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Background: Over the last few years there has been increasing attention to detect early signs of impairment in young Duchenne muscular dystrophy boys but less has been reported on whether the delay may also affect the very early aspects of motor development, such as gross motor milestones. Objective: The aim of this study was to retrospectively assess the age when early motor milestones were achieved in Duchenne muscular dystrophy. Methods: The study is a retrospective analysis of data collected as part of a larger natural history project. Information on past medical history, collected at the time the boys were seen for the first time, were recorded and re available on clinical notes and on electronic CRF. Results: Data were collected in 134 DMD boys. Sitting was achieved at 7.04 months. The % of DMD boys not achieving sitting by 9.4 months was 10%, ranging from 2% in the boys with mutations before exon 44 to 33% in those beyond exon 63. Walking was achieved at a mean age of 16.35 months. The % of DMD boys not achieving independent walking by 18 months was 17%, ranging from 9% in the boys with mutations between 44 and 51 to 42% in those beyond exon 63. Conclusions: Our results showed that the risk of a delay in sitting and walking was increasingly high in patients with mutations predictive of the involvement of different brain dystrophin isoforms.

IntroductionThe aim of the study was to longitudinally assess swallowing abilities in nusinersen-treated patients with type 1 spinal muscular atrophy.MethodsTwenty infants with type 1 SMA (11 female and 9 male) treated with nusinersen between 3 weeks and 15 months of age, were assessed using the Oral and Swallowing Abilities Tool (OrSAT). The duration of the follow-up after treatment ranged between 12 months and 62 months.ResultsTwelve of the 20 infants had normal swallowing and there was no need for tube feeding at the time treatment started. Ten of the 12 had consistently normal swallowing with no need for tube feeding on follow-up. The other two required tube feeding but they regained the ability to eat some food by mouth.The remaining 8 infants already had tube feeding inserted at the time treatment started: 4 of them also had tracheostomy and they showed no changes on the OrSAT Scale. The other 4 who had tube feeding but no tracheostomy had partial functional improvement.ConclusionOur results suggest that the degree of functional impairment at the time treatment is started can help to predict the progression of swallowing abilities. The use of a structured assessment also helped to detect partial improvements.

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5–16 years), and 17 non ambulant (age range 10–30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time.

We describe the development of a new tool specifically designed to record oral abilities, swallowing and, more generally, feeding in young type 1 SMA patients, to be used during the first 24 months of life. The tool is composed by a checklist and a separate section summarizing the functional abilities into levels of feeding/swallowing impairment. The checklist includes 12 questions assessing aspects thought to be clinically meaningful for a type 1 SMA population and developmentally appropriate for infants during the first months of life. Each item is graded with a score of 0 or 1, depending on the child’s ability to perform the activity. As some items are age-dependent, the number of items to be used, and therefore the maximum score, changes with increasing age. The levels of feeding/swallowing impairment include four levels that can be identified using easily identifiable clinical criteria. In an attempt to validate the tool in an untreated population we applied it to 24 type 1 SMA patients (age range: 2.3–24.1 months, mean: 10.8) in whom the same information collected by the new tool had been previously recorded using a less-structured format. When patients were classified in three groups according to the Dubowitz decimal classification, there was a significant difference both at baseline and at follow-up (p

Background: Swallowing is one of the most important aspects in the care of type 1 spinal muscular atrophy. Main text:The aim of this paper is to describe the development of a new tool specifically designed to record different aspects related to oral abilities, swallowing and feeding in young type1 SMA patients. We also report its application to a cohort of type 1 infants to identify possible changes during the first 24 months of life. The new tool includes a checklist with 12 questions for carers and a classification of levels of impairment.The scale was retrospectively used in 24 type 1 patients (8 females and 16 males,age range from2.3 to 24.1 months (average age: 10.8 months), classified according to the Dubowitz's decimal classification into 1.1 (n=8); 1.5 (n=8); 1.9 (n=8). There was a significant difference among the 3 subtypes both at baseline and at follow up (pConclusion: Our results suggest that the new tool may help to routinely capture changes over time in type 1 infants and that the trajectories of progression reflect the overall severity of the disease. The items assessing fatigue during the nursing sessions were the most frequently impaired even in infants who did not have any other obvious clinical sign of swallowing difficulties.

