Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies

Abstract

Localized brain proton MR spectra were acquired from patients with different mitochondrial encephalomyopathies (myoclonus epilepsy with ragged-red fibers [MERRF], Kearns-Sayre syndrome [KSS], and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS]). The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. In MERRF, only one of four patients showed an increase in the lactate/creatine resonance intensity ratio (an index of impairment of oxidative metabolism) in spectra from central (supraventricular) or occipital brain volumes, and this was small. There were significant decreases in N-acetylaspartate/creatine (a measure of neuronal loss or dysfunction) in central cerebral volumes of demented patients and, more prominently, in occipital volumes. In the one patient in whom it was studied, the cerebellum also showed a decreased N-acetylaspartate/creatine. Spectra from two patients with KSS both showed large (four- to sevenfold) increases in lactate/creatine and large decreases in N-acetylaspartate/creatine in central brain volumes. Yet another pattern of regional metabolic abnormality was present in the MELAS syndrome, where proton spectroscopic imaging demonstrated focal localization of abnormally increased lactate/creatine and decreased N-acetylaspartate/creatine to the regions of the stroke-like lesions on conventional MR images. Serial studies emphasized that the regional metabolic abnormalities in MELAS are highly variable as the stroke-like lesions appear and evolve.

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

“…54 As a result, elevated lactate levels are commonly used to diagnose and confirm mitochondrial disorders, particularly those that affect the central nervous system. 16,[55][56][57] Additionally, animal studies have confirmed that significant increases in brain lactate, as well as decreases in pHi, occur as a result of induced, isolated mitochondrial failure. 58 In one study, in which Clausen et al 58 used cyanide to induce mitochondrial failure in the feline brain, an analysis of corresponding extracellular lactate concentrations and brain tissue pH suggests a logarithmic relationship between the two measure-…”

“…13,14 In fact, research on cerebral injury by Demougeot et al 15 has indicated that cellular dysfunction can actually cause greater measurable reductions in NAA than neuronal loss. Abnormally low ratios of NAA/Cr þ PCr have been observed in patients with a number of mitochondrial encephalomyopathies, 16 and studies using mitochondrial respiratory chain inhibitors have also shown that reductions in NAA are correlated with decreases in O 2 consumption and ATP production. 7,14,17 When taken together, these studies suggest that NAA levels are closely related to mitochondrial energy metabolism, and thus may serve as a measure of mitochondrial function.…”

Metabolite measurements in the caudate nucleus, anterior cingulate cortex and hippocampus among patients with mitochondrial disorders: a case-control study using proton magnetic resonance spectroscopy

“…To our knowledge, MRS findings in the brain of patients with mitochondrial disorders have been reported only in individual cases or small series, and most studies were carried out in areas of the brain that appeared abnormal on magnetic resonance imaging (MRI) as part of the clinical investigation of the patient. [7][8][9][10][11][12][13][14][15] The most consistent findings have been higher lactate levels and lower N-acetyl-aspartate levels, although lower creatine and glutamate levels, and altered levels of choline have also been reported. [7][8][9][10][11][12][13][14][15] In this study, we measured metabolites in vivo in patients with mitochondrial disorders compared with age-and sexmatched healthy controls using standardized voxel placement in 3 brain regions commonly implicated in neuropsychiatric disorders: the caudate nucleus, anterior cingulate cortex and hippocampus.…”

“…[7][8][9][10][11][12][13][14][15] The most consistent findings have been higher lactate levels and lower N-acetyl-aspartate levels, although lower creatine and glutamate levels, and altered levels of choline have also been reported. [7][8][9][10][11][12][13][14][15] In this study, we measured metabolites in vivo in patients with mitochondrial disorders compared with age-and sexmatched healthy controls using standardized voxel placement in 3 brain regions commonly implicated in neuropsychiatric disorders: the caudate nucleus, anterior cingulate cortex and hippocampus. [16][17][18][19] Our primary hypothesis was that patients with mitochondrial disorders would have reduced levels of markers of mitochondrial dysfunction (N-acetyl-aspartate and creatine) compared with healthy controls in the 3 candidate brain regions.…”

Positron emission tomography and magnetic resonance spectroscopy of cerebral glycolysis in children with congenital lactic acidosis

“…Possibly, our Patients 2 and 3 had a more severe form of the disease with a massive increase of glycolysis that could not be maintained for a long time. Theoretically, massive lactate accumulation could exert toxic effects [28] and thus contribute to the unfortu nate outcome; but increased cerebral lactate signals have also been described in chronic cases of mitochon drial encephalomyopathies [29].…”