Sudomotor Dysfunction In Patients Research Articles

480-P: Serum Uric Acid–to–Creatinine Ratio Is an Independent Risk Factor of Sudomotor Dysfunction in Patients with Type 2 Diabetes

480-P: Serum Uric Acid–to–Creatinine Ratio Is an Independent Risk Factor of Sudomotor Dysfunction in Patients with Type 2 Diabetes

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 aimSudomotor 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 methodsA 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. ResultsDiabetic 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. ConclusionThe 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.

1483-PUB: SD and CV but Not TIR Are Risk Factors of Sudomotor Dysfunction in Patients with Type 2 Diabetes

Object: This study aimed to explore the relationship between Glycemic variability parameters (GV) and sudomotor function in patients with type 2 diabetes. Methods: All subjects underwent 3d-CGM in parallel with Sudoscan to assess GV and sudomotor function respectively. Sudomotor dysfunction was defined as hands mean electrochemical skin conductance (HESC) < 60 µS. Results: Among the enrolled 60 patients (53% male, 53±14 years old) , 50% patients were presented with sudomotor dysfunction (SDY group) while the other 50% patients were normal (normal group) . Compared with normal group, patients in SDY group showed an increased level of Standard deviation (SD) and coefficient of variation (CV) (P = 0.001) while time in range (TIR) level was decreased (P = 0.034) . In Spearman correlation analysis, HESC was negatively related with SD (r=-0.29, P= 0.03) and CV (r=-0.27, P= 0.04) , respectively. Logistic regression analysis demonstrated that SD (OR = 0.18, P = 0.018) and CV (OR = 0.82, P = 0.015) but not TIR (OR =2.41, P =0.11) were independent risk factors for the presence of sudomotor dysfunction after adjusting for confounding values. Conclusions: SD and CV, but not other glycemic variability parameters including TIR, are risk factors of sudomotor dysfunction in Patients with type 2 diabetes. Key words: Sudomotor Dysfunction; Glycemic Variability; Type 2 Diabetes Disclosure X.Chen: None. H.Xu: None. X.Yang: None. W.Xu: None. Funding Natural Science Foundation of Guangdong Province [2018A030313915]; Medical Scientific Research Foundation of Guangdong Province of China [A2018286].

Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances.

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients -78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing.

Sudomotor dysfunction in patients with gluten neuropathy

Background and aimGluten neuropathy (GN) is a common neurological manifestation of gluten sensitivity (GS), characterized by serological evidence of GS, while other risk factors for developing neuropathy are absent. The degree of small fiber dysfunction in GN has not been studied in depth to date. Small fiber involvement may lead to pain, thermal perception abnormalities, and sweat gland dysfunction. Sudomotor innervation refers to the cholinergic innervation of the sympathetic nervous system through small fibers in the sweat glands. The aim of our study was to assess the sudomotor function of GN patients.MethodsPatients with GN were recruited. Clinical and neurophysiological data were obtained. HLA-DQ genotyping was performed. The skin electrochemical conductance (ESC) was measured with SUDOSCANTM.ResultsThirty-two patients (25 males, mean age 69.5±10.2 years) were recruited. Thirteen patients (40.6%) had abnormal sudomotor function of the hands. Sixteen patients (50%) had abnormal sudomotor function of the feet. Twenty-one patients (65.6%) had abnormal sudomotor function of either the hands or feet.Sudomotor dysfunction did not correlate with the type of neuropathy (length-dependent neuropathy or sensory ganglionopathy), gluten-free diet adherence, severity of neuropathy, and duration of disease or HLA-DQ genotype. No differences in the ESC were found between patients with painful and patients with painless GN.ConclusionSudomotor dysfunction affects two-thirds of patients with GN. The lack of correlation between pain and sudomotor dysfunction suggests different patterns of small fiber involvement in patients with GN.

