Increased fetal heart rate variability in periventricular leukomalacia.

OBJECTIVE: This study used quantitative analysis to determine whether increased variability in fetal heart rate (FHR) is related to the risk of developing periventricular leukomalacia (PVL). METHODS: We analyzed 124 FHR traces of neonates delivered preterm at 27-33 weeks' gestation to 105 mothers. FHR traces 1-3h before delivery were translated into power-spectrum curves using a fast Fourier transformation. The total power (the area under the curve of 1-10 cycles per minute), segmental power of every cycle per minute, peak power, and frequency edges were calculated, and their relationship with the subsequent development of PVL was examined. RESULTS: Total power was significantly higher in the PVL group (n=9, median 1813, range 1064-2426) compared to the non-PVL group (n=114, median 1383, range 381-3324, p=0.029). Infants in the PVL group had greater segmental power in segments with 1-2, 2-3, and 9-10 cycles per minute, than those in the non-PVL group. Total power of ⩾1550 was significantly correlated with the subsequent development of PVL and premature rupture of membranes. Furthermore, the frequency of pregnancy-induced hypertension was significantly reduced in the fetuses with a total power of ⩾1550. CONCLUSION: Our study suggests that a fetus with increased FHR variability is at risk of developing PVL. This study provides additional evidence supporting the contribution of antenatal factors to the subsequent development of PVL.

Characteristics of epilepsy occurring in the first four months.

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.

Differences between periventricular hemorrhagic infarction and periventricular leukomalacia.

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.

A new electroencephalogram classification with reduced recording time in asphyxiated term infants.

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.

Flow chemiluminescence determination of antimony(III,V) using a rhodamine B-cetyltrimethylammonium chloride reversed micelle system following liquid-liquid extraction.

A flow chemiluminescence (CL) method combined with a liquid-liquid extraction technique is proposed for the indirect determination of antimony in aqueous samples using rhodamine B (RB). In the liquid-liquid extraction process, the antimony(V) chloro-complex anion, [SbCl(6)](-), was extracted from an aqueous acidic solution into toluene via ion-pair formation with the protonated RBH(+) ion. Upon mixing the extract with a reversed micellar reagent solution of cetyltrimethylammonium chloride (CTAC) in 1-hexanol-cyclohexane/water (0.60 mol dm(-3) H(2)SO(4)) containing cerium(IV), uptake of the ion-pair by CTAC reversed micelles occurred easily, followed by an oxidation reaction of RB with Ce(IV) in the CL process. The CL signal produced was then measured. Using a flow injection system, the detection limits (DL) of 0.25 µmol dm(-3) Sb(III) and 0.20 µmol dm(-3) Sb(V), and linear calibration graphs with dynamic ranges from the respective DLs to 16 µmol dm(-3) for Sb(III) and Sb(V) were obtained under optimized experimental conditions. The proposed method was successfully applied to a mixture of Sb(III) and Sb(V), where total antimony, Sb(III) + Sb(V), was measured using ceric sulfate as an oxidant to oxidize Sb(III) to Sb(V) prior to extraction, Sb(V) was determined directly without the use of an oxidant, and Sb(III) was calculated by difference.

Amplitude spectral analyses of disorganized patterns on electroencephalograms in preterm infants.

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 10 s 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 29-30 weeks of post-conceptional age. The results were almost similar at 31-32 weeks 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 31-32 weeks of post-conceptional age. Amplitude spectral analyses will contribute to objective evaluation of disorganized patterns.

Amplitude-integrated electroencephalogram 1 h after birth in a preterm infant with cystic periventricular leukomalacia.

We report a preterm infant, who showed abnormal amplitude-integrated electroencephalogram (aEEG) findings 1 h after birth and later developed cystic periventricular leukomalacia (PVL). The patient was a girl with a gestational age of 29 weeks. She was delivered by emergency cesarean section because of placental abruption and intrauterine co-twin demise. Artificial ventilation and administration of surfactant were needed to treat respiratory distress syndrome. Her cardiovascular condition was stable with artificial ventilation. Cranial ultrasonography showed extended cystic PVL after 11 days of age. aEEG 1 h after birth showed a consistently inactive pattern that resolved completely 28 h after birth. The neurophysiological findings of this patient suggest that aEEG findings during the very early period after birth provide significant information for predicting PVL.

