPN severity and autonomic neuropathy.MethodsA cross-sectional assessment of patients who completed neurotoxic chemotherapy 3–24 months prior was undertaken using CIPN patient-reported outcomes (EORTC-QLQ-CIPN20), clinically graded scale (NCI-CTCAE), neurological examination score (TNSc), autonomic outcome measure (SAS), and Sudoscan. Differences in CIPN severity between participants with or without ESC dysfunction were investigated. Linear regression analyses were used to identify whether ESC values could predict CIPN severity.ResultsA total of 130 participants were assessed, with 93 participants classified with CIPN according to the clinically graded scale (NCI-CTCAE/grade ≥ 1), while 49% demonstrated hands or feet ESC dysfunction (n = 46). Participants with ESC dysfunction did not significantly differ from those with no dysfunction on multiple CIPN severity measures (clinical-grade, patient-report, neurological examination), and no differences on the autonomic outcome measure (SAS) (all p > 0.0063). Linear regression analyses showed that CIPN could not be predicted by ESC values.ConclusionsThe inability of ESC values via Sudoscan to predict clinically-graded and patient-reported CIPN or autonomic dysfunction questions its clinical utility for chemotherapy-treated patients. The understanding of autonomic neuropathy with chemotherapy treatment remains limited and must be addressed to improve quality of life in cancer survivors.

Self-Reported Depressive Symptoms Might be Associated with Sudomotor Dysfunction in Chinese T2DM Patients.

To determine the relationships of sudomotor functions, nerve conductions and self-reported depressive symptoms in Chinese type 2 diabetes (T2DM) patients. T2DM patients in a single community health center were included in this study. Demographic, medical and laboratory data were collected. Michigan Neuropathy Screening Instrument (MNSI) examination was conducted in all patients. SUDOSCAN test and Point-of-care Nerve Conduction Device (DPN-check) were conducted and all the patients finished the Patient Health Questionnaire-9 (PHQ-9). A total of 162 T2DM patients (74 males and 88 females) were included. The mean age was 69.0±7.2 years and the mean course of diabetes was 10.5±8.0 years with a mean HbA1c level of 7.3±1.4%. Thirty of them (18.5%) had self-reported depressive symptoms (PHQ-9 scores≥5). Diabetic peripheral neuropathy (DPN) was diagnosed according to the MSNI examination in 74 patients. Electrochemical skin conductance (ESC) values of both hands and feet were significantly lower in patients with depressive symptoms (Hands ESC: 60.63±18.92 vs. 67.64±16.02 μS, p<0.05; Feet ESC: 59.60 ± 15.19 vs. 66.19±14.99 μS, p<0.05). The proportion of patients with moderate to severe depressive symptoms were significantly higher in those with ESC values<60 μS (13.33% vs. 3.846%, p<0.05). Hands ESC values were negatively related to PHQ-9 scores (r =- 0.168, p<0.05). After adjusting for variables, hands and feet ESC values remained negatively related with depressive symptoms (β =- 0.036 and-0.038, p<0.05). Female were positively related to depressive symptoms with odds ratio 3.4 (95%CI 1.1-10.5, p<0.05). Self-reported depressive symptoms might be associated with sudomotor dysfunction in Chinese T2DM patients.

Variability of electrochemical skin conductance for screening diabetes mellitus.

Electrochemical skin conductance (ESC) has been suggested as a noninvasive diabetic screening tool. We examined the relevance of ESC method for screening type 2 diabetes. A meal tolerance test (MTT) was conducted for 40 diabetic and 42 control subjects stratified by age, sex and body mass index (BMI). The glucose levels and ESC were measured before the MTT and every 30min after meal intake up to 120min. There was no correlation between the blood glucose level and ESC (r = 0.249) or ESC variability (ESCV) (r = - 0.173). ESC (ESCV) was higher (lower) in diabetic patients than in normal control (p = 0.02 for ESC and p = 0.06 for ESCV). Receiver operating characteristic analysis showed that the area under the curve (AUC) values of the ESC and ESCV were 0.654 and 0.691, respectively. The novel variable, ESCV, showed 5.7% higher AUC than ESC. Contrary to some previous reports, ESC values in diabetic patients was higher than in age, sex and BMI matched control group. In our study, ESC or ESCV showed a marginal accuracy to be used as a screening tool for diabetes mellitus.

