phosphocreatine and Myositis

31P MRS and 1H MRI of skeletal muscle have become major new tools allowing a complete non invasive investigation of muscle function both in the clinical setting and in basic research. The comparative analysis of normal and diseased muscle remains a major requirement to further define metabolic events surrounding muscle contraction and the metabolic anomalies underlying pathologies. Also, standardized rest-exercise-recovery protocols for the exploration of muscle metabolism by P-31 MRS in healthy volunteers as well as in patients with intolerance to exercise have been developed. The CRMBM protocol is based on a short-term intense exercise, which is very informative and well accepted by volunteers and patients. Invariant metabolic parameters have been defined to characterize the normal metabolic response to the protocol. Deviations from normality can be directly interpreted in terms of specific pathologies in some favorable cases. This protocol has been applied to more than 4,000 patients and healthy volunteers over a period of 15 years. On the other hand, MRI investigations provide anatomical and functional information from resting and exercising muscle. From a diagnostic point of view, dedicated pulse sequences can be used in order to detect and quantify muscle inflammation, fatty replacement, muscle hyper and hypotrophy. In most cases, MR techniques provide valuable information which has to be processed in conjunction with traditional invasive biochemical, electrophysiological and histoenzymological tests. P-31 MRS has proved particularly useful in the therapeutic follow-up of palliative therapies (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is now an accepted diagnostic tool in the array of tests which are used to characterize muscle disorders in clinical routine. As a research tool, it will keep bringing new information on the physiopathology of muscle diseases in animal models and in humans and should play a role in the metabolic characterization of gene and cell therapy.

Topics: Adenosine Triphosphate; Calibration; Energy Metabolism; Equipment Design; Exercise Test; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Metabolism, Inborn Errors; Mitochondrial Myopathies; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Myositis; Neuromuscular Diseases; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rest

To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable.. In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids.. A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine.. Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive.

Topics: Administration, Oral; Creatine; Double-Blind Method; Energy Metabolism; Exercise; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Strength; Muscle Weakness; Myositis; Phosphocreatine; Phosphorus Isotopes; Placebos; Treatment Outcome

The clinical utility of supine in-magnet bicycling in combination with phosphorus magnetic resonance spectroscopy ((31)P MRS) to evaluate quadriceps muscle metabolism was examined in four children with juvenile dermatomyositis (JDM) in remission and healthy age- and gender-matched controls.. Two identical maximal supine bicycling tests were performed using a magnetic resonance-compatible ergometer. During the first test, cardiopulmonary performance was established in the exercise laboratory. During the second test, quadriceps energy balance and acid/base balance during incremental exercise and phosphocreatine recovery were determined using (31)P MRS.. During the first test, no significant differences were found between patients with JDM and their healthy peers regarding cardiopulmonary performance. The outcomes of the first test indicate that both groups attained maximal performance. During the second test, quadriceps phosphocreatine and pH time courses were similar in all but one patient experiencing idiopathic postexercise pain. This patient demonstrated faster phosphocreatine depletion and acidification during exercise, yet postexercise mitochondrial adenosine triphosphate synthesis rate measured by phosphocreatine recovery kinetics was approximately twofold faster than control (time constant 23 seconds vs 43 ± 7 seconds, respectively).. These results highlight the utility of in-magnet cycle ergometry in combination with (31)P MRS to assess and monitor muscle energetic patterns in pediatric patients with inflammatory myopathies.

Topics: Adenosine Triphosphate; Adolescent; Dermatitis; Energy Metabolism; Exercise Test; Female; Humans; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Myositis; Phosphocreatine; Pilot Projects; Quadriceps Muscle

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