Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study.

Objective: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study.

Findings from the Longitudinal CINRG Becker Natural History Study.

Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.

Objective: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.

Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy: A GRASP-LGMD study.

Background: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders.

Methods/design: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes.

Provisional practice recommendation for the management of myopathy in VCP-associated multisystem proteinopathy.

Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe.

Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy.

Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.

Methods: Participants were at least 18 years old and had FSHD1/FSHD2.

Patient reported quality of life in limb girdle muscular dystrophy.

This study determined the frequency and impact of symptoms on quality of life in patients diagnosed with limb girdle muscular dystrophy (LGMD). Participants with a diagnosis of LGMD in registries based at the Coalition to Cure Calpain-3, the Jain foundation, and the Global FKRP Registry competed a survey to report the frequency and relative impact of themes and symptoms of LGMD. Frequency, mean impact, and population impact scores were calculated, and responses were categorized by age, symptom duration, gender, employment status, use of assistive devices, and LGMD subtypes.

Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial.

Importance: Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers.

Limb Girdle Muscular Dystrophies.

The limb girdle muscular dystrophies (LGMDs) are genetic muscle diseases with primary skeletal muscle involvement in persons with the ability to walk independently at some point in the disease course. They usually have increased creatine kinase levels along with patterns of fatty and fibrous deposition on muscle imaging and/or dystrophic features on muscle biopsy. Distinctive clinical features provide valuable diagnostic clues to the diagnosis and sometimes treatment of these disorders.

The CINRG Becker Natural History Study: Baseline characteristics.

We performed an observational, natural history study of males with in-frame dystrophin gene deletions causing Becker muscular dystrophy (BMD). A prospective natural history study collected longitudinal medical, strength, and timed function assessments. Eighty-three participants with genetically confirmed BMD were enrolled (age range 5.

The Limb-Girdle Muscular Dystrophies.

Purpose Of Review: As a group, the limb-girdle muscular dystrophies (LGMDs) are the fourth most prevalent genetic muscle disease, yet they are still not well known or understood. This article defines and describes LGMDs, delineates a diagnostic strategy, and discusses treatment of the LGMDs.

Recent Findings: In 2018, the definition of the LGMDs was further refined, and a new nomenclature was proposed.

Ankle bracing practices in ambulatory, corticosteroid-naive boys with Duchenne muscular dystrophy.

Introduction: Loss of ambulation in Duchenne muscular dystrophy presages scoliosis, respiratory failure, and death. Strategies to maintain ankle range of motion are employed, but little evidence exists to support these approaches and limited information is available concerning current practice.

Methods: In this study we assessed baseline bracing data from 187 boys participating in a multicenter, international clinical trial.

Novel clinical features of glycine receptor antibody syndrome: A series of 17 cases.

Objective: To describe novel clinical features of GlyRα1-IgG-positive patients.

Methods: Patients with a positive serum GlyRα1-IgG were identified during a 2-year period from July 2016 to December 2018 at 2 academic centers and followed prospectively. All patients in this series were evaluated in the Neuroimmunology and Autoimmune Neurology clinics at the University of Utah or the University of Colorado.

Limb-girdle muscular dystrophy: A perspective from adult patients on what matters most.

Introduction: Limb-girdle muscular dystrophy (LGMD) consists of over 30 genetic conditions with varying clinical phenotypes primarily affecting pelvic girdle, shoulder girdle, and other proximal limb muscles. Studies focusing on the physical, mental, and social effects of this disease from the patient's perspective are limited.

Methods: Adults with LGMD were interviewed and asked to identify issues that have the greatest impact on their quality of life.

Take two: Utility of the repeat skeletal muscle biopsy.

Introduction: The utility of repeat muscle biopsy has not been adequately evaluated.

Methods: A retrospective review was undertaken of 144 repeat muscle biopsies performed from 1980 to 2017. Repeat biopsy was considered clinically relevant if it provided a new diagnosis, changed the existing diagnosis, or led to treatment changes or further investigations.

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Objective: Limb-girdle muscular dystrophies (LGMDs), one of the most heterogeneous neuromuscular disorders (NMDs), involves predominantly proximal-muscle weakness with >30 genes associated with different subtypes. The clinical-genetic overlap among subtypes and with other NMDs complicate disease-subtype identification lengthening diagnostic process, increases overall costs hindering treatment/clinical-trial recruitment. Currently seven LGMD clinical trials are active but still no gene-therapy-related treatment is available.

KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth.

KIF1Bβ is a kinesin-3 family anterograde motor protein essential for neuronal development, viability, and function. KIF1Bβ mutations have previously been reported in a limited number of pedigrees of Charcot-Marie-Tooth disease type 2A (CMT2A) neuropathy. However, the gene responsible for CMT2A is still controversial, and the mechanism of pathogenesis remains elusive.

A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial.

Background: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011.

The Effect of Propofol on Chronic Headaches in Patients Undergoing Endoscopy.

Objective: This study determined acute and long-term effects of propofol administration in patients with severe headaches undergoing endoscopic procedures.

Background: Approximately 13% of the US population is affected by migraines or severe headaches. The effect of propofol on headaches more than a few days after the intervention has not been explored.

A CARASIL Patient from Americas with Novel Mutation and Atypical Features: Case Presentation and Literature Review.

Objective: Reporting a novel mutation in the HTRA1 gene in a CARASIL patient from Americas.

Methods: Clinical presentation and neuroimaging were consistent with CARASIL. HTRA1 DNA sequencing was performed using advanced ("next generation") sequencing technology.