Tetsuo Kubota

Anjo Kosei Hospital, Anjō, Aichi, Japan

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Publications (59)111.26 Total impact

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    ABSTRACT: To determine the early changes and evolutions of brain diffusion-weighted imaging (DWI), and analyze prognostic factors of the early changes among patients with neonatal herpes simplex encephalitis (NHSE).
    Brain & development. 08/2014;
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    ABSTRACT: Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and developmental outcome in cryptogenic West syndrome. From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated. At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03). Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.
    American Journal of Neuroradiology 03/2014; · 3.17 Impact Factor
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    ABSTRACT: Background We aimed to assess the characteristics of thalamic lesions in children with acute encephalopathy with biphasic seizures and late reduced diffusion. Methods Using the Tokai Pediatric Neurological Society database, we identified and enrolled 18 children with acute encephalopathy with biphasic seizures and late reduced diffusion from 2008 to 2010. Using diffusion-weighted images, we identified patients with thalamic lesions and compared their clinical factors with those of patients without thalamic lesions. We analyzed the time sequence of thalamic and subcortical/cortical lesions. To study the topography of thalamic lesions, we divided the thalamus into 5 sections: anterior, medial, anterolateral, posterolateral, and posterior. Subsequently, we analyzed the relation between the topography of thalamic lesions and the presence of central-sparing. Results Seven children presented with symmetrical thalamic lesions associated with bilateral subcortical/cortical lesions. No statistical difference in the clinical features was noted between patients with and without thalamic lesions. These lesions were observed only when subcortical/cortical lesions were present. In 5 children, thalamic lesions were present in bilateral anterior and/or anterolateral sections and were associated with subcortical/cortical lesions in bilateral frontal lobes with central-sparing. In the other 2 children, thalamic lesions were extensive and accompanied by diffuse subcortical/cortical lesions without central-sparing. Conclusion Thalamic lesions in patients with acute encephalopathy with biphasic seizures and late reduced diffusion involve the anterior sections. The thalamocortical network may play a role in development of thalamic lesions in patients with acute encephalopathy with biphasic seizures and late reduced diffusion.
    Pediatric Neurology. 01/2014;
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    ABSTRACT: Introduction: Epilepsies with an onset during the early infantile period are relatively rare and their characteristics are not well recognized. The aim of this study was to determine the clinical characteristics of epilepsies with an onset during the early infantile period. Methods: Clinical information on 73 patients with the onset of epilepsy within the first four months was collected from hospitals affiliated with Nagoya University. Patients were categorized into three groups: the idiopathic (20 patients), cryptogenic (19 patients), and symptomatic groups (34 patients). Results: Fourteen (70%) of the 20 patients in the idiopathic group, nine (47%) of the 19 patients in the cryptogenic group, and 10 (29%) of the 34 patients in the symptomatic group had their first seizure within the first month of life. All patients in the idiopathic group, 12 patients (63%) in the cryptogenic group, and 18 patients (53%) in the symptomatic group had partial seizures (PS) alone throughout their clinical course. Four patients in the cryptogenic group and nine in the symptomatic group had PS at the onset, but evolved into spasms later. All patients in the idiopathic group, 13 patients (68%) in the cryptogenic group, and 13 patients (38%) in symptomatic group had experienced no seizures for at least one year at the time of the last follow-up. Conclusions: In patients with non-idiopathic epilepsy, an age-dependent evolution of seizure types was often observed. Recognition of this subgroup of patients could be important for the identification of appropriate candidates for early epilepsy surgery.
