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Duchenne muscular dystrophy (DMD) is a genetic disorder in which the inherited absence of a muscle protein results in the progressive deterioration of muscle strength and eventual death. Research studies have suggested that the downward course of the illness may be slowed significantly by treatment with steroid drugs. In a previous study, it was not only demonstrated that prednisone was superior to placebo in maintaining muscle strength, but also that a daily dose of prednisone was superior to treatment every other day. When these findings became conclusive, 92 boys participating in the study were all placed on daily prednisone therapy. The results from two years of treatment (three, if counting the previous experimental period) now indicate that the steroid therapy has significantly slowed the progression of DMD. Data at the end of three years may indicate that improvement was related to several factors. The boys experienced an increase in muscle strength when they began prednisone treatment; it is possible that this temporary increase gave them an advantage, and that the rate of decline after the first six months has been about the same. Regular measurements of muscle strength and performance indicate that this is not the case. The boys experienced an increase in muscle strength which peaked by six months. However, the decline in muscle strength thereafter occurred at a slower rate than is generally observed among patients with DMD. Indeed, the expected annual decline in muscle performance scores is almost five times greater than the decline that has been observed among the prednisone-treated patients. These results confirm that prednisone slows the progression of DMD for at least three years. The benefits of prednisone must be weighed against the side effects of steroid treatment, which include weight gain and the typical puffiness of the skin. (Consumer Summary produced by Reliance Medical Information, Inc.)

A drug called prednisone improves the strength and ability to move about in patients with Duchenne's muscular dystrophy. The patients tested were all young boys, aged five to 15 years. Improvement began after as little as a month and peaked at three months. They became almost twice as fast at rising from a lying position to a standing position. They could walk short distances about a third again as fast as before. The could climb four stair steps nearly twice as fast and could breathe more deeply. Some boys received a higher dose of the drug and some a lower dose, but the size of the dose did not affect their rate of improvement. However, patients who needed braces or wheelchairs before treatment still needed them following administration of the drug. More of a substance called creatine, produced when muscles grow, was detected in their urine, suggesting that the drug helped their muscles to grow. Adverse side effects include weight gain, excessive hair growth, and an accumulation of fat on the face, neck and trunk.

Introduction: The Accurate Test of Limb Isometric Strength (ATLIS) device can reliably measure the strength of 12 muscle groups using a fixed load cell. The purpose of this study was to analyze ATLIS data from healthy adults to calculate an individual's predicted strength scores., Methods: ATLIS data were collected from 432 healthy adults. Linear regression models were developed to predict each muscle group's strength. The R-squared statistic assessed variability accounted for by the models., Results: Simple main effects models stratified by gender were used to establish regression equations for each muscle using factors of age, weight, and height., Conclusions: Normalizing raw strength scores controls for biometric factors, thus enabling meaningful comparisons between subjects and allowing each muscle to contribute equally to a summary score. Normalized scores are easily interpreted for broad clinical uses, and derived summary scores establish individuals' disease progression rates using a common scale, allowing for more efficient clinical trials., (Copyright © 2012 Wiley Periodicals, Inc.)

We describe a large family with amyotrophic lateral sclerosis (ALS) caused by an I113T mutation in superoxide dismuatse type 1 (SOD1). The proband developed symptoms typical for ALS at age 39 years and is still walking five years later. Marked phenotypic variability is manifested by her mother with onset of gait difficulty and decision-making problems at age 67 years and a five-year course marked by progressive mild upper motor neuron weakness, frontotemporal dementia and chorea. An aunt's initial symptoms included foot numbness and an uncle with the mutation is asymptomatic. Penetrance is only 50% at age 60 years and 88% at age 80 years with an 86-year-old woman harboring the mutation and having a normal neurologic examination. This family highlights the extreme variability in age of onset, clinical manifestations, disease progression and penetrance due to the I113T SOD1 mutation.

Daily prednisone improves strength in boys with Duchenne muscular dystrophy, but side effects are almost universal. We used a different dosing regimen of prednisone to determine if benefit to boys with Duchenne muscular dystrophy might be maintained with fewer side effects. Twice weekly oral prednisone was given each Friday and Saturday (5mg/kg/dose). This total dose is twice as high as the daily low dosage prednisone regimen (0.75 mg/kg/day). Twenty boys (8.0+/-1.2 years) were treated. Historical control groups included 18 untreated boys (6.1+/-1.6 years) and four boys (7.3+/-0.6 years) treated with daily prednisone. Strength (using a hand-held manometer and grip meter) and timed functional testing were measured. There was an improvement in upper extremity strength for 95% of boys (n=20) at 6 months using quantitative strength testing. Improvement in lower extremity strength occurred in all boys with antigravity quadriceps strength (17/17). The improvement (P=0.001 for proximal upper extremities; P=0.002 for grip; and P<0.0001 for proximal lower extremities) was significant compared to untreated boys. Sixteen boys were treated continuously for more than 12 months (22+/-1.5 months). Of these, 15 remained significantly stronger than prior to treatment and 8/16 showed additional gains in strength after six months of treatment. Six boys were on the weekly prednisolone 2 years or longer without interruption. All six had upper and lower extremity strength at follow-up that was as good or better than at baseline. Functional testing improved in boys less than 8 years without contractures. Three boys without antigravity quadriceps strength at the start of treatment lost the ability to walk unassisted within 6 months. Eight other boys lost the ability to ambulate unassisted between 12 and 24 months of treatment. In each, progressive contractures developed. Linear growth was maintained in all boys on weekly treatment. Obesity rates did not differ from untreated boys. Twice weekly prednisone improved strength over 6-12 months in the majority of boys, but did not slow contracture development. Sustained benefit beyond 12 months is possible with fewer side effects compared to daily prednisone.

The purpose of this study was to document the intrarater reliability of manual muscle test (MMT) grades in assessing muscle strength in patients with Duchenne's muscular dystrophy (DMD). Subjects were 102 boys, aged 5 to 15 years, who were participating in a double-blind, multicenter trial to document the effects of prednisone on muscle strength in patients with DMD. Four physical therapists participated in the study. Two identical (duplicate) evaluations were performed within 5 days of each other by the same examiner initially and after 6 and 12 months of treatment. A total of 18 muscle groups were tested on each patient, 16 of them bilaterally, using a modification of the Medical Research Council scale. Reliability of muscle strength grades obtained for individual muscle groups and of individual muscle strength grades was analyzed using Cohen's weighted Kappa. The reliability of grades for individual muscle groups ranged from .65 to .93, with the proximal muscles having the higher reliability values. The reliability of individual muscle strength grades ranged from .80 to .99, with those in the gravity-eliminated range scoring the highest. We conclude the MMT grades are reliable for assessing muscle strength in boys with DMD when consecutive evaluations are performed by the same physical therapist.

There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.