Biomedical subjects

Mark S Scher

Publications and source records attributed to Mark S Scher.

At least 19 recordsLinked to original sources

PubMed2006

Neonatal seizure classification: a fetal perspective concerning childhood epilepsy.

Neonatal seizures are markers for time-specific etiologies during antepartum, intrapartum and neonatal time periods. Seizures with or without encephalopathic signs can represent a continuum of maternal, placental, fetal and neonatal risk factors and disease states. A multi-dimensional classification scheme for neonatal seizures is suggested that will help strategize specific therapeutic interventions to optimize neurologic outcome and anticipate later neurological morbidities including epilepsy risk. This scheme combines "epileptic" and "non-epileptic" seizure descriptions which capture time-specific and brain region-specific mechanisms for seizures. Synchronized video electroencephalographic monitoring provides the most accurate start and endpoints for cortically generated seizures. However, subcortical sites of injury may also initiate abnormal clinical signs with or without the subsequent expression of electrographic seizures. Co-registration of digital neuroimaging techniques such as magnetic resonance imaging with computational electroencephalographic datasets will provide more precise structure-function correlates for neonatal seizures that address both cortical and subcortical sites of injury. Finally, more precise definitions of neonatal status epilepticus need to be established because of the long-term harmful effects on brain development by prolonged seizures expressed as epilepsy and cognitive-behavioral deficits. With this expanded classification scheme for neonatal seizures, novel pharmacologic and surgical strategies can be designed for disease-specific rescue, repair, and regeneration strategies of damaged brain tissue that occur during fetal and neonatal periods, and are later expressed during infancy and childhood. Clinical neuroscientists must strive to develop a classification scheme that bridges bench to bedside concepts of developmental neural plasticity research, recognizing both negative and positive consequences of brain remodeling and repair of the child and adolescent brain. Developmental neural plasticity also extends into adulthood when brain remodeling mechanisms further contribute to epileptogenesis and continues to impair quality of life.

Brain Diseases↗

PubMed2006

Effects of antenatal magnesium sulfate and corticosteroid therapy on sleep states of preterm infants.

This exploratory longitudinal study was designed to compare the neonatal illness severity, sleep-wake, and respiratory sleep behaviors of preterm infants whose mothers received prenatal corticosteroids and/or magnesium sulfate (MgSO4) with those of infants whose mothers did not receive these medications. The 134 infants were divided into four groups: those whose mothers received MgSO4 only, those who received steroids only, those who received both MgSO4 and steroids, and those who received neither. The groups did not differ on infant characteristics or illness severity. Infants exposed to MgSO4 had more active sleep without rapid eye movement, indicating poorly organized active sleep. The MgSO4 -only group had higher quiet sleep regularity scores and fewer state changes. These findings suggest that fetal exposure to MgSO4 may subtly affect the central nervous system.

Adrenal Cortex Hormones↗

PubMed2006

Neurophysiologic assessment of neonatal sleep organization: preliminary results of a randomized, controlled trial of skin contact with preterm infants.

BACKGROUND: Sleep is important to brain organization, but few strategies to promote sleep among premature infants have been tested. Behaviorally based measures of sleep have shown increased quiet sleep (QS) and decreased active sleep (AS) during skin-to-skin contact (SSC) with the mother, but these results have not been confirmed with objective electroencephalographic/polysomnographic measures of sleep organization. Important differences exist between behavioral and electroencephalographic/polysomnographic definitions of sleep state. METHODS: Data for the first 28 relatively healthy, preterm subjects of an ongoing randomized trial of one 2- to 3-hour session of SSC or incubator care between feedings are reported here. Infants were positioned prone, inclined, and nested in an incubator during the 2- to 3-hour pretest period, were fed, and then went into the test period of SSC or incubator care. Infants were left largely undisturbed throughout testing. A mixed-model regression analysis compared the test-pretest differences in outcome measures within and between groups. RESULTS: Results showed that arousals were significantly lower in the SSC group, compared with the control group, for the entire study period and for test-pretest matched segments of QS and AS. Rapid eye movement was significantly lower for the SSC group for the study period and AS segments. Indeterminate sleep was significantly lower for the SSC group when confounding environmental variables were included in the regression analysis. When 4 subjects who experienced excessive ambient light levels during SSC were removed from analysis, QS increased during SSC. CONCLUSIONS: The patterns demonstrated by the SSC group are analogous to more-mature sleep organization. SSC may be used as an intervention to improve sleep organization in this population of preterm infants.

