Compound Muscle Action Potential Amplitude Research Articles

Trend in parameters of motor nerve conduction against the background of gene therapy in early age patients with spinal muscular atrophy

Introduction. In children with spinal muscular atrophy (SMA), reliable indicators (biomarkers) are needed to predict the disease, which could reflect the underlying process of the disease. It is believed that the parameters of motor nerve conduction studies (MNCV) (amplitude and area of the compound muscle action potential (CMAP), the motor unit number estimation) may correlate with the degree of denervation in SMA and with the severity of motor disorders. The purpose of the study. To detect the trend in MNCV parameters in SMA type I patients with clinical manifestations of the disease and children at the presymptomatic stage of the disease, against the background of treatment with onasemnogen abeparvovek. Materials and methods. The study included sixty eight SMA children, including 42 boys (53.2%). All children received gene therapy with the onasemnogen abeparvovek. 33 children were treated at the presymptomatic stage (age at the time of treatment was 2.12 ± 0.91 years (95% CI 1.80–2.45), min — 1.00, max — 5.00). In 35 SMA type I children, treatment started when clinical symptoms of the disease were already present (age at the time of treatment was 3.40 ± 1.85 years (95% CI 3.10–4.25), min — 1.00, max — 7.00). All children included in this study underwent MNCV before the start of therapy and for the next 2 years. The amplitude of the negative peak of the CMAP from the abductor digiti minimi muscle during stimulation of the ulnar nerve and nerve conduction velocity (NCV) along the distal part of the ulnar nerve were determined. Due to the fact that the values of most of the MNCV parameters did not obey the normal distribution, they were described using the values of the median (Me) and the lower and upper quartiles (Q1–Q3), minimum (min) and maximum (max). Results. In the cohort of presymptomatic patients, the CMAP and NCV parameters did not significantly differ from the normative data before the start of therapy, and against the background of treatment with onasemnogen abeparvovek, an increase in the CMAP and NCV amplitude of the was noted with increasing age in patients. The amplitude of the CMAP and NCV before treatment were 5.00 mV (4.30–5.30), min — 1.40, max — 8.00 and 33.60 m/s (32.40–38.10), min — 27.40, max — 48.90, and at the age of 13 to 24 months — 6.25 mV (5.20–6.85), min — 4.70, max — 7.80 and 55.20 m/s (52.80–57.60), min — 49.10, max — 60.30, respectively. All SMA type I patients showed a significant decrease in the amplitude of the M-response both before therapy and during 2-year follow-up after the start of treatment. The amplitude of the CMAP and NCV before treatment were 0.28 mV (0.13–0.65), min — 0.05, max — 2.20 and 31.90 m/s (27.50–35.90), min — 22.30, max — 52.00, and at the age of 13 to 24 months — 0.70 mV (0.46–1.15), min — 0.17, max — 4.60 and 48.40 m/s (43.95–50.98), min — 38.90, max — 56.10, respectively. Conclusion. When comparing the MNCV parameters in presymptomatic with SMA type I patients, significant differences were shown, which were manifested in symptomatic patients with a low amplitude of the CMAP and reduced values of NCV both before therapy and during 2-year follow-up after treatment with onasemnogen abeparvovek. Thus, conducting MNCV in children with SMA is an easily feasible study, and evaluating the amplitude of the CMAP makes it possible to reliably, albeit indirectly, verify degeneration of spinal cord motor neurons in symptomatic patients against the background of pathogenetic treatment.

Electrophysiological Abnormalities in Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease: Three New Patients and Review of the Literature.

Finger Extension Weakness and DOwnbeat Nystagmus Motor Neuron Disease (FEWDON-MND) is characterized by motor weakness predominantly affecting finger extension, accompanied by downbeat nystagmus. To date, only 11 patients have been reported. The present study adds a further three and aims to provide a more detailed description of the electrodiagnostic features of these patients. We present the clinical and electrophysiological features of three French patients from specialized motor neuron centers and review the electrophysiological findings of previously reported patients. These three patients presented with pure motor weakness affecting finger extension and downbeat nystagmus. They exhibited a slowly progressive disease course without respiratory involvement. Nerve conduction studies showed decreased compound muscle action potential amplitudes in the extensor indicis muscles. Abnormal spontaneous activity on needle electromyography (EMG) was rare in two patients, absent in one, and otherwise limited to weak muscles. Additionally, chronic motor axon loss features suggestive of motor neuronopathy were seen in our patients. Importantly, they were also detected in distant asymptomatic muscles. The three patients reported here confirm the typical phenotype of FEWDON-MND, characterized by slowly progressive distal motor weakness initially affecting finger extension, associated with downbeat nystagmus. Although chronic motor axon loss features have been found in all reported patients, our three patients show that active denervation can be absent or rare. Thus, finger drop and diffuse chronic neurogenic changes on EMG should lead clinicians to look for downbeat nystagmus and to consider FEWDON-MND.