Time in range, especially overnight time in range, is associated with sudomotor dysfunction in patients with type 1 diabetes

BackgroundTime in range (TIR) is advocated as key metric of glycemic control and is reported to be associated with microvascular complications of diabetes. Sudomotor dysfunction is among the earliest detectable diabetic peripheral neuropathy (DPN). We set about to research the relationship between TIR including overnight TIR and sudomotor function detected by SUDOSCAN with the intention of exploring the correlation of TIR including overnight TIR and early DPN in type 1 diabetes (T1D).Methods95 patients with T1D were enrolled. TIR including nocturnal TIR of 3.9–10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC < 60µS. Logistic regressions were applied to examine the independent association of TIR and overnight TIR with sudomotor function.ResultsThe overall prevalence of sudomotor dysfunction was 28.42%. Patients with sudomotor dysfunction had significantly lower TIR for the whole recorded phase and for nighttime. The sudomotor dysfunction prevalence progressively declined with the ascending tertiles of TIR and nocturnal TIR (P for trend < 0.05). Correlation analysis showed that the relationship between nocturnal TIR and FESC was stronger than that between TIR and FESC with correlation coefficients were respectively 0.362 and 0.356 (P < 0.001). Finally, logistic regression analysis indicated the independently negative relation between TIR and nocturnal TIR and sudomotor dysfunction (P < 0.05), and the correlation between nocturnal TIR and sudomotor dysfunction was more statistically significant.ConclusionsTIR is negatively correlated with sudomotor dysfunction in T1D independent of HbA1c. Furthermore, decreased nocturnal TIR is more closely related to the impaired function of sudomotor nerves in sweat glands.

Sudomotor dysfunction in patients recovered from COVID-19

Dysautonomia has been reported in COVID-19. Sweat function testing has been proposed to assess autonomic neuropathy. Fifty Indian patients consulting for neurological symptoms participated in this observational study. The NHS questionnaire for neurological symptoms was completed and electrochemical skin conductance was measured using Sudoscan. The 26% of patients with sweat dysfunction i) were older (p = 0.001), ii) were more frequently treated at home (p = 0.008), iii) were more likely to have received antiviral treatment (p = 0.0006), and iv) more frequently reported at least one motor, sensory or autonomic symptom (p = 0.04). This preliminary study suggests that patients with COVID-19 should be screened for dysautonomia.

Predictors of sudomotor dysfunction in patients with type 1 diabetes without clinical evidence of peripheral neuropathy

AimTo investigate the frequency of foot sudomotor dysfunction determined by the electrochemical skin conductance test (ESC) and its independent predictors in individuals with type 1 diabetes mellitus (T1D) and no clinical evidence of diabetic peripheral neuropathy (DPN). MethodsAdults with T1D for longer than 5 years and without DPN defined by the Michigan Neuropathy Screening Instrument and Neuropathy Disability Score were assessed for foot sudomotor dysfunction by ESC. Multivariate logistic regression analysis was used to examine the association between foot sudomotor dysfunction (ESC < 70 µS) and demographic, clinical, and biochemical variables. ResultsA total of 61 individuals with T1D were included. Their mean age was 29.5 ± 8.6 years, and mean diabetes duration was 17.8 ± 7.9 years. Foot sudomotor dysfunction was present in 16 (26.2%) participants, despite no clinical evidence of DPN. Retinopathy, hand sudomotor dysfunction and glycated haemoglobin (HbA1c) levels were identified as independent predictors of foot sudomotor dysfunction by multivariate logistic regression analysis. Retinopathy, hand sudomotor dysfunction, and every 1% increase of HbA1c increased the odds of foot sudomotor dysfunction by 2.48, 2.82, and 1.24-fold, respectively. ConclusionOur findings indicate a high frequency of foot sudomotor dysfunction among individuals with T1D and no overt DPN. Factors associated with DPN, including retinopathy and higher HbA1c levels, independently predicted the occurrence of sudomotor dysfunction, suggesting that ESC assessment is a useful tool in the clinical setting to identify early small-fiber neuropathy.

The Relationship Between β-cell Function Indices and Sudomotor Function in Chinese Patients with Type 2 Diabetes.

