RÉSUMÉ
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.
Sujet(s)
Autoanticorps , Maladies neuromusculaires , Humains , Maladies neuromusculaires/diagnostic , Maladies neuromusculaires/immunologie , Autoanticorps/sang , Autoanticorps/immunologie , Mâle , Femelle , Adulte d'âge moyen , Adulte , Maladies auto-immunes du système nerveux/immunologie , Maladies auto-immunes du système nerveux/diagnostic , Maladies auto-immunes/immunologie , Maladies auto-immunes/diagnostic , Sujet âgé , Marqueurs biologiques/sangRÉSUMÉ
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.
Sujet(s)
Ventilation non effractive , Soins palliatifs , Humains , Ventilation non effractive/méthodes , Soins palliatifs/méthodes , Maladies neuromusculaires/thérapie , Broncho-pneumopathie chronique obstructive/thérapie , Planification anticipée des soinsRÉSUMÉ
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.
Sujet(s)
Myopathie de Duchenne , Humains , Myopathie de Duchenne/traitement médicamenteux , Myopathie de Duchenne/physiopathologie , Myopathie de Duchenne/complications , Amyotrophie spinale/traitement médicamenteux , Amyotrophie spinale/physiopathologie , Maladies neuromusculaires/traitement médicamenteux , Maladies neuromusculaires/physiopathologie , Maladies neuromusculaires/thérapieRÉSUMÉ
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.
Sujet(s)
Maladies neuromusculaires , Humains , Maladies neuromusculaires/thérapie , Maladies neuromusculaires/physiopathologie , Thérapie respiratoire/méthodes , Toux/thérapie , Toux/physiopathologie , Prise en charge des voies aériennes/méthodesRÉSUMÉ
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.
Sujet(s)
Conception d'appareillage , Orthèses , Humains , Orthèses/normes , Conception d'appareillage/normes , Maladies neuromusculaires/physiopathologie , Maladies neuromusculaires/rééducation et réadaptation , Articulation du coude/physiopathologie , Articulation du coude/physiologie , Coude/physiopathologieRÉSUMÉ
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.
Sujet(s)
Dépistage génétique , Rhumatismes , Humains , Dépistage génétique/méthodes , Rhumatismes/génétique , Rhumatismes/diagnostic , Séquençage nucléotidique à haut débit , Rhumatologie , , Maladies neuromusculaires/génétique , Maladies neuromusculaires/diagnostic , Maladies auto-inflammatoires héréditaires/génétique , Maladies auto-inflammatoires héréditaires/diagnostic , RhumatologuesRÉSUMÉ
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.
Sujet(s)
Modèles animaux de maladie humaine , Jonction neuromusculaire , Triose phosphate isomerase , Animaux , Triose phosphate isomerase/déficit , Triose phosphate isomerase/génétique , Triose phosphate isomerase/métabolisme , Souris , Jonction neuromusculaire/anatomopathologie , Jonction neuromusculaire/métabolisme , Anémie hémolytique congénitale non sphérocytaire/génétique , Anémie hémolytique congénitale non sphérocytaire/anatomopathologie , Maladies neuromusculaires/génétique , Maladies neuromusculaires/anatomopathologie , Maladies neuromusculaires/étiologie , Erreurs innées du métabolisme glucidique/génétique , Mutation , HumainsRÉSUMÉ
IMPORTANCE: Caregiver-performed home therapy programs are essential to occupational therapy intervention for infants and children with neuromotor and neuromuscular diagnoses. Factors that facilitate or are barriers to caregiver adherence when making home therapy recommendations should be considered. OBJECTIVE: To identify facilitators of and barriers to caregiver adherence to home therapy recommendations for children with neuromotor and neuromuscular disorders. METHOD: The review followed the five-step methodological framework developed by Arksey and O'Malley (2005) and was guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. DATA SOURCES: Searches with no language or date range limits were performed in MEDLINE, CINAHL Plus with Full Text, PsycINFO, and SocINDEX on the EBSCO platform, and Scopus on the Elsevier platform from database inception through January 24, 2023. STUDY SELECTION AND DATA COLLECTION: Study inclusion criteria included caregiver adherence to home therapy recommendations for children with neuromotor and neuromuscular