Maximizing the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials

Mouse models of amyotrophic lateral sclerosis (ALS) enable testing of novel therapeutic interventions. However, treatments that have extended survival in mice have often failed to translate into human benefit in clinical trials. Compound muscle action potentials (CMAPs) are a simple neurophysiological test that measures the summation of muscle fiber depolarization in response to maximal stimulation of the innervating nerve. CMAPs can be measured in both mice and humans and decline with motor axon loss in ALS, making them a potential translational read-out of disease progression. We assessed the translational potential of CMAPs and ascertained time points when human and mouse data aligned most closely. We extracted data from 18 human studies and compared with results generated from SOD1G93A and control mice at different ages across different muscles. The relative CMAP amplitude difference between SOD1G93A and control mice in tibialis anterior (TA) and gastrocnemius muscles at 70 days of age was most similar to the relative difference between baseline ALS patient CMAP measurements and healthy controls in the abductor pollicis brevis (APB) muscle. We also found that the relative decline in SOD1G93A TA CMAP amplitude between 70 and 140 days was similar to that observed in 12 month human longitudinal studies in APB. Our findings suggest CMAP amplitudes can provide a “translational window”, from which to make comparisons between the SOD1G93A model and human ALS patients. CMAPs are easy to perform and can help determine the most clinically relevant starting/end points for preclinical studies and provide a basis for predicting potential clinical effect sizes.

Investigation of the protective effects of dichloroacetic acid in a rat model of diabetic neuropathy

BackgroundDiabetic neuropathy (DN) is a heterogeneous condition characterized by complex pathophysiological changes affecting both autonomic and somatic components of the nervous system. Inflammation and oxidative stress are recognized contributors to the pathogenesis of DN. This study aims to evaluate the therapeutic potential of dichloroacetic acid (DCA) in alleviating DN symptoms, focusing on its anti-inflammatory and antioxidant properties.MethodsThirty-two adult male Sprague Dawley rats were divided into four groups: Control, Diabetic, and two DCA-treated groups receiving 5 mg/kg and 10 mg/kg of DCA, respectively. Diabetes was induced with streptozotocin (STZ) injections. Assessments included lipid peroxidation levels, plasma fibroblast growth factor-21 (FGF-21) and transforming growth factor-beta (TGF-β) levels, electrophysiological measurements, histological examination of the sciatic nerve, and motor function tests.ResultsTreatment with DCA significantly reduced malondialdehyde (MDA) levels, indicating decreased lipid peroxidation. Plasma TGF-β levels were also lower in the DCA-treated groups, suggesting diminished inflammation. Conversely, plasma FGF-21 levels were elevated. Electrophysiological assessments revealed enhanced compound muscle action potential (CMAP) amplitudes and reduced distal latencies in DCA-treated rats, indicative of improved nerve conduction. Histopathological examinations showed reduced perineural thickness in the sciatic nerves of DCA-treated rats, pointing to decreased fibrosis. Enhanced performance in motor function tests was observed in these rats, implying improved muscle strength and motor capacity.ConclusionsThe study demonstrates that DCA therapy significantly reduces oxidative stress and inflammation in a rat model of DN, thereby ameliorating neuropathic symptoms. These results support the potential of DCA as a promising therapeutic agent for DN treatment. Further research is warranted to explore its clinical applications and to provide more detailed insights.

Motor function and compound muscle action potential amplitude in children with spinal muscular atrophy treated with nusinersen.

Disease-modifying therapies can improve motor function in patients with spinal muscular atrophy (SMA), but efficacy varies between individuals. The aim was to evaluate the efficacy and safety of nusinersen treatment in children with SMA and to investigate prognostic factors. Motor function, compound muscle action potential (CMAP), and other indicators were prospectively collected before and 14months after nusinersen treatment. A total of 55 children were included in our study to assess safety. 41 patients (with at least 6months of nusinersen treatment) were included in the final efficacy analyses, with a median age at first treatment of 4.2years. After 14months of treatment with nusinersen, motor function improved, with increases in CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders), HINE-2 (Hammersmith Infant Neurological Exam-Part 2), HFMSE (Hammersmith Functional Motor Scale-Expanded) and RULM (Revised Upper Limb Module) of 5.5 (95% CI -2.4-13.4), 0.8 (95% CI -0.2-1.9), 5.0 (95% CI 2.5-7.4) and 2.4 (95% CI 0.7-4.1) points, respectively. The CMAP amplitudes of the bilateral tibial, median and ulnar nerves increased, with greatest improvements of 0.87±1.41mV, 1.08±1.71mV and 0.59±1.01mV, respectively. Spearman correlation analysis showed that age at first treatment, disease duration, joint contractures and scoliosis were associated with treatment efficacy (r=-0.4-0.7, P<0.05). Subgroup analyses showed that the mean HFMSE and RULM scores improved in the Physical therapy group (P<0.05). Early treatment, mild bone and joint complications, and regular rehabilitation training were associated with better outcomes. The other motor-related functions, such as respiratory and bullar function, and prognostic factors should be studied in the future.

Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection.

Following transection, nerve repair using the polylactic acid (PLA) conduit is an effective option. In addition, inosine treatment has shown potential to promote nerve regeneration. Therefore, this study aimed to investigate the regenerative potential of inosine after nerve transection and polylactic acid conduit repair. C57/Black6 mice were subjected to sciatic nerve transection, repair with PLA conduit, and intraperitoneal injection of saline or inosine 1 h after injury and daily for 1 week. To assess motor and sensory recovery, functional tests were performed before and weekly up to 8 weeks after injury. Following, to evaluate the promotion of regeneration and myelination, electroneuromyography, morphometric analysis and immunohistochemistry were then performed. Our results showed that the inosine group had a greater number of myelinated nerve fibers (1,293 ± 85.49 vs. 817 ± 89.2), an increase in neurofilament high chain (NFH) and myelin basic protein (MBP) immunolabeling and a greater number of fibers within the ideal g-ratio (453.8 ± 45.24 vs. 336.6 ± 37.01). In addition, the inosine group presented a greater adenosine A2 receptor (A2AR) immunolabeling area. This resulted in greater compound muscle action potential amplitude and nerve conduction velocity, leading to preservation of muscle and neuromuscular junction integrity, and consequently, the recovery of motor and sensory function. Our findings suggest that inosine may enhance regeneration and improve both motor and sensory function recovery after nerve transection when repaired with a poly-lactic acid conduit. This advances the understanding of biomaterials and molecular treatments.

Leptin deficiency leads to nerve degeneration and impairs axon remyelination by inducing Schwann cell apoptosis and demyelination in type 2 diabetic peripheral neuropathy in rats

Diabetic peripheral neuropathy, characterized by symptoms such as paresthesia, neuropathic pain, and potential lower limb amputation, poses significant clinical management challenges. Recent studies suggest that chronic hyperglycemia-induced Schwann cells (SCs) apoptosis contributes to neurodegeneration and impaired nerve regeneration, but the detailed mechanisms are still unknown. Our study investigated a mixed-sex type 2 diabetes mellitus (T2DM) rat model using leptin knockout (KO) to simulate obesity and diabetes-related conditions. Through extensive assessments, including mechanical allodynia, electrophysiology, and microcirculation analyses, along with myelin degradation studies in KO versus wild-type rats, we focused on apoptosis, autophagy, and SCs dedifferentiation in the sciatic nerve and examined nerve regeneration in KO rats. KO rats exhibited notable reductions in mechanical withdrawal force, prolonged latency, decreased compound muscle action potential (CMAP) amplitude, reduced microcirculation, myelin sheath damage, and increases in apoptosis, autophagy, and SCs dedifferentiation. Moreover, leptin KO was found to impair peripheral nerve regeneration postinjury, as indicated by reduced muscle weight, lower CMAP amplitude, extended latency, and decreased remyelination and SCs density. These findings underscore the effectiveness of the T2DM rat model in clarifying the impact of leptin KO on SCs apoptosis, dedifferentiation, and demyelination, providing valuable insights into new therapeutic avenues for treating T2DM-induced peripheral neuropathy.

Use of an electrical stimulation-induced fatigue protocol to evaluate the myotropic effects of metabolic-active agents in db/db mice