SUDOSCAN, a new non-invasive, quick, sensitive and quantitative technique, has been developed to detect diabetic peripheral neuropathy, and the latter is believed to be correlated with impaired β-cell function. The purpose of the present study was to investigate the associations between β-cell function indices and sudomotor function in Chinese type 2 diabetes. A total of 266 Chinese patients with type 2 diabetes were enrolled. Sudomotor function was assessed using electrochemical skin conductance of hands and feet. Pancreatic β-cell function was determined by homeostasis model assessment of β-cell function index, early-phase β-cell function indices and total β-cell function indices. Pearson correlation analysis and multiple linear stepwise regression analysis were carried out to explore the associations between β-cell function indices and sudomotor function. Patients with lower early-phase β-cell function had lower electrochemical skin conductance levels of hands and feet and higher asymmetry ratio of hands and feet. Both Pearson correlation analysis and multiple linear stepwise regression analysis showed significantly positive relationships between early-phase β-cell function and electrochemical skin conductance levels of hands and feet, after controlling for potential confounders (P<0.05). Impaired early-phase β-cell function was positively associated with sudomotor dysfunction in Chinese patients with type 2 diabetes. We speculated that impaired early-phase β-cell function may be associated with the incidence of sudomotor dysfunction in patients with T2DM.

The relationship between sudomotor function and skin microvascular reactivity in individuals with type 1 diabetes of long duration

AimThe aim of this study was to assess the relationship between sudomotor function and microvascular perfusion in patients with type 1 diabetes (DM1). MethodsWe evaluated 415 patients (206 women), with DM1, median age of 41 (IQR: 33–53) years, disease duration of 25 (IQR: 20–32) years. We assessed metabolic control of diabetes and the presence of peripheral and cardiac autonomic neuropathy. Sudomotor function was assessed using Sudoscan device by electrochemical skin conductance (ESC). Microvascular function was measured by laser-Doppler flowmetry with basal perfusion, the peak flow after occlusion (PORHpeak) and THmax which is the percentage change between basal perfusion and the peak flow during thermal hyperemia (TH). The accumulation of advanced glycation end products in the skin was assessed by skin autofluorescence (AF) measurement using AGE Reader. We subdivided patients based on the presence of diabetic peripheral neuropathy (DPN), cardiac autonomic neuropathy (CAN) and according to normal value of ESC. ResultsPatients with abnormal ESC had higher skin AF [2.5 (2.1–2.9) vs 2.1 (1.9–2.5) AU, p < 0.001], lower eGFR [83 (72–96) vs 98 (86–108) ml/min/1.73 m2, p < 0.001], higher basal perfusion [25 (12–81) vs 14 (7–43) PU, p < 0.001], lower THmax [664 (137–1461) vs 1115 (346–1933) %, p = 0.002], higher PORHpeak [104 (59–167) vs 70 (48–135) PU, p < 0.001] as compared to subjects with normal ESC results.We found negative correlation between THmax and TG level (Rs = −0.14, p < 0.005), AF (Rs = −0.19, p = 0.001), vibration perception threshold - VPT (Rs = −0.24, p < 0.001) and positive correlation with HDL level (Rs = 0.14, p = 0.005), Feet ESC (Rs = 0.21, p < 0.001) and Hands ESC (Rs = 0.14, p = 0.004). We found positive correlation between PORHpeak and TG level (Rs = 0.14, p = 0.003), skin AF (Rs = 0.29, p < 0.001), VPT (0.27, p < 0.001) and negative correlation with eGFR (Rs = −0.2, p < 0.001), HDL (Rs = −0.12, p = 0.01), Feet ESC (Rs = −0.27, p < 0.001) and Hand ESC (Rs = −0.16, p = 0.002). ConclusionImpaired microvascular reactivity is associated with sudomotor dysfunction in patients with type 1 diabetes.

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.

Rapid, Objective and Non-invasive Diagnosis of Sudomotor Dysfunction in Patients With Lower Extremity Dysesthesia: A Cross-Sectional Study.

