Function In Duchenne Muscular Dystrophy Research Articles

G.P.9.09 Immediate release oral pentoxifylline is poorly tolerated in Duchenne muscular dystrophy boys

Objectives: The objective of this open label pilot study of oral, immediate release pentoxyfylline was to assess the tolerability, safety and efficacy on muscle strength and function in Duchenne muscular dystrophy (DMD). Methods: This was an open label prospective study with a 3 month lead-in period followed by 12 months of treatment with a 20mg/kg/day dose of pentoxifylline (maximal administered dose was 598mg/day). Study subjects were 4–9 year-old steroid-naive DMD boys. The primary efficacy measure was a total quantitative muscle testing (QMT) score.

Effect of Long-term Steroids on Cough Efficiency and Respiratory Muscle Strength in Patients With Duchenne Muscular Dystrophy

The objective of this study was to determine whether long-term steroid therapy is associated with increased peak cough flow in patients with Duchenne muscular dystrophy and to determine which pulmonary function test variable is most predictive of peak cough flow. In this case-control study, the medical charts of patients who had Duchenne muscular dystrophy and had pulmonary function tests at our institution in the previous 2 years were examined. Steroid-treated patients were on therapy for at least 1 year. The measured pulmonary function tests included forced vital capacity, maximum expiratory pressure, maximum inspiratory pressure, maximum voluntary ventilation, and peak cough flow. Multiple linear regression analysis was used to determine which pulmonary function test measure was most predictive of peak cough flow and assess the influence of steroid treatment and patient age on peak cough flow. Ten steroid-treated and 25 untreated patients were analyzed. Peak cough flow and maximum expiratory pressure were significantly higher in the steroid-treated patients. Each of the pulmonary function test variables was significantly associated with peak cough flow. The linear model that had the highest adjusted r2 value included only 2 variables: maximum voluntary ventilation and steroid treatment, demonstrating that steroid-treated patients had peak cough flow values that were 27 L/min higher than the untreated patients. The interaction between maximum voluntary ventilation and steroid was not statistically significant, suggesting that the steroid-associated increase in peak cough flow was approximately constant over the observed range of maximum voluntary ventilation values. The effects of maximum voluntary ventilation and treatment group on peak cough flow were not confounded with the patient age. Long-term steroid therapy is associated with improved peak cough flow and respiratory muscle strength in patients with Duchenne muscular dystrophy. Maximum voluntary ventilation may be a useful predictor of lung function in Duchenne muscular dystrophy.

Posterior Spinal Fusion for Scoliosis in Duchenne Muscular Dystrophy Diminishes the Rate of Respiratory Decline

To assess the rate of decline in pulmonary function in Duchenne muscular dystrophy (DMD) before and after posterior spinal fusion for scoliosis. To compare the rate of respiratory decline using percent normal forced vital capacity (%FVC) measurements before and after posterior spinal fusion. Posterior spinal fusion for scoliosis is used widely in DMD, although the long-term pulmonary effects have not been well established. Fifty-six patients were assessed. Percent forced vital capacity was the outcome parameter with data analysis using a mixed-model repeated-measures ANOVA and paired t tests. Group 1: Inclusion criteria were a diagnosis of DMD, 2 or more pulmonary function tests presurgery, and 2 or more postsurgery. Group 2: The rates of respiratory decline before and after spinal fusion for the whole study population were determined by within-subjects mixed-model regression analysis to account for the varying number of FVC studies between patients and unequal spacing between tests. Group 1: 20 patients. Mean length of time of respiratory value determination was 2.5 +/- 1.0 years presurgery and 5.6 +/- 2.8 years postsurgery. Mean rate of decline presurgery was 8.0% +/- 4.1% per year, which decreased to 3.9% +/- 1.9% per year postsurgery (paired t test = 4.58, P < 0.0001). Group 2: 56 patients. The respiratory value determinations ranged from 4 years presurgery to 8 years postsurgery. The rates of respiratory decline based on the whole study population were 4% per year presurgery, which decreased to 1.75% per year postsurgery (F-test comparison of slopes = 19.71, P < 0.0001). Posterior spinal fusion for scoliosis in DMD is associated with a significant decrease in the rate of respiratory decline postsurgery compared with presurgery rates.

