Muscle Action Research Articles

MScanFit and StairFit Motor Unit Number Estimation of the Extensor Digitorum Brevis and Abductor Digiti Minimi Muscles.

MScanFit and StairFit are two motor unit number estimation (MUNE) methods derived from a compound muscle action potential (CMAP) scan. This study aims to compare MScanFit and StairFit MUNE values by applying both methods to the same muscles. CMAP scans were recorded from the extensor digitorum brevis (EDB) and abductor digiti minimi (ADM) muscles. MUNE was performed using the MScanFit and the StairFit programs. Twenty healthy subjects (30.1 ± 6.6 years; 11 males, 9 females) participated in the study. The MScanFit and StairFit MUNE values were 79 ± 35 and 63 ± 20 for the EDB muscle, and 124 ± 33 and 80 ± 20 for the ADM muscle, respectively. The StairFit MUNE was significantly lower than the MScanFit MUNE (p < 0.05 for EDB, p < 0.01 for ADM). The different results for MScanFit and StairFit MUNE are likely due to the different strategies used by the two methods. Serial studies are needed to further compare their performances in tracking motor unit number and size changes.

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.

The Higher Positive Amyloid Deposition in Electrophysiologically Proven Idiopathic Carpal Tunnel Syndrome Patients.

Background: Carpal tunnel syndrome (CTS) due to amyloid deposition was reported to precede fatal cardiac amyloidosis by several years. Although nerve conduction study (NCS) supports CTS diagnosis, the incidence of positive amyloid deposition in electrophysiologically proven CTS is unclear. Methods: We retrospectively analysed the demographic data including age, gender, bilateral hand involvement, amyloid deposition and NCS results, of 111 consecutive CTS patients with postoperative symptom improvement (mean 71.1 years old, male/female ratio: 44/67) who simultaneously underwent carpal tunnel release (CTR) and biopsy for amyloid deposition. Results: Electrophysiologically proven CTS patients were 102 (91.9%) out of 111 patients. Amyloid deposition was detected in 62 hands (55.9%), of which 51 were transthyretin amyloid. The NCS severity was associated with a higher prevalence of positive amyloid deposition (p < 0.01). The NCS severity also showed an increased trend between reported risk factors for positive amyloid deposition such as older age, male gender and bilateral hand symptoms (p < 0.01). Conclusions: The prevalence of positive amyloid deposition was higher than previous reports in this study. Abnormal NCS findings in CTS, such as an increased distal motor latency (DML) of abductor pollicis brevis compound muscle action potentials (APB-CMAP) or absent APB-CMAP, may help to increase the pre-test probability of amyloid deposition in tenosynovial biopsy. Level of Evidence: Level IV (Diagnostic Study).

Distinct dynamic regulation of pectoralis muscle metabolomics by insulin and the promotion of glucose-lipid metabolism with extended duration

Birds' glycolipid metabolism has garnered considerable attention due to their fasting blood glucose levels being nearly twice those of mammals. While skeletal muscle is the primary insulin-sensitive tissue in mammals, the effects of insulin on chicken skeletal muscle remain unclear. In this study, the insulin-responsive metabolites were identified in broiler's pectoralis muscle (after 16 h of fasting) using widely targeted metabolomics. Glycolipid concentrations were measured using kits, and the expression of key genes involved in glucose metabolism was assessed via quantitative real-time PCR (qRT-PCR). The insulin tolerance test, performed by injecting 5 IU/kg body weight of insulin, demonstrated a rapid drop in blood glucose levels from 0 to 15 min, with a consistent reduction observed at 120 min (P < 0.01). Insulin did not alter glucose and glycogen content in chicken pectoralis; however, low-density lipoprotein (LDL, P < 0.05) levels were upregulated in the early phase (15 min). With an extended insulin duration (120 min), pectoralis glucose content increased (P < 0.05), accompanied by a reduction in TG levels (P < 0.05). Metabolomic analysis revealed that insulin promotes the downregulation of 63 out of 71 metabolites at 15 min and the upregulation of 101 out of 134 metabolites at 120 min, mainly associated with lysine degradation and thyroid hormone signaling pathways, respectively. 7 metabolites were dynamically modulated in the same manner over time (2 up-up and 5 down-down). Early insulin inhibited glycolysis, evidenced by the reduction in phosphoenolpyruvate levels and hexokinase 2 (HK2) expression; however, insulin promoted glucose uptake through the activation of glucose transporter 4 (GLUT4) and enhanced glycolysis, accompanied by elevated fatty acid metabolism at the later phase. In conclusion, insulin dynamically regulates the metabolomics of the pectoralis muscle over time. Initially, chicken muscle tissues downregulate metabolic activities to accommodate the new signaling state, followed by significant upregulation to meet heightened metabolic demands. Extended insulin monitoring promotes glucose uptake and glycolysis, alongside enhanced fatty acid metabolism. This research provides insights into the potential mechanisms of insulin action in chicken muscles.

