Skeletal muscle in spinal muscular atrophy: Critical insights from pathogenesis to therapeutic strategies.

The objective of this scoping review was to map existing literature on oral health and related care in individuals with Motor Neurone Disease (MND). Specifically, the review aimed to identify barriers and facilitators to maintaining oral hygiene, summarise available clinical guidelines and patient-facing resources, and examine how oral health care is integrated within multidisciplinary management of MND. The review focused on oral health practices without restrictions on language, publication date or study type, excluding studies unrelated to MND or oral health. Data sources included MEDLINE, Embase, CINAHL, and grey literature such as clinical guidelines and patient resources. Screening and data extraction were performed independently by two reviewers to ensure rigor. Of 847 studies screened, eleven primary studies met the inclusion criteria, comprising case reports, case series, self-reports, cross-sectional studies and letters. The grey literature search identified three clinical guidelines and eight patient information leaflets/resources. The included studies spanned diverse populations, including Amyotrophic Lateral Sclerosis (ALS) patients with varying disease subtypes and care needs, and explored oral hygiene difficulties, care barriers and unique insights from the case studies. Identified gaps highlighted the lack of integration of dental professionals into multidisciplinary care teams. Barriers such as physical limitations, caregiver dependency and limited-service accessibility were prevalent. However, caregiver involvement, multidisciplinary collaboration and innovative solutions like antimicrobial photodynamic therapy and adaptive oral aids emerged as enablers. Poor oral health was strongly associated with increased pain, aspiration pneumonia and diminished well-being, emphasising the need for targeted interventions. Embedding oral health management within multidisciplinary care frameworks for MND patients, enhancing caregiver training, improving access to dental services and adopting innovative strategies will improve patient outcomes and inform future research.

This study updates mortality trends of over 214,000 men and women working in various petrochemical and refinery operations of a U.S.-based company through December 31, 2020. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for 112 possible causes of death studied. SMRs for malignant mesothelioma are highest among men hired during the 1940s and 1950s. Increased SMRs are observed for Parkinson's disease and brain cancer in some subgroups with no consistent occupational pattern. Decreasing mortality trends observed for asbestosis, leukemias, motor neuron diseases, brain cancer in upstream men and breast cancer among non-white women. Updates of the mortality surveillance of this large established cohort are useful in evaluating the chronic health status of this workforce. Additional follow-up time provides the statistical power to clarify earlier findings.

TDP-43 proteinopathy is central to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 plays a key role in DNA double-strand break repair (DSBR), though the underlying mechanisms remain unclear. Here, we demonstrate that ALS patients' brains exhibit persistent DNA damage within transcribed genes. Mechanistically, activity of polynucleotide kinase 3'-phosphatase (PNKP), an essential DNA end-processing enzyme required for DSBR in transcribed genes, is impaired in ALS brains and TDP-43-depleted cells. Such defect stems from reduced levels of PNKP-interacting enzyme phosphofructo-2- kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and its metabolic product fructose-2,6- bisphosphate (F2,6BP), an essential cofactor of PNKP. F2,6BP supplementation reduces cytosolic aggregation of phosphorylated and polyubiquitinated TDP-43 in patient-derived induced neurons, rescues PNKP activity in ALS/FTD brain extracts, and improves motor deficits in Drosophila TDP-43 model. Together, these findings reveal a critical link between metabolic dysregulation and genomic instability in TDP-43 pathology-associated motor neuron diseases, and underscore therapeutic potential of F2,6BP.

ALS Untangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review clenbuterol, a β-2 adrenergic agonist, as a potential treatment for amyotrophic lateral sclerosis (ALS). Clenbuterol has biological effects that could be relevant to the pathophysiology of ALS such as inducing muscle hypertrophy, improving mitochondrial function, and reducing neuroinflammation. Two studies in mouse models of motor neuron disease and two open label trials suggest possible benefits. However these have methodological flaws which limit interpretation. Clenbuterol can have an array of side effects, some severe. Drop-outs due to side effects were very common in one of the ALS trials and in a separate expanded access program. Based on this information, we cannot currently endorse clenbuterol as an ALS treatment, but we do hope to see further studies of it, or another long acting β-2 adrenergic agonist in people with ALS.

