Changes In Conduction Velocity Research Articles

Changes in ulnar and median nerve conduction velocity after reverse total shoulder arthroplasty: Correlation with distalization and lateralization

PurposeThe purpose of this study was to assess ulnar and median nerve injury after reverse total shoulder arthroplasty (RSA) by measuring the sensory nerve conduction velocity (SCV). The secondary objective was to evaluate the impact of lateralization and/or distalization on SCV changes. MethodsTwenty consecutive cases were prospectively included and retrospectively reviewed. SCV of the ulnar and median nerves as well as humeral lateralization/distalization quantified by plain radiography were evaluated pre-operatively and at 1 week post-operatively. Changes in SCV were tested using the paired t-test, and correlations between humeral lateralization/distalization and SCV changes were tested using Kendall's rank correlation coefficient and maximal information coefficient (MIC). ResultsThe SCV of the ulnar nerve was delayed from 55.4 ​m/s pre-operatively to 53.0 ​m/s post-operatively (p ​= ​0.021), whereas there was no significant change in the median nerve (p ​= ​0.17). There was a weak to moderate correlation between ulnar nerve SCV delay and lateralization (τ ​= ​−0.38; p ​= ​0.021; MIC ​= ​0.70) but no significant correlation with distalization (p ​= ​0.65; MIC ​= ​0.56). ConclusionsFollowing RSA, a small but significant delay in SCV of the ulnar nerve was observed. A negative correlation was found between lateralization and SCV delay of the ulnar nerve.

Fibrin Glue Acutely Blocks Distal Muscle Contraction after Confirmed Polyethylene Glycol Nerve Fusion: An Animal Study.

Polyethylene glycol (PEG) is a synthetic, biodegradable, and hyperosmotic material promising in the treatment of acute peripheral nerve injuries. Our team set out to investigate the impact of fibrin glue upon PEG fusion in a rat model. Eighteen rats underwent sciatic nerve transection and PEG fusion. Electrophysiologic testing was performed to measure nerve function and distal muscle twitch. Fibrin glue was applied and testing repeated. Due to preliminary findings, fibrin glue was applied to an uncut nerve in five rodents and testing was conducted before and after glue application. Mann-Whitney U tests were used to compare median values between outcome measures. A Shapiro-Wilk test was used to determine normality of data for each comparison, significance set at a P value less than 0.05. PEG fusion was confirmed in 13 nerves with no significant change in amplitude (P = 0.054), latency (P = 0.114), or conduction velocity (P = 0.114). Stimulation of nerves following PEG fusion produced distal muscle contraction in 100% of nerves. Following application of fibrin glue, there was a significant reduction in latency (P = 0.023), amplitude (P < 0.001), and conduction velocity (P = 0.023). Stimulation of the nerve after application of fibrin glue did not produce distal muscle twitch. Five uncut nerves with fibrin glue application blocked distal muscle contraction following stimulation. Our data suggest that fibrin glue alters the nerve's function. The immediate confirmation of PEG fusion via distal muscle twitch is blocked with application fibrin glue in this experimental model. Survival and functional outcome studies are necessary to understand if this has implications on the long-term functional outcomes.

A modelling study to dissect the potential role of voltage-gated ion channels in activity-dependent conduction velocity changes as identified in small fiber neuropathy patients.

Patients with small fiber neuropathy (SFN) suffer from neuropathic pain, which is still a therapeutic problem. Changed activation patterns of mechano-insensitive peripheral nerve fibers (CMi) could cause neuropathic pain. However, there is sparse knowledge about mechanisms leading to CMi dysfunction since it is difficult to dissect specific molecular mechanisms in humans. We used an in-silico model to elucidate molecular causes of CMi dysfunction as observed in single nerve fiber recordings (microneurography) of SFN patients. We analyzed microneurography data from 97 CMi-fibers from healthy individuals and 34 of SFN patients to identify activity-dependent changes in conduction velocity. Using the NEURON environment, we adapted a biophysical realistic preexisting CMi-fiber model with ion channels described by Hodgkin-Huxley dynamics for identifying molecular mechanisms leading to those changes. Via a grid search optimization, we assessed the interplay between different ion channels, Na-K-pump, and resting membrane potential. Changing a single ion channel conductance, Na-K-pump or membrane potential individually is not sufficient to reproduce in-silico CMi-fiber dysfunction of unchanged activity-dependent conduction velocity slowing and quicker normalization of conduction velocity after stimulation as observed in microneurography. We identified the best combination of mechanisms: increased conductance of potassium delayed-rectifier and decreased conductance of Na-K-pump and depolarized membrane potential. When the membrane potential is unchanged, opposite changes in Na-K-pump and ion channels generate the same effect. Our study suggests that not one single mechanism accounts for pain-relevant changes in CMi-fibers, but a combination of mechanisms. A depolarized membrane potential, as previously observed in patients with neuropathic pain, leads to changes in the contribution of ion channels and the Na-K-pump. Thus, when searching for targets for the treatment of neuropathic pain, combinations of several molecules in interplay with the membrane potential should be regarded.

