Doris A. Steppe

Ictal and interictal electrographic seizure durations in preterm and term neonates.

Summary: The effect of gestational age on neonatal ictal and interictal durations has not been investigated. Sixty‐eight neonates with 644 electrographic seizures were identified retrospectively. Thirty‐five full‐term (FT) neonates were compared with 33 preterm (PT) neonates. Eighteen older preterm infants (OPT) [>31 weeks estimated gestational age (EGA)] were also compared with 15 young preterm infants (YPT) of ≤31 weeks EGA. Ictal/ interictal durations were calculated for the total cohort with and without status epilepticus (SE). Statistical analyses were two‐tailed t tests, chi‐square calculations, and one‐way analysis of variance (ANOVA) with Duncans multiple‐range test. Eleven of 35 (33%) FT had SE as compared with 3 of 33 (9%) PT (chi‐square = 7.8, p < 0.05). The mean ictal duration was 14.2 min for FT infants as compared with 3.1 min for PT infants (p < 0.01); only borderline differences were noted after those with SE were excluded. Interictal durations were longer for OPT than YPT (p < 0.05). By ANOVA and Duncans multiple‐range tests, group differences included longer mean ictal durations for FT infants as compared with OPT infants (p = 0.06, ANOVA; p < 0.05, Duncans), and longer mean interictal durations for FT infants versus OPT and OPT versus YPT (p = 0.02, ANOVA; p < 0.05, Duncans). More developed neuronal networks result in longer ictal durations in FT than in PT neonates, including FT infants with SE. Inhibitory networks responsible for longer interictal periods are more dominant in OPT infants than in YPT infants, reflecting maturational changes that suppress seizure activity during the latter part of the third trimester before the infant reaches an FT corrected age.

Changes in forebrain function from waking to REM sleep in depression: preliminary analyses [of 18F]FDG PET studies

Based on recent functional brain imaging studies of healthy human REM sleep, we hypothesized that alterations in REM sleep in mood disorder patients reflect a functional dysregulation within limbic and paralimbic forebrain structures during that sleep state. Six unipolar depressed subjects and eight healthy subjects underwent separate [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans during waking and during their first REM period of sleep. Statistical parametric mapping contrasts were performed to detect changes in relative regional cerebral glucose metabolism (rCMRglu) from waking to REM sleep in each group as well as interactions in patterns of change between groups. Clinical and EEG sleep comparisons from an undisturbed night of sleep were also performed. In contrast to healthy control subjects, depressed patients did not show increases in rCMRglu in anterior paralimbic structures in REM sleep compared to waking. Depressed subjects showed greater increases from waking to REM sleep in rCMRglu in the tectal area and a series of left hemispheric areas including sensorimotor cortex, inferior temporal cortex, uncal gyrus-amygdala, and subicular complex than did the control subjects. These observations indicate that changes in limbic and paralimbic function from waking to REM sleep differ significantly from normal in depressed patients.

Comparisons of EEG spectral and correlation measures between healthy term and preterm infants

Continuous 12-hour electroencephalography (EEG)-sleep studies were acquired by a computerized monitoring system under environmentally controlled conditions for 2 groups of neonates. Eighteen health preterm infants at a postconceptional term age were matched to 18 term infants. These 2 groups were also matched for gender, race, and socioeconomic class. For the entire 12-hour recording, relative spectral power values (i.e., ratio of specific EEG power in specific frequency band compared to total EEG power) were significantly reduced in the preterm group for theta (P < or = .007), alpha (P < or = .001), and beta (P < or = .018) frequency bands, while delta remained unchanged. Correlations between 91 pairs of EEG channels were also calculated and the preterm infants had significantly higher correlation values in 27 of the 91 pairs of channels (P < .05); 14 interhemispheric, 8 intrahemispheric, and 5 sagittal combinations, while 3 intrahemispheric combinations were higher in the term group. Fewer functional neuronal aggregates generate less oscillatory potential (i.e., lower spectral power) in the theta through beta frequency ranges in the preterm infant, while greater cortical connectivity (i.e., higher correlations) exists in many brain regions by postconceptional term ages in this group. These findings suggest a functional alteration in brain development of the preterm infant as a result of prolonged extrauterine experience and/or prematurity.