A new method to evaluate staircase phenomenon in skeletal muscle using piezoelectric sensor.

The staircase phenomenon, which refers to the increases in the force of contraction with repetitive stimulation of the muscle, has been studied for many years, but the method is difficult and not widely used. Our objective was to evaluate the staircase phenomenon in skeletal muscle using a piezoelectric sensor. Thirty-five subjects without neuromuscular diseases (normal controls), 11 patients with Becker muscular dystrophy (BMD), and 19 patients with myotonic dystrophy type 1 (MyD) were studied. Compound muscle action potential (CMAP) and movement-related potential (MRP) waveforms were recorded using piezoelectric sensors during repetitive stimulation of the median nerve, and the amplitudes and durations were measured. Excitation-contraction (E-C) coupling time (ECCT) was calculated from the difference between onset latencies of CMAP and MRP. In normal controls, MRP amplitude ratio (relative to baseline) increased significantly with increase in stimulation duration and with increase in stimulation frequency. In BMD and MyD, however, MRP amplitude ratio did not change significantly with increase in stimulation duration. Especially, in MyD, there was no change in MRP amplitude ratio with increase in frequency. Staircase phenomenon abnormalities can be evaluated easily using piezoelectric sensors, indicating their potential utility for evaluating E-C coupling impairment in myopathies. Piezoelectric sensors may be a useful tool to evaluate staircase phenomenon in skeletal muscle.

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.

A cross-sectional and longitudinal evaluation of serum creatinine as a biomarker in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by proximal muscle weakness and atrophy. The increasing availability of disease-modifying therapies has prompted the development of biomarkers to facilitate clinical assessments. We explored the association between disease severity and serum creatinine (Crn) levels in SMA patients undergoing up to two years of treatment with nusinersen. We measured serum Crn levels and assessed function performance using the Hammersmith Functional Motor Scale-Expanded (HFMSE), Medical Research Council Scale (MRC), 6-Minute Walk Test (6MWT), ulnar Compound Muscle Action Potential (CMAP), and forced vital capacity (FVC) in a cohort comprising 28 adolescent and adult patients with SMA. The association between Crn and disease severity was investigated through partial rank correlation analysis and linear mixed models while accounting for age, gender, and BMI. Linear models were employed to predict functional performance. 28 SMA patients and 28 gender- and age-matched healthy controls (HCs) were included, resulting in a dataset of 185 visits. Compared to HCs, SMA patients exhibited significantly lower Crn values ​​(67.4 ± 14 vs. 23.7 ± 14.8 umol/L, p<0.0001). After adjusting for age, sex, and BMI, Crn showed positive correlations with the HFMSE (p<0.0001, r = 0.884), MRC (p<0.0001, r = 0.827), FVC (p = 0.002, r = 0.730), and ulnar CMAP (p<0.0001, r = 0.807). Patients with SMN2 copy number ≥ 4 had nearly twice as high Crn levels as those with SMN2 copy number < 4 (34.1 ± 3.75 vs. 17.2 ± 2.52 umol/L, p = 0.00145). Ambulant SMA patients had more than double the Crn levels compared to non-ambulant ones (32 ± 2.33 vs. 12.9 ± 2.38 umol/L, p<0.0001). Furthermore, Crn explained that up to 83.5% of the variance in functional performance measured by HFMSE, MRC, and 6MWT was significantly higher than that of traditional biomarkers. These findings suggest that Crn may be a potential biomarker for assessing disease severity in adolescents and adults with SMA, demonstrating its promise in clinical applications.