diagnoses. Eight hundred seventy-five articles underwent title and abstract screening; 64 articles met the criteria for full review. FINDINGS: Twelve articles met the inclusion criteria. Four used qualitative measures, 7 used quantitative measures, and 1 used mixed methods. Qualitative thematic analysis revealed four facilitators: routine, efficacy of caregiver education, positive relationship with therapist, and perceived benefit of treatment. The analysis revealed three barriers: lack of time, lack of confidence, and caregiver stress. CONCLUSIONS AND RELEVANCE: The facilitators and barriers identified are central to best-practice occupational therapy. Therapists can use expertise in analyzing routines and context to maximize the fit between family needs and home therapy recommendations. Plain-Language Summary: Home therapy for children with a neuromotor and neuromuscular diagnosis is common and uses some form of caregiver-performed movement activities or techniques. To support caregivers, occupational therapists need to understand what factors facilitate or serve as barriers to following home therapy recommendations. The review found three barriers: lack of time, lack of confidence, and caregiver stress. The review provides strategies to support home therapy based on core principles of occupational therapy practice. It also identifies the need for more research to support home therapy recommendations that fit within the child's and family's routine, that can be taught in a way that meets the child's and family's learning needs, that facilitate self-efficacy and confidence, and that reflect the values and motivators of all participants.
Sujet(s)
Aidants , Maladies neuromusculaires , Ergothérapie , Humains , Ergothérapie/méthodes , Maladies neuromusculaires/rééducation et réadaptation , Nourrisson , Enfant , Enfant d'âge préscolaire , Services de soins à domicileRÉSUMÉ
Respiratory sequelae are a frequent cause of morbidity and mortality in children with NMD. Impaired cough strength and resulting airway clearance as well as sleep disordered breathing are the two main categories of respiratory sequelae. Routine clinical evaluation and diagnostic testing by pulmonologists is an important pillar of the multidisciplinary care required for children with NMD. Regular surveillance for respiratory disease and timely implementation of treatment including pulmonary clearance techniques as well as ventilation can prevent respiratory related morbidity including hospital admissions and improve survival. Additionally, novel disease modifying therapies for some NMDs are now available which has significantly improved the clinical trajectories of patients resulting in a paradigm shift in clinical care. Pulmonologists are 'learning' the new natural history for these diseases and adjusting clinical management accordingly.
Sujet(s)
Maladies neuromusculaires , Humains , Maladies neuromusculaires/thérapie , Maladies neuromusculaires/complications , Maladies neuromusculaires/diagnostic , Maladies neuromusculaires/physiopathologie , EnfantRÉSUMÉ
Objectives: The functions of eating, drinking, speaking, and breathing demand close coordination of the upper airway musculature which may be challenged by the long-term use of daytime non-invasive ventilation (NIV). This rapid review explores the challenges and practicalities of these interactions in people with neuromuscular disorders. Methods: A search was performed on PubMed (period 2000-2023) using generic terms to refer to eating, drinking, and speaking related to people with neuromuscular disorders on NIV. A narrative approach was used to summarize the available literature. Results: Our review shows only a small number of studies exist exploring the use of NIV on swallowing and speaking in people with neuromuscular disorders. We summarize study findings and provide practical advice on eating, drinking and speaking with NIV. Conclusions: By understanding breathing, NIV mechanics and upper airway interactions, it is possible to optimize swallowing and speaking whilst using NIV. There is a lack of specific guidelines, and concerns regarding aspiration warrant further research and guideline development.