Paraneoplastic motor neuron disease is an uncommon paraneoplastic neurologic syndrome whose existence has fallen into ambiguity. Epidemiologic studies that have addressed the association between cancer and motor neuron disease have provided conflicting results. Case studies that report motor neuron disease presentation at the time of active malignant disease, in the presence of another paraneoplastic neurologic syndrome or onconeural antibody or with neurologic response to antineoplastic treatment provide strong evidence for paraneoplastic motor neuron disease. However, conclusive evidence about the existence and the clinical and laboratory profiles of this neurologic syndrome is lacking. In this study, we report four new cases of paraneoplastic motor neuron disease, two of whom with expression of Sry-like high mobility group box 1 (SOX1) antibody. We also present a systematic review of all cases of paraneoplastic motor neuron disease reported to date that fulfill prespecified inclusion criteria with individual participant data meta-analysis of the demographic, clinical and laboratory features of the disease. Our data demonstrate that motor neuron disease can present as a paraneoplastic neurologic syndrome. Paraneoplastic motor neuron disease spans the whole motor neuron disease phenotypic spectrum, and it is associated with a wide variety of neoplastic diseases, onconeural antibodies and it may present concurrently with other well-recognized paraneoplastic neurologic syndromes. Paraneoplastic motor neuron disease may be clinically indistinguishable from idiopathic motor neuron disease. Its only distinctive clinical feature is the rapidly progressive course. A subset of cases display immune derangements in cerebrospinal fluid, including increased white cell count, elevated protein, albumin index, IgG index and/or oligoclonal band expression. Cancer-induced inflammatory pathways may trigger the disease in genetically predisposed individuals harboring amyotrophic lateral sclerosis-causing genetic deficits. A thorough evaluation for neoplastic diseases should be carried out upon strong suspicion of this rare paraneoplastic neurologic syndrome to increase the diagnostic yield for this entity. Paraneoplastic motor neuron disease apparently results from complex interactions between degenerative and immune pathways and its pathophysiology may elucidate previously unresolved aspects of idiopathic motor neuron disease pathogenesis.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative motor neuron disease with a pathophysiology that features dysregulated natural killer (NK) cells that are capable of damaging neurons. Although NK cells are associated with ALS progression and survival, their specific characteristics and how these characteristics change over the course of disease is unknown. The current study examines NK cell gene expression during ALS with the goal of identifying dysregulated genes and pathways in NK cells over the course of disease in order to identify potential new therapeutic targets. ALS participants with an El Escorial ALS diagnosis were recruited from the University of Michigan Pranger ALS Clinic, and control participants were recruited via internet-based notifications. Blood was collected from participants and NK cells were isolated from participants with ALS at two timepoints (baseline and longitudinal) and age- and sex-matched healthy controls at one timepoint. RNA was extracted from the NK cells and quantified using a transcript-counting technology for 578 immune-related genes. Differential gene expression analysis was used to identify individual genes that were dysregulated in ALS at baseline and longitudinally, While GO and KEGG pathway analyses were performed to identify dysregulated pathways at both timepoints. NK cells from participants with ALS (n=36, median age 62.6 years (54.5-69.4), 50% female) showed a 2-fold or greater reduced expression of four pro-inflammatory genes at baseline relative to control participants (N=35, median age 64.3 years (55.2-71.8), 51% female) including IFNG, FCGR1A/B, and FAS; in ALS participants over 130 genes showed a 2-fold change in expression. Dysregulated genes and pathways at the later timepoint were related to cell polarization, activation, signaling, and cell-cell adhesion. In particular, genes associated with classical Type 1 inflammation decreased while Type 2 genes increased. NK cells grow more dysregulated with ALS progression, shifting from a classical Type 1 phenotype to a Type 2 phenotype, though a larger study will be needed to confirm these initial findings. The findings also suggest NK cells contribute to early, but not late, ALS progression. Targeting specific NK cell pathways during early ALS may be a viable therapeutic strategy.

