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Aim: Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense mutation Duchenne muscular dystrophy. Materials & methods: Placebo data from Phase IIb (ClinicalTrials.gov Identifier: NCT00592553) and ACT DMD (ClinicalTrials.gov Identifier: NCT01826487) ataluren nonsense mutation Duchenne muscular dystrophy clinical trials were retrospectively combined in meta-analyses (intent-to-treat population; for change from baseline to week 48 in 6-min walk distance [6MWD] and timed function tests). Results: Significant improvements in change in 6-min walk distance with deflazacort versus prednisone/prednisolone (least-squares mean difference 39.54 m [95% CI: 13.799, 65.286; p = 0.0026]). Significant and clinically meaningful improvements in 4-stair climb and 4-stair descend for deflazacort versus prednisone/prednisolone. Conclusion: Deflazacort provides clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy.

Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods Seven participants received (−)‐epicatechin 50 mg twice per day for 8 weeks. Pre‐ and postprocedures included biceps brachii biopsy to assess muscle structure and growth‐relevant endpoints by western blotting, mitochondria volume measurement, and cristae abundance by electron microscopy, graded exercise testing, and muscle strength and function tests. Results Western blotting showed significantly increased levels of enzymes modulating cellular bioenergetics (liver kinase B1 and 5′‐adenosine monophosphate–activated protein kinase). Peroxisome proliferator‐activated receptor gamma coactivator‐1alpha, a transcriptional coactivator of genes involved in mitochondrial biogenesis and cristae‐associated mitofilin levels, increased as did cristae abundance. Muscle and plasma follistatin increased significantly while myostatin decreased. Markers of skeletal muscle regeneration myogenin, myogenic regulatory factor‐5, myoblast determination protein 1, myocyte enhancer factor‐2, and structure‐associated proteins, including dysferlin, utrophin, and intracellular creatine kinase, also increased. Exercise testing demonstrated decreased heart rate, maximal oxygen consumption per kilogram, and plasma lactate levels at defined workloads. Tissue saturation index improved in resting and postexercise states. Discussion (−)‐Epicatechin, an exercise mimetic, appears to have short‐term positive effects on tissue biomarkers indicative of mitochondrial biogenesis and muscle regeneration, and produced improvements in graded exercise testing parameters in patients with BMD.

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Contemporary natural history data in Duchenne muscular dystrophy (DMD) is needed to assess care recommendations and aid in planning future trials.The Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 individuals, aged 2-28 years, with DMD in a longitudinal, observational study at 20 centers. Assessments obtained every 3 months for 1 year, at 18 months, and annually thereafter included: clinical history; anthropometrics; goniometry; manual muscle testing; quantitative muscle strength; timed function tests; pulmonary function; and patient-reported outcomes/health-related quality-of-life instruments.Glucocorticoid (GC) use at baseline was 62% present, 14% past, and 24% GC-naive. In those ≥6 years of age, 16% lost ambulation over the first 12 months (mean age 10.8 years).Detailed information on the study methodology of the CINRG DMD-NHS lays the groundwork for future analyses of prospective longitudinal natural history data. These data will assist investigators in designing clinical trials of novel therapeutics.

Assessing burden of disease is a complex process involving identifying the physical, psychological, and socioeconomic aspects that make up the totality of disease burden on patients, families, and caregivers, and society as a whole, with chronic pain affecting all of these aspects. It is the job of the physiatrist to identify disability and promote interventions to minimize it, including facilitating access to appropriate treatment for chronic pain, and ultimately easing disease burden. Chronic pain causes significant psychosocial dysfunction for patients with neuromuscular disease and contributes substantially to the overall disease burden. There are many psychosocial factors closely associated with pain and dysfunction in patients with neuromuscular disease, most notably a perception of inadequate psychosocial support. The assessment of children with neuromuscular disorders must include the parents or guardians as well, given that chronic pain in a child will affect the entire family.

Neuromuscular disorders (NMDs) are a group of myopathic or neuropathic diseases that directly or indirectly affect the functioning of muscle. Physical therapists (PTs) have extensive specialized training in musculoskeletal evaluation and assessment that gives them the tools to meet the significant needs of this population. This article reviews the role of PTs in treating the NMD population with a discussion of available evaluation techniques and interventions and with an effort to differentiate between treatments known to apply to this population and conventional practice of PTs. The status of currently available outcome measures used for research and their applicability to clinics are presented.

