Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study.

Background: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG).

Methods: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded.

A case report of riboflavin transporter deficiency: A novel heterozygous pathogenic variant in the gene.

Riboflavin transporter deficiency (RTD) is a neurodegenerative disorder that presents from infancy to adulthood with a progressive axonal neuropathy characterized by a variety of neurologic symptoms including hearing loss, weakness, bulbar palsy, and respiratory insufficiency. Pathogenic variants in and are implicated in the pathogenesis of RTD type 2 and 3, respectively. Early identification of this disorder is critical, as it is treatable with riboflavin supplementation.

Use of the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) in Spinal Muscular Atrophy.

: Spinal muscular atrophy (SMA) has a remarkable impact on function and participation. Subsequently, the caregivers of individuals with SMA are impacted as well. Providers and the SMA community should be aware of the presence of and likely expectations for the existence of caregiver burden.

A Virtual Reality Exergame: Clinician-Guided Breathing and Relaxation for Children with Muscular Dystrophy.

This study introduces a VR-based breathing and relaxation exergame tailored for individuals with Duchenne muscular dystrophy (DMD). DMD is a rare neuromuscular disease that leads to respiratory muscle dysfunction with anxiety being a common comorbidity. Clinical management requires frequent visits to rare disease specialists to manage symptom progression.

Axonal polyneuropathy and ataxia in children: consider Perrault Syndrome, a case report.

Background: Perrault Syndrome (PRLTS) is a rare, autosomal recessive disorder that presents with bilateral sensorineural hearing loss in all patients and gonadal dysfunction in females. It has been linked to variants in CLPP, ERAL1, HARS2, HSD17B4, LARS2, and TWNK genes. All reported cases due to TWNK variants have included neurologic features, such as ataxia and axonal sensorimotor neuropathy.

Expansion of the phenotypic spectrum associated with pathogenic missense variation in DHX16.

Pathogenic heterozygous variants in DHX16 have been recently identified in association with a variety of clinical features, including neuromuscular disease, sensorineural hearing loss, ocular anomalies, and other phenotypes. All DHX16 disease-causing variants previously reported in affected individuals are missense in nature, nearly all of which were found to be de novo. Here we report on a patient with neuromuscular disease, hearing loss, retinal degeneration, and previously unreported phenotypic features including mitochondrial deficiency and primary ovarian insufficiency, in whom a novel de novo likely pathogenic variant in DHX16 NM_003587.

Measuring the Efficacy of Thymectomy for Pediatric Myasthenia Gravis Across Tertiary Children's Hospitals.

Background: Thymectomy is a treatment for pediatric myasthenia gravis, but the efficacy over time is unknown. Multi-institutional data are also lacking. Therefore, the objective of this study was to determine the efficacy of thymectomy for pediatric myasthenia gravis using medication burden and health care utilization as proxies for disease severity.

Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study.

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of > 4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]).

Longitudinal Assessment of Timed Function Tests in Ambulatory Individuals with SMA Treated with Nusinersen.

Background: Ambulatory individuals with spinal muscular atrophy experience weakness and impairments of speed and endurance. This leads to decreased motor skill performance required for daily living including transitioning from floor to stand, climbing stairs, and traversing short and community distances. Motor function improvements have been reported in individuals receiving nusinersen, but changes in timed functional tests (TFTs) which assess shorter distance walking and transitions have not been well documented.

Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a rare, genetic disease caused by mutations in the DMD gene resulting in an absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, has been shown to increase endogenous dystrophin levels. Herein, long-term (>2 years) functional outcomes in viltolarsen treated patients were compared to a matched historical control group.

An expanded access program of risdiplam for patients with Type 1 or 2 spinal muscular atrophy.

Objective: The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment.

Methods: Patients were enrolled from 23 non-preselected sites across 17 states and treated with risdiplam orally once daily.

Combination molecular therapies for type 1 spinal muscular atrophy.

Background: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking.

Methods: This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy.

Results: Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene).

Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.

Importance: An unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of the disease.

Objective: To evaluate the safety, tolerability, and efficacy of viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping.

Spinal muscular atrophy care in the COVID-19 pandemic era.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in reorganization of healthcare settings affecting the delivery of clinical care to patients with spinal muscular atrophy (SMA). There is a concern that patients with SMA may be at increased risk of manifesting severe symptoms of COVID-19. Currently approved therapies for SMA improve survival and motor function; however, their delivery requires an increased exposure to the health system and a dedicated healthcare team.

The care of patients with Duchenne, Becker, and other muscular dystrophies in the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in the reorganization of health-care settings affecting clinical care delivery to patients with Duchenne and Becker muscular dystrophy (DBMD) as well as other inherited muscular dystrophies. The magnitude of the impact of this public health emergency on the care of patients with DBMD is unclear as they are suspected of having an increased risk for severe manifestations of COVID-19. In this article, the authors discuss their consensus recommendations pertaining to care of these patients during the pandemic.

Utility of Repetitive Nerve Stimulation in Myopathies.

Investigators from the Mayo Clinic, Rochester, MN, evaluated 157 patients with confirmed myopathy who had electrodiagnostic studies done between January 2007 and May 2017.

Spinal Muscular Atrophy Diagnosed by Newborn Screening.

A panel of experts representing academic centers, family foundations and pharmaceutical industry came together to formulate a treatment algorithm for infants diagnosed via newborn screening (NBS) with Spinal muscular atrophy (SMA).

PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype.

PIGQ (OMIM *605754) encodes phosphatidylinositol glycan biosynthesis class Q (PIGQ) and is required for proper functioning of an N-acetylglucosamine transferase complex in a similar manner to the more established PIGA, PIGC, and PIGH. There are two previous patients reported with homozygous and apparently deleterious PIGQ mutations. Here, we provide the first detailed clinical report of a patient with heterozygous deleterious mutations associated with glycosylphosphatidylinositol-anchored protein (GPI-AP) biosynthesis deficiency.

Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that, in most cases, involves homozygous deletion of the SMN1 gene. This causes a deficiency in survival motor neuron (SMN) protein, which plays a critical role in motor neuron development. SMA has a range of phenotype expression resulting in variable age of symptom onset, maximum motor strength achieved, and survival.

Friedreich's Ataxia: Clinical Presentation of a Compound Heterozygote Child with a Rare Nonsense Mutation and Comparison with Previously Published Cases.

Friedreich's ataxia is a neurodegenerative disorder associated with a GAA trinucleotide repeat expansion in intron 1 of the frataxin (FXN) gene. It is the most common autosomal recessive cerebellar ataxia, with a mean age of onset at 16 years. Nearly 95-98% of patients are homozygous for a 90-1300 GAA repeat expansion with only 2-5% demonstrating compound heterozygosity.