Introduction. Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance, impaired glucose tolerance, and hyperglycaemia. T2DM is a proven risk factor for peripheral neuropathies as well as muscle contractility and function impairments. The biguanide metformine, experimental compound maloben, and preparations of various Panax species have a considerable potential for the treatment of T2DM and its skeletal muscle complications. As a test to evaluate muscle contractility and the effectiveness of its recovery, Gregory et al. have developed a protocol of electrical stimulation-induced fatigue (ESIF) which includes measuring grip strength after fatiguing the biceps brachii muscle with high-frequency electrical stimulation using implantable electrodes.Aim. In this work, we attempted to assess the applicability of a modification of said protocol in order to evaluate the myotropic effects of metformin, maloben, and extracts from suspension cell cultures of Panax ginseng C.A. Mey. (PGE), P. vietnamensis Ha &amp; Grushv. (PVE), and P. japonicus (T. Nees) C.A. Mey. (PJE) in the leptin-resistant db/db mice, one of the most popular modern T2DM models.Materials and methods. The experiments were carried out in 60 young adult (2 months old) male C57Bl/Ks-db+/+m (db/db) mice weighing 45–50 g, randomized into 6 groups: 1) Control (n = 10; 0.9 % saline); 2) PGE (n = 10; 50 mg/kg); 3) PVE (n = 10; 50 mg/kg); 4) PJE (n = 10; 50 mg/kg); 5) maloben (n = 10; 60 mg/kg); 6) metformin (n = 10; 300 mg/kg). All drugs were administered via oral gavage using a feeding tube once daily for 2 months. Following the treatment period, forelimb and all-four limb grip strength (g) was assessed using the Grip Strength Meter (TSE Systems, Germany). Using stimulation electroneuromyography, we measured the compound muscle action potential (CMAP) amplitudes in the gastrocnemius induced by single-stimulus sciatic nerve stimulation, and assessed the dynamics of CMAP amplitudes during the first 5 min following the ESIF protocol completion.Results and discussion. Following treatment period completion, no significant changes were observed between the groups in grip strength or gastrocnemius CMAP amplitude under single-stimulus stimulation. Controlled ESIF of the muscle caused a 18.83–35.23 % (relative to baseline) decrease in CMAP amplitudes (p &lt; 0.01 for all groups) that was significantly smaller in the PVE, PJE, and maloben groups vs. control (p &lt; 0.05). The post-ESIF recovery period was associated with a 10.18–14.79 % increase in CMAP amplitudes that was significant in all groups except PGE (p &lt; 0.01 for control, PVE, and PJE; p &lt; 0.05 for maloben and metformin). No significant differences from control were observed in any of the treatment groups regarding net recovery.Сonclusion. The proposed protocol represents a functional test suitable to assess the recovery effectiveness of electrical activity of a skeletal muscle following its controlled fatigue. Using the described protocol, we were able to detect beneficial effects of PVE, PJE, and maloben (but not PGE or metformin) on the recovery of gastrocnemius contractility following tetanization in diabetic db/db mice. The ESIF test is sensitive to the myotropic effects of metabolic agents, minimally invasive, and acceptable under chronic experiment conditions.

Botulinum toxin modulates the blink reflex via the trigeminal afferent system in hemifacial spasm: an early and late-term effect.

There is growing evidence that botulinum neurotoxin (BoNT) can mediate changes at the central level through peripheral mechanisms, leading to alterations in central sensorimotor integration. However, the effect of BoNT on brainstem excitability in patients with hemifacial spasm(HFS) is not yet fully understood, and its long-term effects remain unknown. This study aims to investigate the impact of BoNT on the excitability of the facial nucleus in patients with idiopathic HFS. In order to evaluate the peripheral effect of the toxin, the amplitude of compound muscle action potential (CMAP) of orbicularis oculi (OOc) muscles was evaluated. To investigate the effects of locally injected BoNT on the brainstem, particularly the facial motor nucleus, we evaluated the amplitude and latency of the blink reflex (BR), the synkinetic responses (SR) and the ratio of contralateral R2 (cR2) amplitude of BR/CMAP amplitude in 16 patients with HFS. These measurements were performed before and after the 1 and 4month BoNT injection. Following BoNT therapy there was a significant amplitude reduction and latency prolongation of R1, iR2, cR2 and SR elicited by the stimulation of the side of BoNT injection. The mean CMAP amplitude of OOc muscle was significantly lower after BoNT injection. The ratio of cR2 amplitude/CMAP amplitude of OOc showed a significant decline after BoNT therapy. Our study demonstrated that BoNT suppresses the excitability of facial motor neurons in idiopathic HFS via the trigeminal afferent mechanism. These effects persisted during the fourth month, despite BoNT's diminished activity.

Lonafarnib Protects Against Muscle Atrophy Induced by Dexamethasone.

