Lower Extremity Functional Outcome Measures in Duchenne Muscular Dystrophy-A Delphi Survey

Abstract Background Facioscapulohumeral muscular dystrophy (FSHD) is a patchy and slowly progressive disease of skeletal muscle. For MRI to be a useful biomarker in an FSHD clinical trial, it should reliably detect changes over relatively short time-intervals (~ 1 year). We hypothesized that fatty change over the study course would be most likely in muscles already demonstrating disease progression, and that the degree of MRI burden would be correlated with function. Methods We studied 36 patients with FSHD and lower-extremity weakness at baseline. Thirty-two patients returned in our 12-month longitudinal observational study. We analyzed DIXON MRI images of 16 lower-extremity muscles in each patient and compared them to quantitative strength measurement and ambulatory functional outcome measures. Results There was a small shift to higher fat fractions in the summed muscle data for each patient, however individual muscles demonstrated much larger magnitudes of change. The greatest increase in fat fraction was observed in muscles having an intermediate fat replacement at baseline, with minimally (baseline fat fraction < 0.10) or severely (> 0.70) affected muscles less likely to progress. Functional outcome measures did not demonstrate marked change over the interval; however, overall MRI disease burden was correlated with functional outcome measures. Direct comparison of the tibialis anterior (TA) fat fraction and quantitative strength measurement showed a sigmoidal relationship, with steepest drop being when the muscle gets more than ~ 20% fatty replaced. Conclusions Assessing MRI changes in 16 lower-extremity muscles across 1 year demonstrated that those muscles having an intermediate baseline fat fraction were more likely to progress. Ambulatory functional outcome measures are generally related to overall muscle MRI burden but remain unchanged in the short term. Quantitative strength measurement of the TA showed a steep loss of strength when more fatty infiltration is present suggesting that MRI may be preferable for following incremental change or modulation with drug therapy.

Download Full-text

Functional Outcome Measures Correlated with Strength in Becker Muscular Dystrophy (P02.001)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.p02.001 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. P02.001-P02.001

Author(s):

L. Alfano ◽

L. Lowes ◽

L. Viollet ◽

K. Flanigan ◽

J. Mendell

Keyword(s):

Muscular Dystrophy ◽

Functional Outcome ◽

Outcome Measures ◽

Becker Muscular Dystrophy ◽

Functional Outcome Measures

Download Full-text

P4.25 Functional outcome measures in limb girdle muscular dystrophy 2I: Correlations with MRI

Neuromuscular Disorders ◽

10.1016/j.nmd.2010.07.221 ◽

2010 ◽

Vol 20 (9-10) ◽

pp. 665-666

Author(s):

M. Eagle ◽

A. Mayhew ◽

T.A. Willis ◽

H. Lochmuller ◽

K. Bushby ◽

...

Keyword(s):

Muscular Dystrophy ◽

Functional Outcome ◽

Outcome Measures ◽

Limb Girdle Muscular Dystrophy ◽

Functional Outcome Measures

Download Full-text

837 Clinical Experience Using Functional Outcome Measures in the Outpatient Burn Center

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa024.410 ◽

2020 ◽

Vol 41 (Supplement_1) ◽

pp. S257-S257

Author(s):

Melissa Boals ◽

Lisa Curtis ◽

Amalia Cochran ◽

John Kevin Bailey ◽

Rebecca Coffey

Keyword(s):