Electroencephalography↗

PubMed2005

Cyclicity of neonatal sleep behaviors at 25 to 30 weeks' postconceptional age.

Previous sleep studies of preterm neonates describe the rudimentary expression of sleep state cyclicity after 30 wk postconceptional age (PCA), with stability over multiple cycles only after 36 wk PCA. The research objective for this study was to determine whether sleep state cyclicity was expressed in neonates of 25-30 wk PCA, using two criteria for state identification. Our neonatal sleep consortium includes a total cohort of 359 children who were healthy and medically ill neonates who were recruited from three obstetric-neonatal services and received multiple-hour EEG sleep studies. A subset of the 33 youngest preterm infants were selected to evaluate the first of serial 2- to 3-h EEG-sleep recordings to assess the presence of sleep state cyclicity. One neonatal neurophysiologist visually assigned EEG-sleep characteristics for each record. Rapid eye movement (REM) counts and EEG discontinuity were specifically chosen to assess whether sleep cyclicity was expressed. A combined measure of REM and EEG discontinuity were used in an autocovariance analysis to assess cycling and mean cycle duration. A mean cycle duration of 68 +/- 19 min with a range of 37-100 min was determined from the REM-EEG discontinuity state for 24 neonates. The remaining nine infants had absent or poor sleep cyclicity. Sleep state cyclicity is expressed for a majority of neonates between 25 and 30 wk PCA, reflecting an ultradian biologic rhythm during the early perinatal stage of brain development.

Activity Cycles↗

PubMed2005

Automated state analyses: proposed applications to neonatal neurointensive care.

The two principal challenges of neonatal physiologic monitoring device are: (1) the development of computational strategies that consider the rudimentary forms of neonatal sleep state especially for preterm infants and (2) any physiologic monitoring device for clinical applications in a neonatal intensive care setting must be small, portable, and user-friendly. Our multicenter neonatal sleep consortium has acquired more than 1,100 multihour EEG-sleep recordings on over 370 neonates, ranging from 24 to 44 weeks gestation. Each recording was visually-scored for state, arousals, movements, and rapid eye movements, which were used as templates when applying spectral analyses. The authors have defined a brain dysmaturity index to represent functional brain reorganization as the prenate matures to a full-term age; delayed or accelerated physiologic behaviors have been described for the preterm cohort when compared to the full-term group at the same postmenstrual age. Seven EEG-sleep measures comprise this index: quiet sleep percentage, sleep cycle length, rapid eye movements, arousals, spectral beta EEG energies, spectral EEG correlations, and a spectral measure of respiratory regularity. Linear and nonlinear computational algorithms are being developed to automate the computation of the dysmaturity index and to identify new feature types that correlate with dysmaturity. Automated neonatal sleep monitoring system can potentially improve neonatal neurointensive care by facilitating analyses of pervasive neonatal brain disorders expressed primarily as altered sleep state organization, and help predict altered developmental trajectories of children at higher risk for neurologic sequelae.

Brain↗

PubMed2005

Prediction of neonatal state and maturational change using dimensional analysis.

Nonlinear time series analysis techniques have been used to analyze physiologic signals such as EEG and heart rate. The authors illustrate the application of dimensional analysis (DA) to assess neonatal sleep states at increasing gestational ages up to full-term age. One hundred and sixteen EEG-polygraphic recordings were performed on 55 neonatal subjects between 28 and 43 weeks gestational age from which state assignments were initially scored by visual analysis. A single channel of EEG (i.e., FP1-C3) was selected for dimensional analysis. Two-tailed t-tests were used to test for differences in the correlation dimension (CD) between active and quiet sleep states for both preterm and full-term neonates as a function of maturation. A significant difference in CD between active and quiet sleep states (P < 0.001) was noted for the full-term infant. A positive correlation between CD and increasing conceptional age was noted (P < 0.001). DA showed an increase in the complexity for both active and quiet sleep as the preterm infant matured toward a full-term corrected age. Lower dimensionality (CD), indicative of reduced complexity, was noted for the healthy preterm cohort at corrected full-term age when compared with the full-term group. Dimensional analysis demonstrated a positive correlation for both active and quiet sleep, as the infant matured toward corrected term age. Lower dimensionality was noted for the healthy preterm cohort at corrected full-term age. These findings support the concept of physiologic dysmaturity for the preterm neonate as a reflection of altered neural plasticity of the brain as a result of the conditions of prematurity.