ObjectiveTo report the long-term progression in a cohort of patients with type II spinal muscular atrophy (SMA) assessed with the Hammersmith Functional Motor Scale–Expanded.MethodsSeventy-three patients (age 2.6–25 years) were included in the study. Twenty-eight of the 73 were first assessed before the age of 5 years and had been followed up for ≈5 years or longer. We observed an overall progression that was not linear. A piecewise regression analysis showed an improvement of scores in the younger patients with a point of slope change at ≈5 years of age, a decline between 5 and 13 years of age, and stability/slower decline after that.ResultsPatients with the lowest scores at baseline had the earliest onset of scoliosis and a higher need for noninvasive ventilation compared to those with higher scores. Our results confirm that on the long-term follow-up all patients with type II SMA show a clear and progressive decline.ConclusionThe severity of functional impairment at baseline can help to predict the magnitude of changes over time and the overall progression, including onset of scoliosis and need for noninvasive ventilation.

Purpose To quantitatively describe passive lower extremity range of motion in participants with spinal muscular atrophy (SMA) types 2 and 3, and to establish preliminary thresholds to identify individuals at risk for performing poorly on disease-specific motor function outcome measures. Methods Eighty participants with SMA types 2 and 3, enrolled in an international multicenter natural history study, were evaluated with lower extremity range of motion testing and the Hammersmith Functional Motor Scale-Expanded. Results A hip extension joint angle of -7.5° or less for SMA type 2 and 0° or less for SMA type 3 identified diminished motor ability with good sensitivity. For knee extension, a joint angle of -9.0° or less for SMA type 2 or 0° or less for SMA type 3 was similarly sensitive. Conclusions Minimal hip and knee joint contractures were associated with diminished motor ability. Clinical trial designs should consider the effect of contractures on motor function.

The aim of the study was to evaluate the spectrum of upper limb functional activities and imaging finding in a cohort of patients affected by Duchenne muscular dystrophy. Thirty-one patients of age between 5 and 29 years were included in the study (17 ambulant and 14 non-ambulant). They were all assessed using the Performance of Upper Limb (PUL) test and muscle MRI of shoulder, arm and forearm in order to establish if the functional scores obtained at shoulder, mid and distal level related to specific patterns of involvement in each upper limb segment on muscle MRI. At shoulder level, latissimus dorsi, serratus anterior, infraspinatus and subscapularis were always involved, even in patients with full functional scores at shoulder level. Diffuse and severe involvement of all muscles was found in the patients with a PUL shoulder functional score of ≤ 5. At arm level biceps brachii, brachialis and triceps were generally concordantly involved or spared. Some degree of involvement could already be detected in patients with reduced scores on the PUL mid domain. They were generally severely involved in patients with functional scores less than 6 at mid-level. At distal level supinator and pronator muscles were often involved, followed by brachioradialis and, less frequently, by the muscles of the flexor compartment. The extensor muscles were generally completely spared. A diffuse and severe involvement was found only in patients who had very low scores (8 or below) on the PUL distal domain. The integrated use of functional scales and imaging allowed to establish patterns of involvement at each level, and the functional scores that were more frequently associated with diffuse and severe involvement.

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.8 years), and 90 non-ambulant (age range: 9.08-24.78). The total scores changed significantly over time (p

The aim of the study was to establish if the decrease in gait velocity on the 6 minute walk test relates to signs of neuromuscular junction dysfunction in spinal muscular atrophy type 3 patients. 6 minute walk test and low-rate repetitive nerve stimulation test were performed in fifteen ambulant patients with spinal muscular atrophy type 3 of age between 9 and 66 years. The 6 minute walk distance ranged between 66 and 575 m. The difference between the first and the 6th minute ranged between 0 and −69%. The low-rate repetitive nerve stimulation test measured in % of loss ranged between −31.7% to +4.2% to the axillary nerve. The correlation between 6 minute walk test changes and low-rate repetitive nerve stimulation test changes was 0.86. Our data suggest that the 6 minute walk test can identify fatigue in the ambulant type 3 patients who have a concurrent neuromuscular junction dysfunction. The identification of fatigue with a simple clinical test may help to target patients who may benefit from drugs that facilitate neuromuscular transmission.