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.

Background. A comprehensive, reliable, and valid measurement system is needed to monitor changes in children with neurological conditions who experience lifelong functional limitations. Objective. This article describes the development and psychometric properties of the pediatric version of the Quality of Life in Neurological Disorders (Neuro-QOL) measurement system. Methods. The pediatric Neuro-QOL consists of generic and targeted measures. Literature review, focus groups, individual interviews, cognitive interviews of children and consensus meetings were used to identify and finalize relevant domains and item content. Testing was conducted on 1018 children aged 10 to 17 years drawn from the US general population for generic measures and 171 similarly aged children with muscular dystrophy or epilepsy for targeted measures. Dimensionality was evaluated using factor analytic methods. For unidimensional domains, item parameters were estimated using item response theory models. Measures with acceptable fit indices were calibrated as item banks; those without acceptable fit indices were treated as summary scales. Results. Ten measures were developed: 8 generic or targeted banks (anxiety, depression, anger, interaction with peers, fatigue, pain, applied cognition, and stigma) and 2 generic scales (upper and lower extremity function). The banks reliably ( r > 0.90) measured 63.2% to 100% of the children tested. Conclusions. The pediatric Neuro-QOL is a comprehensive measurement system with acceptable psychometric properties that could be used in computerized adaptive testing. The next step is to validate these measures in various clinical populations.

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, approximately 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 (R(2) = 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.

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.

Background Goniometers are commonly used by physical therapists to measure range-of-motion (ROM) in the musculoskeletal system. These measurements are used to assist in diagnosis and to help monitor treatment efficacy. With newly emerging technologies, smartphone-based applications are being explored for measuring joint angles and movement. Objective This pilot study investigates the intra- and inter-rater reliability as well as concurrent validity of a newly-developed smartphone magnetometer-based goniometer (MG) application for measuring passive shoulder abduction in both sitting and supine positions, and compare against the traditional universal goniometer (UG). Design This is a comparative study with repeated measurement design. Methods Three physical therapists utilized both the smartphone MG and a traditional UG to measure various angles of passive shoulder abduction in a healthy subject, whose shoulder was positioned in eight different positions with pre-determined degree of abduction while seated or supine. Each therapist was blinded to the measured angles. Concordance correlation coefficients (CCCs), Bland–Altman plotting methods, and Analysis of Variance (ANOVA) were used for statistical analyses. Results Both traditional UG and smartphone MG were reliable in repeated measures of standardized joint angle positions (average CCC > 0.997) with similar variability in both measurement tools (standard deviation (SD) ± 4°). Agreement between the UG and MG measurements was greater than 0.99 in all positions. Conclusion Our results show that the smartphone MG has equivalent reliability compared to the traditional UG when measuring passive shoulder abduction ROM. With concordant measures and comparable reliability to the UG, the newly developed MG application shows potential as a useful tool to assess joint angles.

Accurate Energy Expenditure (EE) Estimation is very important to monitor physical activity of healthy and disabled population. In this work, we examine the limitations of applying existing calorimetry equations and machine learning models based on sensor data collected from healthy adults to estimate EE in disabled population, particularly children with Duchene muscular dystrophy (DMD). We propose a new machine learning-based approach which provides more accurate EE estimation for boys living with DMD. Existing calorimetry equations obtain a correlation of 40% (93% relative error in linear regression) with COSMED indirect calorimeter readings, while the non-linear model derived for normal healthy adults (developed using machine learning) gave 37% correlation. The proposed model for boys with DMD give a 91% correlation with COSMED values (only 38% relative absolute error) and uses ensemble meta-classifier with Reduced Error Pruning Decision Trees methodology.

Abdominal muscles are selectively active in normal subjects during stress and may increase the potential energy for inspiration by reducing the end-expiratory lung volume (EELV). We hypothesized that a similar process would occur in subjects with myotonic muscular dystrophy (MMD), but would be less effective, because of to their weakness and altered chest wall mechanics. Fine-wire electromyography (EMG) of the transversus abdominis (TA), internal oblique (IO), external oblique, and rectus abdominis was recorded in 10 MMD and 10 control subjects. EMG activity, respiratory inductive plethysmography, and gastric pressure were recorded during static pressure measurement and at increasing levels of inspiratory resistance breathing. EELV was reduced and chest wall motion was synchronous only in controls. Although the TA and IO were selectively recruited in both groups, EMG activity of the MMD group was twice that of controls at the same inspiratory pressure. In MMD subjects with mildly reduced forced vital capacity, significant differences can be seen in abdominal muscle recruitment, wall motion, work of breathing, and ventilatory parameters.

