65 research outputs found
Gain and loss of abilities in type II SMA: A 12-month natural history study
No full textThe advent of clinical trials in spinal muscular atrophy (SMA) has highlighted the need to define patterns of progression using functional scales. It has recently been suggested that the analysis of abilities gained or lost applied to functional scales better reflects meaningful changes. We defined as “gain” a positive change between scores from 0 to either 1 or 2 and as “loss” a negative change from either 2 or 1 to 0. The aim of this study was to describe, over 12 months, which abilities on the Hammersmith Functional Motor Scale Expanded (HFMSE) were more frequently lost or gained in patients with SMA II. The cohort included 614 12-month assessments from 243 patients (age range: 30 months - 63 years; mean 9.94, SD ±7.91). The peak of abilities gained occurred before the age of 5 years while the highest number of lost abilities was found in the group 5–13 years. A correlation between the HFMSE baseline score and the ordinal number of the items was found for both lost (p<0.001) or gained (p<0.001) activities. No correlation was found with SMN2 copy number. These findings will have implications for clinical trial design and for the interpretation of real-world data using new therapeutic approache
Assessing the Relationship of Patient Reported Outcome Measures With Functional Status in Dysferlinopathy: A Rasch Analysis Approach
No full textCopyright \ua9 2022 Mayhew, James, Moore, Sutherland, Jacobs, Feng, Lowes, Alfano, Muni Lofra, Rufibach, Rose, Duong, Bello, Pedrosa-Hern\ue1ndez, Holsten, Sakamoto, Canal, S\ue1nchez-Aguilera Pr\ue1xedes, Thiele, Siener, Vandevelde, DeWolf, Maron, Gordish-Dressman, Hilsden, Guglieri, Hogrel, Blamire, Carlier, Spuler, Day, Jones, Bharucha-Goebel, Salort-Campana, Pestronk, Walter, Paradas, Stojkovic, Mori-Yoshimura, Bravver, D\uedaz-Manera, Pegoraro, Mendell and Straub.Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation\u27s Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R2 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R2 0.18). EK scores were strongly associated with PUL (Pseudo R2 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R2 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy
Assessing disease progression in spinal muscular atrophy, current gaps, and opportunities: a narrative review
No full textSpinal Muscular Atrophy is a genetic disorder causing muscle atrophy and progressive weakness. People living with the condition can have a significant heterogenous phenotype ranging from arrest of motor development to mild impairment. Assessing disease severity has been done using a range of outcome measures that can be classified by body structure or function, by activities or by participation. Functional outocome measures can be generic measures, used to compare individuals or populations against general norms, or disease-specific measures designed to fit disease characteristics. Outcome measures assessing participation are primarily used to capture patients' perceptions of health-related quality of life, daily activity abilities, caregiver burden, and the impact of physical symptoms like fatigue or pain. When assessing disease progression, often the focus on functional abilities has served as an overall indicator of change. With the appearance of disease modifying therapies and the need to evaluate the impact that they had in the course of the disease, new requirements for the existing assessments measure had appeared. The current available toolkit is able to capture a significant spectrum of both, natural history and effect of new treatments but the increased survival, changes in fatigue, bulbar function and others will benefit from further assessment
Corrigendum to “Assessing disease progression in Spinal Muscular Atrophy, current gaps, and opportunities: a narrative review” [NMD, volume 49, article 105341] (Neuromuscular Disorders (2025) 49, (S0960896625000689), (10.1016/j.nmd.2025.105341))
No full textThe authors regret that the originally listed affiliation for Dr Richard Finkel is incorrect in the original publication. The authors would like to apologise for any inconvenience caused
Quantitative Evaluation of Lower Extremity Joint Contractures in Spinal Muscular Atrophy: Implications for Motor Function.
No full textPURPOSE:
To quantitatively describe passive lower extremity range of motion in participants with spinal muscular atrophy (SMA) types 2 and 3, and to establish preliminary thresholds to identify individuals at risk for performing poorly on disease-specific motor function outcome measures.
METHODS:
Eighty participants with SMA types 2 and 3, enrolled in an international multicenter natural history study, were evaluated with lower extremity range of motion testing and the Hammersmith Functional Motor Scale-Expanded.