ObjectiveTo determine whether patients with lumbosacral (LS) radiculopathy and peripheral polyneuropathy (PPNP) exhibit sudomotor abnormalities and whether SUDOSCAN (Impeto Medical, Paris, France) can complement nerve conduction study (NCS) and electromyography (EMG).MethodsOutpatients with lower extremity dysesthesia underwent electrophysiologic studies and SUDOSCAN. They were classified as normal (group A), LS radiculopathy (group B), or PPNP (group C). Pain severity was measured by the Michigan Neuropathy Screening Instrument (MNSI) and visual analogue scale (VAS). Demographic features, electrochemical skin conductance (ESC) values on hands and feet, and SUDOSCAN-risk scores were analyzed.ResultsThere were no statistical differences in MNSI and VAS among the three groups. Feet-ESC and hands-ESC values in group C were lower than group A and B. SUDOSCAN-risk score in group B and C was higher than group A. With a cut-off at 48 microSiemens of feet-ESC, PPNP was detected with 57.1% sensitivity and 94.2% specificity (area under the curve [AUC]=0.780; 95% confidence interval [CI], 0646–0.915). With a SUDOSCAN-risk score cut-off at 29%, NCS and EMG abnormalities related to LS radiculopathy and PPNP were detected with 64.1% sensitivity and 84.2% specificity (AUC=0.750; 95% CI, 0.674–0.886).ConclusionSUDOSCAN can discriminate outpatients with abnormal electrophysiological findings and sudomotor dysfunction. This technology may be a complementary tool to NCS and EMG in outpatients with lower extremity dysesthesia.

Sudoscan as a noninvasive tool to assess sudomotor dysfunction in patients with Fabry disease: results from a case-control study.

Hypohidrosis is a frequent and early symptom in patients with Fabry disease. Studies have reported improved sweating in patients treated with enzyme-replacement therapy. A new method, Sudoscan, has been developed that is noninvasive, is quantitative, and can quickly evaluate sweat gland function. It is based on the electrochemical reaction between sweat chlorides and stainless-steel electrodes in contact with the palms and soles. The aim of our study was to evaluate the Sudoscan as a tool to assess sudomotor dysfunction in patients with Fabry disease. Consecutive patients were prospectively recruited who had a diagnosis of Fabry disease, which had been confirmed genetically and/or by measurement of α-galactosidase activity in leukocytes. Healthy controls, matched (1:1) for age and sex, were also enrolled. Test results were expressed immediately as electrochemical skin conductance (ESC, µS) for hands and feet. Sudomotor dysfunction was considered absent, moderate, or severe if the ESC measured on the feet was >60 µS, between 60 and 40 µS, or <40 µS, respectively. Among the 18 patients, 11 had hypohidrosis or anhidrosis. Hand and feet ESCs were significantly lower in patients compared to their controls (P=0.0015 and P=0.0047, respectively). Among patients, 8/18 (44.5%) had a sudomotor dysfunction, moderate in three and severe in five cases. Hand and feet ESCs were significantly lower in those with hypohidrosis/anhidrosis compared to those without (P=0.0014 and P=0.0056, respectively). This study showed that Sudoscan provided a quick, noninvasive, and quantitative measurement of sudomotor function in Fabry disease patients.

Sudomotor dysfunction in autoimmune autonomic ganglionopathy: a follow-up study

We have previously shown that sudomotor dysfunction in autoimmune autonomic ganglionopathy is severe, widespread, and predominantly post-ganglionic. However, the long-term changes in sudomotor function have not been studied in detail. Our objective was to characterize the long-term changes in sudomotor dysfunction in patients with autoimmune autonomic ganglionopathy. Changes in sudomotor function were compared in a cohort of nine α3 nAChR antibody positive autoimmune autonomic ganglionopathy patients over an approximate 5-year period. Standard measurements of sudomotor function were used including the thermoregulatory sweat test and quantitative sudomotor axon reflex test. Total body anhidrosis on thermoregulatory sweat testing showed improvement in four of nine patients. Quantitative sudomotor axon reflex testing for both forearm and foot sites was variable with four of nine patients showing improvement in total sweat output. Distribution of sudomotor dysfunction at follow-up was post-ganglionic in seven of nine patients at the foot site and three of nine patients at the forearm site. Overall, sudomotor dysfunction was post-ganglionic in seven of nine patients throughout the follow-up period (62.4 ± 19.4 months). Sudomotor dysfunction in autoimmune autonomic ganglionopathy was severe and widespread throughout the follow-up period for the majority of patients studied. Sudomotor dysfunction was predominantly post-ganglionic throughout the follow-up period.

