A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy

BACKGROUND: Deficiency of 4-aminobutyrate aminotransferase (GABA-T) is a rare disorder of GABA catabolism, with only a single sibship reported. We report on a third case, a Japanese female infant with severe psychomotor retardation and recurrent episodic lethargy with intractable seizures, with the diagnosis facilitated by proton magnetic resonance (MR) spectroscopy ((1)H-MRS). METHODS: Neuroimaging was performed at the first episode of lethargy. For (1)H-MRS, locations were placed in the semioval center and the basal ganglia. Quantification of metabolite concentrations were derived using the LCModel. We confirmed the diagnosis subsequently by enzyme and molecular studies, which involved direct DNA sequence analysis and the development of a novel multiplex ligation-dependent probe amplification test. RESULTS: (1)H-MRS analysis revealed an elevated GABA concentration in the basal ganglia (2.9 mmol/l). Based on the results of quantitative (1)H-MRS and clinical findings, GABA-T deficiency was suspected and confirmed in cultured lymphoblasts. Molecular studies of the GABA-T gene revealed compound heterozygosity for a deletion of one exon and a missense mutation, 275G>A, which was not detected in 210 control chromosomes. CONCLUSIONS: Our results suggest that excessive prenatal GABA exposure in the central nervous system (CNS) was responsible for the clinical manifestations of GABA transaminase deficiency. Our findings suggest the dual nature of GABA as an excitatory molecule early in life, followed by a functional switch to an inhibitory species later in development. Furthermore, quantitative (1)H-MRS appears to be a useful, noninvasive tool for detecting inborn errors of GABA metabolism in the CNS

MR imaging findings in some rare neurological complications of paediatric cancer

Abstract Neurological complications of paediatric cancers are a substantial problem. Complications can be primary from central nervous system (CNS) spread or secondary from indirect or remote effects of cancer, as well as cancer treatments such as chemotherapy and radiation therapy. In this review, we present the clinical and imaging findings of rare but important neurological complications in paediatric patients with cancer. Neurological complications are classified into three phases: pre-treatment, treatment and post-remission. Paraneoplastic neurological syndromes, hyperviscosity syndrome, haemophagocytic lymphohistiocytosis and infection are found in the pre-treatment phase, while Trousseau’s syndrome, posterior reversible encephalopathy syndrome and methotrexate neurotoxicity are found in the treatment phase; though some complications overlap between the pre-treatment and treatment phases. Hippocampal sclerosis, radiation induced tumour, radiation induced focal haemosiderin deposition and radiation-induced white matter injury are found in the post-remission phase. With increasingly long survival after treatment, CNS complications have become more common. It is critical for radiologists to recognise neurological complications related to paediatric cancer or treatment. Magnetic resonance imaging (MRI) plays a significant role in the recognition and proper management of the neurological complications of paediatric cancer. Teaching Points • Neurological complications of paediatric cancer include various entities. • Neurological complications are classified into three phases: pre-treatment, treatment and post-remission. • Radiologists should be familiar with clinical and imaging findings of neurological complications. • MRI features may be characteristic and lead to early diagnosis and proper treatments

Acute pediatric encephalopathy; an analysis of an index, based on the two-compartment-model of in vivo DWI.

【目的】小児急性脳症において, 拡散強調画像(DWI)の異常は高頻度であるが, 実質萎縮に至る症例でも急性期の異常は限局的なことがある. Two-compartment-modelに関する指標が潜在的な脳障害ををより描出できるかについて検討すること.【方法】小児急性脳症症例(脳症群)13例(1-13歳, 平均4.5), 神経学的な異常が認められたが画像所見に異常が無く臨床的に脳症ではないと診断された小児例(正常群)10例(1-9歳, 平均4.5)の脳MRIをretrospectiveに検討. 3T MRIによりb=500,1500,2500としたDWIを撮像し, 画像データからtwo-compartment-modelを想定した指標FH (b=500,1500の信号値から計算上求められるb=0の信号値をa, 同様にb=1500,2500から求められる計算上のb=0の信号値をbとしたときFH=b/a)を算出した. 各症例に皮質･皮質下領域に相当する10カ所のROI (半卵円中心レベルで左右前頭葉, 頭頂葉; 基底核レベルで左右前頭葉, 側頭葉, 後頭葉) を設定し, 脳症群-正常群間で比較した. 加えて, 脳症群のうち内部にDWI異常信号が明瞭でないROIを抽出し, 同様に部位ごとに脳症群と正常群で比較した.【結果】脳症群/正常群の比較ではFHは9カ所において脳症群で有意に高かった(P<0.05). 脳症群ではDWIで異常信号の明瞭でない部位でも正常群との比較でFHは5カ所において有意に高かった(P<0.05). 【結論】FHはDWIより鋭敏に脳症による変化を示す可能性が示唆された.第71回日本医学放射線学会総

Acute hemicerebellitis in a pediatric patient: a case report of a serial MR spectroscopy study

The changes in the signals for brain metabolites in the left cerebellum of a 14-year-old boy with acute hemicerebellitis were monitored using proton magnetic resonance spectroscopy (MRS). From the onset of disease treatment to long-term follow-up, MRS data were serially acquired from the left and right cerebella, basal ganglia (BG), and centrum semiovale (CS). Large fluctuations in his MRS signals were observed in the left cerebellum. At onset (first day), his glutamate/glutamine complex signals were increased (>mean +- 2 standard deviations [SD] of the control), and those for N-acetylaspartate/N-acetylaspartylglutamate and myo-inositol were decreased (<2SD). By the 25th day, these signals had recovered to normal levels, while those for choline (Cho) were increased. In other locations, the signals for mIns in the BG and Cho in the CS were decreased on the seventh day. By the 201st day, the levels of all metabolites in all locations had recovered to within +- 2SD of the control levels. In vivo proton MRS monitoring demonstrated reversible metabolite changes associated with acute hemicerebellitis, which should contribute to its differential diagnosis from brain tumors

The reliability and validity of the Japanese version of the Temperament and Personality Questionnaire for patients with non-melancholic depression

BackgroundParker et al. (2006) proposed a new approach to classify specific sub-types of non-melancholic depression caused by various stress factors and premorbid personality styles: the Temperament and Personality Questionnaire (T&amp;P). The current study aim was to develop the Japanese version of the T&amp;P and evaluate its reliability and validity.MethodsWe studied 114 patients with non-melancholic depression. Reliability was assessed using the test-retest method. Convergent validity of the T&amp;P was compared with the clinician ratings of each patient for the eight personality traits. We also assessed the impact of depressive state on the T&amp;P.ResultsThe test-retest intraclass correlation coefficients among eight constructs of the T&amp;P ranged from 0.77 to 0.89, indicating good-to-excellent reliability. Anxious Worrying (rho=0.29), Perfectionism (rho=0.17), Personal Reserve (rho=0.18), Irritability (rho=0.38), and Social Avoidance (rho=0.32) showed adequate levels of convergent validity; Rejection Sensitivity (rho=0.16), Self-criticism (rho=-0.02), and Self-focus (rho=0.07) showed relatively weak convergent validity. Perfectionism (rho=-0.06), Social Avoidance (rho=0.17), Anxious Worrying (rho=0.40), Personal Reserve (rho=0.30), Irritability (rho=0.28), Rejection Sensitivity (rho=0.35), Self-criticism (rho=0.49), and Self-focus (rho=0.24) showed minimal sensitivity to mood state effects.LimitationsOnly one site was used. While a Likert scale was used, the clinician-rated personality trait measure had not been validated.ConclusionsThe J-T&amp;P is a reliable and valid measure for assessing temperament and personality in Japanese patients with non-melancholic depression