Determinants of electrical propagation and propagation block in Arrhythmogenic Cardiomyopathy

Gap junction and ion channel remodeling occur early in Arrhythmogenic Cardiomyopathy (ACM), but their pathogenic consequences have not been elucidated. Here, we identified the arrhythmogenic substrate, consisting of propagation slowing and conduction block, in ACM models expressing two different desmosomal gene variants. Neonatal rat ventricular myocytes were transduced to express variants in genes encoding desmosomal proteins plakoglobin or plakophilin-2. Studies were performed in engineered cells and anisotropic tissues to quantify changes in conduction velocity, formation of unidirectional propagation, cell–cell electrical coupling, and ion currents. Conduction velocity decreased by 71% and 63% in the two ACM models. SB216763, an inhibitor of glycogen synthase kinase-3 beta, restored conduction velocity to near normal levels. Compared to control, both ACM models showed greater propensity for unidirectional conduction block, which increased further at greater stimulation frequencies. Cell–cell electrical conductance measured in cell pairs was reduced by 86% and 87% in the two ACM models. Computer modeling showed close correspondence between simulated and experimentally determined changes in conduction velocity. The simulation identified that reduced cell–cell electrical coupling was the dominant factor leading to slow conduction, while the combination of reduced cell–cell electrical coupling, reduced sodium current and inward rectifier potassium current explained the development of unidirectional block. Expression of two different ACM variants markedly reduced cell–cell electrical coupling and conduction velocity, and greatly increased the likelihood of developing unidirectional block – both key features of arrhythmogenesis. This study provides the first quantitative analysis of cellular electrophysiological changes leading to the substrate of reentrant arrhythmias in early stage ACM.

Local changes in conduction velocity in the left atrium of atrial fibrillation patients undergoing pulmonary vein isolation

Abstract Background Electro-anatomical maps are standardly used to visualize anatomy and electrophysiological properties of the left atrium (LA) during pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients. Purpose We sought to describe local differences in atrial conduction velocities (CVs), as a proof-of-principle, to study its association with tissue heterogeneity. We hypothesize that the variation and heterogeneity in these velocities throughout the LA carry important prognostic and diagnostic information, reflect the extent of remodeling and, in the future, might discern different subtypes of AF and treatment outcome. Methods We included AF patients who underwent PVI for the first time during 2021-2022. Electro-anatomical maps (EAMs) during sinus rhythm were acquired during the procedure and single data-points were projected on the patient-specific EAM-derived mesh of the LA. Patients were classified as persistent (AF lasting longer than 7 days and usually requiring electrical cardioversion) and paroxysmal (self-terminating AF episodes, lasting shorter than 7 days, mostly shorter than 24 hours) and were followed-up for 6 to 12-months. We determined unipolar voltages, activation times and computed local CVs for these patients. The CVs were normalized for each patients and reported as the median CV for each region containing enough points. Results We included 12 patients: 6 with paroxysmal and 6 with persistent AF. Patients in the paroxysmal group had larger median activation times and median CVs compared to the persistent group. The variability in voltage, activation time and CV was twice as large in the paroxysmal group (Table 1). Figure 1 displays an example of an electro-anatomical reconstruction of the LA of a paroxysmal AF patient showing the local median conduction velocity from an anterior and posterior view (Figure 1A and 1B) and the variance and distribution of median CV (Figure 1C). In this patient, we observed large local CV differences, which might reflect tissue heterogeneity (e.g. fibrosis). Conclusion We provided a proof-of-principle demonstrating that, with the use of conventional electro-anatomical maps, important information on heterogeneity and variance in local CVs can be quantified. We found a large variability in CV within and between patients. This can help discern different AF subtypes and might contribute to understanding different arrhythmogenic substrates and treatment outcome differences.

Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy.

We seek to elucidate the precise nature of mechanical loading that precipitates conduction deficits in a concealed-phase model of arrhythmogenic cardiomyopathy (ACM). ACM is a progressive disorder often resulting from mutations in desmosomal proteins. Exercise has been shown to worsen disease progression and unmask arrhythmia vulnerability, yet the underlying pathomechanisms may depend on the type and intensity of exercise. Because exercise causes myriad changes to multiple inter-dependent hemodynamic parameters, it is difficult to isolate its effects to specific changes in mechanical load. Here, we use engineered heart tissues (EHTs) with iPSC-derived cardiomyocytes expressing R451G desmoplakin, an ACM-linked mutation, which results in a functionally null model of desmoplakin (DSP). We also use a novel bioreactor to independently perturb tissue strain at different time points during the cardiac cycle. We culture EHTs under three strain regimes: normal physiological shortening; increased diastolic stretch, simulating high preload; and isometric culture, simulating high afterload. DSPR451G EHTs that have been cultured isometrically undergo adaptation, with no change in action potential parameters, conduction velocity, or contractile function, a phenotype confirmed by global proteomic analysis. However, when DSPR451G EHTs are subjected to increased diastolic stretch, they exhibit concomitant reductions in conduction velocity and the expression of connexin-43. These effects are rescued by inhibition of both lysosome activity and ERK signaling. Our results indicate that the response of DSPR451G EHTs to mechanical stimuli depends on the strain and the timing of the applied stimulus, with increased diastolic stretch unmasking conduction deficits in a concealed-phase model of ACM.

Comparison of nerve conduction velocities of lower extremities between football players and controls

This study aimed to compare neuronal function in the lower limbs of elite footballers and an age-matched control group. Conduction velocity, response latency and amplitude following electrical stimulation were investigated. Thirty male football players and 30 untrained males comprised the subject and control groups, respectively. We showed that professional football players have significantly slower sural nerve conduction velocity than untrained controls (p&lt;0.05). Although we found no signs of neuropathy, mild changes in nerve conduction velocity were evident in the sural nerve of the players. Motor conduction velocity of tibial nerve was also significantly prolonged in this group when comparing dominant and non-dominant extremities (p&lt;0.05). The tibial nerve muscle action potential amplitude was lower in the players’ dominant limbs compared with the controls (p&lt;0.05). We found no statistical difference in motor conduction velocities, distal latencies and amplitudes of the common peroneal nerve when comparing players and controls in both dominant and non-dominant limbs (p&gt;0.05). Our results showed abnormalities of function in the sural and tibial nerves in football players compared with untrained controls, which may indicate early signs of neuropathy.

Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

PO-02-245 THE IMPACT OF PULSED FIELD ABLATION ON CONDUCTION VELOCITY OVER TIME

Pulsed field ablation (PFA) is an emerging technology that has both reversible and irreversible effects. However, the time course of reversibility of atrial conduction velocity after PFA has not been well characterized. To determine changes in conduction velocity over time after PFA Nine pigs were studied. The Medtronic PVAC GOLD catheter was placed in the superior vena cava (SVC), right atrium (RA), left atrial appendage (LAA) and left pulmonary vein (LPV). One and four trains at 1000 V and 1500V were delivered at these four sites in a random fashion. Activation mapping was done at baseline and 10-20 minute intervals post ablation using ESI mapping system. Conduction velocity was obtained between a site of entry and exit identified by wavefront propagation in the scar at the 5-minute time point post ablation. Regional conduction slowing was defined as <31 cm/s and recovery was studied at 120 minutes time point. Recovery was defined as 50% recovery of baseline conduction velocity compared to the 5 minutes time point. The baseline conduction velocity was >100 cm/s across all experimental conditions. At 1000V x 1 and 1000V x 4 application, the average velocity was 21[HDM1] ±9 cm/s and 44 ±30 cm/s respectively. At 1500V x 1 and 1500V x 4 application, the average velocity was 27 ±16 cm/s and 33 ±15 cm/s respectively. The lowest conduction velocity occurred at the 5-minute time point (31 cm/s (5-100 cm/s). At 1000V x 1 and 1000V x 4 application, 2/8 and 2/8 animals recovered conduction at 120 min respectively. At 1500V x 1 and 1500V x 4, 1/8 animals and 0/8 animals recovered conduction at 120 min respectively. Median time to conduction recovery was 72 min (25-160 min). (Figure 1) Recovery of conduction is observed post PFA, more often with lower voltage ablations in this porcine model. The time course of conduction velocity recovery exceeds the standard clinical post ablation wait time suggesting that retesting for conduction block 20 min post ablation may be of limited value.