Autonomic Neuropathy in Diabetes Mellitus and Obesity: An Update

Autonomic neuropathy, although not rare, is one of the most insidious complications of diabetes mellitus, especially in those patients with long-standing and poorly controlled disease. A lot of attention has been given to the cardiovascular aspect of autonomic dysfunction, which has been implicated in increased mortality, especially in view of recent reports regarding the association of very tight glycaemic control with increased mortality, which could be attributed to hypoglycemia-induced arrhythmias. However, cardiac autonomic neuropathy is only one of the many facets of this complication, which leaves virtually no organ system unaffected. In this special issue of the journal, we have invited authors to submit reviews and research articles regarding autonomic neuropathy in patients with diabetes and obesity, since this last condition is also associated with autonomic dysfunction, due to concomitant insulin resistance. The issue includes papers on cardiac autonomic neuropathy, sudomotor dysfunction, skin blood perfusion, insulin secretion, and exocrine pancreatic insufficiency. In an extensive and elaborate review, Dr. C. Voulgari et al. examine the application of a simple, inexpensive, yet extremely useful tool, the electrocardiogram, in assessing diabetic patients with possible cardiac autonomic neuropathy and screening them for cardiovascular disease. In the following research papers, H.-W. Huang et al. investigate the applicability of using frequency domain analysis on laser Doppler flowmetry data in the study of carpal tunnel syndrome and diabetic polyneuropathy, while N. Papanas et al. examine the association between serum uric acid levels and sudomotor dysfunction in patients with type 2 diabetes mellitus and find it to be positive, a fact which leads them to speculation on the potential role of serum uric acid in sudomotor dysfunction. Returning to cardiac autonomic function, Dr. S. Liatis et al. demonstrate that in young patients with type 1 diabetes, even in the absence of macrovascular and renal complications, large arterial stiffness can be present and diagnosed with pulse wave velocity analysis, and, furthermore, cardiac parasympathetic function, as assessed by the classic tests proposed by Ewing and Clarke, is strongly associated with this condition, thus highlighting the importance of cardiac autonomic dysfunction in predicting cardiovascular disease risk, even in the absence of overt diabetic complications. Apart from diabetes, obesity, a condition which predisposes to diabetes and is characterized by insulin resistance, has been proposed to be associated with impaired autonomic function. This is addressed in the research paper by Dr. A. E. Andreazzi et al., in which prediabetic obese rats are demonstrated to have low sympathoadrenal activity, which, according to the authors, contributes to glucose intolerance and hyperinsulinemia during an intravenous glucose tolerance test. Finally, Drs. P. D. Hardt and N. Ewald present an elegant review on exocrine pancreatic insufficiency, in which they address its increased frequency in type 1 and 2 diabetes and discuss whether it is a complication of the disease or a concomitant condition to underlying pancreatic diseases which also lead to diabetes, and the possible role of diabetic neuropathy in its manifestation, after carefully guiding the reader through the relevant literature. The present special issue should by no means be considered a comprehensive “primer” on all the facets of autonomic neuropathy, and this was never its original aim. The purpose was to present the reader with an update on as many as possible of the aspects of autonomic dysfunction in diabetes and obesity, and in these terms, we consider it to have achieved its goal. We believe that both the research papers, as well as the review articles contained herein are of high quality and address key issues in the presentation and diagnosis of this condition. We hope that this issue will underscore the importance of autonomic dysfunction as a condition that is not at all rare, but is often overlooked by clinicians both in terms of diagnosis as well as treatment and that it will also serve as a reminder of the need for further research in this field. Nicholas L. Katsilambros Andrew J. Boulton Nicholas Tentolouris Alexander Kokkinos Stavros Liatis