Ugalde V, Breslin EH, Walsh SA, Bonekat HW, Abresch RT, Carter GT. Pursed lips breathing improves ventilation in myotonic muscular dystrophy. Arch Phys Med Rehabil 2000;81:472-8. Objective: To determine the effects of pursed lips breathing on ventilation, chest wall mechanics, and abdominal muscle recruitment in myotonic muscular dystrophy (MMD). Design: Before-after trial. Setting: University hospital pulmonary function laboratory. Participants: Eleven subjects with MMD and 13 normal controls. Intervention: Pursed lips breathing. Outcome Measures: Electromyographic (EMG) activity of the transversus abdominis, external oblique, internal oblique, and rectus abdominis was recorded with simultaneous measures of gastric pressure, abdominal plethysmography, and oxygen saturation. Self-reported sensations of dyspnea, respiratory effort, and fatigue were recorded at the end of each trial. Results: Pursed lips breathing and deep breathing led to increased tidal volume, increased minute ventilation, increased oxygen saturation, reduced respiratory rate, and reduced end-expiratory lung volume. Dyspnea, respiratory effort, and fatigue increased slightly with pursed lips breathing. EMG activity of the transversus abdominis and internal oblique muscles increased in MMD only and was associated with an increase in gastric pressure. Conclusions: Pursed lips breathing and deep breathing are effective and easily employed strategies that significantly improve tidal volume and oxygen saturation in subjects with MMD. Abdominal muscle recruitment does not explain the ventilatory improvements, but reduced end-expiratory lung volume may increase the elastic recoil of the chest wall. Further clinical studies are needed to ascertain if the ventilatory improvements with pursed lips breathing and deep breathing improve pulmonary outcomes in MMD. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

This article explains how animal models can be utilized to develop rehabilitation strategies to help treat the pathophysiology of neuromuscular diseases (NMDs) and illustrates how these models can be used to test the effects of physical interventions, such as exercise, stretching, and immobilization, in this setting.

Introduction: One of the major challenges in the neuromuscular field has been lack of upper extremity outcome measures that can be useful for clinical therapeutic efficacy studies. Using vision-based sensor system and customized software, 3- dimensional (3D) upper extremity motion analysis can reconstruct a reachable workspace as a valid, reliable and sensitive outcome measure in various neuromuscular conditions where proximal upper extremity range of motion and function is impaired. Methods: Using a stereo-camera sensor system, 3D reachable workspace envelope surface area normalized to an individual's arm length (relative surface area: RSA) to allow comparison between subjects was determined for 20 healthy controls and 9 individuals with varying degrees of upper extremity dysfunction due to neuromuscular conditions. All study subjects were classified based on Brooke upper extremity function scale. Right and left upper extremity reachable workspaces were determined based on three repeated measures. The RSAs for each frontal hemi-sphere quadrant and total reachable workspaces were determined with and without loading condition (500 gram wrist weight). Data were analyzed for assessment of the developed system and validity, reliability, and sensitivity to change of the reachable workspace outcome. Results: The mean total RSAs of the reachable workspace for the healthy controls and individuals with NMD were significantly different (0.586 ± 0.085 and 0.299 ± 0.198 respectively; p Abstract Introduction: One of the major challenges in the neuromuscular field has been lack of upper extremity outcome measures that can be useful for clinical therapeutic efficacy studies. Using vision-based sensor system and customized software, 3- dimensional (3D) upper extremity motion analysis can reconstruct a reachable workspace as a valid, reliable and sensitive outcome measure in various neuromuscular conditions where proximal upper extremity range of motion and function is impaired. Methods: Using a stereo-camera sensor system, 3D reachable workspace envelope surface area normalized to an individual's arm length (relative surface area: RSA) to allow comparison between subjects was determined for 20 healthy controls and 9 individuals with varying degrees of upper extremity dysfunction due to neuromuscular conditions. All study subjects were classified based on Brooke upper extremity function scale. Right and left upper extremity reachable workspaces were determined based on three repeated measures. The RSAs for each frontal hemi-sphere quadrant and total reachable workspaces were determined with and without loading condition (500 gram wrist weight). Data were analyzed for assessment of the developed system and validity, reliability, and sensitivity to change of the reachable workspace outcome. Results: The mean total RSAs of the reachable workspace for the healthy controls and individuals with NMD were significantly different (0.586 ± 0.085 and 0.299 ± 0.198 respectively; p Abstract Introduction: One of the major challenges in the neuromuscular field has been lack of upper extremity outcome measures that can be useful for clinical therapeutic efficacy studies. Using vision-based sensor system and customized software, 3- dimensional (3D) upper extremity motion analysis can reconstruct a reachable workspace as a valid, reliable and sensitive outcome measure in various neuromuscular conditions where proximal upper extremity range of motion and function is impaired. Methods: Using a stereo-camera sensor system, 3D reachable workspace envelope surface area normalized to an individual's arm length (relative surface area: RSA) to allow comparison between subjects was determined for 20 healthy controls and 9 individuals with varying degrees of upper extremity dysfunction due to neuromuscular conditions. All study subjects were classified based on Brooke upper extremity function scale. Right and left upper extremity reachable workspaces were determined based on three repeated measures. The RSAs for each frontal hemi-sphere quadrant and total reachable workspaces were determined with and without loading condition (500 gram wrist weight). Data were analyzed for assessment of the developed system and validity, reliability, and sensitivity to change of the reachable workspace outcome. Results: The mean total RSAs of the reachable workspace for the healthy controls and individuals with NMD were significantly different (0.586 ± 0.085 and 0.299 ± 0.198 respectively; p