Developmental Disabilities↗

PubMed2004

Pediatric neurology participation in a fetal diagnostic service.

Fetal neurologic consultations were provided to 166 maternal-fetal pairs over a 5-year period. Consultations were initiated during the second trimester in 46% (74/166) of pairs. Fifty-percent (83/166) of these consultations involved brain malformations, of which 55% (46/83) were also associated with other organ abnormalities. Brain malformations principally consisted of encephalocele, dorsal neural tube defects, holoprosencephaly, schizencephaly, cerebellar dysgenesis, and ventriculomegaly. Non-central nervous system organ system anomalies were observed in another 50% (83/166), in decreasing order of occurrence-cardiac, renal, gastrointestinal, pulmonary, in utero growth restriction, and hydrops fetalis. Outcome data on 128 children included survival at delivery for 86/128 or 67.2%, termination in 16/128 (12.5%), stillborn 6/128 (4.7%), and postnatal deaths in 20/128 (15.6%). Maternal medical histories were abnormal for 65% of women. Placental pathology was abnormal in 80% (72/102) of available specimens, consisting of both chronic and acute lesions. Postnatal diagnoses were obtained in 128 neonates; 64% (82/128) remained the same diagnosis, 28.1% (36/128) had a worse or improved diagnosis, and 10/128 (7.8%) were normal. Pediatric neurologists can provide useful fetal consultations early during gestation, and must consider multiple organ diagnoses and maternal-placental diseases. Postnatal diagnoses may be different from the fetal diagnoses which will influence continuity of care for the child at older ages.

Adolescent↗

PubMed2004

Automated EEG-sleep analyses and neonatal neurointensive care.

Clinical applications of neonatal EEG-sleep studies can improve neurointensive care for preterm and fullterm infants. Behavioral and physiologic assessments of neonatal sleep by nursing and physician personnel can result in more developmentally appropriate state regulation for infants, particularly for those who require medical care for many weeks to months in the intensive care unit. Secondly, prediction of altered expressions of EEG-sleep patterns for those children at higher risk for neurological sequelae can anticipate the need for aggressive interventional strategies. The application of digital analyses of specific cerebral and noncerebral physiologic measures for long-term monitoring periods can utilize efficient and novel strategies of automated EEG and sleep state identification which can also assist in daily medical care and prediction of neurodevelopmental outcome.

Brain Diseases↗

PubMed2003

Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use.

A prospective study of the efficacy of seizure cessation by phenobarbital versus phenytoin administration utilized both clinical and electroencephalographic expressions of seizure behaviors. The phenomenon of uncoupling was defined as the persistence of electrographic seizures despite the suppression of >or=50% clinical seizures after either one or both antiepileptic drugs use. Fifty-nine neonates (25 to 43 weeks estimated gestational age) with electrically-confirmed seizures were assigned to either of two drugs and continuously monitored over a 24-hour period. Nine of the fifty-nine patients had only electrographic seizure expression both before and after drug administration. Of the remaining 50 patients who had both electrical and clinical seizure expression before treatment, 24 infants responded to the first choice of an antiepileptic drug with no further seizures. Fifteen of the remaining 26 infants (58%) with persistent seizures after treatment had uncoupling of electrical and clinical expressions of seizures; no difference in the uncoupling effect was noted for neonates who were treated with either antiepileptic drug or based on prematurity or gender. Serial electroencephalographic monitoring helps document continued electrographic seizure expression after antiepileptic drug use, following complete or partial suppression of clinical seizure behaviors.

Anticonvulsants↗

PubMed2003

Fetal neurologic consultations.

