Publication Type Academic Article
Authors Weiduschat N, Kaufmann P, Mao X, Engelstad K, Hinton V, DiMauro S, De Vivo D, Shungu D
Journal Neurology
Volume 82
Issue 9
Pagination 798-805
Date Published 01/29/2014
ISSN 1526-632X
Keywords Acidosis, Lactic, Cerebral Cortex, DNA, Mitochondrial, MELAS Syndrome, Mutation
Abstract OBJECTIVE: To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging ((1)H MRSI) and to assess their potential as prognostic biomarkers. METHODS: In this prospective cohort study, we investigated 135 clinically heterogeneous A3243G mutation carriers and 30 healthy volunteers (HVs) with (1)H MRSI. Mutation carriers included 45 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); 11 participants who would develop the MELAS syndrome during follow-up (converters); and 79 participants who would not develop the MELAS syndrome during follow-up (nonconverters). The groups were compared with respect to MRSI metabolic indices of 1) anaerobic energy metabolism (lactate), 2) neuronal integrity (N-acetyl-l-aspartate [NAA]), 3) mitochondrial function (NAA; lactate), 4) cell energetics (total creatine), and 5) membrane biosynthesis and turnover (total choline [tCho]). RESULTS: Consistent with prior studies, the patients with MELAS had higher lactate (p < 0.001) and lower NAA levels (p = 0.01) than HVs. Unexpectedly, converters showed higher NAA (p = 0.042), tCho (p = 0.004), and total creatine (p = 0.002), in addition to higher lactate levels (p = 0.032), compared with HVs. Compared with nonconverters, converters had higher tCho (p = 0.015). Clinically, converters and nonconverters did not differ at baseline. Lactate and tCho levels were reliable biomarkers for predicting the risk of individual mutation carriers to develop the MELAS phenotype. CONCLUSIONS: (1)H MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype.
DOI 10.1212/WNL.0000000000000169
PubMed ID 24477106
PubMed Central ID PMC3945652
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