Cognitive and behavioral changes affect up to 50% of people with Amyotrophic Lateral Sclerosis (ALS) and are associated with worse outcomes, yet remain under-recognized in clinical care. Understanding patient and caregiver perspectives is important for engagement with cognitive screening. Semi-structured interviews were conducted with 10 patients with ALS and 9 caregivers, analyzed using reflexive thematic analysis. Participants were recruited via a multidisciplinary ALS clinic and the Motor Neurone Disease Association UK. Engagement with testing was shaped by emotional readiness, personal values, relational dynamics, practical barriers, and perceived value. Views ranged from seeing testing as an opportunity for preparedness and autonomy, to concerns it could undermine identity or add distress. Caregivers often valued testing to support planning but faced challenges balancing advocacy with respect for patient autonomy. Limited awareness of cognitive symptoms in ALS and unclear communication from clinicians reduced perceived relevance. Testing was most meaningful when tailored to personal priorities, introduced sensitively, and linked to actionable outcomes. Cognitive screening in ALS requires a flexible, patient-centered approach that considers emotional readiness, relational contexts, and clear communication. Tailoring discussions and delivery to patient and caregiver needs may enhance acceptance and integration of cognitive assessment into holistic ALS care.

This study outlines the changes in the age- and sex-specific burden of motor neuron disease (MND) in China from 1990 to 2021, focusing on the prevalence, incidence, number of disability-adjusted life years and mortality. Additionally, these trends are evaluated in comparison to the Global Burden of Disease data. Public data from the Global Burden of Disease database covering the period from 1990 to 2021 were analyzed to explore the burden of motor neuron disease in China and worldwide. Trends in prevalence, incidence, disability-adjusted life years (DALYs) and mortality were examined in the analysis. The average annual percentage change was calculated using Joinpoint, and the relevant 95% confidence intervals (95% CIs) were examined to identify changes in the MND burden over time. Additionally, a thorough comparative analysis was performed to investigate the differences in the MND burden between China and other regions worldwide, considering factors such as age, sex, and time periods. From 1990 to 2021, the age-standardized incidence rate (ASIR) of motor neuron disease (MND) in China declined from 0.65 per 100,000 to 0.46 per 100,000, whereas the global ASIR decreased slightly from 0.81 per 100,000 to 0.77 per 100,000. In contrast, the age-standardized prevalence rate (ASPR) in China increased from 2.131 per 100,000 to 2.298 per 100,000, whereas the global ASPR decreased slightly from 3.356 per 100,000 to 3.31 per 100,000. The age-standardized mortality rate (ASMR) in China increased from 0.151 per 100,000 to 0.181 per 100,000; the global ASMR also increased from 0.38 per 100,000 to 0.46 per 100,000 during this period. Moreover, the age-standardized disability-adjusted life year (ASDR) rate in China decreased slightly from 7.995 per 100,000 to 7.672 per 100,000, whereas the global ASDR increased from 11.221 per 100,000 to 12.167 per 100,000. The average annual percentage changes (AAPCs) for the ASPR, ASIR, ASDR, and ASMR in China were -1.10%, 0.25%, 0.57%, and -0.14%, respectively. In contrast, the global AAPCs were -0.16%, -0.04%, 0.58%, and 0.26%, respectively. Age and sex played distinct roles in shaping MND burden. The ASIR of MND decreased but then increased for both sexes, remaining higher for males. Its ASPR trends differed: a slight increase in males versus an increase then decrease in females. While the ASMR was consistently higher for males, the DALYs for males started to decrease but surpassed those for females. Global MND rates have remained stable. The prevalence, incidence, DALYs and mortality of motor neuron disease in China decreased between 1990 and 2021, suggesting a relative decrease in the total burden of MND in the country. Age influences the burden of MND, with a higher occurrence incidence in children and middle-aged individuals; the prevalence of MND is highest in the younger population, whereas MND-related mortality is the highest within the middle-aged and senior populations. Compared with females, males are more likely to be affected by MND and have a greater likelihood of death. Given the rapid population aging in China, MND is expected to remain a significant public health issue.

