Compound Muscle Action Potential Amplitude Research Articles

Nerve conduction study on the split-hand plus index in Amyotrophic lateral sclerosis: correlations with lower motor neuron impairment.

In the arms of patients with Amyotrophic lateral sclerosis (ALS) two peculiar patterns of dissociated muscular atrophy have been described: the split-hand sign (with predominant atrophy of the lateral aspect of the hand, compared to hypothenar eminence) and the split-hand-plus sign (SHPS), a predominant abductor pollicis brevis (ABP) atrophy with sparing of flexor pollicis longus (FPL). In this case-control study, we evaluated the diagnostic utility of a neurophysiological indicator of SHPS and assessed its association with clinical features. We prospectively studied 59 incident ALS patients, 61 patients with ALS-mimic disorders (OND) and 61 non-neurological controls (NNCs). ABP and FPL compound muscle action potentials (CMAP) amplitudes were obtained by supramaximal stimulation of median nerve at elbow. Split-hand plus index (SHPI) was calculated according to the formula: APB-CMAP/FPL-CMAP. SHPI was significantly lower in ALS compared to OND patients and NNCs (p < 0.0001). SHPI value < 1 was observed in 2% of NNCs and 9% of OND patients and demonstrated an accuracy of 71% in differentiating ALS from OND and an accuracy of 74% in differentiating ALS from NNC. SHPI was associated with higher LMN score, and higher disease severity as quantified by the ALSFRS-r. Our results indicate that SHPI is a reliable indicator to distinguish ALS patients from ONDs and NNCs. SHPI was significantly associated to the degree of lower motor neuron impairment but showed no association with upper motoneuron impairment.

Longitudinal Assessment of Outcome Measures of Diaphragm Motor Unit Connectivity As Biomarkers of Phrenic Motor Unit Degeneration and Compensation

Phrenic motor neurons (MNs) form the final link from the central nervous system (CNS) to the diaphragm muscle. Ventilatory function is modulated by the CNS via groups of muscle fibers each controlled by a single MN (motor units). Processes such as injury, aging, and neurodegeneration can result in losses of MNs, and their motor unit (MU) counterparts, but MNs and MUs have some capacity for compensation through mechanisms such as axonal sprouting and collateral sprouting to regain connectivity with denervated muscle. Motor unit number (motor unit number estimation, MUNE), MU size (single motor unit potential amplitude, SMUP), and summated muscle excitation (compound muscle action potential amplitude, CMAP) have been used clinically and preclinically for decades to track MU connectivity but efforts have largely focused on limb muscles. We aimed to apply these measures to a model of phrenic MN degeneration (intrapleural injection of cholera toxin B fragment conjugated to saporin, CTB-SAP).We hypothesized that CTB-SAP-induced phrenic motor neuron death would result in loss of diaphragm MU number and compensatory increases in MU size. Under isoflurane anesthesia, rats were bilaterally, intrapleurally injected with CTB-SAP (25 μg) to target phrenic MNs and extra CTB (25 μg) to label surviving phrenic MNs, and control rats received unconjugated CTB (25 μg) and SAP (25 μg). Diaphragm CMAP, SMUP, and MUNE were acquired bilaterally and averaged at baseline/pre-injection (n=14), as well as 7 (n=14), 14 (n=14), 21 (n=6), and 28 (n=14) days post-injection. No baseline differences between groups were found. MUNE showed a significant change for time (p&lt;0.05), treatment (p&lt;0.001), and interaction time x treatment (p&lt;0.01) with ~40% reduction of MUNE in CTB-SAP rats. Average SMUP of CTB-SAP rats demonstrated a significant change with time (p&lt;0.05) and treatment (p&lt;0.01), but no significant interaction with ~50-60% increase in SMUP amplitude. CMAP showed no significant change. Our results show a significant ~40% loss of MUs in CTB-SAP rats, similar to previous studies on morphological MN counts. In parallel with MU loss, MUs enlarged (increased SMUP), consistent with compensatory increases of MU size likely through MU collateral sprouting. In conclusion, our findings suggest that the use of diaphragm MU electrophysiological measures can provide insights into the onset and progression of CTB-SAP-induced pathology concerning the loss of phrenic MU integrity. Hence, these biomarkers can be used to investigate mechanisms of phrenic motor neuron degeneration and compensation, and to expedite the translation of experimental findings to clinical testing. Supported by a Spinal Cord Injury and Disease Research grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

