Nerve Fiber Function Research Articles

PHOTOGRAMMETRIC 3D ACQUISITION AND ANALYSIS OF MEDICAMENTOUS INDUCED PILOMOTOR REFLEX (“GOOSE BUMPS”)

In a current study at the University Hospital Dresden, Department of Neurology, the autonomous function of nerve fibres of the human skin is investigated. For this purpose, a specific medicament is applied on a small area of the skin of a test person which results in a local reaction (goose bumps). Based on the extent of the area, where the stimulation of the nerve fibres is visible, it can be concluded how the nerve function of the skin works. The aim of the investigation described in the paper is to generate 3D data of these goose bumps. Therefore, the paper analyses and compares different photogrammetric surface measurement techniques in regard to their suitability for the 3D acquisition of silicone imprints of the human skin. Furthermore, an appropriate processing procedure for analysing the recorded point cloud data is developed and presented. It was experimentally proven that by using (low-cost) photogrammetric techniques medicamentous induced goose bumps can be acquired in three dimensions and can be analysed almost fully automatically from the perspective of medical research questions. The relative accuracy was determined with 1% (RMSE) of the area resp. the volume of an individual goose bump.

Serum Neuroinflammatory Markers’ Levels and Evaluation of Peripheral Large Nerve Fibre Function in Patients with Psoriasis

Objective: Currently, tumor necrosis factoralpha (TNF-α) inhibitors are widely used all over the world, especially in the treatment of severe psoriasis. However, multiple sclerosis (MS) and peripheral neuropathy occurrence associated with TNF-α inhibitors have been reported in the treatment of patients with psoriasis. It is not known whether TNF-α inhibitors reveal underlying neurological disorders in patients with psoriasis. The aim of this study was to investigate whether there is an association between psoriasis and MS or peripheral neuropathy. Methods: In this study, 50 psoriasis patients and 25 healthy controls were enrolled. Neurological examination and needle electromyography test were performed. Serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), S-100 calcium-binding protein (S100B) and neuron specific enolase (NSE), which are involved in neuroinflammatory process, were measured. Results: Serum MMP-9 levels were higher in psoriasis patients compared to healthy controls. Serum MMP-2 and NSE levels were decreased in psoriasis patients compared to healthy controls. There was no significant difference in S100B levels between two groups. All neurophysiological parameters in each individual patient and control were found to be within normal limits and there was no difference between groups. Conclusion: NSE and MMP-9 might play role in the occurrence of MS in psoriasis patients. Especially, we are in the opinion that it might be useful to measure the serum levels of these markers before the administration of TNF-α inhibitors in psoriasis patients with family history of MS.

Sympathetic Skin Response and Boston Questionnaire in Carpal Tunnel Syndrome

We aimed to determine relations between the sudomotor efferent nerve fiber function and Boston questionnaire in idiopathic carpal tunnel syndrome (CTS). Median-nerve sympathetic skin responses (SSRs) evoked by wrist stimulation were recorded in 108 CTS patients and compared with those in 88 healthy volunteers. The Boston questionnaire form (BQF) was applied to patients. All patients and healthy individuals were questioned about the autonomic symptoms in the hand (red or purple coloration, excessive sweating, and feeling cold). The average SSR latencies of the patients with CTS were significantly longer than those in the control group (P < 0.001). Positive significant, while weak, correlation was found between the SSR latency, autonomic symptoms, and total sympathetic system scores. No statistically significant relationship was found between the Boston symptom severity, functional capacity scores, and SSR latency. The latter obtained through wrist stimulation was sensitive to support the sudomotor sympathetic dysfunction in patients with CTS. As we found no relationship between the BQF and SSR, these indices may evaluate different aspects of CTS.

Elevated pain threshold in patients with asymptomatic diabetic neuropathy: an intraepidermal electrical stimulation study.

The loss of epidermal nerve fibers is regarded as an early pathological change in human diabetes. We investigated epidermal Aδ nerve fiber function by examining pain threshold by means of intraepidermal electrical stimulation (IES) in early diabetic neuropathy. We recruited 20 asymptomatic diabetic patients. Eighteen age-matched, healthy subjects served as controls. We placed the IES electrode onto the skin of the foot dorsum and delivered weak electrical stimulation. We defined pain threshold as the minimum electrical intensity at which a subject felt a pricking sensation. The mean pain thresholds in the patient group were significantly higher (0.053 ± 0.036 mA; P < 0.01) than in the control group (0.027 ± 0.006 mA). We confirmed that the pain threshold was elevated in early diabetic neuropathy. We conclude that the IES electrode is a useful tool to evaluate early diabetic polyneuropathy. Muscle Nerve 54: 146-149, 2016.

