Action Potential Amplitude Research Articles

Diosmin and Hesperidin Have a Protective Effect in Diabetic Neuropathy via the FGF21 and Galectin-3 Pathway.

Background and Objectives: This study aimed to investigate the protective effect of diosmin and hesperidin in diabetic neuropathy using a rat model, focusing on their impact on nerve regeneration through the fibroblast growth factor 21 (FGF21) and galectin-3 (gal3) pathway. Materials and Methods: Forty adult male Wistar rats were used in this study. Diabetes was induced using streptozotocin (STZ), and the rats were divided into control, diabetes and saline-treated, diabetes and diosmin + hesperidin (150 mg/kg) treated, and diabetes and diosmin + hesperidin (300 mg/kg) treated groups. Electromyography (EMG) and inclined plane testing were performed to assess nerve function and motor performance. Sciatic nerve sections were examined histopathologically. Plasma levels of FGF21, galectin-3, and malondialdehyde (MDA) were measured as markers of oxidative stress and inflammation. Results: Diabetic rats treated with saline displayed reduced nerve conduction parameters and impaired motor performance compared to controls. Treatment with diosmin and hesperidin significantly improved compound muscle action potential (CMAP) amplitude, distal latency, and motor performance in a dose-dependent manner. Histopathological examination revealed decreased perineural thickness in treated groups. Additionally, treatment with diosmin and hesperidin resulted in increased plasma FGF21 levels and reduced plasma levels of galectin-3 and MDA, indicating decreased oxidative stress and inflammation. Conclusions: Diosmin and hesperidin exhibited protective effects in diabetic neuropathy by promoting nerve regeneration, enhancing nerve conduction, and improving motor performance. These effects were associated with modulation of the FGF21 and galectin-3 pathway. These findings suggest that diosmin and hesperidin may hold potential as adjunctive therapies for diabetic neuropathy.

The long-term impact of rehabilitation in upper limb plexopathies

The main objective of the research consists in providing evidence that a long-term rehabilitation protocol is favorable for the patient. In adult brachial plexus (BP) palsies, after several surgical attempts, the lack of results in the upper limb’s functionality leads to less compliance to rehabilitation therapy. The upper limb’s functionality of 22 patients with posttraumatic operated chronic BP paresis (either on the right or left, regardless the dominant limb) was assessed retrospectively. The patients were evaluated regarding MRC scaling, dynamometric tests and electroneuromyographic examination. All patients have gone through at least one rehabilitation interval (10 days) after an initial evaluation, and were evaluated again, by same methods, at a second session, at least 6 months later, but no more than one year.. Mild and inconstant improvements were obtained in a total of 9 patients, especially in better dynamometric results and improved amplitudes of motor and sensory action potentials. The electrodiagnosis correlates with dynamometric parameters (muscle strength) and slight amelioration of the motor deficit. Given the small sample size as a limitation, as well as no standardized therapeutic protocol, it should be noted that the 9 patients were the only ones who either attended more than one interval or did more procedures as frequency in time (more often meaning 3 times weekly for 6 months, in 6 patients). Although the most frequent procedures were neuromuscular electrical stimulation (NMES) and proprioceptive neuromuscular facilitation (PNF), the results suggest that regardless of the techniques, the more active patients had better results. Proving the need for long-term rehabilitation, even contrary to the less visible results, can be the trigger point for future research and therapy strategies, as the results suggest central mechanisms involved, adding the cortical ongoing plasticity into the equation.

