24 Month Longitudinal Data in Ambulant Boys with Duchenne Muscular Dystrophy

Elena Mazzone ,Enrico Bertini,Silvia Frosini,Elena Pegoraro,Antonella Pini,Marika Pane,Roberta Scalise,Michele Sacchini,Maria Pia Sormani,Claudio Bruno,Roberto De Sanctis,Adele D’Amico,Luisa Politano,Gianluca Vita,Maria Chiara Motta,Roberta Battini,Angela Berardinelli,Tiziana Mongini,Emanuela Viggiano,Gessica Vasco,Luca Bello,Francesca Magri,Eugenio Mercuri,Yvan Torrente,Sonia Messina,Sara Napolitano,Enrica Rolle,Francesca Rossi,Maria Alice Donati,Giacomo P Comi ,L Doglio ,Paola D′Ambrosio ,Stefano C Previtali ,S Bonfiglio ,F Bianco ,Fabio Cavallaro

doi:10.1371/journal.pone.0052512

Abstract

ObjectivesThe aim of the study was i) to assess the spectrum of changes over 24 months in ambulant boys affected by Duchenne muscular dystrophy, ii) to establish the difference between the first and the second year results and iii) to identify possible early markers of loss of ambulation.MethodsOne hundred and thirteen patients (age range 4.1–17, mean 8.2) fulfilled the inclusion criteria, 67 of the 113 were on daily and 40 on intermittent steroids, while 6 were not on steroids. All were assessed using the 6 Minute Walk Test (6MWT), the North Star Ambulatory Assessment (NSAA) and timed test.ResultsOn the 6MWT there was an average overall decline of −22.7 (SD 81.0) in the first year and of −64.7 (SD 123.1) in the second year. On the NSAA the average overall decline was of −1.86 (SD 4.21) in the first year and of −2.98 (SD 5.19) in the second year. Fourteen children lost ambulation, one in the first year and the other 13 in the second year of the study. A distance of at least 330 meters on the 6MWT, or a NSAA score of 18 at baseline reduced significantly the risk of losing ambulation within 2 years.ConclusionsThese results can be of help at the time of using inclusion criteria for a study in ambulant patients in order to minimize the risk of patients who may lose ambulation within the time of the trial.

Highlights

In the last few years the increasing number of potentially effective therapeutical approaches for patients affected by Duchenne muscular dystrophy (DMD) has stimulated the interest in outcome measures to be used in clinical trials
We have recently reported data from a multicentric longitudinal study, describing the changes on both 6 minute walk test (6MWT) and North Star Ambulatory Assessment (NSAA) observed over 12 months in ambulant DMD boys
Boys who were below the age of 7 at baseline had some improvement on both NSAA and 6MWT in the first year and, a small improvement on 6MWT was found in the second year

Summary

Introduction

In the last few years the increasing number of potentially effective therapeutical approaches for patients affected by Duchenne muscular dystrophy (DMD) has stimulated the interest in outcome measures to be used in clinical trials. Its use has been reported in international multicenter clinical trials and longitudinal natural history studies in DMD ambulant patients [1,2,3,4]. Functional scales, such as the North Star Ambulatory Assessment (NSAA) represent an ideal additional tool to the 6MWT, as they provide information on a wider spectrum of functions that reflect everyday life activities [5]. We have recently reported data from a multicentric longitudinal study, describing the changes on both 6MWT and NSAA observed over 12 months in ambulant DMD boys The NSAA has been developed for ambulant DMD boys and has been validated and used in multicentric longitudinal studies [3,4,6,7,8].

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