Maturational trends of EEG-sleep measures in the healthy preterm neonate

Five physiologic groupings of 45 EEG-sleep measures were acquired from serial 24-channel EEG-sleep recordings (i.e., sleep architecture, continuity, EEG spectral, phasic, and autonomic measures), utilizing 129 studies on 56 healthy preterm infants from 28 to 43 weeks postconceptional age (PCA) who were neurodevelopmentally normal on follow-up. Regression analyses chose the least number of measures that best reflected maturation. Four of 45 variables (i.e., spectral alpha energy during quiet sleep, total spectral EEG energy, arousal number during active sleep, and percentage of EEG discontinuity) most significantly explained brain maturation in neonates < 36 weeks PCA. Three of 45 variables (i.e., spectral theta and beta energies during active sleep and spectral alpha energy during quiet sleep) were most representative after 36 weeks PCA. Spectral EEG energies were the strongest indicators of maturation compared with other measures, particularly in near-term neonates.

Maturation of phasic and continuity measures during sleep in preterm neonates.

ABSTRACT: Different physiologic measures during EEG sleep periods in preterm neonates are postulated to change with maturation and reflect functional brain development. Forty- three healthy preterm neonates received 3-h EEG sleep studies in an environmentally controlled setting. Postconceptional ages of neonates at each recording session ranged from 28 to 35 wk. Minute-by-minute analyses of EEG discontinuity, motility, arousals, and REM were performed. Eight phasic events and continuity measures of sleep were tabulated. Data were analyzed using Spearman rank order correlation coefficients. Increases in arousal numbers (p < 0.001) and durations (p < 0.001) were noted with age only during continuous periods of EEG activity (i.e. active sleep). REM also increased with corrected age during indeterminate or transitional sleep (p < 0.002) and decreased during quiet sleep (p < 0.01). Decreases in small body movements per minute (p = 0.02) and large body movements per minute (p < 0.001) occurred only during discontinuous periods of EEG activity (i.e. quiet sleep). Sleep efficiency (p < 0.001), maintenance (p < 0.001), and latency (p = 0.01) also decreased with increasing postconceptional age. Cycle length between two segments of continuous EEG with an intervening period of EEG discontinuity also lengthened with maturation (p < 0.001). These findings are discussed in the context of previously reported differences in phasic and continuity measures noted between preterm and full-term infants at matched full-term postconceptional ages. Changes in phasic and continuity measures with increasing postconceptional ages reflect maturation of specific neuronal processes of the CNS within a rudimentary sleep cycle of the preterm neonate.

Physiological significance of sharp wave transients on EEG recordings of healthy pre-term and full-term neonates.

One EEG sleep cycle was selected from each of ninety-four 3 h studies on 52 healthy neonates from 29 to 43 weeks post-conceptional ages (CA) (28 pre-term (PT)/24 full-term infants (FT); 51 are normal up to at least 18 months of age). Each record was reviewed to identify sharp wave transients (SWTs). No spike discharges were noted. 364 SWTs were tabulated in terms of amplitude, morphology, left:right predominance, anatomical site and EEG sleep state. Mean number of SWTs per hour for full-term, pre-term, and pre-term at post-conceptional term age (PTT) infants were 11.7 (+/- 12), 10.0 (+/- 7), and 13 (+/- 10). Mean amplitudes (microV) were 98.8 (+/- 23.2), 84.9 (+/- 38.3), and 99.4 (+/- 28.8) for FT, PT, and PTT infants respectively. FP1, FP2, T4 and C3 accounted for 94%, 83% and 84% of SWT sites for FT, PT and PTT groups, respectively. Biphasic waves were noted more frequently, and triphasic waves almost exclusively in PT infants (chi 2 = 130.8, P = 0.001). Spearman correlations were significant for amplitude of SWTs with CA (and r = 0.45, P = 0.0001). Significant differences (ANOVA) were found, for instance, between SWT frequency with the site and sleep state (R2 = 0.63, P = 0.0001) between SWT amplitude with sleep state and morphology (R2 = 0.59, P = 0.0001). Brain maturation alters the location and morphology of SWTs in healthy neonates. Descriptions of SWTs on EEG recordings of healthy neonates will improve the assessment of encephalopathic recordings of infants studied for clinical reasons.