Inhibition of KIF5b-mediated Nav1.8 transport by ropivacaine contributes to axonal regeneration following sciatic nerve injury in rats

Peripheral nerve injury (PNI), typically caused by traumatic accidents or medical events, is currently one of the most common diseases that leads to limb disability. After PNI, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated at the lesion site. Our earlier study suggested that ropivacaine promotes axon regrowth by regulating Nav1.8-mediated macrophage signaling. Nevertheless, the mechanism of ropivacaine in regulation of Nav1.8 expression remains incompletely understood. Kinesin family 5b (KIF5b) was reported to mediate the Nav1.8 axonal transport from dorsal root ganglia (DRGs) to lesion site. Herein, we investigated whether ropivacaine promotes axon regeneration through inhibition of KIF5b-mediated Nav1.8 transport. Reduced levels of KIF5b and Nav1.8 in DRGs coincide with their increase at the lesion site. Nav1.8 mRNA was significantly increased at the lesion site but not in DRGs. Surprisingly, ropivacaine reversed the alterations of Nav1.8 and KIF5b protein expression without affecting Nav1.8 mRNA level. Due to KIF5b overexpression in DRGs, Nav1.8 protein level was significantly decreased in DRGs and increased at the lesion site. We also found KIF5b overexpression significantly impaired behavioral functions, reduced the recovery index of compound muscle action potential (CMAP) amplitude, inhibited axonal regrowth, slowed M1 macrophage infiltration and shift to M2 phenotype, and delayed myelin debris clearance. Notably, all aforementioned results caused by KIF5b overexpression were alleviated by ropivacaine. Furthermore, we demonstrated that inhibition of Nav1.8 transport by A-803467 produced mitigating effects on the impairment of regenerative capacity induced by KIF5b overexpression similar to ropivacaine. These results suggest that ropivacaine promotes axonal regeneration at least partially by inhibiting KIF5b-mediated Nav1.8 forward transport.

Track-A-Worm 2.0: A Software Suite for Quantifying Properties of C. elegans Locomotion, Bending, Sleep, and Action Potentials.

Comparative analyses of locomotor behavior and cellular electrical properties between wild-type and mutant C. elegans are crucial for exploring the gene basis of behaviors and the underlying cellular mechanisms. Although many tools have been developed by research labs and companies, their application is often hindered by implementation difficulties or lack of features specifically suited for C. elegans. Track-A-Worm 2.0 addresses these challenges with three key components: WormTracker, SleepTracker, and Action Potential (AP) Analyzer. WormTracker accurately quantifies a comprehensive set of locomotor and body bending metrics, reliably distinguish between the ventral and dorsal sides, continuously tracks the animal using a motorized stage, and seamlessly integrates external devices, such as a light source for optogenetic stimulation. SleepTracker detects and quantifies sleep-like behavior in freely moving animals. AP Analyzer assesses the resting membrane potential, afterhyperpolarization level, and various AP properties, including threshold, amplitude, mid-peak width, rise and decay times, and maximum and minimum slopes. Importantly, it addresses the challenge of AP threshold quantification posed by the absence of a pre-upstroke inflection point. Track-A-Worm 2.0 is potentially a valuable tool for many C. elegans research labs due to its powerful functionality and ease of implementation.

Electrophysiological properties of neurons in the visual sensory layers of the superior colliculus in early postnatal mice

