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ABSTRACT: We report on a 6-year-old boy with nephrotic syndrome (NS) who developed Wernicke’s encephalopathy (WE) concomitantly with
posterior reversible encephalopathy syndrome (PRES). In this case, the recurrence of encephalopathy with different causes
made his clinical picture complex, and the follow-up findings of magnetic resonance imaging (MRI) were critically useful for
the adequate diagnosis and timely management of the patient. This case suggests the need to consider WE as a possible serious
complication in patients with NS, and also emphasizes the usefulness of MRI in the diagnosis of WE, especially in pediatric
cases with complex clinical symptoms.
European Journal of Pediatrics 04/2012; 168(6):731-734. · 1.88 Impact Factor
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Pediatrics International 04/2012; 54(2):305-6. · 0.63 Impact Factor
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ABSTRACT: Glucose transporter type 1 (Glut1) is expressed in vascular endothelial cells comprising blood-brain barrier. Glut1 deficiency syndrome is characterized by low cerebrospinal fluid (CSF) concentration of glucose with normoglycemia, infantile seizure, acquired microcephaly, developmental delay and ataxia. As Glut1 is also expressed in erythrocytes, the diagnosis is confirmed by a decreased uptake of 3-O-methylglucose (3-OMG) into erythrocytes. However, patients with T295M mutation in the Glut1 gene show normal 3-OMG uptake. An in vitro study has proved that the T295M affects efflux rather than influx of glucose, explaining the discrepancy. However, the normal 3-OMG uptake in erythrocytes still indicates a possibility that the phenotype associated with this particular mutation may be milder. We compared the phenotype of three T295M-associated patients with that of other Glut1-deficient patients.
Two patients are from our clinic and one is a patient reported elsewhere. The phenotype and biochemical data of patients with mutations other than T295M were obtained from a review and our previous report.
Despite the normal 3-OMG uptake into erythrocytes, all patients with T295M showed decreased glucose levels in CSF (33, 31 and 38mg/dl, respectively). The levels were comparable to those in patients with mutations other than T295M (31±4.3mg/dl (n=45)). All patients had convulsion, ataxia, speech delay, microcephaly and spasticity.
Despite the normal 3-OMG uptake in erythrocytes, phenotype of T295M-associated Glut1 deficiency was not significantly different from that of patients with a deficient 3-OMG uptake, indicating that T295M affects the glucose transport at the blood-brain barrier as much as other mutations.
Brain & development 04/2011; 33(4):316-20. · 1.74 Impact Factor
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Tatsuji Hasegawa,
Kei Yamada, Masafumi Morimoto,
Shigemi Morioka,
Takenori Tozawa,
Kenichi Isoda,
Aki Murakami,
Tomohiro Chiyonobu,
Sachiko Tokuda,
Akira Nishimura,
Tsunehiko Nishimura,
Hajime Hosoi
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ABSTRACT: Callosal injury in preterm infants is a key factor affecting neurodevelopmental outcome. We investigated the characteristics of corpus callosum (CC) in preterm infants without apparent white matter lesions. We studied 58 preterm infants divided into three groups of 23-25, 26-29, and 30-33 wk GA. Diffusion tensor imaging (DTI) was obtained at term-equivalent age. The CC was parcellated into the genu, body, isthmus, and splenium. We measured fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of each CC subdivision using tractography and manual region of interest analysis. The cross-sectional areas were also measured. At the isthmus and splenium in the 23-25 GA group, the FA was significantly lower and the size was also significantly reduced. Furthermore, the FA and cross-sectional areas in the posterior CC decreased linearly with decreasing GA. There were no differences in FA and cross-sectional areas in other CC subdivisions, and no differences in ADC in any CC subdivisions, among the GA groups. We demonstrated that preterm infants without apparent white matter lesions affect development of the posterior CC depending on the degree of prematurity.
