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1.  The glucocorticoid receptor N363S polymorphism and steroid response in Duchenne dystrophy 
Background
Steroid administration is beneficial in Duchenne muscular dystrophy (DMD), but the response, incidence, and the severity of side effects are variable.
Aims
To investigate whether glucocorticoid receptor (GRL) gene polymorphisms may be responsible for glucocorticoid sensitivity in DMD.
Methods
Forty eight DMD patients treated either with prednisone or deflazacort were subjected to genetic analyses of the GRL gene.
Results
Mutation studies revealed an heterozygous A to G mutation at GRL cDNA position 1220 in three DMD patients resulting in an asparagine to serine amino acid change at amino acid position 363 (N363S). The N363S carrier DMD patients showed a trend towards a later age at loss of ambulation in comparison with non‐carrier patients.
Conclusions
These data suggest that the N363S GRL polymorphism may be implicated in the long term response to glucocorticoids.
doi:10.1136/jnnp.2005.078345
PMCID: PMC2077532  PMID: 16980656
Duchenne muscular dystrophy; glucocorticoid receptor; SNP; steroid therapy
2.  Long term treatment of polymyalgia rheumatica with deflazacort. 
Annals of the Rheumatic Diseases  1994;53(5):331-333.
OBJECTIVES--To evaluate the long term efficacy and tolerability of deflazacort, a corticosteroid reputed to have only minor side effects, in the treatment of polymyalgia rheumatica (PMR). METHODS--In a prospective open study, deflazacort was administered at an average initial dose of 21.8 mg/day for a mean period of 19 months in 40 patients with PMR. RESULTS--A highly significant improvement of clinical and laboratory parameters occurred one month after therapy onset. This improvement persisted for the whole study period. Laboratory parameters of tolerability did not change during the study. Mild to moderate steroid-related side effects occurred in 57.9% of the patients. CONCLUSIONS--Deflazacort is effective in the treatment of PMR. Its long term safety profile may be superior to that of other corticosteroids.
PMCID: PMC1005333  PMID: 8017988
3.  Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial 
Background
Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B).
Methods
We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences.
Results
During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects.
Conclusion
Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.
Trial registration
This clinical trial was registered at http://www.ClincalTrials.gov, identifier: NCT00527228, and was always freely accessible to the public.
doi:10.1186/1750-1172-8-26
PMCID: PMC3617000  PMID: 23406536
Limb girdle muscular dystrophy (LGMD); Dysferlinopathy; Therapy; Deflazacort; Muscle strength; Steroids
4.  Deflazacort for Type-1 Autoimmune Hepatitis in a Korean Girl 
Journal of Korean Medical Science  2006;21(4):758-760.
Prednisone or prednisolone are the mainstay drug treatments for autoimmune hepatitis in children. However, long-term use of corticosteroid is associated with the risk of steroid-induced toxicities, and this situation requires newer immuno-suppressive agents for the treatment of autoimmune hepatitis, especially in growing children. An 11-yr-old Korean girl with type-1 autoimmune hepatitis discontinued prednisolone due to toxicities, i.e., hirsutism, buffalo hump, and skin striae, and remained clinical and biochemical remission under replacement of deflazacort and ursodeoxycholic acid combination therapy. A follow-up liver biopsy after 19 months of deflazacort and ursodeoxycholic acid treatment showed histologic remission.
doi:10.3346/jkms.2006.21.4.758
PMCID: PMC2729905  PMID: 16891827
Hepatitis, Autoimmune; deflazacort; Child
5.  Changes in bone mass during low dose corticosteroid treatment in patients with polymyalgia rheumatica: a double blind, prospective comparison between prednisolone and deflazacort. 
Annals of the Rheumatic Diseases  1996;55(2):143-146.
