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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. We will perform a multi-center, 12-month study of 188 LGMD patients within the established Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Research Consortium, which is comprised of 11 sites in the United States and 2 sites in Europe. Enrolled patients will be clinically affected and have mutations in CAPN3 (LGMDR1), ANO5 (LGMDR12), DYSF (LGMDR2), DNAJB6 (LGMDD1), SGCA (LGMDR3), SGCB (LGMDR4), SGCD (LGMDR6), or SGCG (LGMDR5, or FKRP-related (LGMDR9). Discussion: To the best of our knowledge, this will be the largest consortium organized to prospectively validate clinical outcome assessments (COAs) in LGMD at its completion. These assessments will help clinical trial readiness by identifying reliable, valid, and responsive outcome measures as well as providing data driven clinical trial decision making for future clinical trials on therapeutic agents for LGMD. The results of this study will permit more efficient clinical trial design. All relevant data will be made available for investigators or companies involved in LGMD therapeutic development upon conclusion of this study as applicable. Trial registration: Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019. [ABSTRACT FROM AUTHOR]

Objective The North Star Assessment for limb-girdle type muscular dystrophies (NSAD), a clinician-reported outcome measure (ClinRO) of motor performance, was initially developed and validated for use in dysferlinopathy, an autosomal recessive form of limb-girdle muscular dystrophy (LGMD R2/2B). Recent developments in treatments for limb-girdle muscular dystrophies (LGMD) have highlighted the urgent need for disease-specific ClinROs. The purpose of this study was to understand the ability of the NSAD to quantify motor function across the broad spectrum of LGMD phenotypes. Methods Assessments of 130 individuals with LGMD evaluated by the physical therapy teams at Nationwide Children's Hospital and the John Walton Muscular Dystrophy Research Centre were included in the analysis. NSAD, 100-m timed test (100MTT), and Performance of Upper Limb 2.0 assessment data were collected. Psychometric analysis with Rasch measurement methods was used to examine the NSAD for suitability and robustness by determining the extent to which the observed data "fit" with predictions of those ratings from the Rasch model. The NSAD score was correlated with the 100MTT and Performance of Upper Limb 2.0 assessment scores for external construct validity. Results The NSAD demonstrated a good spread of items covering a continuum of abilities across both individuals who had LGMD and were ambulatory and individuals who had LGMD and were weaker and nonambulatory. Items fit well with the construct measured, validating a summed total score. The NSAD had excellent interrater reliability [intraclass correlation coefficient (ICC) = 0.986, 95% CI = 0.981–0.991] and was highly correlated with the 100MTT walk/run velocity (Spearman rho correlation coefficient of rs(134) = .92). Conclusion Although LGMD subtypes may differ in age of onset, rate of progression, and patterns of muscle weakness, the overall impact of progressive muscle weakness on motor function is similar. The NSAD is a reliable and valid ClinRO of motor performance for individuals with LGMD and is suitable for use in clinical practice and research settings. Impact Recent developments in potential pharmacological treatments for LGMD have highlighted the urgent need for disease-specific outcome measures. Validated and meaningful outcome measures are necessary to capture disease presentation, to inform expected rates of progression, and as endpoints for measuring the response to interventions in clinical trials. The NSAD, a scale of motor performance for both individuals who have LGMD and are ambulatory and those who are nonambulatory, is suitable for use in clinical and research settings. [ABSTRACT FROM AUTHOR]

Critical components of successful evaluation of clinical outcome assessments (COAs) in multisite clinical trials and clinical practice are standardized training, administration, and documented reliability of scoring. Experiences of evaluators, alongside patient differences from regional standards of care, may contribute to heterogeneity in clinical center's expertise. Achieving low variability and high reliability of COA is fundamental to clinical research and to give confidence in our ability to draw rational, interpretable conclusions from the data collected. The objective of this manuscript is to provide a framework to guide the learning process for COAs for use in clinics and clinical trials to maximize reliability and validity of COAs in neuromuscular disease (NMD). This is a consensus-based guideline with contributions from fourteen leading experts in clinical outcomes and the field of clinical outcome training in NMD. This framework should guide reliable and valid assessments in NMD specialty clinics and clinical trials. This consensus aims to expedite study start up with a progressive training pathway ranging from research naïve to highly experienced clinical evaluators. This document includes recommendations for education guidelines and roles and responsibilities of key stakeholders in COA assessment and implementation to ensure quality and consistency of outcome administration across different settings. [ABSTRACT FROM AUTHOR]

