Fumio Hayakawa

Neonatal EEG: a powerful tool in the assessment of brain damage in preterm infants

Serial EEG recordings beginning immediately after birth are not only of great diagnostic and prognostic value but also useful to elucidate the timing and the mode of brain injuries in the preterm newborn. It is extremely useful to distinguish between acute stage and chronic stage EEG abnormalities. The former is characterized by findings of acute depression such as increased discontinuity, decreased faster frequency activities, and lowered amplitudes. The latter mainly includes dysmature patterns and disorganized patterns. The timing of brain insult can be assessed by considering EEG findings in relation to the time of birth. Different modes of brain injury are associated with different types of EEG abnormalities and different types of neurological outcome. Sudden strong brain insults are usually associated with findings of severe depression followed by disorganized pattern and later cerebral palsy, while persistent mild insults are usually associated with prolonged mild depression followed by dysmature pattern and later mental retardation. Routine serial EEG studies in preterm infants demonstrated that one fourth of cerebral palsies in these infants were of antenatal origin, two thirds of perinatal origin and postnatal injuries played the least role. Periventricular leucomalacia (PVL) manifesting itself on the ultrasound in the late neonatal period and suggesting postnatal origin was often found to be of antenatal origin with an EEG soon after birth. PVL without apparent causes was often associated with abnormal fetal heart rate patterns and early neonatal EEG abnormalities, and considered to have originated in the antepartum period.

Background electroencephalographic (EEG) activities of very preterm infants born at less than 27 weeks gestation: a study on the degree of continuity

AIMS To clarify the features of the background electroencephalographic (EEG) activities in clinically well preterm infants born at less than 27 weeks gestation and to outline their chronological changes with increasing postconceptional age (PCA). METHODS EEGs of clinically well premature infants born at less than 27 weeks gestation were recorded during the early postnatal period. The infants were separated into three groups according to their PCA at the time of EEG recording (21–22 weeks PCA, 23–24 weeks PCA, and 25–26 weeks PCA). The mean and maximum duration of interburst intervals (IBIs), the mean duration of bursts, and the percentage of continuous and discontinuous patterns in each PCA group were evaluated. RESULTS There were three infants at 21–22 weeks PCA, seven at 23–24 weeks PCA, and five at 25–26 weeks PCA. Eighteen EEG recordings were obtained. The mean and maximum IBI duration decreased with increasing PCA. The percentage of continuous patterns increased with increasing PCA. Conversely, the percentage of discontinuous patterns decreased with increasing PCA. CONCLUSIONS In premature infants born at less than 27 weeks gestation, the characteristics of the background EEG activities were similar to those of older premature infants. These changes reflect the development of the central nervous system in this period. Key messages At less than 27 weeks gestational age, the characteristics of background EEG activities were found to be as follows: the mean and maximum IBI duration decreased with increasing PCA the percentage of continuous patterns increased with increasing PCA the percentage of discontinuous patterns increased with increasing PCA the mean burst duration during discontinuous patterns increased as PCA increased

MRI findings in patients with spastic cerebral palsy. II: correlation with type of cerebral palsy

The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan in 1993 and 1994. Eighty‐one patients had diplegia, 45 had quadriplegia, and 26 had hemiplegia. Of patients with diplegia, 72 had periventricular leukomalacia (PVL) and very few had other types of lesions. In patients with quadriplegia, three main types of brain lesions were observed: PVL in 12 patients, term‐type brain injury in 22, and brain anomaly in 10. In the 26 patients with hemiplegia, 17 had a unilateral lesion (rare in patients with diplegia and quadriplegia), and bilateral lesions were seen in seven others.