Efficacy of cold and cryo-preserved nerve allografts with low-dose FK506 for motor nerve regeneration: a preclinical study

BackgroundDespite their ability to regenerate as well as autografts, the use of nerve allografts is limited by the need for immunosuppression and the risk of disease transmission. Further, decellularized allografts lacking Schwann cells limit axonal regeneration in long nerve defects. This study evaluated sciatic nerve regeneration in rats implanted with cold- or cryopreserved allografts, and examined the effects of FK506, an immunosuppressant that targets calcineurin function, on motor recovery.MethodsSixty-five male Lewis rats were divided into five groups of 13, each with a 10-mm sciatic nerve gap. Group I received an autograft, whereas Groups II and III received allografts pretreated with cryopreservation and cold preservation, respectively. Groups IV and V were also implanted with cryo- and cold-preserved allografts, but were treated with a low dose of FK506. Motor regeneration was assessed at 20 weeks by the measurement of ankle contracture, compound muscle action potential, maximal isometric tetanic force, wet muscle weight of the tibialis anterior, peroneal nerve histomorphometry, and immunohistochemistry of the reconstructed sciatic nerve.ResultsSimilar motor recovery was observed between the autografts and both types of allografts. The groups treated with FK506 showed improved recovery, particularly in terms of ankle angle and tibialis anterior muscle weight. Histomorphometry revealed a superior myelinated fiber area and nerve ratio in the cold-preserved allograft group, while Group II displayed a less well-organized morphology.ConclusionThis study demonstrates that cold- or cryopreserved nerve allografts represent effective alternatives to autografts for peripheral nerve reconstruction, with low-dose FK506 enhancing motor recovery without necessitating immunosuppression.Level of Evidence IBasic Science Level I.

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.

Optimizing Anti-Myelin-Associated Glycoprotein and IgM-Gammopathy Testing for Neuropathy Treatment Evaluation.

Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies. European Academy of Neurology/Peripheral Nerve Society 2021 guidelines were used to assess patients with neuropathy using anti-MAG Bühlmann titration units (BTU) and IgM-gammopathy with Mass-Fix (mass spectrophotometry) and serum protein immunofixation electrophoresis (SPIEP). The immunotherapy outcome was reviewed by inflammatory neuropathy cause and treatment (INCAT) and summated compound muscle action potential (CMAP) nerve conduction changes. Seven hundred and fifty-two patients (average age: 63.8 years, female: 31%) were identified over 30 months: (1) typical anti-MAG neuropathy (n = 104); (2) atypical anti-MAG neuropathy (n = 13); (3) distal or sensory-predominant CIDP (n = 25), including 7 without IgM-gammopathy; (4) typical CIDP (n = 47), including 36 without IgM-gammopathy; (5) axonal IgM-gammopathy-associated neuropathy (n = 104); and (6) IgM-gammopathy-negative, anti-MAG-negative axonal neuropathies (n = 426); and (7) without neuropathy (n = 33) anti-MAG negative. IgM-gammopathy was evaluated by Mass-Fix (n = 493), SPIEP (n = 355), or both (n = 96). Mass-Fix detected 4 additional IgM-gammopathies (3%, 4/117) among patients with anti-MAG antibodies and 7 additional patients (2%, 7/376) without anti-MAG not detected by SPIEP testing. Immunotherapy follow-up was available in 123 (mean: 23 months, range: 3-120 months) including 47 with CIDP (28 without IgM-gammopathy) and 76 non-CIDP (5 without IgM-gammopathy, 45 anti-MAG positive). Treatments included IVIG (n = 89), rituximab (n = 80), and ibrutinib or zanubrutinib (n = 24). An optimal anti-MAG-positive cutoff was identified at ≥1,500 BTU (78% sensitivity, 96% specificity) and at ≥10,000 BTU (74% sensitivity, 100% specificity) for typical anti-MAG neuropathy. Improvements in INCAT scores (p < 0.0001) and summated CMAP (p = 0.0028) were associated with negative anti-MAG (<1,500 BTU, n = 78) and absence of IgM-gammopathy (n = 34). Among 47 patients with electrodiagnostically confirmed CIDP, all anti-MAG negative, the presence of IgM-gammopathy (n = 19) also correlated with a worse treatment response (INCAT scores p = 0.035, summated CMAP p = 0.049). A cutoff of 10,000 BTU seems optimal for typical anti-MAG neuropathy while ≥1,500 BTU reduces the likelihood of immune-treatable CIDP. Mass-Fix improves IgM-gammopathy detection in anti-MAG and other IgM-gammopathy neuropathies. Patients with IgM-gammopathy lacking MAG antibodies show reduced treatment response.

Nerve cross-sectional area in vincristine-induced polyneuropathy: A nerve ultrasound pilot study.

