Muscle & Nerve最新文献

Introduction/aims: VAChT-Cre is a transgenic mouse line targeting slow-twitch fatigue-resistant and fast-twitch fatigue-resistant motor neurons that innervate oxidative type I and type IIa muscle fibers. To ablate these neurons, VAChT-Cre mice were crossbred with NSE-DTA mice, leading to the expression of diphtheria toxin A after Cre-mediated excision. The resulting VAChT-Cre;NSE-DTA mice exhibited motor deficits, abnormal locomotion, muscular atrophy, and tremor, making them a useful model for studying motor neuron physiology and pathology. In this study, we conducted a kinematic analysis to examine their abnormal locomotor phenotype.

Methods: The quadrupedal walking of VAChT-Cre;NSE-DTA and control mice along a 500 mm acrylic tunnel was analyzed using an X-ray fluoroscopic system. Stride duration, stride length, footfall patterns, and limb and trunk kinematics were quantified and compared between the two groups.

Results: Our results demonstrated that VAChT-Cre;NSE-DTA mice walked more slowly than control mice (99.2 ± 43.5 mm/s vs. 120.5 ± 27.0 mm/s) and had a longer cycle duration (0.54 ± 0.19 s vs. 0.41 ± 0.09 s). In addition, the hindlimb was comparatively more flexed during the stance phase, the trunk was more rounded and humpbacked, and the cervix was lower in VAChT-Cre;NSE-DTA mice than in the control mice during locomotion.

Discussion: These characteristic differences in the gait kinematics might be attributed to a malfunctioning of the motor units with slow-twitch fatigue-resistant and fast-twitch fatigue-resistant types in VAChT-Cre;NSE-DTA mice. The basic description of the locomotor characteristics of this transgenic mouse line may serve as a basis for future comparative analyses.

Introduction/aims: Claims-based analyses have demonstrated high medical costs associated with myasthenia gravis (MG). We examined the economic burden of MG from the perspective of affected people and their families.

Methods: The Muscular Dystrophy Association developed and conducted an online survey of people with MG and their caregivers between October 26 and December 6, 2021. Major themes were: MG-associated financial decisions, quality of life, employment and direct/indirect costs of diagnosis, healthcare insurance, medical visits, medications/treatments, medical equipment/devices, and caregiving.

Results: Eight hundred people with MG and 238 caregivers responding on behalf of a person with MG completed the survey. Most respondents were white (85%) and about half (55%) had received a 4 year college degree or higher education. Respondents indicated that MG impacted their health, recreation, and finances. 70% reported making financial adjustments or seeking financial assistance. Annual out-of-pocket costs (mean, $15,798; median, $7750) were primarily driven by medications, cost to receive a diagnosis, and healthcare insurance premiums. People receiving infusions paid significantly more across all care domains. Demographic disparities were observed, with people of color, women, and those on disability paying significantly more to receive a diagnosis than their counterparts.

Discussion: The economic burden on people with MG and their families is substantial, primarily driven by direct costs. There is a need to engage more broadly with the MG community for generalizable information. Respondents were self-selected, which may impact results. The results will be used to educate the public and inform advocacy work, with the goal of improving the lives of people with MG.

Introduction/aims: Accurate assessment of diabetic peripheral neuropathy (DPN) is essential to prevent further complications, yet current methods have limitations. Perception threshold tracking (PTT) offers promise as a novel approach for rapid evaluation of both large and small fiber dysfunction. To enhance efficiency, this study explores the Psi method compared to the Method of Limits (MoL) in estimating perception thresholds. The aim is to assess agreement, uncertainty, and the number of stimuli required for adequate estimation by each method.

Methods: Forty-three participants with diabetes underwent an estimated sural nerve conduction study, quantitative sensory testing, vibration perception threshold testing, and PTT. PTT utilized both patch and pin electrode configurations to activate large and small fibers, respectively. The uncertainty of perception thresholds was estimated as the inverse slope of the psychometric functions.