EEG for predicting early neurodevelopment in preterm infants: an observational cohort study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Transient reduced diffusion in the cortex in a child with prolonged febrile seizures.

We report on a 4-year-old boy with transient reduced diffusion in the cortex, thalamus, and hippocampus on diffusion-weighted imaging (DWI) performed after prolonged febrile seizures (PFS). He had experienced intermittent right hemiconvulsions lasting about 90 min during the febrile illness, but his neurological symptom resolved completely after several hours. DWI performed immediately after the PFS showed abnormally high signal intensities in the left extended cortex and pulvinar of the ipsilateral thalamus. Two days later, these DWI lesions resolved completely, but abnormally high signal intensities were observed in the left hippocampus. Three months later, the DWI was normal, and no atrophy or gliosis was seen. This patient had unique lesions on DWI after PFS, but it is nevertheless important to attend to such lesions on the DWI of patients with PFS.

Prognostic factors in acute encephalopathy with reduced subcortical diffusion.

OBJECTIVES: 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. MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Acute encephalopathy with 2009 pandemic flu: comparison with seasonal flu.

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.

Evaluation of brain maturation in pre-term infants using conventional and amplitude-integrated electroencephalograms.

OBJECTIVE: To investigate the accuracy of conventional electroencephalograms (cEEGs) and amplitude-integrated EEGs (aEEGs) in the evaluation of brain maturation in normal pre-term infants. In addition, extrauterine acceleration of brain maturation was investigated. METHODS: A total of 129 EEGs recorded between 27 and 37 weeks of postconceptional age (PCA) from 37 clinically stable pre-term infants were analysed. One expert investigator blindly estimated PCA using cEEG and total cerebral function monitoring (CFM) score on aEEG. The estimated PCA (ePCA) on aEEG was calculated from a regression equation. RESULTS: The linear regression analysis showed a significant correlation between chronological PCA (cPCA) and ePCA on cEEG and between cPCA and total CFM score on aEEG. The estimation gap was smaller on cEEG, which was between -2 and +2 weeks in 96.9%. No significant correlation was observed between postnatal age and the estimation gap on cEEG or aEEG. CONCLUSIONS: Estimated brain maturation was well correlated with cPCA on cEEG and aEEG. However, the evaluation of brain maturation was much more accurate on cEEG than aEEG. Extrauterine acceleration of brain maturation was not observed on either cEEG or aEEG. SIGNIFICANCE: cEEG and aEEG will be valuable tools for evaluation of brain maturation in pre-term infants.

Amplitude-integrated electroencephalography in preterm infants with cystic periventricular leukomalacia.

AIM: This study aimed to assess amplitude-integrated electroencephalography (aEEG) findings in preterm infants with cystic periventricular leukomalacia (cPVL) in the early neonatal period. METHODS: We analyzed five infants with cPVL, whose gestational age was between 27 and 30 weeks, and 15 matched control infants. Two-channel (C3-O1 and C4-O2) aEEG was obtained by digital conversion from a conventional electroencephalogram, which was recorded at days 0-5, 6-13, and 21-34 in each infant. We evaluated the averaged two-channel values of several measurements using visual and quantitative analyses. RESULTS: Infants with cPVL had a significant higher maximal upper-margin amplitude value, with a median of 47.5 µV (range of 42.5-60) compared with the control infants (median, 33.8; range, 23.8-50) in the second visual-analysis record. Infants with cPVL also had a significantly higher mean upper-margin amplitude value, with a median of 18.8 µV (range, 17.7-23.2) compared with the control infants (median, 16.3; range, 10.3-19.0) in the second quantitative-analysis record. CONCLUSIONS: We demonstrated that the upper-margin amplitude of aEEG in infants with cPVL was significantly higher than that in the control infants at 6-13 days after birth.

Prolonged EEG depression in term and near-term infants with hypoxic ischemic encephalopathy and later development of West syndrome.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Early diffusion-weighted images in infants with subcortical leukomalacia.

We describe two infants with subcortical leukomalacia and decreased water diffusivity in widespread white matter on magnetic resonance imaging. In both infants, diffusion-weighted imaging at age 1 day revealed a widespread increase in signal intensities, predominantly in subcortical areas. The corticospinal tract in the brainstem was not involved. Subsequently, diffusion-weighted imaging produced apparently normal results, and conventional magnetic resonance imaging indicated diffuse but subcortical-dominant white matter lesions in the subacute phase. Follow-up magnetic resonance imaging revealed a volume loss and gliosis of the white matter. In one infant, psychomotor development was mildly delayed, and epilepsy occurred. The other infant experienced normal development and no epilepsy. Neither infant developed spastic cerebral palsy. These infants represent a characteristic group with perinatal brain injury.