Objective: To investigate the action potential firing patterns of neurons in the visual sensory layers of the superior colliculus in early postnatal mice and the electrophysiological characteristics of neurons with different firing patterns. Methods: This experimental study utilized whole-cell patch-clamp recordings performed on neurons in the visual sensory layers of the superior colliculus using brain slices from 57 healthy male C57BL/6J mice aged 14 to 20 days (weighing 5.0 to 8.9 g) using brain slices. In current-clamp mode, action potential characteristics were analyzed based on the first action potential generated by depolarizing current, and the firing patterns of neurons were recorded using step depolarizing currents. Neuronal firing patterns were analyzed using hierarchical clustering, and the active electrical properties of neurons with different firing patterns were compared. Results: A total of 135 neurons from the visual sensory layers of the superior colliculus were successfully recorded. Cluster analysis of the neuronal firing patterns identified three types of firing patterns: tonic firing (97, 72%), phasic firing (26, 19%), and single firing (12, 9%). The number of action potentials for each firing pattern was 13.30±7.38, 3.73±3.61, and 0.83±0.39, respectively, with significant differences (P<0.001). There was no significant difference in the membrane potential response to step currents among the three firing pattern types (P>0.05). The action potential amplitudes were (60.45±12.22), (53.67±13.20), and (44.04± 12.92) mV, and the afterhyperpolarization amplitudes were (13.45±13.79), (12.02±13.11), and (20.75±2.85) mV, respectively. The maximum rising slopes were (171.29±77.46), (130.14±61.83), and (78.89±37.08) V/s, and the maximum falling slopes were (-76.33±33.61), (-68.17±31.65), and (-47.97±13.92) V/s, respectively, with all differences being statistically significant (all P<0.05). There were no significant differences in the resting membrane potential, action potential threshold, half-width, and afterhyperpolarization duration among the three firing pattern types (all P>0.05). Conclusions: In the early postnatal mice, neurons in the visual sensory layers of the superior colliculus exhibit three distinct firing patterns: tonic, phasic, and single firing. These firing pattern types show significant differences in action potential amplitude, afterhyperpolarization amplitude, maximum rising slopes, and maximum falling slopes.

Fluorescein Angiography for Monitoring Neural Blood Flow in Chronic Nerve Compression Neuropathy: Experimental Animal Models and Preliminary Clinical Observations.

Pathologies associated with neural blood disturbance have been reported in patients with chronic nerve compression (CNC) neuropathy. Fluorescein angiography (FAG) and laser Doppler flowmetry (LDF) are effective for real-time peripheral nerve blood flow assessment. However, their reliability in severe neuropathy models in large animals or clinical conditions remains unclear. Initially, we aim to apply FAG to two different CNC animal models and evaluate their characteristics in comparison with those of LDF. In FAG, we quantified the peak luminance at the compression site following fluorescein injection. Then, we positioned the LDF probe at the center of the compression site and recorded the blood flow. Subsequently, we analyzed whether the FAG characteristics obtained in this animal experiment were consistent with those of clinical studies in patients with severe carpal tunnel syndrome (CTS). In the CNC rat model, FAG and LDF effectively monitored reduced neural blood flow over time. We observed significant blood flow reduction using both techniques in a newly developed severe CNC rabbit model. Notably, FAG correlated strongly with the compound muscle action potential (CMAP) amplitude in electrodiagnostic findings, unlike LDF. As a next step, we performed FAG after open carpal tunnel release in clinical cases of CTS. FAG correlated significantly with preoperative CMAP amplitude. This indicates FAG's importance for assessing nerve blood flow during surgery, potentially improving diagnostic accuracy and surgical outcomes.

Sensory dysfunction in SMA type 2 and 3 - adaptive mechanism or concomitant target of damage?

BackgroundThe motor neuron survival protein performs numerous cellular functions; hence, spinal muscular atrophy (SMA) is considered to be a multi-organ disease with possible sensory system damage. The controversy surrounding the presence of sensory disturbances, prompted us to conduct standard electrophysiological studies and assess the sensory thresholds for different modalities in adults with SMA types 2 and 3. The study group consisted of 44 adult SMA patients (types 2 and 3). All patients underwent neurological examination using the Hammersmith Functional Motor Scale – Expanded (HFMSE). Standard sensory electrophysiological studies in the ulnar nerve and the estimation of vibratory, temperature, and warm- and cold-induced pain thresholds with temperature dispersion assessment were performed using quantitative sensory testing (QST).ResultsThe most repeatable result was the high amplitude of the sensory nerve action potentials (SNAP) in SMA patients compared to controls. This was higher in type 2 patients compared to type 3a and 3b patients and patients with low HFSME scores. Patients with SMA, especially type 3b presented a longer sensory latency and slower conduction velocity than did controls. Cold pain threshold was higher and warm dispersion larger in SMA. The vibratory limit was higher in patients with high HFSME scores.ConclusionsA high SNAP amplitude suggests sensory fibre hyperactivity, which may be based on overactivation of metabolic pathways as an adaptive mechanism in response to SMN protein deficiency with additionally coexisting small C- and A-delta fibre damage. SMA patients seem to have a concomitant, mild demyelinating process present at the early SMA stage.

Long-term impact of nusinersen on motor and electrophysiological outcomes in adolescent and adult spinal muscular atrophy: insights from a multicenter retrospective study.

5q spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease. We aimed to assess the effects of nusinersen on motor function and electrophysiological parameters in adolescent and adult patients with 5q SMA. Patients with genetically confirmed 5q SMA were eligible for inclusion, and clinical data were collected at baseline (V1), 63days (V4), 180days (V5), and 300days (V6). The efficacy of nusinersen was monitored by encompassing clinical assessments, including the Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 6-Minute Walk Test (6MWT), and percent-predicted Forced Vital Capacity in sitting position (FVC%) and Compound Muscle Action Potential (CMAP) amplitude. The patients were divided into "sitter" and "walker" subgroups according to motor function status. 54 patients were screened, divided into "sitter" (N = 22) and "walker" (N = 32), with the mean age at baseline of 27.03years (range 13-53years). The HFMSE in the walker subgroup increased significantly from baseline to V4 (mean change +2.32-point, P = 0.004), V5 (+3.09, P = 0.004) and V6 (+4.21, P = 0.005). The patients in both the sitter and walker subgroup had no significant changes in mean RULM between V1 and the following time points. Significant increases in CMAP amplitudes were observed in both upper and lower limbs after treatment. Also, patients with RULM ≥ 36 points showed significant CMAP improvements. Our analysis predicted that patients with CMAP amplitudes of trapezius ≥ 1.76mV were more likely to achieve significant motor function improvements. Nusinersen effectively improves motor function and electrophysiological data in adolescent and adult patients with SMA. This is the first report on the CMAP amplitude changes in the trapezius after treatment in patients with SMA. The CMAP values effectively compensate for the ceiling effect observed in the RULM, suggesting that CMAP could serve as an additional biomarker for evaluating treatment efficacy.

Abstract P436: Prorenin Increases the Firing Activity of Hypothalamic Arcuate Nucleus AgRP Neurons

The arcuate nucleus of the hypothalamus (ARC) serves as a key regulator of the cardiovascular and sympathetic regulating center. While neurons in the ARC expressing agouti-related peptide (AgRP) are implicated in the regulation of energy- and glucose homeostasis, our recent findings show that acute chemogenic activation of ARC AgRP neurons reduces blood pressure (BP), whereas inhibition of these neurons has the opposite effect. Together, these observations indicate ARC AgRP neuronal activity as a determinant of basal BP and suggest that tonic activity of these neurons may be required to maintain BP in the normal range. Importantly, most AgRP neurons express the (pro)renin receptor (PRR), a pivotal component of the brain renin-angiotensin system critical for BP regulation. Accordingly, we hypothesized that prorenin may regulate AgRP neuron activity through PRR, and thereby contributing to the autonomic regulation of BP. This study employed whole-cell patch clamp methodology in brain slices of ARC to investigate the effect of prorenin on AgRP neuron firing activity and understand mechanisms. Male and female mice expressing tdTomato in the AgRP neurons were used. Prorenin (2.5 nM) depolarized the resting membrane potential (-41.9 ± 8.7 mV vs. -47.2 ± 7.8 mV, P &lt; 0.001) and increased the frequency of action potential (AP) (2.3 ± 1.3 Hz vs. 1.2 ± 0.8 Hz, P &lt; 0.001) compared with the control (artificial cerebrospinal fluid (aCSF), n=10 neurons from 7mice). Analysis of AP waveforms revealed that prorenin decreased the amplitude of AP (61.0 ± 14.4 mV vs. 70.2 ± 14.3 mV, P &lt; 0.001) and threshold potential (-31.8 ± 6.0 mV vs. -35.5 ± 4.8 mV, P &lt; 0.001), and increased the rise time (2.3 ± 0.7 ms vs. 1.9 ± 0.6 ms, P &lt; 0.001), decay time (2.6 ± 1.1 ms vs. 2.0 ± 0.9 ms, P &lt; 0.01) and half-width (2.2 ± 0.7 ms vs. 1.8 ± 0.6 ms, P &lt;0.01) compared with the control. These changes suggest that alterations in the intrinsic conductance underlying the AP waveform likely coincide with the observed decrease in resting membrane potentials, while the ion channels involved remained to be determined. In summary, prorenin increases the firing activity of the ARC AgRP neurons by depolarizing the resting membrane potential, implicating that activation of PRR in the ARC AgRP neurons may reduce BP and protect against hypertension development.