Muscle atrophy, including glucocorticoid-induced muscle wasting from treatments such as dexamethasone (DEX), results in significant reductions in muscle mass, strength and function. This study investigates the potential of lonafarnib, a farnesyltransferase inhibitor, to counteract DEX-induced muscle atrophy by targeting key signalling pathways. We utilized invitro models with C2C12 myotubes treated with DEX and invivo models with Caenorhabditis elegans and DEX-treated Sprague-Dawley rats. Myotube morphology was assessed by measuring area, fusion index and diameter. Muscle function was evaluated by grip strength and compound muscle action potential (CMAP) in the gastrocnemius (GC) and tibialis anterior (TA) muscles. Molecular mechanisms were explored through RNA sequencing and Western blotting to assess changes in mitochondrial function and muscle signalling pathways. Lonafarnib (2 μM) significantly improved myotube area (1.49 ± 0.14 × 105 μm2 vs. 1.03 ± 0.49 × 105 μm2 in DEX, p < 0.05), fusion index (18.73 ± 1.23% vs. 13.3 ± 1.56% in DEX, p < 0.05) and myotube diameter (31.89 ± 0.89 μm vs. 21.56 ± 1.01 μm in DEX, p < 0.05) in C2C12 myotubes. In C. elegans, lonafarnib (100 μM) increased the pharyngeal pumping rate from 212 ± 7.21 contractions/min in controls to 308 ± 17.09 contractions/min at day 4 (p < 0.05), indicating enhanced neuromuscular function. In DEX-induced atrophic rats, lonafarnib improved maximal grip strength (DEX: 13.91 ± 0.78 N vs. 1 μM lonafarnib: 16.18 ± 0.84 N and 5 μM lonafarnib: 16.71 ± 0.83 N, p < 0.05), increased muscle weight in GC, and enhanced CMAP amplitudes in both GC and TA muscles. Western blot analysis showed that lonafarnib treatment upregulated UCP3 and ANGPTL4 and increased phosphorylation of mTOR and S6 ribosomal protein (p < 0.05), indicating enhanced mitochondrial function and protein synthesis. Knockdown models further demonstrated that lonafarnib could partially rescue muscle atrophy phenotypes, indicating its action through multiple molecular pathways. Lonafarnib mitigates dexamethasone-induced muscle atrophy by enhancing mitochondrial function and activating anabolic pathways. These findings support further investigation of lonafarnib as a therapeutic agent for muscle atrophy in clinical settings.

Electrophysiological Monitoring of Asymptomatic Transthyretin Mutation Carriers.

It is imperative to screen asymptomatic carriers of transthyretin (TTR) mutations to initiate treatment early. The protocol for repeated electrodiagnostic (EDX) assessments over time lacks standardization. Our aim was to report the electrophysiological evolution of a cohort of asymptomatic carriers and to determine which biomarkers were most sensitive to change. We performed a retrospective review of medical records of asymptomatic carriers identified by screening families with amyloid neuropathy. Carriers who underwent two EDX assessments with a minimum 1-year interval between studies were selected. EDX included analysis of median, ulnar, tibial, fibular and sural nerves, motor unit number index (MUNIX), electrochemical skin conductance, sympathetic skin response, and heart rate variability on deep breathing. Measurements were compared at first and second examinations. Twenty-three carriers were included with a median age of 49 years (interquartile range 37-58). Median time between examinations was 3 years (2-4). Compound muscle and sensory nerve action potential (CMAP and SNAP) amplitudes, nerve conduction velocities, autonomic small fiber testing and MUNIX remained stable except for motor distal latency of the median nerve (+0.07 ms/year) and CMAP duration of the ulnar (+0.10 ms/year) and fibular (+0.12 ms/year) nerves. The CMAP duration of the ulnar nerve was the most sensitive biomarker to change when performed within 10 years preceding the age of the youngest case in the family, with a standardized response mean of 0.91. Nerve conduction parameters remain relatively stable in asymptomatic TTR carriers. Changes can only be detected using multimodal and extensive electrophysiological tests.

Reliability of MScanFit Motor Unit Number Estimation in the Trapezius Muscle.

MScanFit motor unit number estimation (MUNE) is the most recent MUNE method which has shown promising results in extremity muscles, but it has not been applied to bulbar muscles. Bulbar muscles are particularly important in the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the feasibility and reliability of MScanFit MUNE in the accessory nerve and trapezius muscles. A total of twenty healthy participants were examined twice within 1-2 weeks. We extracted the MScanFit MUNE and size parameter, and compound muscle action potential (CMAP) amplitude values. The reliability of these parameters was assessed using the intra-rater coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland-Altman plots. We also correlated MUNE values with CMAP amplitudes using correlation coefficients. Mean MUNE values (Day 1 = 132.1 and Day 2 = 137.4), CMAP amplitudes (Day 1 = 9.71 mV and Day 2 = 10.10 mV) and size parameters did not differ between the two sessions (p > 0.05). CoV showed excellent reliability for MUNE values, size parameters, and CMAP amplitudes (CoV < 7%) whereas ICCs showed moderate reliability for MUNE values (ICC = 0.619), poor to moderate reliability for size parameters (between 0.393 and 0.689), and good reliability for CMAP amplitude (ICC = 0.864) There was no correlation between MUNE values and CMAP amplitudes. MScanFit MUNE is applicable and mostly reliable in the trapezius muscle. Further studies in patients are needed to investigate the sensitivity of MScanFit in this muscle in detecting motor unit loss, particularly in ALS.