Lower Extremity ◽

Functional Outcome ◽

Grip Strength ◽

Upper Extremity ◽

Outcome Measures ◽

Maximal Function ◽

Burn Patients ◽

Function Score ◽

Functional Outcome Measures

Abstract Introduction For patients with severe burns, the emphasis has shifted from survival to maximizing functional outcomes. Outcome measures are tools that help establish a baseline status and monitor progression towards meaningful tasks such as activities of daily living (ADLs) and mobility (Staley et al. 1996). The goal of this retrospective study is to describe the use of functional outcome measures in burn patients in an outpatient setting using standardized measures. Methods A retrospective chart review of burn patients seen in the outpatient burn clinic between February 1, 2017 and May 31, 2019 was conducted. Only patients seen for burn injury, treated as outpatients, and with functional outcome measures recorded were included in the study. Pertinent demographic and clinical data were collected as well as outcome measures. All patients had grip strength dynamometry performed. Patients with upper extremity and lower extremity burns were administered the The Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Lower Extremity Functional Scale (LEFS). Return to work data was also collected if the patient was employed at baseline. Results A total of 113 out patients were included in the analysis. Mean age was 43 years (20–88 years) with a mean TBSA of 6.1% (0.1 -67%). The mean number of OT and PT visits in the clinic were both 1.4. Initial grip strength measurements were obtained in 67 patients at a mean of post burn day (PBD) 33 and an average grip strength of 21.29 kg (right) and 26.8 kg (left). Follow up grip strength measurements were obtained in 45 patients on mean PBD 43 with right hand 49.98 kg and left hand of 51.28 kg. Initial QuickDASH was administered to 89 patients on PBD 47 with a mean percent disability of 48.72 (0–100). Second QuickDASH was given to 45 patients on PBD 68 with a mean percent disability score of 37.01 (0 – 95.45) - Initial LEFS was given to 77 patients mean PBD 61 with a mean % of maximal function score of 44%. Second LEFS was given to 40 patients mean PBD 71 with a mean % maximal function score of 58%. Mean return to work for the 46 patients who were employed was 53.6 days post burn. Conclusions Positive improvements were shown in grip strength and lower extremity function, but a decline in function was demonstrated for upper extremity function. This decline may be the result of a nearly 50% attrition rate on follow up QuickDASH measures due to discharge of highly functional individuals, meaning the remaining upper extremity burn patients had more severe injuries and dysfunction. Applicability of Research to Practice Ongoing research is needed to identify the best timing of outcome measures and how to best incorporate this information into burn treatment plans.

Download Full-text

Muscle MRI and functional outcome measures in Becker muscular dystrophy

Scientific Reports ◽

10.1038/s41598-017-16170-2 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 7

Author(s):

Andrea Barp ◽

Luca Bello ◽

Luca Caumo ◽

Paola Campadello ◽

Claudio Semplicini ◽

...

Keyword(s):

Muscular Dystrophy ◽

Functional Outcome ◽

Outcome Measures ◽

Becker Muscular Dystrophy ◽

Muscle Mri ◽

Functional Outcome Measures

Download Full-text

Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study

BMC Neurology ◽

10.1186/s12883-021-02336-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Karlijn Bouman ◽

Jan T. Groothuis ◽

Jonne Doorduin ◽

Nens van Alfen ◽

Floris E. A. Udink ten Cate ◽

...

Keyword(s):

Muscular Dystrophy ◽

Natural History ◽

Functional Outcome ◽

Outcome Measures ◽

Early Onset ◽

Pulmonary Function Tests ◽

Natural History Study ◽

X Ray ◽

Link Type ◽

Functional Outcome Measures

Abstract Background SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness. Methods LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient’s age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed. Discussion Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up. Conclusion Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD. Trial registration This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017–3911) and is registered at ClinicalTrial.gov (NCT04478981).

Download Full-text

Adapting MRI as a clinical outcome measure for a facioscapulohumeral muscular dystrophy trial of prednisone and tacrolimus: case report

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03910-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Leo H. Wang ◽

Laura M. Johnstone ◽

Michael Bindschadler ◽

Stephen J. Tapscott ◽

Seth D. Friedman

Keyword(s):

Muscular Dystrophy ◽

Functional Outcome ◽

Immunosuppressive Therapy ◽

Outcome Measures ◽

Facioscapulohumeral Muscular Dystrophy ◽

Muscle Mri ◽

Patient Reported ◽

Fat Fraction ◽

Functional Outcome Measures ◽

Autoimmune Myopathy

Abstract Background Facioscapulohumeral muscular dystrophy (FSHD) is a patchy and slowly progressive disease of skeletal muscle. MRI short tau inversion recovery (STIR) sequences of patient muscles often show increased hyperintensity that is hypothesized to be associated with inflammation. This is supported by the presence of inflammatory changes on biopsies of STIR-positive muscles. We hypothesized that the STIR positivity would normalize with targeted immunosuppressive therapy. Case presentation 45-year-old male with FSHD type 1 was treated with 12 weeks of immunosuppressive therapy, tacrolimus and prednisone. Tacrolimus was treated to a goal serum trough of > 5 ng/mL and prednisone was tapered every month. Quantitative strength exam, functional outcome measures, and muscle MRI were performed at baseline, week 6, and week 12. The patient reported subjective worsening as reflected in quantitative strength exam. The MRI STIR signal was slightly increased from 0.02 to 0.03 of total muscle; while the T1 fat fraction was stable. Functional outcome measures also were stable. Conclusions Immunosuppressive therapy in refractive autoimmune myopathy in other contexts has been shown to reverse STIR signal hyperintensity, however this treatment did not reverse STIR signal in this patient with FSHD. In fact, STIR signal slightly increased throughout the treatment period. This is the first study of using MRI STIR and T1 fat fraction to follow treatment effect in FSHD. We find that STIR might not be a dynamic marker for suppressing inflammation in FSHD.

Download Full-text