Introduction: There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients. Methods: An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale. Results: Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups. Discussion: The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. This article is protected by copyright. All rights reserved.

Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P Conclusions: Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.

Objective To estimate the frequency of sleep disorders in young persons with type 2 and type 3 spinal muscular atrophy (SMA), and to evaluate the relationship between sleep disorders and different variables such as motor impairment, age, use of ventilation, and use of night orthoses. Methods A total of 85 young persons (6–25 years of age) with type 2 and type 3 SMA were assessed using the Sleep Disturbance Scale for Children (SDSC), a scale assessing different sleep factors, and the Hammersmith Functional Motor Scale Expanded (HFMSE), a scale evaluating motor impairment. Results An abnormal total sleep score was found in 16.4% of children with SMA; an additional 16.7% had an abnormal score on at least one of the sleep factors assessed by the SDSC. No specific correlation was observed between sleep disturbances and functional level as expressed by the SDSC and total HFMSE scores, but the relationship with individual items on the scale was different. The SDSC total score was significantly associated with the ability to half roll on both sides and to roll from prone to supine on the HMFSE. Conclusion Our results demonstrate that sleep disorders are common in children with SMA.

BACKGROUND: The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys. SUBJECTS AND METHODS: A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS). RESULTS: The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p

The advent of therapeutic approaches for Duchenne muscular dystrophy (DMD) has highlighted the need to identify reliable outcome measures for young boys with DMD. The aim of this study was to develop a revised version of the North Star Ambulatory Assessment (NSAA) suitable for boys between the age of 3 and 5 years by identifying age appropriate items and revising the scoring system accordingly. Using the scale in 171 controls between the age of 2.9 and 4.8 years, we identified items that were appropriate at different age points. An item was defined as age appropriate if it was completed, achieving a full score, by at least 85% of the typically developing boys at that age. At 3 years (±3months) there were only 8 items that were age appropriate, at 3 years and 6 months there were 13 items while by the age of 4 years all 17 items were appropriate. A revised version of the scale was developed with items ordered according to the age when they could be reliably performed. The application of the revised version of the scale to data collected in young DMD boys showed that very few of the DMD boys were able to complete with a full score all the age appropriate items. In conclusion, our study suggests that a revised version of the NSAA can be used in boys from the age of 3 years to obtain information on how young DMD boys acquire new abilities and how this correlates with their peers.

The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3%) lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14%) and 11 between 24 and 36 months (12%). The 6 minute walk test showed an average overall decline of -15.8 (SD 77.3) m at 12 months, of -58.9 (SD 125.7) m at 24 months and -104.22 (SD 146.2) m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m) (p0.001). The changes were also significantly different according to steroid treatment (p = 0.01). Similar findings were found for the North Star Ambulatory Assessment. These are the first 36 month longitudinal data using the 6 minute walk test and North Star Ambulatory Assessment in Duchenne muscular dystrophy. Our findings will help not only to have a better idea of the progression of the disorder but also provide reference data that can be used to compare with the results of the long term extension studies that are becoming available.

Highlights • The paper reports the effect of steroids on upper limb function in non ambulant DMD boys. • Boys continuing steroids after loss of ambulation perform better than those who stopped at the time of loss of ambulation. • The Performance of Upper Limb test can reliably capture change over time and the effect of intervention., The aim of this study was to establish the possible effect of glucocorticoid treatment on upper limb function in a cohort of 91 non-ambulant DMD boys and adults of age between 11 and 26 years. All 91 were assessed using the Performance of Upper Limb test. Forty-eight were still on glucocorticoid after loss of ambulation, 25 stopped steroids at the time they lost ambulation and 18 were GC naïve or had steroids while ambulant for less than a year. At baseline the total scores ranged between 0 and 74 (mean 41.20). The mean total scores were 47.92 in the glucocorticoid group, 36 in those who stopped at loss of ambulation and 30.5 in the naïve group (p