Determination of timing of brain injury in preterm infants with periventricular leukomalacia with serial neonatal electroencephalography

Objective. The aim of this study was to determine the timing of brain injury in infants with periventricular leukomalacia (PVL) with serial electroencephalography (EEG) recordings during the neonatal period. Patients and Methods. We evaluated 172 preterm infants having a gestational age <33 weeks and weighing <2000 g. Initial EEG was recorded within 72 hours of life and then recorded once every 1 to 4 weeks. Serial cranial ultrasonography was performed and cystic PVL was diagnosed when multiple cystic formations of >3 mm in diameter were observed. Results. Of the172 infants studied, 26 were diagnosed as having cystic PVL by ultrasonography. EEG abnormalities were observed in 25 of 26 infants with PVL, although EEG abnormalities were seen in 20 of 146 infants without PVL. The initial EEG recordings were normal in 7 infants, but EEG abnormalities were observed later in 6 of these infants. In these 6 infants, the timing of injury was presumed to be postpartum. Only acute stage abnormalities were observed on initial EEG recording in 14 infants, and the timing of injury was presumed to be just before or around birth. Chronic stage abnormalities were recognized already on initial EEG recordings in the other 5 infants, and the timing of injury was presumed to be some time before birth. Conclusions. Our study indicates that it may be possible to determine the timing of injury in infants with PVL by serial EEG recordings.

Quantitative evaluation of thalami and basal ganglia in infants with periventricular leukomalacia

Quantitative analyses of cross‐sectional areas of the thalami, caudate nuclei, and lentiform nuclei were performed in 29 preterm infants (16 males, 13 females; mean age 29.6 weeks, age range 27 to 24 weeks,) with periventricular leukomalacia (PVL). MRI was carried out in the infants between 9 and 18 months of corrected age and in 16 control infants. Bilateral thalami, caudate nuclei, lentiform nuclei, cerebral hemispheres, and cerebellum were measured by computer. Ratios of the areas of the thalami (Th), caudate nuclei (Ca), lentiform nuclei (Le), and cerebral hemispheres (CH) to that of the cerebellum (Ce) were calculated in each infant. The ratio of Th:Ce was significantly smaller in infants with moderate and severe PVL than in the control group bilaterally. Abnormal intensity areas were not observed in the thalami in any infants with PVL. CH:Ce was also smaller in infants with severe PVL than in the control group. No significant difference was observed between the groups in ratios Le:Ce or Ca:Ce. Results of our study suggest that the volume of the thalami is reduced and that thalamic involvement is present in infants with white matter lesions who have moderate to severe PVL.

Dysmature EEG pattern in EEGs of preterm infants with cognitive impairment: maturation arrest caused by prolonged mild CNS depression

The significance of mild sustained brain injury in the pathogenesis of perinatal brain damage was investigated using serial EEG recordings performed on 102 early preterm infants surviving beyond 2 years of age. Sixteen infants (16%) elicited mild depression of background EEG activities in the neonatal period. Of nine infants with mild depression of prolonged duration (more than 3 weeks), five (56%) were diagnosed as having cognitive impairment in the follow up study. Four showed no signs of cerebral palsy, while one had cerebral palsy. The infants with cognitive impairment showed mild prolonged depressions in background EEG activities in the early neonatal period and dysmature EEG patterns in the late neonatal period. They also showed maturation arrest in EEG patterns during prolonged mild depression of background EEG activities. In addition to strong sudden depression of CNS causing deep white matter injury and motor impairment, prolonged mild depression is another mode of brain injury in early preterm infants which can induce future cognitive impairment.

Abnormal sharp transients on electroencephalograms in preterm infants with periventricular leukomalacia.

OBJECTIVE To determine the clinical significance of abnormal sharp transients other than positive rolandic sharp waves (PRS), electroencephalograms were used for the diagnosis of periventricular leukomalacia (PVL). STUDY DESIGN We evaluated 126 electroencephalograms from 93 preterm infants; 31 infants had PVL, and 62 were control infants. Frontal sharp waves (FS) were defined as sharp transients of positive polarity with an amplitude >100 microV. Occipital sharp waves (OS) were defined as those of negative polarity with an amplitude >150 microV. FS, OS, or PRS were considered to be present when there were >0.1 per minute. RESULTS The number of FS per minute was significantly higher in the PVL group than in the control group during days 0 to 4 and 5 to 7. The number of OS per minute was also significantly higher in the PVL group than in the control group during days 0 to 4, 5 to 7, and 8 to 14. The sensitivity of FS or OS was relatively high but that of PRS was low. The presence of two or more types of abnormal sharp transients was correlated with a poor outcome. CONCLUSIONS FS or OS may be useful for predicting which infant will have PVL.