We present mobile health (mHealth) applications utilizing embedded phone sensors as an angle-measuring device for upper-limb range of motion (ROM) and estimation of reachable workspace to assist in evaluation of upper limb functional capacity. Our results show that the phone can record accurate measurements, as well as provide additional functionalities for clinicians.

Duchenne muscular dystrophy (DMD) is an X-linked degenerative disorder of the dystrophin protein that causes progressive muscle weakness, usually leading to death in early adulthood.1 DMD is the most common neuromuscular disease of childhood and occurs with an incidence of about 30 per 100,000 live-born males across all ethnic groups.2 Although it is accepted that a majority of cases of DMD are inherited, studies have demonstrated that between 20% and 50% of DMD cases in various populations are the result of spontaneous mutations.3–6 The course of physical impairment is severe and inexorably progressive, and its description has varied little since Meryon’s and Duchenne’s early descriptions of the disease in the mid-19th century.7,8 In early childhood, motor developmental milestones are delayed and, by 4–5 years of age, these children rise from the floor in the classic adaptive standing pattern first described by Gowers,9 have increasing difficulty climbing stairs, and begin to have frequent falls. Muscles show a classic pattern of pseudohypertrophy, most notably in the calf muscles. With disease progression, boys begin to walk with a characteristic waddling gait with compensatory lumbar lordosis, shortened stride length, and widened base of support, which advances to a point where they require constant physical support and stabilization.10,11 Mean age to loss of ambulation in steroid-naive children is between ages 9 and 10 years.12–16 Over the ensuing years, patients typically develop worsening contractures, scoliosis, and progressive impairment of respiratory and cardiac function. From the earliest reports until the 1960s, death has typically occurred in the early to mid-teens due to respiratory complications or cardiac failure, but advances in preventive and supportive respiratory and cardiac therapies have led to a median survival in the middle to late twenties and growing chances of survival into the thirties for patients who receive aggressive care.13 Clinical trials have demonstrated that administering glucocorticoid (GC) therapy improves strength within weeks to a few months, and that these increases in strength can preserve ambulation for up to 2–3 years longer than for steroid-naive patients.17–22 However, few studies have assessed the long-term impact of GC-mediated improvements on maintaining strength, preserving function, and developing or preventing secondary health conditions. The aims of this study were to: (1) assess baseline levels of impairment and prevalence of secondary conditions from age 2 years to adulthood; and (2) evaluate the effect of chronic GCs in DMD on: (a) preservation of functional capabilities using a novel composite functional “milestone” scale scale showing clinically meaningful mobility and upper limb abilities; (b) progression of strength loss based on manual muscle testing versus historical reports of strength loss in steroid-naive patients; and (c) preservation of respiratory function based on pulmonary function tests (PFTs) across the age span.