Painful heating for evaluating trigeminal small nerve fiber function in patients with migraine

Objective To study any functional changes in the trigeminal nociceptive system in cases of migraine with aura (MWA) using painful heat-evoked potentials (CHEPs), and to explore the value of CHEP in evaluating the trigeminal small nerve fibers of patients with MWA. Methods Sixty patients with MWA were recruited as the MWA group, and 60 healthy persons were selected as a normal control group. Thermal stimulation at 51 ℃ was applied to the skin above the patients' right and left eyebrows. The N wave latencies and N-P amplitudes of the CHEPs were recorded at the vertex (Cz) of the head. The intensity of the stimulus was graded using a visual analogue scale (VAS). Results In the control group the simulation produced no significant differences in the N550 or P750 latencies or in the N-P amplitudes. In the MWA group no significant differences were observed when the headache side was stimulated, but the N550 and P750 latencies were both significantly shorter than those of the control group and the N-P amplitude was significantly greater than that of the control group. The average VAS score on both sides in the patients with migraine was significantly higher than those of the control group. However, there was no significant difference in average VAS scores between the headache and non-headache sides of the patients with migraine. Conclusions CHEP is a reliable method for detecting any pathological changes in the trigeminal small nerve sensory pathway. Increased cutaneous allodynia in acute migraine attacks is detectable using CHEPs. Key words: Pain; Heat-evoked potentials; Migraine; Aura; Trigeminal nerves

Neurophysiological changes associated with implant placement.

The objective of the study was to evaluate the feasibility of a standardized Quantitative Sensory Testing (QST) protocol extra- and intraoral in patients to detect and quantify sensory disturbances of the inferior alveolar nerve due to the proximity of implantation procedures to the inferior alveolar nerve canal. Patients who had obtained an implant placement were examined by implementing a comprehensive QST protocol for extra- and intraoral use. The study included 33 patients after implant placement in the lower jaw and one patient suffering from an inferior alveolar nerve injury. Patients were tested bilaterally (chin and mucosal lower lip). Comparing the implanted vs. the control side, QST parameters revealed no significant neurophysiological changes in all parameters. Evaluating the development of sensory disturbances in dependency of the proximity of the implant to the inferior alveolar nerve canal, mechanical QST parameters showed no significant correlation. The mean distance of the inserted implant to the inferior nerve canal was 2.65±1.75mm. In the case of one patient suffering from impairment of the nerve function due to implant placement, we found abnormal sensory responses to touch coexisting with numbness and temperature algesia. Monitoring of trigeminal nerve fiber functions by QST intra- and extraoral is feasible to evaluate oral sensory pattern after implantation procedures. Sensory disturbances of the inferior alveolar nerve were shown to be avoided by keeping an average safety zone of 2.65mm between implant and nerve.

Reproducibility of axon reflex-related vasodilation assessed by dynamic thermal imaging in healthy subjects

IntroductionSmall nerve fiber dysfunction is an early feature of diabetic neuropathy. There is a strong clinical need for a non-invasive method to assess small nerve fiber function. Small nerve fibers mediate axon reflex-related vasodilation and play an important role in thermoregulation. Assessing the reflex vasodilation after local heating might elucidate some aspects of small fiber functioning. In this study, we determined the reproducibility of the reflex vasodilation after short local heating in healthy subjects, assessed with thermal imaging and laser Doppler imaging. MethodsHealthy subjects underwent six heating rounds in one session (protocol I, N=10) or spread over two visits (protocol II, N=20). Reflex vasodilation was elicited by heating the skin to 42°C with an infrared lamp. Skin temperature and skin blood flow were recorded during heating and recovery with a thermal imaging camera and a laser Doppler imager. Skin temperature curves were fitted with a mathematical model to describe the heating and recovery phase with time constant tau (tauHeat and tauCool1). ResultsThe reproducibility of tau within a session was moderate to excellent (intra-class correlation coefficient 0.42–0.86) and good (0.71–0.72) between different sessions. Within one session the differences in tauHeat were small (bias±SD −1.3±18.9s); the bias between two visits was −1.2±12.2s. For tauCool1 the differences were also small, 1.4±6.6s within a session and between visits −1.4±11.6s. ConclusionsThe heat induced axon reflex-related vasodilation, assessed with thermal imaging and laser Doppler imaging, was reproducible both within a session and between different sessions. Tau describes the temporal profile in one parameter and represents the effects of all changes including blood flow and as such, is an indicator of the vasodilator function. TauHeat and tauCool1 can accurately describe the dynamics of the axon reflex-related vasodilator response in the heating and recovery phase respectively.