GCPII Inhibition in Macrophages Delays Age-related Muscle Atrophy in Mice

Age-related loss of muscle mass and strength (Sarcopenia) significantly impairs quality of life in the elderly, yet lacks effective treatments. We previously demonstrated that inhibition of GCPII delayed muscle function decline and neuromuscular junction (NMJ) denervation in an amyotrophic lateral sclerosis (ALS) animal model. As sarcopenia shares NMJ deterioration with ALS, we tested the potent GCPII inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) in aging mice, and found that it also preserved muscle function and NMJ integrity. By immunofluorescent staining, we demonstrated that aged mice muscles were associated with GCPII-positive infiltrating macrophages. We next developed a macrophage-targeting GCPII inhibitor delivery system by covalently attaching 2-PMPA to 4th-generation polyamidoamine (G4-PAMAM) dendrimers (D-2-PMPA). The D-2-PMPA was found to inhibit GCPII with IC50= 3.50±0.05 nM. Aged mice muscle showed increased GCPII activity specifically in CD11b+ enriched macrophage cells (138.6±3.0 vs. 336.6±52.9; p&lt;0.05) but not in CD11b− cells. Systemic D-2-PMPA therapy (20 mg/kg 2-PMPA equivalent; IP 3 × /week) completely inhibited the elevated GCPII activity (336.5±52.8 vs. 21.8±9.2 fmol/mg/h; p&lt;0.001). 5-months of D-2-PMPA therapy initiated with 15-month-old mice significantly preserved calf muscle volume (95.0±0.8% vs. 90.4±0.7%; p &lt;0.001), enhanced isometric force (230.2±13.3 vs. 184.0±9.0 mN, female p&lt;0.05; 257.3±21.0 vs. 189.7±19.3 mN, male p&lt;0.05), improved grip strength (96.1±1.6 vs. 90.2±2.2 % of maximum p&lt;0.001) and increased rotarod latency (119.0±6.6 vs. 93.5±9.3 s, female p&lt;0.05; 104.5±5.2 vs. 79.3±4.2 s, male p&lt;0.001). Age-related decline of nerve signal conductivity to muscles was also delayed with D-2-PMPA as observed by improved compound muscle action potential (CMAP) latency (1.28±0.02 vs. 1.38±0.04 ms; p&lt; 0.05) and amplitude (15.2±0.5 vs. 1.27±0.6 mV; p&lt;0.01). Furthermore, NMJ integrity was preserved with treatment as demonstrated by single fiber jitter (5.4±0.3 vs. 7.5±0.5 μs; p&lt;0.01). Overall, our current results support that excessive GCPII activity in muscle macrophages is associated with age-related muscle atrophy, which is improved by GCPII inhibition. This study highlights GCPII inhibition in macrophages as a new therapeutic approach to delay sarcopenia. R01AG078181, R01AG068130, R01NS093416. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A c.1775C > T Point Mutation of Sodium Channel Alfa Subunit Gene (SCN4A) in a Three-Generation Sardinian Family with Sodium Channel Myotonia.