    Brain & development 11/2013; · 1.74 Impact Factor
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    ABSTRACT: Purpose: To clarify the differences between infants with periventricular hemorrhagic infarction (PVHI) and those with periventricular leukomalacia (PVL). Methods: We retrospectively evaluated the clinical features, ultrasonography, and electroencephalogram (EEG) findings in 22 preterm infants with PVHI and 49 with PVL. EEG and cranial ultrasonography were serially performed in all participants starting immediately after birth. Acute and chronic stage EEG abnormalities were evaluated separately. Results: Gestational age and birth weight were significantly lower in infants with PVHI than those with PVL. EEGs were normal in the majority of infants with PVHI on days 1-2. However, EEG abnormalities appeared after ultrasonography abnormalities. The majority of infants with PVL showed acute-stage EEG abnormalities on days 1-2. The rate of infants with acute-stage EEG abnormalities decreased with age, whereas the rate of infants with chronic-stage EEG abnormalities increased with age. Normal EEG before ultrasonography abnormalities was more common in infants with PVHI than in those with PVL. However, deterioration of acute-stage EEG abnormalities was more frequent in infants with PVHI than in those with PVL. Conclusions: PVHI was presumed to cause mostly postnatal injury, whereas PVL was presumed to cause mostly pre-or perinatal injury.
    Brain & development 08/2013; · 1.74 Impact Factor
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    ABSTRACT: Background and objectives: Conventional electroencephalogram (cEEG) is a reliable predictor of outcome in term infants with hypoxic ischemic encephalopathy (HIE). Early therapeutic hypothermia initiated within 6h after birth is a beneficial treatment in these infants. However, a classification system with reduced cEEG recording time to determine early intervention has not been reported. The aim of this study is to propose a new classification of depression on cEEG with reduced recording time in infants with HIE and to examine the correlation between the classification and short-term outcome. Patients and methods: We retrospectively investigated 20 term infants with HIE in whom cEEG was performed within 12h after birth, and deaths or outcomes at 18months of age were assessed. We determined grades 0-3 EEG depression in each 10-min epoch based on the most common EEG patterns of each 20s epoch defined by our criteria. Results: Eighteen infants could be assessed by depression grade. The Spearman's rank correlation coefficient Rs between the maximum depression grade in 10-min epochs and three-grade outcomes was 0.68 (P=0.002), and that between the minimum one and outcomes was 0.66 (P=0.003). The area under the receiver operating characteristic curve of the maximum and minimum depression grades for predicting abnormal outcome were 0.885 and 0.869, respectively. Conclusions: We demonstrated a new cEEG depression classification with a recording time of at least 10min in term infants with HIE and a good correlation with short-term outcome.
    Brain & development 07/2013; · 1.74 Impact Factor
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    ABSTRACT: We performed diffusion tensor imaging (DTI) in children with periventricular leukomalacia (PVL) to quantify the relationship between the fractional anisotropy (FA) values of DTI and the severity of PVL. In this study, we performed DTI in 16 children (seven males, nine females) with PVL. To evaluate the FA values, we used region-of-interest (ROI) measurements and tractography-based measurements. We classified the patients into two groups based on the severity of the magnetic resonance imaging (MRI) findings: the mild group had white matter injury limited to a triangular zone around the lateral ventricle (n = 9) and the severe group had it extended forward (n = 7). Then, we performed ROI measurements for these two groups to evaluate the FA values. We also divided the patients into two groups based on their motor ability :those that could (n = 10) and could not (n = 6) stand. We used tractography-based measurements to evaluate the FA values. To reduce the bias caused by age, we divided the patients into two groups: those younger than 3 years and those 3 years of age and older. All data were analyzed using the Mann-Whitney U-test, and p < 0.05 was considered statistically significant. In the ROI measurements, regardless of age, the severe group showed a more significant FA reduction in the white matter of the parietal and occipital lobes, including the middle/posterior part of the centrum ovale, superior longitudinal fasciculus, arcuate fascicullus, and thalamic radiation. In the tractography-based measurements, regardless of age, the measured FA values were significantly lower in the group that could not stand. This study suggested that the measured FA values could be used to evaluate the severity of PVL quantitatively, and that DTI provides much more information for understanding the pathophysiology of PVL, as compared with conventional MRI.