Oligodendrocyte-mediated myelin plasticity and its role in neural synchronization.

Temporal synchrony of signals arriving from different neurons or brain regions is essential for proper neural processing. Nevertheless, it is not well understood how such synchrony is achieved and maintained in a complex network of time-delayed neural interactions. Myelin plasticity, accomplished by oligodendrocytes (OLs), has been suggested as an efficient mechanism for controlling timing in brain communications through adaptive changes of axonal conduction velocity and consequently conduction time delays, or latencies; however, local rules and feedback mechanisms that OLs use to achieve synchronization are not known. We propose a mathematical model of oligodendrocyte-mediated myelin plasticity (OMP) in which OLs play an active role in providing such feedback. This is achieved without using arrival times at the synapse or modulatory signaling from astrocytes; instead, it relies on the presence of global and transient OL responses to local action potentials in the axons they myelinate. While inspired by OL morphology, we provide the theoretical underpinnings that motivated the model and explore its performance for a wide range of its parameters. Our results indicate that when the characteristic time of OL's transient intracellular responses to neural spikes is between 10 and 40 ms and the firing rates in individual axons are relatively low (10 Hz), the OMP model efficiently synchronizes correlated and time-locked signals while latencies in axons carrying independent signals are unaffected. This suggests a novel form of selective synchronization in the CNS in which oligodendrocytes play an active role by modulating the conduction delays of correlated spike trains as they traverse to their targets.

Transcarpal Motor Conduction Velocity: Repeatability and Application in Carpal Tunnel Syndrome.

Conduction velocity of the short segment of the median motor nerve, across wrist (transcarpal motor conduction velocity (TCMCV)), has been used to increase diagnostic yield in carpal tunnel syndrome (CTS). However, repeatability of this parameter has not been studied till date. It has not been used as an indicator of response to treatment. Using surface stimulation techniques, it is difficult to localize the sites of stimulation of transcarpal segment of median nerve in palm. As a result, small errors in measurements of TCMCV can be magnified and variability of TCMCV may occur on successive measurements. Despite this possible variation, TCMCV can be a useful tool for assessing response to therapy, if its repeatability is assessed and a cut-off value determined for a significant change in nerve conduction velocity. In this study, it was determined whether TCMCV is repeatable. If found to be repeatable, we show a method to determine the cut-off value of the change in this parameter for it to be considered significant. Difference between values of TCMCV on successive measurements was obtained in hands of 26 controls. Repeatability of this parameter was determined in this control population following criteria of British Standards Institution. In 19 patients of CTS, treated with intracarpal steroid injection, pre-treatment and post-treatment values of TCMCV, and of symptom severity scale (SSS) and functional status scale (FSS), were obtained at 1, 2, and 3 months after treatment. Repeat measurements of TCMCV were made in each hand of all controls. After applying criteria of British Standards Institution, to such recordings, TCMCV was found to be repeatable and the cut-off value for significant change determined. According to this cut-off value, 4 patients of CTS showed improvement in TCMCV, with consistent improvement in SSS and FSS. Change in TCMCV corroborated qualitatively with changes in SSS and FSS. Repeatability of TCMCV can be assessed by criteria of British Standards Institution and a cut-off value determined to use it as an indicator of response to treatment in CTS.

Chronic Kidney Disease Induces Proarrhythmic Remodeling.

