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.
Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo.
Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a ...non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.
At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007).
This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials.
Clinicaltrials.gov NCT00227266.
Recent advances in technology and expanding therapeutic opportunities in neuromuscular disorders has resulted in greater interest in and development of remote assessments. Over the past year, the ...rapid and abrupt COVID-19 shutdowns and stay-at-home orders imposed challenges to routine clinical management and clinical trials. As in-person services were severely limited, clinicians turned to remote assessments through telehealth to allow for continued care. Typically, disease-specific clinical outcome assessments (COAs) for neuromuscular disorders (NMD) are developed over many years through rigorous and iterative processes to fully understand their psychometric properties. While efforts were underway towards developing remote assessments for NMD before the pandemic, few if any were fully developed or validated. These included assessments of strength, respiratory function and patient-reported outcomes, as well as wearable technology and other devices to quantify physical activity and function. Without many choices, clinicians modified COAs for a virtual environment recognizing it was not yet known how they compared to standard in-person administration. Despite being able to quickly adapt to the demands of the COVID-19 pandemic, these experiences with remote assessments uncovered limitations and opportunities. It became clear that existing COAs required modifications for use in a virtual environment limiting the interpretation of the information gathered. Still, the opportunity for real-world evaluation and reduced patient burden were clear benefits to remote assessment and may provide a more robust understanding and characterization of disease impact in NMD. Hence, we propose a roadmap navigating an informed post-pandemic path toward development and implementation of safe and successful use of remote assessments for patients with NMD.
Aim
This study examined the reliability and validity of the Test of Arm Selective Control (TASC) to examine upper extremity selective voluntary motor control in children and adolescents with all ...types of spastic cerebral palsy (CP).
Method
Fifty‐six participants with CP, ranging in age from 5 years 9 months to 18 years 11 months (average 11y 7mo, SD 3y 9mo; 25 males, 31 females), participated in this prospective cross‐sectional study. They were evaluated using the TASC and several clinical measures.
Results
TASC and Manual Ability Classification System (r=−0.529, p<0.001), TASC and ABILHAND‐Kids (r=0.596, p<0.001), and TASC and affected extremities (r=−0.486, p=0.001) were moderately correlated. There was a weak correlation between the TASC and Gross Motor Function Classification System (r=−0.363, p=0.006) and no correlation between the TASC and age (p=0.366) or rater (p=0.713). Interrater reliability for upper extremity total score (intraclass correlation coefficient ICC=0.92–0.94) and upper extremity limb scores (ICC=0.92–0.96) was high for two independent rater groups (p≤0.001). Average time to administer was 16 minutes, 18 seconds.
Interpretation
The TASC is a reliable and valid tool for objective assessment of selective voluntary motor control. Clinically this measure may guide the selection of medical, surgical, or therapy interventions and may improve outcome prognosis.
What this paper adds
The Test of Arm Selective Control (TASC) demonstrates a high degree of reliability and multiple aspects of validity when assessing upper extremity selective control in those with cerebral palsy.
The TASC is an upper limb companion to the Selective Control Assessment of the Lower Extremity.
Resumen
La validez y la fiabilidad de la prueba de control selectivo del brazo para niños con parálisis cerebral: un estudio prospectivo de corte transversal
Objetivo
Este estudio examinó la fiabilidad y la validez de la prueba de control selectivo de brazo (TASC) para examinar el control motor voluntario selectivo de extremidad superior en niños y adolescentes con todos los tipos de parálisis cerebral espástica (PC).
Método
Cincuenta y seis participantes con PC, con edades comprendidas entre 5 años 9 meses a 18 años y 11 meses (promedio 11 años y 7 meses, DS 3 años y 9 meses, 25 hombres, 31 mujeres), participaron en este estudio prospectivo de corte transversal. Fueron evaluados usando el TASC y varias medidas clínicas.
Resultados
TASC y el Sistema de Clasificación de Habilidad Manual (r=−0,529, p<0,001), TASC y ABILIHAND‐Niños (r=0,596, p<0,001), y TASC y extremidades afectadas (r=−0,486, p=0,001) fueron moderadamente correlacionado. Hubo una correlación débil entre el TASC y el Sistema de Clasificación de la Función Motora Gruesa (r=−0,363, p=0,006) y ninguna correlación entre el TASC y la edad (p=0,366) o el evaluador (p=0,713). La confiabilidad inter‐operador para la puntuación total de la extremidad superior (coeficiente de correlación intraclase CCI=0,92–0,94) y las puntuaciones de la extremidad de la extremidad superior (CCI=0,92–0,96) fue alta para dos grupos evaluadores independientes (p≤0,001). El tiempo promedio para administrar fue de 16 minutos, 18 segundos.
Interpretación
El TASC es una herramienta confiable y válida para la evaluación objetiva del control motor voluntario selectivo. Clínicamente esta medida puede guiar la selección de intervenciones médicas, quirúrgicas o terapéuticas y puede mejorar el pronóstico de resultados.