    No to hattatsu. Brain and development 01/2013; 45(1):21-5.
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    ABSTRACT: Mutations in PRRT2 genes have been identified as a major cause of benign infantile epilepsy and/or paroxysmal kinesigenic dyskinesia. We explored mutations in PRRT2 in Japanese patients with BIE as well as its related conditions including convulsion with mild gastroenteritis and benign early infantile epilepsy. We explored PRRT2 mutations in Japanese children who had had unprovoked infantile seizures or convulsion with mild gastroenteritis. The probands included 16 children with benign infantile epilepsy, 6 children with convulsions with mild gastroenteritis, and 2 siblings with benign early infantile epilepsy. In addition, we recruited samples from family members when PRRT2 mutation was identified in the proband. Statistical analyses were performed to identify differences in probands with benign infantile epilepsy according to the presence or absence of PRRT2 mutation. Among a total of 24 probands, PRRT2 mutations was identified only in 6 probands with benign infantile epilepsy. A common insertion mutation, c.649_650insC, was found in 5 families and a novel missense mutation, c.981C>G (I327M), in one. The family history of paroxysmal kinesigenic dyskinesia was more common in probands with PRRT2 mutations than in those without mutations. Our study revealed that PRRT2 mutations are common in Japanese patients with benign infantile epilepsy, especially in patients with a family history of paroxysmal kinesigenic dyskinesia.
    Brain & development 11/2012; · 1.74 Impact Factor
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    ABSTRACT: Using a standard digital EEG system, we conducted simulations to determine the optimal locations and numbers of electrodes for seizure detection in neonates with reduced-channel EEG monitoring. The results showed that C3-C4 should be selected for a one-channel recording, but two-channel seizure monitoring is recommended for increased accuracy.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 10/2012; · 3.45 Impact Factor
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    ABSTRACT: To clarify the prognostic value of conventional EEG for the identification of preterm infants at risk for subsequent adverse neurodevelopment in the current perinatal care and medicine setting. We studied 780 EEG records of 333 preterm infants born <34 weeks' gestation between 2002 and 2008. Serial EEG recordings were conducted during 3 time periods; at least once each within days 6 (first period), during days 7 to 19 (second period), and days 20 to 36 (third period). The presence and the grade of EEG background abnormalities were assessed according to an established classification system. Neurodevelopmental outcomes were assessed at a corrected age of 12 to 18 months. Of the 333 infants, 33 (10%) had developmental delay and 34 (10%) had cerebral palsy. The presence of EEG abnormalities was significantly predictive of developmental delay and cerebral palsy at all 3 time periods: the first period (n = 265; odds ratio [OR], 4.5; 95% confidence interval [CI], 2.2-9.4), the second period (n = 278; OR, 7.6; 95% CI, 3.6-16), and the third period (n = 237; OR, 5.9; 95% CI, 2.8-13). The grade of EEG abnormalities correlated with the incidence of developmental delay or cerebral palsy in all periods (P < .001). After controlling for other clinical variables, including severe brain injury, EEG abnormality in the second period was an independent predictor of developmental delay (OR, 3.2; 95% CI, 1.1-9.7) and cerebral palsy (OR, 6.8; 95% CI 2.0-23). EEG abnormalities within the first month of life significantly predict adverse neurodevelopment at a corrected age of 12 to 18 months in the current preterm survivor.
    PEDIATRICS 09/2012; 130(4):e891-7. · 4.47 Impact Factor
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    ABSTRACT: Background: Dexmedetomidine hydrochloride, a highly selective 2-adrenoceptoragonist, is used in combination with local anesthetics for sedation and analgesia. It is known to be efficacious in adult patients and is enthusiastically expected to be successful for sedation in neonates. Patient: The present case report details a term infant who was sedated by dexmedetomidine during artificial ventilation. He underwent electroencephalograms that confirmed epileptic seizures and non-epileptic abnormal movements. Twelve hours after the discontinuation of dexmedetomidine, both symptoms gradually disappeared without the use of any antiepileptic medication. After then, he had achieved normal development, with no obvious neurological abnormalities. Conclusion: Dexmedetomidine acts throughout the central nervous system and leads to a reduction in the anticonvulsant activity of the locus coeruleus. This case suggests potential adverse effects of dexmedetomidine in terms of inducing both epileptic seizures and non-epileptic movements in neonates.
