The 6‐minute walk test in Duchenne/Becker muscular dystrophy: Longitudinal observations

McDonald, Craig M.; Henricson, E.; Han, Jay J.; Abresch, Richard T.; Nicorici, Alina; Atkinson, Leone; Elfring, Gary L.; Reha, A.; Miller, Langdon L.

doi:10.1002/mus.21808

Cited by 154 publications

(184 citation statements)

References 32 publications

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“…The 6MWT was performed by specifically trained physiotherapists according to accepted clinical standards 19. Assessments were done annually for the Italian DMD Registry, and at routine clinical visits in the LNMRC study.…”

Section: Methodsmentioning

confidence: 99%

“…The 6MWT is an ambulatory outcome measure that has been utilized in clinical trials for 3 DMD therapeutics (eteplirsen, drisapersen, and ataluren) and has been shown to be accurate and reproducible 13. Understanding of DMD disease progression as measured by 6MWT has increased in recent years with publications of natural history data14, 15, 16, 17, 18, 19 as well as placebo‐arm reporting from DMD trials 20, 21, 22. Published data support that on average, 6MWT distance is stable or increases in patients <7 years of age, whereas it declines in older patients 15, 17, 18, 23, 24.…”

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confidence: 99%

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Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Mendell

Goemans²,

Lowes

et al. 2016

Annals of Neurology

453

392

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ObjectiveTo continue evaluation of the long‐term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three‐year progression of eteplirsen‐treated patients was compared to matched historical controls (HC).MethodsAmbulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open‐label basis. The primary functional assessment in this study was the 6‐Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.ResultsAt 36 months, eteplirsen‐treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen‐treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.InterpretationOver 3 years of follow‐up, eteplirsen‐treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. Ann Neurol 2016;79:257–271

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Mendell

Goemans²,

Lowes

et al. 2016

Annals of Neurology

453

392

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“…However, 6MWT distance did not show a significant difference in cross-sectional comparisons between corticosteroidtreated and corticosteroid-naive boys. Although the 6MWT has been established as a clinically meaningful outcome measure in DMD, 31 it is less sensitive in monitoring muscle response to disease progression in younger boys (,7 years old). 31,32 The reduced sensitivity of the 6MWT in younger boys with DMD has been attributed to the fact that disease-related progressive loss of muscle strength and function might be overshadowed by normal growth and development.…”

Section: Impact Of Initiation Of Corticosteroid Therapy In Boysmentioning

confidence: 99%

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

et al. 2014

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Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS).Methods: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. Results:Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation.Conclusions: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD. Duchenne muscular dystrophy (DMD) is a devastating form of muscular dystrophy caused by the absence of dystrophin, making muscle cell membranes fragile and susceptible to mechanical damage.1,2 Currently, there is no cure for the disease. Corticosteroids have been reported to slow disease progression in DMD.3-7 However, the mechanism by which corticosteroids preserve muscle function in DMD is not fully understood.Among several proposed mechanisms, corticosteroids are thought to reduce inflammation in dystrophic muscles. 8,9 MRI, in particular T2-weighted MRI, is sensitive to alterations in muscle chemistry and structure induced by processes like damage/inflammation and fat infiltration, [10][11][12][13][14][15][16][17] and therefore may have the potential to detect the effects of corticosteroid treatment on dystrophic muscles. Magnetic resonance spectroscopy (MRS) allows quantification of chemical compounds and can separate lipid and water components, allowing a more targeted investigation of skeletal muscles in DMD. 18-21The overall goal of this study was to examine the ability of MRI/MRS to detect the effects of corticosteroids on skeletal muscles in boys with DMD. The specific aims of the study were to (1) perform a cross-sectional comparison between the lower extremity muscles of 5-to 6.9-year-old

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“…Os pacientes com DMD possuem algumas características como disfunção miocárdica e/ou redução de massa muscular esquelética funcional 21 , além da ausência da proteína distrofina que é crítica para a estabilidade estrutural do esqueleto, do diafragma, e dos músculos do coração 22 . Em um estudo recente com utilização do teste TC6 em pacientes com DMD no solo, foi verificado um maior gasto energético durante esse teste, nesses indivídu-os 23 .…”

Section: Discussionunclassified

Energy expenditure analysis in Duchenne muscular dystrophy in land and aquatic environment

Silva

Hengles²,

Verdiani³

et al. 2015

RNC

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original RESUMO Introdução. A Distrofia Muscular de Duchenne (DMD) é uma doença progressiva, caracterizada pela degeneração progressiva das fibras musculares necessitando de maior demanda energética durante as atividades funcionais. Desta forma, é imprescindível a avaliação clínica do gasto energético em diferentes atividades e ambientes. Objetivos. Analisar o gasto energético de crianças com DMD durante a marcha nos ambientes aquático e terrestre. Método. Participaram deste estudo 8 meninos com DMD (10,4±0,5 anos), deambuladores, colaborativo para a realização dos testes, não estavam inseridos em programas de reabilitação e não apresentaram doenças associadas. Foi realizado o Teste de caminhada de 6 minutos e calculamos o índice de gasto energético (IGE) através da fórmula: FC final -FC inicial dividida pela velocidade (metros/segundo), sendo expresso em batimentos/ minuto nos meios aquático e terrestre. Resultados. Observamos que no ambiente aquático os pacientes com DMD percorreram um distância menor, comparado ao solo (p=0,012). Quanto ao Índice de Gasto Energético (IGE), os pacientes com DMD obtiveram uma média no solo de 0,43±0,15 e na água de 3,69±0,44 (p=0,012). Conclusões. Os pacientes percorreram uma distância menor e com um gasto energéti-co maior no ambiente aquático, quando comparado com o terrestre.Unitermos. Distrofia Muscular de Duchenne, Marcha, Metabolismo Energético, Ambiente Aquático Citação. Silva KM, Hengles RC, Verdiani MB, Cecconi ME, Rocco FM, Braga DM. Análise do gasto energético na Distrofia muscular de Duchenne nos ambientes aquático e terrestre. ABSTRACTIntroduction. Duchenne muscular dystrophy (DMD) is a progressive genetic disease, characterized by progressive and irreversible degeneration of muscle fibers, requiring energy demand during functional activities. Given this characteristic, energy expenditure becomes a key factor in a rehabilitation program. So, it is essential energy expenditure clinical assessment in different environments. Objective. Analyze the energy expenditure of children with DMD during gait in aquatic and land environments. Method. The study included 8 boys with DMD (10.4±0.5 years), ambulating and collaborative for testing. They were not included in rehabilitation programs and had no associated diseases. It was applied 6-minute walk test (6MWT) in land and aquatic environment, and calculate energy expenditure index by the formula: End FC -divided by the initial speed FC (meters/ second) and is expressed in beats/minute in the aquatic and terrestrial. Results. It was observed that DMD patients walked (p=0.012) a shorter distance in water in relation to the ground. DMD patients had (p=0.012) higher average of energy expenditure in aquatic environment (3.69±0.44) when compared to land (0.43±0.15). Conclusion. The patients walked a shorter distance and with higher energy expenditure in aquatic environment.Keywords. Muscular Dystrophy Duchenne, Gait, Energy Metabolism, Aquatic Environment Citation. Silva KM, Hengles RC, Verdiani MB, Cecconi ME, Rocco FM, Braga DM....

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The 6‐minute walk test in Duchenne/Becker muscular dystrophy: Longitudinal observations

Cited by 154 publications

References 32 publications

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Energy expenditure analysis in Duchenne muscular dystrophy in land and aquatic environment

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