A description of variant transthyretin amyloidosis (ATTRv) stage 1 patients and asymptomatic carriers in Spain: the EMPATIa study.

BACKGROUND: Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain. METHODS: National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected. RESULTS: The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group. CONCLUSIONS: The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.

Sudoscan's Effectiveness in Identifying Chronic Kidney Disease in Patients With Type 2 Diabetes.

Chronic kidney disease (CKD) represents a significant public health issue, particularly prevalent among patients with type 2 diabetes mellitus (T2DM). CKD occurs in approximately 20% to 40% of adults with diabetes mellitus. Sudoscan potentially detects CKD early, providing a non-invasive and convenient alternative to traditional screening methods that rely on serum creatinine and urine albumin levels. This research involves 271 patients from a single medical center over one year, with all participants providing informed consent. The prevalence of CKD in our group was 26.5% (n = 72). This study integrates a comprehensive examination, including anthropometric measurements, biochemical profiles, and Sudoscan's electrochemical skin conductance testing. CKD diagnosis was confirmed via estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). The aim of this study was to explore the utility of Sudoscan in detecting CKD among patients with T2DM. Statistical analysis reveals moderate correlations between Sudoscan scores and traditional CKD markers like eGFR and albuminuria. It is beneficial in settings where conventional testing is less accessible, suggesting potential for broader CKD screening programs. Key findings suggest that Sudoscan can identify early renal dysfunction with reasonable sensitivity and specificity. Integrating Sudoscan in regular CKD screening could enhance early detection, allowing for timely interventions to prevent progression to end-stage renal disease and reduce healthcare burdens associated with advanced CKD. The results contribute to the ongoing assessment of innovative technologies in managing chronic diseases related to diabetes.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

The Importance of Evaluating Sudomotor Function in the Diagnosis of Cardiac Autonomic Neuropathy.

INTRODUCTION:  Cardiac autonomic neuropathy (CAN) is a disorder affecting the autonomic nerves that regulate the cardiovascular system, leading to irregular heart rate and blood pressure control. It is commonly associated with diabetes mellitus but can also result from other conditions such as autoimmune disorders, chronic kidney disease, alcohol abuse, and certain medications. Screening for CAN is essential, particularly in individuals with poor glycemic control, cardiovascular risk factors, or complications. Early identification of CAN is vital for timely intervention to prevent or manage cardiovascular complications effectively. Regular screening helps detect CAN before symptoms emerge, enabling early intervention to slow or halt its progression. This study examined the relationship between sudomotor function and cardiovascular reflex tests. MATERIAL AND METHODS:  This was a cross-sectional study conducted between June 2019 and June 2020. The study included 271 subjects aged 18 years and above who provided informed consent, were diagnosed with type 2 diabetes mellitus (T2DM), and were overweight or obese. Exclusion criteria encompassed patients with other types of diabetes, pregnant women, those with recent neoplasm diagnoses, stroke sequelae, history of myocardial infarction, or pelvic limb amputations. The assessment of cardiac autonomic neuropathy involved conducting an electrocardiogram and evaluating the QTc interval in the morning before taking medication. Additionally, cardiovascular reflex tests (CART) were conducted, including assessments of heart rate variability during deep breathing, the Valsalva maneuver, and changes in orthostatic position. Simultaneously, the diagnosis of CAN was assessed by performing a sweat test using a Sudoscan assessment (Impeto Medical, Moulineaux, France).  Results: More than half of the participants (52%, n=143) were female. Significant differences in statistical measures were noted between females and males regarding age, systolic blood pressure, fasting blood glucose, A1c level, total cholesterol, triglycerides, gamma-glutamyl transferase, and bilirubin levels. Within the CAN-diagnosed group (CAN+), 40.92% were classified as mild cases (n=90), 47.27% as moderate cases (n=104), and 11.81% as severe cases (n=26). Among the CAN+ group, 54% (n=119) were women. Electrochemical skin conductance was lower in the CAN+ group than the CAN- group in hands (67.34±15.51 µS versus 72.38±12.12 µS, p=0.008) and feet (73.37±13.38 µS versus 82.84 ±10.29 µS, p<0.001). The Sudoscan-CAN score significantly correlated with Ewing scores (r= 0.522, p<0.001). In multiple linear regression analysis, the Sudoscan-CAN score remained significantly associated with age, high BMI, long-standing diabetes, and Ewing score. CONCLUSIONS:  Sudoscan demonstrates potential in identifying patients with an increased risk of CAN. Its integration into clinical practice can improve patient outcomes through early detection, risk stratification, and personalized treatment approaches. Its non-invasive, portable, and user-friendly features render it suitable for utilization in outreach programs or resource-constrained settings as part of screening efforts designed to pinpoint high-risk individuals for additional assessment.