    Brain & development 06/2012; · 1.74 Impact Factor
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    ABSTRACT: The aim of this study is to clarify the differences of EEG activities according to the presence or absence of disorganized patterns using amplitude spectral analysis. We compared EEGs of 17 preterm infants with disorganized patterns with those of 34 matched controls. Amplitude was defined as a square root of EEG power analyzed by fast Fourier transform algorithm, and was calculated in the 9 frequency bands. Six EEG segments of 10s were collected from the part of EEG with continuous high voltage slow waves in the absence of artifacts. The results were separately evaluated according to the post-conceptional age at EEG recordings. In patients with disorganized patterns, reduced amplitude of delta waves in the central areas and increased amplitude of beta waves in the occipital areas were observed at 29-30weeks of post-conceptional age. The results were almost similar at 31-32weeks of post-conceptional age. Amplitude in theta or alpha frequency bands was not different between those with and without disorganized patterns either at 29-30 or 31-32weeks of post-conceptional age. Amplitude spectral analyses will contribute to objective evaluation of disorganized patterns.
    Brain & development 02/2012; · 1.74 Impact Factor
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    ABSTRACT: It is important to predict the neurological prognoses of preterm infants as part of their normal follow-up. Previous reports have shown that conventional magnetic resonance imaging (MRI) and electroencephalography are useful in predicting neurological prognoses. Diffusion tensor imaging (DTI) is a relatively new method of evaluating the central nervous system (CNS) that can detect abnormalities quantitatively. We compared DTI at term-equivalent age in two extremely-low-birth-weight infants diagnosed with periventricular leukomalacia (PVL) with conventional MRI and DTI in three control extremely-low-birth-weight infants. DTI was analyzed using the free software, "Volume-one" and "dTVII SR." We compared the fractional anisotropy (FA) values at the corpus callosum, posterior limbs of the internal capsule, cerebral peduncle, and corticospinal tract using manual region of interest (ROI) analysis, and at the commissural fibers and corticospinal tract using tract-specific analysis. The FA values were lower in patients with PVL than in control infants at all measurement points, except the commissural fibers on tract-specific analysis. These measurement points showed no abnormality using conventional MRI. This suggests that DTI can detect CNS abnormalities that cannot be detected with conventional MRI. However, our sample size was very small and we examined only cases in which PVL was detected with conventional MRI. Further study is necessary to examine the correlation of DTI findings and neurological prognoses in infants who have no abnormality on conventional MRI.
    No to hattatsu. Brain and development 01/2012; 44(1):19-24.
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    ABSTRACT: Acute encephalopathy with reduced subcortical diffusion (AED) covers a spectrum including not only typical acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) but also atypical AESD with monophasic clinical course, or more severe subtypes. Aim of this study is to analyze prognostic factors of AED. We recruited 33 children with AED, that is, widespread diffusion restriction in cortical and subcortical structures. Their clinical courses, laboratory data, MRI, and the efficacy of treatment were analyzed retrospectively. Of the 33 children, 20 were males and the mean age at diagnosis was 22 months. Eighteen children had good outcome and 15 had poor outcome. Univariate analysis showed loss of consciousness 24 h after the onset, prolonged seizure at the onset, and mechanical ventilation to be weak predictors of poor outcome. Maximal aspartate aminotransferase, alanine aminotransferase, and creatinine kinase levels were significantly higher in the poor outcome group. Multivariate analysis showed loss of consciousness 24 h after the onset and prolonged seizure at the onset to be poor predictors of AED. Treatment with steroids and/or immunoglobulins did not result in better outcome. Prolonged seizure at the onset and loss of consciousness 24 h after the onset were seen at early stages of severe AED. Using these features, a prospective study of early intervention in AED should be conducted to further analyze the efficacy of its treatment.