The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation. Next-generation sequencing including the CLCN1 and SCN4A genes was performed in patients with clinical neuromuscular disorders. Electromyography, Short Exercise Test, in vivo and in vitro electrophysiology, site-directed mutagenesis and heterologous expression were collected. A heterozygous point mutation (c.1775C > T, p.Thr592Ile) of muscle voltage-gated sodium channel α subunit gene (SCN4A) has been identified in five female patients over three generations, in a family with non-dystrophic myotonia. The muscle stiffness and myotonia involve mainly the face and hands, but also affect walking and running, appearing early after birth and presenting a clear cold sensitivity. Very hot temperatures, menstruation and pregnancy also exacerbate the symptoms; muscle pain and a warm-up phenomenon are variable features. Neither paralytic attacks nor post-exercise weakness has been reported. Muscle hypertrophy with cramp-like pain and increased stiffness developed during pregnancy. The symptoms were controlled with both mexiletine and acetazolamide. The Short Exercise Test after muscle cooling revealed two different patterns, with moderate absolute changes of compound muscle action potential amplitude. The p.Thr592Ile mutation in the SCN4A gene identified in this Sardinian family was responsible of clinical phenotype of myotonia.

Transsynaptic degeneration of ventral horn motor neurons exists but plays a minor role in lower motor system dysfunction in acute ischemic rats.

As a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated. Using a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed. At 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process. This study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

Estimation of the number of motor units in the human extensor digitorum brevis using MScanFit.

Our aim was to determine the number and size parameters of EDB motor units in healthy young adults using MScanFit, a novel approach to motor unit number estimation (MUNE). Since variability in MUNE is related to compound muscle action potential (CMAP) size, we employed a procedure to document the optimal EDB electromyographic (EMG) electrode position prior to recording MUNE, a neglected practice in MUNE. Subjects were 21 adults 21-44 y. Maximum CMAPs were recorded from 9 sites in a 4 cm2 region centered over the EDB and the site with the largest amplitude was used in the MUNE experiment. For MUNE, the peroneal nerve was stimulated at the fibular head to produce a detailed EDB stimulus-response curve or "MScan". Motor unit number and size parameters underlying the MScan were simulated using the MScanFit mathematical model. In 19 persons, the optimal recording site was superior, superior and proximal, or superior and distal to the EDB mid-belly, whereas in 3 persons it was proximal to the mid-belly. Ranges of key MScanFit parameters were as follows: maximum CMAP amplitude (3.1-8.5 mV), mean SMUP amplitude (34.4-106.7 μV), mean normalized SMUP amplitude (%CMAP max, 0.95-2.3%), largest SMUP amplitude (82.7-348 μV), and MUNE (43-103). MUNE was not related to maximum CMAP amplitude (R2 = 0.09), but was related to mean SMUP amplitude (R2 = -0.19, P = 0.05). The EDB CMAP was highly sensitive to electrode position, and the optimal position differed between subjects. Individual differences in EDB MUNE were not related to CMAP amplitude. Inter-subject variability of EDB MUNE (coefficient of variation) was much less than previously reported, possibly explained by better optimization of the EMG electrode and the unique approach of MScanFit MUNE.

Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration

BackgroundLate-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. Material and methodsA group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. ResultsEight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48–0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0–0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. ConclusionsOur study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.

Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D.

Inhibition of HDAC6 has been proposed as a broadly applicable therapeutic strategy for Charcot-Marie-Tooth disease (CMT). Inhibition of HDAC6 increases the acetylation of proteins important in axonal trafficking, such as α-tubulin and Miro, and has been shown to be efficacious in several preclinical studies using mouse models of CMT. Here, we sought to expand on previous preclinical studies by testing the effect of genetic deletion of Hdac6 on mice carrying a humanized knockin allele of Gars1, a model of CMT-type 2D. Gars1ΔETAQ mice were bred to an Hdac6 knockout strain, and the resulting offspring were evaluated for clinically relevant outcomes. The genetic deletion of Hdac6 increased α-tubulin acetylation in the sciatic nerves of both wild-type and Gars1ΔETAQ mice. However, when tested at 5 weeks of age, the Gars1ΔETAQ mice lacking Hdac6 showed no changes in body weight, muscle atrophy, grip strength or endurance, sciatic motor nerve conduction velocity, compound muscle action potential amplitude, or peripheral nerve histopathology compared to Gars1ΔETAQ mice with intact Hdac6. Our results differ from those of two previous studies that demonstrated the benefit of the HDAC6 inhibitor tubastatin A in mouse models of CMT2D. While we cannot fully explain the different outcomes, our results offer a counterexample to the benefit of inhibiting HDAC6 in CMT2D, suggesting additional research is necessary.

