INTRODUCTION/AIMS:Despite disease-modifying therapies, fatigability persists in spinal muscular atrophy (SMA). Performance fatigability (PF) during the six-minute walk test (6MWT) is mostly unchanged in treated SMA. This cross-sectional study characterized PF using instrumented insoles. METHODS:Ambulatory individuals with SMA (n = 14) and controls (HC) (n = 10) were included. Spatiotemporal and kinetic parameters were collected with custom-engineered instrumented insoles during the 6MWT. Linear mixed models analyzed parameter trends, with trend slope representing PF. Changes in mean velocity (Vavg) and stride-by-stride parameters were compared between minute 1 and 6 and between groups. RESULTS:Decreases in Vavg were greatest for severe SMA (p < 0.001). Changes were found in stride length (SL) (p = 0.048) and stride velocity (SV) (p = 0.030) for severe SMA, and in stance phase (%St) (p = 0.012) and percent terminal double support (%DS) (p = 0.02) for mild SMA. SMA subgroups showed downward trends from minute 1 to 6 in SL, SV, and anterior-posterior center of pressure (AP-COP) (p < 0.001), and increases in Absolute COP-Cyclogram Asymmetry Index (|ASI|) (p < 0.05). Trends differed between severe SMA and other groups for SL, SV, %St, and %DS (p < 0.001), and for AP-COP and |ASI| (p < 0.05). Trends for SL (p < 0.001), SV and AP-COP (p < 0.01) differed between HC and mild SMA. DISCUSSION:PF in SMA manifests as changes in gait parameters. Instrumented insoles revealed fatigue-related changes not captured with the conventional method of comparing the first and last minutes of the 6MWT. Spatiotemporal and kinetic parameters contribute to understanding of impairments and inform therapeutic development. TRIAL REGISTRATION:ClinicalTrials.gov: NCT04193085.

Background: Fatigue and fatigability are commonly reported in spinal muscular atrophy (SMA). Physical fatigability, proposed to be the most relevant to SMA pathophysiology, encompasses performance-based and perceived physical fatigability (PPF) assessments. While performance-based measures have highlighted physical fatigability as an SMA hallmark, PPF is not well characterized due to the lack of disease- and construct-specific scales. Objective: Our aim was to create a patient-reported outcome measure tailored for SMA, named the SMA EFFORT, to improve PPF assessment. Here, we describe the scale development process, assess scale properties, and discuss future research and application. Methods: SMA and scale development experts organized a comprehensive physical activity item bank, relevant across the SMA phenotypic spectrum. Activities were systematically categorized by varying intensities and durations. The SMA EFFORT was completed by an international cohort of individuals with all types of SMA. To compare PPF across demographic and clinical variables, SMA EFFORT PPF percent (PPF%) composite scoring was established. Results: One hundred eighteen participants completed the SMA EFFORT. Total PPF% scores were broadly distributed within functional groups, with differences between non-sitters (35.1 ± 21.0) and sitters (24.9 ± 15.1) ( p = 0.006), and those with (34.4 ± 18.1) and without respiratory support (26.4 ± 17.8) ( p = 0.02). Participants treated with disease modifying therapy (DMT) showed similar scores to those without treatment ( p = 0.70). Further, no differences in scores were observed in participants with scoliosis surgery and those without ( p = 0.71). Subscale analyses revealed differences in mean PPF% subscale scores by functional group. Conclusions: The novel SMA EFFORT standardizes PPF ratings by anchoring activity to intensity and duration. Item and scale data insights will inform the next iteration, which will undergo additional investigation. The SMA EFFORT aims to improve upon current measures to better assess treatment impact on physical well-being across the SMA spectrum.

