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OBJECTIVE: Diagnostic assessment of ADHD is challenging due to comorbid psychopathologies and symptoms overlapping with other psychiatric disorders. In this study, we investigate if a distinct pattern of neuromuscular dysregulation previously reported in ADHD, can help identifying ADHD in psychiatric patients with diverse and complex symptoms. METHOD: We explored the impact of neuromuscular dysregulation, as measured by The Motor Function Neurologic Assessment (MFNU), on the likelihood of being diagnosed with ADHD, affective disorder, anxiety disorder, or personality disorder among adults (n = 115) referred to a psychiatric outpatient clinic. RESULTS: Logistic regression revealed that neuromuscular dysregulation was significantly associated with ADHD diagnosis only (OR 1.15, p < .01), and not with affective-, anxiety-, or personality disorders. Sensitivity and specificity for ADHD at different MFNU scores is provided. CONCLUSIONS: A test of neuromuscular dysregulation may promote diagnostic accuracy in differentiating ADHD from other psychiatric disorders in patients with an overlapping symptom picture. This may have important implications for clinical practice. More studies are needed.

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Neuromuscular diseases impact on children's health related quality of life but there is a lack of studies in Latin America that measured this construct. To respond to this need, this study aimed to explore quality of life and its relationship with age, functional dependence and specific diagnosis in children and adolescents in Latin America. A cross-sectional correlation study was carried out with 133 caregivers on children (2-18 years old) with various neuromuscular disorders. Parents reported on their children's health related quality of life through the PedsQL GCS and the PedsQL NMM. Differences in quality of life were found when comparing children with high functional dependence with those with mild dependence (p = 0.05). No significant differences were found regarding the child diagnosis. Finally, quality of life was highly correlated with the child's age, even when controlling for functional dependence differences between ages. Children and adolescents with neuromuscular show a diminished health related quality of life, not only in physical functioning but in their psychosocial functioning. Health related quality of life may vary according to the child's age and functional dependence.

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Magnetic Resonance (MR) parameters mapping in muscle Magnetic Resonance Imaging (mMRI) is predominantly performed using pattern recognition-based algorithms, which are characterised by high computational costs and scalability issues in the context of multi-parametric mapping. Deep Learning (DL) has been demonstrated to be a robust and efficient method for rapid MR parameters mapping. However, its application in mMRI domain to investigate Neuromuscular Disorders (NMDs) has not yet been explored. In addition, data-driven DL models suffered in interpretation and explainability of the learning process. We developed a Physics Informed Neural Network called Myo-Regressor Deep Informed Neural NetwOrk (Myo-DINO) for efficient and explainable Fat Fraction (FF), water-T2 (wT2) and B1 mapping from a cohort of NMDs.A total of 2165 slices (232 subjects) from Multi-Echo Spin Echo (MESE) images were selected as the input dataset for which FF, wT2,B1 ground truth maps were computed using the MyoQMRI toolbox. This toolbox exploits the Extended Phase Graph (EPG) theory with a two-component model (water and fat signal) and slice profile to simulate the signal evolution in the MESE framework. A customized U-Net architecture was implemented as the Myo-DINO architecture. The squared L2 norm loss was complemented by two distinct physics models to define two 'Physics-Informed' loss functions: Cycling Loss 1 embedded a mono-exponential model to describe the relaxation of water protons, while Cycling Loss 2 incorporated the EPG theory with slice profile to model the magnetization dephasing under the effect of gradients and RF pulses. The Myo-DINO was trained with the hyperparameter value of the 'Physics-Informed' component held constant, i.e. λmodel = 1, while different hyperparameter values (λcnn) were applied to the squared L2 norm component in both the cycling loss. In particular, hard (λcnn=10), normal (λcnn=1) and self-supervised (λcnn=0) constraints were applied to gradually decrease the impact of the squared L2 norm component on the 'Physics Informed' term during the Myo-DINO training process. Myo-DINO achieved higher performance with Cycling Loss 2 for FF, wT2 and B1 prediction. In particular, high reconstruction similarity and quality (Structural Similarity Index > 0.92, Peak Signal to Noise ratio > 30.0 db) and small reconstruction error (Normalized Root Mean Squared Error < 0.038) to the reference maps were shown with self-supervised weighting of the Cycling Loss 2. In addition muscle-wise FF, wT2 and B1 predicted values showed good agreement with the reference values. The Myo-DINO has been demonstrated to be a robust and efficient workflow for MR parameters mapping in the context of mMRI. This provides preliminary evidence that it can be an effective alternative to the reference post-processing algorithm. In addition, our results demonstrate that Cycling Loss 2, which incorporates the Extended Phase Graph (EPG) model, provides the most robust and relevant physical constraints for Myo-DINO in this multi-parameter regression task. The use of Cycling Loss 2 with self-supervised constraint improved the explainability of the learning process because the network acquired domain knowledge solely in accordance with the assumptions of the EPG model.