The importance of medial plantar nerve conduction study in detectıon of polyneuropathy in inflammatory bowel disease

Background &amp; Objective: Peripheral neuropathy is the most frequent neurologic complication of inflammatory bowel disease (IBD). We aimed to evaluate the clinical utility of medial plantar nerve conduction study (NCS) in the detection of distal sensory polyneuropathy in IBD patients. Methods: The study was performed with 21 Crohn’s disease (Group 1) patients, 24 Ulcerative Colitis (Group 2) patients without clinical peripheral neuropathy and 28 healthy participants (Group 3). Each patient group underwent electrophysiological conduction studies. The findings were analyzed statistically. Results: Abnormal medial plantar nerve conduction was present on both sides in 11 (24.4 %) patients with IBD; 5 (11.1 %) patients had low sural nerve amplitude, and 5 (11.1 %) had low superficial peroneal nerve amplitude bilaterally. There were significant differences between the IBD groups (Group 1 and 2) and Group 3 in the mean sensory nerve action potential amplitude of the right medial plantar nerve (p&lt;0.024), and in the mean sensory nerve action potential amplitude of the left medial plantar nerve (p&lt;0.025). The polyneuropathy pattern was mostly of the sensory axonal type in patients with IBD. Conclusions: These electrophysiologic findings indicate that peripheral neuropathy is more prevalent in IBD. In IBD patients the amplitudes of the medial plantar nerve were abnormal more than in the sural and superficial peroneal nerves.

Motor unit number index in Bell's palsy: A potential electrophysiological biomarker for early evaluation.

Reliable, noninvasive early diagnostics of neuromuscular function in Bell's palsy, which causes facial paralysis and reduced quality of life, remain to be established. Here, we aimed to evaluate the utility of the motor unit number index (MUNIX) for the quantitative electrophysiological assessment of early-stage Bell's palsy, its correlation with clinical assessments, changes following treatment, and association with clinical prognosis. MUNIX measures were recorded from the bilateral zygomaticus, orbicularis oculi, and orbicularis oris muscles of 10 healthy individuals and 64 patients with Bell's palsy. The patients were assessed by two specialist neurologists using the House-Brackmann and Sunnybrook Facial Grading Systems. Repeat assessments were performed on 20 patients with Bell's palsy who received treatment. Additionally, the 64 patients were reassessed using clinical scales after a 1-month interval. The MUNIX values of the main affected muscles on the affected side were lower than those on the healthy side in patients with Bell's palsy (p<.05). The MUNIX measurements significantly correlated with the clinical facial nerve palsy scale scores (p<.05). Significant improvements were observed in the MUNIX values on repeat testing following treatment (p<.05). The baseline motor unit size index (the compound muscle action potential amplitude divided by MUNIX) was positively associated with improved clinical presentation after 1 month (p<.05). MUNIX can be used as an electrophysiological biomarker for the quantitative assessment of facial nerve palsy and treatment response, and as a prognostic biomarker, in patients with early Bell's palsy, and is recommended as a complement to conventional neurophysiological examinations.