PURPOSE:The study compares moderate- to vigorous-intensity physical activity (MVPA) as evaluated by the Exercise Vital Signs (EVS) and Physical Activity Vital Signs (PAVS) questionnaires to accelerometry, and evaluates the reliability of the questionnaires in ethnically diverse adults. METHODS:Ninety-nine participants (mean age 38.1 y; 49.5% women; Hispanics 43.8%; European American 18.8%; African American 14.6%) were included in the analyses. Participants wore an accelerometer at the hip for at least 7 days and completed the EVS and PAVS questionnaires at the beginning (T1) and at the end (T2) of the 7 days. Associations between the questionnaires and accelerometry were examined using Spearman rho. The reliability of the questionnaires was evaluated using intraclass correlation coefficient. Sensitivity and specificity were also calculated. RESULTS:Weak positive correlations were observed between the accelerometer MVPA and the EVS MVPA at T2 (ρ = .263, P = .013), and the PAVS MVPA at T2 (ρ = .327, P = .003). The sensitivity of the EVS and PAVS was 73.2% and 82.6%, respectively. The specificity for each questionnaire was 35.3%. The reliability for the EVS questionnaire (intraclass correlation coefficient = .855; 95% CI, .791-.901; P < .001) was good, while the reliability of the PAVS questionnaire (intraclass correlation coefficient = .652; 95% CI, .511-.758; P < .001) was moderate. CONCLUSION:Caution should be used when utilizing the EVS and PAVS questionnaires in ethnically diverse adults.

Background: Individuals with spinal muscular atrophy (SMA) are at risk for low bone mass (LBM). The objectives of this study were to compare bone mineral density (BMD) in ambulatory SMA and control participants, identify LBM, and evaluate the associations of function and physical activity (PA) with LBM. Methods: Thirty-five children and adults, nineteen SMA and sixteen healthy controls, participated. Dual-energy absorptiometry determined BMD, T-scores, and Z-scores. The six-minute walk test (6MWT) and Timed Up and Go (TUG) assessed function. The International Physical Activity Questionnaire Short Form (IPAQ-SF) evaluated PA. Results: Group comparisons and factors associated with BMD were analyzed. Area under the receiver operating characteristic (ROC) curve (AUC) assessed the ability to identify individuals with LBM. SMA participants had lower BMD (p < 0.001) and increased odds of having LBM relative to controls (OR = 16.7; 95%CI: 1.8–152.8; p = 0.004). Conclusions: Ten SMA and one control had LBM. Z-score was associated with 6MWT (rs = 0.65; p < 0.001) and TUG (rs = −0.61; p < 0.001). IPAQ-SF and Z-score were weakly associated (rs = 0.36, p < 0.03). 6MWT (AUC: 0.80; 95% CI: 0.65–0.94; p = 0.006) and TUG (AUC: 0.85; 95% CI: 0.71–0.98; p = 0.002) identified individuals with LBM. Function, assessed by the 6MWT and TUG, is associated with BMD and shows promise for use in identifying individuals with LBM.

BACKGROUND:Protein phosphatase 2 regulatory subunit B' Delta (PPP2R5D)-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the PPP2R5D gene. Clinical signs include hypotonia, gross motor delay, intellectual disability (ID), epilepsy, speech delays, and abnormal gait among other impairments. As this disorder was recognized within the last decade, there are only 103 people published diagnoses to date. A thorough understanding of the motor manifestations of this disorder has not yet been established. Knowledge of the natural history of PPP2R5D related neurodevelopmental disorder will lead to improved standard of care treatments as well as serve as a baseline foundation for future clinical trials. Appropriate outcome measures are necessary for use in clinical trials to uniformly measure function and monitor potential for change. The aim of this study was to validate the gross motor function measure (GMFM) in children and adults with PPP2R5D-related neurodevelopmental disorder in order to better characterize the disorder. RESULTS:Thirty-eight individuals with PPP2R5D pathogenic variants, median age 8.0 years (range 1-27) were evaluated. Gross motor, upper limb and ambulatory function were assessed using the GMFM-66, six-minute walk test (6MWT), 10-meter walk run (10MWR), timed up and go (TUG), and revised upper limb module (RULM). The pediatric disability inventory computer adapted test (PEDI-CAT) captured caregiver reported assessment. Median GMFM-66 score was 60.6 (SD = 17.3, range 21.1-96.0). There were strong associations between the GMFM-66 and related mobility measures, 10MWR (rs = -0.733; p < 0.001), TUG (rs= -0.747; p = 0.003), 6MWT (r = 0.633; p = 0.006), RULM (r = 0.763; p < 0.001), PEDICAT-mobility (r = 0.855; p < 0.001), and daily activities (r = 0.822; p < 0.001) domains. CONCLUSIONS:The GMFM is a valid measure for characterizing motor function in individuals with PPP2R5D related neurodevelopmental disorder. The GMFM-66 had strong associations with the RULM and timed function tests which characterized gross motor, upper limb and ambulatory function demonstrating concurrent validity. The GMFM-66 was also able to differentiate between functional levels in PPP2R5D related neurodevelopmental disorder demonstrating discriminant validity. Future studies should examine its sensitivity to change over time, ability to identify sub-phenotypes, and suitability as an outcome measure in future clinical trials in individuals with PPP2R5D variants.