Steroid Treatment for Cardiac Function in Duchenne Muscular Dystrophy

Cardiology & Cardiac Surgery| May 01 2006 Steroid Treatment for Cardiac Function in Duchenne Muscular Dystrophy AAP Grand Rounds (2006) 15 (5): 58–59. https://doi.org/10.1542/gr.15-5-58-a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Steroid Treatment for Cardiac Function in Duchenne Muscular Dystrophy. AAP Grand Rounds May 2006; 15 (5): 58–59. https://doi.org/10.1542/gr.15-5-58-a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cardiac function, duchenne's muscular dystrophy, steroid therapy Source: Markham LW, Spicer RL, Khoury PR, et al. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005;26:768–771. A 7-year experience at 2 institutions, Cincinnati’s Children’s Hospital Medical Center, Ohio, and the University of Iowa, Iowa City, was reviewed to test the hypothesis that corticosteroid treatment for long-term Duchenne muscular dystrophy (DMD)1,2 stabilizes cardiac muscle function. One hundred eleven subjects under age 21 years with DMD were divided into treated (steroid treatment >6 months, n=48) and untreated (steroid treatment <6 months, n=63) groups. Of the 48 treated patients, 29 received prednisone, and 19 received deflazacort (a derivative of prednisolone reported to cause less weight gain).3 Steroid treatment was begun at a mean age of 6.7 years and continued, on average, for 3 years. Treatment dose was not evaluated owing to variability within the study group. Ten subjects had had a prior course of corticosteroids (mean duration 4 years) that had been discontinued. Shortening fraction (SF), derived from M-mode echocardiography, was obtained in all cases and compared between the treated and untreated groups. The mean SF in the treated group was 36% compared with 30% in the untreated group (P<.001). For each year of age, the odds of a depressed SF increased 30% in the untreated group relative to the treated group. There were no demonstrable differences in cardiac function between the prednisone and deflazacort treatment subgroups. The group of patients who had a prior course of steroids maintained a mean SF of 35%, which was significantly higher than that of the untreated group but not demonstrably different from those actively receiving corticosteroids. The authors conclude that the clinical benefits of steroid therapy in DMD extend to cardiac function, that these benefits appear to persist even after discontinuation of therapy, and that the benefits outweigh the risks of side effects from chronic steroid use. Dr. Danford has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Pediatricians and cardiologists are taught as general dogma that chronic use of corticosteroids is to be avoided, in part because of the cardiovascular damage that might be done. Contrary to this widespread belief, the above report strongly suggests that in DMD these medications are actually helpful for the heart. The retrospective study design is a weakness that leaves room for other interpretations of the data. We wonder, of course, if the patients who received steroid treatment were the beneficiaries of more meticulous management of their disease apart from the use of steroids. The authors acknowledge the shortcomings of their retrospective study, but point out that the general noncardiac advantages of steroid treatment for DMD are so great that a placebo-controlled trial design, in which treatment is withheld from some subjects, would be unethical. The best evidence we have (and the best evidence we are likely to... You do not currently have access to this content.

Impaired primary hemostasis with normal platelet function in Duchenne muscular dystrophy during highly-invasive spinal surgery

A defective, normal or enhanced hemostasis has been reported in Duchenne muscular dystrophy (DMD). A retrospective analysis of intra-and postoperative (up to 36 h) estimated blood losses was performed in 156 patients undergoing spinal surgery for: DMD ( n=31), idiopathic scoliosis (IS) ( n=70), poliomyelitis ( n=10), cerebral palsy (CP) ( n=28), spinal muscular atrophy (SMA) ( n=17). Platelet aggregation and bleeding times were also investigated in DMD patients. Immunohistochemistry for dystrophin was performed in platelets, megakaryocytes and blood vessels of normal tissues. DMD patients showed significantly higher intraoperative estimated blood losses (DMD: 3495±890 ml; IS: 2269±804 ml; poliomyelitis: 2582±1252 ml; CP: 2071±683 ml; SMA: 2464±806 ml; P<0.05), while postoperative blood losses were similar among different groups. Higher estimated blood losses in DMD were independent of the duration of surgery, body weight, gender, age, vertebral levels or preoperative Cobb angle. DMD children had significantly prolonged bleeding times, but retained normal platelet function. From control samples dystrophin was expressed in vascular smooth muscle cells, but not in platelets. DMD appears to be characterized by immediate bleeding during highly-invasive surgery and increased bleeding time without platelet abnormalities. Considering dystrophin expression in normal vascular smooth muscle cells, these results altogether suggest a selective defect of primary hemostasis in DMD, likely to be due to impaired vessel reactivity.