The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3%) lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14%) and 11 between 24 and 36 months (12%). The 6 minute walk test showed an average overall decline of -15.8 (SD 77.3) m at 12 months, of -58.9 (SD 125.7) m at 24 months and -104.22 (SD 146.2) m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m) (p

ObjectiveIn the last few years some of the therapeutical approaches for Duchenne muscular dystrophy (DMD) are specifically targeting distinct groups of mutations, such as deletions eligible for skipping of individual exons. The aim of this observational study was to establish whether patients with distinct groups of mutations have different profiles of changes on the 6 minute walk test (6MWT) over a 12 month period.MethodsThe 6MWT was performed in 191 ambulant DMD boys at baseline and 12 months later. The results were analysed using a test for heterogeneity in order to establish possible differences among different types of mutations (deletions, duplications, point mutations) and among subgroups of deletions eligible to skip individual exons.ResultsAt baseline the 6MWD ranged between 180 and 560,80 metres (mean 378,06, SD 74,13). The 12 month changes ranged between -325 and 175 (mean -10.8 meters, SD 69.2). Although boys with duplications had better results than those with the other types of mutations, the difference was not significant. Similarly, boys eligible for skipping of the exon 44 had better baseline results and less drastic changes than those eligible for skipping exon 45 or 53, but the difference was not significant.Conclusionseven if there are some differences among subgroups, the mean 12 month changes in each subgroup were all within a narrow Range: from the mean of the whole DMD cohort. This information will be of help at the time of designing clinical trials with small numbers of eligible patients.

The aim of this prospective longitudinal multi centric study was to evaluate the correlation between the Hammersmith Functional Motor Scale and the 20 item version of the Motor Function Measure in non ambulant SMA children and adults at baseline and over a 12 month period. Seventy-four non-ambulant patients performed both measures at baseline and 49 also had an assessment 12 month later. At baseline the scores ranged between 0 and 40 on the Hammersmith Motor function Scale and between 3 and 45 on the Motor Function Measure 20. The correlation between the two scales was 0.733. The 12 month changes ranged between -11 and 4 for the Hammersmith and between -11 and 7 for the Motor Function Measure 20. The correlation between changes was 0.48. Our results suggest that both scales provide useful information although they appeared to work differently at the two extremes of the spectrum of abilities. The Hammersmith Motor Function Scale appeared to be more suitable in strong non ambulant patients, while the Motor Function Measures appeared to be more sensitive to capture activities and possible changes in the very weak patients, including more items capturing axial and upper limb activities. The choice of these measures in clinical trials should therefore depend on inclusion criteria and magnitude of expected changes.

Recent studies have suggested that in non-ambulant patients affected by spinal muscular atrophy the Upper Limb Module can increase the range of activities assessed by the Hammersmith Functional Motor Scale Expanded. The aim of this study was to establish 12-month changes in the Upper Limb Module in a cohort of non-ambulant spinal muscular atrophy patients and their correlation with changes on the Hammersmith Functional Motor Scale Expanded. The Upper Limb Module scores ranged between 0 and 17 (mean 10.23, SD 4.81) at baseline and between 1 and 17 at 12 months (mean 10.27, SD 4.74). The Hammersmith Functional Motor Scale Expanded scores ranged between 0 and 34 (mean 12.43, SD 9.13) at baseline and between 0 and 34 at 12 months (mean 12.08, SD 9.21). The correlation betweeen the two scales was 0.65 at baseline and 0.72 on the 12 month changes. Our results confirm that the Upper Limb Module can capture functional changes in non-ambulant spinal muscular atrophy patients not otherwise captured by the other scale and that the combination of the two measures allows to capture changes in different subgroups of patients in whom baseline scores and functional changes may be influenced by several variables such as age.