Amplitude spectral analysis of maturational changes of delta waves in preterm infants.

The aim of this study is to clarify the usefulness of amplitude spectral analysis for an evaluation of maturational changes of delta activities in preterm infants. We chose each ten healthy infants without complications who were 29-30, 31-32, and 33-34 weeks of post-conceptional age (PCA) at electroencephalogram (EEG) recordings. Fast Fourier transform algorithm was applied for amplitude spectral analysis. The analyzed data were divided into four frequency bands; D1 0.53-1, D2 1-2, D3 2-3, and D4 3-4Hz. The average amplitude of six segments with high voltage slow waves was calculated in each frequency band. A significant reduction of the amplitude along with PCA was present in all leads in D1 band. On the other hand, a significant negative correlation with PCA was observed only in the occipital leads in D2, D3 or D4 bands. In conclusion, maturational EEG changes assessed by amplitude spectral analysis were prominent in the occipital areas, and in the frequency less than 1Hz.

Combination of neonatal electroencephalography and ultrasonography: sensitive means of early diagnosis of periventricular leukomalacia

This study was performed to assess the predictive value of ultrasonography and electroencephalography (EEG) in order to identify infants with periventricular leukomalacia (PVL) during the early neonatal period, especially non-cystic cases, and to clarify the combination of ultrasonographic and EEG findings that are the most useful. We studied 288 eligible infants, whose gestational ages ranged between 27 and 32 weeks. PVL was observed in 49 infants (26 cystic PVL and 23 non-cystic PVL). On ultrasonography, 31 infants with PVL were detected on the basis of definite periventricular echodensity (PVE). Thirty-seven infants had at least one of equivocal or definite PVE or cystic changes, but the other 12 did not have any of them. The sensitivity and specificity were 0.76 and 0.81, respectively. In EEG findings, acute stage abnormalities (ASA) of grade II or more were recognized in 31 infants with PVL. The sensitivity and specificity were 0.63 and 0.91, respectively. Equivocal or definite chronic stage abnormalities (CSA) were seen in 43 infants, the sensitivity and specificity being 0.88 and 0.84. The sensitivity of CSA was higher than that of ASA, and the specificity of ASA was higher than that of CSA. When these EEG findings were combined, 45 infants with PVL were detected. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.92, 0.77, 0.45, and 0.98, respectively. Moreover, ultrasonographic and EEG findings were combined, 46 out of the 49 infants with PVL were detected with a sensitivity of 0.94 and a specificity of 0.64. The results indicated that EEG may be suitable for detecting infants at risk for development of PVL on the basis of its high sensitivity, and ultrasonography may be useful for confirming the presence of PVL on the grounds of its high specificity. Appropriate use of these measurements will make an early diagnosis of infants with PVL possible, even in non-cystic cases.

Serum levels of cytokines and EEG findings in children with influenza associated with mild neurological complications

We studied the relation among serum cytokine levels, EEG changes, and mild neurological complications (delirium and febrile seizure) in children with influenza. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble tumor necrosis factor receptor-1 (sTNFR-1) were measured in 27 children with proven influenza infection with mild neurological complications (10 patients with delirium and 17 with febrile seizures) and seven control children. EEG was recorded in 14 children with neurological complications. EEG showed focal slowing in four of nine patients with delirium and in four of five with febrile seizures. Generalized slowing was observed in one patient with delirium. The median serum IL-6 level was 31.2+/-15.1 pg/ml (range, 7.5-64.5 pg/ml) in the delirium group, 42.3+/-44.0 pg/ml (range, 8.0-196.0 pg/ml) in the febrile seizure group, and 15.4+/-7.0 pg/ml (range, 7.2-28.0 pg/ml) in the control group. Serum TNF-alpha and sTNFR-1 levels were not different among three groups. Mild neurological complications associated with influenza were related to the mildly abnormal serum IL-6 levels and EEG findings. The combination of these parameters will be useful for early diagnosis and differentiation of neurological complications in children with influenza. Further studies will be necessary for investigating that IL-6 has the diagnostic value for differentiation between severe encephalopathy and mild neurological complications in children with influenza.