Pediatric Research 03/2011; 69(3):249-54. · 2.70 Impact Factor
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ABSTRACT: We report a 2-year-old girl who demonstrated "benign convulsions with gastroenteritis (CwG)" with transient splenial lesions twice during the winter. The first episode was associated with noro-virus and the second with rota-virus. During each episode, seizures occurred in clusters without clinical signs of dehydration, hypoglycemia, electrolyte derangement or cerebrospinal fluid abnormalities, and her consciousness was clear during the interictal period. Those findings were consistent with CwG. As transient splenial lesions were not accompanied by any neurological abnormalities other than seizures, she was not diagnosed as having encephalopathy, but as having CwG. Diffusion-weighted magnetic resonance imaging of the brain demonstrated hyperintense lesions in the splenium of the corpus callosum, which disappeared within a week. We speculate that CwG is likely to lead to transient splenial lesions.
No to hattatsu. Brain and development 11/2010; 42(6):449-53.
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Pediatrics International 05/2009; 51(2):293-5. · 0.63 Impact Factor
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ABSTRACT: Preterm or low birth weight infants display a greater propensity for white matter injury caused by hypoxic-ischemic encephalopathy in the perinatal period. Such episodes can result in periventricular leukomalacia, which may substantially influence later brain development. Noninvasive methods of assessing the severity of injury at the earliest stage of life have not yet been established.
We used diffusion tensor imaging to evaluate sensorimotor fibers in periventricular leukomalacia. Region-of-interest measurements and tractography-based measurements were performed for 10 patients with periventricular leukomalacia. The mean age of the patients was 19 +/- 9.5 months (range: 9-41 months). Motor functions were assessed at a mean age of 28 +/- 14.5 months.
Measured fractional anisotropy values of the motor tract were significantly higher in all mild periventricular leukomalacia cases than in severe cases. A fractional anisotropy cutoff value of <0.5 was useful for predicting severe periventricular leukomalacia. Region-of-interest measurements were less sensitive, compared with tractography-based measurements.
Fiber-tracking techniques can provide information on the pathophysiologic features of motor disability in patients with periventricular leukomalacia. Early screening of patients with a history of asphyxia may facilitate early intervention (eg, rehabilitation), to achieve better motor function.
PEDIATRICS 10/2008; 122(3):500-6. · 4.47 Impact Factor
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ABSTRACT: We report on a 6-year-old boy with nephrotic syndrome (NS) who developed Wernicke's encephalopathy (WE) concomitantly with posterior reversible encephalopathy syndrome (PRES). In this case, the recurrence of encephalopathy with different causes made his clinical picture complex, and the follow-up findings of magnetic resonance imaging (MRI) were critically useful for the adequate diagnosis and timely management of the patient. This case suggests the need to consider WE as a possible serious complication in patients with NS, and also emphasizes the usefulness of MRI in the diagnosis of WE, especially in pediatric cases with complex clinical symptoms.
European Journal of Pediatrics 10/2008; 168(6):731-4. · 1.88 Impact Factor
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ABSTRACT: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is most commonly associated with a mitochondrial DNA A to G point mutation at nucleotide 3243 (A3243G) and individuals with the disorder present a wide range of multisystemic symptoms. Seizures in MELAS patients are often intractable and require multiple antiepileptic drugs. Here we report a MELAS patient who presented with acute intestinal pseudo-obstruction following the administration of phenytoin (PHT) as an antiepileptic treatment. She presented with the first stroke-like episode at the age of 6 years and mitochondrial DNA analysis revealed A3243G with 94% mutation load in skeletal muscle. Despite treatment with phenobarbital and clobazam at the age of 16 years, she developed status epilepticus which ceased following PHT infusion. Thereafter, she was started on PHT treatment. One month later, however, she was readmitted because of remarkable abdominal distention. Although abdominal CT showed acute ileus with hepatic portal venous gas mimicking surgical emergency, the abdominal distention gradually recovered over several days following the discontinuation of PHT. Our clinical observations suggest the possibility that intestinal pseudo-obstruction in this patient related to PHT therapy. Careful clinical observation including gastrointestinal symptoms is required in the management of epilepsy in MELAS patients.