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The relevance of the study of neuromuscular dysfunction's causes and mechanisms is undeniable, considering the large number of nosologies accompanied by malfunction of muscles. Adequate diagnosis and correction of these disorders is impossible without understanding of their pathogenetic mechanisms. Currently, manual muscle testing (MMT) is a widespread technique. MMT is an agile diagnostic tool used by physiatrists, doctors in sports medicine, osteopaths and rehabilitation physicians to assess the functional status of muscles. Unconditionally, this method attracts with its low cost, which will optimize the financial costs of hospital and the healthcare system as a whole. In addition, there is no clear substantiation of the objectivity and validity of the MMT to date. The article considers the issues of neurophysiological principles, classification of methods and approaches, assessment criteria of repeatability and accuracy of MMT. Understanding of the pathophysiological mechanisms of MMT effectiveness will allow to timely correct the therapy and improve the results of treatment and rehabilitation of patients with neuromuscular dysfunction.

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Background and objective: Pathogenic variants of RYR1, the gene encoding the principal sarcoplasmic reticulum calcium release channel (RyR1) with a crucial role in excitation-contraction coupling, are among the most common genetic causes of non-dystrophic neuromuscular disorders. We recently conducted a questionnaire study focusing on functional impairments, fatigue, and quality of life (QoL) in patients with RYR1-related diseases (RYR1-RD) throughout the recognized disease spectrum. In this previous questionnaire study the medical perspective was taken, reflective of a study protocol designed by neurologists and psychologists. With this present study we wanted to specifically address the patient perspective. Methods: Together with affected individuals, family members, and advocates concerned with RYR1-RD, we developed an online patient survey that was completed by 227 patients or their parents/other caretakers (143 females and 84 males, 0-85 years). We invited 12 individuals, representing most of the patient group based on age, sex, race, and type and severity of diagnosis, to share their personal experiences on living with a RYR1-RD during an international workshop in July 2022. Data were analyzed through a mixed-methods approach, employing both a quantitative analysis of the survey results and a qualitative analysis of the testimonials. Results: Data obtained from the combined quantitative and qualitative analyses provide important insights on six topics: 1) Diagnosis; 2) Symptoms and impact of the condition; 3) Physical activity; 4) Treatment; 5) Clinical research and studies; and 6) Expectations. Conclusions: Together, this study provides a unique patient perspective on the RYR1-RD spectrum, associated disease impact, suitable physical activities and expectations of future treatments and trials, and thus, offers an essential contribution to future research.

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Triosephosphate isomerase deficiency (TPI Df) is a rare multisystem disorder with severe neuromuscular symptoms which arises exclusively from mutations within the TPI1 gene. Studies of TPI Df have been limited due to the absence of mammalian disease models and difficulties obtaining patient samples. Recently, we developed a novel murine model of TPI Df which models the most common disease-causing mutation in humans, TPI1E105D. Using our model in the present study, the underlying pathogenesis of neuromuscular symptoms has been elucidated. This is the first report detailing studies of neuromuscular pathology within a murine model of TPI Df. We identified several contributors to neuromuscular symptoms, including neurodegeneration in the brain, alterations in neurotransmission at the neuromuscular junction, and reduced muscle fiber size. TPI Df mice also exhibited signs of cardiac pathology and displayed a deficit in vascular smooth muscle functionality. Together, these findings provide insight into pathogenesis of the neuromuscular symptoms in TPI Df and can guide the future development of therapeutics.

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 This meeting report summarizes the presentations and discussions held at the summit on Challenges in Gene Therapy hosted by the Muscular Dystrophy Association (MDA) in 2023. Topics covered include safety issues, mitigation strategies and practical considerations pertaining to the clinical translation of gene therapies for neuromuscular disease. The listing of actionable recommendations will assist in overall efforts in the field to achieve safe and efficacious translation of gene therapies for neuromuscular disease patients.