Reference values for nerve conduction studies of the peroneal, tibial, and sural nerve derived from a large population-based cohort: Associations with demographic and anthropometric characteristics-The Maastricht study.

Nerve conduction studies (NCSs) are widely used to support the clinical diagnosis of neuromuscular disorders. The aims of this study were to obtain reference values for peroneal, tibial, and sural NCSs and to examine the associations with demographic and anthropometric factors. In 5099 participants (aged 40-79 years) without type 2 diabetes of The Maastricht Study, NCSs of peroneal, tibial, and sural nerves were performed. Values for compound muscle action potential (CMAP) and sensory nerve action potential amplitude, nerve conduction velocity (NCV), and distal latency were acquired. The association of age, sex, body mass index (BMI), and height with NCS values was determined using uni- and multivariate linear regression analyses. Detailed reference values are reported per decade for men and women. Significantly lower NCVs and longer distal latencies were observed in all nerves in older and taller individuals as well as in men. In these groups, amplitudes of the tibial and sural nerves were significantly lower, whereas a lower peroneal nerve CMAP was only significantly associated with age. BMI showed a multidirectional association. After correction for anthropometric factors in the multivariate analysis, the association between sex and NCS values was less straightforward. These values from a population-based dataset could be used as a reference for generating normative values. Our findings show the association of NCS values with anthropometric factors. In clinical practice, these factors can be considered when interpreting NCS values.

Outcome measures in pediatric chronic inflammatory demyelinating polyradiculoneuropathy.

Objective outcome measures in children undergoing treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are lacking. The aim of the study was to record serial grip strength and motor nerve conduction studies to assess interval change. This was a retrospective review of 16 children (8 females and 8 males; median age, 9.7 years; interquartile range, 6-13 years) with CIDP followed at a tertiary children's hospital from 2013 to 2021. Subjects were treated with intravenous immunoglobulin (IVIG). Right and left grip strength measurements were obtained at each clinic visit using a handheld dynamometer. Annual right median motor nerve conduction study data were recorded during the study period. Mean duration of follow-up was 2.9 years. Grip strength (right: 0.19 kg/month, p < 0.001; left 0.23 kg/month, p < 0.001) and median F-wave latencies (-0.23/month, p = 0.015) showed significant improvement over time. Akaike information criterion showed time + IVIG frequency <21 days as best fit for grip strength and distal compound muscle action potential amplitude. Our study results indicate serial grip strength measurements are a feasible and objective way to assess motor strength improvement in children with CIDP receiving immunotherapy.

Pathologic classification of a late-onset peripheral neuropathy in a spontaneous Labrador retriever dog model.

Late-onset peripheral neuropathy (LPN) is a heritable canine neuropathy commonly found in Labrador retrievers and is characterized by laryngeal paralysis and pelvic limb paresis. Our objective was to establish canine LPN as a model for human hereditary peripheral neuropathy by classifying it as either an axonopathy or myelinopathy and evaluating length-dependent degeneration. We conducted a motor nerve conduction study of the sciatic and ulnar nerves, electromyography (EMG) of appendicular and epaxial musculature, and histologic analysis of sciatic and recurrent laryngeal nerves in LPN-affected and control dogs. LPN-affected dogs exhibited significant decreases in compound muscle action potential (CMAP) amplitude, CMAP area, and pelvic limb latencies. However, no differences were found in motor nerve conduction velocity, residual latencies, or CMAP duration. Distal limb musculature showed greater EMG changes in LPN-affected dogs. Histologically, LPN-affected dogs exhibited a reduction in the number of large-diameter axons, especially in distal nerve regions. In conclusion, LPN in Labrador retrievers is a common, spontaneous, length-dependent peripheral axonopathy that is a novel animal model of age-related peripheral neuropathy that could be used for fundamental research and clinical trials.