Patients with chronic kidney disease (CKD) are at increased risk of developing cardiac arrhythmogenesis and sudden cardiac death; however, the basis for this association is incompletely known. Here, using murine models of CKD, we examined interactions between kidney disease progression and structural, electrophysiological, and molecular cardiac remodeling. C57BL/6 mice with adenine supplemented in their diet developed progressive CKD. Electrocardiographically, CKD mice developed significant QT prolongation and episodes of bradycardia. Optical mapping of isolated-perfused hearts using voltage-sensitive dyes revealed significant prolongation of action potential duration with no change in epicardial conduction velocity. Patch-clamp studies of isolated ventricular cardiomyocytes revealed changes in sodium and potassium currents consistent with action potential duration prolongation. Global transcriptional profiling identified dysregulated expression of cellular stress response proteins RBM3 (RNA-binding motif protein 3) and CIRP (cold-inducible RNA-binding protein) that may underlay the ion channel remodeling. Unexpectedly, we found that female sex is a protective factor in the progression of CKD and its cardiac sequelae. Our data provide novel insights into the association between CKD and pathologic proarrhythmic cardiac remodeling. Cardiac cellular stress response pathways represent potential targets for pharmacologic intervention for CKD-induced heart rhythm disorders.

Schwann cell stimulation induces functional and structural changes in peripheral nerves.

Signal propagation is the essential function of nerves. Lysophosphatidic acid 18:1 (LPA) allows the selective stimulation of calcium signaling in Schwann cells but not neurons. Here, the time course of slowing and amplitude reduction on compound action potentials due to LPA exposure was observed in myelinated and unmyelinated fibers of the mouse, indicating a clear change of axonal function. Teased nerve fiber imaging showed that Schwann cell activation is also present in axon-attached Schwann cells in freshly isolated peripheral rat nerves. The LPA receptor 1 was primarily localized at the cell extensions in isolated rat Schwann cells, suggesting a role in cell migration. Structural investigation of rat C-fibers demonstrated that LPA leads to an evagination of the axons from their Schwann cells. In A-fibers, the nodes of Ranvier appeared unchanged, but the Schmidt-Lanterman incisures were shortened and myelination reduced. The latter might increase leak current, reducing the potential spread to the next node of Ranvier and explain the changes in conduction velocity. The observed structural changes provide a plausible explanation for the functional changes in myelinated and unmyelinated axons of peripheral nerves and the reported sensory sensations such as itch and pain.

Subclinical peripheral neuropathy is common in neuronal intranuclear inclusion disease with dominant encephalopathy.

Neuronal intranuclear inclusion disease (NIID) is associated with CGG repeat expansion in the NOTCH2NLC gene. Although pure or dominant peripheral neuropathy has been described as a subtype of NIID in a few patients, most NIID patients predominantly show involvements of the central nervous system (CNS). It is necessary to further explore whether these patients have subclinical peripheral neuropathy. Twenty-eight NIID patients, clinically characterized by CNS-dominant involvements, were recruited from two tertiary hospitals. Standard nerve conduction studies were performed in all patients. Skin and sural nerve biopsies were performed in 28 and 15 patients, respectively. Repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to screen the CGG repeat expansion in NOTCH2NLC. All 28 patients can be diagnosed with NIID based on skin pathological and genetic changes. All patients predominantly showed CNS symptoms mainly characterized by episodic encephalopathy and cognitive impairments, but no clinical symptoms of peripheral neuropathy could be observed initially. Electrophysiological abnormalities were found in 96.4% (27/28) of these patients, indicating that subclinical peripheral neuropathy is common in NIID patients with CNS-dominant type. Electrophysiological and neuropathological studies revealed that demyelinating degeneration was the main pathological pattern in these patients, although mild axonal degeneration was also observed in some patients. No significant association between CGG repeat size and the change of nerve conduction velocity was found in these patients. This study demonstrated that most patients with CNS-dominant NIID had subclinical peripheral neuropathy. Electrophysiological examination should be the routinely diagnostic workflow for every NIID patient.

