phosphocreatine and Myotonic-Dystrophy

Creatine monohydrate (CrM) supplementation may increase strength in some types of muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1) did not find a significant treatment effect, but measurements of muscle phosphocreatine (PCr) were not performed. We completed a randomized, double-blind, cross-over trial using 34 genetically confirmed adult DM1 patients without significant cognitive impairment. Participants received CrM (5 g, approximately 0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out. Spirometry, manual muscle testing, quantitative isometric strength testing of handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion endurance, functional tasks, activity of daily living scales, body composition (total, bone, and fat-free mass), serum creatine kinase activity, serum creatinine concentration and clearance, and liver function tests were completed before and after each intervention, and muscle PCr/beta-adenosine triphosphate (ATP) ratios of the forearm flexor muscles were completed at the end of each phase. CrM supplementation did not increase any of the outcome measurements except for plasma creatinine concentration (but not creatinine clearance). Thus, CrM supplementation at 5 g daily does not have any effects on muscle strength, body composition, or activities of daily living in patients with DM1, perhaps because of a failure of the supplementation to increase muscle PCr/beta-ATP content.

Topics: Activities of Daily Living; Adult; Body Mass Index; Creatine; Cross-Over Studies; Exercise Tolerance; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Proteins; Muscle Weakness; Muscle, Skeletal; Myotonic Dystrophy; Phosphocreatine; Respiratory Function Tests; Treatment Failure

To evaluate by magnetic resonance spectroscopy the age-related cerebral alterations present in myotonic dystrophy (MD) and to compare these results with those obtained by magnetic resonance imaging.. Twenty-one patients (aged 16-63 years) with MD were compared with 16 age-matched healthy control subjects.. In magnetic resonance spectroscopy, the mean (+/- SD) ratio of N-acetylaspartate to creatine and phosphocreatine in the patients with MD (1.09 +/- 0.32) was significantly lower than that in the control subjects (1.93 +/- 0.43) (P<.001). The mean ratio of N-acetylaspartate to choline-containing compounds in the patients with MD (1.70 +/- 0.44) was also significantly lower than that in the control subjects (2.75 +/- 0.53) (P<.001). These changes could be observed already in the younger patients. In magnetic resonance imaging, the mean brain area was significantly decreased and the mean ventricular space was significantly increased in patients with MD compared with the control subjects. Although we have confirmed brain atrophy in patients with MD in previous reports, a regression analysis indicated that the brain shrinks progressively with age in patients with this disorder and in control subjects, resulting in overlapping values for younger subjects.. Magnetic resonance spectroscopy indicates that the cerebral abnormalities in patients with MD may be present at an early stage, when the results of magnetic resonance imaging studies are still equivocal.

Topics: Adolescent; Adult; Aspartic Acid; Atrophy; Case-Control Studies; Cerebral Cortex; Creatine; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myotonic Dystrophy; Phosphocreatine

We have used 31P magnetic resonance spectroscopy to investigate skeletal muscle bioenergetics in a total of 31 patients with myotonic dystrophy. Results from resting flexor digitorum superficialis and calf muscle showed a significant elevation in the concentration ratio of inorganic phosphate to ATP and a significant reduction in the phosphorylation potential. In addition, in resting calf muscle the concentration ratio of phosphocreatine to ATP was reduced, and the resting intracellular pH and calculated free cytosolic ADP concentration were elevated. In general, the abnormalities observed were more marked in those patients who were more severely affected as judged by their ability to exercise. During aerobic exercise in both calf muscle and flexor digitorum superficialis, phosphocreatine was depleted more rapidly in patients than in control subjects but the muscle acidified less and ADP concentrations were higher. Calculated ATP turnover was significantly elevated. Analysis of the recovery kinetics for phosphocreatine following exercise provides evidence for a small but significant reduction in mitochondrial function. Analysis of the response of flexor digitorum superficialis to ischaemic exercise provides evidence of a reduction in the relative utilization of glycogen to produce ATP which may account, in part, for the reduced acidification seen in exercising muscle in myotonic dystrophy. There was no definite evidence of an alteration in proton handling capacity in this condition.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Anaerobiosis; Exercise; Fingers; Humans; Hydrogen-Ion Concentration; Leg; Magnetic Resonance Spectroscopy; Muscle, Skeletal; Myotonic Dystrophy; Phosphocreatine; Phosphorus; Rest; Time Factors

Skeletal muscle function of 15 patients with myotonic dystrophy (dystrophia myotonica, DM) was investigated using 31P magnetic resonance spectroscopy to evaluate bioenergetics and intracellular pH at rest and during exercise and recovery. Results from DM patients, normal controls and mitochondrial myopathy patients were compared in order to assess the possible contribution of abnormal mitochondrial metabolism to muscle dysfunction in DM. In resting DM muscle, intracellular pH (pHi) was normal, but there were significant elevations in the concentration ratios of Pi/ATP, phosphomonoesters/ATP and phosphodiesters/ATP. In patients with the most severe exercise intolerance the phosphocreatine/ATP ratio was also reduced. Resting muscle of 11 mitochondrial myopathy patients showed similar changes to those of the most exercise-intolerant DM patients. In exercising DM muscle, energy stores were rapidly depleted as in mitochondrial myopathy. Muscle acidified in all subjects, but in DM the decrease in pHi was less than in normal muscle. Recovery half-times for phosphocreatine, Pi and ADP were normal in DM but slow in mitochondrial myopathy. The initial rate of phosphocreatine repletion after exercise was rapid in DM, consistent with high [ADP], but slow in mitochondrial myopathy in spite of elevated [ADP]. Because recovery is an oxidative process, we conclude that there was no decrease in the oxidative capacity of the muscles in this group of DM patients. In the subjects in whom it could be measured, the rate of recovery of intracellular pH was greater in the 3 DM patients (0.14, 0.15 and 0.16 U/min) than in the 7 normal controls (0.08-0.12 U/min, mean 0.10). The results do not rule out a minor abnormality in glycogenolysis, but they suggest that the failure to acidify normally during exercise is probably due to rapid proton efflux.

Topics: Adenosine Diphosphate; Adult; Energy Metabolism; Exercise; Female; Forearm; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondrial Myopathies; Muscles; Myotonic Dystrophy; Phosphates; Phosphocreatine; Rest

Concentrations of the high-energy phosphates, ATP and creatine phosphate, were investigated in slow-twitch (ST) and fast-twitch (FT) muscle fibres of patients with myotonia congenita (n = 6), dystrophia myotonica (n = 5), myopathia ocularis (n = 2) and hyperornithinemia with gyrate atrophy (HOGA) (n = 3) and compared with those of normal subjects (n = 4). At rest, the patients with HOGA had lower values of ATP in ST muscle fibres than the controls (P less than 0.05). They also had lower values of creatine phosphate in these fibres than the patients with dystrophia myotonica (P less than 0.03) and myotonia congenita (P less than 0.05). After 30 s bicycle ergometer exercises there was an increase in ATP in the ST muscle fibres of the patients with myotonia congenita, but in all other patient groups there was a decrease.

Topics: Adenosine Triphosphate; Adolescent; Adult; Female; Humans; Male; Middle Aged; Muscles; Myotonia Congenita; Myotonic Dystrophy; Neuromuscular Diseases; Oculomotor Muscles; Organ Specificity; Ornithine; Phosphocreatine; Physical Exertion; Syndrome

Topics: Adult; Female; Humans; Male; Middle Aged; Myotonic Dystrophy; Phosphocreatine