A 79-year-old former marathoner, with memory impairment since age 78, developed increasing stumbling and progressively worsening waddling gait. Three months after gait disturbance onset, she noted mild dysphagia. With declining walking distance and endurance, she presented to our hospital six months after onset, exhibiting frontal signs, Parkinsonism with marked trunk rigidity, and hyperreflexia of the jaw and limbs. L-dopa challenge tests showed no improvement. At seven months post-onset, she had difficulty rising. By nine months, she relied on a walker, and speech disturbance appeared. At 10-11 months, both dysarthria and dysphagia rapidly worsened, she became bed-ridden, and upper limb weakness developed (though she could still use chopsticks). Neurological examination at one year revealed severe dysarthria/dysphagia, four extremity fasciculations and muscle weakness (grade 2 in upper limbs, grade 1 in lower limbs), trunk-dominant rigidity, and hyperreflexia in the jaw and limbs. Brain MRI, specifically susceptibility-weighted imaging, revealed motor band signs. Cerebrospinal fluid study revealed albuminocytological dissociation. Needle electromyography revealed acute denervation and chronic reinnervation in the cranial nerve, cervical, and lumbar areas, which was suggestive of motor neuron disease (MND). Serum anti-GQ1b antibodies were detected. Immunotherapy was followed by mild improvement, which might suggest a reversible component, although definitive pathological overlap remains unconfirmed. This case highlights a diagnostic challenge where an acute immune-mediated neuropathy could potentially be superimposed on a chronic neurodegenerative process. Anti-GQ1b antibodies should be interpreted with caution, as they may reflect either a true clinicopathological overlap with Guillain-Barré syndrome or a secondary phenomenon (epiphenomenon) related to the primary neurodegenerative process.

The N88S mutation in human seipin causes a dominant motor neuron disease marked by ER stress and inclusion body formation, lipid imbalance, and oxidative damage. However, the metabolic mechanisms connecting these defects remain poorly understood. Previous proteomic profiling in our yeast model of N88S human seipinopathy revealed decreased protein levels of enzymes involved in the tricarboxylic acid cycle, fatty acid and carboxylic acid metabolism, and the glyoxylate cycle, suggesting impaired downstream utilization of peroxisome-derived acetyl-CoA. Guided by these findings, we investigated how peroxisomal function contributes to cellular dyshomeostasis. N88S seipin-expressing cells exhibited increased peroxisome abundance but defective routing of acetyl-CoA into mitochondrial and glyoxylate pathways, resulting in elevated reactive oxygen species (ROS), impaired glyoxylate cycle activation, and reduced metabolic adaptability to non-fermentable carbon sources. Loss of peroxisomes or forced cytosolic redirection of acetyl-CoA further exacerbated ER stress, ROS accumulation, lipid peroxidation, and the growth defect on N88S seipin-expressing cells, whereas inhibition of fatty acid synthesis mitigated oxidative damage. These findings demonstrate that N88S seipin triggers a futile cycle in which misrouted cytosolic acetyl-CoA drives lipogenesis, amplifying oxidative damage and ER stress. We conclude that defective peroxisome-mitochondria metabolic coupling and acetyl-CoA misrouting may represent central pathogenic mechanisms driving cellular dysfunction in N88S-linked seipinopathy.

Motor neuron diseases (MND) affect the upper and/or lower motor neurons. Radiological diagnostics primarily serve to systematically exclude treatable mimics and support the clinical and electrophysiological diagnosis. The focus is on amyotrophic lateral sclerosis (ALS); supplementary progressive muscular atrophy (PMA, purely lower motor neuron, LMN disease) and spinal muscular atrophy (SMA). Which imaging signs support the diagnosis of ALS, how do electromyography/magnetic resonance imaging (EMG/MRI) fit into the Gold Coast criteria and which other motor neuron diseases are relevant? Overview of clinical criteria (Gold Coast), genetics and typical MRI findings of the brain, spinal cord and musculature. Gold Coast core: progressive motor deterioration, upper motor neuron (UMN) and LMN signs in ≥ 1 region or LMN in ≥ 2regions and exclusion of alternative causes. susceptibility-weighted imaging (SWI) motor band sign as UMN marker; T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities along the corticospinal tract with low sensitivity, moderate specificity; T1 bright tongue as an indication of chronic denervation in bulbar involvement. EMG: detection of subclinical LMN involvement, sometimes limited in UMN-dominant/bulbar courses. PMA: Pure purely LMN symptoms, often continuum to ALS. SMA: Autosomal autosomal recessive (SMN1 deletion). The diagnosis remains primarily clinical; EMG and MRI are supportive. The radiological priority is the exclusion of mimics. The UMN markers increase diagnostic certainty in the context of clinical/EMG findings but do not replace them. Clear findings facilitate classification according to Gold Coast. The PMA and SMA require careful differential diagnostics; characteristic MRI patterns support progression and treatment planning.