A Preliminary Finding: N-butyl-phthalide Plays a Neuroprotective Role by Blocking the TLR4/HMGB1 Pathway and Improves Mild Cognitive Impairment Induced by Acute Cerebral Infarction.

Most acute cerebral infarctions (ACI) may develop vascular dementia (VD), which involves almost all types of cognitive impairment. Unfortunately, there is currently no effective treatment for VD. Most patients exhibit mild cognitive impairment (MCI) before the development of VD. N-butyl-phthalide (NBP) is used to treat ACI and improve cognitive function. The oxygen and glucose deprivation (OGD) model of neurons is an in vitro model of ischemia, hypoxia, and cognitive dysfunction. We conducted clinical studies and in vitro experiments to investigate the clinical efficacy and mechanism of action of NBP for treating ACI-induced MCI. Patients with ACI-induced MCI were randomly divided into control (Ctrl) and NBP groups. We assessed various indicators, such as clinical efficacy, montreal cognitive assessment scale (MOCA), activities of daily living (ADL), and cerebral infarct size in both groups before and after treatment. We observed the morphology of neurons and detected the survival rate, action potentials (APs), expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the interaction between TLR4 and HMGB1. The MOCA and ADL scores increased significantly after treatment in the NBP group. A OGD model of neurons was established, and the neurons were divided into Ctrl and NBP groups. We observed that the survival rate and APs amplitude of the neurons were significantly increased in the NBP group, whereas TNF-α expression was decreased. Furthermore, the interaction between TLR4 and HMGB1 decreased in the NBP group. NBP plays a neuroprotective role by inhibiting the TLR4/HMGB1 pathway and ameliorating ACI-induced MCI.

CAMP reduces action potential amplitude and conduction velocity over long axonal distance.

cAMP reduces action potential amplitude and conduction velocity over long axonal distance.

Long-chain n-3 polyunsaturated fatty acid supplementation and neuromuscular function in older adults.

This review aims to explore the latest research investigating the effects of marine-derived long-chain n -3 polyunsaturated fatty acid (LC n -3 PUFA) supplementation on neuromuscular function in older adults. Ageing results in a decline in skeletal muscle strength and mass. There is growing evidence that LC n -3 PUFA supplementation increases muscle strength and mass in healthy older adults, yet the mechanisms underlying these effects remain elusive. Recent studies investigating LC n -3 PUFA supplementation have demonstrated effects on neuromuscular function such as increases in the compound muscle action potential (M-wave) amplitude and surface electromyography alongside increases in muscular strength. Therefore, evidence suggests that LC n -3 PUFA may elicit a beneficial effect at the neuromuscular junction and possess neuroprotective properties in older adults. LC n -3 PUFA supplementation may increase or maintain neuromuscular function throughout the ageing process. Further research is warranted to investigate the long-term effects LC n -3 PUFA supplementation on neuromuscular outcomes such as single motor unit properties and cortical/supraspinal networks, utilizing state-of-the-art techniques in neuromuscular physiology.

Lactate dehydrogenase-1 may play a key role in the brain energy disturbance caused by cryptococcal meningitis

BackgroundCryptococcal meningitis (CM) may affect the conversion of lactate to pyruvate in the brain, resulting in abnormal levels of adenosine triphosphate (ATP) throughout the brain. Lactate conversion to pyruvate is mainly caused by lactic dehydrogenase 1 (LDH1), which is composed of four LDHB subunits. However, the underlying mechanism of LDH1 in CM remains unclear. MethodsCerebrospinal fluid (CSF) from 17 patients was collected, including eight patients with non-infectious diseases of the central nervous system and nine patients with CM. Based on clinical data and laboratory reports, data regarding intracranial pressure, CSF white cell counts, lactate dehydrogenase (LDH), adenosine deaminase, glucose, protein, and chloridion were collected. Meanwhile, LDH1, LDH5, lactate, pyruvate, and ATP levels were detected in CSF. Whereafter, the levels of lactate, pyruvate, ATP, and the amplitude and frequency of action potentials in the neurons with low expression of LDHB were explored. ResultsIntracranial pressure and white cell count in CSF were significantly increased in patients with CM. In patients with CM, the LDH1, pyruvate, and ATP levels in the CSF were significantly decreased, and the levels of lactate were found to be increased. Furthermore, pyruvate and ATP levels were decreased, while lactate was increased in the neurons with low expression of LDHB. The amplitude and frequency of APs in the neurons with low expression of LDHB were significantly decreased. ConclusionReduced levels of LDH1 in the brain of patients with CM may lead to increased lactate levels, decreased pyruvate and ATP levels, and negatively affect neuronal activity.