Paraneoplastic Cerebellar Degeneration and Symptomless Lambert–Eaton Myasthenic Syndrome With SOX‐1 Antibodies

ABSTRACTA 62‐year‐old man was diagnosed with paraneoplastic cerebellar degeneration (PCD) at a previous hospital due to cerebellar ataxia, positive serum SOX‐1 antibodies, and small cell lung cancer. Although the tumor has shrunk by chemotherapy, the cerebellar ataxia progressed and left him unable to walk. Lambert–Eaton myasthenic syndrome (LEMS) was suspected, because nerve conduction studies showed that reduced compound muscle action potential amplitudes disproportionate to muscle weakness. PCD‐LEMS with SOX‐1 antibodies was diagnosed on the basis of waxing by high‐frequency repetitive nerve stimulation test and high P/Q‐type voltage‐gated calcium channel antibody levels. Immunoglobulin therapy and 3,4‐diaminopyridine contributed to improved activities of daily living by improving muscle weakness masked by cerebellar symptoms. In patients with SOX‐1 antibodies, investigating for tumors and LEMS is necessary, even if muscle weakness is not noticeable.

Early and Late Intrinsic Hand Muscle Reinnervation After End-to-Side AIN to Ulnar Motor Nerve Transfer.

The "supercharge" end-to-side (SETS) anterior-interosseous-nerve (AIN) to ulnar-motor nerve transfer is used to improve intrinsic muscle recovery in cases of severe ulnar nerve compression or proximal axonotmetic injuries. Previous work has found differing intrinsic muscle recovery after this transfer. The objectives of this study were to examine the patterns of recovery in first dorsal interossei (FDI) and abductor digiti minimi (ADM) and the impact of AIN transfer to a specific fascicular location on the ulnar-motor nerve. A retrospective review of one fellowship-trained surgeon's consecutive patients at a single center from December 2019 to September 2021 was conducted. Patients who had an AIN to ulnar-motor nerve transfer for any indication were included and were excluded if they had less than 9 months follow-up. Seventeen patients were included (88% male, mean age 55 ± 14 years). At early follow-up, compound muscle action potential amplitudes for ADM and FDI did not increase. Compound muscle action potential amplitude for ADM significantly increased at late follow-up (P < .01). Average British Medical Research Council (BMRC) strength increased at early follow-up for FDI (P < .05), but not ADM. The proportion of patients with BMRC ≥ 3 increased for FDI (P < .01) and ADM (P < .05) at late follow-up. Volar-ulnar AIN insertion position did not have a clear effect on outcomes. The SETS AIN to ulnar-motor nerve transfer demonstrates clinical and electrophysiologic evidence of intrinsic muscle recovery and reinnervation, with differing recovery of outcomes. The role of specific fascicular targeting is still unclear and required further examination as does the mechanism behind differing intrinsic recovering.

Clinical Features of Conduction Block in Ulnar Neuropathy at the Elbow: The Surgery of the Ulnar Nerve (SUN) Multicenter Clinical Trial.

In ulnar neuropathy at the elbow, weakness is classically a sign of severe disease. Weakness is associated with motor axonal loss as measured by decreased distal compound muscle action potential (CMAP) amplitude. Conduction block, a demyelinating phenomenon that recovers readily, can also cause weakness, creating ambiguity for the treating clinician. This cross-sectional study evaluated baseline blinded data collected from 2020-2023 from the Surgery of the Ulnar Nerve randomized controlled trial comparing in-situ decompression versus transposition procedures. Adult patients underwent electrodiagnostic testing, clinical motor and sensory testing, and completed the Michigan Hand Questionnaire and Carpal Tunnel Questionnaire. 177 patients were categorized into 3 distinct groups based on normal distal CMAP amplitudes (77 patients), presence of conduction block with or without distal CMAP amplitude loss (37 patients), or pure axonal loss with distal CMAP amplitude loss in the absence of conduction block (63 patients). Compared to the normal group, patients with conduction block had significantly decreased pinch strength and worse function domain scores on the Michigan Hand Questionnaire and Carpal Tunnel Questionnaire, but shorter duration of disease. Patients with pure axonal loss had decreased pinch strength, worse 2-point discrimination, and worse overall, function and aesthetics domain scores on the Michigan Hand Questionnaire. There was a significant interaction between the effects of conduction block and distal CMAP amplitude on pinch strength, indicating that higher degrees of conduction block resulted in more pronounced loss of pinch strength in patients with relatively preserved distal CMAP amplitude. Our findings support the paradigm that ulnar neuropathy at the elbow presenting with conduction block represents a distinct and intermediate pathophysiology, distinguished by quicker onset with less advanced neurological deficits. Prognostic Level II.

Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model.

Background and Objectives: It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the treatment of cytokine storm and critical illness neuromyopathy (CINM) in a rat sepsis model. Materials and Methods: Rats were assigned into three groups, and a feces intraperitoneal-injection group (FIP) procedure was carried out on 30 rats to induce a model of sepsis for critical illness polyneuromyopathy (CINM). The study groups were as follows: Group 1: control (nonoperative and orally fed control, n = 10), Group 2: FIP with 0.9% NaCl saline was given as 1 mL/kg/day by oral gavage (n = 10), and Group 3: FIP with 10 mg/kg/day of hydroxychloroquine (Plaquenil 200 mg) administered by oral gavage (n = 10). Electrophysiological recordings (EMG) were conducted six days after surgery. EMG was carried out three times on the right sciatic nerve, which was stimulated with supramaximal intensity utilizing a bipolar needle electrode at the sciatic notch. Tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), lactic acid levels, and interleukin-6 (IL-6) were evaluated. Results: In terms of TNF-α, MDA, lactic acid levels, and IL-6, there was a statistically significant decrease in the CINM + 10 mg/kg HCQ group compared to the CINM and saline group (p < 0.0001, p < 0.05, p < 0.05, and p < 0.05, respectively). Compound muscle action potentials (CMAPs) latency and duration were decreased in the CINM + 10 mg/kg HCQ group compared to other groups (p < 0.01 and p < 0.001). However, CMAP amplitude was significantly higher in the CINM + 10 mg/kg HCQ group unlike the CINM and saline group (p < 0.001). Conclusions: This is the first study to demonstrate the effects of HCQ on CINM in a rat model of sepsis. The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress.

Ultrasound as a Complementary Tool to Electrodiagnostics in the Evaluation of Compressive Neuropathy of the Common Fibular Nerve

Background: Compressive neuropathy of the common fibular nerve (CFN) is increasingly recognized as an etiology for foot drop and falls. Electrodiagnostic (EDX) studies are widely used to evaluate this condition, but such tests are invasive and costly. As with carpal and cubital tunnel syndromes, there may be patients with characteristic symptoms of CFN compressive neuropathy but normal EDX studies in which ultrasound may aid in decision-making. Purpose: We sought to examine the association between ultrasound and nerve conduction studies (NCS) and electromyography (EMG) in the diagnosis of compressive neuropathy of the CFN. Methods: We performed a retrospective review identifying 104 patients who underwent CFN decompression from January 1, 2015, to June 30, 2023. Patients were included if they had both ultrasound and NCS/EMG prior to CFN decompression for compressive neuropathy and if they were older than 18 years at time of surgery. Patients were excluded if they had entrapment secondary to trauma, iatrogenic injury, or if they had had superficial fibular decompression alone without CFN decompression. After applying exclusion criteria, 17 patients remained in the cohort. Results: Mean ultrasound cross-sectional area and side-to-side (STS) ratios were significantly higher in those with abnormal compound muscle action potential (CMAP) amplitudes versus those with normal CMAP amplitudes. The probability of having an abnormal CMAP amplitude when STS ratio was abnormal was 18 times greater compared with those with normal STS ratio. With each unit increase in STS ratio, CMAP amplitude was reduced by 2.79 mV. Conclusions: This retrospective review found that ultrasound may provide complementary diagnostic information to EMG/NCS for compressive neuropathy of the CFN. Further study is needed to examine the relationship between ultrasound findings for CFN compressive neuropathy and results of surgical decompression.