We present a real-time algorithm for human pose detection and tracking from vision-based 3D data and its application to tele-rehabilitation in virtual environments. We employ stereo camera(s) to capture 3D avatars of geographically dislocated patient and therapist in real-time, while sending the data remotely and displaying it in a virtual scene. A pose detection and tracking algorithm extracts kinematic parameters from each participant and determines pose similarity. The pose similarity score is used to quantify patient's performance and provide real-time feedback for remote rehabilitation.

Background and Aims: Mobile phones are pervasive computing technologies that offer opportunities for sensing personal behaviors and exposures to environmental hazards. The CalFit system uses the co...

Objective To investigate the efficacy of acupuncture for the treatment of mild to moderate carpal tunnel syndrome (CTS). Design Prospective, randomized, placebo-controlled, double-blinded study. Setting Single-center study. Participants Forty-one acupuncture-naive adult subjects with mild to moderate CTS enrolled in the study. Thirty-four subjects completed the study. Methods Clinical diagnosis of CTS was supported by electrodiagnostic findings. Subjects were randomly assigned to either (1) acupuncture (n = 21) or (2) placebo acupuncture (n = 20) with use of Streitberger placebo acupuncture needles. Both groups received weekly sessions of acupuncture for 6 weeks. Wrist braces were provided to both groups to wear at night, and compliance was monitored. Main Outcome Measurements The primary outcome measurement was subject-reported change in the Carpal Tunnel Self Assessment Questionnaire (CTSAQ) Symptom and Function scales immediately after and at 2 weeks and 3 months after the final treatment. The secondary outcomes included tip and key pinch strength and combined sensory index. Results Compared with pretreatment baseline values, subjects in the acupuncture group had 0.58 improvement ( P = .03) on the CTSAQ Symptom scale score at 3 months after the last treatment, whereas 0.81 improvement ( P = .001) was noted in the placebo acupuncture group. No statistically significant difference was found between the groups treated with acupuncture and placebo acupuncture with respect to improvement in CTS symptoms, function, tip/key pinch, or combined sensory index. Conclusions To our knowledge, this study is the first randomized, placebo-controlled, double-blinded prospective study of traditional acupuncture for CTS. Both the treatment and placebo groups demonstrated improvements from baseline. Acupuncture was not shown to be superior to placebo acupuncture when used in conjunction with bracing for patients with mild to moderate CTS.

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.

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, approximately 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; P0.0001; unpaired t-test). Test-retest correlation for boys with DMD was high (r = 0.91). Stride length (R(2) = 0.89; P0.0001) 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.

To determine whether a new upper extremity exercise device integrated with a video game (GameCycle) requires sufficient metabolic demand and effort to induce an aerobic training effect and to explore the feasibility of using this system as an exercise modality in an exercise intervention.Pre-post intervention.University-based research facility. SUBJECT POPULATION: A referred sample of 8 adolescent subjects with spina bifida (4 girls, 15.5 +/- 0.6 years; 4 boys, 17.5 +/- 0.9 years) was recruited to participate in the project. All subjects had some level of mobility impairment that did not allow them to participate in mainstream sports available to their nondisabled peers. Five subjects used a wheelchair full time, one used a wheelchair occasionally, but walked with forearm crutches, and 2 were fully ambulatory, but had impaired gait.Peak oxygen uptake, maximum work output, aerobic endurance, peak heart rate, rating of perceived exertion, and user satisfaction.Six of the 8 subjects were able to reach a Vo2 of at least 50% of their Vo2 reserve while using the GameCycle. Seven of the 8 subjects reached a heart rate of at least 50% of their heart rate reserve. One subject did not reach either 50% of Vo2 reserve or 50% of heart rate reserve. Seven of the 8 subjects increased their maximum work capability after training with the GameCycle at least 3 times per week for 16 weeks.The data suggest that the GameCycle seems to be adequate as an exercise device to improve oxygen uptake and maximum work capability in adolescents with lower extremity disability caused by spinal cord dysfunction. The subjects in this study reported that the video game component was enjoyable and provided a motivation to exercise.