Sudomotor dysfunction in patients with optic neuritis

Optic neuritis (ON) is a frequent initial manifestation of multiple sclerosis (MS). Autonomic failure affecting the pupillary function is known to exist in ON patients, and patients with MS are known to have more widespread autonomic dysfunction. For example, sudomotor dysfunction is well known in MS. We carried out a study investigating sudomotor abnormalities in ON patients, and later followed these patients at risk of developing MS. Firstly, sudomotor function was measured by sympathetic skin responses (SSRs) in 13 ON patients and in 22 healthy controls. Secondly, thermoregulatory sweating was measured by an evaporimeter after a heating stimulus in 13 ON patients and in 14 healthy control subjects. The SSR latencies to electrical stimuli in the ON patients were significantly prolonged in the upper and lower extremities (p = 0.013-0.002), indicating sudomotor dysfunction. No statistically significant thermoregulatory sweating dysfunction could be found in the ON patients compared to the controls. All ON patients underwent a follow-up (mean duration 12.5 years) during which eight ON patients (62%) converted to clinically definite MS. It seemed that SSRs had no value for identifying patients who later developed MS. Our results enlarge the knowledge of autonomic disorders in ON patients, showing that sudomotor function may also be involved.

The sympathetic skin response--a useful method for the diagnosis of reflex sympathetic dystrophy?

The aim of the present study was to examine the value of the sympathetic skin response (SSR) in the diagnosis of reflex sympathetic dystrophy (RSD). SSR was recorded in 20 normal subjects and in 24 patients with predominantly chronic RSD. In 3 patients with RSD, additional recordings of the SSR were performed before and several times after administration of local anaesthetics via a plexus catheter on the diseased side. SSR was recorded with standard EMG apparatus. Disc electrodes were positioned on the middle of the volar and dorsal surfaces of the hands and feet. Electrical stimuli were applied to the middle of the forehead at irregular intervals longer than 60 s. In normal subjects inter- and intraindividually different monophasic, biphasic and triphasic potentials without difference in the waveform between sides were recorded. SSR abnormalities were found in 15 patients with RSD and correlated with the severity of the disease. In patients with slight dystrophy SSR was predominantly normal, while in most of those with intermediate dystrophy differences in the SSR waveform between sides were observed. In the presence of severe dystrophy SSR amplitude was predominantly decreased on the affected side. Following the administration of local anaesthetics via a plexus catheter, the differences in SSR waveform became smaller in patients with initial distinct side difference of the waveform. However, differences in SSR amplitudes or latencies between sides were not affected. Side differences in SSR waveform could be due to a mild, reversible unilateral sudomotor dysfunction, whereas differences in SSR amplitude or latency indicate more serious damage to sudomotor activity, possibly due to dysfunction of autonomic fibres. In patients with slight dystrophy sweat secretion is predominantly normal, while in severe dystrophy more serious damage to the sweat secretory system can be observed. SSR provides useful information on sudomotor dysfunction in patients with RSD. However, as there is no consensus on the clinical criteria for diagnosis of RSD, it is also not possible to determine the diagnostic value of SSR in the diagnosis of RSD.

Sympathetic skin response in patients with reflex sympathetic dystrophy

The sympathetic skin response (SSR) originates from synchronized activation of the sweat glands as a response to a volley discharge in efferent sympathetic nerve fibres. The aim of the study was to verify the diagnostic value of SSR in patients with reflex sympathetic dystrophy (RSD). SSR was recorded in 20 normal subjects and in 24 patients with predominantly chronic RSD. In normal subjects inter- and intra-individually different mono-, bi- and triphasic potentials could be recorded without difference of the waveform from side to side. SSR abnormalities were found in 15 patients and correlated with the severity of the disease. In patients with slight dystrophies, SSR was predominantly normal. In intermediate dystrophies, mainly differences of the SSR waveform between sides could be recorded, indicating unilateral sudomotor dysfunction. In severe dystrophies abnormalities of SSR amplitude or latency were found, indicating more serious disturbance of sudomotor activity, possibly due to a lesion of sympathetic fibres. The SSR provides useful information on sudomotor dysfunction in patients with RSD. However, as there is no consensus in the literature for the clinical criteria to diagnose RSD, it is not yet possible to determine the final diagnostic value of SSR for the diagnoses of RSD.