Purpose or Case Report: Proton MRS (1H-MRS) is a technique to non-invasively study brain metabolites in vivo. 1H-MRS has been shown to detect abnormal brain accumulation of lactate in primary mitochondrial disorders (PMDs). However, differences in lactate concentration among the different PMDs have not been explored. We aimed to explore differences in quantitative 1H-MRS derived metabolite concentrations, particularly of lactate, and their ratios, in PMDs. We analyzed quantitative 1H-MRS data of the brain in pediatric patients with different types of genetically confirmed PMDs to evaluate differences in metabolite concentration and ratios.
Methods & Materials: Forty-six PMDs patients were evaluated with quantitative 1H-MRS using LCModel. Thirty-two patients were scanned in a 3T (TR/TE, 1700/20ms with 192 averages) and fourteen in a 1.5T scanner (TR/TE, 1500/20ms with 256 averages). Single voxel 1H-MRS spectra were obtained from the right basal ganglia of all the patients. According to the type of DNA mutation, there were twenty-six patients with nuclear (nDNA) and twenty with mitochondrial DNA (mtDNA) mutations. According to phenotypes, there were fifteen patients with Leigh syndrome (LS), seven patients with POLG related disorders (POLGRD), and five patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The rest of the patients had Cockayne, Pearson, Kearns-Sayre syndrome, complex IV deficiency, COQ4, CPEO-plus, pyruvate deficiency, MT-ATP6, SCA28, MPV17 or LHON. The remaining eight patients had no defined specific phenotype. For group comparison, t-tests and Wilcoxon rank-sum tests were applied.
Results: There was no statistically significant difference between lactate concentrations, lactate ratios, or other metabolite concentrations in PMDs with mtDNA compared to those with nDNA mutations (1.67±0.24 vs 1.155±0.205, p=0.132). There was a statistically significant difference between lactate concentrations in LS vs POLGRDs (1.776±0.25 vs 0.97±0.353, p<0.039). The lactate/Creatine ratio was higher in LS than the others combined (p<0.045), which may be explained by a significant lower creatine concentration in LS (3.542±0.259 vs 4.267±0.186, p<0.029). Myo-Inositol/Creatine ratio was also higher in LS (0.52±0.074 vs 0.325±0.053, p<0.03).
Conclusions: Lactate/Creatine and Myo-Inositol/Creatine ratios were significantly higher in LS patients than other PMDs combined, along with lower creatine. LS patients also had significantly higher lactate concentration compared to POLGRDs patients.