Results: Perception thresholds were significantly higher for the patch electrode (2.5 [2.1-3.0] mA) compared to the pin electrode (0.71 [0.56-0.91] mA; rmANOVA, p < 0.001). Bland-Altman analysis revealed a non-significant 3.3% bias between the methods, but wide limits of agreement (-42%-84%). Uncertainty was lower for the Psi method (0.80 [0.58;1.11] mA) compared to MoL (2.0 [1.2;2.9] mA; rmANOVA, p < 0.005). The Psi method achieved acceptable perception threshold estimation with only 30 stimuli.

Discussion: At the group level, the MoL and Psi methods produced similar perception thresholds. However, the Psi method required fewer stimuli and yielded less uncertainty in perception threshold estimation compared to MoL. Future studies should prioritize the Psi method for its efficiency and reliability.

Introduction/aims: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell dyscrasia. Polyneuropathy in POEMS syndrome may present as a subacute or chronic symmetric sensorimotor polyneuropathy, with electrophysiological features suggesting demyelination. Motor conduction block (CB), which is mostly seen in chronic inflammatory demyelinating polyneuropathy (CIDP), is considered an atypical electrophysiological feature in POEMS syndrome. We examined the frequency of motor CB in POEMS syndrome.

Methods: Patients with POEMS syndrome from the database of our department who had been examined between August 2017 and December 2022 were included in this study. All of the patients' clinical and electrophysiological data were retrospectively collected and analyzed.

Results: We present the data of seven POEMS syndrome patients. Twenty-eight upper extremity motor nerve conduction studies were performed on these patients, and partial CB was detected in seven upper extremity motor nerves (25%) of six of the patients. One patient had motor CB in both the median and ulnar nerves.

Discussion: The distinction between POEMS syndrome and CIDP is important since these conditions require different treatments. Motor CB in POEMS may be more common than has been generally believed. Clinicians should consider this when evaluating patients with demyelinating polyneuropathies and be meticulous in identifying CB. Data from much larger numbers of patients are needed.

Introduction and aims: Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast-twitch skeletal muscle-specific mitochondrial transcription factor A knockout (Tfam KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in vivo mitochondrial energy production.

Methods: Mice were treated with CsA for 4 weeks, beginning at 12 weeks (i.e., before the terminal disease phase). Hindlimb plantar flexor muscles were fatigued by 80 contractions (40 Hz, 1.5 s on, 6 s off) while measuring force and energy metabolism using phosphorus-31 magnetic resonance spectroscopy.

Results: Force decreased at similar rates in Tfam KO mice with and without the CsA treatment, reaching 50% of the baseline value after ~14 ± 1 contractions, which was faster than in control mice (25 ± 1 contractions). Phosphocreatine (PCr) decreased to ~10% of the control concentration in Tfam KO mice, independent of the treatment, which was larger than the ~20% observed in control mice. The time constant of PCr recovery was higher in untreated Tfam KO than that in control muscle (+100%) and similar in untreated and CsA-treated Tfam KO mice.

Discussion: The results do not support improved mitochondrial energy production as a mechanism underlying the prolonged lifespan of Tfam KO mitochondrial myopathy mice treated with CsA. Thus, other mechanisms must be involved, such as the previously observed CsA-mediated protection against excessive mitochondrial Ca²⁺ accumulation.

Introduction: The COVID-19 pandemic has resulted in a post-infectious syndrome designated as long-COVID or post-COVID condition (PCC) that presents with numerous symptoms including fatigue and myalgias. This study evaluated myopathic electromyography (EMG) findings in non-hospitalized PCC patients in relation to symptom severity, quality of life (QoL), and physical function.

Methods: Twenty-nine PCC patients with persistent symptoms ≥ 3 months after laboratory-confirmed SARS-CoV-2 infection, without hospitalization or comorbidities, were included. EMG, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed. Symptom severity was measured with visual analog scales, QoL with validated questionnaires, and physical function with the 6-min walk test, cardiopulmonary exercise testing, handgrip strength, and isokinetic dynamometry.

