Practice Parameter: Corticosteroid treatment of Duchenne dystrophy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

Department of Neurology, University of Rochester School of Medicine and Dentistry, NY, USA.
Neurology (Impact Factor: 8.29). 02/2005; 64(1):13-20. DOI: 10.1212/01.WNL.0000148485.00049.B7
Source: PubMed


The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence.
To review available evidence on corticosteroid treatment of boys with Duchenne dystrophy.
Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification, and areas for future research are defined.
Seven class I studies and numerous less rigorous trials all demonstrated that corticosteroid treatment for 6 months with prednisone (0.75 or 1.5 mg/kg/day) increased muscle strength, performance, and pulmonary function and significantly slowed the progression of weakness. Two class I trials examined the effect of lower dosage of prednisone (0.30 and 0.35 mg/kg/day), demonstrated lesser but similar benefits, and showed a lower frequency of side effects (e.g., weight gain). The only significant side effects in all class I trials were weight gain and development of a cushingoid facial appearance. One longer-term trial of daily prednisone (0.3 to 0.7 mg/kg/day), a class III study, showed prolongation of functional ability and slower progression of weakness in patients during 3 years of treatment. One class IV, open trial of alternate-day prednisone (2 mg/kg for 2 months, then two-thirds dose every other day) extended ambulation by approximately 2 years in treated compared with untreated patients. Deflazacort, a corticosteroid similar in structure to prednisone, produced similar improvement in muscle strength and function with a similar side effect profile.
Prednisone has been demonstrated to have a beneficial effect on muscle strength and function in boys with Duchenne dystrophy and should be offered (at a dose of 0.75 mg/kg/day) as treatment. If side effects require a decrease in prednisone, tapering to dosages as low as 0.3 mg/kg/day gives less robust but significant improvement. Deflazacort (0.9 mg/kg/day) can also be used for the treatment of Duchenne dystrophy in countries in which it is available. Benefits and side effects of corticosteroid therapy need to be monitored. The offer of treatment with corticosteroids should include a balanced discussion of potential risks.