KIF1A-associated neurological disorder (KAND) is a neurodegenerative and often lethal ultrarare disease with a wide phenotypic spectrum associated with largely heterozygous de novo missense variants in KIF1A. Antisense oligonucleotide treatments represent a promising approach for personalized treatments in ultrarare diseases. Here we report the case of one patient with a severe form of KAND characterized by refractory spells of behavioral arrest and carrying a p.Pro305Leu variant in KIF1A, who was treated with intrathecal injections of an allele-specific antisense oligonucleotide specifically designed to degrade the mRNA from the pathogenic allele. The first intrathecal administration was complicated by an epidural cerebrospinal fluid collection, which resolved spontaneously. Otherwise, the antisense oligonucleotide was safe and well tolerated over the 9-month treatment. Most outcome measures, including severity of the spells of behavioral arrest, number of falls and quality of life, improved. There was little change in the 6-min Walk Test distance, but qualitative changes in gait resulting in meaningful reductions in falls and increasing independence were observed. Cognitive performance was stable and did not degenerate over time. Our findings provide preliminary insights on the safety and efficacy of an allele-specific antisense oligonucleotide as a possible treatment for KAND. A personalized antisense oligonucleotide developed for a female with a KIF1A-associated neurological disorder was well tolerated and led to preliminary improvements in mobility and behavioral arrest after 9 months of follow-up.

BACKGROUND:Individuals with PPP2R5D-related neurodevelopmental disorder have an atypical gait pattern characterized by ataxia and incoordination. Structured, quantitative assessments are needed to further understand the impact of these impairments on function.RESEARCH QUESTION:How do gait parameters and ambulatory function of individuals with PPP2R5D-related neurodevelopmental disorder compare to age and sex matched healthy norms?METHODS:Twenty-six individuals with PPP2R5D pathogenic genetic variants participated in this observational, single visit study. Participants completed at least one of the following gait assessments: quantitative gait analysis at three different speeds (preferred pace walking (PPW), fast paced walking (FPW) and running, six-minute walk test (6MWT), 10-meter walk run (10MWR), and timed up and go (TUG). Descriptive statistics were used to summarize gait variables. Percent of predicted values were calculated using published norms. Paired t-tests and regression analyses were used to compare gait variables.RESULTS:The median age of the participants was 8 years (range 4-27) and eighteen (69.2 %) were female. Individuals with PPP2R5D-related neurodevelopmental disorder walked slower and with a wider base of support than predicted for their age and sex. Stride velocity ranged from 48.9 % to 70.1 % and stride distance from 58.5 % to 81.9 % of predicted during PPW. Percent of predicted distance walked on the 6MWT ranged from 30.6 % to 71.1 % representing varied walking impairment. Increases in stride distance, not cadence, were associated with changes in stride velocity in FPW (R2 = 0.675, p =< 0.001) and running conditions (R2 = 0.918, p =< 0.001).SIGNIFICANCE:We quantitatively assessed the abnormal gait in individuals with PPP2R5D-related neurodevelopmental disorder. These impairments may affect ability to adapt to environmental changes and participation in daily life. Rehabilitative interventions targeting gait speed and balance may improve function and safety for individuals with PPP2R5D-related neurodevelopmental disorder.