Electrophysiological and functional signs of Guillain–Barré syndrome predicted by a multiscale neuromuscular computational model

Objective. The diagnosis of nerve disorders in humans has relied heavily on the measurement of electrical signals from nerves or muscles in response to electrical stimuli applied at appropriate locations on the body surface. The present study investigated the demyelinating subtype of Guillain–Barré syndrome using multiscale computational model simulations to verify how demyelination of peripheral axons may affect plantar flexion torque as well as the ongoing electromyogram (EMG) during voluntary isometric or isotonic contractions. Approach. Changes in axonal conduction velocities, mimicking those found in patients with the disease at different stages, were imposed on a multiscale computational neuromusculoskeletal model to simulate subjects performing unipodal plantar flexion force and position tasks. Main results. The simulated results indicated changes in the torque signal during the early phase of the disease while performing isotonic tasks, as well as in torque variability after partial conduction block while performing both isometric and isotonic tasks. Our results also indicated changes in the root mean square values and in the power spectrum of the soleus EMG signal as well as changes in the synchronization index computed from the firing times of the active motor units. All these quantitative changes in functional indicators suggest that the adoption of such additional measurements, such as torques and ongoing EMG, could be used with advantage in the diagnosis and be relevant in providing extra information for the neurologist about the level of the disease. Significance. Our findings enrich the knowledge of the possible ways demyelination affects force generation and position control during plantarflexion. Moreover, this work extends computational neuroscience to computational neurology and shows the potential of biologically compatible neuromuscular computational models in providing relevant quantitative signs that may be useful for diagnosis in the clinic, complementing the tools traditionally used in neurological electrodiagnosis.

Xiaoketongbi Formula vs pregabalin for painful diabetic neuropathy: A single-center, randomized, single-blind, double-dummy, and parallel controlled clinical trial.

BackgroundWe assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN).MethodsPatients with PDN (n = 68) were included in a single‐center, randomized, single‐blind, double‐dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI‐DPN). Secondary outcomes evaluated included the reduction of BPI‐DPN >50%, changes in the numeric rating scale‐11 (NRS‐11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events.ResultsAfter 10 weeks of treatment, the BPI‐DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group (P s < 0.001), respectively. The difference in the absolute change in BPI‐DPN score between both groups was −1.79 (95% CI: −9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI‐DPN reduction >50% (p = 0.038), respectively. There were no significant differences between groups in NRS‐11 and DSID (P s > 0.05). A significantly greater number of patients in the XF group felt “significantly improved” or “improved” than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group −2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group.ConclusionsXF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.

TWO-YEAR RESPONSES OF HEART RATE AND HEART RATE VARIABILITY TO FIRST OCCUPATIONAL LEAD EXPOSURE

Objective: Because of the falling lead exposure, the literature relating autonomous nervous function to blood lead has limited relevance. Design and method: In the longitudinal Study for Promotion of Health in Recycling Lead (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02243904), we recorded the 2-year responses of heart rate, heart rate variability (Cardiax, International Medical Equipment Developing, Budapest, Hungary), and median nerve conduction velocity (Brevio, NeuMed, West Trenton, NJ), a routine test in occupational medicine, to first lead exposure in 195 newly hired workers (91.3% men; mean age, 27.8 years). High- and low-frequency heart rate variability power and orthostatic heart rate variability responses were derived from 5-minute eletrocardiograms in the supine and standing positions by Fourier transform and autoregression. Blood lead was determined by inductively coupled plasma mass spectrometry. Results: From baseline to follow-up, blood lead increased from 4.22 to 14.1 ug/dL and supine/standing HR from 63.6/75.5 to 67.1/78.8 beats per minute. In analyses stratified by fourths of blood lead changes, trends in heart rate and Fourier/autoregressive heart rate variability did not reveal a dose-response curve (0.074&lt; = P&lt; = 0.98). In multivariable-adjusted mixed models, heart rate, Fourier/autoregressive heart rate variability, and nerve conduction velocity changes were unrelated to blood lead except for a weak inverse association between supine heart rate and blood lead changes (-0.55%; P = 0.029). The expected associations between heart rate variability and heart rate changes were preserved with no differences at baseline/follow-up. Analyses ichotomised by baseline median blood lead or cumulative blood lead index (4.30 ug/dL or 32.1 ug/dL × year) suggested an heart rate variability increase versus decrease in the low versus high baseline exposure group. Conclusions: Thus, a &gt; 3-fold blood lead increment did not affect autonomous neural function as captured by heart rate variability.

