Sudomotor dysfunction in patients with gluten neuropathy

Background and aim Gluten 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. Methods Patients with GN were recruited. Clinical and neurophysiological data were obtained. HLA-DQ genotyping was performed. The skin electrochemical conductance (ESC) was measured with SUDOSCANTM. Results Thirty-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. Conclusion Sudomotor 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

Background Time 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). Methods 95 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. Results The 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. Conclusions TIR 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.

Time in Range, Especially Overnight Time in Range, Is Associated With Sudomotor Dysfunction in Patients With Type 1 Diabetes

Background: To research the relationship between time in range (TIR) including overnight TIR and sudomotor function detected by SUDOSCAN in type 1 diabetes (T1D).Methods: 95 patients with T1D were enrolled. 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.Results: The 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 coefficient was 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), notably, more statistically significant results were obtained between nocturnal TIR and sudomotor dysfunction. Conclusions: TIR 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.

Electrochemical Skin Conductance Alterations during Spinal Cord Stimulation: An Experimental Study

Despite the well-known clinical effects of spinal cord stimulation (SCS), the mechanisms of action have not yet been fully unraveled. The primary aim of this study was to measure whether electrochemical skin conductance, as a measure of peripheral sympathetic autonomic function, is altered by SCS. A second aim was to compare skin conductance levels of patients with failed back surgery syndrome (FBSS) with age- and sex-matched healthy controls. Twenty-three patients with FBSS treated with SCS participated in this study. Sudomotor function was measured with the SudoscanTM instrument on the hands and feet during SCS on and off states. Difference scores in skin conductance between patients and age- and sex-matched healthy controls were calculated. Normal sudomotor function at the painful lower limb was revealed for 61% of the patients when SCS was activated. Skin conductance levels were not altered between on and off states of SCS. Differences in scores between patients and healthy controls were significantly different from zero. This study showed that SCS does not influencing the sympathetic nervous system in patients with FBSS, as measured by skin conductance levels. Moreover, it suggested that there is no normalization of the functioning of the sympathetic nervous system, despite the effectiveness of SCS to reduce pain intensity.

Randomized Sham-Controlled Pilot Study of Neurocardiac Function in Patients With Acute Ischaemic Stroke Undergoing Heart Rate Variability Biofeedback

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS).Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months.Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns).Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03865225.

Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial

Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). Patients and methods: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). Results: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). Conclusions: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

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

IntroductionIn 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 methodsA 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.ResultsAt 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.ConclusionsOur 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.