PURPOSE: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, marked by insufficient production of SMN protein leading to motor neuron dysfunction. Although ubiquitously produced throughout the body, motor neurons and muscle cells are selectively impacted by decreased SMN which has been linked to impaired oxidative phosphorylation causing altered metabolic function and exercise intolerance. Nusinersen, administered directly to the central nervous, is an approved therapy that increases SMN protein in an effort to restore motor neuron function. The purpose was to evaluate the impact of treatment on markers of exercise tolerance in children and adults treated with nusinersen. METHODS: Nusinersen treated ambulatory children and adults with SMA completed a maximal cardiopulmonary exercise (CPX) test on a cycle ergometer at two visits 6 months apart. Oxygen uptake (VO2) at peak exercise, oxygen uptake efficiency slope (OUES), and ventilatory equivalent for oxygen (VE/VO2) at peak exercise were determined. Paired sample t-tests were used to evaluate change between visits. RESULTS: Nine ambulatory children and adults with SMA (89% male) (mean age = 32.4, range = 13-57 years) were included. The average length of time participants had received treatment was 1.05 years (range = 0.59 - 1.30 years). VO2 significantly increased from 13.49 ml/kg/min to 16.52 ml/kg/min (P = 0.03), OUES increased from 1324 to 1495 ml/min O2/L min, and VE/VO2 increased from 44.9 to 49.0 between visits. No significant differences were found in OUES or VE/VO2. (P < 0.05) CONCLUSION: These results show potential to mitigate exercise intolerance with nusinersen treatment in individuals with SMA. VO2 was significantly improved but an attenuated OUES and exaggerated hyperventilation response, representative measures of efficiency, persists. As aerobic capacity reflects the integrative function of multiple body systems, the improvement observed may be attributed to tissues not directly targeted by Nusinersen. Exercise testing is a valuable method of assessing muscle oxygen kinetics and suggested mitochondrial dysfunction observed in SMA. Combining exercise with drug therapies may further enhance benefits seen by treatment alone and developing specific muscle targeted therapies may be warranted.

PURPOSE: To compare the moderate-to-vigorous intensity PA (MVPA) as evaluated by the Exercise Vital Sign (EVS) and Physical Activity Vital Sign (PAVS) questionnaires against accelerometry, and to evaluate the reliability of the EVS and PAVS questionnaires in a multi-ethnic group. METHODS: Participants (mean age 40 years; 48.5% females) from New York City (NYC) were asked to wear an accelerometer at the hip for 7 days and complete both questionnaires at the beginning (T1) and end (T2) of the wear period. The Freedson (1998) cut-points were used to determine accelerometer-derived MVPA. The relationship between the EVS, the PAVS and the accelerometer MVPA was evaluated using Spearman’s rho (ρ). The sensitivity (meeting PA guidelines) and specificity (not meeting PA guidelines) of the questionnaires was evaluated against accelerometer data. Test-retest reliability was calculated using intraclass correlation coefficient (ICC) between EVS and PAVS responses at T1 and T2. RESULTS: One hundred multi-ethnic participants were included. PAVS-determined MVPA at T2 was significantly higher than the accelerometer MVPA (383 ± 307 vs. 263 ± 156 min/week, respectively) (p = .001). EVS-determined MVPA at T2 was higher than the MVPA determined by accelerometry, but not statistically significant (312 ± 270 vs. 263 ± 156, respectively) (p = .347). A weak but significant positive correlation was observed between the accelerometer-determined MVPA min/week and the EVS MVPA min/week at T2 (ρ = 0.263, p = .013), and the PAVS MVPA min/week at T2 (ρ = 0.327, p = .003). The sensitivity of the EVS and PAVS were 73.2% and 82.6%, respectively. The specificity for each questionnaire was 35.3%. The reliability for the EVS questionnaire (ICC = 0.855; 95% CI: .791-.901)(p < .001) was good, while the reliability of the PAVS questionnaire (ICC = 0.652; 95% CI: .511-.758)(p < .001) was moderate. CONCLUSIONS: The EVS and PAVS show weak associations with accelerometer MVPA. Furthermore, they overestimate MVPA in a multi-ethnic urban cohort when compared to accelerometry. Both questionnaires performed poorly in identifying those who are physically inactive, while they were reasonably able to detect those who met PA recommendations. Caution should be used when utilizing these questionnaires given their measurement properties.