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.

OBJECTIVE: The 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. METHODS: Participants 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. RESULTS: Participants 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.

Association of sudomotor dysfunction with risk of diabetic retinopathy in patients with type 2 diabetes.

PURPOSE: Sudomotor dysfunction is considered as one of the earliest manifestations of diabetic peripheral neuropathy. We aimed to investigate the association between sudomotor dysfunction non-invasively detected by the SUDOSCAN device and diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: A total of 2010 patients admitted to a tertiary hospital located in Shanghai were included from March 2020 to September 2023. Sudomotor function was assessed by the SUDOSCAN device, and sudomotor dysfunction was defined as feet electrochemical skin conductance (FESC) <60 µs. Fundus radiography was used for DR assessment, which was graded according to the severity, specifically: (1) non-DR; (2) mild nonproliferative DR (NPDR); (3) moderate NPDR/vision-threatening DR (VTDR). RESULTS: Among the enrolled 2010 patients, 525 patients had sudomotor dysfunction; 648 were diagnosed with DR, which was equivalent to 32.2% of all patients. Patients with sudomotor dysfunction had a significantly higher prevalence of DR, compared to those with normal sudomotor function (40.8% vs. 29.2%, P < 0.05). After controlling for confounding factors including HbA1c, sudomotor dysfunction was significantly associated with any DR (odd ratio [OR] = 1.57, 95% CI 1.26-1.96). When FESC was considered as a continuous variable, the multivariable-adjusted OR of DR was 1.29 (95% CI 1.17-1.42) for per 1-SD decrease in FESC. Furthermore, multinomial logistic regression revealed significant associations between sudomotor dysfunction and all stages of DR (mild NPDR: OR = 1.40, 95% CI 1.11-1.78; moderate NPDR/VTDR: OR = 2.35, 95% CI 1.60-3.46). CONCLUSIONS: Sudomotor dysfunction was significantly associated with DR in patients with type 2 diabetes.

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

BACKGROUND: Dysfunction 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 METHODS: Between 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. RESULTS: ESC 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). CONCLUSION: This 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.

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.

OBJECTIVE: This 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). METHODS: Fifty 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. RESULTS: The 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.

Electrochemical skin conductances values and clinical factors affecting sudomotor dysfunction in patients with prediabetes, type 1 diabetes, and type 2 diabetes: A single center experience.