    Brain & development 12/2011; 34(8):632-9. · 1.74 Impact Factor
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    ABSTRACT: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome. Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms. There were seven boys and eight girls. A mutation of the SCN1A gene was present in nine (truncation in six and missense in three). The frequency of seizures during the 3 months before the onset of acute encephalopathy was monthly in seven children and none in three. The median age at the onset of acute encephalopathy was 44 months (range 8-184 months). All children had status epilepticus followed by coma as the initial manifestation. Two different distributions of brain lesions were observed on diffusion-weighted images during the acute phase: cerebral cortex-dominant lesions with or without deep gray matter involvement and subcortical-dominant lesions. Four children died; nine survived with severe sequelae, and two had moderate sequelae. We must be aware that acute encephalopathy is an important complication in children with Dravet syndrome, and associated with fulminant clinical manifestations and a poor outcome.
    Epilepsia 11/2011; 53(1):79-86. · 3.96 Impact Factor
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    ABSTRACT: Many types of spinocerebellar ataxias (SCAs) manifest as progressive disorders with cerebellar involvement. SCA type 27 (SCA27) is a rare type of SCA caused by mutations in the fibroblast growth factor 14 gene (FGF14). FGF14 disruption caused by a de novo reciprocal chromosomal translocation between chromosomes 13 and 21 was identified in a patient with the phenotype of paroxysmal non-kinesigenic dyskinesia (PNKD). This indicated genetic heterogeneity of PNKD, since 60% of the patients with PNKD exhibit mutations in another gene responsible for PNKD, the myofibrillogenesis regulator 1 gene (MR-1). We hypothesized that the remaining 40% of patients with PNKD may have FGF14 mutations; therefore, the nucleotide sequences of MR-1 and FGF14 were analyzed in another six patients with PNKD, but no nucleotide alterations were observed in these genes for these patients. Further studies should be conducted on the phenotypic heterogeneity of FGF14 mutations and/or haploinsufficiency in SCA27 and PNKD.
    Brain & development 05/2011; 34(3):230-3. · 1.74 Impact Factor
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    ABSTRACT: To clarify the features of acute encephalopathy associated with 2009 pandemic flu. We identified 51 patients with acute encephalopathy with seasonal flu from the data base accumulated by Tokai Pediatric Neurology Society. We also collected 10 patients with acute encephalopathy with 2009 pandemic flu. The clinical course, laboratory data, neuroimaging findings, treatment, and the outcome of these patients were recruited using a structured research form. These data were compared between the two groups. The age was larger in the 2009 pandemic flu group (median, 109.5months) than in the seasonal flu group (median, 44months). There was no significant difference in other demographic data, neurologic symptoms, laboratory and neuroimaging findings, and treatment. Various degrees of neurologic sequelae including death were observed in 32% of the patients in the seasonal flu group, and in 50% in the 2009 pandemic flu groups. The analyses of patients with ages of 6years or older revealed that moderate or more severe sequelae were more frequent in patients with 2009 pandemic flu. Acute encephalopathy with 2009 pandemic flu occurred mainly among children with 6years of age or older, and the outcome was worse in this age group compared with acute encephalopathy with seasonal flu.
