Performance of the Asthma Clinical Score in the Evaluation of Acute Asthma in the Emergency Department.

Objective: The primary objective of this study was to examine the performance of the Asthma Clinical Score (ACS) relative to the Pediatric Respiratory Assessment Measure (PRAM). Our secondary objectives were to determine interrater reliability, discriminative validity, responsiveness, and predictive validity of the ACS and PRAM.

Methods: This was a single-site prospective observational study of children ages 2 to < 18 years presenting to the emergency department (ED) for asthma exacerbations.

Transitioning From Nusinersen to Risdiplam for Spinal Muscular Atrophy in Clinical Practice: A Single-Center Experience.

Background: Nusinersen and risdiplam are U.S. Food and Drug Administration (FDA)-approved treatments for spinal muscular atrophy (SMA).

Continued safety and long-term effectiveness of onasemnogene abeparvovec in Ohio.

5q spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by absence of the SMN1 gene with three FDA approved genetic therapies which significantly improve outcomes. The AAV9 mediated gene replacement therapy, onasemnogene abeparvovec, has the greatest potential for side effects. Here we report the safety and outcomes from 46 children treated with onasemnogene abeparvovec in the state of Ohio between December 2018 and January 2023.

Respiratory Insufficiency in Neuromuscular Disease (RIND): A Delphi Study to Establish Consensus Criteria to Define and Diagnose Hypoventilation in Pediatric Neuromuscular Disease.

Unlabelled: Chronic respiratory failure is a common endpoint in the loss of respiratory muscle function in patients with progressive neuromuscular disease (NMD). Identifying the onset of hypoventilation is critical to allow for the timely introduction of ventilator support and effectively manage respiratory failure [1-3]. While there are accepted criteria governing the diagnosis of hypoventilation during polysomnography (PSG) [4], there is concern that criteria are insufficient for identifying hypoventilation in the earlier stages of respiratory insufficiency related to NMD.

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial.

Introduction/aims: Delandistrogene moxeparvovec is indicated in the United States for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Long-term delandistrogene moxeparvovec microdystrophin protein (a shortened dystrophin that retains key functional domains of the wild-type protein) expression may positively alter disease progression in patients with DMD. We evaluated long-term safety and functional outcomes of delandistrogene moxeparvovec in patients with DMD.

Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial.

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset.

Patients with Spinal Muscular Atrophy Type 1 Achieve and Maintain Bulbar Function Following Onasemnogene Abeparvovec Treatment.

Background: Improvement and maintenance of bulbar function are goals of disease-modifying treatments for spinal muscular atrophy (SMA). Lack of standardized measures and a widely accepted definition of bulbar function represents a gap in SMA care.

Objective: A multidisciplinary team conducted post-hoc analyses of pooled data from one phase 1 (START) and two phase 3 (STR1VE-US, STR1VE-EU) studies to define and evaluate bulbar function of infants with SMA type 1 after receiving one-time gene replacement therapy, onasemnogene abeparvovec.

Protocol-driven early tracheal extubation in patients with flaccid neuromuscular scoliosis and pre-existing lung disease.

Purpose: To review the results of a postoperative respiratory pathway for patients with muscular dystrophy (MD) and spinal muscular atrophy (SMA) undergoing spinal surgery.

Methods: With IRB approval, a retrospective review was done on all patients with SMA and MD undergoing spinal surgery on a neuromuscular protocol. Baseline demographics, perioperative results, and long-term outcomes were collected.

Validity and Reliability of the Neuromuscular Gross Motor Outcome.

Background: Approved treatments in spinal muscular atrophy (SMA) have resulted in unprecedented gains for many individuals. Use of available outcomes, typically developed for a specific type of SMA, do not cover the range of progression, often resulting in a battery of functional testing being completed at visits. Our objective was to validate the Neuromuscular Gross Motor Outcome (GRO) as a tool to quantify function in SMA across the span of abilities.

EVALI versus MIS-C, one more overlapping diagnosis to consider.

We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased D-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities.

Five-Year Extension Results of the Phase 1 START Trial of Onasemnogene Abeparvovec in Spinal Muscular Atrophy.

Importance: This ongoing study assesses long-term safety and durability of response in infants with spinal muscular atrophy (SMA) type 1 after dosing with onasemnogene abeparvovec gene replacement therapy.

Objective: The primary objective of this ongoing study is to assess safety. The secondary objective is to determine whether developmental milestones achieved in the START phase 1 clinical trial were maintained and new milestones gained.

A 17-Year-Old With Becker Muscular Dystrophy and Unusual Polysomnography Findings.

A 17-year-old male patient who was diagnosed with Becker muscular dystrophy (nonsense mutation [c.3822C>A] within exon 28 of the DMD gene) at 6 years of age was evaluated in the multidisciplinary neuromuscular clinic for loss of ambulation for 1 year. From a pulmonary perspective, there were no acute or chronic respiratory symptoms, and no history of pneumonia or aspiration.