Report of a Muscular Dystrophy Campaign funded workshop Birmingham, UK, January 16th 2004. Osteoporosis in Duchenne muscular dystrophy; its prevalence, treatment and prevention

A Muscular Dystrophy Campaign funded workshop to look into the potential problems of osteoporosis occurring in boys with DMD treated with steroids took place in Birmingham (UK) on the 16th January 2004. Fourteen participants met from varied backgrounds including, paediatric neuromuscular disease, neurology, paediatric and adult metabolic bone disease, paediatric rheumatology, genetics, physiotherapy and medical physics together with a representative from the Muscular Dystrophy Campaign. The aims of the workshop were to assess the evidence for the risk of osteoporosis in Duchenne muscular dystrophy (DMD), to assess the adverse effects of corticosteroid (steroid) treatment relating to bone mineral density and longitudinal growth and to assess the current evidence for the prevention and treatment of osteoporosis. Steroids are increasingly used in boys with DMD following the evidence from randomised controlled trials on their short-term benefit. However, the balance between long-term benefit and side effects has not been established. Long-term steroid use may be associated with significant side effects including weight gain, growth failure, cataracts and osteoporosis, so the development of strategies to prevent or treat these complications is important. We reviewed the literature to determine

Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) causes a progressive impairment of muscle function leading to hypercapnic respiratory failure. Most studies of respiratory function in DMD have been cross-sectional rather than longitudinal, and these data have not been related to survival. We retrospectively studied 58 patients with DMD with at least 2 yr of follow-up spirometry and known vital status. Spirometry was abnormal at entry: median FEV(1) 1.60 L (range 0.4 to 2.6 L), FVC 1.65 L (range 0.45 to 2.75 L), FVC 64% predicted (range 29 to 97%). Individual rates of change of vital capacity varied, with a median annual change of -0.18 L (range 0.04 to -0.74 L), -8.0% predicted FVC (range 2 to -39%). During the study 37 patients died; the median age of death, calculated by Kaplan-Meier analysis, was 21.5 yr (range 15 to 28.5 yr). The age when vital capacity fell below 1 L was a strong marker of subsequent mortality (5-yr survival 8%). The maximal vital capacity recorded and its rate of decline (however expressed) predicted survival time. Repeated spirometric measurement provides a simple and relatively powerful means of assessing disease progression in these patients and should be considered when planning treatment trials.

Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is not treatable; there is no cure. More than a decade ago, randomized trials demonstrated that oral steroid therapy was of benefit to DMD patients by prolonging ambulation. Although few significant side effects were reported, study patients were followed for 18 months or less. However, when treating DMD with steroids, the clinician must consider beginning treatment in mid-childhood and continuing until adolescence or longer, a total of at least 10 years. There is no evidence that steroids are associated with prolonged life or with improved pulmonary or cardiac function in DMD. It is clear that the risk of side effects increases with duration of use of oral steroids. Therefore, oral steroids are not recommended for treatment of DMD on a routine basis. If, in certain cases, one does institute therapy, the patient should be monitored carefully for side effects, maintain dietary restriction, and exercise regularly.

Correlation between progression of spinal deformity and pulmonary function in Duchenne muscular dystrophy.

The purpose of this study was to investigate how age at and value of the plateau of vital capacity (VC plateau) correlate with the severity of the progression of spinal deformity in patients with Duchenne muscular dystrophy (DMD). Changes in spinal deformity and pulmonary function in 36 DMD patients were examined in a retrospective longitudinal study. Patterns of progression of spinal deformity were classified into three types according to Oda's classification. Of the 32 patients who showed spinal deformity, six were classified as type 1, 19 as type 2, and seven as type 3. The correlation between the patterns of progression of spinal deformity and the VC plateau was examined using a discriminant analysis. Rapid and severe progression of spinal deformity could be expected in patients whose VC plateau was less than 1,900 mL and in those in which it occurred before age 14 years. Thus VC plateau may be an indicator of the severity of the progression of spinal deformity in DMD patients.

Correlation between Progression of Spinal Deformity and Pulmonary Function in Duchenne Muscular Dystrophy

The purpose of this study was to investigate how age at and value of the plateau of vital capacity (VC plateau) correlate with the severity of the progression of spinal deformity in patients with Duchenne muscular dystrophy (DMD). Changes in spinal deformity and pulmonary function in 36 DMD patients were examined in a retrospective longitudinal study. Patterns of progression of spinal deformity were classified into three types according to Oda's classification. Of the 32 patients who showed spinal deformity, six were classified as type 1, 19 as type 2, and seven as type 3. The correlation between the patterns of progression of spinal deformity and the VC plateau was examined using a discriminant analysis. Rapid and severe progression of spinal deformity could be expected in patients whose VC plateau was less than 1,900 mL and in those in which it occurred before age 14 years. Thus VC plateau may be an indicator of the severity of the progression of spinal deformity in DMD patients.