Brain and Development 07/2008; 30(6):430-3. · 2.12 Impact Factor
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ABSTRACT: An 11-year-old girl who had been given antiepileptic drugs (AEDs) for occipital lobe epilepsy was hospitalized with alternative psychosis and dysgraphia accompanied by forced normalization of the EEG. Her epileptic seizures and psychosis disappeared after administration of carbamazepine. She developed dysgraphia for Kanji words (Japanese morphograms). The EEG showed sporadic spikes predominantly in the left occipital region, and [123I]iomazenil single-photon-emission computed tomography (IMZ-SPECT) imaging revealed an area of hypoperfusion in the left occipital lobe. Interestingly, the left posterior inferior temporal area is known to play an important role in writing Kanji words. It is assumed that abnormal discharges in the left occipital lobe were projected into the left posterior inferior temporal area and that a functional disorder in that area led to dysgraphia; however, further exploration is needed.
Epilepsy & Behavior 05/2008; 12(3):481-5. · 2.34 Impact Factor
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Tomohiro Chiyonobu,
Shin Hayashi,
Kazuhiro Kobayashi, Masafumi Morimoto,
Yuri Miyanomae,
Akira Nishimura,
Akemi Nishimoto,
Chiyomi Ito,
Issei Imoto,
Tohru Sugimoto,
Zhengping Jia,
Johji Inazawa,
Tatsushi Toda
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ABSTRACT: The genetic factors underlying mental retardation (MR) are very heterogeneous. Recent studies have identified a number of genes involved in MR, several of which lie on the X-chromosome, but the current understanding of the monogenic causes of MR is far from complete. Investigation of chromosomal rearrangements in patients with MR has proven particularly informative in the search for novel genes. Using array-based comparative genomic hybridization analysis, we identified a small copy number gain at Xq25, which was undetectable by conventional G-band analysis, in a boy with unexplained MR. Further characterization revealed a partial tandem duplication of GRIA3, an alteration also present on one allele in his mother. RT-PCR analysis of lymphoblastoid cell RNA revealed remarkably reduced GRIA3 transcript levels in the patient. The mother, whose cognitive level is normal, also demonstrated remarkably reduced GRIA3 transcript levels in lymphoblastoid cells, and X-chromosome inactivation (XCI) was completely skewed in her peripheral lymphocytes. It is possible that XCI in the brain is not completely skewed and that GRIA3 expression from the normal allele may account for the mother's normal cognitive function. Taken together with previous findings of GRIA3 disruptions in the patients with MR, our study strengthens the idea that GRIA3 is a candidate gene for X-linked MR and that severely reduced GRIA3 expression results in MR.
American Journal of Medical Genetics Part A 08/2007; 143A(13):1448-55. · 2.39 Impact Factor
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ABSTRACT: Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms.
Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9.
Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model.
These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.
Stroke 02/2007; 38(1):162-9. · 5.73 Impact Factor
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Masafumi Morimoto,
Emi Mazaki,
Akira Nishimura,
Tomohiro Chiyonobu,
Yasuko Sawai,
Aki Murakami,
Keiko Nakamura,
Ikuyo Inoue,
Ikuo Ogiwara,
Tohru Sugimoto,
Kazuhiro Yamakawa
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ABSTRACT: To investigate the genetic background of familial severe myoclonic epilepsy in infancy (SMEI) cases.
We performed mutation analyses of the sodium-channel gene SCN1A in two Japanese brothers with clinical features of SMEI and their parents, who had no history of febrile and epileptic seizures.
Each patient showed nucleotide changes (c.[730G>T; 735G>T; 736A>T]) in the coding exon 6 of SCN1A that led to a truncation of the channel protein. Their father showed no mutations, but their mother showed the same mutation in a subpopulation of lymphocytes.
The maternal mosaicism explains the identical SCN1A mutations in the two brothers. This highlights the importance of investigating parental mosaicism even in sporadic SMEI cases.