OBJECTIVE: To compare the long term effects of low dosage prednisolone or deflazacort treatments on bone mass in patients with polymyalgia rheumatica. METHODS: Thirty patients with polymyalgia rheumatica were allocated on a random double blind basis to receive treatment with prednisolone or deflazacort. Bone mineral content (BMC) was measured in the lumbar spine and in the distal forearm before treatment and three, six, and 12 months after treatment. RESULTS: At three months the decrease in lumbar BMC and bone mineral density (BMD) was significantly greater in the deflazacort group than in the prednisolone group (p < 0.05), but at six and 12 months there was no difference between the two groups. In all patients after one year there was a significant loss of BMC: a 6.4% loss in lumbar BMC and a 1.8% loss in distal forearm BMC. Loss in lumbar BMC after six months was correlated to the cumulative dose of corticosteroid (r = 0.4; p < 0.05) and was significantly greater in the group of patients who had persisting symptoms of polymyalgia at six weeks, three months, or both, after treatment started (p = 0.05). CONCLUSION: This low dose study failed to reveal any calcium sparing properties of deflazacort compared with prednisolone. Possible explanations for this finding are discussed.
PMCID: PMC1010111  PMID: 8712867
6.  Old and new therapeutic developments in steroid treatment in Duchenne muscular dystrophy 
Acta Myologica  2012;31(1):9-15.
Steroids have been used since two decades and several trials were conducted to establish their efficacy in DMD patients with various regimens. The clinical outcomes showed increased function in the treated boys, and in a single trial with deflazacort, prolongation of ambulation but with different side effects. Steroids clinical efficacy is now established. The main concern is to increase steroid efficacy and decrease side effect and toxicity. A trial comparing daily prednisone, deflazacort and intermittent glucocorticoids (prednisone 10 days on/10 days off) (FOR-DMD) is starting under NIH grant. The primary outcomes will be muscle strength, forced vital capacity and patient/parents satisfaction.
PMCID: PMC3440806  PMID: 22655511
Steroids; Duchenne; DMD; side effect; quality of life
7.  Worsening of Cardiomyopathy Using Deflazacort in an Animal Model Rescued by Gene Therapy 
PLoS ONE  2011;6(9):e24729.
We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV) 2/8 by a single intraperitoneal injection into BIO14.6 Syrian hamsters at ten days of age to rescue the phenotype. We then treated the hamsters with deflazacort. Treatment was administered to half of the hamsters that had received the AAV and the other hamsters without AAV, as well as to normal hamsters. Both horizontal and vertical activities were greatly enhanced by deflazacort in all groups. As in previous experiments, the AAV treatment alone was able to preserve the ejection fraction (70±7% EF). However, the EF value declined (52±14%) with a combination of AAV and deflazacort. This was similar with all the other groups of affected animals. We confirm that gene therapy improves cardiac function in the BIO14.6 hamsters. Our results suggest that deflazacort is ineffective and may also have a negative impact on the cardiomyopathy rescue, possibly by boosting motor activity. This is unexpected and may have significance in terms of the lifestyle recommendations for patients.
doi:10.1371/journal.pone.0024729
PMCID: PMC3170375  PMID: 21931833
8.  Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with Duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiovascular magnetic resonance 
Background
Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (εcc).
Methods
We used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (εcc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results.
Results
Patients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although εcc magnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, εcc worsened regardless of treatment group.
Conclusions
These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.
doi:10.1186/1532-429X-13-60
PMCID: PMC3207955  PMID: 22011358
9.  A Dutch guideline for the treatment of scoliosis in neuromuscular disorders 
Scoliosis  2008;3:14.
Background
Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.
Methods
The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.
Results
For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.
Conclusion
In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.
doi:10.1186/1748-7161-3-14
PMCID: PMC2567289  PMID: 18822133
10.  Emerging Drugs for Duchenne Muscular Dystrophy 
Expert opinion on emerging drugs  2012;17(2):261-277.
Introduction
Duchenne muscular dystrophy (DMD) is the most common, severe childhood form of muscular dystrophy. Treatment is limited to glucocorticoids that have the benefit of prolonging ambulation by approximately 2 years and preventing scoliosis. Finding a more satisfactory treatment should focus on maintaining long-term efficacy with a minimal side effect profile.
