Neuromuscular problems of the critically Ill neonate and child.

Acute neuromuscular disorders occasionally occur in the Pediatric Neurologic Intensive Care Unit. Many of these are primary disorders of the motor unit that may present acutely or exacerbate during an intercurrent illness. Additionally, acute neuromuscular disorders may develop during an acute systemic illness requiring intensive care management that predispose the child to another set of acute motor unit disorders. This chapter discusses acute neuromuscular crises in the infant, toddler, and adolescent, as well as neuromuscular disorders resulting from critical illness.

Molecular mechanisms and therapeutic strategies for neuromuscular diseases.

Neuromuscular diseases encompass a heterogeneous array of disorders characterized by varying onset ages, clinical presentations, severity, and progression. While these conditions can stem from acquired or inherited causes, this review specifically focuses on disorders arising from genetic abnormalities, excluding metabolic conditions. The pathogenic defect may primarily affect the anterior horn cells, the axonal or myelin component of peripheral nerves, the neuromuscular junction, or skeletal and/or cardiac muscles. While inherited neuromuscular disorders have been historically deemed not treatable, the advent of gene-based and molecular therapies is reshaping the treatment landscape for this group of condition. With the caveat that many products still fail to translate the positive results obtained in pre-clinical models to humans, both the technological development (e.g., implementation of tissue-specific vectors) as well as advances on the knowledge of pathogenetic mechanisms form a collective foundation for potentially curative approaches to these debilitating conditions. This review delineates the current panorama of therapies targeting the most prevalent forms of inherited neuromuscular diseases, emphasizing approved treatments and those already undergoing human testing, offering insights into the state-of-the-art interventions.

Patient-Reported Outcome Measures in Neuromuscular Diseases: A Scoping Review.

 Patient-reported outcome measures (PROMs) are valuable in comprehensively understanding patients' health experiences and informing healthcare decisions in research and clinical care without clinicians' input. Until now, no central resource containing information on all PROMS in neuromuscular diseases (NMD) is available, hindering the comparison and choice of PROMs used to monitor NMDs and appropriately reflect the patient's voice. This scoping review aimed to present a comprehensive assessment of the existing literature on using PROMs in children and adults with NMD. A scoping methodology was followed using Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to assess the literature on PROMs in NMDs. Eligibility criteria encompassed articles describing psychometric development or evaluation of generic or disease-specific PROM-based instruments for adults and children with specific NMDs. The data charting process involved extracting measurement properties of included PROMs, comprising validity, reliability, responsiveness, and interpretability information. The review identified 190 PROMs evaluated across 247 studies in individuals with NMDs. The majority of PROMs were disease specific. The physical functioning domain was most assessed. Validity was the most frequently investigated measurement property, with a limited number of PROMs sufficiently evaluated for a range of psychometric characteristics. There is a strong need for further research on the responsiveness and interpretability of PROMs and the development of PROMs on social functioning in NMD.

A Mobile Health App to Support Home-Based Aerobic Exercise in Neuromuscular Diseases: Usability Study.

BACKGROUND: Home-based aerobic exercise in people with neuromuscular diseases (NMDs) has benefits compared to exercise in the hospital or a rehabilitation center because traveling is often cumbersome due to mobility limitations, and societal costs are lower. Barriers to home-based aerobic exercise include reduced possibilities for monitoring and lack of motivation. To overcome these and other barriers, we developed a mobile health app: Keep on training with ReVi (hereafter referred to as ReVi). OBJECTIVE: We aimed to determine the usability of the ReVi app. METHODS: Patients followed a 4-month, polarized, home-based aerobic exercise program on a cycle or rowing ergometer, with 2 low-intensity sessions and 1 high-intensity session per week supported by the ReVi app. The app collected training data, including heart rate and ratings of perceived exertion, provided real-time feedback on reaching target intensity zones, and enabled monitoring via an online dashboard. Physiotherapists instructed patients on how to use the ReVi app and supervised them during their training program. Patients and physiotherapists separately evaluated usability with self-developed questionnaires, including 9 questions on a 5-point Likert scale, covering the usability elements efficiency, effectiveness, and satisfaction. RESULTS: Twenty-nine ambulatory adult patients (n=19 women; mean age 50.4, SD 14.2 years) with 11 different slowly progressive NMDs participated. Both patients and physiotherapists (n=10) reported that the app, in terms of its efficiency, was easy to use and had a rapid learning curve. Sixteen patients (55%) experienced 1 or more technical issue(s) during the course of the exercise program. In the context of effectiveness, 23 patients (81%) indicated that the app motivated them to complete the program and that it helped them to exercise within the target intensity zones. Most patients (n=19, 70%) and physiotherapists (n=6, 60%) were satisfied with the use of the app. The median attendance rate was 88% (IQR 63%-98%), with 76% (IQR 69%-82%) of time spent within the target intensity zones. Four adverse events were reported, 3 of which were resolved without discontinuation of the exercise program. CONCLUSIONS: The usability of the ReVi app was high, despite the technical issues that occurred. Further development of the app to resolve these issues is warranted before broader implementation into clinical practice.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).

BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS). METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available. RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management. CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

The Importance of Early Treatment of Inherited Neuromuscular Conditions.

There has been tremendous progress in treatment of neuromuscular diseases over the last 20 years, which has transformed the natural history of these severely debilitating conditions. Although the factors that determine the response to therapy are many and in some instance remain to be fully elucidated, early treatment clearly has a major impact on patient outcomes across a number of inherited neuromuscular conditions. To improve patient care and outcomes, clinicians should be aware of neuromuscular conditions that require prompt treatment initiation. This review describes data that underscore the importance of early treatment of children with inherited neuromuscular conditions with an emphasis on data resulting from newborn screening efforts.

Peripheral nervous system and neuromuscular disorders in the emergency department: A review.

INTRODUCTION: Acute presentations and emergencies in neuromuscular disorders (NMDs) often challenge clinical acumen. The objective of this review is to refine the reader's approach to history taking, clinical localization and early diagnosis, as well as emergency management of neuromuscular emergencies. METHODS: An extensive literature search was performed to identify relevant studies. We prioritized meta-analysis, systematic reviews, and position statements where possible to inform any recommendations. SUMMARY: The spectrum of clinical presentations and etiologies ranges from neurotoxic envenomation or infection to autoimmune disease such as Guillain-Barré Syndrome (GBS) and myasthenia gravis (MG). Delayed diagnosis is not uncommon when presentations occur "de novo," respiratory failure is dominant or isolated, or in the case of atypical scenarios such as GBS variants, severe autonomic dysfunction, or rhabdomyolysis. Diseases of the central nervous system, systemic and musculoskeletal disorders can mimic presentations in neuromuscular disorders. CONCLUSIONS: Fortunately, early diagnosis and management can improve prognosis. This article provides a comprehensive review of acute presentations in neuromuscular disorders relevant for the emergency physician.

Gene-based therapies for neuromuscular disorders.

Neuromuscular diseases (NMD) include a broad group of medical conditions with both acquired and genetic causes. In recent years, important advances have been made in the treatment of genetically caused NMD, and most of these advances are due to the implementation of therapies aimed at gene regulation. Among these therapies, gene replacement, small interfering RNA (siRNA), and antisense antinucleotides are the most promising approaches. More importantly, some of these therapies have already gained regulatory approval or are in the final stages of approval. The review focuses on motor neuron diseases, neuropathies, and Duchenne muscular dystrophy, summarizing the most recent developments in gene-based therapies for these conditions.

Doenças neuromusculares (DNM) compõem um grupo amplo de doenças de causa tanto adquiridas quanto genéticas. Nos últimos anos, importantes avanços ocorreram quanto ao tratamento das DNM de causa genética e grande parte desses avanços se deve à implementação de terapias voltadas para a modificação gênica. Dentre essas terapias, destacam-se as terapias de reposição gênica, uso de RNA de interferência, uso de antinucleotídeos antisense, entre outras. E, mais importante, algumas dessas terapias já se tornaram realidade na prática médica e já foram aprovadas, ou estão a poucos passos da aprovação, por órgãos governamentais regulatórios. Esta revisão aborda aspectos mais recentes quanto ao uso das terapias genéticas avançadas para algumas das formas mais comuns de DNM, em especial para doenças do neurônio motor (esclerose lateral amiotrófica e atrofia muscular espinhal), neuropatias e distrofia muscular de Duchenne.