Relationship between Gravidity, Parity, and Neurophysiological Features in Carpal Tunnel Syndrome (CTS) Patients with a History of Pregnancy.

It is not yet clear if gravidity and parity have any relationships with the electrodiagnostic parameters of carpal tunnel syndrome (CTS). To determine whether there is a relationship between electrodiagnostic findings, gravidity, and parity number in CTS. Female patients over 18 years of age with CTS were included in this retrospective cohort study. The gravidity/parity number, median nerve compound muscle action potential (CMAP), and compound nerve action potential (CNAP) of the patients were analyzed. The two subgroups of the Boston carpal tunnel syndrome questionnaire (BCTSQ): The Symptom Severity Scale (SSS) and Functional Severity Scale (FSS) were applied to the patients. CTS patients were divided into two groups aged at first pregnancy ≤20 years and >20 years. One hundred and eight CTS extremities (seven right-sided CTS, three left-sided CTS, 49 bilateral CTS) of 59 patients were included. The median (interquartile range: 25%-75%) number of gravidity, parity, and abortion were 3 (2-5), 3 (2-4), and 0 (0-0), respectively. Right-sided CTS patients at the age of first pregnancy ≤20 years had higher BCTSQ-SSS/FSS scores and median nerve CMAP latency compared to patients at the age of first pregnancy >20 years (P = 0.029 for SSS; P = 0.042 for FSS; and P = 0.041 for CMAP latency). A negative correlation was found between the gravidity/parity numbers and median nerve CNAP/CMAP amplitudes (P = 0.028/0.031, r = -0.293/-0.289 for CNAP amplitude; and P = 0.006/0.035, r = -0.363/-0.283 for CMAP amplitude). Neurophysiological findings worsen as the number of gravidity and parity increase. Electrodiagnostic and clinical features of CTS may be worsening in females below 20 years at first pregnancy.

Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients. Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria. The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations. This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria.

Value of MUNE versus compound muscle action potential in assessing motor unit loss in patients with carpal tunnel syndrome

BackgroundThe most prevalent nerve entrapment disorder, known as carpal tunnel syndrome (CTS), is brought on by wrist-based median nerve compression. Focal demyelination progresses to axonal dysfunction as the condition worsens. In order to detect motor unit (MU) loos, this study compares two motor unit number estimation (MUNE) techniques with compound muscle action potential (CMAP) amplitude. The CMAP amplitude and MUNE of the median nerve in 137 hands of 70 neurophysiologically approved CTS patients, aged 40.27 ± 10.06 years were examined. Another 90 hands from 56 healthy volunteers who are age- and gender-matched serve the control group.ResultsIn contrast to 192.5 and 248.5 in controls, the median nerve values of incremental and adapted multipoint stimulation (aMPS) MUNE in CTS patients were, respectively, 111 and 133 (p < 0.0001). Patients with severe CTS compared to those with mild CTS using both methods had significantly lower MUNE. MUNE values are the same regardless of gender or hand dominance. In comparison to MUNE methods (cutoff values of 106.5 and 203, respectively), CMAP amplitude had a sensitivity and specificity of more than 60% in detecting MU loss (cutoff value of 6.85 mV). The CTS grading had no effect on the CMAP amplitude. MUNE values had positive with CMAP amplitude and negative with CTS grading and Phalen test positivity.ConclusionsWhen identifying motor nerve involvement in CTS patients, the MUNE technique is more accurate than a standard motor nerve conduction study (NCS). It was emphasized that MUNE evaluation in determining MU loss in the early stages of CTS may be helpful in diagnosis and treatment. There was no correlation between handedness and the number of MUs as determined by MUNE techniques. Both methods almost equally identify MU loss and have the same sensitivity and specificity.

The Effect of Liraglutide on Axon Regeneration and Functional Recovery after Peripheral Nerve Lesion.