    Brain & development 01/2011; 34(1):13-9. · 1.74 Impact Factor
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    ABSTRACT: Rotavirus is one of the most common causes of gastroenteritis in children and is known to accompany some neurological disorders such as encephalitis/encephalopathy and seizures. Although cerebellar disorders sometime occur as a complication of rotavirus gastroenteritis in Japan, few reports have addressed these issues. Here, we report three cases of insulted cerebellums in addition to encephalitis/encephalopathy associated with rotavirus. Similar to posterior fossa syndrome after surgery, mutism was a notable symptom that lasted about 1 month. Brain diffusion-weighted imaging (DWI) revealed chronological changes, i.e., marked hyperintensity in the bilateral dentate nucleus followed by the vermis and cerebellar hemisphere. The bilateral dentate nucleus is known to be a key lesion site for mutism, and these clinical and radiological findings may be tightly connected in rotavirus-associated cerebellitis/cerebellopathy.
    Brain & development 01/2011; 33(1):21-7. · 1.74 Impact Factor
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    ABSTRACT: Periventricular leukomalacia (PVL) is one of the most important causes of adverse outcome of preterm infants. We hypothesized that inflammatory or some other specific pathways will have been activated at birth in preterm infants who later develop PVL. The aim of this study is to examine the difference in mRNA expression in umbilical cord blood according to the presence or absence of PVL. A total of 61 umbilical cord blood samples were collected from preterm infants with gestational age less than 33 weeks together with the patients' medical information during perinatal period. RNA expression patterns in the collected cord bloods were analyzed by microarray. On the basis of cranial ultrasonography and brain MRI examination, 3 infants (4.9%) were diagnosed as cystic PVL and selected as the subjects. Five patients who showed similar perinatal factors to those of infants with PVL but did not show PVL were selected as the normal control. Five of the 15 up-regulated genes are coding ribosomal proteins, and another encodes a translation elongation factor. Three of the 7 down-regulated genes encode proteins that may be related to immune response and/or inflammation. Up-regulation of the ribosomal proteins may indicate an activation of lymphocytes during the fetal period.
    Early human development 10/2010; 86(10):665-7. · 2.12 Impact Factor
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    ABSTRACT: This study was performed to clarify the relationship between prolonged depression of electroencephalography (EEG) in term and near-term infants with hypoxic ischemic encephalopathy (HIE) and the later development of West syndrome (WS). We investigated 17 term and near-term infants with HIE. Inclusion criteria were as follows: ≥35 weeks of gestation, clinical signs of HIE, magnetic resonance imaging (MRI) lesions corresponding to HIE, assessment of outcome at >18 months of age, depression of EEG, and serial EEG examinations. The 17 infants were divided into the following two groups: Group A (n = 4) with prolonged EEG depression over 21 days of age, and group B (n = 13) with disappearance of EEG depression by 21 days of age. WS developed in all four infants in group A, but in only one of 13 infants in group B. WS occurred significantly more frequently in group A than in group B. For the prediction of subsequent development of WS, prolonged EEG depression over 21 days of age showed sensitivity of 0.80 and specificity of 1.0. In both groups, abnormal irregular faster waves with or without EEG depression were seen in 11 infants between 2 and 28 days of age. They had no significant relationship with WS, but were significantly related to an adverse developmental outcome. Prolonged depression of EEG over 21 days of age in term or near-term infants with HIE is a valuable predictor of the later development of WS.
    Epilepsia 09/2010; 51(12):2392-6. · 3.96 Impact Factor

Publication Stats

285 Citations
111.26 Total Impact Points


  • 2001–2014
    • Anjo Kosei Hospital
      Anjō, Aichi, Japan
  • 2010–2013
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 2012
    • Washington University in St. Louis
      • Department of Pediatrics
      Saint Louis, MO, United States
  • 2007–2012
    • Juntendo University
      • • Faculty of Medicine
      • • Department of Paediatrics
      Edo, Tōkyō, Japan
  • 1998–2006
    • Nagoya University
      • Division of Pediatrics
      Nagoya-shi, Aichi-ken, Japan
  • 2004
    • The Graduate University for Advanced Studies
      • Department of Integrative Physiology
      Miura, Kanagawa-ken, Japan