Areas covered
Authors discuss different therapeutic strategies that have been used in pre-clinical and clinical settings.
Expert opinion
Multiple treatment approaches have emerged. Most attractive are molecular-based therapies that can express the missing dystrophin protein (exon skipping or mutation suppression) or a surrogate gene product (utrophin). Other approaches include increasing the strength of muscles (myostatin inhibitors), reducing muscle fibrosis, and decreasing oxidative stress. Additional targets include inhibiting NF-κB to reduce inflammation, or promoting skeletal muscle blood flow and muscle contractility using phosphodiesterase inhibitors or nitric oxide (NO) donors. The potential for each of these treatment strategies to enter clinical trials is a central theme of discussion. The review emphasizes that the goal of treatment should be to find a product at least as good as glucocorticoids with a lower side effect profile or with a significant glucocorticoid sparing effect.
doi:10.1517/14728214.2012.691965
PMCID: PMC3486431  PMID: 22632414
Duchenne muscular dystrophy; exon skipping; mutation suppression; stop codon readthrough; utrophin; myostatin inhibition; nitric oxide; phosphodiesterase inhibitors; NF-κB inhibition
11.  Acute Urticaria Induced by Oral Methylprednisolone 
Although corticosteroids have immunosuppressive, anti-inflammatory, and anti-allergic effects, allergic reactions are rare. We report a case involving a 52-year-old-female with acute urticaria caused by oral methylprednisolone. The patient had experienced aspirin-exacerbated respiratory disease (AERD) for 13 years with frequent asthma exacerbations. Symptoms of asthma exacerbations improved with short-term treatments of systemic steroids, including methylprednisolone or deflazacort, which had been well tolerated. However, the current admission was prompted by the development of acute generalized urticaria following the oral ingestion of methylprednisolone (8 mg) for relief of symptoms. An oral provocation test with 4 mg oral methylprednisolone led to generalized urticaria 20 minutes later, confirming the causal association. This is the first report of acute urticaria caused by oral methylprednisolone in a patient with AERD.
doi:10.4168/aair.2011.3.4.277
PMCID: PMC3178827  PMID: 21966609
Drug hypersensitivity; methylprednisolone; urticaria
12.  Effect of spinal surgery on lung function in Duchenne muscular dystrophy. 
Thorax  1995;50(11):1173-1178.
BACKGROUND--The effect on subsequent respiratory function of spinal stabilisation for scoliosis in Duchenne muscular dystrophy is unclear. In order to clarify this clinical problem, changes in the forced vital capacity of a group of children with Duchenne muscular dystrophy who had undergone spinal surgery were measured and compared with a group of children with Duchenne muscular dystrophy who had not had surgery. METHODS--In this retrospective study 17 boys with Duchenne muscular dystrophy who underwent spinal stabilisation at a mean age of 14.9 years (surgical group) were compared with 21 boys with Duchenne muscular dystrophy who had not had surgery (non-surgical group). The mean (SD) Cobb angle of the surgical group at 14.9 years was 57 (16.4) degrees, and of the non-surgical group at 15 years was 45 (29.9) degrees. Forced vital capacity expressed as percentage predicted (% FVC) was measured in total over a seven year period in the surgical group and over 6.5 years in the non-surgical group, and regression equations were calculated. Survival curves for both groups were also constructed. RESULTS--No difference was found between spinal stabilisation (surgical group) and the non-surgical group in the rate of deterioration of % FVC which was 3-5% per year. There was no difference in survival in either group. CONCLUSIONS--Spinal stabilisation in Duchenne muscular dystrophy does not alter the decline in pulmonary function, nor does it improve survival.
PMCID: PMC475089  PMID: 8553273
13.  Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures 
BMC Neurology  2012;12:91.
Background
The aim of this study was to perform a longitudinal assessment using Quantitative Muscle Testing (QMT) in a cohort of ambulant boys affected by Duchenne muscular dystrophy (DMD) and to correlate the results of QMT with functional measures. This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or thee 6-min walk test (6MWT).