The aim of this study was to establish the suitability of the North Star Ambulatory Assessment for use in young boys with Duchenne muscular dystrophy. We studied 147 typically developing and 144 boys affected by Duchenne muscular dystrophy between the ages of 3 and 5 years. More than 85% of the typically developing boys by the age of 4 years had full scores on all the items with total scores ≥33/34. Before the age of 4 years more than 15% of the typically developing boys did not achieve full scores on all the items. Some items, such as standing on one leg, showed significant improvement with age. In contrast, other activities were rarely achieved even in the older boys. Even if there was a progressive increase in scores with age, both total and individual item scores in Duchenne were still far from those obtained in the typically developing children of the same age. Our findings suggest that the North Star Ambulatory Assessment can be reliably used at least from the age of 4 years. Longitudinal natural history data studies are needed to assess possible changes over time and the possible effect of early steroids.

The Performance of Upper Limb was specifically designed to assess upper limb function in Duchenne muscular dystrophy. The aim of this study was to assess (1) a cohort of typically developing children from the age of 3years onwards in order to identify the age when the activities assessed in the individual items are consistently achieved, and (2) a cohort of 322 Duchenne children and young adults to establish the range of findings at different ages. We collected normative data for the scale validation on 277 typically developing subjects from 3 to 25years old. A full score was consistently achieved by the age of 5years. In the Duchenne cohort there was early involvement of the proximal muscles and a proximal to distal progressive involvement. The scale was capable of measuring small distal movements, related to activities of daily living, even in the oldest and weakest patients. Our data suggest that the assessment can be reliably used in both ambulant and non ambulant Duchenne patients in a multicentric setting and could therefore be considered as an outcome measure for future trials.

The aim of our longitudinal multicentric study was to establish the changes on the 6min walk test (6MWT) in ambulant SMA type III children and adults over a 12month period. Thirty-eight ambulant type III patients performed the 6MWT at baseline and 12months after baseline. The distance covered in 6min ranged between 75 and 510m (mean 294.91, SD 127) at baseline and between 50 and 611m (mean 293.41m, SD 141) at 12months. The mean change in distance between baseline and 12months was -1.46 (SD 50.1; range: -183 to 131.8m). The changes were not correlated with age or baseline values (p>.05) even though younger patients reaching puberty, had a relatively higher risk of showing deterioration of more than 30m compared to older patients. Our findings provide the first longitudinal data using the 6MWT in ambulant SMA patients.

The recent development of therapeutic approaches for Spinal Muscular Atrophy (SMA) has highlighted the need to identify clinical outcome measures for planned therapeutic clinical trials that could be used across spectrum of abilities. The Hammersmith Motor Function Scale (HMFS) is a functional scale already used in ongoing clinical trials. In order to assess functions related to everyday activities an add on module exploring upper limb (ULM) was developed in 2009 with the aim of better measuring weaker patients. This is also being used in an ongoing clinical trial in SMA. We report the results of a longitudinal study showing the changes on both the Hammersmith Functional Motor Scale and on the Upper Limb Module over a 12 month period exploring the correlation between the two measures. Longitudinal data, including at least one assessment at baseline and one performed 12 months later was obtained in 80 non ambulant SMA patients. Our results showed that the ULM widens the spectrum of functional aspects assessed, especially at the weaker end of the spectrum of non ambulant SMA. A proportion of the patients with very low scores on the HFMS were still able to achieve a few upper limb activities. Our findings suggest that the combined use of the two scales will help to improve the sensitivity of the HMFS in detecting changes over time.

In the last few years a number of therapeutical approaches have become available for patients affected by Duchenne muscular dystrophy (DMD). The majority of the approaches proposed so far are specifically targeting distinct group of mutations, such as stop codon point mutations or groups of deletions as in exon skipping studies. Because of this, the number of patients eligible for these studies is limited to those having specific mutations or groups of mutations. This has raised the question of whether natural history data should be used as controls in studies with few eligible patients and, more specifically, whether individual groups of mutations follow the general natural history of boys of DMD or have distinct profiles of progression of functional impairment. The aim of this study was to report 12 month longitudinal changes of the 6 min walk test (6MWT) in a large cohort of DMD ambulant patients subdivided according to type and site of mutations. 6MWT was performed in 198 DMD ambulant boys, older than 4 years at baseline and repeated after 12 months. 137 had deletions, 18 had duplications and 43 point mutations. Patients with deletions were further subdivided into subgroups according to whether they had mutations eligible for skipping in different exons, selecting those who were currently or likely to be part of clinical trials, eligible for skipping 44 (n = 18), eligible for skipping 45 (n = 16), eligible for skipping 51 (n = 27), eligible for skipping 53 (n = 28). Patients with point mutations were also subdivided identifying those with stop codon mutations. The 6MWD showed 12 months changes between −325 and 175 (mean −10) m. There was no significant difference between deletions, duplications and point mutations neither at baseline nor in the 12 month changes. When patients were subdivided into different subgroups of deletions according to their eligibility to skip specific exons, there was little difference between the individual subgroups and the patients with the whole cohort. The subgroup eligible for skipping exon 44 however had a trend to perform better at baseline and to show less deterioration than the other subgroups.

