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

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.

scholarly journals Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Leo H. Wang ◽  
Dennis W. W. Shaw ◽  
Anna Faino ◽  
Christopher B. Budech ◽  
Leann M. Lewis ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Lower Extremity ◽  
Functional Outcome ◽  
Outcome Measures ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Strength Measurement ◽  
Small Shift ◽  
Lower Extremity Weakness ◽  
Fat Fraction ◽  
Functional Outcome Measures

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.

scholarly journals Muscle MRI and functional outcome measures in Becker muscular dystrophy

2017 ◽  
Vol 7 (1) ◽  
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

scholarly journals The use of an iPad to Collect Patient-Reported Functional Outcome Measures in Hand Surgery

Hand ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 522-528 ◽  
Author(s):  
Mark Yafef ◽  
Nitin Goyal ◽  
Daniel Kokmeyer ◽  
Gregory A Merrel
Keyword(s):  
Functional Outcome ◽  
Outcome Measures ◽  
Hand Surgery ◽  
Patient Reported ◽  
Functional Outcome Measures

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

Neurology ◽  
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

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

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

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

2019 ◽  
Vol 6 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Claudia R. Senesac ◽  
Donovan J. Lott ◽  
Rebecca J. Willcocks ◽  
Tina Duong ◽  
Barbara K. Smith
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Lower Extremity ◽  
Functional Outcome ◽  
Outcome Measures ◽  
Delphi Survey ◽  
Functional Outcome Measures

scholarly journals Primary mitochondrial myopathy

2020 ◽  
Vol 6 (6) ◽  
pp. e519
Author(s):  
Vincenzo Montano ◽  
Francesco Gruosso ◽  
Valerio Carelli ◽  
Giacomo Pietro Comi ◽  
Massimiliano Filosto ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Outcome Measures ◽  
Mitochondrial Myopathy ◽  
Nuclear Dna ◽  
Age At Onset ◽  
Point Mutations ◽  
Timed Up And Go ◽  
Functional Measures ◽  
Patient Reported ◽  
Functional Outcome Measures

ObjectiveTo determine whether a set of functional tests, clinical scales, patient-reported questionnaires, and specific biomarkers can be considered reliable outcome measures in patients with primary mitochondrial myopathy (PMM), we analyzed a cohort of Italian patients.MethodsBaseline data were collected from 118 patients with PMM, followed by centers of the Italian network for mitochondrial diseases. We used the 6-Minute Walk Test (6MWT), Timed Up-and-Go Test (x3) (3TUG), Five-Times Sit-To-Stand Test (5XSST), Timed Water Swallow Test (TWST), and Test of Masticating and Swallowing Solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional Pain Inventory as patient-reported outcome measures; and FGF21, GDF15, lactate, and creatine kinase (CK) as biomarkers.ResultsA total of 118 PMM cases were included. Functional outcome measures (6MWT, 3TUG, 5XSST, TWST, and TOMASS) and biomarkers significantly differed from healthy reference values and controls. Moreover, functional measures correlated with patients' perceived fatigue and pain severity. Patients with either mitochondrial or nuclear DNA point mutations performed worse in functional measures than patients harboring single deletion, even if the latter had an earlier age at onset but similar disease duration. Both the biomarkers FGF21 and GDF15 were significantly higher in the patients compared with a matched control population; however, there was no relation with severity of disease.ConclusionsWe characterized a large cohort of PMM by evaluating baseline mitochondrial biomarkers and functional scales that represent potential outcome measures to monitor the efficacy of treatment in clinical trials; these outcome measures will be further reinvestigated longitudinally to define the natural history of PMM.

scholarly journals Measuring recovery after open lower limb fractures: combined objective functional tests and global perceived recovery outperform narrower metrics and a standard generic patient reported outcome measure

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ian Pallister ◽  
Gregory Jack Handley ◽  
Sharon Maggs ◽  
Ann-Marie Davies ◽  
Amanda Kyle ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Outcome Measures ◽  
Lower Limb ◽  
Gait Speed ◽  
Spearman Correlation ◽  
Lower Limb Fractures ◽  
Patient Reported ◽  
Functional Outcome Measures ◽  
Limb Fractures ◽  
Objective Functional

Abstract Background Open lower limb fractures are serious injuries requiring combined ortho-plastic surgery and have significantly worse outcomes than similar closed fractures. There is little objective published data to determine which functional outcome measures best reflect progress or completeness of physical recovery. Our hypothesis was that objective measures combining strength, mobility and balance would better reflect recovery than isolated parameters (e.g. range of motion ROM) and would compare well to patients’ perceived recovery. Methods Adult open lower limb fracture patients were reviewed 6 and 12 weeks, 6, 9 and 12 months post-injury. The mechanism, injury pattern, age, gender and treatment were recorded. Isolated parameter objective functional outcome measures (OFOMs) (ROM and MRC strength grade) were compared to combined OFOMs (timed up and go, comfortable gait speed and fast gait speed, Edgren Side Step Test (TUAG, CGS, FGS, ESST) and Single Leg balance. Patient reported outcomes were recorded (Global Perceived Effect (GPE) score and Disability Rating Index (DRI)). Statistical analysis used non-parametric tests (e.g. Spearman correlation) compared each with time since injury. Results Sixty-eight patients (54 male) with a median age of 45(20–75) years. Of the 19 isolated OFOMs, only knee flexion and ankle plantar flexion ROM and strength improved with time (Spearman correlation p = 0.042, 0.008, 0.032, 0.036 respectively). TUAG, ESST, CGS, FGS and GPE scores showed significant improvement (Spearman correlation p < 0.001). Patients’ estimation of recovery paralleled these measures (Spearman correlation p < 0.001) with all but 2 patients achieving the minimum clinical important difference in DRI by 12 months compared to baseline. However, the GPE score had a higher proportion of improving responses than DRI at each time-point. Discussion Functional recovery is a key determinant in patients returning to work, providing for themselves and their family or resuming independent living for older patients. This study has demonstrated time-related improvements in combined OFOMs measuring mobility, strength, agility and balance paralleling patients’ perception of recovery in the 12 months after open lower limb fractures. Over the same time-frame, the simple GPE score compared favourably with the DRI. Such parameters could become part of a defined core outcomes set. Focussing rehabilitation towards these combined OFOMs may help hasten recovery. Trial registration South West Wales REC 06/WMW02/10).

scholarly journals 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 ◽  
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).

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