Bioactive MXene hydrogel promotes structural and functional regeneration of skeletal muscle through improving autophagy and muscle innervation

Complete skeletal muscle regeneration after traumatic injuries remains a challenge due to impaired regenerative capability and dysregulated microenvironments. Autophagy plays a crucial role in the muscle regeneration process by regulating myogenic and non-myogenic cells. Herein, we report a bioactive MXene hydrogel (FPGM) capable of upregulating autophagy and increasing muscle innervation to restore skeletal muscle structure and function. FPGM possessed excellent electrical conductivity, tissue adhesive ability and antioxidation, which could eliminate excess reactive oxygen species to reduce oxidative stress and decrease the secretion of pro-inflammatory cytokine. FPGM upregulated the autophagy level of myoblasts and promoted the migration and tube formation of endothelial cells as well as myogenic differentiation with negligible toxicity. FPGM accelerated muscle fiber formation and skeletal muscle regeneration by improving autophagy, which could regulate microenvironment through raising M2 macrophages to alleviate excessive inflammation, facilitating angiogenesis and decreasing fibrous scar tissue formation in vivo. Importantly, FPGM could efficiently restore muscle function by improving muscle innervation, tibialis anterior compound muscle action potential amplitude and neuromuscular conduction. This work demonstrates that bioactive MXene hydrogel should be a promising candidate for complete skeletal muscle regeneration.

Neurofilament light chain as a biomarker for hereditary ATTR amyloidosis − correlation between neurofilament light chain and nerve conduction study

Background Neurofilament light chain (NfL) is a biomarker of neuronal injury in hereditary ATTR (ATTRv) amyloidosis. However, the correlation between NfL and nerve conduction study (NCS), the standard test for ATTRv neuropathy, has not been investigated. Objective Elucidate the correlation between NfL and NCS parameters. Methods 227 serum NfL measurements were performed in 45 ATTRv patients, 5 asymptomatic carriers, and 12 controls. Among them, 177 simultaneous analyses of NCS and NfL were conducted in 45 ATTRv patients. Results NfL levels of symptomatic patients were significantly higher than those of asymptomatic carriers and controls. Serum NfL levels were correlated with NCS parameters, especially compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes, indicators of axonal damage. CMAP and/or SNAP amplitudes were undetectable in 9 patients (no-amplitude group) due to advanced neuropathy. NfL levels in the no-amplitude group were significantly higher than those in patients with detectable CMAP/SNAP. NfL levels significantly decreased with patisiran, although no significant changes were observed in CMAP and SNAP. Conclusions NfL levels are found to be correlated with CMAP/SNAP amplitudes. Compared with NCS, NfL can be a more sensitive biomarker for detecting treatment response and active nerve damage even in patients with advanced neuropathy.

Structural and Functional Alterations of the Deltoid Muscle After Arthroscopic Rotator Cuff Repair: A 2-Year Longitudinal Observation Study.

Deltoid muscle detachment and atrophy have been reported to occur after shoulder surgery. To investigate the 2-year changes in deltoid muscle structure and function after arthroscopic rotator cuff repair (ARCR) using magnetic resonance imaging (MRI) and electrophysical examination. Case series; Level of evidence, 4. A total of 72 patients (72 shoulders) who underwent ARCR between 2015 and 2020 were enrolled. Whole deltoid muscle volume and regional (anterior, lateral, and posterior) muscle thicknesses were determined on T2-weighted MRI scans of both shoulders taken preoperatively and at 1, 3, 6, 12, and 24 months postoperatively, and their correlations with compound muscle action potentials (CMAPs), shoulder abduction muscle strength, and Constant scores were investigated. Comparison between groups was performed using paired or Student t tests, and the relationship between deltoid muscle volume and various factors was determined using Pearson correlation analysis. The volume of the deltoid muscle on the affected side decreased from 44,369 ± 12,371 mm3 preoperatively to 38,139 ± 10,615 mm3 at 1 month postoperatively (P < .05), representing a 14% decrease. The deltoid muscle volume of the contralateral side also significantly decreased during the same time frame, from 43,278 ± 12,248 to 40,273 ± 11,464 mm3 (P < .05), representing a 7% decrease at 1 month postoperatively. Subsequently, the deltoid muscle volume on both sides recovered to preoperative levels at 12 months and was maintained at 24 months. Only the thickness of the anterior part of the deltoid was markedly decreased, from 13.9 ± 3.7 mm preoperatively to 12.0 ± 3.2 mm at 1 month postoperatively (P < .05), representing a 14% reduction. The CMAP amplitude showed a significant decrease at 1 month postoperatively; however, no significant difference was observed after 12 months when compared with the preoperative values or the values on the contralateral side. Positive correlations were found between deltoid muscle volume and CMAP amplitude at 24 months as well as between deltoid muscle volume and shoulder abduction muscle strength (R 2 = 0.698; P < .05) and Constant score (R 2 = 0.133; P < .05). Our study demonstrated that the early structural and functional decline of the deltoid muscle after ARCR was fully recovered within 1 year, confirming that this procedure does not negatively affect the deltoid muscle.