We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P less than 0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects.

Two-hundred eighty-three boys with Duchenne dystrophy and 10 with Becker dystrophy have been followed for up to 10 years in a protocol that accurately measured their function, strength, contractures, and back curvature. Clinical heterogeneity is noted. Patients whose muscles were stronger were more likely to die from a cardiomyopathy. Weaker patients died from respiratory failure. A series of milestones is defined, which is of use in following the illness in an individual patient. This approach permits a scoring system that allows the severity of the disease to be defined in an individual boy. Evaluation of physical therapy and surgical intervention shows that night splints and scoliosis surgery are effective forms of treatment.

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.

Prednisone has been shown to improve strength in Duchenne dystrophy. Azathioprine often benefits corticosteroid-responsive diseases and can reduce the dose of prednisone needed. The present study reports a randomized, controlled trial of prednisone and azathioprine designed to assess the longer-term effects of prednisone and to determine whether azathioprine alone, or in combination with prednisone, improves strength. Ninety-nine boys (aged five to 15 years) with Duchenne dystrophy were randomized to one of three groups: (I) placebo; (II) prednisone 0.3 mg/kg/d; or (III) prednisone 0.75 mg/kg/d. After 6 months, azathioprine 2 to 2.5 mg/kg/d was added in groups I and II and placebo added in group III. The study showed that the beneficial effect of prednisone (0.75 mg/kg/d) is maintained for at least 18 months and is associated with a 36% increase in muscle mass. There was weight gain, growth retardation, and other side effects. Azathioprine did not have a beneficial effect. This study suggests that prednisone's beneficial effect is not due to immunosuppression.

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.