Methods
This is a single centre, prospective, non-randomised, study assessing QMT using the Kin Com® 125 machine in a study cohort of 28 ambulant DMD boys, aged 5 to 12 years. This cohort was assessed longitudinally over a 12 months period of time with 3 monthly assessments for QMT and with assessment of functional abilities, using the NSAA and the 6MWT at baseline and at 12 months only. QMT was also used in a control group of 13 healthy age-matched boys examined at baseline and at 12 months.
Results
There was an increase in QMT over 12 months in boys below the age of 7.5 years while in boys above the age of 7.5 years, QMT showed a significant decrease. All the average one-year changes were significantly different than those experienced by healthy controls. We also found a good correlation between quantitative tests and the other measures that was more obvious in the stronger children.
Conclusion
Our longitudinal data using QMT in a cohort of DMD patients suggest that this could be used as an additional tool to monitor changes, providing additional information on segmental strength.
doi:10.1186/1471-2377-12-91
PMCID: PMC3482602  PMID: 22974002
14.  Prednisolone improves walking in Japanese Duchenne muscular dystrophy patients 
Journal of Neurology  2013;260:3023-3029.
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.
doi:10.1007/s00415-013-7104-y
PMCID: PMC3843366  PMID: 24057148
Duchenne muscular dystrophy; Prednisolone; Walking; National registry; Natural history
15.  Retinal signal transmission in Duchenne muscular dystrophy: evidence for dysfunction in the photoreceptor/depolarizing bipolar cell pathway. 
Journal of Clinical Investigation  1994;93(6):2425-2430.
There have been reports of abnormal retinal neurotransmission determined by electroretinography in boys with Duchenne and Becker muscular dystrophy. Dystrophin may play a role in transmitting signals between photoreceptors and the excitatory synapse of the ON-bipolar cell. These electroretinographic changes appeared to be limited to the rod ON-pathway but we felt there was also similar abnormality in the cone ON-pathway. We used long-duration stimuli to separate ON-(depolarizing bipolar cell) and OFF (hyperpolarizing bipolar cell) contributions to the cone-dominated ERG to better understand how the retina functions in boys with Duchenne muscular dystrophy. We recorded the electroretinograms of 11 boys with Duchenne muscular dystrophy and found abnormal signal transmission at the level of the photoreceptor and ON-bipolar cell in both the rod and cone generated responses. The OFF-bipolar cell that responds to the offset of the stimulus continues to function normally. The results support our hypothesis that retinal dystrophin plays a role in receptor function or controlling ion channels at the level of the photoreceptor and depolarizing bipolar cell.
PMCID: PMC294450  PMID: 8200977
16.  Physical training in boys with Duchenne Muscular Dystrophy: the protocol of the No Use is Disuse study 
BMC Pediatrics  2010;10:55.
Background
"Use it or lose it" is a well known saying which is applicable to boys with Duchenne Muscular Dystrophy (DMD). Besides the direct effects of the muscular dystrophy, the increasing effort to perform activities, the fear of falling and the use of personal aids indirectly impair leg and arm functions as a result of disuse. Physical training could oppose this secondary physical deterioration. The No Use is Disuse (NUD) study is the first study in human subjects with DMD that will examine whether a low-intensity physical training is beneficial in terms of preservation of muscle endurance and functional abilities. The study consists of two training intervention studies: study 1 "Dynamic leg and arm training for ambulant and recently wheelchair-dependent boys with DMD and, study 2 "Functional training with arm support for boys with DMD who have been confined to a wheelchair for several years". This paper describes the hypotheses and methods of the NUD study.
Methods
Study 1 is an explorative randomized controlled trial with multiple baseline measurements. Thirty boys with a DNA-established diagnosis of DMD will be included. The intervention consists of a six-months physical training during which boys train their legs and arms with active and/or assisted cycling training equipment. The primary study outcomes are muscle endurance and functional abilities, assessed with a Six-Minute Bicycle Test and the Motor Function Measure. Study 2 has a within-group repeated measurements design and will include ten boys with DMD who have already been confined to a wheelchair for several years. The six-months physical training program consists of 1) a computer-assisted training and 2) a functional training with an arm support. The primary study outcome is functional abilities of the upper extremity, assessed with the Action Research Arm Test.