Results: Myopathic findings on EMG were present in 62% of PCC patients (n = 18). Symptom severity (muscle pain and fatigue) and QoL (physical function and fatigue) were similar between patients with and without myopathic EMG findings. The 6-min walk test (457 ± 81 vs. 459 ± 86 m) and peak VO₂ (29 ± 9 vs. 28 ± 6 mL/kg/min) were similar between patients with and without myopathic EMG findings. Handgrip strength (32 [29-43] vs. 33 [29-50] kg) and quadriceps muscle strength (136 [111-191] vs. 136 [114-184] Nm) were comparable between the groups. NCS and QST results were normal in all patients.

Discussion: Myopathic findings on EMG are common in PCC patients, but no significant differences in symptom severity, QoL, or physical function were found between those with and without myopathic EMG findings. Myopathic EMG changes in PCC patients should be interpreted with caution, considering the overall clinical context.

Limb-girdle muscular dystrophies (LGMDs) constitute a diverse group of inherited disorders primarily affecting skeletal muscle. Despite the absence of cures, rehabilitative treatments offer potential for preventing and mitigating loss of muscle strength. However, the role of exercise training in LGMD patients remains contentious. This review aims to provide an overview of the currently available motor rehabilitation strategies for the most common subtypes of LGMD. To identify relevant articles, we performed a systematic search in PubMed, Embase, Cochrane Library, and Web of Science, focusing on muscular and respiratory interventions. The search resulted in 560 potentially relevant articles, of which 16 were included in the review. Eight studies concentrated on neuromuscular functional rehabilitation therapy programs, seven combined both neuromuscular rehabilitation and interventions to maintain or enhance respiratory functionality and one focused on respiratory intervention only. Altogether, the papers examined offered a comprehensive view on the rehabilitative strategies available and provided an indication of the most valuable practices to deal with patients' health and needs. Upon analysis, we conclude that, when tailored to individual needs, muscle training can enhance strength and functional abilities, positively impacting psychological well-being. However, generic protocols may lead to limited benefits, fatigue, pain, and compliance issues. Moreover, early management of respiratory symptoms and personalized respiratory physiotherapy can enhance patients' well-being and their capability to participate in muscle training exercises. Future studies should not only refine rehabilitation approaches but also assess their impact on patients' quality of life, including psychological factors like depression and self-esteem.

Introduction/aims: Studies have demonstrated the potential of muscle MRIs to measure disease progression in ALS. However, the responsiveness and utility of quantitative muscle MRIs in an ALS clinical trial remain unknown. This study aimed to determine the responsiveness of quantitative muscle MRIs to measure disease progression in ALS.

Methods: Longitudinal quantitative muscle MRIs were obtained in an ALS study that delivered human neural progenitor cells to the spinal cord (NCT02943850). Participants underwent MRIs at baseline, 1, 3, 6, 9, and 12 months. MRI measures included fat fraction (ff), water T2 (T _2m), cross-sectional area (CSA), and remaining muscle area (RMA). Non-MRI measures included strength via Accurate Test of Limb Isometric Strength (ATLIS) and the ALSFRS-R. Standardized response means (SRM) were calculated at 1, 3, 6, and 12 months.

Results: Significant increases in muscle FF and decreases in CSA and RMA were seen as early as 1 month from baseline. At 6 months, the most responsive measures were muscle FF (SRM_thigh = 1.85, SRM_calf = 1.39), T _2m (SRM_thigh = 1.2, SRM_calf = 1.71), CSA (SRM_thigh = -1.58, SRM_calf = -1.14), RMA (SRM_thigh = -1.77, SRM_calf = -1.28), and strength tested via ATLIS (SRM_{knee extension} = -1.79, SRM_{knee flexion} = -1.3). The ALSFRS-R was the least responsive at 6 months (SRM = -0.85). Muscle FF and T _2m correlated with ALSFRS-R leg subscores and MRI measures demonstrated varying degrees of correlation with strength.

Discussion: High responsiveness and low variability make quantitative muscle MRI a novel and complementary outcome measure for ALS clinical trials.

Introduction/aims: 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.

Methods: 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.

Results: 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.

Discussion: 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.