BACKGROUND:Physical activity (PA) provides many substantial benefits to help reduce risk for cardiometabolic disease, improve cognitive function, and improve quality of life. Individuals with neuromuscular disorders (NMDs), such as spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are characterized by muscular weakness and fatigue, which limits the capacity to reach the recommended guidelines of PA. Measuring PA in these populations can provide insight to participation in daily activities, track disease progression, and monitor efficacy of drug treatments.OBJECTIVE:The objective of this study was to identify how PA is measured in SMA and DMD using instrumented and self-report methods, and how these methods are employed in ambulatory and non-ambulatory groups.METHODS:A scoping review was performed to identify studies that reported PA in these neuromuscular disorders. Inclusion was determined after a multi-stage review process by several reviewers, followed by an in-depth analysis of metrics reported by each tool that was used.RESULTS:A total of nineteen studies were identified and included in this review. Sixteen studies included instrumented measures and four studies utilized self-reported measures, with eleven studies also reporting PA information from a non-ambulatory group. A variety of metrics have been reported using both classes of measurement tools.CONCLUSION:Although a wide variety of research exists that details both instrumented and self-reported measurement tools, feasibility, cost, and study aims are important factors to consider in addition to testing methodology when selecting which type of tool to use. We recommend using a combination of instrumented and self-report measures to provide context to the PA measured in these populations. Improvements in both instrumented and self-report methodologies will add valuable knowledge about the disease burden and efficacy of treatment and disease management methods in SMA and DMD.

Measuring center-of-pressure (COP) trajectories in out-of-the-lab environments may provide valuable information about changes in gait and balance function related to natural disease progression or treatment in neurological disorders. Traditional equipment to acquire COP trajectories includes stationary force plates, instrumented treadmills, electronic walkways, and insoles featuring high-density force sensing arrays, all of which are expensive and not widely accessible. This study introduces novel deep recurrent neural networks that can accurately estimate dynamic COP trajectories by fusing data from affordable and heterogeneous insole-embedded sensors (namely, an eight-cell array of force sensitive resistors (FSRs) and an inertial measurement unit (IMU)). The method was validated against gold-standard equipment during out-of-the-lab ambulatory tasks that simulated real-world walking. Root-mean-square errors (RMSE) in the mediolateral (ML) and anteroposterior (AP) directions obtained from healthy individuals (ML: 0.51 cm, AP: 1.44 cm) and individuals with neuromuscular conditions (ML: 0.59 cm, AP: 1.53 cm) indicated technical validity. In individuals with neuromuscular conditions, COP-derived metrics showed significant correlations with validated clinical measures of ambulatory function and lower-extremity muscle strength, providing proof-of-concept evidence of the convergent validity of the proposed method for clinical applications.

Fatiguability and perceived fatigue are common unrelated symptoms in ambulatory individuals with spinal muscular atrophy (SMA). Ratings of perceived exertion (RPE) measures the sense of effort during an activity and has been used as a proxy for fatigue. Relationships between perceived fatigue, fatiguability, and RPE have been described in healthy populations, but the relationship in SMA has not been examined.

Fatigue, a common symptom, together with the characteristic of performance fatigability, are well-documented features of SMA that impact quality of life and function. Importantly, establishing associations between multidimensional self-reported fatigue scales and patient performance has proven difficult. This review was conducted to evaluate the various patient-reported fatigue scales applied in SMA, with the objective of considering the limitations and advantages of each measure. Variable use of fatigue-related nomenclature, including conflicting terminology interpretation, has affected assessment of physical fatigue attributes, specifically perceived fatigability. This review encourages the development of original patient-reported scales to enable perceived fatigability assessment, providing a potential complementary method of evaluating treatment response.

Wrist-worn and smartphone-embedded inertial sensors are among the most widely used sensing modalities for activity classification. Insoles instrumented with inertial and force sensors have also become available to researchers and the general public. However, little is known about how classification accuracy is affected by the combination of these three sensing modalities. This study compares the performances of 7 activity classification models, each relying on a combination of 3, 2, or a single sensing modality, under unstructured and free-living conditions. In each model, a genetic algorithm was applied for optimal feature selection, and multi-session leave-one-out cross-validation was used to evaluate model performance. Results for the unstructured condition indicated that the insole-embedded sensors can classify six common ambulatory activities with at least 95% accuracy when used alone or in combination with any of the other sensing modalities. In free-living conditions, sensor combinations that included the insole-embedded sensors demonstrated high levels of agreement with a silver-standard activity tracker. These results provide new insights into the feasibility of using instrumented insoles in combination with phone-embedded or wrist-worn sensors to enhance the accuracy of conventional methods for ambulatory activity classification.