BACKGROUND AND AIM: Sudomotor dysfunction is linked to small fibers damage. We investigated sudomotor dysfunction in a large group of participants with diabetes, prediabetes, and nondiabetic healthy subjects. This study aimed to complete knowledge on sudomotor dysfunction in this population, especially regarding the threshold values for the electrochemical skin conductance (ESC) and factors affecting it. MATERIALS AND METHODS: A total of 690 volunteers in four groups were included in the study (type 1 [T1DG]: n = 80, 61.3% women; type 2 diabetes [T2DG]: n = 438, 63.5% women; prediabetes [Pre-DG]: n = 88, 80.7% women; healthy control [HC-G]: n = 84, 67.5% women). All subjects were investigated for clinical diabetic peripheral polyneuropathy and sudomotor dysfunction. The characteristics of participants obtained from outpatient records were evaluated. We used the Sudoscan device to measure ESC which was normalized for BMI, to improve the discriminative capability of the method. RESULTS: Diabetic polyneuropathy was found in 17.5% of T1DG, 27.4% of T1DG, and 10.2% of Pre-DG. The mean ESC/BMI was lower in subgroups with diabetic polyneuropathy than those without. Mean ESC/BMI was lowest in T2DG and highest in HC-G but comparable in T1DG and Pre-DG. We accepted the "mean ESC/BMI-1 SD" in the HC-G as the threshold for sudomotor dysfunction. Accordingly, the prevalence of sudomotor dysfunction was 18.8%, 44.3%, 59.1%, and 15% in T1DG, T2DG, Pre-DG, and HC-G, respectively. In T2DG, sudomotor dysfunction was found in 66.7% of persons with retinopathy, of which 56.3% had clinical diabetic polyneuropathy. The prevalence of sudomotor dysfunction in subjects with peripheral artery disease, chronic kidney disease, cardiovascular disease, and hypertension was 46.7%, 47.4%, 43.4%, and 50%, respectively, and 42.9%, 38.9%, 45.5%, and 37.3% of whom in the same order detected with clinical diabetic polyneuropathy. Considering the entire group, a logistic regression model demonstrated that the variables associated with SMD were: retinopathy (OR: 2.969; 95% CI: 1.723, 5.114), female gender (OR: 1.952; 95% CI: 1.287, 2.962), and e-GFR (OR: 0.989; 95% CI: 0.981, 0.998). Since the rate of complications was very low in T1DG, excluding this group, a new model similarly revealed that retinopathy and female gender were associated with SMD, however, the association with e-GFR was disappeared. CONCLUSION: The prevalence of sudomotor dysfunction is high when established peripheral polyneuropathy was present in diabetes. Even though, sudomotor dysfunction can also occur before clinical polyneuropathy in both types of diabetes (T1DG: 18.8%, T2DG 44.3%), prediabetes (59.1%), and nondiabetic healthy subjects (15%). The variables associated with sudomotor dysfunction were retinopathy and female sex. Normalization of ESC for BMI would be a beneficial approach. However, before this method is included in the routine screening programs for diabetic polyneuropathy, large-scale and prospective studies are required to reach a consensus on the pathological threshold values.

The value of electrochemical skin conductance measurement by Sudoscan® for assessing autonomic dysfunction in peripheral neuropathies beyond diabetes.

The diagnosis and follow-up of peripheral neuropathies involving small-diameter nerve fibers require specific examinations beyond conventional nerve conduction studies which only concern large-diameter nerve fibers. Among these tests, some are dedicated to the investigation of cutaneous innervation by the autonomic nervous system, mainly by unmyelinated sympathetic C fibers. To this end, various laboratory tests have been proposed, but the measurement of electrochemical skin conductance (ESC) by Sudoscan® is increasingly becoming the most widely used technique, because it allows a quick and simple assessment of the sudomotor function of the limb extremities. This technique is based on the principles of reverse iontophoresis and chronoamperometry and since its introduction in 2010, has been the source of nearly 200 publications. In the clinical field, most of these publications concern the evaluation of diabetic polyneuropathy, for which the value of Sudoscan® no longer needs to be demonstrated. However, there is also evidence for a role for Sudoscan® in the testing of the autonomic nervous system in various peripheral neuropathies of other origins or diseases primarily affecting the central nervous system. In this article, a comprehensive review of the literature on the clinical value of Sudoscan® outside of diabetes is presented, detailing ESC changes in neuropathies associated with various clinical conditions, such as hereditary amyloidosis or other genetic pathologies, chemotherapy neurotoxicity, dysimmune or infectious disorders, fibromyalgia, parkinsonism or other neurodegenerative diseases.

Assessment of autonomic nervous system dysfunction associated with peripheral neuropathies in the context of clinical neurophysiology practice.