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The 274th ENMC workshop for optimizing bone strength in neuromuscular disorders (NMDs) was held on January 19-21, 2024. The group of participants included experts in the fields of bone health and neuromuscular medicine along with the patient voice. Bone strength represents a crucial aspect of the management of pediatric and adult patients with NMDs. Bone strength may be compromised due to different pathophysiologic mechanisms, including disrupted bone-muscle "cross-talk", loss of biomechanical loading, nutritional insufficiency, inadequate weight-bearing physical activity, muscle weakness and/or immobility, and drug treatment. While for Duchenne muscular dystrophy recommendations for evaluation and treatment of bone strength have been published, evidence on bone strength in other hereditary and acquired NMDs is scarce. Enhanced knowledge is needed to understand the development and maintenance of bone strength in patients with NMDs. This workshop aimed to develop a strategy to improve bone strength and thus prevent fractures in patients with NMDs.

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Neuromuscular disorders are a group of rare heterogenous diseases with profound impact on quality of life, for which overall pediatric prevalence has rarely been reported. The purpose of this study was to determine the point prevalence of pediatric neuromuscular disorders and its subcategories in the central region of Portugal. Retrospective case identification was carried out in children with neuromuscular disorders seen between 1998 and 2020 from multiple data sources. Demographics, clinical and molecular diagnoses were registered. On January 1, 2020, the point overall prevalence in the population <18 years of age was 41.20/100 000 (95% confidence interval 34.51-49.19) for all neuromuscular disorders. The main case proportion were genetic disorders (95.7%). We found a relatively higher occurrence of limb-girdle muscular dystrophies, congenital myopathies, and spinal muscular atrophy and a slightly lower occurrence of Duchenne muscular dystrophy, hereditary spastic paraparesis, and acquired neuropathies compared to previous studies in other countries. Molecular confirmation was available in 69.5% of pediatric neuromuscular patients in our cohort.Total prevalence is high in comparison with the data reported in the only previous study on the prevalence of pediatric neuromuscular disorders in our country. Our high definitive diagnostic rate underscores the importance of advances in investigative genetic techniques, particularly new sequencing technologies, in the diagnostic workup of neuromuscular patients.

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BACKGROUND: After receiving a diagnosis of a neuromuscular condition, patients have to make their way through a convoluted network of community and state resources as health care shifts from being family and child centered to adult focused. This study examined the barriers to successful transition from patient and clinician perspectives. METHODS: Adolescents with a primary diagnosis of a neuromuscular condition who were aged 16 years and over in Queensland, Australia, and who had started the transition process were eligible. Surveys were collected over six months and statistics used to characterize survey responses. RESULTS: There was a high degree of anxiety reported about the transition, with almost 50% of patients and families surveyed reporting concerns about moving across to the adult hospital system. The main barriers to effective transition identified by clinicians were limited time (84%), clinic space (58%), and a lack of an identified transition coordinator (79%). CONCLUSIONS: This study has provided a checklist to assist patients with neuromuscular disorders in transitioning from pediatric to adult care. A new model has been developed to enable a slow, personalized transition that is led by a multidisciplinary team.

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INTRODUCTION: Recovering from neuromuscular injuries or conditions can be a challenging journey that involves complex surgeries and extensive physical rehabilitation. During this process, individuals often rely on orthotic devices to support and enable movement of the affected limb. However, users have criticized current commercially available powered orthotic devices for their bulky and heavy design. To address these limitations, we developed a novel powered myoelectric elbow orthosis. MATERIALS AND METHODS: The orthosis incorporates 3 mechanisms: a solenoid brake, a Bowden cable-powered constant torque elbow mechanism, and an extension limiter. The device controller and battery are in a backpack to reduce the weight on the affected arm. We performed extensive calculations and testing to ensure that the orthosis could withstand at least 15 Nm of elbow torque. We developed a custom software effectively control the orthosis, enhancing its usability and functionality. A certified orthotist fitted a subject who had undergone a gracilis free functioning muscle transfer surgery with the device. We studied the subject under Mayo clinic IRB no. 20-006849 and obtained objective measurements to assess the orthosis's impact on upper extremity functionality during daily activities. RESULTS: The results are promising since the orthosis significantly improved elbow flexion range of motion by 40° and reduced compensatory movements at the shoulder (humerothoracic joint) by 50°. Additionally, the subject was able to perform tasks which were not possible before, such as carrying a basket with weights, highlighting the enhanced functionality provided by the orthosis. CONCLUSION: In brief, by addressing the limitations of existing devices, this novel powered myoelectric elbow orthosis offers individuals with neuromuscular injuries/conditions improved quality of life. Further research will expand the patient population and control mechanisms.