Continuous gait monitoring may aid the early diagnosis of neurological and musculoskeletal conditions and help validate the effectiveness of new treatments. However, consumer-grade activity trackers can only capture summary gait metrics, whereas most of the research-grade devices capable of estimating fine-grained gait parameters are too cumbersome for extended-time use in real-life environments. Instrumented footwear may offer a promising alternative tool owing to their good accuracy and relatively small form factor, but their ability to detect stride-by-stride spatial gait parameters in free-living conditions has not been well explored to date. This work describes machine learning (ML) inference models for an insole system capable of accurately estimating stride time (ST), length (SL), and velocity (SV) in real-life environments. Functional validity was assessed through unstructured tests including straight-line walking, curve walking, and turns. Ecological validity was examined in free-living conditions. The ML models demonstrated better accuracy than conventional data processing methods (mean absolute errors in unstructured conditions were 3.55% for SL and 3.59% for SV). Real-life gait parameters estimated with the ML models showed stronger associations with a standardized walking test compared with the same parameters obtained with conventional methods. These results indicate proof-of-concept feasibility of using instrumented insoles and ML inference models for free-living spatiotemporal gait analysis.

The purpose of this systematic review is twofold: 1) to identify, evaluate, and synthesize the heretofore disparate scientific literatures regarding the effects of direct exposure to microgravity on the musculoskeletal system, taking into account for the first time both bone and muscle systems of both humans and animals; and 2) to investigate the efficacy and limitations of exercise countermeasures on the musculoskeletal system under microgravity in humans.The Framework for Scoping Studies (Arksey and O'Malley 2005) and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT 2011) were used to guide this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was utilized in obtaining the combined results (Moher, Liberati et al. 2009). Data sources,PubMed, Embase, Scopus, and Web of Science were searched for published articles through October 2019 using the Mesh terms of microgravity, musculoskeletal system, and exercise countermeasures. A total of 84 references were selected, including 40 animal studies and 44 studies with human participants. The heterogeneity in the study designs, methodologies, and outcomes deemed this review unsuitable for a meta-analysis. Thus, we present a narrative synthesis of the results for the key domains under five categories: 1) Skeletal muscle responses to microgravity in humans 2) Skeletal muscle responses to microgravity in animals 3) Adaptation of the skeletal system to microgravity in humans 4) Adaptation of the skeletal system to microgravity in animals 5) Effectiveness of exercise countermeasures on the human musculoskeletal system in microgravity. Existing studies have produced only limited data on the combined effects on bone and muscle of human spaceflight, despite the likelihood that the effects on these two systems are complicated due to the components of the musculoskeletal system being anatomically and functionally interconnected. Bone is directly affected by muscle atrophy as well as by changes in muscle strength, notably at muscle attachments. Given this interplay, the most effective exercise countermeasure is likely to be robust, individualized, resistive exercise, primarily targeting muscle mass and strength.

Background and purpose With the availability and development of disease-modifying therapies for individuals with spinal muscular atrophy (SMA), new emerging phenotypes must be characterized, and potential new treatment paradigms tested. There is an urgent demand to develop an educational program that provides physical therapists (PTs) worldwide the necessary knowledge and training to contribute to best-practice care and clinical research. A competency based education framework is one that would focus on outcomes not process and where progression of learners would occur only after competencies are demonstrated. The first step toward such a framework is defining outcomes. The purpose of this Delphi study was to develop consensus on those competencies deemed essential within the SMA PT community. Methods Purposive selection and snowball sampling techniques were used to recruit expert SMA PTs. Three web-based survey rounds were used to achieve consensus, defined as agreement among >80% of respondents. The first round gathered demographic information on participants as well as information on clarity and redundancy on a list of competencies; the second round, collected the same information on the revised list and whether or not participants agreed if the identified domains captured the essence of a SMA PT as well as the definitions for each; and the third asked participants to rank their agreement with each competency. Results Consensus revealed 35 competencies, organized under 6 domains, which were deemed essential for a PT working with persons with SMA. Discussion In order to develop a curriculum to meet the physical therapy needs of persons with SMA, it is imperative to establish defined outcomes and to achieve consensus on those outcomes within the SMA community. Conclusions This study identified essential competencies that will help to provide guidance in development of a formal education program to meet these defined outcomes. This can foster best-practice care and clinical decision-making for all PTs involved in the care of persons with SMA in a clinical and research setting.