Quantitative sensory testing using DFNS protocol in Europe: an evaluation of heterogeneity across multiple centers in patients with peripheral neuropathic pain and healthy subjects.

Quantitative sensory testing (QST) in accordance with the DFNS (German Research Network on Neuropathic Pain) protocol assesses the function of afferent nerve fibers on the basis of 13 parameters. Within the consortia IMI (Innovative Medicines Initiative) Europain and Neuropain, QST results from pain research units experienced in QST across Europe can be compared for the first time. Aim of this analysis was to identify possible biases in the QST assessment between 10 centers from 8 different European countries. In total, 188 healthy subjects, 217 patients with painful polyneuropathy, and 150 patients with painful peripheral nerve injury were included in the analysis. Mixed effects models were constructed for each of the 11 normally distributed QST parameters with z-value as the dependent variable, and center as the random effect. The I statistic for heterogeneity was calculated, an index ranging from 0% (no heterogeneity) to 100% (perfect heterogeneity). Data from healthy subjects were comparable with the existing reference data base. Patients with polyneuropathy mainly displayed loss of sensory function, whereas patients with peripheral nerve injury often showed sensory loss combined with mechanical hyperalgesia. Heterogeneity was overall low between different centers and parameters. There was no systematic heterogeneity for patients with painful peripheral nerve injury and painful polyneuropathy. For healthy subjects, only blunt pressure pain threshold showed a considerable heterogeneity of 42% (95% confidence interval: 0%-66%). In conclusion, QST of both healthy subjects and patients with peripheral neuropathic pain is largely homogenous within the European centers, an essential prerequisite for performing multicenter QST-based studies.

ID 346 – Transthyretin familial amyloid polyneuropathy (TTR-FAP): Efficacy of liver transplant versus tafamidis in nerve fiber function

Objective To evaluate the effect of Tafamidis versus liver transplant in nerve conduction studies of TTR-FAP patients over 24 months. Methods Nerve conduction data from 48 stage I TTR-FAP patients was analysed retrospectively for 24 months after treatment. 26 patients (37.73 ± 9.19 years) submitted to liver transplant were compared to 22 patients on Tafamidis (40.00 ± 8.74). Sympathetic skin response, Motor and Sensory composed scores were obtained after respective summing of nerve amplitudes. Disease duration to baseline and Karnofsky index were also evaluated. Progression was evaluated using a Repeated Measures ANOVA. Results Sensory composed score in the Tafamidis group was the single measure to progress significantly on the first 12 months, stabilizing afterwards. No other significantly differences were found between groups over time. Conclusions Efficacy of Tafamidis on nerve fiber function of TTR-FAP patients, seems to be similar to liver transplant, over 2 years, despite a slight progression on the first 6 months with stabilization afterwards. These findings are consistent with the clinical stabilization reported in the literature with both treatments. Key message Efficacy of tafamidis is similar to liver transplant in the stabilization of the neuropathy.

A neurophysiological study of large- and small-diameter nerve fibers in the hands of hemodialysis patients

Polyneuropathy in patients with advanced clinical kidney disease is a very disabling condition. The aim of this study was to evaluate neurophysiological abnormalities of large- and small-diameter nerve fibers in the hands of hemodialysis patients. A total of 38 hemodialysis patients and 38 healthy control subjects underwent a conventional electrophysiological examination. The function of small nerve fibers was assessed using cutaneous silent period (CSP) measurement. Slower median nerve motor conduction velocities were recorded in patients with fistula (p < 0.0001) and without fistula (p < 0.001). Sensory median and ulnar nerve conduction velocities were slower in both patient groups compared with the control group (p = 0.001). Median sensory nerve action potential amplitudes were lower in patients with fistulas (p = 0.009) and without fistulas (p = 0.005) compared with the control group. Significantly prolonged F-wave latencies of the median (p = 0.002) and ulnar nerves (p = 0.023) in patients with fistulas hands were observed. In 12/38 (32 %) patients, the onset latencies of CSPs were significantly delayed (p = 0.001). There was an inverse correlation of β2-microglobulin and decreased conduction velocities of the median nerves, while Kt/V was associated with improved sensory nerve conduction velocity of the median nerve. An inverse correlation between motor velocity of both nerves and hemodialysis duration was observed in the patient groups. The measurement of CSPs provides a useful method for assessing small nerve fibers. The role of A-delta fibers is often overlooked.