Available from: Christine K Wade
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    • "Corticosteroids have been proposed as a pharmacological therapy for dystrophinopathies, in order to counteract muscle necrosis, inflammation and to reduce the muscle membrane susceptibility to damage (Abdel-Hamid and Clemens, 2012). In particular, prednisone (Griggs et al., 1991, 1993; Bonifati et al., 2000) and deflazacort (Bonifati et al., 2000) induce improvement and a long-term stabilization of the muscle strength (Bonifati et al., 2000), as well as a substantial reduction of weakness progression in DMD patients (Moxley et al., 2005). Moreover, since the elevation of cytosolic calcium concentration can trigger apoptotic and/or necrosis events in the dystrophic muscles, such physiological alteration represents another important glucocorticoid-based therapeutic target. "
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    ABSTRACT: There are no specific treatments for muscular degeneration caused by muscular dystrophies and for muscle wasting caused by cachexia or sarcopenia. Corticosteroid medications for dystrophic patients only helps to control inflammatory process and slightly delay the progression of the disease. Walkers and wheel chairs are the only options to maintain patients’ independence and walking capabilities until respiratory muscles become weak and mechanical ventilation is mandatory. On the other hand myostatin inhibition, melanocortin-4 receptor antagonists, β-blockers, IL-6 antagonism, and synthetic ghrelin are promising treatments for cachectic animal models. Although in both cases muscular degeneration is relevant the translational therapeutic attempts to find a possible cure are well defined. Molecular treatments are common options to explore beneficial treatments for cachexia, and gene/cell therapies are mostly employed to induce the phenotypic improvement of dystrophic muscles. This review deals with the use of molecular administrations and gene/stem cell therapy to treat muscular degenerations. It reviews previous trials using cell delivery protocols in mice and patients starting with the use of donor myoblasts, outlining the likely causes for their poor results and briefly focusing on satellite cell studies that raise new hope. Then it proceeds to describe recently identified stem/progenitor cells in relationship to their ability to home within a dystrophic muscle and to differentiate into skeletal muscle cells. Different known features of various stem cells are compared in this perspective, and the few available examples of their use in animal models of muscular degeneration are reported. This review also provides an outline of the role of microRNAs to control myogenic commitment. Finally, based on our current knowledge and the rapid advance in stem cell biology a prediction of clinical translation for cell therapy protocols combined with molecular treatments is discu
    Frontiers in Physiology 04/2014; 5:119. DOI:10.3389/fphys.2014.00119 · 3.53 Impact Factor
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    • "Glucocorticosteroids have become the standard treatment for DMD and are the only medication currently available that slows the decline in muscle strength and function, which in turn reduces the risk of scoliosis [21] [22] [23] [24]. However, patients who receive glucocorticosteroids have an increased risk of osteoporosis and vertebral fractures. "
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    ABSTRACT: Objective Presentation of previously unreported results and 5-year follow-up of balloon kyphoplasty used to treat an 8-year-old patient with refractory vertebral compression fractures resulting from 3 years of corticosteroid treatment for Duchenne muscular dystrophy. Summary of Background Data Long-term corticosteroid treatment in patients with DMD has been used to try and improve muscle strength, prolong ambulation, and lower the prevalence of scoliosis. However, these patients have an increased risk of osteoporosis and vertebral fractures. Methods The patient was an 8-year-old boy with Duchenne muscular dystrophy who had received corticosteroid treatment for 3 years, with refractory vertebral compression fractures at T11, L1, and L3. Balloon kyphoplasty was performed at the 3 vertebral bodies using careful technique. Results The patient achieved immediate pain relief after the procedure. The height of the treated vertebrae remained stable without further collapse over a 5-year follow-up period. At 5-year follow-up, the patient developed 2 new vertebral compression fractures at T12 and L2 adjacent to the treated vertebrae. The treatment also did not affect the growth of the treated vertebrae or the patient's overall growth. Conclusions Because the procedure resulted in rapid stabilization of the treated vertebrae, effective analgesia, and no effect on the growth of the treated vertebrae over a 5-year follow-up period, balloon kyphoplasty was a good therapeutic option for this pediatric patient.
    03/2014; 2(2):152–157. DOI:10.1016/j.jspd.2013.10.001
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    • "However, discontinuation of the drug due to intolerable side effects leads to exclusion of clinical trial participants, while in our study patients were not excluded from PSL group, even if they discontinued the medication shortly after starting it. The American Academy of Neurology [27] and the Cochrane review [6] evaluated all RCTs on the use of GCs in DMD and concluded that PSL administered at 0.75 mg/kg/day was effective. However, a broadly accepted GC dose–response relationship has not been defined [6]. "
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    ABSTRACT: We evaluated the long-term efficacy of prednisolone (PSL) therapy for prolonging ambulation in Japanese patients with genetically confirmed Duchenne muscular dystrophy (DMD). There were clinical trials have shown a short-term positive effect of high-dose and daily PSL on ambulation, whereas a few study showed a long-term effect. Especially in Japan, "real-life" observation was lacking. We utilized the national registry of muscular dystrophy in Japan for our retrospective study. We compared the age at loss of ambulation (LOA) between patients in PSL group and those in without-PSL group. Out of 791 patients' in the Remudy DMD/BMD registry from July 2009 to June 2012, 560 were matched with inclusion criteria. Of the 560, all were genetically confirmed DMD patients, 245 (43.8 %) of whom were treated with PSL and 315 (56.2 %) without PSL. There was no difference between the two groups regarding their mutational profile. The age at LOA was significantly greater (11 month on average) in the PSL group than in the without-PSL group (median, 132 vs. 121 months; p = 0.0002). Although strictly controlled clinical trials have shown that corticosteroid therapies achieved a marked improvement in ambulation, discontinuation of the drug due to intolerable side effects led to exclusion of clinical trial participants, which is considered as unavoidable. In our study, patients were not excluded from the PSL group, even if they discontinued the medication shortly after starting it. The results of our study may provide evidence to formulate recommendations and provide a basis for realistic expectations for PSL treatment of DMD patients in Japan, even there are certain limitations due to the retrospectively captured data in the registry.
    Journal of Neurology 09/2013; 260(12). DOI:10.1007/s00415-013-7104-y · 3.38 Impact Factor
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