Jay J. Han

The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy.

Walking abnormalities are prominent in Duchenne muscular dystrophy (DMD). We modified the 6‐minute walk test (6MWT) for use as an outcome measure in patients with DMD and evaluated its performance in 21 ambulatory boys with DMD and 34 healthy boys, ages 4 to 12 years. Boys with DMD were tested twice, ∼1 week apart; controls were tested once. The groups had similar age, height, and weight. All tests were completed. Boys who fell recovered rapidly from falls without injury. Mean ± SD [range] 6‐minute walk distance (6MWD) was lower in boys with DMD than in controls (366 ± 83 [125–481] m vs. 621 ± 68 [479–754] m; P < 0.0001; unpaired t‐test). Test‐retest correlation for boys with DMD was high (r = 0.91). Stride length (R2 = 0.89; P < 0.0001) was the major determinant of 6MWD for both boys with DMD and controls. A modified 6MWT is feasible and safe, documents disease‐related limitations on ambulation, is reproducible, and offers a new outcome measure for DMD natural history and therapeutic trials. Muscle Nerve, 2010

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

In this study we used the 6‐minute walk distance (6MWD) to characterize ambulation over time in Duchenne/Becker muscular dystrophy (DBMD). The 6MWD was assessed in 18 boys with DBMD and 22 healthy boys, ages 4–12 years, over mean [range] intervals of 58 [39–87] and 69 [52–113] weeks, respectively. Height and weight increased similarly in both groups. At 52 weeks, 6MWD decreased in 12 of 18 (67%) DBMD subjects (overall mean [range]: 357 [125–481] to 300 [0–510] meters; Δ −57 meters, −15.9%), but increased in 14 of 22 (64%) healthy subjects (overall mean [range]: 623 [479–754] to 636 [547–717] meters; Δ +13 meters, +2.1%). Two DBMD subjects lost ambulation. Changes in 6MWD depended on stride length and age; improvements usually occurred by 7–8 years of age; older DBMD subjects worsened, whereas older healthy subjects were stable. The 6MWD changes at 1 year confirm the validity of this endpoint and emphasize that preserving ambulation must remain a major goal of DBMD therapy. Muscle Nerve, 2010

The cooperative international neuromuscular research group duchenne natural history study—a longitudinal investigation in the era of glucocorticoid therapy: Design of protocol and the methods used

Contemporary natural history data in Duchenne muscular dystrophy (DMD) is needed to assess care recommendations and aid in planning future trials.

The 6-Minute Walk Test and Person-Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons and Clinically-Meaningful Changes Over One Year.

Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference and “clinically meaningful” person-reported outcomes (PROs) at differing levels of ambulatory ability. Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. Results: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p<0.00001). In DMD, 6MWD and 10-meter run/walk velocity were correlated with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship (r=0.79 and r=0.76). In DMD, 6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI transfer/mobility scores (r=0.76 and r=0.93). PODCI global and PODCI transfer/mobility scales provided the best estimates of 6MWT performance. A “meaningful” 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, the change in 6MWD distance associated with a “meaningful” change in PODCI scores was almost 46m. Discussion: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score.

Percent-predicted 6-minute walk distance in duchenne muscular dystrophy to account for maturational influences.

We recently described a modified version of the 6-minute walk test (6MWT) for Duchenne muscular dystrophy (DMD) based partly on the American Thoracic Society (ATS) guidelines. This measure has shown reliability, validity and utility as a primary outcome measure in DMD clinical trials. Because loss of muscle function in DMD occurs against the background of normal childhood growth and development, younger children with DMD can show increase in distance walked during 6MWT over ~1 year despite progressive muscular impairment. In this study, we compare 6-minute walk distance (6MWD) data from DMD boys (n=17) and typically developing control subjects (n=22) to existing normative data from age- and sex-matched children and adolescents. An age- and height-based equation fitted to normative data by Geiger and colleagues was used to convert 6MWD to a percent-predicted (%-predicted) value in boys with DMD. Analysis of %-predicted 6MWD data represents a method to account for normal growth and development, and shows that gains in function at early ages represents stable rather than improving abilities in boys with DMD. Boys with DMD from 4-7 years of age maintain a stable 6MWD approximately 80% of that of typically developing peers, with the deficit progressing at a variable rate thereafter.