Clinical outcome assessments of function or strength, assessed by physical therapists, are commonly used as primary endpoints in clinical trials, natural history studies and within clinics for individuals with neuromuscular disorders. These evaluations not only inform the efficacy of investigational agents in clinical trials, but also importantly track disease trajectory to prospectively advise need for equipment, home and work modifications, and other assistive devices. The COVID-19 pandemic had a global impact on the safety and feasibility of in-person visits and assessments, necessitating rapid development of mitigation strategies to ensure ongoing collection of key clinical trial endpoints and access to expert clinical care despite travel restrictions. Physical therapists who are expert in neuromuscular disorders working across clinics, countries, and clinical trials developed initial guidelines and methods for the suitability and feasibility of performing remote evaluations. A number of Sponsors introduced amendments to their study protocols to enable remote evaluations, supported by live video streaming of the assessment to their local clinical evaluators. Similarly, application of these techniques to clinical telemedicine enabled objective evaluations for use in payer discussions, equipment procurement, and general access to expert physical therapy services. Here we report on our methodology for adapting current practices to remote testing and considerations for remote evaluations. [ABSTRACT FROM AUTHOR]

Objective: To continue evaluation of the long-term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three-year progression of eteplirsen-treated patients was compared to matched historical controls (HC).Methods: Ambulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open-label basis. The primary functional assessment in this study was the 6-Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.Results: At 36 months, eteplirsen-treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen-treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.Interpretation: Over 3 years of follow-up, eteplirsen-treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. [ABSTRACT FROM AUTHOR]

The evidence for Constraint-Induced Movement Therapy (CIMT) effectiveness for infants and toddlers with unilateral cerebral palsy is minimal. We performed a pilot study of CIMT using one-month usual care, one-month intervention, and one-month maintenance (return to usual care) phases on five infants (7- to 18-month old). For the CIMT phase, the infants received 2 hr of occupational therapy and 1 hr of parent-implemented home program for five days/week. The infants were casted for the first 23 days, and bimanual therapy was provided for the last three days. Fine motor skills for the more affected arm and gross motor skills improved significantly during the CIMT; these gains were maintained at one-month follow-up. Individual infant data show mixed effects. This pilot study provides initial evidence that CIMT is feasible for infants with unilateral cerebral palsy, and presents preliminary data for CIMT on fine and gross motor performance. [ABSTRACT FROM AUTHOR]

Purpose: To present an algorithm with accompanying treatment parameters for the management of congenital muscular torticollis (CMT) based on the best available literature. Methods: A systematic search of PubMed, MEDLINE, CINHAL, and Cochrane databases was conducted to identify evidence to guide the conservative management of CMT. Results: An evidence-based algorithm was created based on three prognostic factors that influence treatment duration and outcome, including a sternocleidomastoid fibrotic mass, passive range of motion rotation deficit, and age at initiation of treatment. Preliminary treatment parameter recommendations for clinic and home programming accompany the algorithm. Conclusion: Use of the proposed evidence-based algorithm with accompanying preliminary treatment parameter recommendations may improve consistency of care and outcomes for infants with CMT. While a higher level of evidence supports the three prognostic factors utilized in the algorithm, research gaps continue to exist with regards to treatment parameters. [ABSTRACT FROM AUTHOR]

An abstract of the study "Delivery of Constraint-Induced Movement Therapy Through a Video Game for Individuals with Hemiparesis Post-Stroke," by Jana Jaffe, Linda Lowes, Alexandra Borstad, Lise Worthen-Chaudhari, Roger Crawfis, David Maung, Amelia Siles and Lynne Gauthier is presented.

• Remote outcomes may reduce travel burden and access to quality care and research. • Remote testing strategies were implemented in response to the pandemic. • Validation of remote methodologies are needed prior to broad implementation. • Remote testing and alternative monitoring strategies are currently being investigated. [ABSTRACT FROM AUTHOR]