Sujet(s)
Déglutition , Maladies neuromusculaires , Ventilation non effractive , Humains , Maladies neuromusculaires/complications , Maladies neuromusculaires/physiopathologie , Ventilation non effractive/méthodes , Déglutition/physiologie , Parole/physiologie , Troubles de la déglutition/étiologie , Troubles de la déglutition/thérapie , Troubles de la déglutition/physiopathologieRÉSUMÉ
Introduction: Neuromuscular diseases (NMD) include different types of diseases depending on the deficient component of the motor unit involved. They may all be interested by a progressive and sometimes irreversible pump respiratory failure which unfortunately for some NMD may start soon after the diagnosis. Within this vast group of patients those affected by muscle diseases are a subgroup who comprises patients with an average earlier onset of symptoms compared to other NMD. Indeed it is also important to comprehend not just the patient's burden but also the surrounding families'. Defining the end of life (EoL) phase in these patients is not simple especially in the young patient population. Consequently, the late stage of disease remains poorly defined and challenging. Objectives: The aim of this review is to describe the EoL phase in NMD patients with attention to QoL and psycological status. Methods: The focus would be on one hand on the management of the psychological burden, the communication barriers, and tone of humor. Results: Those topics have been described being crucial in this group of patients as they increase tensions and burden of both patient and family, and between them and the outside world. Thus also causing their social isolation, increasing anxiety and reducing their quality of life. On the other hand the use of cough clearance devices and all the respiratory supports and their withdrawn are carefully evaluated in the view of alleviating respiratory symptoms, improving patient quality of life and above all reaching the patient's goals of care. Conclusions: Although there is no cure, the advent of supportive interventions including multidisciplinary care (MDC) has improved all the aspects of dying for patients affected by NMD; nevertheless there still a long pathway ahead.
Sujet(s)
Maladies neuromusculaires , Soins palliatifs , Qualité de vie , Soins terminaux , Humains , Soins palliatifs/méthodes , Maladies neuromusculaires/thérapie , Maladies neuromusculaires/psychologie , Soins terminaux/méthodesRÉSUMÉ
Neuromuscular diseases (NMDs) comprise a heterogeneous group of conditions characterized by extreme progressive muscle weakness leading to respiratory failure. Noninvasive mechanical ventilation (NIV) has emerged as a cornerstone in the management of respiratory complications associated with NMDs. This review aims to elucidate the role of NMV in respiratory function, improving quality of life, and prolonging survival in individuals with NMD. The physiological basis of respiratory impairment in NMDs, principles of NMV application, evidence supporting its efficacy, patient selection criteria, and potential challenges in its application are discussed.
Sujet(s)
Maladies neuromusculaires , Ventilation non effractive , Insuffisance respiratoire , Humains , Maladies neuromusculaires/physiopathologie , Maladies neuromusculaires/thérapie , Maladies neuromusculaires/complications , Ventilation non effractive/méthodes , Insuffisance respiratoire/thérapie , Insuffisance respiratoire/étiologie , Insuffisance respiratoire/physiopathologie , Qualité de vieRÉSUMÉ
The neuromuscular patients may experience the need for respiratory support due to the onset of respiratory failure. Some skills are essential to achieve therapeutic success. In addition to technical knowledge, it is essential to have knowledge relating to individual neuromuscular diseases. The availability of alternative respiratory supports and various interfaces can be a valuable weapon at different moments in the course of the neuromuscular disease. Furthermore, the doctor-patient relationship plays a key role as does taking care of the patient's psychological sphere.
Sujet(s)
Maladies neuromusculaires , Ventilation non effractive , Insuffisance respiratoire , Humains , Maladies neuromusculaires/thérapie , Ventilation non effractive/méthodes , Insuffisance respiratoire/thérapie , Insuffisance respiratoire/étiologieRÉSUMÉ
(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.