The role of high-resolution nerve ultrasound (HRUS) in the diagnosis of chemotherapy-induced polyneuropathy is unclear. The present prospective longitudinal controlled study evaluates the utility of HRUS in vincristine-induced polyneuropathy (VIPN). Twelve patients receiving vincristine and 12 healthy age-matched controls were included. Visits before and 3weeks, 8weeks, and 6months after the start of vincristine treatment included clinical examination, the total neuropathy score (TNS), nerve conduction studies (NCSs), and HRUS of the bilateral median, ulnar, radial, tibial, peroneal, and sural nerve cross-sectional areas (CSAs). Median TNS increased from 0 points (interquartile range [IQR] 0) to 0.5 points (IQR 1, p=.26) at Week 3 and to 4 points (IQR 2.5, p<.001) at Week 8. At 6months, there was a nonsignificant decrease to 2 points (IQR 2, p=.66). HRUS of individual nerve sites showed no significant changes in CSA and intranerve variability. The total CSA of all entrapment sites increased significantly (p=.007) at Week 8. Sensory nerve action potentials decreased significantly after 6months (sural nerve, p=.001; radial nerve, p=.004; ulnar and median nerve, p<.001). The tibial nerve compound muscle action potential (p=.006) and nerve conduction velocity (p<.001) were reduced. At mid-treatment, there is an increase in the total CSA at entrapment sites parallel to an increase in clinical symptoms. In individual nerve sites, HRUS does not detect significant signs of VIPN. NCSs exhibit signs of a predominantly sensory axonal polyneuropathy. The clinical examination remains the most sensitive tool in the early detection of VIPN.

Granulocyte colony-stimulating factor promotes regeneration of severed facial nerve in rats.

The administration of growth and neurotrophic factors has been attempted experimentally as a new therapeutic strategy for severe facial paralysis. Granulocyte colony-stimulating factor (G-CSF) has an effect on the treatment of central nervous system injuries, such as cerebral infarction and spinal cord injury. This study aimed at examining the effects of G-CSF on facial nerve regeneration in rats. The left facial nerve of rats was either partially resected (resection group) or severed and sutured (suture group) at the main trunk outside the temporal bone. In each surgical group, saline or G-CSF was administered via the gelatin hydrogel drug delivery system. The suture group was further divided into two subgroups for the late administration of G-CSF (2 weeks after surgical treatment) or immediate administration of G-CSF after surgical treatment. Recovery of the facial nerve was assessed by the evaluation of facial movements (after 12 weeks), complex muscle action potential amplitude measurements (after 2, 4, 8, and 12 weeks), electroneurography values (after 12 weeks), and histological evaluation (comparison of myelinated axon diameters among the groups). Recovery of the function and morphology of damaged nerves was faster in the suture groups than in the resection group. In the suture groups, recovery was faster for G-CSF-treated rats than for saline-treated rats. Furthermore, recovery was faster in the group that received G-CSF immediately after surgical treatment than in the group that received G-CSF 2 weeks later. However, the group that received G-CSF 2 weeks later also showed faster recovery than did the control group. G-CSF effectively promoted nerve regeneration during facial nerve paralysis. Thus, G-CSF may be a potential treatment strategy for injured facial nerves as it has been safely administered in clinical treatments for hematological diseases.

Quantifying the split-elbow sign: a comprehensive study in amyotrophic lateral sclerosis.

The split-elbow sign (SES), characterized by preferential dysfunction of the biceps brachii compared to the triceps, is a clinical feature observed in amyotrophic lateral sclerosis (ALS). However, the quantified SES index has not been extensively investigated, and its role in diagnosing ALS remains unknown. Therefore, this study aimed to investigate the split-elbow index (SEI) derived from compound muscle action potential (CMAP), motor unit number index (MUNIX), and echo intensity (EI) in ALS. A cohort comprising 70 individuals diagnosed with ALS, along with 41 disease controls and 40 healthy controls, was recruited for the study. The SEI was calculated by dividing the recorded values of CMAP, MUNIX, and EI obtained over the biceps brachii by the corresponding value measured in the triceps, resulting in SEICMAP, SEIMUNIX, and SEIEI, respectively. Receiver operating characteristic (ROC) curves of the three methods were used for comparison. Statistical analyses were performed using SPSS V.26.0 and R software. Both SEICMAP and SEIMUNIX exhibited significant reductions in ALS patients compared to that in controls (PSEICMAp < 0.0001, PSEIMUNIX < 0.0001), while SEIEI showed an elevation (P < 0.0001). Furthermore, there was a notable decrease in SEIMUNIX values as the disease progressed (p < 0.001). Moreover, ROC for SEIMUNIX exhibited superior diagnostic performance (AUC = 0.846), and a comprehensive diagnostic approach combining SEICMAP, SEIMUNIX, and SEIEI resulted in AUC (0.90) on the ROC curve. Our study suggested that SES has emerged as a significant clinical characteristic in ALS and indicated the potential of SES indicators as biomarkers for both diagnosis and assessment of disease progression in ALS.