The pediatric neurologist can fulfill a useful role as a subspecialty consultant concerning the fetus with a suspected brain disorder, given that neurologic disease may occur before the intrapartum period. Brain disorders detected in the neonatal period may also reflect fetal brain damage before dysfunction is first documented. Medical conditions during the antepartum or intrapartum periods can alternatively predispose the fetus or neonate to express brain dysfunction at a later period, with either de novo or compounded brain injury. The pediatric neurologist must, therefore, consider maternal, placental, and fetal diseases on which a neonatal encephalopathy may be superimposed. This review article provides the neurologist with an integrative approach to fetal neurology, emphasizing perspectives from other subspecialties concerning maternal-fetal medicine, pathology, and neonatology, as well as other pediatric subspecialties. Evaluation of future strategies for either fetal or neonatal brain resuscitation will need to consider the developmental context in which a suspected brain injury occurred during the antepartum, intrapartum, and neonatal periods.

Female↗

PubMed2003

Neonatal seizures and brain damage.

There are four unresolved clinical issues at bedside with respect to the recognition, differential diagnosis, prognosis, and treatment of infants who present with seizures. There is also an overriding fifth question which bridges these four clinical issues, based on a laboratory researcher's perspective at the "bench". Given the increasing understanding of the neurobiologic and pathophysiologic explanations for seizures in animal models, one must consider the question of whether neonatal seizures cause brain injury or are a surrogate of injury resulting from other etiologies.

Animals↗

PubMed2003

Temperature differences during sleep between fullterm and preterm neonates at matched post-conceptional ages.

OBJECTIVE: Altered physiologic behaviors during sleep have been described for healthy preterm neonates at post-conceptional fullterm ages. These differences may reflect brain dysmaturity as a result of conditions of prematurity. The present study examines if differences in state-specific temperature changes exist in a healthy preterm cohort as another expression of brain dysmaturity. METHODS: Rectal and skin temperatures during sleep state transitions are reported in 59 asymptomatic post-conceptional age term infants, comparing 25 full term and 34 preterm infants. Three-hour 24-channel electroencephalogram (EEG)-sleep studies were recorded for each child. One of 4 sleep states were assigned for each of 7339 min, based on both cerebral and non-cerebral measures. For each study, average rectal and skin temperatures for each sleep state were calculated. Repeated measures MANOVA were performed using 4 explanatory variables, average skin and rectal temperatures and variance of rectal and skin temperatures, comparing preterm/fullterm status and 4 sleep states. RESULTS: Rectal temperature differences between neonatal cohorts during specific sleep states were noted: F=8.58, P<0.0001. Significant differences were noted for both average and variance of rectal temperatures during all 4 sleep states with higher temperatures in the preterm group. For all neonates, both skin and rectal temperature differences were also noted among sleep states (F=4.22, P<0.0004). Differences were specifically noted between two specific EEG segments, mixed frequency active sleep and tracé alternant quiet sleep (P<0.0004). CONCLUSIONS: In summary, significant differences in temperatures were noted across sleep state transitions for two neonatal cohorts, with higher average rectal temperatures in the preterm cohort. These findings highlight an altered measure of brain function during sleep in preterm infants affecting temperature regulation. This altered physiologic behavior reflects adaptation of the infant's brain function to conditions of prematurity which may contribute to vulnerabilities at older ages.

Body Temperature↗

PubMed2003

Functional brain maturation in neonates as measured by EEG-sleep analyses.

OBJECTIVE: Seven measures of neonatal EEG-sleep behavior were evaluated using multivariate analyses to ascertain if physiologic differences exist between healthy full- and preterm cohorts. METHODS: A total of 381 24-channel EEG-sleep studies were analyzed, including 125 recordings on 50 healthy fullterm and 256 recordings on 59 asymptomatic preterm infants between 28 and 70.6 weeks post-conceptional age. One EEG study for each subject was randomly assigned (109 studies) within the time window of 38-44 weeks post-conceptional age. A multivariate analytic procedure was applied to the data sets, by which a 'dysmaturity index' was assigned for each infant, based on 7 EEG-sleep measures. This index was defined in terms of the distance from the fullterm group's centroid (i.e. Mahalanobis distance). Receiver-operating characteristic curves (ROCs) were calculated for several different combinations of 7 EEG-sleep measures to describe differences between neonatal cohorts. RESULTS: The ROC curve corresponding to all 7 EEG-sleep measures covered the substantially largest area among the curves for the sets of variables considered, suggesting that all 7 measures of sleep behavior were required to best discriminate between cohorts. CONCLUSIONS: This methodology exemplifies how EEG-sleep analyses can be applied to the study of functional brain maturation of infants at risk for neurodevelopment problems. SIGNIFICANCE: Changes in EEG-sleep behavior in the preterm infant may represent altered activity-dependent development of neural circuitry, resulting in remodeling of the immature brain as a reflection of adaptation to conditions of prematurity.