The electromyographic (EMG) characteristics of human Duchenne muscular dystrophy (DMD) have been well-described. However, to our knowledge, no prior needle electromyographic (EMG) studies of motor unit morphology have been undertaken in muscles from the mdx mouse, an animal that is genetically homologous to DMD. There are significant phenotypic differences between the human and murine dystrophic conditions, bringing into question whether the mdx mouse is an appropriate animal model for DMD. This study was done in order to characterize the EMG findings in mdx mice, compared to normal wild-type mice, and to assess for similarities to DMD. The tibialis anterior and gastrocnemius/soleus muscles from 34 mice (16 C57 wild-type and 18 mdx), divided into four age groups (3, 12, 18, and 24 months), were examined. Wild-type muscles showed normal insertional activity and no abnormal activity at rest. Motor unit action potential (MUAP) parameters were characterized. In contrast to wild-type muscles, mdx muscles showed increased insertional activity, abnormal spontaneous potentials, and the presence of complex repetitive discharges (CRDs). MUAPs showed increased numbers of phases (4.0 ± 0.6, P < 0.001) and duration (7.1 ± 1.2 ms, P < 0.02), as well as late components (15%). These EMG data indicate that mdx muscles display EMG characteristics similar to those found in muscles from boys with DMD, lending credence to the mdx mouse as an animal model for this disease. The data obtained in this study indicate a potential role for EMG as an in vivo, objective measurement tool that could be used longitudinally to monitor the effects of therapeutic interventions in mdx mice. This is important as there are few objective measures of muscle function in murine models that do not require killing the animal. Muscle Nerve, 2006

Chronic Pain in Persons with Neuromuscular Disease Amy J. Hoffman, MPH, Mark P. Jensen, PhD, R. Ted Abresch, MS, Gregory T. Carter, MD* Department of Rehabilitation Medicine, Box 356490, University of Washington School of Medicine, Seattle, WA 98195-6490, USA Multidisciplinary Pain Center, University of Washington Medical Center–Roosevelt, 4245 Roosevelt Way Northeast, Seattle, WA 98105-6920, USA Department of Physical Medicine and Rehabilitation, PM&R TB 191, University of California, Davis, CA 95616, USA

McDonald CM, Widman L, Abresch RT, Walsh SA, Walsh DD. Utility of a step activity monitor for the measurement of daily ambulatory activity in children. Arch Phys Med Rehabil 2005;86:793-801. Objectives: To evaluate the reliability and validity of the StepWatch Activity Monitor (SAM) as a reliable and valid measurement tool for assessing ambulatory activity in able- bodied children and to assess the ambulatory activity of able- bodied children. Design: Descriptive study. Setting: General community. Participants: Ninety-seven able-bodied children, aged 6 to 20 years. Interventions: Not applicable. Main Outcome Measures: Anthropometric parameters, cal- ibration of a step activity monitor to ensure accuracy, and 3 days of simultaneous heart rate and step activity monitoring. Results: The SAM had an accuracy of 99.87% compared with the observer-counted steps and was shown to be valid and reliable when compared with heart rate monitoring. The sub- jects in all age groups (6 -10y, 11-15y, 16 -20y) spent most of their active time at low step rate but took the fewest steps at this rate. Although the least amount of time was spent at high step rate, it accounted for the most steps. The 6- to 10-year-old group took more total steps per day than any of the other groups. Boys spent significantly more time at high step rate than girls in all age groups (mean for boys, 664min/d; girls, 474 min/d). Conclusions: The SAM is an accurate, valid, and useful tool for measuring continuous, time-based step activity during real

McDonald CM, Widman LM, Walsh DD, Walsh SA, Abresch RT. Use of step activity monitoring for continuous physical activity assessment in boys with Duchenne muscular dystrophy. Arch Phys Med Rehabil 2005;86:802–8. Objectives To evaluate the StepWatch Activity Monitor (SAM) as a quantitative measure of community ambulation, to investigate activity patterns and heart rate of ambulatory boys with Duchenne muscular dystrophy (DMD), and to correlate the step activity with measures of body composition and strength. Design Case-control study. Setting General community and laboratory. Participants Sixteen ambulatory boys with DMD and 20 male controls (age range, 5–13y). Interventions Not applicable. Main outcome measures Laboratory determinations of body composition, knee extension strength, and minute-by-minute step rate and heart rate during 3 days of community activity. Results During the 3 days of activity, DMD subjects, when compared with controls, (1) had significantly more inactive minutes (1096±90min/d vs 1028±85min/d), (2) took significantly fewer steps and spent fewer minutes at moderate (66±31min/d vs 94±30min/d) and high step rates (43±30min/d vs 72±38min/d), (3) had higher resting heart rate (110±12 beats/min vs 94±7 beats/min) and lower increase in heart rate with increased step rate, and (4) had lower maximum heart rates (164±24 beats/min vs 208±16 beats/min). Percentage of body fat and knee extension strength correlated with total step activity in the DMD group but not in the control group. Conclusions Step-rate monitoring with the SAM provides useful outcome measures with which to evaluate the activity of ambulatory boys with DMD. Their heart rate did not increase with activity to the same degree as observed in the control group.

