North Star Ambulatory Assessment, 6-minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy
Introduction
In the last few years there have been an increasing number of therapeutical approaches in children with Duchenne muscular dystrophy (DMD). This has highlighted the need to have validated outcome measures that could reliably assess possible changes following treatment.
Most of the previous studies in children with neuromuscular disorders have assessed strength [1], [2], [3], [4], [5], [6], [7] while more recent studies have proposed the use of functional scales. This includes general scales that can be used in different neuromuscular disorders, such as the Gross Motor Function Measure [8], [9], the Motor Function Measure [10], [11], the Vignos scale [12], or other scales that have been specifically designed to assess aspects of function in specific cohorts, such as the Hammersmith Functional Motor Scale in non ambulant patients with spinal muscular atrophy [13], or the Hammersmith Motor Ability Scale for DMD boys [2].
The North Star Ambulatory Assessment (NSAA) is a functional scale specifically designed for ambulant DMD boys. This scale has been developed as an adaptation of the Hammersmith Motor Ability Scale [2]. It also includes a number of new items assessing aspects of function, such as hopping and running, usually not observed in untreated DMD children, in order to allow the detection of possible improvement following treatment. The scale has been developed and piloted in the United Kingdom by the North Star Clinical Network for Paediatric Neuromuscular Disease Management with good intra and interobserver reliability and has recently been used in a large multicentric study confirming its suitability for use in multicentric studies [14], [15], [16], [17].
The NSAA also includes timed items such as the 10 m timed walk/run test or timed rising from the floor, that have previously been used in DMD boys both in clinical and research settings to detect changes over time and, for the 10 m timed walk/run test, also to predict age of loss of ambulation [18].
It has been recently suggested that the 6-minute walk test (6MWT) may also be used as a primary outcome measures for DMD natural history and therapeutic trials [19]. The 6MWT is a frequently used measure of functional capacity [20] and has already been validated in paediatric populations in which normative data are available [21]. The test measures endurance, thus reflecting an important aspect of everyday living function and it has already been used in patients with myotonic dystrophy [22], Pompe disease [23], spinal and bulbar muscular atrophy [24], diabetic neuropathies [25], and is in the recent trial using Ataluren (PTC 124) in DMD boys [19].
The aim of this multicentric prospective study was to assess a cohort of DMD ambulant boys using a functional scale (NSAA), timed tests and 6MWT. More specifically, we wished to establish the spectrum of findings for each measure and the possible correlation between the individual measures.
Section snippets
Subjects and methods
The study is a prospective multicentric study involving nine tertiary neuromuscular centers in Italy and one centre in UK. The study was approved by the Ethical Committee of each centre.
Patient inclusion criteria was: genetically proven DMD diagnosis, patient still ambulant and able to walk at least 10 m independently, without any help, no severe or moderate learning difficulties or behavioural problems.
Genetic and treatment information were collected. As the various centers used different types
Results
One hundred and fourteen ambulant DMD boys fulfilled the inclusion criteria. Two of the 114 did not complete the 6MWT because of poor collaboration, while all 114 were able to complete the NSAA. The final cohort consisted in 112 boys who completed both NSAA and 6MWT. Their age ranged between 4.10 and 17 years (mean 8.18 ± 2.3 DS); 91 of them were on steroids, 37 on intermittent and 54 on daily regimen.
Discussion
The aim of this study was to assess a cohort of ambulant DMD boys using some of the measures that have recently been suggested to be suitable for multicentric trials in DMD. We have previously reported that the NSAA can be reliably used in a multicentric setting. Similar evidence has been suggested for 6MWT that has also been used in trials in different pediatric disorders and has recently been chosen as the primary outcome measures in a large international therapeutic trial with Ataluren
Acknowledgments
The study is supported by a Telethon UILDM Grant (GUP07009) and by TREAT NMD. The authors also wish to thank Francesco Muntoni, Adnan Manzur, Michelle Eagle and Elaine Scott for their help and suggestions.
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Both authors contributed equally.