The aim was to examine the engagement and acceptability of Telehealth in MND (TiM) as part of usual care within two specialist centers. Fifty people with MND (pwMND) completed questionnaires. Eight pwMND and carers participated in interviews. In Shefield, 163 pwMND were invited to TiM with 52% registering and 85% engagement. In Dublin, 98 pwMND were invited to TiM, with 63% registering, and 95% engagement.High levels of acceptability were reported, with users rating TiM as very low in burden. Similar findings were demonstrated within the interviews, with ease of use a strength. However, participants discussed a need for more regular feedback from TiM. Future opportunities relating to integrating TiM with community services were discussed. TiM is feasible and acceptable to pwMND. The high engagement can generate a wealth of data facilitating solution-focused clinical appointments. The study's findings support the further implementation of TiM in other MND services.

ABSTRACT Mutations in superoxide dismutase 1 (SOD1) cause paralysis in familial amyotrophic lateral sclerosis and promote its misfolding into neurotoxic aggregates. Previous studies have shown that mice expressing the ALS-causing G85R variant of SOD1 develop paralysis much faster after intraspinal injection of spinal homogenates from paralysed G85R SOD1 mice. These findings, and other studies in cell models, established the prionoid templating properties of misfolded mutant SOD1. Previously, however, we noted that the widely used Gur1-G93A SOD1 mice, which express at high levels and develop paralysis by 6 months of age, were resistant to seeding by homogenates from paralysed G93A mice. A line of G93A mice that expresses at very low levels (VLE-G93A) was responsive to seeding but at low efficiency. The poor susceptibility of G93A-SOD1 mice to seeding was not what we expected if prion-like propagation is essential to SOD1 ALS pathogenesis. In our prior studies, seeding homogenates from paralysed G93A-SOD1 mice were injected into the spine of newborn mice, leading us to question whether older G93A SOD1 mice might be more susceptible to seeding. Here, we establish that adult VLE G93A SOD1 mice (up to 12 months of age) injected intrathecally with seeding homogenates containing misfolded G93A or G85R SOD1 developed accelerated motor neuron disease efficiently. Thus, we demonstrate that both the route and age of inoculation can influence the efficiency of SOD1 seeding to induce motor neuron disease in VLE G93A-SOD1 mice. These data, together with our earlier reports, suggest that prion-like templating contributes to disease progression in SOD1-ALS.

Cyclase-associated protein 2 (CAP2) is a synaptic actin-binding protein involved in cofilin-mediated spine remodelling, Alzheimer’s Disease synaptic failure and myofibril maintenance, indicating its potential involvement in motor neuron disease (MND). This study examined cerebrospinal fluid (CSF) levels of CAP2 in 60 patients with MND and 40 healthy controls (HC) to assess its diagnostic and prognostic value and its relationship with neuronal, glial and synaptic markers. Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated and total tau (p-Tau 181, t-Tau), CAP2 and synaptosomal-associated protein 25 (SNAP-25) were quantified using ELISA, Lumipulse and SIMOA platforms. MND patients displayed increased GFAP, NfL, t-Tau, p-Tau 181 levels and CAP2 while SNAP-25 was reduced. CAP2 correlated with tau markers, but not with NfL or GFAP. Unlike NfL, which was higher in upper motor neuron–predominant cases and predicted faster progression and poorer survival, CAP2 did not vary with disease subtypes or severity. The study showed that CAP2 is associated with MND independently from neuronal, glial and presynaptic dysfunction. Integrating CAP2 into multi-marker panels could enhance understanding of synaptic pathology in MND.

Conventional medicine and public health have collectively improved health and saved the lives of millions. Yet, as we confront the escalating crisis of non-communicable diseases (NCDs), it becomes increasingly clear that conventional approaches alone are no longer sufficient. A new, evidence-based paradigm shift is necessary. Integrative health, which combines conventional medicine with complementary and lifestyle medicine, offers that shift. To assess its effectiveness, we identified and reviewed 14 clinical trials published within the past 5 years in widely read, high-impact factor journals (and their sub-specialty counterparts) – including The New England Journal of Medicine , the Lancet , the BMJ and JAMA. These trials directly compared integrative health interventions with conventional medical treatments across conditions such as insomnia, obesity, age-related disorders, Parkinsonism, and motor neuron disease. The included trials assessed outcomes related to mental health, pain management, and quality of life. Across these studies, we found that integrative health interventions were consistently associated with improved health outcomes. While we acknowledge that stronger evidence is needed, the research findings represent an important step toward exploring a well-balanced, evidence-based approach to integrative health.