Differences in the time course of splenial and white matter lesions in clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS).

Two patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) exhibiting lesions in the white matter and entire corpus callosum (type 2) are reported. The time course differed between the splenial lesion and other lesions in the white matter and corpus callosum other than the splenium; the latter disappeared earlier than the former. These findings strongly suggest that MERS type 2 resolves completely through MERS type 1 exhibiting an isolated splenial lesion, and MERS types 1 and 2 have the same pathophysiology. The possible prior white matter lesions in patients with MERS type 1 may explain the neurological symptoms or EEG abnormalities.

Nutritional state, maturational delay on electroencephalogram, and developmental outcome in extremely low birth weight infants.

The aim of this study is to clarify the relation among developmental outcome, nutritional state during the neonatal period, maturational electroencephalographic changes. Thirteen extremely low birth weight infants who completed 6- or 9-year follow-up were a subject of this study. Undernutrition was defined as enteral feeding below 100mL/kg/day at 3 weeks of age. Dysmature patterns were defined as the persistence of EEG patterns 2 weeks or more immature for post-conceptional age. IQ was examined at 6 and 9 years of age. Body height and weight, and head circumference at 6 years of age were stratified by the percentile grades. Full and verbal IQ was significantly lower in infants with undernutrition than those with normal nutrition. Among infants with undernutrition, those with persistent dysmature patterns tended to have lower full and performance IQ than those without persistent dysmature patterns. Head circumference was 50 percentile or larger in all infants with normal nutrition, whereas it was below 50 percentile in six of eight infants with undernutrition. Extremely low birth weight infants with undernutrition had worse neurodevelopmental outcome at 6 or 9 years of age than those with normal nutrition. Among infants with undernutrition, developmental outcome was relatively worse in those with persistent dysmature patterns than those without.

Chronologic changes in neonatal EEG findings in periventricular leukomalacia.

OBJECTIVE: This study sought to clarify chronologic changes in neonatal electroencephalographic (EEG) findings in periventricular leukomalacia (PVL). METHODS: We obtained serial EEG findings for all premature infants who were admitted to our hospital at gestational age of < or =33 weeks between 1997 and 2006. EEG recordings were obtained on days 1 to 4, 5 to 14, 15 to 28, 29 to 56, and 57 to 84. Abnormal EEG findings were classified as acute-stage abnormalities (ASAs) or chronic-stage abnormalities (CSAs) and were subclassified as mild, moderate, or severe. PVL was classified as noncystic, localized cystic, or extensive cystic. The final diagnosis of PVL was made through neurologic assessment and MRI findings at 24 months. RESULTS: Fifty-five infants were diagnosed as having PVL, including 23 with noncystic PVL, 9 with localized cystic PVL, and 23 with extensive cystic PVL. ASAs were observed most frequently on days 1 to 4 and were observed rarely thereafter in all groups. CSAs were observed most frequently on days 5 to 14, were most severe on days 5 to 14, and then resolved within 1 to 2 months in all groups. CSAs in patients with extensive cystic PVL were more severe and persisted longer, compared with other groups. ASA and CSA severity was correlated with PVL severity. CONCLUSIONS: EEG findings in PVL differed according to the severity of PVL and the time of recording. To detect PVL, > or =2 EEG recordings are recommended, 1 within 48 hours after birth, to detect ASAs, and 1 in the second week of life, to detect CSAs.

Callosal lesions and delirious behavior during febrile illness.

We retrospectively reviewed electroencephalography and magnetic resonance imaging findings for 21 children exhibiting delirious behavior during febrile illness. Among these, five patients had transient callosal lesions with or without white matter lesions on diffusion-weighted images. We compared the clinical characteristics, duration, and components of delirious behavior, the duration and severity of reduced consciousness, and EEG findings among patients with or without callosal lesions. No significant differences were detected in these items according to the presence or absence of callosal lesions. Adding insight into the pathogenesis of this condition, our study revealed that callosal lesions are not uncommon in patients exhibiting delirious behavior during febrile illness.