Peripheral nerve injuries inflict severe consequences, necessitating innovative therapeutic strategies. This study investigates the potential of liraglutide, a glucagon-like peptide-1 receptor agonist, in mitigating the consequences of peripheral nerve injury. The existing treatment methods for such injuries underscore the importance of ongoing translational research efforts. Thirty adult Wistar rats underwent sciatic nerve dissection and repair surgery. The nerves were surgically transected using micro scissors at a precise location located 1.5 cm proximal to the trifurcation site. The study included a control group and two experimental groups, one treated with saline (placebo group) and the other with liraglutide (experimental group) for 12 weeks. Motor function, electromyography (EMG), and biochemical and histopathological analyses were performed after 12 weeks of treatment. Electrophysiological assessments revealed that liraglutide improved the compound muscle action potential (CMAP) amplitude and motor function compared to the saline-treated group. Histological and immunohistochemical analyses demonstrated increased NGF expression, total axon number, and diameter and reduced fibrosis in the liraglutide group. Biochemical analyses illustrated liraglutide's antioxidative properties, evidenced by reduced malondialdehyde (MDA) levels. Galectin-3 levels were suppressed and GDF-11 levels were modulated by liraglutide, indicating anti-inflammatory and anti-apoptotic effects. Liraglutide is a promising therapeutic intervention for peripheral nerve injuries, promoting functional recovery and histopathological improvement. Its multifaceted positive impact, beyond glycemic control, suggests constructive effects on the acute and chronic inflammatory processes associated with peripheral neuropathy. These findings warrant further research to elucidate molecular mechanisms and facilitate clinical translation. The study contributes valuable insights to the growing understanding of GLP-1 receptor agonists' neuroprotective properties in the context of peripheral nerve injuries.

Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy: A Multicenter Cohort Study in South Korea.

Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

Efficacy of collagen conduit wrapping with collagen fibers on nerve regeneration in sciatic nerve injury with partial transection: An experimental study in the rat model.

Peripheral nerve injuries (PNIs) include complete and partial transection, crushing, and chronic compression injuries. Hollow absorbable conduits are used to treat complete transection with short defects, while wrapping the injured part with an absorbent material promotes nerve recovery by inhibiting inflammatory cell infiltration and scar tissue formation in crush injuries. For treatment of partially transected nerve injuries (PTNIs), such as injection-related iatrogenic PNI, whether wrapping the entire nerve, including the injury site, or bridging the transected fascicle with an artificial nerve conduit (ANC) is beneficial remains to be verified. The purpose of this study was to investigate whether wrapping the injured nerve and placing collagen fibers as scaffolds at the nerve defect site contribute to neural recovery in PTNI. A unilateral 5-mm partial nerve defect was created at the mid-thigh level in a rat sciatic nerve injury model. Fifty-four Sprague-Dawley (SD) rats (150-250 g) were divided into three groups (n = 9 each): group 1, collagen fibers were placed in the nerve defect and the sciatic nerve was wrapped with collagen conduit; group 2, the sciatic nerve was wrapped by collagen conduit without collagen fibers; and group 3, nerve defect was reconstructed with collagen-filled conduit. Nerve regeneration was evaluated by analyses of gait, electrophysiology, wet muscle weight, and axon numbers with immunohistochemistry at 12 and 24 weeks. Dorsiflexion angles among all groups improved significantly from 12 to 24 weeks postoperatively. At 24 weeks postoperatively, compound muscle action potential amplitudes (CMAPs) of tibialis anterior were 5.26 ± 4.64, 1.31 ± 1.17, and 0.14 ± 0.24 mV (p < .05), CMAPs of gastrocnemius were 21.3 ± 5.98, 15.4 ± 5.46, and 13.11 ± 3.91 mV in groups 1, 2, and 3, respectively; and the value of group 1 was significantly higher than that of group 3 (p < .05). Axon numbers were 2194 ± 629; 1106 ± 645; and 805 ± 907 in groups 1, 2, and 3, respectively (p < .05). For PTNI reconstruction, artificial nerve wrap (ANW) was superior to ANC. Providing collagen scaffold at the nerve defect site enhanced nerve recovery during reconstruction with ANW.