Electrochemical Skin Conductance as a Marker of Painful Oxaliplatin-Induced Peripheral Neuropathy.

Purpose Oxaliplatin is a platinum compound widely used in gastrointestinal cancer treatment but produces dose-limiting peripheral neuropathy. New insights into oxaliplatin-induced peripheral neuropathy (OIPN) assessment are needed to detect more effectively this condition. In this context, we conducted Canaloxa study, a prospective preliminary clinical trial that aimed to investigate how Electrochemical Skin Conductance (ESC), a parameter used in small fiber neuropathy assessment, could be helpful in OIPN diagnosis. Methods Cancer patients treated for at least three months with oxaliplatin and suffering from clinically OIPN were included. Electrochemical Skin Conductance, thermal thresholds, and neuropathic pain were assessed in all included patients. Results During one year, 36 patients were included. The main result was the correlation between ESC and Neuropathic Pain Symptom Inventory score for hands (rho value = -0.69, p < 0.0001) and feet (rho value = -0.79, p < 0.0001). ESC values were lower in neuropathic patients with painful symptoms than in ones without painful symptoms (p = 0.0003 and p < 0.0001 for hands and feet, respectively). No correlation was observed between ESC and thermal thresholds. Conclusion These preliminary data suggest that ESC could be a useful objective marker of painful oxaliplatin-induced neuropathy and could complement the use of subjective clinical scales. This study was prospectively registered on clinicaltrials.gov (NCT02827916) before patient recruitment has begun.

Sudomotor function testing by electrochemical skin conductance: does it really measure sudomotor function?

Electrochemical skin conductance (ESC) is a non-invasive test of sweat function developed as a potential marker of small fiber neuropathy. Here we systematically review the evolution of this device and the data obtained from studies of ESC across different diseases. Electronic databases, including MEDLINE, and Google Scholar were searched through to February 2018. The search strategy included the following terms: "electrochemical skin conductance," "EZSCAN," and "Sudoscan." The data values provided by each paper were extracted, where available, and input into tabular and figure data for direct comparison. Thirty-seven studies were included this systematic review. ESC did not change by age or gender, and there was significant variability in ESC values between diseases, some of which exceeded control values. Longitudinal studies of disease demonstrated changes in ESC that were not biologically plausible. Of the 37 studies assessed, 25 received support from the device manufacturer. The extracted data did not agree with other published normative values. Prior studies do not support claims that ESC is a measure of small fiber sensory function or autonomic function. Although many papers report significant differences in ESC values between disease and control subjects, the compiled data assessed in this review raises questions about the technique. Many of the published results violate biologic plausibility. A single funding source with a vested interest in the study outcomes has supported most of the studies. Normative values are inconsistent across publications, and large combined data sets do not support a high sensitivity and specificity. Finally, there is insufficient evidence supporting the claim that Sudoscan tests sudomotor or sensory nerve fiber function.

High Level of Gingival Inflammation in Subjects with Type 1 Diabetes Despite Regular Dental Visits and Limited Microvascular Complications