RATIONALE Respiratory symptoms in patients with presumed severe/refractory asthma may, in a minority of cases, reflect underlying neuromuscular disorders (NMDs) rather than primary airway disease. Failure to recognize respiratory muscle dysfunction can lead to inappropriate escalation of asthma-directed therapy and delayed diagnosis of treatable conditions. OBJECTIVES The objectives of this study were to describe the prevalence, clinical characteristics and diagnostic features of NMDs identified through systematic evaluation in a tertiary severe asthma clinic. METHODS We performed a retrospective chart review of 896 patients referred for evaluation of difficult-to-treat/severe asthma between 2015 and 2025. According to ERS/ATS criteria, severe asthma was confirmed as the primary cause of respiratory symptoms in only 155 patients. Based on symptoms disproportionate to airflow limitation, 15 patients underwent targeted assessment for possible neuromuscular involvement using pulmonary function testing, imaging, electrophysiological studies and ancillary investigations. MEASUREMENTS AND MAIN RESULTS Seven patients were confirmed to have NMDs contributing significantly to respiratory symptoms. Diagnoses included inflammatory or autoimmune myopathies (n = 3), motor neuron disease (n = 1) and unilateral diaphragmatic dysfunction due to phrenic nerve involvement (n = 3), including 1 case with subsequent manifestation of myasthenia gravis. Features prompting reconsideration of asthma included disproportionate exertional or positional dyspnea, nonobstructive or mixed spirometry patterns, unexplained reductions in vital capacity with preserved gas exchange and limited response to asthma-specific therapy. CONCLUSIONS In a large tertiary cohort of patients labeled as severe poorly-controlled asthma, NMDs represented a small but clinically significant cause of refractory respiratory symptoms. Systematic evaluation can reveal alternative diagnoses with significant therapeutic implications.

Motor neurons derived from induced human pluripotent stem cells offer a powerful model to study motor neuron diseases, such as amyotrophic lateral sclerosis. While widely used, our knowledge of the proteomic changes in these models is rather rudimentary. In this study, we conducted a comparative proteomic analysis of induced pluripotent stem cell-derived motor neurons carrying amyotrophic lateral sclerosis-associated mutations in C9ORF72, TARDBP, or FUS. This revealed both mutation-specific and shared proteomic signatures, unveiling common and divergent disease mechanisms. Using these new insights, we then evaluated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. These experiments showed a functional effect of mesenchymal stem cell-derived extracellular vesicles in amyotrophic lateral sclerosis-FUS motor neurons in vitro and their ability to reverse proteomic changes more generally in motor neurons with different amyotrophic lateral sclerosis genetic backgrounds. These findings highlight key molecular pathways involved in amyotrophic lateral sclerosis at the protein level and support the potential of mesenchymal stem cell-derived extracellular vesicles as a versatile therapeutic approach.

Neuromuscular junction (NMJ) disorders such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism are characterized by impaired synaptic transmission leading to weakness. This review examines the electrodiagnostic evaluation of these conditions, emphasizing the importance of techniques such as repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) for confirming the diagnosis and distinguishing presynaptic from postsynaptic defects. The reduced safety factor of neuromuscular transmission (NMT) in postsynaptic disorders produces a decrement in compound muscle action potential (CMAP) amplitude and area with low-frequency stimulation, whereas presynaptic disorders show small baseline CMAPs that increase markedly in amplitude and area (postactivation facilitation) after brief exercise or during high-frequency stimulation. SFEMG, the most sensitive test of abnormal NMT, measures neuromuscular jitter-temporal variability in action potential generation-and also reflects a compromised safety factor. Fiber density remains normal in primary NMJ disorders, distinguishing them from conditions with neuropathic reinnervation, such as motor neuron disease. Proper performance and interpretation of these electrodiagnostic studies are essential for accurate diagnosis, assessment of disease severity, and guiding management of NMJ disorders.

Trajectory of Mobility Function Decline for People With Motor Neuron Disease.