Compound muscle action potential of whole-forearm flexors: A clinical biomarker for inclusion body myositis

ObjectiveThis study aimed to investigate the potential of whole-forearm flexor muscle (WFFM) compound muscle action potential (CMAP) as a quantitative biomarker for inclusion body myositis (IBM) pathology. MethodsWe prospectively enrolled 14 consecutive patients (10 men and 4 women) diagnosed with IBM based on muscle biopsies. We evaluated the baseline-to-peak amplitude of the WFFM CMAP and other quantitative parameters, including grip and pinch strength, Inclusion Body Myositis Functional Rating Scale (IBMFRS) score, and other routine muscle CMAP amplitudes. ResultsThe WFFM CMAP was strongly correlated with disease duration and the IBMFRS score. The WFFM CMAP on the more affected side was lower than that on the less affected side. Furthermore, grip power was strongly correlated with the WFFM CMAP, whereas lateral pinch strength was strongly correlated with the WFFM and first dorsal interosseous CMAPs. The 3-point pinch strength was also correlated with the WFFM CMAP. ConclusionsThis study demonstrates that the WFFM CMAP may serve as a biomarker of severity in IBM. SignificanceIdentification of this biomarker can support drug development, diagnosis, prognosis, and treatment options for patients with IBM.

Temporary and highly variable recovery of neuromuscular dysfunction by electrical stimulation in the follow-up of acute critical illness neuromyopathy: a pilot study

BackgroundIn sepsis-associated critical illness neuromyopathy (CIPNM) serial electrical stimulation of motor nerves induces a short-lived temporary recovery of compound muscle action potentials (CMAPs) termed facilitation phenomenon (FP). This technique is different from other stimulation techniques published. The identification of FP suggests a major functional component in acute CIPNM.MethodsFrom our previous study cohort of 18 intensive care unit patients with sepsis associated CIPNM showing profound muscle weakness and low or missing CMAPs on nerve conduction studies, six patients with different severity could be followed. In a pilot sub-study we analyzed the variability of FP during follow up. Over up to 6 weeks we performed 2–6 nerve conduction studies with our novel stimulation paradigm. Motor nerves were stimulated at 0.2–0.5 Hz with 60–100 mA at 0.2–0.5 ms duration, and CMAP responses were recorded. Standard motor nerve conduction velocities (NCV) could be done when utilizing facilitated CMAPs. Needle electromyography was checked once for spontaneous activity to discover potential denervation and muscle fiber degeneration. Serum electrolytes were checked before any examination and corrected if abnormal.ResultsIn all six patients a striking variability in the magnitude and pattern of FP could be observed at each examination in the same and in different motor nerves over time. With the first stimulus most CMAPs were below 0.1 mV or absent. With slow serial pulses CMAPs could gradually recover with normal shape and near normal amplitudes. With facilitated CMAPs NCV measurements revealed low normal values. With improvement of muscle weakness subsequent tests revealed larger first CMAP amplitudes and smaller magnitudes of FP. Needle EMG showed occasional spontaneous activity in the tibialis anterior muscle.ConclusionIn this pilot study striking variability and magnitude of FP during follow-up was a reproducible feature indicating major fluctuations of neuromuscular excitability that may improve during follow-up. FP can be assessed by generally available electrophysiological techniques, even before patients could be tested for muscle strength. Large scale prospective studies of the facilitation phenomenon in CIPNM with or without sepsis are needed to define diagnostic specificity and to better understand the still enigmatic pathophysiology.Trial registration: This trial was registered at the Leipzig University Medical Center in 2021 after approval by the Ethics Committee.

Combination of stem cells and nerve guide conduit for the treatment of peripheral nerve injury: A meta-analysis.

Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta-analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence. A systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta-analysis. Fifty-five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow-up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose-derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified. The findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.