Muscle & Nerve最新文献

Introduction/aims: Nerve regeneration after injury must occur in a timely fashion to restore function. Current methods of assessment provide limited information following trauma, resulting in delayed management and suboptimal outcomes. In this study, we evaluated the ability of diffusion magnetic resonance imaging (MRI) and a mathematical model based on the Gompertz function to monitor nerve regeneration after injury and repair.

Methods: Sprague Dawley rats were assigned to two treatment groups (sham = 2, cut, immediate repair = 7), and in vivo diffusion tensor imaging (DTI) was performed every 2 weeks until 12 weeks post-surgery. Functional recovery was evaluated weekly over the same time period via the sciatic functional index (SFI).

Results: After injury, SFI and DTI-derived fractional anisotropy (FA) values exhibited similar longitudinal trends and distinctions in both sham and cut/repair (C/R) cohorts. FA values at the distal section displayed the highest correlation with behavioral indices at the region nearest to the injury (r = 0.84, p < 0.001), followed by FA values at the central section (r = 0.82, p < 0.001) and the section farthest from the injury (r = 0.70, p < 0.001).

Discussion: Findings suggest that automated analyses of FA profiles along the nerve may provide insights for distinguishing successful/unsuccessful nerve recovery. This tool, once proven in a larger-scale study, can provide clinicians with the needed tool to early diagnose nerve recovery and identify cases requiring a second repair surgery.

Introduction/aims: There is a lack of information about startle reflex (SR) in primary lateral sclerosis (PLS). This study examined the presence and prevalence of SR in PLS and compared findings with amyotrophic lateral sclerosis (ALS).

Methods: 46 PLS and 54 ALS participants were assessed through structured interviews in this cross-sectional study. Fisher's exact test was used to compare reported SR prevalence. Multivariable linear regression was utilized to study associations between disease group and SR frequency in response to sudden stimuli.

Results: SR differed markedly between the two groups, with a higher prevalence in PLS (93.5%) than ALS (20.4%; p < 0.001). Among ALS patients, SR was present in all upper motor neuron (UMN)-predominant cases, which accounted for 54.5% of the SR-positive ALS group, but only 10.4% of probable/definite ALS cases. In SR-positive patients, response frequency to sudden stimuli exceeded 60% in both ALS and PLS, most often triggered by auditory stimuli. Younger age, shorter disease duration, and PLS diagnosis were associated with more frequent SR.

Discussion: SR is significantly more common in PLS than in ALS. Notably, UMN-predominant ALS, although limited in number, showed a higher prevalence of SR (6 out of 6, 100%), indicating that predominant UMN involvement may be a key determinant of SR across both conditions. These hypothesis-generating findings suggest that SR may serve as a novel clinical marker in PLS and UMN-predominant ALS, warranting further validation through prospective studies.

Introduction/aims: Pneumothorax is a complication of mechanical ventilation (MV) in patients with amyotrophic lateral sclerosis (ALS); however, its clinical features and risk factors are not well defined. This study aimed to characterize the incidence, risk factors, and prognostic impact of pneumothorax in patients with ALS undergoing MV.

Methods: We retrospectively analyzed clinical data from patients with ALS admitted to our center between 2014 and 2024. Patient demographics and baseline characteristics, pneumothorax occurrence, MV details, chest computed tomography (CT) findings, and survival outcomes were reviewed. We analyzed independent risk factors for pneumothorax and evaluated cumulative incidence and survival.

Results: Among the 131 patients with ALS, 95 underwent MV, 19 of whom developed pneumothorax. Only low body mass index (BMI) (< 18.5 kg/m²; p = 0.015) was identified as an independent risk factor. The cumulative incidence rates of pneumothorax at 1, 3, 5, and 10 years after MV initiation were 4.5%, 13.4%, 24.3%, and 32.0%, respectively. The median post-pneumothorax survival was 16 months (95% confidence interval [CI]: 6-67), with no significant difference in overall survival from the time of initiation of MV between patients with and without pneumothorax (p = 0.88).

Discussion: This study identified low BMI as a potential risk factor for pneumothorax in ALS patients receiving MV. However, given the limited sample size, these findings should be interpreted with caution. Larger, multicenter studies are warranted to validate this association and to further elucidate long-term pulmonary effects and preventive strategies.