Peripheral neuropathies may involve the small diameter nerve fibers of the autonomic nervous system. In the presence of clinical signs compatible with dysautonomia, it is very difficult to affirm that these signs are really linked to an alteration in postganglionic autonomic innervation, and not to a lesion of the central nervous system or to a direct damage to the tissues and innervated organs. Also, in the context of the investigation of peripheral neuropathies, there is an interest in performing objective and quantitative assessment of distal autonomic innervation. The corresponding autonomic tests are mainly based on the exploration of sudomotor or vasomotor disorders of the limb extremities. In this article, we provide an overview of the various tests available for the study of the autonomic nervous system in clinical practice, including vasomotor reactivity tests, in particular based on laser Doppler techniques, and sudomotor tests, based on axon-reflexes produced by iontophoresis of cholinergic drugs or on the simpler measurement of electrochemical skin conductance by the Sudoscan® device.

Assessing the Feasibility of Using Electrochemical Skin Conductance as a Substitute for the Quantitative Sudomotor Axon Reflex Test in the Composite Autonomic Scoring Scale and Its Correlation with Composite Autonomic Symptom Scale 31 in Parkinson's Disease.

The Composite Autonomic Scoring Scale (CASS) is a quantitative scoring system that integrates the sudomotor, the cardiovagal, and the adrenergic subscores, and the Composite Autonomic Symptom Scale 31 (COMPASS 31) is based on a well-established comprehensive questionnaire designed to assess the autonomic symptoms across multiple domains. We tested the hypothesis that electrochemical skin conductance (Sudoscan) can be a substitute for the quantitative sudomotor axon reflex test (QSART) in the sudomotor domain and assessed its correlation with COMPASS 31 in patients with Parkinson's disease (PD). Fifty-five patients with PD underwent clinical assessment and cardiovascular autonomic function tests and completed the COMPASS 31 questionnaire. We compared the modified CASS (integrating the Sudoscan-based sudomotor, adrenergic, and cardiovagal subscores) and CASS subscores (the sum of the adrenergic and cardiovagal subscores). The total weighted score of COMPASS 31 was significantly correlated with both the modified CASS and the CASS subscore (p = 0.007 and p = 0.019). The correlation of the total weighted score of COMPASS 31 increased from 0.316 (CASS subscores) to 0.361 (modified CASS). When we added the Sudoscan-based sudomotor subscore, the case numbers for autonomic neuropathy (AN) increased from 22 (40%, CASS subscores) to 40 (72.7%, modified CASS). The modified CASS not only better reflects the exact autonomic function, but also improves the characterization and quantification of AN in patients with PD. In areas in which a QSART facility is not easily available, Sudoscan could be a time-saving substitution.

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

OBJECTIVES: The 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. METHODS: A 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. RESULTS: Mean 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. CONCLUSIONS: ESC in palms and soles has a high diagnostic accuracy for sudomotor dysfunction as detected by absent SSR in patients with MSA and PN.

Functional and morphometric assessment of small-fibre damage in late-onset hereditary transthyretin amyloidosis with polyneuropathy: the controversial relation between small-fibre-related symptoms and diagnostic test findings.

INTRODUCTION: We aimed at investigating whether functional and morphometric tests assessing small-fibre damage, ie quantitative sensory testing, Sudoscan and skin biopsy, reliably reflect neuropathic pain and autonomic symptoms in patients with late-onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). METHODS: In 30 patients with late-onset ATTRv-PN, we collected quantitative sensory testing, Sudoscan and skin biopsy with assessment of intraepidermal, piloerector muscle and sweat gland nerve fibre density. We then correlated these functional and morphometric parameters with neuropathic pain and autonomic symptoms as assessed with the Neuropathic Pain Symptom Inventory (NPSI) and Composite Autonomic Symptom Score-31 (COMPASS-31). RESULTS: 50% of patients showed small-fibre damage in the form of a pure small-fibre neuropathy, 47% in the context of a mixed fibre neuropathy with small and large fibre involvement. All patients complained of at least one autonomic symptom and 60% had neuropathic pain. Whereas quantitative sensory testing and Sudoscan parameters correlated with neuropathic pain and autonomic symptoms as assessed by NPSI and COMPASS-31, intraepidermal, piloerector muscle and sweat gland nerve fibre density quantification did not. CONCLUSIONS: Our findings indicate that functional test parameters reliably reflect neuropathic pain and autonomic symptoms related to small-fibre damage. These findings might help to identify clinically useful biomarkers to assess patient follow-up.

