phosphocreatine and Lupus-Erythematosus--Systemic

Creatine supplementation has emerged as a promising non-pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE).. C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one-maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial.. Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 ± 2.6, Post: 20.4 ± 4.1, placebo-Pre: 19.8 ± 2.0; Post: 20.2 ± 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed.. A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients.. Clinicaltrials.gov number: NCT01217320.

Topics: Adolescent; Anaerobic Threshold; Body Composition; Bone Remodeling; Child; Creatine; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Exercise Test; Exercise Tolerance; Female; Hand Strength; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Male; Muscle, Skeletal; Phosphocreatine; Quality of Life

Our objective was to investigate axonal dysfunction in patients with systemic lupus erythematosus (SLE) using proton magnetic resonance spectroscopy (1H-MRS). We studied prospectively 90 SLE patients (mean age of 32.5 years) and 23 normal volunteers (mean age of 33.8 years). We performed single voxel proton MRS using point resolved spectroscopy sequence over the superior-posterior region of the corpus callosum. We measured signals from N-acetyl compounds [N-acetylaspartate (NAA)] at 2.01 p.p.m., choline-based compounds (Cho) at 3.2 p.p.m. and creatine and phosphocreatine containing compounds (Cr) at 3.0 p.p.m. and determined NAA/Cr ratios. After 12 months, MRI and MRS were repeated in 50 patients and 9 volunteers. Patients were divided according to disease activity (measured by SLE disease activity index) during initial and follow-up MRS. We performed paired t-test and ANOVA with Tukey's post hoc comparisons to evaluate group differences. At study entry, 29 patients had active SLE with involvement of central nervous system (CNS) and 28 patients had active SLE without CNS manifestations. A total of 14 patients had inactive SLE with past CNS presentation, and 19 had inactive SLE without history of CNS involvement. NAA/Cr ratios were significant lower in patients with active SLE, independently of CNS involvement, when compared with patients with inactive SLE (P = 0.005) and controls (P = 0.01). We observed a significant increase in NAA/Cr ratio in 15 patients who had active SLE at initial MRS and inactive SLE at follow-up (P = 0.04). In 10 patients with active SLE both at initial and at follow-up MRS we observed a reduction in NAA/Cr ratio (P = 0.02). By contrast, there was a significant reduction of NAA/Cr ratio in 15 patients who had inactive SLE at initial MRS and active SLE at follow-up (P = 0.001). In 10 patients with inactive SLE both at initial and at follow-up MRS NAA/Cr ratio did not change (P = 0.2). This study shows evidence of axonal dysfunction in patients with active SLE, independently of CNS manifestations that may be reversible, at least in part, during periods of inactivity of disease.

Topics: Adult; Analysis of Variance; Antibodies, Antiphospholipid; Aspartic Acid; Axons; Biomarkers; Brain; Case-Control Studies; Choline; Creatine; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Prospective Studies; Protons

To determine whether cerebral atrophy in systemic lupus erythematosus is associated with decreased levels of the neuronal marker N-acetyl-aspartic acid.. Two groups of patients with systemic lupus erythematosus were studied, those with significant atrophy (n = 11) and those without significant atrophy (n = 10), using proton MR spectroscopy on a 1.5-T imaging unit. The solvent-suppressed, short-echo, volume-localized proton spectroscopy technique showed typical brain metabolites, including N-acetylaspartate, creatine/phosphocreatine, and choline-containing compounds.. The N-acetylaspartate-to-creatine/phosphocreatine ratio was smaller in those patients with significant cerebral atrophy (1.68 +/- 0.27) than in those patients with minimal or no atrophy (2.17 +/- .30). The degree of atrophy was negatively correlated with the N-acetylaspartate-to-creatine/phosphocreatine ratio. The choline-to-creatine/phosphocreatine ratio was not significantly altered in systemic lupus erythematosus patients with atrophy.. These data suggest that cerebral atrophy in systemic lupus erythematosus is associated with neuronal dropout (or damage), which results in decreased N-acetylaspartate ratios. A change in choline ratios is not implicated in the biochemical changes associated with cerebral atrophy. Proton MR spectroscopy may be useful in correlating brain metabolites with cerebral structural changes in patients with autoimmune diseases.

Topics: Adolescent; Adult; Aspartic Acid; Atrophy; Brain; Choline; Creatine; Energy Metabolism; Female; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine

Systemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high-energy phosphates in the central nervous system of 10 patients with SLE and 10 age-matched normal controls. 31P NMR spectroscopy was performed on a 1.5-Tesla unit equipped with a dual-tuned 1H-31P surface coil and a software-directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean +/- SD 0.81 +/- 0.11 versus 0.91 +/- 0.05; P less than 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high-energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adrenal Cortex Hormones; Adult; Central Nervous System; Energy Metabolism; Female; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Spectroscopy; Middle Aged; Phosphates; Phosphocreatine; Phosphorus; Reference Values