Resumo
A validade e confiabilidade do teste do controle seletivo do braço para crianças com paralisia cerebeal: um estudo prospectivo transversal
Objetivo
Este estudo examinou a confiabilidade e validade do Teste do Controle Seletivo do Braço (TASC) para examinar o controle motor voluntário seletivo da extremidade superior em crianças e adolescentes com todos os tipos de paralisia cerebral espástica (PC).
Método
Cinquenta e seis participantes com PC, com idade variando de 5 anos e 9 meses a 18 anos e 11 meses (média 11a 7m, DP 3a 9m; 25 do sexo masculino, 31 do sexo feminino), participaram neste estudos prospectivo transveral. Eles foram avaliados usando a TASC e várias medidas clínicas.
Resultados
O TASC e o Sistema de Classificação da Habilidade Manual (MACS) (r= –0,529, p<0,001), o TASC e o ABILIHAND‐Kids (r=0,596, p<0,001), e o TASC e as extremidades afetadas (r= –0,486, p=0,001) foram moderadamente correlacionados. Houve uma correlação fraca entre o TASC e o Sistema de Classificação da Função Motora Grossa (r= −0,363, p=0,006), e nenhuma correlação entre o TASC e idade (p=0,366) ou examinador (p=0,713). A confiabilidade inter‐examinadores para o escore total da extremidade superior (coeficiente de correlação intraclasse CCI=0,92–0,94) e escores do membro (CCI=0,92–0,96) foi alta para dois grupos de examinadores independentes (p≤0,001). O tempo médio de administração foi de 16 minutos e 18 segundos.
Interpretação
O TASC é uma ferramenta confiável e válida para avaliação objetiva do controle motor voluntário seletivo. Clinicamente esta medida pode guiar a seleção de intervenções médicas, cirúrgicas ou terapêuticas, e pode melhorar o prognóstico de resultados.
What this paper adds
The Test of Arm Selective Control (TASC) demonstrates a high degree of reliability and multiple aspects of validity when assessing upper extremity selective control in those with cerebral palsy.
The TASC is an upper limb companion to the Selective Control Assessment of the Lower Extremity.
This article is commented on by Rudisch on page 333 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of ...therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p<or=0.001); however, significant improvement was almost entirely restricted to participants <5 years of age. Full length SMN levels were unchanged and Delta7SMN levels were significantly reduced for 2 of 3 treatment visits. In contrast, bone mineral density (p<or=0.0036) and maximum ulnar CMAP scores (p<or=0.0001) increased significantly.
While VPA appears safe and well-tolerated in this initial pilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various candidate outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects.
ClinicalTrials.gov.
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.
Selective voluntary motor control (SVMC) in the upper extremity is often impaired in individuals with cerebral palsy (CP) and can be assessed quantitatively and qualitatively using the Test of Arm ...Selective Control (TASC).
Fifty-six individuals with spastic CP (5-18 years old) were included. Descriptors associated with administration of the TASC were analyzed according to the type of CP and arm joint using Chi-square and Kruskal-Wallis tests. ABILHAND-Kids scores were compared between participants with and without mirror movements using a t-test.
All groups of children with spastic CP had incidence of TASC movement descriptors. There was a main effect of topography of CP on extra movements, decreased active range of motion, tightness, spasticity, and mirroring, and an additional main effect of joint on mirroring. Participants with mirroring had lower ABILHAND-Kids scores than those without mirroring.
Systematically observing arm movements using the TASC revealed differences across participants.
•10MWRT times are slower for those with SMA compared to typically developing peers.•Direction and magnitude of 12-month change in 10MWRT varies by age in those with SMA.•Age, SMA type, SMN2 copy ...number and BMI predict 10MWRT progression over time.•SMA type 3b, four SMN2 copies, and lower BMI were associated with faster 10MWRT time.•10 MWRT times are 74 percent slower for SMA type 3a versus 3b across ages.•In SMA a 1.0 kg/m2 increase in BMI was associated with a mean 3% slower 10MWRT time.
As trials and treatments for spinal muscular atrophy (SMA) rapidly evolve, understanding the natural history and potential utility of the 10-meter walk/run test (10MWRT) in ambulant individuals is critical. Study aims were to: 1) establish change over time and across age for 10MWRT time in an untreated natural history cohort of young, ambulatory participants with SMA and 2) identify relations between 10MWRT time and age, SMA type, SMN2 copy number and anthropometrics. Untreated individuals (n = 56) age 2 to 21 years who were enrolled in a long-term natural history study between 2005 and 2014 and met inclusion criteria were included. Linear mixed effects models were used to assess changes in 10MWRT time with age and associations with SMA type, SMN2 copy number, and body mass. SMA type 3b (versus 3a), SMN2 copy number 4 (versus 3) and lower body mass were associated with faster 10MWRT. 10MWRT performance improved between 3 and 8 years of age, was stable between 9 and 10, and gradually declined from 11 to 18. Findings provide the first longitudinal natural history report of 10MWRT time in young individuals with SMA and offer a critical foundation for interpreting childhood change in short distance walking speed with pharmacologic treatment.
Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral ...VPA and l-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA.
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