Open AccessMitochondrial dysfunction and cerebral metabolic abnormalities in patients with mitochondrial encephalomyopathy subtypes: Evidence from proton MR spectroscopy and muscle biopsy
Author(s) -
Niu FengNan,
Meng HaiLan,
Chang LeiLei,
Wu HongYan,
Li WeiPing,
Liu RenYuan,
Wang HuiTing,
Zhang Bing,
Xu Yun
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12714
Subject(s) - mitochondrial encephalomyopathy , mitochondrial encephalomyopathies , melas syndrome , lactic acidosis , chronic progressive external ophthalmoplegia , mitochondrial myopathy , mitochondrial disease , muscle biopsy , creatine , medicine , pathology , endocrinology , biopsy , mitochondrial dna , biology , biochemistry , gene
Summary Aims Accumulated evidence indicates that cerebral metabolic features, evaluated by proton magnetic resonance spectroscopy ( 1 H‐ MRS ), are sensitive to early mitochondrion dysfunction associated with mitochondrial encephalomyopathy ( ME ). The metabolite ratios of lactate (lac)/Cr, N‐acetyl aspartate ( NAA )/creatine (Cr), total choline ( tC ho)/Cr, and myoinositol ( mI )/Cr are measured in the infarct‐like lesions by 1 H‐ MRS and may reveal metabolic changes associated with ME . However, the application of this molecular imaging technique in the investigation of the pathology of ME subtypes is unknown. Methods In this study, cerebral metabolic features of pathologically diagnosed ME cases, that is, 19 mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes ( MELAS ); nine chronic progressive external ophthalmoplegia ( CPEO ); and 23 healthy controls, were investigated using 1 H‐ MRS . Receiver operating characteristics ( ROC ) analysis was used to evaluate the diagnostic power of the cerebral metabolites. Histochemical evaluation was carried out on muscle tissues derived from biopsy to assess the abnormal mitochondrial proliferation. The association between cerebral metabolic and mitochondrial cytopathy was examined by correlation analysis. Results Patients with MELAS or CPEO exhibited a significantly higher Lac/Cr ratio and a lower NAA /Cr ratio compared with controls. The ROC curve of Lac/Cr ratio indicated prominent discrimination between MELAS or CPEO and healthy control subjects, whereas the NAA /Cr ratio may present diagnostic power in the distinction of MELAS from CPEO . Lower NAA /Cr ratio was associated with higher Lac/Cr in MELAS , but not in CPEO . Furthermore, higher ragged‐red fibers ( RRF s) percentages were associated with elevated Lac/Cr and reduced NAA /Cr ratios, notably in MELAS . This association was not noted in the case of mI /Cr ratio. Conclusions Mitochondrial cytopathy (lactic acidosis and RRF s on muscle biopsy) was associated with neuronal viability but not glial proliferation, notably in MELAS . Mitochondrial neuronopathy and neuronal vulnerability are considered significant causes in the pathogenesis of MELAS , particularly with regard to stroke‐like episodes.