Structural and functional characterization of nerve fibres in polyneuropathy and healthy subjects

ObjectivesQuantification of intraepidermal nerve fibre density (IENFD) is an important small fibre measure in distal symmetric polyneuropathies (DSP), but quantitative evaluation of additional structural and functional factors may help in elucidating the underlying mechanisms, and in improving the diagnostic accuracy in DSP. The literature reports a weak or moderate relationship between IENFD and spontaneous and evoked pain in neuropathies, but the relationship between functional and structural small fibre parameters in patients with DSP is unclear. The objectives of the current study, therefore, were to determine morphological and functional parameters related to small nerve fibres in subjects with distal symmetric polyneuropathy (DSP) and healthy controls, and to characterize the interplay among these parameters in these two groups. Materials and Methods17 patients with painful DSP (≥4 on 0–10 numerical rating scale) and with symptoms and signs of small fibre abnormality (with or without large fibre involvement) and 19 healthy control subjects underwent comprehensive functional and structural small fibre assessments that included quantitative sensory testing, response to 30min topical application of 10% capsaicin and analysis of skin biopsy samples taken from the distal leg (IENFD, epidermal and dermal nerve fibre length densities (eNFLD, dNFLD) using global spatial sampling and axonal swelling ratios (swellings/IENFD and swellings/NFLD)). ResultsDSP patients had reduced sensitivity to cold (median −11.07°C vs. −2.60, P≤0.001) and heat (median 46.7 vs. 37.70, P≤0.001), diminished neurovascular (median 184 vs. 278 mean flux on laser Doppler, P=0.0003) and pain response to topical capsaicin (median 10 vs. 35 on 0–100 VAS, P=0.0002), and lower IENFD, eNFLD and dNFLD values combined with increased swelling ratios (all P<0.001) compared to healthy controls. The correlation between structural and functional parameters was poor in DSP patients, compared with healthy controls. In healthy controls eNFLD and dNFLD, IENFD and eNFLD, IENFD and dNFLD all correlated well with each other (r=0.81; P≤0.001, r=0.58; P=0.009, r=0.60; P=0.007, respectively). In DSP, on the other hand, only eNFLD and dNFLD showed significant correlation (r=0.53, P=0.03). A diagnostic approach of combined IENFD and eNFLD utilization increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%. ConclusionsThis study presents a rigorous comparison between functional and morphological parameters, including parameters such as eNFDL and dNFLD that have not been previously evaluated in this context. The correlation pattern between functional and structural small fibre parameters is different in patients with DSP when compared to healthy controls. The findings suggest a more direct relationship between structure and function of nerve fibres in healthy controls compared to DSP. Furthermore, the findings suggest that combining IENFD with measurement of NFLD improves the diagnostic sensitivity and specificity of DSP. ImplicationsCombining small fibre parameters may improve the diagnostic accuracy of DSP.

Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers

The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

English

A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed 100 patients of clinically proven Hansen's will take in study and given diagnosis is made by dermatologist and neurologist. For Study of Clinical, Neuropathological, Neurophysiological Pattern of leprous neuropathy and results shows that Peripheral neuropathy is common neurological disorder, although population based studies are scarce. It is a diverse group of disorder with varying etiologies. Many of these are amenable to treatment while others are not. It affects all age groups are different etiologies in various age groups. Disorder is more common in males. Leprosy is still most common cause of peripheral neuropathy in this part of world. GBS is commonest cause in acutely presenting patients of peripheral neuropathy. Vacuities is also common especially in undiagnosed peripheral neuropathy patients and revealed by nerve biopsy. Tingling and numbness are two most common sensory complains. On objective sensory examination impairment of pain/temperature was most common. Evidence of large fiber dysfunction was less common. Almost half of leprous neuropathy had impaired joint position and vibration. Anesthetic patches and thickened nerve are two commonest indicators of leprous neuropathy. Among DTRs ankle jerk was most commonly affected. Almost half of GBS patients had history of preceding illness. Overall sensorimotor polyneuropathy was most common type of pattern after clinical- electrophysiological evaluation. Multiple mononeuropathy was most common in leprous neuropathy. Most patients had axonal type of involvement. In GBS patients predominantly motor neuropathy was found Skin smear examination is readily available and easy test to diagnosed leprosy, if done carefully. Sural nerve biopsy is useful in doubtful diagnosis. Around 16. 47% patient remains undiagnosed even after all investigation. Further population based studies are need of the day for evaluating the changing epidemiology of peripheral neuropathy.

