Brain Advance Access published online on October 20, 2009
Brain, doi:10.1093/brain/awp259
Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A>G mutation
1 Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland 2 Department of Neurology, University of Turku and Turku University Hospital, Turku, Finland 3 Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland 4 Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland 5 Department of Neurology, University of Oulu, Oulu, Finland
Correspondence to:
Kari Majamaa, Department of Neurology, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland E-mail: kari.majamaa{at}oulu.fi
The m.3243A>G mutation is the most common pathogenic mutation in mitochondrial DNA. It leads to defective oxidative phosphorylation, decreased oxygen consumption and increased glucose utilization and lactate production in vitro. However, oxygen and glucose metabolism has not been studied in the brain of patients harbouring the m.3243A>G mutation. Therefore, 14 patients with the m.3243A>G mutation, not experiencing acute stroke-like episodes and 14 age-matched controls underwent positron emission tomography using 2-[18F]fluoro-2-deoxyglucose, [15O]H2O and [15O]O2 as the tracers during normoglycaemia. The metabolic rate of oxygen and glucose were determined using a quantitative region of interest analysis. Metabolites in unaffected periventricular tissue were measured using magnetic resonance spectroscopy. We found that the cerebral metabolic rate of oxygen was decreased by 26% (range 18%–29%) in the grey as well as the white matter of patients with the m.3243A>G mutation. A decrease in the metabolic rate of glucose was found with predilection to the posterior part of the brain. No major changes were detected in cerebral blood flow or the number of white matter lesions. Our results show that the m.3243A>G mutation leads to a global decrease in oxygen consumption in the grey matter including areas where no other signs of disease were present.
Key Words: 2-[18F]fluoro-2-deoxyglucose; oxygen; positron emission tomography; magnetic resonance spectroscopy; mitochondrial encephalomyopathy
Abbreviations: ATP, adenosine triphosphate; [18F]FDG, 2-[18F]fluoro-2-deoxyglucose; Cr, creatine; NAA, N-acetyl aspartate; CBF, cerebral blood flow; CMRO2, cerebral metabolic rate of oxygen; GMR, glucose metabolic rate; MRS, magnetic resonance spectroscopy; OGI, oxygen-to-glucose index; ROI, region of interest; SPM, Statistical Parametric Mapping
Received June 26, 2009. Revised August 14, 2009. Accepted August 27, 2009.