Multidisciplinary Treatment in Patients with Craniofacial, Neurocognitive, and Neuromuscular Disorders with Obstructive Sleep Apnea: A Systematic Review of the Literature.

Obstructive sleep apnea (OSA) is a respiratory disorder that has a high prevalence in patients with craniofacial, neurocognitive, and neuromuscular disorders. Currently, the treatments for this population are diverse and depend on the individual conditions of the patient and the severity of the case. However, there are no multidisciplinary dental treatment guidelines. The aim of the present study was to determine the multidisciplinary dental treatment alternatives in patients with craniofacial, neurocognitive, and neuromuscular disorders with a diagnosis of OSA through evidence-based medicine. A systematic review of the literature has been performed by searching scientific articles in the PubMed, Cochrane, Ovid, ScienceDirect and Scopus databases, through controlled and uncontrolled language. Articles were classified according to the level of evidence and grades of recommendation through the Scottish Intercollegiate Guidelines Network. A total of 19,439 references were identified, of which 15 articles met the predetermined requirements to be included in the investigation. The articles included for this systematic review showed that mandibular distraction osteogenesis and adenotonsilectomy are the first-choice therapies for craniofacial and neurocognitive disorders. However, for neuromuscular disorders, the findings reported were not enough to provide information about surgical or nonsurgical alternatives. Despite the reported high frequency of OSA in those children with craniofacial, neurocognitive, and neuromuscular disorders, the evidence on the surgical and nonsurgical therapeutic success for OSA in these patients is scarce. It is necessary to perform future studies to investigate successful therapies for OSA in children. [Pediatr Ann. 2024;53(2):e62-e69.].

The experience of clinical study and trial participation in rare diseases: A scoping review of centronuclear myopathy and other neuromuscular disorders.

The design of a clinical trial for a rare disease can be challenging. An optimal study design is required to effectively study the clinical outcomes for possible therapies for these types of disorders. Understanding the study participants' experiences as well as barriers and facilitators of participation are important to optimize future research and to inform clinical trial management. Centronuclear myopathies (CNMs) including X-linked myotubular myopathy (XLMTM) are a group of rare congenital myopathies for which there is no cure currently. Since 2014, a number of natural history studies and clinical trials have been conducted in CNMs. Two trials have been prematurely terminated because of severe adverse events. Since no research has been conducted regarding trial experience in CNM, we performed a scoping literature research on clinical trial experience of patients with neuromuscular disorders in general. The most common barriers to trial participation of patients comprise concerns about potential harmful effects, opportunity loss and the expected burden on daily life. The most common facilitators were an expected benefit on the disease course, altruism and collateral benefit. While several results are in line with trial experiences of other types of patients, for example oncological patients, distinctions can be made for patients with CNM and other neuromuscular disorders. However, the limited availability of relevant literature suggests that future (qualitative) research should focus on trial experiences in CNM patients.

Musculoskeletal injections for palliative treatment of neuromuscular hip dysplasia patients: how I do it.

This review describes our institution's standardized technique as well as potential pitfalls for therapeutic steroid injections in children with symptomatic neuromuscular hip dysplasia. Symptomatic, painful neuromuscular hip dysplasia can dramatically affect quality of life. Steroid injections are used to identify the source of perceived pain, temporarily treat pain while awaiting surgical intervention, or for therapeutic management for nonoperative hip joints.

Neuromuscular ultrasound: Impact on diagnosis and management.

INTRODUCTION/AIM: High-resolution ultrasound (HRUS) is increasingly used in evaluating neuromuscular conditions. Its potential advantages include its ability to discern anatomic information and make specific etiological diagnoses. Although many studies have demonstrated HRUS effectiveness, especially in mononeuropathies, more information is needed to better determine how often and to what extent useful information is obtained; how it influences diagnosis, clinical decision-making, and patient management; and how it is used with electrodiagnostic (EDx) studies. METHODS: A retrospective cohort study was performed on patients referred for HRUS at a university laboratory during 2021. Demographic information, referral diagnoses, clinical information, HRUS findings, and follow-up patient management were analyzed. For patients who had EDx, results were compared with HRUS. Determinations were made whether HRUS did or did not aid in the diagnosis. For patients in whom HRUS resulted in a diagnosis, determination was made whether it confirmed the diagnosis made clinically or by EDx but did not change management; added additional important information; and/or made a decisive impact on subsequent management. RESULTS: Five hundred two patients were analyzed, most referred for mononeuropathy, brachial plexopathy, and polyneuropathy. HRUS was abnormal in 81.7% of patients. HRUS added additional useful information in 79.0% and was decisive in management in 62.7%. In patients who also had abnormal EDx, HRUS resulted in decisive management in 49.5%. DISCUSSION: HRUS is an effective diagnostic tool that frequently adds localizing and structural information that is otherwise not obtainable by clinical and EDx evaluation. In a substantial number of patients selected for HRUS, it is decisive in guiding further management.

Identification and Management of Acute Neuromuscular Respiratory Failure in the ICU.

Respiratory failure is a common and potentially life-threatening complication of neuromuscular diseases. Prompt recognition and accurate diagnosis of new or worsening chronic neuromuscular disease have important clinical management and prognostic implications. In this article, we present an approach to the acute presentation of undifferentiated neuromuscular respiratory failure in the ICU and guidance for determination and respiratory management of the underlying disorder.

Sleep in pediatric neuromuscular disorders.

Sleep disordered breathing (SDB) is prevalent among children with neuromuscular disorders (NMD). The combination of respiratory muscle weakness, altered drive, and chest wall distortion due to scoliosis make sleep a stressful state in this population. Symptomatology can range from absent to snoring, nocturnal awakenings, morning headaches, and excessive daytime sleepiness. Sequelae of untreated SDB includes cardiovascular effects, metabolic derangements, and neurocognitive concerns which can be compounded by those innate to the NMD. The clinician should have a low threshold for obtaining polysomnography and recognize the nuances of individual disorders due to disproportionately impacted muscle groups such as hypoventilation in ambulating patients from diaphragm weakness. Non-invasive or invasive ventilation are the mainstay of treatment. In this review we explore the diagnosis and treatment of SDB in children with various NMD.

Abordaje paliativo en enfermedades respiratorias avanzadas / Palliative Approach in Advanced Respiratory Diseases

Las enfermedades respiratorias crónicas avanzadas son prevalentes y producen deterioro de la calidad de vida, en particular la enfermedad pulmonar obstructiva crónica (EPOC), las enfermedades pulmonares intersticiales difusas (EPID) y las enfermedades neuromusculares progresivas con compromiso diafragmático (ENM). Quienes las padecen presentan síntomas persistentes que no son siempre adecuada-mente controlados por los tratamientos recomendados por las guías clínicas de mane-jo. El tratamiento paliativo de los síntomas persistentes es un punto relevante y suelen presentarse barreras para su implementación.Este artículo ofrece una revisión narrativa sobre una perspectiva latinoamericana acerca del rol de los cuidados paliativos en enfermedades respiratorias avanzadas.

Advanced chronic respiratory diseases are prevalent and cause deterioration in qual-ity of life, particularly chronic obstructive pulmonary disease (COPD), diffuse intersti-tial lung diseases (ILD) and progressive neuromuscular diseases with diaphragmatic involvement (NMD). Those who suffer from them usually present persistent symptoms that are not always adequately controlled by the treatments recommended by the clinical management guidelines. Palliative treatment of persistent symptoms is a relevant point, but the pal-liative approach usually presents barriers to its implementation.This article offers a narrative review over Latin American perspective on the role of pal-liative care in advanced respiratory diseases.

Ventilatory failure in chronic neuromuscular disease.

Patients with neuromuscular diseases (NMD) can present to the neurologist with symptoms and signs of respiratory failure, either acutely or as an insidious process in the outpatient setting. Since the advent of non-invasive ventilation, the outcomes of patients with ventilatory failure due to NMD have dramatically improved. However, the natural history of different NMDs requires a nuanced approach to respiratory investigation and management. Respiratory failure dictates the prognosis of many NMDs and timing the most appropriate investigation and referral to ventilation services is crucial in optimising care.