The 6 min walk test (6MWT) has been recently chosen as the primary outcome measure in several international multicenter clinical trials in Duchenne muscular dystrophy (DMD) ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment and with age and 6MWT values at baseline. 96 patients from 11 centers were assessed at baseline and 1, 2 and 3 years after baseline. Three boys (3%) lost the ability to perform the test within 12 months, another 13 between 12 and 24 months (14%) and other 11 between 24 and 36 months (12%). The 6MWT showed an average overall decline of −15.8 (SD 77.3) meters in the first year, of −58.9 (SD 125.7) in the second year and −104.22 (SD 146.2) in the third year. The changes were significantly different in the two baseline age groups and according to the baseline 6MWT values (below and above 350 m) (test for interaction, p

The 6 min walk test (6MWT) has been recently chosen as the primary outcome measure in several international multicenter clinical trials in Duchenne muscular dystrophy (DMD) patients. In the last few years there has been increasing attention to the assessment of upper limbs. The Performance of Upper Limb (PUL) has been specifically developed for the assessment of upper limbs in DMD providing information of three domains (shoulder, elbow and distal). The first published data have shown that involvement of upper limb is present not only in non ambulant patients and early signs of involvement can also be found in younger ambulant DMD boys. The aim of this longitudinal Italian multicentric study was to evaluate the correlation between the 6MWT and the PUL in ambulant DMD boys. As part of this study all boys are assessed using both measures. The preliminary results in over 100 DMD boys show that early signs of shoulder involvement can already be found after the age of 8 and become increasingly more marked with age. Boys with 6MWT results above 400 m generally have full scores or one or two points below the full score. Their scores slightly decrease between 350 and 400 m with a more obvious fall in scores below the cut off point of 350 that become increasingly more marked with the decrease in meters on the 6MWT. Our results suggest that upper limb involvement can already be found in DMD boys even in the ambulant phase and the scores on the PUL reflect to some extent the overall impairment observed on the 6MWT.

While there have been considerable advances for ambulant children with Duchenne Muscular Dystrophy (DMD), no prospective study has so far been devoted to outcome measures in non ambulant patients, with increasing complaints from families and patients. This information appears to be relevant not only for a better understanding of the disease progression but also for possible enrolment of patients in future trials. As a result of an international effort, a new tool, the Performance of Upper Limb (PUL) was specifically designed to assess upper limb function in DMD boys. The purpose of the PUL is to assess changes that occurs in motor performance of the upper limb over time from when a boy is still ambulant to the time he loses all arm function when non-ambulant. The aim of the present study was to use the PUL in: (1) a cohort of typically developing children from the age of 3 years onwards in order to identify the age when the activities assessed in the individual items are consistently achieved. (2) a cohort of DMD children and young adults to assess the range of findings at different ages. We collected normative data for the scale validation on 258 typically developing children from 3 to 14 years old. A full score was consistently achieved (>85%) by the age of 3.5 years. Below the age of 3.5 years there was a significant number (>15%) who had difficulties in the items involving stacking cans, opening a Ziploc container, tearing a piece of paper and in lifting the heavier weights. After the age of 3.5 years difficulties were only occasionally found in tearing a sheet of paper. When the PUL was performed in the 211 DMD patients (age range 2.8–23 years), we observed a progressive deterioration of scores with age, with early involvement of the proximal muscles that was more obvious after the age of 10 years. Even the oldest and weakest DMD patients were still able to perform some of the distal items, suggesting that the scale is capable of measuring small.