The aim of the study was to evaluate small fiber neuropathy and periodontal health conditions on a cohort of patients with type 1 diabetes. The study participants were 18 females and 23 males with a mean age of 37.9 years (age range: 18-83 years). First, a routine medical examination was conducted at the Diabetology Clinics of the Geneva Universtity Hospital. Electrochemical skin conductance (ESC) was measured by Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy. Participants were further examined for presence of periodontal disease by means of Plaque and Gingival indices (PI and GI respectively), probing depth (PD) and bleeding on probing. Self-reported attitudes and behavior regarding dental care was also collected during the visit. The mean duration of affliction with diabetes was 14.6 ±11.9 years, with a mean glycosylated heamoglobin (HbA1c) of 7.96±1.68%. The Sudoscan measurements showed an average ESC value between right and left sides for the hands of 68.2±13.4 microSiemenns (µS) and for the feet an ESC value of 79±6.9 µS. Seven percent of the subjects presented moderate dysfunction (ESC values 60-40 µS) whereas only one subject presented severe dysnfunction (&amp;lt; 40 µS). The periodontal examination revealed that all patients (except from 2) had signs of gingivitis, defined as presence of at least 2 sites with a GI&amp;gt;1. Gingival inflammation and bleeding on probing was present in 66% of the participants in more than 20% of sites independently of the presence of small fiber neuropathy. Periodontitis was observed in 15% of the subjets with a mean of 13 sites with PD&amp;gt;4mm and bleeding on probing. The majority of subjects (70%) reported having regular dental visits at least once per year. In the present cohort of patients with type 1 diabetes the main finding was the occurrence of pronounced gingival inflammation in the majority of subjects independently of small fiber neuropathy and despite regular dental visits. Disclosure M. Roy: None. G. Gastaldi: Speaker's Bureau; Self; Abbott, Eli Lilly and Company, Novo Nordisk A/S, Medtronic, Dexcom, Inc., Sanofi, Roche Diabetes Care Health and Digital Solutions, Boehringer Ingelheim GmbH. A. Mombeli: None. C. Giannopoulou: None.

T33. Electrochemical skin conductance as a marker of neuropathic pain in hereditary amyloid polyneuropathy related to transthyretin

Neuropathic pain (NP) is one of the most common symptoms of small fiber dysfunction in hereditary amyloid polyneuropathy related to transthyretin (hATTR-FAP), contributing to a poor quality of life in these patients. Despite being a common problem in many neurological conditions, there are few neurophysiological tests with high sensitivity to assess pain, with the notable exception of laser evoked potentials. Electrochemical skin conductance (ESC), measured by Sudoscan©, is a fast and reliable method capable of measuring sudomotor function, tested in various diseases. Since sudomotor function is mediated by post ganglionic sympathetic C fibers, we sought to assess the ESC in hATTR-FAP patients as a predictor of NP. 200 consecutive hATTR V30M amyloidosis patients (104 carriers, 96 symptomatic), with a mean age of 45.5 ± 13.6 years (118 females) were studied. ESC, measured by Sudoscan©, was recorded in both hands and feet. Neuropathy Impairment Scale (NIS) and Body mass index (BMI) were recorded. The presence of NP was evaluated by clinical signs and symptoms, and was graded in a 3 point scale (absent, moderate, severe). Independent-samples T test, One-Way ANOVA and Binary logistic regression were used for comparisons (level of significance set at 0.01). ROC curve analysis were also performed. Both feet and hands ESC were significantly lower in the symptomatic group when compared to carriers (75.8 ± 8.7 vs 38.1 ± 26.5 and 72.2 ± 10.3 vs 56.5 ± 21.2 respectively, p < 0.001). Feet ESC was significantly different between all degrees of NP (74.0 ± 12.9 vs 47.2 ± 27.7 vs 30.2 ± 22.7, p < 0.001), while hands ESC and NIS were only significantly lower in the severe NP group. In the regression model analysis, after adjustment for age, gender, BMI, stage of disease and NIS, feet ESC was a significant independent predictor for the presence of NP (B = 0.955 p = 0.005). The ROC curve of this model showed an area under the curve of 0.958 (p < 0.001). ROC curve analysis of Feet ESC as a predictor of NP showed an area under the curve of 0.850 (p < 0.001). ESC, measured by Sudoscan©, has already been acknowledged as a promising tool for small fiber dysfunction. In this study a clear relationship was demonstrated between NP and ESC values, independent of disease stage or neuropathy degree. ESC is a rapid and noninvasive neurophysiological tool for the evaluation of NP.

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.

Normative Values for Electrochemical Skin Conductance Measurements for Quantitative Assessment of Sudomotor Function in Healthy Indian Adults.