Use of hyperelastic models and sliding connections to model the mechanical behavior of musculoskeletal structures

The generation of movement and force produced by the musculoskeletal system in various parts of the body is a topic of high interest in academic research. The increasingly detailed and precise knowledge of the biomechanical behavior of these structures is required to meet the demands of health care and human well-being. The use of structural analysis tools is essential for that purpose. In some situations, in vivo or in vitro tests present a series of inconveniences; therefore, computational simulations prove to be complementary to experimental tests to analyze human movements and generally offer advantages in terms of cost and time. To contribute to the construction of a more precise understanding of the mechanical behavior of biological structures, this work aims to numerically simulate the planar behavior of the upper limb of the human body through the action of skeletal muscles and the movement of adjacent joints. The mechanical simulation is performed through a computational code developed based on the Positional Finite Element Method (PFEM), capable of performing geometric nonlinear analyses directly in its formulation. The proposed modeling treats the muscle tissue as a composite material made of a three-dimensional matrix and embedded simple bar elements, which represent the muscle fibers. Despite the three-dimensional nature of the model, it is important to emphasize that the work aims at a two-dimensional application, simulating the mechanical behavior of musculoskeletal structures on a single plane. The Saint-Venant-Kirchhoff hyperelastic constitutive model is used to define the relationship between stresses and strains in the materials, highlighting its potential and limitations. Additionally, the active muscle behavior is considered through a numerical strategy that represents fiber contraction by allows controlling the initial length of the bar element. The joint studied in the model is the elbow, modeled through the formulation of sliding connections, allowing relative movement between connected surfaces. Since the mechanical simulation is planar, only flexion and extension movements are reproduced. The kinematic conditions imposed on the system to promote sliding are introduced into the problem using Lagrange multipliers. The proposed model has the potential to describe the mechanical response of human body members in a simplified manner.

Measuring Compound Muscle Action Potentials by Stimulating the Phrenic Nerve in a Rat

Measuring Compound Muscle Action Potentials by Stimulating the Phrenic Nerve in a Rat

Measuring Compound Muscle Action Potentials by Stimulating the Phrenic Nerve in a Rat

Measuring Compound Muscle Action Potentials by Stimulating the Phrenic Nerve in a Rat

The safety and efficacy of stem cell therapy for diabetic peripheral neuropathy in animal studies: A systematic review and meta-analysis.

Diabetic peripheral neuropathy (DPN) is the most common form of diabetic neuropathy, representing 75% of cases and posing a substantial public health challenge. Emerging evidence from animal studies indicates that stem cell therapy holds significant promise as a potential treatment for diabetic neuropathy. Nevertheless, a comprehensive evaluation of the safety and efficacy of stem cell therapy for DPN in animal studies remains outstanding. A systematic search of MEDLINE, Embase, Scopus, the Web of Science, and the CENTRAL was performed. The time period was up to January 31, 2024. All animal studies investigating the stem cell therapy for treating DPN were included. A random-effects model to combine effect sizes in our meta-analysis was applied. 29 out of the 5431 records met the eligibility criteria. In these studies, stem cell therapy improved motor and sensory nerve conduction velocity, compound muscle action potential (CMAP), and sciatic nerve blood flow. Post-treatment, mechanical and thermal nociceptive thresholds decreased. Rats had significant improvement in axonal circularity, nerve growth factor, and transforming growth factor beta 1; mice had significant increase in weight, CMAP, and angiopoietin 1. The stem cell subgroup analysis showed that dental pulp stem cells had the greatest effects across all parameters, while bone marrow mononuclear cells had strong biochemical responses. Stem cell therapy demonstrates promising efficacy in ameliorating neuropathic symptoms in DPN animal models. Human patient studies and targeted treatment procedures for specific neuropathic disorders are advocated to improve therapeutic outcomes.