Application of NMR spectroscopy to monitoring MELAS treatment: a case report.
1H magnetic resonance spectroscopy (MRS) of the brain and (31)P MRS and saturation transfer of resting skeletal muscle were used to investigate intracellular metabolites and fluxes through the creatine kinase (CK) reaction in a patient with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Acute cortical lesions were characterized by severely elevated lactate levels and reduced concentrations of N-acetylaspartyl compounds, glutamate, and myo-inositol. Similar but less extreme alterations were also observed in gray matter regions that appeared normal on magnetic resonance images. Investigation of the gastrocnemius muscle at rest demonstrated a reduced phosphocreatine level, elevated concentrations of inorganic phosphate and free adenosine 5'-diphosphate, and an abnormally low phosphorylation potential. Besides a moderately increased muscular phosphocreatine concentration, none of the metabolic disturbances detected on MRS improved with oral creatine supplementation. Forward and reverse fluxes through the CK reaction did not significantly change upon creatine treatment. Follow-up MRS investigations may thus provide objective markers of treatment response in vivo without the hazards or inconvenience of biopsy.
Möller
Harald E
HE
Institut für Physikalische Chemie, Universität Münster, Münster, Germany. moeller@cns.mpg.de
Wiedermann
Dirk
D
Kurlemann
Gerhard
G
Hilbich
Thorsten
T
Schuierer
Gerhard
G
D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D003401:Creatine / Q000627:therapeutic use; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D017241:MELAS Syndrome / Q000378:metabolism* / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D010766:Phosphorylation
D010725:Phosphocreatine; D010758:Phosphorus; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine