Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic seizures and late reduced diffusion.

INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis. METHODS: Five Japanese patients with AESD (three boys and two girls, 1 year of age) were enrolled in this study. MR spectroscopy was acquired from the frontal white matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or 3.0-T scanner. MR spectroscopy was performed four times for two patients, three times for one patient, and two times for two patients. Quantification of Glu and Gln was performed using LCModel. RESULTS: Glu was elevated in three of four studies on days 1-4 and became normal or low afterward. Gln was normal in three studies on days 1-2, elevated in all seven studies on days 4-12, and became normal or low afterward. CONCLUSION: These findings suggest that MR spectroscopy may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln elevation, suggesting that a disrupted Glu-Gln cycle may play an important role.

Neurochemistry in shiverer mouse depicted on MR spectroscopy.

PURPOSE: To evaluate the neurochemical changes associated with hypomyelination, especially to clarify whether increased total N-acetylaspartate (tNAA) with decreased choline (Cho) observed in the thalamus of msd mice with the plp1 mutation is a common finding for hypomyelinating disorders. MATERIALS AND METHODS: We performed magnetic resonance imaging (MRI) and proton MR spectroscopy ((1) H-MRS) of the thalamus and cortex of postnatal 12-week shiverer mice devoid of myelin basic protein (mbp), heterozygous and wild-type mice with a 7.0T magnet. Luxol Fast Blue staining and immunohistochemical analysis with anti-Mbp, Gfap, Olig2, and NeuN antibodies were also performed. RESULTS: In the thalamus, decreased Cho and normal tNAA were observed in shiverer mice. In the cortex, tNAA, Cho, and glutamate were decreased in shiverer mice. Histological and immunohistochemical analysis of shiverer mice brains revealed hypomyelination in the thalamus, white matter, and cortex; astrogliosis and an increased number of total oligodendrocytes in the white matter; and a decreased number of neurons in the cortex. CONCLUSION: The reduction of Cho on (1) H-MRS might be a common marker for hypomyelinating disorders. A normal tNAA level in the thalamus of shiverer mice might be explained by the presence of mature oligodendrocytes, which enable neuron-to-oligodendrocyte NAA transport or NAA catabolism.

Increased N-acetylaspartate in model mouse of Pelizaeus-Merzbacher disease.

PURPOSE: To evaluate the N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) biochemical pathways in the brain of myelin synthesis-deficient (msd) mouse, a model of Pelizaeus-Merzbacher disease (PMD). MATERIALS AND METHODS: We performed magnetic resonance imaging and proton magnetic resonance spectroscopy (¹H-MRS) of the thalamus for msd and wildtype mice with a 7.0 T magnet. NAA and NAAG were independently measured by high-performance liquid chromatography (HPLC). Immunohistochemical analysis using anti-Mbp, Gfap, Ng2, and NeuN antibodies were also performed. RESULTS: ¹H-MRS in msd mice revealed increased total NAA (tNAA, NAAþNAAG), creatine, glutamine, and glutamate and decreased choline (Cho). HPLC analysis revealed increases of both NAA and NAAG in the msd brains. Histologically, the msd brains revealed hypomyelination and astrogliosis. Oligodendrocyte progenitor cells and neurons were normal in number in the thalamus wherein ¹H-MRS was obtained. CONCLUSION: The evidence suggests that the neurochemical derangement in the msd mice may be a primary increase of NAA resulting in a secondary increase of NAAG. Increased tNAA with decreased Cho detectable on ¹H-MRS may be an important marker for PMD, and might be used to distinguish it from more common neurological disorders that have decreased tNAA.

Pituitary cysts in childhood evaluated by MR imaging.

BACKGROUND AND PURPOSE: Pituitary cysts are common findings on pathologic examination and imaging studies. They are generally considered to be rarer in children than in adults; however, no good data exist to substantiate this opinion. We reviewed MR imaging studies to evaluate the frequency and imaging features of pituitary cysts in children. METHODS: We retrospectively reviewed T1-weighted sagittal images in 341 patients <15 years of age to evaluate for pituitary cysts. Paramagnetic contrast was administered in 86 of the 341 patients. Sagittal or coronal fast spin-echo T2-weighted images were performed in 166 patients. For patients having pituitary cysts, pituitary function was examined by assessing blood levels of pituitary hormones. RESULTS: A cystic pituitary lesion was recognized in 4 patients (1.2%) aged 1-4 years. None of the 4 manifested endocrinologic signs or symptoms or were the results of their laboratory studies abnormal. All the lesions were sharply demarcated and situated just posterior to the anterior pituitary lobe. All were iso- or hypointense compared with the pons on T1-weighted images without contrast enhancement, suggesting a Rathke cleft cyst. MR imaging of a patient with probable low-grade gliomas in the left hypothalamic region and optic chiasma showed complete resolution of a pituitary cyst at a 1-year follow-up study. CONCLUSION: The frequency of pituitary cysts on MR imaging in childhood is almost equal to that of Rathke cleft cysts, as assessed in autopsy studies of subjects aged 10 to 29 years. These cysts are common in children and should be considered, in the absence of signs or symptoms of pituitary dysfunction, as incidental findings.