An open label trial of modafinil was conducted to determine whether it would be tolerated and effective in treating fatigue for people with amyotrophic lateral sclerosis (ALS). Fifteen patients with ALS were treated for two weeks with either 200 mg or 400 mg of modafinil. Reported side effects of the medication were mild and included diarrhea, headache, nervousness, and insomnia. Side effects did not result in any study dropouts. Following treatment, mean scores on the Fatigue Severity Scale (FSS) decreased from 51.3 (SD 9.2) to 42.8 (SD 10.2). On the Epworth Sleepiness Scale (ESS), mean scores decreased from 8.2 (SD 2.0) to 4.5 (SD 2.4). Reductions in both the FSS and the ESS were significant at p < 0.001. Mean scores on the self-report version of the Functional Independence Measure (FIM-SR) increased from 115.2 (SD 5.6) to 118.1 (SD 5.4), with p < 0.01. This pilot study suggests that modafinil is well-tolerated and may reduce symptoms of fatigue in ALS. Further blinded, controlled studies of modafinil in larger numbers of ALS patients are warranted.

This article reviews the current status of exercise training and contraction-induced muscle-injury investigations in animal models of muscular dystrophy. Most exercise-training studies have compared the adaptations of normal and dystrophic muscles with exercise. Adaptation of diseased muscle to exercise occurs at many levels, starting with the extracellular matrix, but also involves cytoskeletal architecture, muscle contractility, repair mechanisms, and gene regulation. The majority of exercise-injury investigations have attempted to determine the susceptibility of dystrophin-deficient muscles to contraction-induced injury. There is some evidence in animal models that diseased muscle can adapt and respond to mechanical stress. However, exercise-injury studies show that dystrophic muscles have an increased susceptibility to high mechanical forces. Most of the studies involving exercise training have shown that muscle adaptations in dystrophic animals were qualitatively similar to the adaptations observed in control muscle. Deleterious effects of the dystrophy usually occur only in older animals with advanced muscle fiber degeneration or after high-resistive eccentric training. The main limitations in applying these conclusions to humans are the differences in phenotypic expression between humans and genetically homologous animal models and in the significant biomechanical differences between humans and these animal models.

This review summarizes the literature regarding the fatigue properties of skeletal muscles in animal models of neuromuscular disease and the effect of exercise training on these properties in diseased muscles. Results of these studies are not consistent. Reasons for the variability may include the use of differing experimental conditions, varying stimulation protocols, different methods of muscle preparation, and a range of temperatures and ages. Despite the variability and small sample sizes, these studies of muscle fatigue have revealed definite trends. Whereas the slow oxidative soleus muscle from the diseased animals fatigued more slowly or at the same rate as controls, the extensor digitorum longus (a fast, glycolytic muscle) from the diseased animals fatigued more rapidly than controls. The diaphragm-a fast, oxidative, glycolytic muscle that is generally fatigue resistant- did not reveal significant changes in fatigability. Exercise training had a minimal impact on the fatigue properties of skeletal muscle from diseased animals. As molecular and biochemical mechanisms are further identified and defined, additional therapeutic interventions may become available for these disorders. It is hoped that this review will serve as a guide for investigators who use an animal model to evaluate interventions for neuromuscular diseases.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, ultimately fatal, motor neuron disease that poses a myriad of clinical and end-of-life problems. The needs of advanced ALS patients are well suited to the interdisciplinary, multi-modality setting of hospice, where comprehensive palliative strategies may ease suffering and allow the patient to die with dignity in the home. Unfortunately, hospice services are far underutilized in this setting. There is a great need to increase awareness of both patients and clinicians regarding the effectiveness of hospice in the care of advanced ALS patients.