Case reportProton magnetic resonance spectroscopy to study the metabolic changes in the brain of a patient with Leigh syndrome
Introduction
Leigh syndrome is a progressive neurodegenerative disorder in infancy or childhood with variable clinical presentations, lactic acidosis and characteristic pathological findings in the brain, i.e. symmetrical foci of necrosis in the basal ganglia, thalamus, brainstem, dentate nuclei and optic nerves 1, 2. This disease is due to a disturbance of aerobic metabolism. Defects in pyruvate dehydrogenase (PDH) and cytochrome c oxidase (COX) are often associated with Leigh syndrome, and are inherited as autosomal recessive or X-linked traits 3, 4. Recently, some patients with Leigh syndrome were reported to carry specific mitochondrial (mt) DNA point mutations: A8344G [5], T8993G [6]and T8993C [7]mutations. A T→G point mutation at nt 8993 in the ATPase 6 gene of mtDNA was initially described in a family with neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) [8], and was later found to result in maternally inherited Leigh syndrome when present at a high level [6].
We performed localized proton magnetic resonance spectroscopy (MRS) to study the metabolic changes in the brain of a patient with Leigh syndrome, who had a T→G point mutation at nt 8993 of mtDNA. The patient was treated with thiamine and sodium dichloroacetate (DCA), which have lactate-lowering effects. Proton-MRS allows non-invasive measurement of brain metabolites, such as N-acetylaspartate (NAA), a choline-containing compound (Cho), creatine and phosphocreatine (Cr), and lactate (Lac). NAA is present in neurons and appears to be a possible indicator of neuronal function 9, 10. Choline is involved in the synthesis of a neurotransmitter, acetylcholine, and the synthesis and breakdown of membrane phospholipids [10]. The presence of lactate indicates the occurrence of anaerobic glycolysis in the brain. The aim of this study was to demonstrate a clinical usefulness of proton-MRS in evaluating an effectiveness of treatment in Leigh syndrome.
Section snippets
Case report
The patient was a Japanese boy born at term after an uncomplicated pregnancy. He was the second child of healthy and non-consanguineous parents. A 3-year-old sister was healthy. His birth weight was 2842 g and the Apgar scores were six and eight at 1 and 10 min, respectively. Generalized hypotonia was noted at birth. He developed apnea attacks and altered consciousness after upper respiratory infections at the ages of 2 and 4 months. At the age of 9 months, he was admitted to our hospital due
Discussion
We reported here the use of localized proton-MRS to study the metabolic changes in the brain of a patient with Leigh syndrome. This approach allowed us to examine various brain regions directly and non-invasively, and to correlate the regional metabolic changes with biochemical changes or lesions observed on MRI. Under normal conditions, the lactate concentration in the brain is at the limit of detectability on proton-MRS [13]. The presence of lactate indicates the occurrence of anaerobic
Acknowledgements
We wish to thank Dr. Teruo Kimura, Department of Neurosurgery, and Drs. Takumi Goto and Hidetoshi Ono, Department of Radiology, Asahikawa Medical College, for the helpful comments regarding the proton-MRS studies.
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Detection of increased intracerebral lactate in a mouse model of Leigh syndrome using proton MR spectroscopy
2019, Magnetic Resonance ImagingCitation Excerpt :However, with the progressive neuronal loss, intracerebral lactate levels decrease and finally normalize in the chronic stage, which is compatible with our explanation. According to a few case reports regarding Leigh syndrome in humans, NAA + NAAG levels were decreased in brain lesions [34–36], and GPC + PCh levels were slightly increased [35,36]; however there are no reports systemically evaluating intracerebral metabolites other than lactate in Leigh syndrome. In the present study, unlike previous reports, NAA + NAAG levels were not significantly different and GPC + PCh levels were slightly decreased in a mouse model of Leigh syndrome.
Proton MR Spectroscopy in leukodystrophies
2015, Egyptian Journal of Radiology and Nuclear MedicineCitation Excerpt :Other peaks detected at short TE include myo-inositol (mI), marker of glial function and lactate (lac) marker of anaerobic glycolysis (7,8). The detection of lactate resonance peak in brain parenchyma indicates cerebral lactic acidosis with reliability higher than blood and CSF lactate levels (9). Absolute and relative concentrations of these metabolites vary with age.
Magnetic Resonance Spectroscopy in Metabolic Disorders
2013, Neuroimaging Clinics of North AmericaCitation Excerpt :Under abnormal conditions, including inherited metabolic disorders, other metabolites may become detectable on 1H-MRS. The most important of these is lactate, whose presence indicates anaerobic metabolism and must be considered abnormal, with the sole exception of newborns, in which mild amounts of lactate may be physiologic. MRS detection of lactate in the brain parenchyma is a more precise indicator of cerebral lactic acidosis than blood and cerebrospinal fluid (CSF) lactate levels.8 Lactate is particularly elevated during phases of metabolic unbalance in mitochondrial diseases, and may be used to monitor the response to therapy.9
Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature
2010, European Journal of RadiologyCitation Excerpt :The lactate represents the end product of anaerobic metabolism [37]. In the literature decreased NAA/Cr and increased Cho/Cr ratios with lactate peak are reported [35–37]. In our cases together with the imaging findings and markedly elevated lactate made possible the diagnosis of mitochondrial encephalopathy.
Metabolic changes in 37 newly diagnosed Wilson's disease patients assessed by magnetic resonance spectroscopy
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