The electrodiagnostic instrument is foundational to the acquisition of electrophysiologic data and its subsequent interpretation and diagnostic implications. The initiation of data acquisition occurs at the three recording electrodes which consist of: E-1 (the noninverting amplifier port), E-2 (the inverting amplifier port), and E-0 (the so-called ground electrode). All three electrodes are essential in forming the recording montage. They must have similar, high-quality impedance and be properly connected to the amplifier. Their recording surfaces and the tissues from which they record must have low impedance and be properly prepared and applied at the recording site to ensure an accurate representation of the electrophysiologic signal. Both surface and needle electrodes can be used, contingent on the technique and data required (i.e., nerve conduction studies or needle electromyography, respectively). These biologic signals are small, ranging from millivolts to microvolts, depending on the generator source (e.g., muscle and nerve). Therefore, they must be amplified and subsequently filtered. Artifacts, distorted signal amplification, or inappropriate filtration will result in waveform distortion leading to erroneous interpretation (i.e., false positives or negatives). The electrodiagnostic medicine consultant (EMC) has other tools to deal with this, such as averaging. The signal is then digitized and displayed visually and acoustically through an analog-to-digital converter/loudspeaker requiring appropriate amplification and time scale to avoid any signal distortion. The EMC can then visually as well as auditorily analyze the signal of interest and store or print out the data for further interpretation. Current technology in instrumentation permits greater precision and accuracy in data analysis. Failure at any one of the above sequential processing steps can lead to data misinterpretation. It is incumbent upon the EMC to be thoroughly familiar with all of the steps in this process, including potential shortcomings.

Introduction/aims: Glycosylation defects are a recognized cause of congenital myasthenic syndrome (CMS), affecting the stability and functions of the neuromuscular junction proteins. Mutations in five genes (GFPT1, DPAGT1, GMPPB, ALG2, and ALG14) are currently associated with glycosylation-related CMS. This cohort describes Iranian patients with CMS and variants in these genes.

Methods: A retrospective study was conducted to examine demographic, clinical, genetic, and histological data from Iranian patients with confirmed CMS-glycosylation defects. Patients were identified and recruited through the Neuromuscular Clinics of Tehran University of Medical Sciences. Only patients with complete clinical and genetic data available were included.

Results: Twenty-three genetically confirmed patients with glycosylation-related CMS were enrolled. Genetic analysis revealed the mutations in the GFPT1, GMPPB, and ALG2 genes, with those in GFPT1 and GMPPB being the most common. The median age of onset and diagnosis was 6 and 16 years, respectively. Common clinical features were limb-girdle muscle weakness with minimal ocular involvement. Consanguinity and a positive family history were common, identified in 21 and 14 patients, respectively. Muscle biopsies revealed tubular aggregates in patients with GFPT1 and GMPPB variants. In addition, novel genetic variants were identified, and phenotypic variability was observed even within families sharing identical mutations.

Discussion: This study identifies novel variants and phenotypic variability in glycosylation-related CMS, with GFPT1 and GMPPB as the predominant subtypes in Iran. These findings expand the genotypic and phenotypic spectrum and underscore the importance of early genetic testing in high-consanguinity populations to improve diagnosis and management.

Introduction/aims: Lipid storage myopathies (LSM) are rare disorders characterized by abnormal lipid accumulation in muscle fibers, commonly resulting in proximal muscle weakness and elevated creatine kinase (CK) levels. Within the category of LSM, there are various subtypes categorized by biochemical markers and genetic mutations. While LSM often is hereditary, there are ways that these myopathies can be acquired. Multiple acyl-CoA dehydrogenase deficiency (MADD) is a subtype of lipid storage myopathy associated with sertraline use. Sertraline has been linked to respiratory chain inhibition. The mainstay of treatment for MADD is high-dose riboflavin supplementation. We present two patients with acquired, sertraline-associated MADD who experienced full clinical recovery with riboflavin treatment before discontinuation of sertraline.

Methods: We describe two adult-onset patients with an acquired, sertraline-associated MADD-like disorder.

Results: Both patients showed clinical and serological improvement with riboflavin supplementation, even prior to sertraline discontinuation. Clinically, strength in the affected muscles returned to baseline (5/5) within 2 months. Serologically, the patients saw a 650-700 U/L decrease in CK levels (to baseline or near baseline) within 1 month and acylcarnitine profiles showed a marked decrease in medium and long-chain fatty acids within 6 months of initiating therapy.

Discussion: Although riboflavin therapy is often reserved for genetically confirmed patients, our findings support its efficacy in sertraline-associated, genetically negative MADD. These cases underscore the importance of recognizing medication-associated metabolic myopathies and the potential for targeted riboflavin therapy.

While randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of therapies in amyotrophic lateral sclerosis (ALS), post hoc analyses can provide critical insights into clinical effectiveness, treatment durability, and subpopulation responses. Several post hoc analyses of Study MCI186-19 (Study 19), the pivotal phase 3 RCT that supported the United States Food and Drug Administration approval of intravenous edaravone, have been performed to explore the broader clinical impact of this therapy. These analyses assessed the long-term treatment efficacy, changes in individual ALS Functional Rating Scale-Revised item scores, survival and additional milestone events, and the impact of edaravone in patient subgroups defined by disease progression trajectories using latent class analysis. Collectively, these findings reinforce the long-term clinical benefit of edaravone and demonstrate that edaravone may offer benefits across a spectrum of ALS disease trajectories, beyond those defined in the original study criteria. These studies help address questions not captured in the original RCT and may inform future trial design and treatment decisions.