Neonatal EEG-sleep disruption mimicking hypoxic-ischemic encephalopathy after intrapartum asphyxia.

OBJECTIVES EEG-sleep organization of asphyxiated and non-asphyxiated full-term neonates was compared during the first 3 days after birth. BACKGROUND Aggressive fetal and neonatal resuscitative efforts have reduced the severe expression of the neonatal brain disorder termed hypoxic-ischemic encephalopathy. Neonates may alternatively express altered EEG-sleep organization over the first days of life after asphyxia which may mimic mild or moderate hypoxic-ischemic encephalopathy. None of ten asphyxiated infants had EEG-confirmed seizures or pharmacologically-induced encephalopathies. All asphyxiated infants expressed fetal distress on fetal heart monitoring prior to delivery, and required neonatal resuscitation, as reflected in depressed 1, 5, and 10 min Apgar scores. Moderate to severe metabolic acidosis was also documented at birth in the asphyxiated group. All ten asphyxiated infants displayed either hyperalertness/irritability or somnolence/lethargy during the first 24 h after birth, suggesting mild to moderate post-asphyxial encephalopathy. Twenty-two 1 h 21-channel EEG polygraphic studies were obtained from the first through third days of life on nine asphyxiated infants and scored for EEG-sleep states. Studies on 23 non-asphyxiated newborns were also obtained between 1 and 3 days of life and scored for EEG-sleep state. EEG-sleep states were assigned to every minute of each record by visual analyses, without knowledge of the presence or absence of asphyxia. Comparisons of active, quiet, and indeterminate sleep percentages between neonatal groups were performed. Nested MANOVA was used which took into account multiple observations per child in the asphyxiated group. RESULTS The percent of active sleep was 44.7% (+/-14.7), the percent of quiet sleep was 38.7% (+/-14.3), and the percent of indeterminate sleep was 13.3% (+/-11.4) in the non-asphyxiated group. The percent of active sleep was 18.9% (+/-18.5), the percent of quiet sleep was 46.5% (+/-21.1), and the percent of indeterminate sleep was 33.4% (+/-19.7) in the asphyxiated group. A significant decrease in active sleep (F=39.5, P<0.0001), and significant increases in quiet sleep (F=4.6, P<0.05) and indeterminate sleep (F=21.5, P<0.0005) were noted in the asphyxiated group. Shorter active sleep bout lengths were noted (F=21.8, P<0.001), while the quiet sleep bout lengths remained unchanged for the asphyxiated group. CONCLUSIONS An increased percentage of quiet sleep and indeterminate sleep at the expense of decreased active sleep reflects postnatal brain adaptation to asphyxia in infants despite the absence of overt clinical or electrographic evidence of hypoxic-ischemic encephalopathy. Brain adaptation in newborns after acute asphyxial stress may be expressed as altered sleep organization, despite clinical signs which may masquerade as mild to moderate post-asphyxial encephalopathy. EEG-sleep studies can assist in a more accurate classification of newborn encephalopathy that does not satisfy the criteria for hypoxic-ischemic encephalopathy.

Neonates With Electrically Confirmed Seizures and Possible Placental Associations

Placental specimens were reviewed from 73 singleton pregnancies of women whose offspring received electroencephalogram (EEG) studies in the neonate period. A group of 43 neonates (postconception age [PCA] 23-44 weeks) with electrically confirmed seizures in the immediate neonate period were compared with 30 healthy preterm and term infants of comparable PCA who had no electrographic seizures. Pathologic placental changes were separated: Group A consisted of chorioamnionitis, edema, meconium staining, and/or retroplacental hematoma. Group B consisted of abnormal villous maturation, infarction, and/or chronic villitis. Logistic regression analyses calculated the odds ratio of having Group A or Group B placental lesions in each neonate group as a function of increasing PCA. For the seizure group, the odds of having Group B with or without Group A placental lesions increased by a factor of 1.2 for each postconception week up to 43 weeks PCA. For a 15-week interval the odds of having Group B lesions for the seizure group increased by a factor of 12.1 (P < 0.007). Ratios were not significant for Group A lesions alone in the seizure group or for either Group B or Group A findings in the neonate group without seizures. Pathophysiologic events in utero leading to Group B rather than Group A findings are associated with electrically confirmed seizures in near-term and term infants. Group A lesions were considered more likely to have intrapartum or peripartum associations, whereas Group B lesions were considered more likely to have antepartum associations.