The respiratory impact of novel therapies for spinal muscular atrophy.

The phenotype of spinal muscular atrophy (SMA) has been changing with the recent availability of three FDA-approved treatments: intrathecal nusinersen, intravenous onasemnogene abeparvovec-xioi, and enteral risdiplam. The degree of improvement in muscle strength and respiratory health varies with SMA genotype, severity of baseline neuromuscular and pulmonary impairment, medication used, and timing of the first dose. A spectrum of pulmonary outcomes has been reported with these novel medications when used early and in conjunction with proactive multidisciplinary management of comorbidities.

Bronchiectasis associated with electronic cigarette use: A case series.

Bronchiectasis (BE) is defined as a permanent, irreversible dilation of the bronchial tree. In the pediatric population, this disease process is most commonly associated with patients with cystic fibrosis (CF). However, BE unrelated to CF is increasingly noted as a cause of chronic respiratory related morbidity worldwide.

Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial.

Importance: Micro-dystrophin gene transfer shows promise for treating patients with Duchenne muscular dystrophy (DMD) using recombinant adeno-associated virus serotype rh74 (rAAVrh74) and codon-optimized human micro-dystrophin driven by a skeletal and cardiac muscle-specific promoter with enhanced cardiac expression (MHCK7).

Objective: To identify the 1-year safety and tolerability of intravenous rAAVrh74.MHCK7.

Eosinophilic Pneumonia and Lymphadenopathy Associated With Vaping and Tetrahydrocannabinol Use.

Idiopathic acute eosinophilic pneumonia is a rare and potentially life-threatening condition that is defined by bilateral pulmonary infiltrates and fever in the presence of pulmonary eosinophilia. It often presents acutely in previously healthy individuals and can be difficult to distinguish from infectious pneumonia. Although the exact etiology of idiopathic acute eosinophilic pneumonia remains unknown, an acute hypersensitivity reaction to an inhaled antigen is suggested, which is further supported by recent public health risks of vaping (electronic cigarette) use and the development of lung disease.

AVXS-101 (Onasemnogene Abeparvovec) for SMA1: Comparative Study with a Prospective Natural History Cohort.

Background: Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma®) gene replacement therapy, are emerging.

Objective: This study evaluated the effectiveness of AVXS-101 in infants with spinal muscular atrophy type 1 (SMA1) compared with a prospective natural history cohort and a cohort of healthy infants.

Methods: Twelve SMA1 infants received the proposed therapeutic dose of AVXS-101 (NCT02122952).

Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy.

Background: This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1).

Methods: This study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: (1) early dosing/low motor, dosed age less than three months with scores <20 (n = 3), (2) late dosing, dosed at age three months or greater (n = 6), and (3) early dosing/high motor, dosed age less than three months with scores ≥20 (n = 3).

Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy.

Background: Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent-ventilation by 13.6 months. This study assessed the health outcomes of SMA1 infants treated with AVXS-101 gene replacement therapy.

Respiratory Management of the Patient With Duchenne Muscular Dystrophy.

In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the Centers for Disease Control and Prevention, was published in , and in 2018, these guidelines were updated. Since the publication of the first set of guidelines, survival of individuals with Duchenne muscular dystrophy has increased. With contemporary medical management, survival often extends into the fourth decade of life and beyond.

Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: Super Babies for SMA!

Background/aims: Recruitment and retention of research participants are challenging and critical components of successful clinical trials and natural history studies. Infants with spinal muscular atrophy (SMA) have been a particularly challenging population to study due to their fragile and complex medical issues, poor prognosis and, until 2016, a lack of effective therapies. Recruitment of healthy infants into clinical trials and natural history studies is also challenging and sometimes assumed to not be feasible.

Low-level expression of EPG5 leads to an attenuated Vici syndrome phenotype.

Vici syndrome is a multisystem disorder characterized by agenesis of the corpus callosum, oculocutaneous hypopigmentation, cataracts, cardiomyopathy, combined immunodeficiency, failure to thrive, profound developmental delay, and acquired microcephaly. Most individuals are severely affected and have a markedly reduced life span. Here we describe an 8-year-old boy with a history of developmental delay, agenesis of the corpus callosum, failure to thrive, myopathy, and well-controlled epilepsy.

Natural history of infantile-onset spinal muscular atrophy.

Objective: Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes.

Methods: A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants and 27 control infants aged <6 months.

Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy.

Background: Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve motor milestones and in death or the need for mechanical ventilation by 2 years of age. We studied functional replacement of the mutated gene encoding survival motor neuron 1 (SMN1) in this disease.

Methods: Fifteen patients with SMA1 received a single dose of intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA encoding the missing SMN protein.