Sujet(s)
Transplantation cardiaque , Maladies neuromusculaires , Humains , Transplantation cardiaque/effets indésirables , Mâle , Femelle , Adulte d'âge moyen , Maladies neuromusculaires/génétique , Adulte , Qualité de vie , , Muscles squelettiques/anatomopathologie , Muscles squelettiques/physiopathologie , Sujet âgé , Défaillance cardiaque/génétique , Défaillance cardiaque/chirurgie , Défaillance cardiaque/étiologie , Cardiomyopathies/génétique , Cardiomyopathies/étiologie , Faiblesse musculaire/étiologie , Faiblesse musculaire/génétique , Connectine/génétiqueRÉSUMÉ
Hypercapnic respiratory failure arises due to an imbalance in the load-capacity-drive relationship of the respiratory muscle pump, typically arising in patients with chronic obstructive pulmonary disease, obesity-related respiratory failure, and neuromuscular disease. Patients at risk of developing chronic respiratory failure and those with established disease should be referred to a specialist ventilation unit for evaluation and consideration of home noninvasive ventilation (NIV) initiation. Clinical trials demonstrate that, following careful patient selection, home NIV can improve a range of clinical, patient-reported, and physiological outcomes. This narrative review provides an overview of the pathophysiology of chronic respiratory failure, evidence-based applications of home NIV, and monitoring of patients established on home ventilation and describes technological advances in ventilation devices, interfaces, and monitoring to enhance comfort, promote long-term adherence, and optimise gas exchange.
Sujet(s)
Services de soins à domicile , Ventilation non effractive , Insuffisance respiratoire , Humains , Ventilation non effractive/méthodes , Ventilation non effractive/instrumentation , Insuffisance respiratoire/thérapie , Broncho-pneumopathie chronique obstructive/thérapie , Monitorage physiologique/méthodes , Maladies neuromusculaires/thérapie , Maladies neuromusculaires/complicationsRÉSUMÉ
Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.
Sujet(s)
Ferrosulfoprotéines , Humains , Ferrosulfoprotéines/génétique , Ferrosulfoprotéines/métabolisme , Mâle , Femelle , Maladies neuromusculaires/génétique , Maladies neuromusculaires/enzymologie , Maladies neuromusculaires/métabolisme , Maladies neuromusculaires/anatomopathologie , Enfant , Noyau de la cellule/métabolisme , Noyau de la cellule/enzymologie , Noyau de la cellule/génétique , Cytoplasme/métabolisme , Cytoplasme/enzymologie , MétallochaperonsRÉSUMÉ
Understanding the development and function of the human neuromuscular system is crucial for deciphering the mechanisms of neuromuscular disorders and developing effective therapies. However, limitations of animal models necessitate the development of human-specific in vitro models to study such complex diseases effectively. Here, we discuss different approaches for in vitro neuromuscular junction (NMJ) modeling: complex self-organized models that rely on the inherent abilities of cells to form NMJs based on embryonic developmental principles and assembled models that depend on integrating different cell types for controlled NMJ formation. Finally, we discuss the advantages and limitations of these models and the need for continued advancements enhanced by bioengineering approaches to deepen our understanding of human NMJ biology and pave the way for personalized medicine.
Sujet(s)
Jonction neuromusculaire , Humains , Animaux , Maladies neuromusculaires/génétique , Maladies neuromusculaires/anatomopathologie , Modèles biologiquesRÉSUMÉ
INTRODUCTION/AIMS: Fatigue is a common and debilitating symptom encountered in the neuromuscular clinic. The 7-item Fatigue Severity Scale (FSS-7) is a Rasch-modified assessment validated in inflammatory neuropathies but not across a typical neuromuscular patient population. The aim of this study was to validate this measure in neuromuscular disorders and to compare between patient sex, age and diagnoses. METHODS: The modified FSS-7 was mailed to patients recruited from a specialist neuromuscular clinic at the Walton Centre. Responses were subjected to Rasch analysis and descriptive statistics were performed on the Rasch converted data. RESULTS: The mFSS-7 met the Rasch model expectations with an overall Chi-square probability of 0.4918, a strict unidimensional scale free from differential item functioning (DIF) that satisfied the model with substantial test-retest reliability using Lin's concordance correlation coefficient 0.71 (95% CI 0.63-0.77). A 15.7% ceiling effect was observed in this patient cohort. Post hoc analysis did not show any significant difference in fatigue between sex, age or neuromuscular diagnoses. DISCUSSION: The self-completed Rasch mFSS-7 showed acceptable test-retest reliability across patients with varied disorders under follow-up in a specialist neuromuscular clinic. The ceiling effect constrains its use for those with the most severe fatigue. Future considerations could include assessment of the benefits of clinical interventions, particularly multidisciplinary team input or dedicated fatigue clinics.