Evaluation of upper extremity reachable workspace using Kinect camera

BACKGROUND In clinical evaluation of upper extremity, there is a lack of assessment methods that are quantitative, reliable, and informative of the overall functional capability of an individual. OBJECTIVE We present new methodology for the assessment of upper extremity impairments based on the concept of 3-dimensional reachable workspace using Microsoft Kinect. METHODS We quantify the reachable workspace by the relative surface area representing the portion of the unit hemi-sphere that is covered by the hand movement. We examine accuracy of joint positions, joint angles, and reachable workspace computation between the Kinect and motion capture system. RESULTS The results of our analysis in 10 healthy subjects showed that the accuracy of the joint positions was within 66.3 mm for our experimental protocol. We found that the dynamic angle measurements had relatively large deviations (between 9° to 28°). The acquired reachable workspace envelope showed high agreement between the two systems with high repeatability between trials (correlation coefficients between 0.86 and 0.93). CONCLUSIONS The findings indicate that the proposed Kinect-based 3D reachable workspace analysis provides sufficiently accurate and reliable results as compared to motion capture system. The proposed method could be promising for clinical evaluation of upper extremity in neurological or musculoskeletal conditions.

Assessment of regional body composition with dual-energy X-ray absorptiometry in Duchenne muscular dystrophy: correlation of regional lean mass and quantitative strength.

The purpose of this study was to assess regional body composition and its correlation with regional strength in Duchenne muscular dystrophy (DMD) subjects and able‐bodied controls. Regional dual‐energy X‐ray absorptiometry (DEXA) measurements and isometric strength were obtained for 23 DMD subjects and 23 control subjects. DMD subjects showed a decreased regional lean mass (P < 0.001). The correlation between regional strength and regional lean mass was stronger for controls than for DMD subjects. DMD subjects had decreased regional lean mass, increased regional fat mass, and decreased strength. Muscle Nerve 39: 647–651, 2009

Development and application of stereo camera-based upper extremity workspace evaluation in patients with neuromuscular diseases.

Background The concept of reachable workspace is closely tied to upper limb joint range of motion and functional capability. Currently, no practical and cost-effective methods are available in clinical and research settings to provide arm-function evaluation using an individual’s three-dimensional (3D) reachable workspace. A method to intuitively display and effectively analyze reachable workspace would not only complement traditional upper limb functional assessments, but also provide an innovative approach to quantify and monitor upper limb function. Methodology/Principal Findings A simple stereo camera-based reachable workspace acquisition system combined with customized 3D workspace analysis algorithm was developed and compared against a sub-millimeter motion capture system. The stereo camera-based system was robust, with minimal loss of data points, and with the average hand trajectory error of about 40 mm, which resulted to ∼5% error of the total arm distance. As a proof-of-concept, a pilot study was undertaken with healthy individuals (n = 20) and a select group of patients with various neuromuscular diseases and varying degrees of shoulder girdle weakness (n = 9). The workspace envelope surface areas generated from the 3D hand trajectory captured by the stereo camera were compared. Normalization of acquired reachable workspace surface areas to the surface area of the unit hemi-sphere allowed comparison between subjects. The healthy group’s relative surface areas were 0.618±0.09 and 0.552±0.092 (right and left), while the surface areas for the individuals with neuromuscular diseases ranged from 0.03 and 0.09 (the most severely affected individual) to 0.62 and 0.50 (very mildly affected individual). Neuromuscular patients with severe arm weakness demonstrated movement largely limited to the ipsilateral lower quadrant of their reachable workspace. Conclusions/Significance The findings indicate that the proposed stereo camera-based reachable workspace analysis system is capable of distinguishing individuals with varying degrees of proximal upper limb functional impairments.

Exercise in neuromuscular diseases.

This article reviews the current knowledge regarding the benefits and contraindications of exercise on individuals with neuromuscular diseases (NMDs). Specific exercise prescriptions for individuals with NMDs do not exist because the evidence base is limited. Understanding the effect of exercise on individuals with NMDs requires the implementation of a series of multicenter, randomized controlled trials that are sufficiently powered and use reliable and valid outcome measures to assess the effect of exercise interventions-a major effort for each NMD. In addition to traditional measures of exercise efficacy, outcome variables should include measures of functional status and health-related quality of life.

Rehabilitation management of neuromuscular disease: The role of exercise training

This paper summarizes the current state of knowledge regarding exercise and neuromuscular diseases/disorders (NMDs) and reviews salient studies in the literature. Unfortunately, there is inadequate evidence in much of the NMDs to make specific recommendations regarding exercise prescriptions. This review focuses on the role of exercise in a few of the specific NMDs where most research has taken place and recommends future research directions.