Discussion
The NUD study will fill part of the gap in the current knowledge about the possible effects of training in boys with DMD and will increase insight into what type of exercise should be recommended to boys with DMD. The study will finish at the end of 2010 and results are expected in 2011.
Trial registration
The Netherlands National Trial Register1631
doi:10.1186/1471-2431-10-55
PMCID: PMC2929216  PMID: 20691042
17.  Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report 
Introduction
Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental.
Case presentation
We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin.
Conclusion
Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.
doi:10.1186/1752-1947-5-216
PMCID: PMC3123644  PMID: 21639928
18.  Drug treatment of Duchenne muscular dystrophy: available evidence and perspectives 
Acta Myologica  2012;31(1):4-8.
Duchenne muscular dystrophy (DMD) is a disease linked to the X-chromosome which affects 1 in 3,600-6,000 newborn males. It is manifested by the absence of the dystrophin protein in muscle fibres, which causes progressive damage leading to death in the third decade of life. The only medication so far shown to be effective in delaying the progression of this illness are corticosteroids, which have been shown to increase muscle strength in randomised controlled studies; long-term studies have demonstrated that they prolong walking time and retard the progression of respiratory dysfunction, dilated cardiomyopathy and scoliosis. Several potential drugs are now being investigated. Genetic therapy, involving the insertion of a dystrophin gene through a vector, has proven effective in animals but not humans. Currently under clinical study is Ataluren, a molecule that binds with ribosomes and may allow the insertion of an aminoacid in the premature termination codon, and exon-skipping, which binds with RNA and excludes specific sites of RNA splicing, producing a dystrophin that is smaller but functional. There are also studies attempting to modulate other muscular proteins, such as myostatin and utrophin, to reduce symptoms. This paper does not address cardiomyopathy treatment in DMD patients.
PMCID: PMC3440798  PMID: 22655510
Duchenne muscular dystrophy; drug treatment; clinical trials
19.  Autologous bone marrow mononuclear cell transplantation in Duchenne muscular dystrophy – a case report 
Patient: Male, 9
Final Diagnosis: Duchenne muscular dystrophy
Symptoms: Hyporeflexia • hypotonia • weaknes of lower limbs
Medication: —
Clinical Procedure: —
Specialty: Neurology
Objective:
Congenital defects/diseases
Background:
Duchenne muscular dystrophy (DMD) is a fatal, genetic, progressive, degenerating muscle disorder. Current treatment options are palliative. Newer options of cellular therapy promise to alter the disease process. Preclinical studies have successfully tested myogenic, neurogenic potential and dystrophin expression of bone marrow mononuclear cells.
Case Report:
We treated a 9-year-old boy suffering from DMD with serial autologous bone marrow mononuclear cell transplantations followed by multidisciplinary rehabilitation. Brooke-Vignos score was 10 and he was wheelchair-bound. Over 36 months, gradual progressive improvement was noticed in muscle strength, ambulation with assistive devices, fine motor movements, Brooke-Vignos score, and functional independence measure score. Nine months after the transplantation, electromyography findings showed development of new normal motor unit potentials of the vastus medialis muscle.
Conclusions:
Magnetic resonance imaging scan of musculoskeletal systems showed no increase in fatty infiltration. This case report provides early investigative findings or the restorative effects of cellular therapy in DMD.
doi:10.12659/AJCR.890078
PMCID: PMC3976215  PMID: 24711886
Stem Cell Transplantation; Autologous Bone Marrow Mono Nuclear Cells; Electromyography; Muscular Dystrophy; Duchenne – congenital
20.  Deflazacort in comparison to other steroids for nephrotic syndrome 
Indian Journal of Nephrology  2012;22(4):239-245.
Patients with nephrotic syndrome require steroids for long time and sometimes repeatedly resulting in various adverse effects. Deflazacort (DFZ) had been described as equally effective and with fewer side effects as compared with other steroids. This review evaluates the literature on efficacy and toxicity of DFZ as compared with other therapies for nephrotic syndrome. A systematic review of Pubmed database and Cochrane Central Register of Controlled Trials with last search date of 20th April 2011. Search terms included “nephrotic AND deflazacort” without any limitations. Randomized control trials comparing DFZ vs placebo or other therapies in subjects with nephrotic syndrome were included. Two authors extracted data independently. Three studies meet inclusion criteria and data were synthesized qualitatively. The limited evidence suggested that DFZ appeared to be equally effective in inducing remission or decreasing proteinuria in patients with nephrotic syndrome. It caused significantly less decrease in bone mineral content (BMC) in spine as compared with prednisolone. The results related to weight change, blood pressure change, Cushingoid symptoms, and urinary calcium excretion were inconsistent between included studies. By reviewing the available limited evidence, DFZ appears to be of similar efficacy for nephrotic patients, but there were inconsistent results regarding side effect profile of DFZ as compared with other steroids except for decrease in BMC where DFZ was better. There is need for larger randomized controlled trials to evaluate effectiveness and adverse effect profile of DFZ as compared with other steroids in nephrotic syndrome.
doi:10.4103/0971-4065.101238
PMCID: PMC3495343  PMID: 23162265
Bone mineral content; deflazacort; nephrotic syndrome; prednisolone
21.  Surgical management of severe scoliosis with high risk pulmonary dysfunction in Duchenne muscular dystrophy: patient function, quality of life and satisfaction 
International Orthopaedics  2010;34(5):695-702.
In a previous study, the authors reported the clinical and radiological results of Duchenne muscular dystrophy (DMD) scoliosis surgery in 14 patients with a low FVC of <30%. The purpose of this study was to determine if surgery improved function and QOL in these patients. Furthermore, the authors assessed the patients’ and parents’ satisfaction. %FVC increased in all patients after preoperative inspiratory muscle training. Scoliosis surgery in this group of patients presented no increased risk of major complications. All-screw constructions and fusion offered the ability to correct spinal deformity in the coronal and pelvic obliquity initially, intermediate and long-term. All patients were encouraged to continue inspiratory muscle training after surgery. The mean rate of %FVC decline after surgery was 3.6% per year. Most patients and parents believed scoliosis surgery improved their function, sitting balance and quality of life even though patients were at high risk for major complications. Their satisfaction was also high.
doi:10.1007/s00264-010-0957-0
PMCID: PMC2903179  PMID: 20155495
22.  Obstructive apnoeas in Duchenne muscular dystrophy. 
Thorax  1994;49(2):157-161.
BACKGROUND--In order to clarify the treatment of sleep hypoxaemias in Duchenne muscular dystrophy polysomnographic studies were performed on patients at home with the purpose of recruiting them into two clinical therapeutic trials. Observations concerning the nature of sleep hypoxaemia in these patients are presented. METHODS--Twenty one non-ambulant patients with Duchenne muscular dystrophy aged 13-23 years with no symptoms of sleep hypoventilation or apnoea were studied for two consecutive nights with eight channel polysomnography. A comparative study was performed in 12 age matched normal male subjects. The evolution of sleep hypoxaemia with age was studied in 14 patients with Duchenne muscular dystrophy. RESULTS--Thirteen of the 21 patients had hypoxaemia below 90% during sleep, and 12 of the 13 had discrete hypoxaemic dips in association with apnoeas; 60% of all apnoeas were obstructive in nature. The hypoxaemic periods became more frequent with increasing age and, in two patients at three year follow up, were more frequently associated with central or possibly "pseudocentral" apnoeas. Although the normal subjects had a few apnoeic episodes, none had sleep hypoxaemia below 90% saturation. CONCLUSION--The sleep related breathing abnormality in Duchenne muscular dystrophy is initially obstructive and this has implications for management.