Central habituation and distraction alter C‐fibre‐mediated laser‐evoked potential amplitudes

Recent studies applied laser-evoked potentials (LEP) for the analysis of small nerve fibre function and focused on the detection of stable C-fibre-mediated potentials (C-LEPs); high technical requirements were needed. The diagnostic significance is still controversially discussed. So far, only few studies focused on the susceptibility of C-LEPs to distraction and other influences. We hypothesized that C-LEPs are altered by habituation processes and distraction. Twelve subjects were tested with a C-fibre laser set-up (neodymium:yttrium-aluminium-perovskite laser with a 10-mm beam diameter and 10-ms stimulus time) at the left perioral area. In condition I, the subjects received repetitive painful laser stimuli at the right hand to induce habituation. In condition II, the subjects had to fulfil an auditory discrimination task (where the subjects had to estimate the pitch of different tones on a scale for 20min). C-LEPs were retrieved before and after the habituation or distraction paradigm. C-LEPs were also measured in a control group who was not influenced by laser stimuli or other disturbances during a 23-min break between the two test sessions. In both test conditions, there was significant C-LEP amplitude reduction. The LEP amplitudes of the control group remained unchanged. In the approach of detecting C-fibre-mediated potentials with LEP, future studies should take the high susceptibility to distraction and habituation into account.

The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes.

To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, and normalized measures of serum oxidative stress and triglycerides but had no effect on LDLs or total cholesterol. Moreover, although pioglitazone treatment normalized renal function, it had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals revealed an unanticipated increase in genes related to adipogenesis, adipokine signaling, and lipoprotein signaling, which likely contributed to the blunted therapeutic response. Similar analyses of dorsal root ganglion neurons revealed a salutary effect of pioglitazone on pathways related to defense and cytokine production. These data suggest differential susceptibility of small and large nerve fibers to specific metabolic impairments associated with T2DM and provide the basis for discussion of new treatment paradigms for individuals with T2DM and DPN.

Different Clinical Parameters to Diagnose Glaucoma Disease: A Review

Glaucoma is a severe human eye disease that causes permanent loss of vision. The main cause of glaucoma eye disease is the continuous loss of retinal nerve fiber layers due to the increase in the intra ocular pressure inside the eyes. The function of these retinal nerve fibers is the transformation of recognized object information in the form of signals to the brain, where these signals are recognized as object. Damages to these nerve fibers generate blind spots and these blind spots leads to permanent blindness. Therefore, Retinal Nerve Fiber Layer Thickness is the main parameter to diagnose glaucoma. Other parameters also leading to glaucoma are Intraocular Pressure, Vertical Cup to Disc Ratio, Neuro Retinal Rim Thickness, Central Cornea Thickness, Inferior Superior Nasal and Temporal Sector Ratio etc. Therefore, the identification of these parameters plays the major role in glaucoma assessment, since it allows timely treatment to prevent the vision loss caused by glaucoma. To estimate these parameters, clinical instruments such as Tonometry, Ophthalmoscopy, Heidelberg Retinal Tomography, Perimetry, Pachymetry, Optical Coherence Tomography, GDx etc are adopted. This paper presents the various parameters, as mentioned above, used to analyze and diagnose the Glaucoma disease and associated advantages, disadvantages and the different instruments used to analyze each clinical parameter. General Terms Glaucoma, Clinical Parameters

Cardiovagal and somatic sensory nerve functions in healthy subjects.