Brain↗

PubMed2003

Fetal and neonatal neurologic case histories: assessment of brain disorders in the context of fetal-maternal-placental disease. Part 1: Fetal neurologic consultations in the context of antepartum events and prenatal brain development.

The pediatric neurologist can contribute to a fetal diagnostic service that includes the maternal-fetal specialist as well as placental and pediatric pathologists, neonatologists, neurosurgeons, geneticists, and other pediatric subspecialists. Selected case histories of patients who presented to our fetal neurology service illustrate the wide spectrum of disease entities that are highly dependent on the time during gestation, location of brain injury, and the direct as well as indirect effects of fetal/maternal/placental disease processes on brain maturation. The pediatric neurologist has the opportunity to provide an important consultative role, bridging prenatal to neonatal life and integrating medical and ethical concerns for the child in the context of the family.

Adolescent↗

PubMed2003

Fetal and neonatal neurologic case histories: assessment of brain disorders in the context of fetal-maternal-placental disease. Part 2: Neonatal neurologic consultations in the context of adverse antepartum and intrapartum events.

The more conventional role of the pediatric neurologist involves the evaluation of the child after birth. Although the pediatric neurologist rarely attends the delivery of the neonate, consultation by the neurologist should begin immediately following stabilization by the neonatal resuscitation team. Four interrelated aspects of the neurologist's clinical assessment will be discussed in the context of reaching a consultative opinion, which must incorporate knowledge of chronologic events before as well as during labor and delivery. This evaluation encompasses an assessment of levels of arousal, increased or decreased muscle tone, presence of seizures, and effects of systemic diseases on the central nervous system, which are the essential elements of a complete neurologic examination. Documentation of the neonate's neurologic condition, together with knowledge of maternal, fetal, and placental diseases, will help anticipate neuroresuscitative decisions, as well as subsequent neurologic deficits.

Arousal↗

PubMed2003

Prenatal contributions to epilepsy: lessons from the bedside.

While epilepsy can present at any age, this condition often occurs because of adverse events early in life. Pathogenetic mechanisms also cause deleterious consequences to the brain during prenatal life. For the epileptologist to fully appreciate developmental epileptogenesis, one must apply an ontogenetic approach (i.e. "nature-nurture-niche") in order to study the epileptic condition from a fetal neurology perspective. Genetic susceptibility can involve pre-fertilization and post-fertilization mechanisms that dictate the timing and form of major malformations associated with specific epileptic syndromes. Maternal, fetal, and placental disease conditions also contribute to either brain malformations or injuries, depending on events during the first or second half of pregnancy. Sequential stages during prenatal brain development, from embryonic through perinatal periods, specify which gray and white matter structures may be adversely altered, with later expression of seizures in the context of motor, cognitive and behavioral deficits. Translational research from bench to bedside should consider the acquired causes of pediatric and adult epilepsies in the context of the patient's genetic environment.

Brain↗

PubMed2002

Cerebral infarctions in the fetus and neonate: maternal-placental-fetal considerations.

Historical data, clinical examination findings, and laboratory information must be integrated along a variable timeline that includes antepartum, intrapartum, and postnatal time periods when cerebral infarction can occur, in the context of the neonates genetic endowment. Genetic susceptibility or prenatal acquired vulnerabilities regarding stroke syndromes may set in motion a cascade of molecular pathways that ultimately cause or exacerbate brain injury when the vulnerable child experiences adverse medical conditions. The clinician must consider maternal, placental, and fetal conditions on which a stroke syndrome may be superimposed, with or without additional brain injury from other pathogenic mechanisms. Evaluation of fetal and neonatal cerebral infarction requires knowledge of mechanisms of brain injury that cross medical disciplines and may involve consultation with maternal/fetal specialists, placental and pediatric pathologists, neonatologists, geneticists, and other pediatric subspecialties. Comprehensive evaluations of survivors of cerebral infarction are needed to better understand structural and functional plasticity of the developing brain after a cerebrovascular event in the fetal and neonatal periods.

Algorithms↗

PubMed2002

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.

Journal Article↗