RESULTS:
A hip extension joint angle of -7.5° or less for SMA type 2 and 0° or less for SMA type 3 identified diminished motor ability with good sensitivity. For knee extension, a joint angle of -9.0° or less for SMA type 2 or 0° or less for SMA type 3 was similarly sensitive.
CONCLUSIONS:
Minimal hip and knee joint contractures were associated with diminished motor ability. Clinical trial designs should consider the effect of contractures on motor function
Serial casting for contractures in SMA: consensus derived guidelines for treatment
No full textCopyright \ua9 2025 Brown, Hoffman, Corbo-Galli, Kelley, Carry, Civitello, Coratti, DeSanctis, Duong, Driscoll, Flickinger, Glanzman, Jones, Maczek, Moat, Montes, Muni-Lofra, Nelson, Pasternak, Valle and Krosschell.Background: Individuals with Spinal Muscular Atrophy (SMA) often present with muscle contractures. Serial casting has been used in a variety of other peripheral nerve, muscle, and central nervous system disorders to improve knee and ankle range of motion limitations and functional performance in both ambulatory and non-ambulatory individuals. Objective: The goal of this study was to reach a consensus about the parameters, considerations and general guidelines that should inform practice when serial casting to improve flexibility in individuals with SMA. Methods: This international effort was conducted between August 2020 and May 2023. An expert panel of physical therapists was assembled with multiple panel meetings and a 2-round Delphi survey performed covering topics relevant to serial casting which included three domains: clinical appropriateness, program-based considerations and program adherence/feasibility. Consensus was reached for all items in the three topic areas using a validity index of >75%. Following completion of the Delphi survey, community insights from patients and caregivers were collected via semi-structured interview. Results: This study included the synthesis of meetings from the initial expert panel which produced a comprehensive survey for the different considerations when performing serial casting for an individual with SMA. The study also included the completion of a Delphi survey by 18 therapists in round 1 and 15 therapists in round 2 for a consensus on 296 items. Strong consensus was obtained in all three domains with 96.6% agreement for clinical appropriateness, 95.0% agreement for program-based considerations, and 96.9% for program adherence/feasibility. A guideline document was developed enumerating the specific items detailed in the survey. Community perspectives were utilized to support the results of the Delphi survey and to add insight into real-world experience. Conclusion: The serial casting guidelines developed upon collaborative discussions from the expert panel and from the Delphi survey consensus and semi-structured interviews, should be utilized when applying serial casts to patients with spinal muscular atrophy. Future endeavors should look to apply the guideline recommendations to determine casting efficacy for improving joint contracture and impact on function for those with SMA
Prevalence of pain within limb girdle muscular dystrophy r9 and implications for other degenerative diseases
No full text\ua9 2021 by the authors. Licensee MDPI, Basel, Switzerland.Our primary aim was to establish the prevalence of pain within limb girdle muscular dystrophy R9 (LGMDR9). As part of the Global FKRP Registry, patients are asked to complete the Short Form McGill Pain Questionnaire (SF-MPQ) annually. We used the results of this questionnaire to determine individuals’ maximum pain score and total pain score and examined overall pain intensity and associations between pain intensity and LGMDR9 genotypes, age, and ambulatory status. We also considered the pain descriptors used and pain progression over time. Of the 502 patients, 87% reported current pain and 25% reported severe current pain. We found no associations in pain severity between the different genotypes of LGMDR9. However, we did find statistically significant associations between pain severity and ambulatory status and between our paediatric and adult populations. We found pain descriptors to be more common words that one may associate with non-neural pain, and we found that a significant number of individuals (69%) reported a fluctuating pain pattern over time. We concluded that pain should be considered a significant issue among individuals with LGMDR9 requiring management. Implications regarding assessment of pain for other degenerative diseases are discussed
Revised upper limb module for spinal muscular atrophy: 12 month changes
No full textAbstract
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.
© 2019 Wiley Periodicals, Inc.
KEYWORDS:
Functional assessment; Longitudinal Data; Neuromuscular disorders; Outcome measures; Spinal Muscular Atrophy; Upper lim
Development of the SMA EFFORT: A new approach to characterize perceived physical fatigability in spinal muscular atrophy
No full textBACKGROUND: 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
Clinical Variability in Spinal Muscular Atrophy Type III
No full textObjective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12-month assessments. Results: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = −1.15, p < 0.0001) and IIIB (β = −0.69, p = 0.002). Interpretation: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real-world data of patients treated with commercially available drug
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