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BackgroundTo collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial.MethodsTwenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT).ResultsRMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine.ConclusionsThe relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.

Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is characterized by progressive motor neuron degeneration, leading to widespread weakness and respiratory failure. While a variety of mechanisms have been proposed as causes of this disease, a full understanding remains elusive. Electrophysiological alterations, including increased motor axon excitability, likely play an important role in disease progression. There remains a critical need for non-animal disease models that can integrate electrophysiological tools to better understand underlying mechanisms, track disease progression, and evaluate potential therapeutic interventions. This review explores the integration of electrophysiological technologies with ALS disease models. It covers cellular and clinical electrophysiological tools and their applications in ALS research. Additionally, we examine conventional animal models and highlight advancements in humanized models and 3D organoid technologies. By bridging the gap between these models, we aim to enhance our understanding of ALS pathogenesis and facilitate the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective. To evaluate electrical impedance myography (EIM) in conjunction with machine learning (ML) to detect infantile spinal muscular atrophy (SMA) and disease progression. Approach. Twenty-six infants with SMA and twenty-seven healthy infants had been enrolled and assessed with EIM as part of the NeuroNEXT SMA biomarker study. We applied a variety of modern, supervised ML approaches to this data, first seeking to differentiate healthy from SMA muscle, and then, using the best method, to track SMA progression. Main Results. Several of the ML algorithms worked well, but linear discriminant analysis (LDA) achieved 88.6% accuracy on subject muscles studied. This contrasts with a maximum of 60% accuracy that could be achieved using the single or multifrequency assessment approaches available at the time. LDA scores were also able to track progression effectively, although a multifrequency reactance-based measure also performed very well in this context. Significance. EIM enhanced with ML promises to be effective for providing effective diagnosis and tracking children and adults with SMA treated with currently available therapies. The normative trends identified here may also inform future applications of the technology in very young children. The basic analyses applied here could also likely be applied to other neuromuscular disorders characterized by muscle atrophy. [ABSTRACT FROM AUTHOR]

We sought to determine whether thoracic electrical impedance tomography (EIT) could characterize pulmonary function in amyotrophic lateral sclerosis (ALS) patients, including those with facial weakness. Thoracic EIT is a noninvasive, technology in which a multi-electrode belt is placed across the chest, producing real-time impedance imaging of the chest during breathing. We enrolled 32 ALS patients and 32 age- and sex-matched healthy controls (HCs) without underlying lung disease. All participants had EIT measurements performed simultaneously with standard pulmonary function tests (PFTs), including slow and forced vital capacity (SVC and FVC) in upright and supine positions and maximal inspiratory and expiratory pressures (MIPs and MEPs, respectively). Intraclass correlation coefficients (ICCs) were calculated to assess the immediate reproducibility of EIT measurements and Pearson's correlations were used to explore the relationships between EIT and PFT values. Data from 30 ALS patients and 27 HCs were analyzed. Immediate upright SVC reproducibility was very high (ICC 0.98). Correlations were generally strongest between EIT and spirometry measures, with R values ranging from 0.64 to 0.82 (p < 0.001) in the ALS cohort. There were less robust correlations between EIT values and both MIPs and MEPs in the ALS patients, with R values ranging from 0.33 to 0.44. There was no significant difference for patients with and without facial weakness. There were no reported adverse events. EIT-based pulmonary measures hold the promise of providing an alternative approach for lung function assessment in ALS patients. Based on these early results, further development and study of this technology are warranted. [ABSTRACT FROM AUTHOR]