Age related changes in skin sensitivity assessed with smartphone vibration testing

The capacity to perceive tactile input at the fingertips, referred to as tactile sensitivity, is known to diminish with age due to regressive changes to mechanoreceptor density and morphology. Sensitivity is measured as perceptual responses to stimuli of varying intensity. Contrary to traditional sensitivity monitoring instruments, smartphones are uniquely suited for remote assessment and have shown to deliver highly calibrated stimuli along a broad spectrum of intensity, which may improve test reliability. The aim of this study was to evaluate a vibration-emitting smartphone application, the Vibratus App, as a mode of estimating tactile sensory thresholds in the aging adult. The peripheral nerve function of 40 neurologically healthy volunteers (ages 18–71) was measured using monofilaments, a 128-Hz tuning fork, the Vibratus App, and nerve conduction studies (NCS). Between group differences were analyzed to determine each measurement’s sensitivity to age. Spearman correlation coefficients depicted the associative strength between hand-held measurements and sensory nerve action potential (SNAP) amplitude. Inter-rater reliability of traditional instruments and the software-operated smartphone were assessed by intraclass correlation coefficient (ICC2,k). Measurements taken with Vibratus App were significantly different between age groups (p < 0.001). The inter-rater reliability of monofilament, smartphone vibration, and tuning fork testing was moderate to good (ICC2,k = 0.65, 0.69, and 0.79, respectively). The findings of this study support further investigation of smartphones as sensitivity monitoring devices for at home monitoring of skin sensitivity.

Dropping Objects in Carpal Tunnel Syndrome: Clinical and Electrophysiological Features.

Background Dysfunction in both afferent sensory and efferent motor components of the median nerve may contribute to the manifestation of the symptom of dropping objects (DO) in carpal tunnel syndrome (CTS). The objective of this study was to compare the clinical and electrophysiological characteristics of CTS patients with dropping objects (wDO) and those without dropping objects (w/oDO). The study evaluated the correlation between DO symptoms and median partial conduction block, as well as the reduction in median motor conduction velocity at the wrist. Methodology An examination for CTSand the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) were performed. Median and ulnar sensory and motor nerve conduction studies were conducted in both upper extremities, and the percentage decrease in the median compound motor action potential amplitude at the wrist level was calculated. Results The study included 201 female participants aged between 22 and 88 years, comprising 57 patients withCTSwDO, 78 patients with CTSw/oDO, and 66 healthy controls. In the CTSwDO group, compared to the CTSw/oDO group, BCTQscores were significantly higher, the prevalence of sensory deficits was more pronounced, and a larger number of hands, both dominant and non-dominant, were classified as stage 3 or higher in the clinical CTS classification. However, no correlation was found between the presence of DO symptoms and any neurophysiological findings. Conclusions DO may be a symptom of clinical severity in CTS, as previously reported.No neurophysiological parameter that could be associated with DO was identified.