Heart rate response to deep breathing (HRDB), which depends on the integrity of cardiac vagal preganglionic neurons and efferent fibers, and the function of sural nerve fibers are both associated with an age-related decline process. The aim of this study was to determine whether the effects attributed to aging on cardiovagal and sural nerve function decline are associated. HRDB and sural sensory nerve action potential (SNAP) amplitude, latency, and conduction velocity (SCV) were measured in one hundred healthy asymptomatic subjects (aged 14-92 years, 41 women). Multiple and simple linear regressions were used to analyze the relationships between the variables. There were significant linear relationships between sural SNAP amplitude and HRDB with age. There was also a significant linear relationship between sural SNAP amplitude and HRDB (correlation coefficient 0.46, p<0.0001), but the model explained only 21.5% of the variability in HRDB. Cardiovagal function assessed by HRDB is associated with sural SNAP amplitude in healthy subjects. Age-related decline only partially explained the variability seen in the association. Other genetic and environmental factors may also play a role.

Vitamin D Insufficiency is Associated With Reduced Parasympathetic Nerve Fiber Function in Type 2 Diabetes

Vitamin D insufficiency is prevalent in subjects with type 2 diabetes mellitus (T2DM) and is associated with peripheral neuropathy. However, there are little data regarding vitamin D status in patients with cardiovascular autonomic neuropathy. Our objective was to evaluate the association of cardiovascular autonomic function, 25-hydroxyvitamin D (25[OH]D) insufficiency (i.e., levels <30 ng/mL), and multiple metabolic parameters in subjects with T2DM. We examined 50 individuals with T2DM. Cardiovascular autonomic function (i.e., parasympathetic function) was assessed by RR-variation during deep breathing (i.e., mean circular resultant [MCR] and expiration/inspiration [E/I] ratio). Metabolic parameters included measures of adiposity, glycemic control, insulin resistance, calcium metabolism, and 25(OH)D. Participants with 25(OH)D insufficiency (n = 26) were younger (66 ± 9 vs. 60 ± 10 years, P<.05), more insulin resistant, had a higher body mass index (BMI) and lower adiponectin levels. The MCR (39.5 ± 26.3 vs. 27.6 ± 17.2, P<.01) and E/I ratio (1.21 ± 0.17 vs. 1.15 ± 0.09, P<.01) were lower for those with 25(OH)D insufficiency after controlling for age. A stepwise selection procedure regressing MCR and E/I ratio on a number of metabolic parameters resulted in a model identifying age and 25(OH)D insufficiency as significant determinants for both measures. The interaction of age x 25(OH)D insufficiency was also included (MCR model, R2 = 0.491, P<.001; E/I ratio, R2 = 0.455, P<.001). Neither glycemic control nor other metabolic parameters were selected. Our results suggest that 25(OH)D insufficiency is associated with reduced parasympathetic function, with a stronger association in younger persons with T2DM. Studies are needed to determine if vitamin D supplementation into the sufficient range could prevent or delay the onset of cardiovascular autonomic dysfunction.

Spatial summation of thermal stimuli assessed by a standardized, randomized, single-blinded technique

Background and aimsQuantitative sensory testing of thermal perception (QTT) is a valuable method in clinical and experimental assessment of the function of small nerve fibres. Previous studies have indicated existence of spatial summation for warmth, cool and heat pain stimulation, but study designs and assessment methods have not always been mutually consistent. The aims of this study were, first, to examine spatial summation of QTT by differently sized contact thermodes, and, second, to evaluate if these differences are significant from a clinical and scientific perspective. MethodsSixteen healthy subjects were included. Warmth detection (WDT), cool detection (CDT) and heat pain (HPT) thresholds were assessed in random order, with the stimulation areas of the contact thermodes of 3.0, 6.3 and 12.5cm2, blinded to the subjects. Assessments were made bilaterally at volar part of the distal arm and medial part of the lower leg. Data analyses were by a mixed model with random effect for subject and fixed-effects for the variables, site (arm/leg), thermode area (ln thermode area) and side (dominant/non-dominant), in addition to conventional pairwise non-parametric comparisons. ResultsData from 2 subjects were excluded. In the remaining 14 subjects only 4 subjects were able to identify the correct sequence of thermode sizes. The model demonstrated highly statistical significant relationships regarding main effects: thermode area (P<0.0001) and stimulation site (P<0.0001; except for CDT P=0.011). The only significant interaction was between thermode area*site (P=0.005) for CDT. The study demonstrated in 17 of 18 possible comparisons between thermode size and stimulation site, a significant spatial summation for WDT, CDT and HPT. ConclusionThis randomized, single-blind study of thermal thresholds demonstrated spatial summation and that considerable deviations may occur if values obtained with differing thermode sizes are used uncritically. ImplicationsData from the present study enable interpolation of thermal thresholds with differing thermode sizes, facilitating comparisons across studies.

The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.