Introduction
Ambulatory individuals with spinal muscular atrophy (SMA) experience muscle weakness, gait impairments, and fatigue that affect their walking ability. Improvements have been observed in ...motor function in children treated with nusinersen, but its impact on fatigue has not been studied.
Methods
Post hoc analyses were used to examine changes in 6‐minute walk test (6MWT) distance and fatigue in children and adolescents with SMA type II and III who received their first dose of nusinersen in the phase Ib/IIa, open‐label CS2 study and were ambulatory during CS2 or the extension study, CS12.
Results
Fourteen children performed the 6MWT. Median (25th, 75th percentile) distance walked increased over time by 98.0 (62.0, 135.0) meters at day 1050, whereas median fatigue changed by −3.8% (−19.7%, 1.4%).
Discussion
These results support previous studies demonstrating clinically meaningful effects of nusinersen on motor function in children and adolescents with later‐onset SMA.
ABSTRACT
Introduction: The Six‐Minute Walk Test (6MWT) was adopted as a clinical outcome measure for ambulatory spinal muscular atrophy (SMA). However, a systematic review of measurement properties ...reported significant variation among chronic pediatric conditions. Our purpose was to assess the reliability/validity of the 6MWT in SMA. Methods: Thirty participants performed assessments, including the 6MWT, strength, and function. Reproducibility was evaluated by intraclass correlation coefficients. Criterion/convergent validity were determined using Pearson correlation coefficients. Results: Test–retest reliability was excellent. The 6MWT was associated positively with peak oxygen uptake, Hammersmith Functional Motor Scale Expanded (HFMSE), lower extremity manual muscle testing, knee flexion hand‐held dynamometry, and inversely with 10‐m walk/run. The 6MWT discriminates between disease severity, unlike the HFMSE. Conclusions: This study documents measurement properties of reproducibility, positive criterion validity, and convergent validity with established clinical assessments and reaffirms the value of the 6MWT as a pivotal outcome measure in SMA clinical trials. Muscle Nerve 54: 836–842, 2016
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.
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.
Consensus revealed 35 competencies, organized under 6 domains, which were deemed essential for a PT working with persons with SMA.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are 'fit for ...purpose'. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disease-modifying therapies for spinal muscular atrophy (SMA) are rapidly changing the outlook for many individuals by substantially altering the clinical course, phenotypic expression, and ...functional outcomes. Physical therapists have played critical roles in the effective conduct and execution of clinical trials leading to the approval of these therapies. Given the treatment landscape, educating practicing clinicians to understand best practice is of great importance, and a timely call to action to facilitate knowledge translation from SMA researchers to clinicians is necessary. The SMA Clinical Trial Readiness Program engaged clinical and research centers, identified physical therapy knowledge gaps related to evaluation and outcomes assessment, and provided educational resources, including the development of a SMA Best Practices Clinical Evaluator Toolkit. Toolkit content synthesizes evidence and covers a breadth of issues relevant to practice, including background on SMA and the drug pipeline; therapist roles and responsibilities related to research; clinical and research evaluation; and useful materials and resources for additional education, training, and professional development. Surveys and telephone interviews were conducted with physical therapists managing individuals with SMA to determine their SMA practice experience and educational needs. Their recommendations, along with synthesized SMA research evidence, provided input into toolkit content development and assisted in identifying gaps important to address. Impact was assessed over time via utilization feedback surveys downloaded by clinicians across various settings. Open-ended feedback supported beneficial use of the toolkit for clinicians and researchers working with individuals with SMA. Next steps should include timely dissemination to bring this resource and others into practice in a systematic, efficacious, and engaging manner. As the treatment landscape for SMA evolves, the therapist's role in multidisciplinary care and research is of great importance, and a call to action for the development, implementation, evaluation and reporting of informed knowledge using evidence-based knowledge translation strategies is critical.
Partnership among patient advocacy groups, industry collaborators, and key opinion leaders/experts can optimize essential resource development to address the knowledge gap for best practices in physical therapy. This partnership model can be replicated for other diseases, providing an efficient way to support clinical trial readiness and target early development of evidence-based content and resources related to both research and best practice clinical evaluation for physical therapist researchers, clinicians, and patients. While identifying knowledge gaps and resource development are initial steps toward change in SMA practice, a rapidly changing rehabilitation outlook warrants a call to action for enhanced efforts aimed at improving rehabilitation evaluation, assessment, and care for this population. It is critical to forge a timely path forward for development, implementation, and sustainability of effective knowledge translation to practice for SMA.
Background and purpose
Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important ...difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort.
Methods
The study employed two distinct methods. MDC was calculated using distribution‐based approaches to consider standard error of measurement and effect size change in a population of 321 patients (176 SMA II and 145 SMA III), allowing for stratification based on age and function. MCID was assessed using anchor‐based methods (receiver operating characteristic ROC curve analysis and standard error) on 76 patients (52 SMA II and 24 SMA III) for whom the 12‐month HFMSE could be anchored to a caregiver‐reported clinical perception questionnaire.
Results
With both approaches, SMA type II and type III patients had different profiles. The MCID, using ROC analysis, identified optimal cutoff points of −2 for type II and −4 for type III patients, whereas using the standard error we found the optimal cutoff points to be 1.5 for improvement and −3.2 for deterioration. Furthermore, distribution‐based methods uncovered varying values across age and functional status subgroups within each SMA type.
Conclusions
These results emphasize that the interpretation of a single MCID or MDC value obtained in large cohorts with different functional status needs to be made with caution, especially when these may be used to assess possible responses to new therapies.
Introduction: The aim of the study was to assess 12 month changes in upper limb function in patients affected by spinal muscular atrophy type 2 and 3. Methods: Longitudinal 12 month data was ...collected in 114 patients, 60 type 2 and 54 type 3, using the Revised Upper Limb Module. Results: The 12 month changes ranged between ‐7 and 9 (mean: ‐0.41; SD: 2.93). The mean changes were not significantly different between the three spinal muscular atrophy groups (‐0.45 in type 2, ‐0.23 in non‐ambulant type 3 and ‐0.34 in ambulant type 3, p = 0.96) and the relationship between 12 month change and age classes was not significantly different among the three types of SMA patients. Discussion: Our results confirm that the Module explores a wide range of functional abilities and can be used in ambulant and non‐ambulant patients of different ages in conjunction with other functional scales. Muscle Nerve 59:426–430, 2019
Advances in the Therapy of Spinal Muscular Atrophy Klotz, Jenna; Tesi Rocha, Carolina; Dunaway Young, Sally ...
The Journal of pediatrics,
September 2021, 2021-09-00, 20210901, Letnik:
236
Journal Article
ABSTRACT
Introduction
Gait impairment is common in spinal muscular atrophy (SMA) and is described using clinical assessments and instrumented walkways. Continuous over‐ground walking has not been ...studied.
Methods
Nine SMA participants completed the 6‐minute walk test (6MWT) and 10‐meter walk/run wearing instrumented footwear (SoleSound). Data were simultaneously collected using a reference system (GAITRite). The root‐mean‐square error (RMSE) indicated criterion validity. The decrease in walking speed represented fatigue. Foot loading patterns were evaluated using force sensors.
Results
The RMSE for stride time, length, and velocity ranged from 1.3% to 1.7%. Fatigue was 11.6 ± 9.1%, which corresponded to an average deceleration of 0.37 ± 0.28 mm/s2. Participants spent most of their stance without heel contact. Forefoot contact occurred early in the gait cycle.
Conclusions
These results suggest that footwear‐based devices are an alternative to specialized equipment for gait assessment. Better understanding of gait disturbances should inform ongoing treatment efforts and provide a more sensitive outcome measure. Muscle Nerve 56: 230–236, 2017
•Real world data on functional changes following nusinersen treatment are needed.•At 12 months from the 1st dose of nusinersen, functional increase was observed.•Age and HFMSE score are predictive of ...the 12-month changes on both scales.•The interpretation of nusinersen effect should consider different variables.•These data confirm and expand the ones already reported in the Cherish study.
Previous natural history studies suggest that type II SMA patients remain stable over one year but show some progression over two years. Since nusinersen approval, there has been increasing attention to identify more specific age-related changes. The aim of the study was to establish 12-month changes in a cohort of pediatric type II SMA treated with nusinersen and to establish possible patterns of treatment effect in relation to different variables such as age, baseline value and SMN2 copy number. The Hammersmith Functional Motor Scale Expanded and the Revised Upper Limb Module were performed at T0 and 12 months after treatment (T12). Data in treated patients were compared to available data in untreated patients collected by the same evaluators.Seventy-seven patients of age between 2.64 and 17.88 years (mean:7.47, SD:3.79) were included. On t-test there was an improvement, with increased mean scores between T0 and T12 on both scales (p < 0.001). Using multivariate linear regression analysis, age and baseline scores were predictive of changes on both scales (p < 0.05) while SMN2 copy number was not. Differences were also found between study cohort and untreated data on both scales (p < 0.001). At 12 months, an increase in scores was observed in all the age subgroups at variance with natural history data. Our real-world data confirm the treatment effect of nusinersen in pediatric type II SMA patients and that the data interpretation should take into account different variables. These data confirm and expand the ones already reported in the Cherish study.
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