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Background: Analysis of serum biomarkers and magnetic resonance spectroscopy (MRS) are useful for monitoring disease progression in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). We evaluated the correlation of serum biomarkers and MRS parameters during changes associated with stroke-like episodes.Methods: In 13 symptomatic MELAS patients carrying the A3243G mutation, we retrospectively obtained 207 voxels from 41 MRS studies, which were divided into three groups according to the temporal association with stroke-like episodes. The MRS NAA/Cr, Cho/Cr, NAA/Cho ratios, the presence of a lactate peak, serum biomarkers, serum lactate level and the pyruvate (Lac/Pyr) ratio were determined.Results: In regions with acute infarcts, the severity of serum Lac/Pyr and that of the MRS lactate peak (P = 0.0007) correlated; serum lactate (P = 0.02), severity of elevated serum lactate (P = 0.04), and serum Lac/Pyr (P = 0.02) correlated weakly. In previously infarcted regions, the severity of the MRS lactate peak and serum Lac/Pyr (P = 0.03), as well as the severity of serum Lac/Pyr (P = 0.02) were weakly correlated. In structurally normal regions, we found a weak to moderate negative correlation between serum lactate and MRS NAA/Cr (P = 0.008), and between the severity of elevated serum lactate and MRS NAA/Cr (P = 0.002) as well as MRS NAA/Cho (P = 0.02).Conclusions: MRS parameters correlate with specific serum biomarkers, and are useful for monitoring changes in brain metabolites, particularly as related to stroke-like episodes.