Research in powered prostheses and orthoses has relied on COP measurements to inform a device’s controller about the body’s progression through the gait cycle, and to provide sensory substitution for prosthesis users, thereby helping them maintain balance during locomotion. Obtaining accurate COP measurements in out-of-the-lab contexts currently requires pressure sensitive insoles with dense arrays of sensing elements, which are expensive and bulky, limiting the accessibility and scalability of this technology. In this paper, we present a new method to reconstruct COP trajectories in over-ground walking tasks, using an affordable sensor array with eight sensing elements embedded in shoe insoles. The method leverages Gaussian Process Regression (GPR) to perform predictions from raw sensor data using Bayesian inference. A preliminary validation was carried out with a convenience sample of healthy individuals and patients with neuromuscular disorders. Combined mediolateral (ML) and anteroposterior (AP) errors where 2% and 3% for healthy individuals and patients, respectively. The analysis evidenced larger stride-to-stride variability in the ML COP excursion for the patient group, suggesting higher levels of motor noise associated with selective muscle weakness. These promising results indicate the potential of the proposed method to accurately estimate COP trajectories for future applications in wearable robotics and out-of-the-lab clinical gait assessments.

Abstract Objective To estimate muscle oxygen uptake and quantify fatigue during exercise in ambulatory individuals with spinal muscular atrophy (SMA) and healthy controls. Methods Peak aerobic capacity (VO2peak) and workload (Wpeak) were measured by cardiopulmonary exercise test (CPET) in 19 ambulatory SMA patients and 16 healthy controls. Submaximal exercise (SME) at 40% Wpeak was performed for 10 minutes. Change in vastus lateralis deoxygenated hemoglobin, measured by near‐infrared spectroscopy, determined muscle oxygen uptake (ΔHHb) at rest and during CPET and SME. Dual energy X‐ray absorptiometry assessed fat‐free mass (FFM%). Fatigue was determined by percent change in workload or distance in the first compared to the last minute of SME (FatigueSME) and six‐minute walk test (Fatigue6MWT), respectively. Results ΔHHb‐PEAK, ΔHHb‐SME, VO2peak, Wpeak, FFM%, and 6MWT distance were lower (P < 0.001), and Fatigue6MWT and FatigueSME were higher (P < 0.001) in SMA compared to controls. ΔHHb‐PEAK correlated with FFM% (r = 0.50) and VO2peak (r = 0.41) only in controls. Only in SMA, Fatigue6MWT was inversely correlated with Wpeak (r = −0.69), and FatigueSME was inversely correlated with FFM% (r = −0.55) and VO2peak (r = −0.69). Interpretation This study provides further support for muscle mitochondrial dysfunction in SMA patients. During exercise, we observed diminished muscle oxygen uptake but no correlation with aerobic capacity or body composition. We also observed increased fatigue which correlated with decreased aerobic capacity, workload, and body composition. Understanding the mechanisms underlying diminished muscle oxygen uptake and increased fatigue during exercise in SMA may identify additional therapeutic targets that rescue symptomatic patients and mitigate their residual disease burden.

Background: Technology is prevalent in almost every aspect of life, from handheld phones to computers. Increases in cervical flexion can cause a strain on the neck and muscles of the upper extremity. Objective: To examine the effect of 30 minutes of cervical flexion at 45 degrees. It was hypothesized that muscle strength will decrease after flexion, and there would be no significant differences between dominant and nondominant arms or genders. Study design: Twenty-four participants (12 male, 12 female) (n = 24; height = 173.1 + 9.3 cm; weight = 73.33 + 22.58kg) were measured before and after cervical flexion using a MicroFET2 Hand Held Digital Muscle Tester to test the middle deltoid, biceps brachii, and triceps brachii of each arm. Results: Compared to pre-measures significant differences were found in both middle deltoids and both biceps brachii, but not in either triceps brachii (p < 0.05). Overall no limited significant differences were found between genders of muscles of either arm. Significant differences (p < 0.05) were found in the dominant biceps brachii, non-dominant biceps brachii, dominant triceps brachii, dominant deltoid, and non-dominant deltoid. Conclusion: These results suggest that a normal daily degree of cervical flexion will decrease some upper extremity strength over the course of 30 minutes.