phosphocreatine and Dermatomyositis

It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients.. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements.. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported.. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter.

Topics: Adolescent; Body Composition; Bone Density; Child; Creatine; Cross-Over Studies; Cytokines; Dermatomyositis; Dietary Supplements; Double-Blind Method; Eating; Exercise; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Muscle, Skeletal; Phosphocreatine; Quality of Life; Sensitivity and Specificity; Surveys and Questionnaires; Visual Analog Scale; Young Adult

Quantitative MRI and phosphorus magnetic resonance spectroscopy ((31)P-MRS) were used to investigate skeletal muscle metabolism in vivo in patients with dermatomyositis (DM) and polymyositis (PM) in order to evaluate the role of mitochondrial abnormalities in the pathogenesis and clinical expression of these conditions. Nine patients with DM (mean age +/- SD, 57 +/- 14 years) and five with PM (42 +/- 12 years) and with age at disease onset 53 +/- 16 and 38 +/- 12 years, respectively, were included in the study together with 18 age-matched controls. Post-exercise (31)P-MRS indices of muscle oxidative metabolism were all impaired in DM and PM. In both groups of patients, the phosphocreatine and adenosine diphosphate recovery half-times were almost twice as long as in controls (P < 0.05 for each variable) and the maximum rate of mitochondrial ATP production was half that found in normal subjects (P < 0.001). The rate of proton efflux from muscle fibres was significantly reduced in DM (P < 0.001) and PM (P = 0.02). The impairment of (31)P-MRS recovery indices in DM and PM patients was similar to that found in a group of 10 patients with a primary mitochondrial disorder that showed a normal proton efflux rate. There was no correlation between the MRS-detectable abnormalities and the degree of inflammation or fatty infiltration of the muscle, as measured by MRI. The in vivo findings in DM and PM patients indicate impaired muscle aerobic function, which, considering the reduced proton efflux, is likely to be secondary to an impaired blood supply. Our results suggest that the abnormal mitochondria seen in some muscle biopsies are unlikely to be the primary cause of the oxidative insufficiency in these patients.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aged; Capillaries; Dermatomyositis; Exercise Test; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria; Mitochondrial Diseases; Muscle, Skeletal; Oxidative Phosphorylation; Phosphocreatine; Phosphorus Isotopes; Physical Exertion; Polymyositis; Protons; Reference Values; Rest; Water

(31)P magnetic resonance spectroscopy (MRS) is useful for evaluating metabolic disturbances in dermatomyositis (DM). However, short-term alterations of metabolic parameters such as Pi/PCr (inorganic phosphate/phosphocreatine) have not been assessed in detail, although they may reveal insights into the origin of the known long-term changes. We therefore performed real-time functional (31)P MRS to find out if there are characteristic short-term alterations of metabolic dynamics during muscular exercise and if they are of diagnostic relevance.. MRS measurements were performed on lower calf muscles of 10 DM patients and 18 healthy subjects throughout five short (1 min) cycles of submaximal exercise (50% maximum voluntary contraction).. Pi/PCr ratios during exercise increased in patients and controls. They rapidly returned to baseline values in the controls, but both Pi and PCr remained above baseline values in patients and resulted in irregular Pi/PCr ratios. This was true for each individual patient, but resulted in broad variation in individual Pi/PCr values. To compare groups with limited patient numbers, it was therefore more appropriate to use a recovery index, i.e. the quotient of the Pi/PCr ratio during and after exercise, which was independent of individual parameters, such as age and the work/energy cost ratio.. Evaluation of short-term changes by real-time functional (31)P MRS provides insight into alterations of Pi/PCr ratios and could improve diagnostic parameters in DM.

Topics: Adenosine Triphosphate; Adult; Aged; Dermatomyositis; Exercise; Female; Humans; Hydrogen-Ion Concentration; Immunoglobulins, Intravenous; Longitudinal Studies; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphates; Phosphocreatine

Topics: Adenosine Triphosphate; Adult; Azathioprine; Dermatomyositis; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Hydroxychloroquine; Immunosuppressive Agents; Longitudinal Studies; Magnetic Resonance Spectroscopy; Methotrexate; Muscle Contraction; Muscle, Skeletal; Phosphates; Phosphocreatine; Phosphorus Isotopes; Prednisone

To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM.. Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise.. Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest.. Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.

Topics: Adult; Aged; Dermatomyositis; Exercise; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Muscular Diseases; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rest; Skin Diseases; Work Capacity Evaluation

Dermatomyositis is an autoimmune disease characterized by an erythematous rash and severe muscle weakness. 31P Magnetic resonance spectroscopy (MRS) provides quantitative data for longitudinal monitoring of disease status and responses to immunosuppressive therapy. A disease variant, amyopathic dermatomyositis, presents with a typical rash but no clinical muscle weakness. However, metabolic abnormalities in the oxidative capacity of muscles of amyopathic patients during exercise were detected with 31P MRS. Because MRS provided the best quantitative data for evaluating dermatomyositis, the 31P metabolic parameters derived from the MR spectra were further processed using an artificial neural network (XERION). The neural network analyses provided additional clinical information from the weighted correlations of multiple 31P parameters, namely, inorganic phosphate, phosphocreatine, ATP, phosphodiesters, and selected ratios. This investigation analyzes the relative importance of the various metabolic parameters for accurate patient characterization and provides insights into the pathogenesis of the disease.

Topics: Adenosine Triphosphate; Adolescent; Adult; Aged; Dermatomyositis; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Muscular Diseases; Neural Networks, Computer; Phosphates; Phosphocreatine

To explore alterations in energy utilization as a potential etiology for weakness in polymyositis and dermatomyositis (PM/DM).. P-31 magnetic resonance spectroscopy studies were performed in patients with acute and treated PM/DM and in normal controls, at rest and with exercise.. Patients with acute and treated PM/DM showed increased ratios of inorganic phosphate to phosphocreatine (PCr) during exercise, with loss of ATP disproportional to loss of PCr.. This study demonstrates changes in energy utilization in PM/DM, thus supporting the notion of a metabolic etiology for the weakness associated with these diseases.

Topics: Adenosine Triphosphate; Dermatomyositis; Energy Metabolism; Exercise; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Muscles; Myositis; Phosphates; Phosphocreatine; Phosphorus

Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment.

Topics: Adult; Dermatomyositis; Evaluation Studies as Topic; Exercise; Female; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphates; Phosphocreatine; Phosphorus

Topics: Adrenal Cortex Hormones; Cardiomegaly; Cardiomyopathies; Dermatomyositis; Diagnosis, Differential; Electrocardiography; Female; Humans; Middle Aged; Mitral Valve Insufficiency; Phosphocreatine; Tachycardia