Low-level vagus nerve stimulation during cardiac surgery: smart neuromodulation

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): CVON-AFFIP Dutch Heart Foundation Objective The goal of this study is to unravel the anti-arrhythmogenic effects of low-level vagus nerve stimulation (LL-VNS) by performing high-resolution and high-density epicardial mapping studies before and after transcutaneous LL-VNS in patients undergoing primary cardiac surgery. Background Vagus nerve stimulation has pro-arrhythmogenic and anti-arrhythmogenic properties. LL-VNS has been proven to reduce AF incidence and burden, but the anti-arrhythmogenic effect of LL-VNS remains largely unexplored thereby hampering clinical implementation and optimal patient selection. Methods 10 patients (90% male, age 75±6 years) undergoing coronary artery bypass surgery (CABG) were included in this study. Epicardial sinus rhythm mapping of the right atrium and Bachmann’s bundle (BB) was performed prior, after acute- and chronic transcutaneous LL-VNS. Results LL-VNS did not result in any significant changes in potential fractionation, conduction block, conduction velocity or voltage. Potential duration prolonged from 37.5 [31.0-56.0] ms to 48 [36.0-50.0] ms during acute (p=0.002) and 52.5 [45.8-61.0] ms during chronic LL-VNS (p=0.007). Conclusions This is the first epicardial mapping study in humans investigating the effect of LL-VNS on atrial conduction. Compared to no LL-VNS, acute and chronic LL-VNS prolonged potential duration significantly.

Recording Saltatory Conduction Along Sensory Axons Using a High-Density Microelectrode Array.

Myelinated fibers are specialized neurological structures used for conducting action potentials quickly and reliably, thus assisting neural functions. Although demyelination leads to serious functional impairments, little is known the relationship between myelin structural change and increase in conduction velocity during myelination and demyelination processes. There are no appropriate methods for the long-term evaluation of spatial characteristics of saltatory conduction along myelinated axons. Herein, we aimed to detect saltatory conduction from the peripheral nervous system neurons using a high-density microelectrode array. Rat sensory neurons and intrinsic Schwann cells were cultured. Immunofluorescence and ultrastructure examination showed that the myelinating Schwann cells appeared at 1 month, and compact myelin was formed by 10 weeks in vitro. Activity of rat sensory neurons was evoked with optogenetic stimulation, and axon conduction was detected with high-density microelectrode arrays. Some conductions included high-speed segments with low signal amplitude. The same segment could be detected with electrical recording and immunofluorescent imaging for a myelin-related protein. The spatiotemporal analysis showed that some segments show a velocity of more than 2 m/s and that ends of the segments show a higher electrical sink, suggesting that saltatory conduction occurred in myelinated axons. Moreover, mathematical modeling supported that the recorded signal was in the appropriate range for axon and electrode sizes. Overall, our method could be a feasible tool for evaluating spatial characteristics of axon conduction including saltatory conduction, which is applicable for studying demyelination and remyelination.

Excitability properties of mouse and human skeletal muscle fibres compared by muscle velocity recovery cycles

Mouse models of skeletal muscle channelopathies are not phenocopies of human disease. In some cases (e.g. Myotonia Congenita) the phenotype is much more severe, whilst in others (e.g. Hypokalaemic periodic paralysis) rodent physiology is protective. This suggests a species’ difference in muscle excitability properties. In humans these can be measured indirectly by the post-impulse changes in conduction velocity, using Muscle Velocity Recovery Cycles (MVRCs). We performed MVRCs in mice and compared their muscle excitability properties with humans. Mouse Tibialis Anterior MVRCs (n = 70) have only one phase of supernormality (increased conduction velocity), which is smaller in magnitude (p = 9 × 10−21), and shorter in duration (p = 3 × 10−24) than human (n = 26). This abbreviated supernormality is followed by a period of late subnormality (reduced velocity) in mice, which overlaps in time with the late supernormality seen in human MVRCs. The period of late subnormality suggests increased t-tubule Na+/K+-pump activity. The subnormal phase in mice was converted to supernormality by blocking ClC-1 chloride channels, suggesting relatively higher chloride conductance in skeletal muscle. Our findings help explain discrepancies in phenotype between mice and humans with skeletal muscle channelopathies and potentially other neuromuscular disorders. MVRCs are a valuable new tool to compare in vivo muscle membrane properties between species and will allow further dissection of the molecular mechanisms regulating muscle excitability.