The Spectrum of Childhood-Onset Lower Motor Neuron Disease of Spinal Muscular Atrophy Phenotype Associated with Survival Motor Neuron-2 Gene Deletion

AbstractPediatric lower motor neuron disease is clinically and genetically heterogeneous. We characterized disease progression among children with the spinal muscular atrophy (SMA) phenotype having 2:0 (group A) and 2:1 (group B) of the survival motor neuron 1/2 (SMN1:SMN2) genotype over 1 year. We included children aged 0 to 12 with the SMA phenotype between January 2018 and December 2021. Their demographic, clinical (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP-INTEND] scores), electrophysiological, radiological, and genetic data were collected from past medical records. The sequential CHOP-INTEND scores and the compound muscle action potential (CMAP) amplitudes were compared using an analysis of covariance test, controlling for age and sex. A linear regression was run to determine the association between the ages of the patients and the CHOP-INTEND scores. Among nine children in group A and six in group B, the decline of the mean (standard deviation) CHOP-INTEND score from the initial value to the 12th-month follow-up value was significant only in group A. CHOP-INTEND scores did not significantly differ between the two groups at the first admission but were significantly lower in group A at the subsequent visits. Group A patients had significantly lower CMAP amplitudes than patients in group B. There was a moderate, negative association between the age of patients and the CHOP-INTEND scores in group A. Group A patients had a significantly higher age-dependent decline in CHOP-INTEND scores and CMAP values than group B, although their age and the severity of weakness did not significantly differ at presentation.

The Inter-Phase Gap Offset Effect as a Measure of Neural Health in Cochlear Implant Users With Residual Acoustic Hearing.

The inter-phase gap (IPG) offset effect is defined as the dB offset between the linear parts of electrically evoked compound action potential (ECAP) amplitude growth functions for two stimuli differing only in IPG. The method was recently suggested to represent neural health in cochlear implant (CI) users while being unaffected by CI electrode impedances. Hereby, a larger IPG offset effect should reflect better neural health. The aims of the present study were to (1) examine whether the IPG offset effect negatively correlates with the ECAP threshold and the preoperative pure-tone average (PTA) in CI recipients with residual acoustic hearing and (2) investigate the dependency of the IPG offset effect on hair cell survival and intracochlear electrode impedances. Seventeen adult study participants with residual acoustic hearing at 500 Hz undergoing CI surgery at the University Hospital of Zurich were prospectively enrolled. ECAP thresholds, IPG offset effects, electrocochleography (ECochG) responses to 500 Hz tone bursts, and monopolar electrical impedances were obtained at an apical, middle, and basal electrode set during and between 4 and 12 weeks after CI surgery. Pure-tone audiometry was conducted within 3 weeks before surgery and approximately 6 weeks after surgery. Linear mixed regression analyses and t tests were performed to assess relationships between (changes in) ECAP threshold, IPG offset, impedance, PTA, and ECochG amplitude. The IPG offset effect positively correlated with the ECAP threshold in intraoperative recordings (p < 0.001) and did not significantly correlate with the preoperative PTA (p = 0.999). The IPG offset showed a postoperative decrease for electrode sets that showed an ECochG amplitude drop. This IPG offset decrease was significantly larger than for electrode sets that showed no ECochG amplitude decrease, t(17) = 2.76, p = 0.014. Linear mixed regression analysis showed no systematic effect of electrode impedance changes on the IPG offset effect (p = 0.263) but suggested a participant-dependent effect of electrode impedance on IPG offset. The present study results did not reveal the expected relationships between the IPG offset effect and ECAP threshold values or between the IPG offset effect and preoperative acoustic hearing. Changes in electrode impedance did not exhibit a direct impact on the IPG offset effect, although this impact might be individualized among CI recipients. Overall, our findings suggest that the interpretation and application of the IPG offset effect in clinical settings should be approached with caution considering its complex relationships with other cochlear and neural health metrics.

Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. Tomivosertib treatment also decreased action potential amplitude and produced alterations in the magnitude of after hyperpolarizing currents, suggesting modification of Na+ and K+ channel activity as a consequence of drug treatment. Parallel to the effects on electrophysiology, eFT508 treatment led to a profound loss of eIF4E serine 209 phosphorylation in primary sensory neurons, a specific substrate of MNK, within 2 min of drug treatment. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.