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Pediatric skeletal muscle channelopathies include a spectrum of conditions including nondystrophic myotonias and periodic paralyses. They are rare inherited conditions that can cause significant morbidity. They are characterized by episodic stiffness and weakness. While there is significant phenotypic variability, there are distinct diagnostic features. The nondystrophic myotonias encompass myotonia congenita, paramyotonia congenita, and sodium channel myotonia caused by mutations in chloride and sodium channels. The clinical manifestations vary across age groups and a small subset with sodium channel mutations may have severe presentation with fetal akinesia, laryngospasm, or congenital myopathy. The periodic paralyses include hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and Andersen-Tawil syndrome. The phenotypic differences between the groups can be helpful in diagnosis. It is important to review the cardiac phenotype in Andersen-Tawil syndrome due to a risk of life-threatening cardiac arrhythmias. Early and accurate diagnosis utilizing clinical features aided by investigations is important across all the pediatric channelopathies, as effective symptomatic treatment is available and can substantially improve quality of life.

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Rare neuromuscular diseases (NMDs) encompass various disorders of the nervous system and skeletal muscles, and present intricate challenges in diagnosis, treatment, and research due to their low prevalence and often diverse multisystemic manifestations. Leveraging collected patient data for secondary use and analysis holds promise for advancing medical understanding in this field. However, a certain level of data quality is a prerequisite for the methods that can be used to analyze data. The heterogeneous nature of NMDs poses a significant obstacle to the creation of standardized documentation, as there are still many challenges to accurate diagnosis and many discrepancies in the diagnostic process between different countries. This paper proposes the development of an information model tailored to NMDs, aiming to augment visibility, address deficiencies in documentation, and facilitate comprehensive analysis and research endeavors. By providing a structured framework, this model seeks to propel advancements in understanding and managing NMD, ultimately benefiting patients and healthcare providers worldwide.

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Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders.

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OBJECTIVE: This article reviews autoimmune neuromuscular disorders and includes an overview of the diagnostic approach, especially the role of antibody testing in a variety of neuropathies and some other neuromuscular disorders. LATEST DEVELOPMENTS: In the past few decades, multiple antibody biomarkers associated with immune-mediated neuromuscular disorders have been reported. These biomarkers are not only useful for better understanding of disease pathogenesis and allowing more timely diagnosis but may also aid in the selection of an optimal treatment strategy. ESSENTIAL POINTS: Recognition of autoimmune neuromuscular conditions encountered in inpatient or outpatient neurologic practice is very important because many of these disorders are reversible with prompt diagnosis and early treatment. Antibodies are often helpful in making this diagnosis. However, the clinical phenotype and electrodiagnostic testing should be taken into account when ordering antibody tests or panels and interpreting the subsequent results. Similar to other laboratory investigations, understanding the potential utility and limitations of antibody testing in each clinical setting is critical for practicing neurologists.

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Palliative care is important for many patients who require noninvasive ventilation. The particular needs of patients with neuromuscular disease and chronic obstructive pulmonary disease are explored. Advance care planning is explored with tips for undertaking this important communication task. Brief comments regarding symptom burden, weaning, voluntary assisted dying, and self-care are included.

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Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are neuromuscular disorders that affect muscular function. The most common causes of morbidity and mortality are respiratory complications, including restrictive lung disease, ineffective cough, and sleep-disordered breathing. The paradigm of care is changing as new disease-modifying therapies are altering disease trajectory, outcomes, expectations, as well as patient and caregiver experiences. This article provides an overview on therapeutic advances for SMA and DMD in the last 10 years, with a focus on the effects of disease-modifying therapies on respiratory function.

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High-quality respiratory care and airway clearance is essential for people with neuromuscular disease (pwNMD) as respiratory tract infections are a major cause of morbidity and mortality. This review expands on published guidelines by highlighting the role of cough peak flow along with other options for cough evaluation, and discusses recent key research findings which have influenced the practice of respiratory therapy for pwNMD.

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Advances in DNA sequencing technologies, especially next-generation sequencing (NGS), which is the basis for whole-exome sequencing (WES) and whole-genome sequencing (WGS), have profoundly transformed immune-mediated rheumatic disease diagnosis. Recently, substantial cost reductions have facilitated access to these diagnostic tools, expanded the capacity of molecular diagnostics and enabled the pursuit of precision medicine in rheumatology. Understanding the fundamental principles of genetics and diversity in genetic variant classification is a crucial milestone in rheumatology. However, despite the growing availability of DNA sequencing platforms, a significant number of autoinflammatory diseases (AIDs), neuromuscular disorders, hereditary collagen diseases, and monogenic bone diseases remain unsolved, and variants of uncertain significance (VUS) pose a formidable challenge to addressing these unmet needs in the coming decades. This article aims to provide an overview of the clinical indications and interpretation of comprehensive genetic testing in the medical field, addressing the related complexities and implications.

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