Epilepsia 11/2006; 47(10):1732-6. · 3.96 Impact Factor
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ABSTRACT: N-Methyl-D-aspartate-mediated neurotoxicity is known to involve nitric oxide production and to be augmented in an environment of reactive oxygen species. We used TUNEL staining and homogenous cytosolic immunoreactivity of cytochrome c in an acute brain slice preparation to investigate the influence of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, on N-methyl-D-aspartate-induced apoptosis. Cerebrocortical slices were obtained from parietal lobes of 7-day-old Sprague-Dawley rats, superfused with well-oxygenated artificial cerebrospinal fluid, and metabolically recovered. Subsequent 30-min exposures to 10 microM N-methyl-D-aspartate in treated and untreated slices were followed by 4 h of recovery superfusion with oxygenated artificial cerebrospinal fluid. Outcomes were compared for three groups of slices: "the N-methyl-D-aspartate-only group"; "the edaravone treatment group", which had 20 microM edaravone present throughout and subsequent to N-methyl-D-aspartate exposure; the "control group", in which slices were superfused only with oxygenated artificial cerebrospinal fluid. At the conclusion of recovery (t = 4 h), the percentage of TUNEL-positive cells in the edaravone treatment group (7.0+/-3.3%) was significantly reduced from the percentage for the N-methyl-D-aspartate-only group (21.9+/-4.1%), and insignificantly greater than the percentage for the control group (3.4+/-2.1%). Percentages of cytochrome c positive cells at t = 1 h were significantly increased (p < 0.01) in the N-methyl-d-aspartate-only group (30.6+/-1.9%) compared to percentages for both the control group (11.4+/-2.6%) and the edaravone treatment group (15.2+/-2.1%). Edaravone's reduction in TUNEL staining and cytochrome c release provides evidence of reactive oxygen species mechanisms and antioxidant benefits in cytochrome c-mediated apoptosis during N-methyl-D-aspartate excitotoxicity.
International Journal of Developmental Neuroscience 10/2006; 24(6):349-56. · 2.42 Impact Factor
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ABSTRACT: A 1-year-old female with acute bilateral striatal necrosis secondary to exanthema subitum associated with human herpesvirus 6 (HHV-6) infection is reported. The patient was previously healthy. She presented with progressive neurologic signs of oral dyskinesia and involuntary movements, after suffering from exanthema subitum. Initial magnetic resonance imaging (MRI) demonstrated abnormal signals in the bilateral striatal regions. In addition, the serum HHV-6 IgM class antibody level was significantly increased. The patient is thought to be the first case of HHV-6 infection related infantile bilateral striatal necrosis (IBSN).
Brain and Development 11/2005; 27(7):527-30. · 2.12 Impact Factor
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ABSTRACT: Mineralocorticoid receptor (MR) is a ligand-dependent transcription factor involved in gene regulation in association with another corticosteroid receptor, glucocorticoid receptor. In the absence of ligand, MR resides both in the cytoplasm and in the nucleus. Agonists increase the number of MRs residing in the nucleus. Importins are docking proteins for karyopherin-mediated binding of substrate in a nuclear import pathway. To investigate the interactions between MR and importins, we analyzed the subcellular distribution of MR and importins in response to ligand in living COS-1 cells, which do not express endogenous MR, by using fusion proteins labeled with different spectral variants of green fluorescent protein. In the cells coexpressing fluorescent protein-tagged (FP)-MR and FP-importin alpha, the proteins simultaneously moved into the nucleus from the cytoplasm upon activation with ligand treatment. In the cells coexpressing FP-MR and FP-importin beta, FP-MR moved into the nucleus from the cytoplasm, but the distribution of FP-importin beta was little changed upon ligand treatment. Analysis of a mutant of MR, in which nuclear localization signal (NLS) is inactivated, demonstrated that the intact NLS is necessary for the trafficking of MR related to importin alpha. This is the first visual evidence of the nuclear import of MR in association with importin alpha in single living cells.
Cell and Tissue Research 07/2005; 320(3):447-53. · 3.11 Impact Factor
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Masafumi Morimoto,
Byongmun An,
Aya Ogami,
Noriko Shin,
Yuriko Sugino,
Yasuko Sawai,
Tomohiro Usuku,
Masayuki Tanaka,
Kiyoshi Hirai,
Akira Nishimura,
Koh Hasegawa,
Tohru Sugimoto
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ABSTRACT: A patient with Williams syndrome, craniosynostosis, and infantile spasms is described. At age 6 months, the infant demonstrated infantile spasms and craniosynostosis and was operated on for craniosynostosis and treated with adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely controlled the seizures, but was halted because of the progression of ventricular hypertrophy. The seizure returned, and he was found to have elfin face, failure-to-thrive, developmental delay, and dental malformation in addition to congenital heart defects. High-resolution chromosome analysis revealed interstitial deletion of 7q11.22-q11.23. Therefore his clinical and cytogenetic diagnosis was Williams syndrome. Thyrotropin-releasing hormone (TRH) therapy reduced his seizures and improved the findings of EEG without cardiac side effects. In addition, his psychomotor development was slightly improved.