Regional differences in spectral EEG measures between healthy term and preterm infants

State-specific spectral electroencephalographic (EEG) values were compared among 14 bipolar channel derivations between two healthy neonatal cohorts. Fifty-five healthy preterm neonates of < or = 32 weeks gestational age at birth were studied with 24-channel recordings over 3 hours at term conceptional age. These were compared with studies of 45 healthy term neonates. Five spectral measures for each channel (i.e., total spectral EEG, delta, theta, alpha, and beta frequency ranges) were calculated for each minute, which was identified as active or quiet sleep, based on visual analysis. Using multivariate analysis of variance, differences at each channel were assessed between neonatal cohorts for both states and cohorts; higher total EEG spectral values were noted during active sleep; whereas higher delta and theta spectral values were noted during quiet sleep. The term cohort had higher values for spectral theta, alpha, and beta power spectra in multiple channels, most significantly in the left central (i.e., C3O1) and sagittal regions (FzCz, CzPz) during both states (P < .0001, adj r2 > or = .2). Both interhemispheric and intrahemispheric differences in spectral values were present. For a healthy preterm cohort, lower spectral energies are expressed during sleep in specific head regions. Physiologic asymmetries exist in the newborn brain which are unique for the preterm infant, emphasizing functional alterations in brain development. How these asymmetries are altered by prenatal or postnatal stress or disease states needs to be explored.

Cardiorespiratory behavior during sleep in full-term and preterm neonates at comparable postconceptional term ages.

ABSTRACT: Cardiorespiratory behavior during sleep has been investigated by comparing visually analyzed minutes of EEG sleep with the digitized values of these two physiologic variables for each corresponding minute. Continuous 3-h nighttime sleep studies on 37 full-term and preterm neonates at comparable postconceptional term ages were acquired under controlled conditions, using a 24-channel computerized monitoring system and an automated eventmarker program. Five thousand, two hundred ninety-four minutes were assigned an EEG state by traditional criteria. Eighteen preterm infants were compared with 19 full-term infants with respect to six cardiac and six respiratory measures: two nonspectral calculations (i.e. average per minute and variance of the means) and four spectral calculations of the cardiorespiratory signal (i.e. bandwidth, spectral edge, mean frequency, and ratio of harmonics). The relative capabilities of these measures to predict a sleep state change were investigated using discriminant analysis. A stepwise selection algorithm in discriminant analysis was used to identify the order of significance for the remaining variables. Eight cardiorespiratory measures were then submitted to multivariate analysis of variance to assess sleep state or preterm–full-term differences: mean frequency, bandwidth, average per minute, and ratio of harmonics for cardiac signals; and spectral edge, mean frequency, logarithm of variance, and ratio of harmonics for respiratory signals. Differences among the sleep states and between neonatal groups were highly significant (p < 0.0001). Interaction between sleep state and neonatal group was also significant (p < 0.034). Two variables differentiated preterm from full-term respiratory behavior: ratio (p ≤ 0.001) and mean frequency (p ≤ 0.02). Three variables demonstrated differences between preterm and full-term cardiac behavior: average heart rate per minute (p ≤ 0.001), ratio (p ≤ 0.05), and bandwidth (p ≤ 0.08). Notably, the lowest values for most spectral measures were noted during tracé alternant quiet sleep compared with the three other segments of the ultradian sleep cycle. Our findings demonstrate sleep state–specific differences in cardiorespiratory behavior in neonates regardless of prematurity. Differences between preterm and full-term infants reflect altered functional development of the brain because of adaptation to prematurity, an extrauterine experience, or both and may contribute to a model of physiologic vulnerability of certain infants for sudden infant death syndrome.