The effect of methylprednisolone on intracellular calcium of normal and dystrophic human skeletal muscle cells

Clinical trials have shown that a glucocorticoı̈d, the methyiprednisolone (PDN), has a beneficial effect on muscle strength and function in Duchenne muscular dystrophy (DMD) patients. The aim of this study was to test if the effect of PDN could be mediated via a possible action on intracellular calcium. The intracellular calcium activity, at rest and during calcium mobilizing drug superfusion protocols was recorded in normal and dystrophic human cocultured muscle cells. PDN (10 μM) pretreatment induced an elevation of the resting calcium concentration of 51, 34 and 38% in proliferating normal myoblasts, DMD myoblasts and DMD myotubes, respectively, while normal myotubes resting [Ca2+]i was not altered.

Quantitative MR relaxometry study of muscle composition and function in Duchenne muscular dystrophy.

Magnetic resonance imaging and maps of T1 and T2 values were used to study muscle composition in Duchenne muscular dystrophy (DMD). The mean T2 of anterior tibial muscle was 27 msec in healthy control subjects and 43 msec with increased fatty infiltration in DMD patients. In stronger DMD patients, the distribution of muscle T2 values was narrow, centered at 27 msec as in the controls, with a nonoverlapping fat peak centered at 49 msec. In weaker DMD patients, the width of the muscle T2 peak increased and the peak shifted toward the fat peak. Mean muscle T1 decreased from 1.7 to 0.6 second with increasing fatty infiltration. These results show that quantitative T1 and T2 maps may be used to assess muscle status and monitor DMD progression.

Dystrophin expression and somatic reversion in prednisone‐treated and untreated Duchenne dystrophy

The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript.

Methylprednisolone increases dystrophin levels by inhibiting myotube death during myogenesis of normal human muscle in vitro

The glucocorticoid methylprednisolone (Mepd) increased dystrophin and myosin heavy chain levels in differentiated cultures of cloned human myoblasts. Mepd increased the number of myotubes per area by preventing myotube death and detachment during myogenesis in vitro. Myotube death was the result of an endogenous process initiated early during myoblast fusion. It occurred between days 4 and 5 of differentiation (3 days after its initiation) and was inhibited by cycloheximide, indicating that a programmed death mechanism may be involved. Inhibition of myotube death accounted for the increased levels of muscle-specific proteins; the amount of dystrophin per myonucleus was the same with or without Mepd treatment. These effects of glucocorticoids on primary muscle cultures may bear on the recent observation that prednisone transiently enhances muscle function in Duchenne muscular dystrophy.

The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

Selenium and vitamin E treatment of Duchenne muscular dystrophy: no effect on muscle function.

16 boys with Duchenne muscular dystrophy (DMD) were treated with sodium selenite and vitamin E for one year. One group of patients (10 boys) was examined using a battery of tests to assess muscular strength and function and cardiopulmonary function, and by CT scanning of 2 muscle groups over the 4 years prior to treatment. Six boys with DMD entered the study when the treatment was begun. Tests of muscular force and function, cardiopulmonary tests and CT-scanning were performed at the onset of treatment, and after 6 and 12 months. No beneficial effect on either muscular force or function was found during the treatment period. It is concluded that selenium and vitamin E in high doses do not improve muscle function in DMD.

Correlation of scoliosis and pulmonary function in Duchenne muscular dystrophy.

Pulmonary function was correlated with patient age and degree of thoracic scoliosis in 25 patients with Duchenne muscular dystrophy in a retrospective, longitudinal study. The observed forced vital capacity (FVC) was found to peak at approximately the age when standing ceases, then to decline rapidly. Thoracolumbar curves were found to be insignificant in adversely affecting pulmonary function in patients with Duchenne muscular dystrophy. Percent FVC was found to be the parameter of pulmonary function that was most strongly correlated with age and scoliosis measurements. In addition, age and thoracic scoliosis together were better predictors of percent FVC than either one alone. Each 1 year of age had approximately the same negative influence on percent FVC that each 10 degrees of thoracic scoliosis had; both decreased percent FVC by approximately 4%. A regression equation for percent FVC is presented which predicts that the patient who has had scoliosis progression halted by spinal fusion would, subsequent to the surgery, show a slower rate of decline of percent FVC and that this rate is quantifiable, predictable, and dependent solely on the patient's advancing age. Therefore, early spinal instrumentation and fusion is advocated in the patient with Duchenne muscular dystrophy.