Current rodent models of anorexia nervosa (AN) often have accelerated weight loss that often do not allow for investigation of physiological ramifications of prolonged low weight status characteristic of AN. The purpose of this project was to refine a rodent model of AN to extend the duration of low weight status and allow for investigation of recovery. Eight‐week‐old female Sprague Dawley rats underwent 50%–60% food restriction for 30 days. Rats were group‐housed except during feeding, where AN rats were individually housed and given up to 2 h to consume food. Control (CON) rats were allowed to consume food ad libitum. To simulate recovery, a separate cohort of animals underwent the same food restriction protocol for 30 days, then rats (AN‐R) were allowed to consume food ad libitum to facilitate weight recovery for an additional 30 days. AN‐R rats were compared to age matched controls (CON‐R). AN rats lost ~15% bodyweight and were ~30% lighter than CON. Compared to CON, AN rats had ~35% lower fat content, ~18% lower bone mineral density, ~22% smaller plantaris muscle mass and ~52% smaller ovaries. Upon reintroduction of food, AN‐R rats achieved comparable bodyweights to CON‐R rats after ~10 days. However, after 30 days of recovery, AN‐R rats still had ~14% lower bone mineral density and ~11% smaller plantaris mass and ~21% smaller ovaries. This refinement of rodent AN results in physiological side effects of AN without reaching excessive weight loss requiring euthanasia. Moreover, some physiological consequences of simulated AN are not resolved with weight restoration. [ABSTRACT FROM AUTHOR]

Objectives(1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG.MethodsThree experienced academic electromyographers interpreted 3 compact discs with 20 EMG videos (10 normal, 10 radiculopathy) in a blinded, standardized fashion without information regarding the nature of the study. The EMGs were interpreted 3 times (discs A, B, C) 1 month apart. Clinical information was provided only with disc C. Intrarater reliability was calculated by comparing interpretations in discs A and B, interrater reliability by comparing interpretation between reviewers. Confirmation bias was estimated by the difference in correct interpretations when clinical information was provided.ResultsSensitivity was similar to previous reports (77%, confidence interval [CI] 63%-90%); specificity was 71%, CI 56%-85%. Intrarater reliability was good (κ 0.61, 95% CI 0.41-0.81); interrater reliability was lower (κ 0.53, CI 0.35-0.71). There was no substantial confirmation bias when clinical information was provided (absolute difference in correct responses 2.2%, CI -13.3% to 17.7%); the study lacked precision to exclude moderate confirmation bias.ConclusionsThis study supports that (1) serial EMG studies should be performed by the same electromyographer since intrarater reliability is better than interrater reliability; (2) knowledge of clinical information does not bias EMG interpretation substantially; (3) EMG has moderate diagnostic accuracy for radiculopathy with modest specificity and electromyographers should exercise caution interpreting mild abnormalities.Classification of evidenceThis study provides Class III evidence that EMG has moderate diagnostic accuracy and specificity for radiculopathy.

The objective of this study was to determine the potential value of electrical impedance myography (EIM) for assessing lumbosacral paraspinal muscle (LPM) condition in lower back pain (LBP) patients. Standard methods for assessing the condition of LPMs, such as magnetic resonance imaging, are inconvenient and expensive. One tool that could be useful for this purpose is electrical impedance myography (EIM) a technique that can be performed rapidly at the bedside. After undergoing a screening history and examination, subjects were studied with the mView EIM device (Myolex, Inc, Boston). Bilateral LPMs were measured three times each and the two closest sets of measurements averaged on each side. Data analysis included non-parametric two-group comparisons between healthy subjects and back pain patients, receiver-operating curve analyses, and correlation analyses to age and body mass index. A total of 86 healthy individuals (median age (interquartile range) (IQR), 45.5 years (30.3–56.0 years), 42 men, 44 women) and 47 LBP (median age 51.0 year (39.5–57.5) years, 21 men, 26 women) were enrolled. Median EIM 100kHz phase was lower in the LBP patients (9.3°(IQR 8.4°–10.6°) versus 11.4°(IQR 9.4°–13.0°), p = 0.0007). Significantly increased normalized side-to-side differences were present for all three EIM variables (e.g., median 100 kHz phase 0.15 (IQR 0.07–0.31 in LBP patients versus 0.09 (IQR 0.04–0.17) in healthy individuals). A significant correlation between 100 kHz EIM phase and reactance was found with age (Rspearman=−0.46, P=0.0002 and Rspearman=−0.440, P=0.0003) but not for resistance. This study provides early evidence supporting that EIM has the potential to serve as a useful tool for evaluating the condition of LPMs.