Context:Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, which is one of the earliest-detected neurophysiologic abnormalities in diabetic patients with distal symmetric polyneuropathy.Aims:This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex, and body mass index (BMI) on ESC measurements.Settings and Design:A sample of 217 healthy participants aged 18–75 years were recruited and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet.Statistical Analysis Used:The Shapiro–Wilk test was used to assess the normality of the data. Pearson's correlation was used to evaluate the association between age, gender, and BMI, and ESC measurements.Results:The mean age of the participants was 43.3 ± 13.2 years, and mean BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet was 68.9 ± 13.1 and 71 ± 12.9 micro-Siemens, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.0001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.0001). ESC values of both hands and feet declined with age. A weak but significant inverse correlation between ESC and age was observed for the hands (r = 0.02, P = 0.01) and for the feet (r = 0.12, P < 0.0001). There was no significant difference in hand or feet ESC measurement between male and female participants. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis.Conclusions:Normative values for Indians are lower than that reported for Caucasians.

Osteopontin and clusterin levels in type 2 diabetes mellitus: differential association with peripheral autonomic nerve function.

Osteopontin (OPN) and clusterin are secreted glycoproteins potentially associated with nerve function. Sudomotor dysfunction is associated with the development of foot ulcerations. The purpose of this study was to investigate the potential relationship of OPN and clusterin with sudomotor function (i.e., autonomic nerves that control sweating) in participants with type 2 diabetes mellitus (T2DM). Sudomotor function was assessed using SUDOSCAN® which measures electrochemical skin conductance (ESC) of the hands and feet. Demographics (e.g., age, gender, race, body mass index (BMI)), HbA1c, 25-hydroxyvitamin D, creatinine, OPN, and clusterin were also determined for the participants. Fifty individuals with T2DM (age=59±11years; 23/27 male/female; 13 African Americans) participated in this study. Lower ESC for the hands and feet were observed in African Americans versus Caucasians/Asians (p<0.05). No significant ESC differences were observed for good [HbA1c <7%] versus poor [HbA1c ≥7%] glycemic control. With regard to gender, ESC values were lower for the hands for females (p<0.05). In linear regression with ESC for the hands or feet as the dependent variable, increased OPN levels, but not clusterin, were independently associated with reduced sudomotor function while adjusting for age, gender, race, BMI, and glycemic control (ESC hands model R 2=0.504, p<0.001; ESC feet model R 2=0.534, p<0.001). The association between OPN and reduced sudomotor function found in our study warrants further investigation to delineate the underlying mechanisms and determine if OPN is neuroprotective, involved in the pathogenesis of sudomotor dysfunction, or simply a bystander.

Normative Values for Electrochemical Skin Conductances and Impact of Ethnicity on Quantitative Assessment of Sudomotor Function.

Sudomotor dysfunction is one of the earliest pathophysiologic abnormalities in diabetes. Sudoscan™ (Impeto Medical, Paris, France) was developed as a noninvasive, rapid, and quantitative assessment of sudomotor function and has been shown to be sensitive in the detection of neuropathy. This global collaborative analysis aimed to establish reference values in healthy subjects of different ethnic groups, age, and gender, to define factors potentially affecting results, and to provide standardization of the methodology. Data from 1,350 generally healthy study participants who underwent sudomotor function testing were collected and analyzed. The relationship between age, height, weight, gender, glycemic and lipid profiles, ethnicity, and hand and foot electrochemical skin conductance (ESC) was assessed among subgroups of participants. Lower mean hands and feet ESC values were observed in African American, Indian, and Chinese subjects (P < 0.0001). No participant discomfort or safety concern was reported in 1,376 tests. No significant difference in ESC was observed between women and men at the hands (75 [57-87] vs. 76 [56-89] μS; P = 0.35) or feet (83.5 [71-90] vs. 82.5 [70-91] μS; P = 0.12). The coefficient of correlation between right and left side ESC was r = 0.96, P < 0.0001 for hands and r = 0.97, P < 0.0001 for feet. A significant but weak correlation was observed between ESC and age: for hands, r = -0.17, P < 0.0001; for feet, r = -0.19, P < 0.0001. A normative reference range was established in whites showing that there was no effect of sex or body mass index and a slight decrease in ESC with age. Ethnicity influenced ESC scores, but additional studies are necessary to validate this effect and determine its mechanism and impact on nerve function.