PMCID: PMC474334  PMID: 8128406
23.  Computer method for the analysis of evoked motor unit potentials. 2. Duchenne, limb-girdle, facioscapulohumeral and myotonic muscular dystrophies. 
Single motor unit potentials recorded from surface electrodes over the extensor digitorum brevis muscle and evoked by stimulation of the anterior tibial nerve at the ankle were obtained by a computer subtraction method. Their latencies, durations, amplitudes, and areas were measured in control subjects and patients with Duchenne, limb-girdle, facioscapulohumeral, and myotonic muscular dystrophy. Lateral popliteal motor nerve conduction velocities were also recorded. In the muscular dystrophies there was a significant increase in both the latencies and durations of motor unit potentials, the latter in notable contrast with the findings of conventional needle electromyography. Fastest motor conduction velocities were significantly reduced in the limb-girdle, facioscapulohumeral, and myotonic muscular dystrophy patients, while the shortest distal motor latencies were significantly prolonged in these patients and those with Duchenne muscular dystrophy. The results support the presence of a definitive neurogenic influence in the muscular dystrophies.
PMCID: PMC491993  PMID: 1151411
24.  The Effect of Enalapril and Carvedilol on Left Ventricular Dysfunction in Middle Childhood and Adolescent Patients With Muscular Dystrophy 
Korean Circulation Journal  2012;42(3):184-191.
Background and Objectives
In Duchenne and Becker muscular dystrophies, cardiac function deteriorates with time resulting in heart failure which is often fatal. We prospectively evaluated the effect of enalapril and carvedilol on left ventricular (LV) dysfunction in middle childhood and adolescent patients with muscular dystrophy.
Subjects and Methods
Twenty-three patients with LV dysfunction (22 with Duchenne muscular dystrophy, 1 with Becker muscular dystrophy) were enrolled. We prescribed enalapril (13 patients) or carvedilol (10 patients) randomly from July 2008 to August 2010 and followed up the patients until September 2011. The changes in LV function parameters before and after the treatment were evaluated by echocardiography.
Results
The mean age at the start of treatment with enalapril or carvedilol was 12.6±3.7 years (median 13 years), and mean follow-up duration was 20.1±8.9 months. In the enalapril group, LV fractional shortening (FS) increased from 25.8±2.1 to 26.6±3.0 (p=0.241). In the carvedilol group, LV FS increased from 26.4±1.1 to 28.6±4.2 (p=0.110). In all 23 patients, LV FS significantly increased from 26.1±1.7 (before) to 27.6±3.7 (after treatment) (p<0.046). Indexed LV dimension at end diastole and LV end-diastolic volume decreased slightly, but without statistical significance by tri-plane volumetry. LV diastolic functional parameters were maintained during follow-up period.
Conclusion
Enalapril or carvedilol could improve LV systolic function in middle childhood and adolescent patients with muscular dystrophy without significant adverse effects.
doi:10.4070/kcj.2012.42.3.184
PMCID: PMC3318090  PMID: 22493613
Cardiomyopathies; Carvedilol; Echocardiography; Enalapril; Muscular dystrophies
25.  Insights into bone health in Duchenne muscular dystrophy 
BoneKEy reports  2012;1:9.
Poor bone health is a significant problem for patients with Duchenne muscular dystrophy (DMD), a progressive, disabling disease. Although the primary focus of DMD disease pathogenesis is degeneration of striated muscle, impairment of bone health likely has a role in the disease that has only been superficially examined to date. Deficiency of bone mineral density and increased incidence of bone fractures are well-recognized clinical components of the DMD phenotype. Furthermore, therapy with corticosteroids, an approved treatment for DMD that prolongs ambulation, may have multiple effects on bone health in DMD patients. This review examines the evidence in preclinical models and in human DMD disease that provides insight into the role performed by bone in the disease pathogenesis and phenotype of DMD. The information reviewed here points toward the need for mechanistic and therapeutic studies to optimize bone health in DMD patients.
doi:10.1038/bonekey.2012.5
PMCID: PMC3727795  PMID: 23951421

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