Epilepsia 12/2003; 44(11):1459-62. · 3.96 Impact Factor
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Masafumi Morimoto,
Byongmun An,
Aya Ogami,
Noriko Shin,
Yuriko Sugino,
Yasuko Sawai,
Tomohiro Usuku,
Masayuki Tanaka,
Kiyoshi Hirai,
Akira Nishimura,
Koh Hasegawa,
Tohru Sugimoto
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ABSTRACT: A patient with Williams syndrome, craniosynostosis, and infantile spasms is described. At age 6 months, the infant demonstrated infantile spasms and craniosynostosis and was operated on for craniosynostosis and treated with adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely controlled the seizures, but was halted because of the progression of ventricular hypertrophy. The seizure returned, and he was found to have elfin face, failure-to-thrive, developmental delay, and dental malformation in addition to congenital heart defects. High-resolution chromosome analysis revealed interstitial deletion of 7q11.22-q11.23. Therefore his clinical and cytogenetic diagnosis was Williams syndrome. Thyrotropin-releasing hormone (TRH) therapy reduced his seizures and improved the findings of EEG without cardiac side effects. In addition, his psychomotor development was slightly improved.
Epilepsia 10/2003; 44(11):1459 - 1462. · 3.96 Impact Factor
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ABSTRACT: Three patients showing epileptic seizures and with mosaicism of ring chromosome 14 and monosomy for chromosome 14 are described. Patients were a 17-year-old boy, karyotype 46, XY, r(14)(p12q32.33)/45, XY, -14, a 7-month-old boy, karyotype 46, XY, r(14)(p11.2q32.33)/45, XY, -14, and a 10-month-old boy, karyotype 46, XY, r(14)(p12q32.31)/45, XY, -14. Microcephaly and alopecia were observed in the first patient. However, few dysmorphic features were found typical of ring 14 chromosome. He had exhibited complex partial seizures with secondary generalization at age 3 months and had mild motor and mental retardation. Both other patients had atonic seizures followed by staring, perioral cyanosis, and respiratory arrest at age 7 or 8 months. Both also showed mild developmental delay and had a few minor anomalies compatible with ring 14 chromosome. Interictal spikes were observed in the second patient in the right occipital region, whereas an interictal encephalogram of the third patient showed sporadic spikes in the left central region. In all three cases, seizures were resistant to common antiepileptic drugs.
Epilepsia 10/2003; 44(9):1245-9. · 3.96 Impact Factor
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ABSTRACT: Glucocorticoid receptor (GR) acts as a ligand-dependent transcription factor after nuclear transport from the cytoplasm in the liganded state. Importins are docking proteins for karyopherin-mediated binding of substrate in a nuclear import pathway. To investigate the spatial and temporal relation between GR and importins, we analyzed the subcellular distribution of GR and importins in response to ligand in single living cells using fusion proteins labeled with different spectral variants of green fluorescent protein. Upon activation with ligand treatment, fluorescent protein-tagged (FP-) GR was translocated from the cytoplasm to the nucleus, showing a similar time course as FP-importin-alpha in the coexpressed cells with the fusion proteins. In contrast to FP-importin-alpha, the distribution of FP-importin-beta was little changed upon ligand treatment in the coexpressed cells with FP-GR and FP-importin-beta. Analysis using fluorescence resonance energy transfer proved that GR directly interacted with importin-alpha in the whole area of the cytoplasm upon ligand treatment and detached importin-alpha shortly after nuclear import. However, direct interaction between GR and importin-beta was not detected. These studies showed visual evidence of the nuclear importing of GR in association with importin-alpha in single living cells.
Endocrinology 10/2003; 144(9):4070-9. · 4.46 Impact Factor