Electrochemical Skin Conductance by Sudoscan in Non-Dialysis Chronic Kidney Disease Patients.

BACKGROUND: Peripheral neuropathy is prevalent among patients with chronic kidney disease (CKD). Sudoscan non-invasively detects polyneuropathy by measuring electrochemical skin conductance (ESC). We conducted a study on sudomotor function in CKD patients across various stages based on their estimated glomerular filtration rate (eGFR). METHODS: In this cross-sectional study of 700 CKD patients, all underwent Sudoscan. Pathological ESC was defined as hands < 40 µS or feet < 50 µS. Clinical neuropathy scores including Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique en 4 questionnaire (DN4) were obtained. RESULTS: Among participants, 344 had diabetes and 356 did not. Hands and feet ESC decreased with CKD progression (median (IQR) in stage 1-2, 3, 4-5: 54.0 (39.0-68.0), 45.5 (30.0-63.0), 41.8 (26.5-60.5), p trend < 0.001; 64.5 (53.5-74.0), 60.5 (43.0-72.5), 55.0 (39.0-69.8), p trend < 0.001). Pathological hands and feet ESC increased in later CKD stages (stage 1-2, 3, 4-5: 26.6%, 40.9%, 45.7%, p trend < 0.001; 21.7%, 34.0%, 40.6%, p trend < 0.001). Positive hands and feet ESC-eGFR correlation existed irrespective of diabetes. Diabetic patients had lower hands and feet ESC than non-diabetics as CKD progressed. However, multivariate regression found no significant ESC-eGFR association. Sudoscan correlated with clinical neuropathy scores. CONCLUSION: Pathological sudomotor function was common in non-dialysis CKD stages 4-5. Diabetic patients had worse function. Sudomotor dysfunction progressed with renal disease but eGFR was not an independent risk factor.

Consistency Analysis Between SUDOSCAN Examinations and Electromyography Results in Patients with Diabetes.

Objective: To evaluate the consistency between SUDOSCAN examinations and electromyography (EMG) results in patients with diabetes. Methods: A total of 326 patients with diabetes (201 males and 125 females) who were hospitalized in the endocrinology ward of the Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine) from June 2020 to February 2021 were selected as participants. All the patients were tested using a SUDOSCAN conductance analyzer for electrical skin conductivities and EMG for nerve conduction. The differences and consistencies between the results of the two examinations were analyzed. McNemar's test was used to analyze the differences between the results, and Cohen's kappa test was utilized to test the consistencies. Results: A total of 174 patients had abnormal SUDOSCAN results, and 152 patients had normal SUDOSCAN results. The EMG results of 299 patients were abnormal, and the EMG results of 27 patients were normal. The McNemar test result was P = 0.000, and the differences between the results of the SUDOSCAN and EMG examinations were statistically significant (P < 0.01). No significant consistency was found between the SUDOSCAN and EMG results, meaning that the consistency between the two examination results was not statistically significant (P = 0.868, P > 0.05). The difference between the results was statistically significant (P < 0.05), and the consistency was poor (kappa = 0.005). Conclusion: Differences existed between the SUDOSCAN examination and EMG results, and the results of the two examination methods were inconsistent, indicating that SUDOSCAN examinations cannot replace EMG examinations for DSPN.

SUDOSCAN, an Innovative, Simple and Non-Invasive Medical Device for Assessing Sudomotor Function.

Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with widely used tests for neuropathy. A total of 33 patients were included in the study. Different scoring systems (the Toronto Clinical Neuropathy Score-TCNS; the Neuropathy Disability Score-NDS; and the Neuropathy Symptom Score-NSS) were applied to record diabetic neuropathy (DN), while the SUDOSCAN medical device was used to assess sudomotor function, detect diabetic autonomic neuropathy and screen for cardiac autonomic neuropathy (CAN). Fifteen (45.5%) patients had sudomotor dysfunction. The SUDOSCAN CAN risk score was positively correlated with the hands' electrochemical sweat conductance (ESC), diastolic blood pressure (DBP), the level of the glycated hemoglobin, as well as with the TCNS, NDS and NSS. Performing SUDOSCAN tests together with other tests for DN proved to be a feasible approach that could be used in daily clinical practice in order to screen for DN, as well as for the early screening of CAN, before more complex and time-consuming tests.

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

PURPOSE: Chemotherapy-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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: The 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.

Diagnostic utility of Sudoscan for detecting bortezomib-induced painful neuropathy: a study on 18 patients with multiple myeloma.

Introduction: In the past few years, treatment of multiple myeloma has undergone a deep change for the employment of novel treatment comprising proteasome inhibitors. Bortezomib is a first-line drug in therapy of multiple myeloma. The onset of peripheral neuropathy is a dose-limiting collateral effect of the drug. This neuropathy is a distal symmetric neuropathy that affects both large and small fibers. Nerve conduction study (NCS) can be used for the diagnosis of bortezomib neuropathy, but this technique demonstrates alterations of the large nerve fibers. Sudoscan is a novel technique utilized to offer an evaluation of sudomotor function. The main objective of this study was to compare the sensitivity and diagnostic specificity of Sudoscan with respect to the nerve conduction study after bortezomib treatment. Material and methods: A total of 18 multiple myeloma patients were studied, 10 (55.5%) men and 8 (44.5%) women. Patients were analyzed at baseline and after 6 months of treatment with bortezomib. Subjects were submitted to nerve conduction study and electrochemical skin conductance evaluation with the Sudoscan device. Patients were also submitted to a clinical measure of pain and neuropathy. Results: At baseline NCS showed that only the mean sural SAP amplitude was below the 2SD lower limit of normal in 3 (16.7%) patients, while at same time we found an alteration of Sudoscan profiles in 2 (11.1%) patients. After 6 months of treatment, the NCS profiles were altered in 13 (72.2%) patients, and the Sudoscan profiles were modified in 11 (61.1%) subjects. Conclusions: Our results suggest that Sudoscan can be considered for the diagnosis of bortezomib-induced neuropathy. It is objective, reproducible, and surely easier than the traditional nerve conduction study. Sudoscan may be a useful help to manage the therapeutic interventions in multiple myeloma.

The application of sudoscan for screening microvascular complications in patients with type 2 diabetes.

The aim of the study was to evaluate the performance of sudoscan in screening diabetic microvascular complications in patients with type 2 diabete mellitus (T2DM). 515 patients with T2DM aged from 23 to 89 years were included for analysis in our study. The mean age was 60.00 ± 11.37 years and the mean duration of T2DM was 8.44 ± 7.56 years. Electrochemical skin conductance (ESC) in hands and feet was evaluated by SUDOCAN. Diabetic peripheral neuropathy (DPN) was diagnosed in 378 patients (44.3%), diabetic kidney disease (DKD) in 161 patients (31.26%), diabetic retinopathy (DR) in 148 patients (28.74%). Hands and feet ESC was significantly and independently associated with the presence of DPN, DKD and DR. Patients with a lower ESC (<60 µS) had 5.63-fold increased likelihood of having DPN, 4.90-fold increased likelihood of having DKD, 1.01-fold increased likelihood of having DR, than those with a higher ESC. Age, duration of T2DM, smoking, renal function and vibration perception thresholds were negatively correlated with ESC. Sudoscan parameters were correlated with diabetic microvascular complications, especially with DPN. Sudoscan could be an effective screening tool in primary health care for early screening microvascular complications.