Development of epilepsy in newborns with moderate hypoxic-ischemic encephalopathy and neonatal seizures

Background: Hypoxic-ischemic encephalopathy (HIE) is one of the most frequent causes of neonatal death or neurological handicaps such as cerebral palsy, mental delay, and epilepsy. Moreover, an acute consequence of HIE are neonatal seizures which can cause an additional brain damage. The neurodevelopmental outcome is known in the mild or severe cases of HIE, but in the moderate conditions the predictivity results, to date, unsatisfying. Objective: The purpose of this prospective study was to appraise the development of post-neonatal epilepsy in a cohort of term infants with moderate HIE and neonatal seizures. Methods: This study considered all newborns admitted to Neonatal Intensive Care Unit of the University of Parma between January 2000 and December 2002 for perinatal asphyxia, then followed by Neonatal Neurology Service. In all patients, neonatal variables such as type of delivery, birth weight, gestational age, Apgar scores, the need for resuscitation and assisted ventilation soon after birth, and arterial-blood pH were analyzed. Results: Ninety-two newborns were enrolled in the study because of perinatal asphyxia. Of these, 27 subjects developed mild HIE, 25 moderate, and five severe HIE. Neonatal seizures were present in 13 subjects with moderate HIE and in all newborns with severe HIE. At the last follow-up, only three infants belonging to patients with severe HIE developed epilepsy. Conclusion: Moderate HIE seems not to be related to post-neonatal epilepsy either if associated or not with neonatal seizures.     

Machine learning for the early prediction of infants with electrographic seizures in neonatal hypoxic-ischemic encephalopathy

Objective

To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic-ischemic encephalopathy (HIE).

Methods

Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure-prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases. The earliest EEG hour provided a qualitative analysis (discontinuity, amplitude, asymmetry/asynchrony, sleep–wake cycle [SWC]) and a quantitative analysis (power, discontinuity, spectral distribution, inter-hemispheric connectivity) from full montage and two-channel amplitude-integrated EEG (aEEG). Subgroup analysis, only including infants without anti-seizure medication (ASM) prior to EEG was also performed. Machine-learning (ML) models (random forest and gradient boosting algorithms) were developed to predict infants who would later develop seizures and assessed using Matthews correlation coefficient (MCC) and area under the receiver-operating characteristic curve (AUC).

Results

The study included 162 infants with HIE (53 had seizures). Low Apgar, need for ventilation, high lactate, low base excess, absent SWC, low EEG power, and increased EEG discontinuity were associated with seizures. The following predictive models were developed: clinical (MCC 0.368, AUC 0.681), qualitative EEG (MCC 0.467, AUC 0.729), quantitative EEG (MCC 0.473, AUC 0.730), clinical and qualitative EEG (MCC 0.470, AUC 0.721), and clinical and quantitative EEG (MCC 0.513, AUC 0.746). The clinical and qualitative-EEG model significantly outperformed the clinical model alone (MCC 0.470 vs 0.368, p-value .037). The clinical and quantitative-EEG model significantly outperformed the clinical model (MCC 0.513 vs 0.368, p-value .012). The clinical and quantitative-EEG model for infants without ASM (n = 131) had MCC 0.588, AUC 0.832. Performance for quantitative aEEG (n = 159) was MCC 0.381, AUC 0.696 and clinical and quantitative aEEG was MCC 0.384, AUC 0.720.

Significance

Early EEG background analysis combined with readily available clinical data helped predict infants who were at highest risk of seizures, hours before they occur. Automated quantitative-EEG analysis was as good as expert analysis for predicting seizures, supporting the use of automated assessment tools for early evaluation of HIE.     

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in perinatal asphyxia

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) play important roles in the function of the blood–brain-barrier (BBB). We investigated the roles of MMP-9 and TIMP-1 in the pathogenesis of hypoxic–ischemic encephalopathy following perinatal asphyxia. Serum concentrations of MMP-9 and TIMP-1 were determined by ELISA in 12 neonates with perinatal asphyxia and 15 controls on the birth day and the next day. Serum MMP-9 concentrations in asphyxiated neonates with neurological sequelae (n = 5) were significantly higher than concentration in asphyxiated neonates without sequelae (n = 7) and controls on birth day (p = 0.003 and p < 0.001, respectively). The ratios of serum MMP-9/TIMP-1 on birth day in asphyxiated neonates with neurological sequelae were significantly higher than those in asphyxiated neonates without sequelae (p = 0.048). There were no significant differences in the serum MMP-9 concentrations or the ratios of MMP-9/TIMP-1 between asphyxiated neonates with and without neurological sequelae on the day after birth. Our preliminary study suggests that serum MMP-9 levels on birth day are important for predicting neurological prognosis of neonates with asphyxia.     

Una década después de la implantación en España de la hipotermia terapéutica en el recién nacido con encefalopatía hipóxico-isquémica perinatal

IntroductionMore than a decade has passed since therapeutic hypothermia (TH) was introduced in Spain; this is the only neuroprotective intervention that has become standard practice in the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). This article aims to provide a current picture of the technique and to address the controversies surrounding its use.DevelopmentIn the last 10 years, TH has been successfully implemented in the vast majority of tertiary hospitals in Spain, and more than 85% of newborns with moderate or severe HIE currently receive the treatment. The factors that can improve the efficacy of TH include early treatment onset (first 6 hours of life) and the control of comorbid factors associated with perinatal asphyxia. In patients with moderate HIE, treatment onset after 6 hours seems to have some neuroprotective efficacy. TH duration longer than 72 hours or deeper hypothermia do not offer greater neuroprotective efficacy, but instead increase the risk of adverse effects. Unclarified aspects are the sedation of patients during TH, the application of the treatment in infants with mild HIE, and its application in other scenarios. Prognostic information and time frame are one of the most challenging aspects.ConclusionsTH is universal in countries with sufficient economic resources, although certain unresolved controversies remain. While the treatment is widespread in Spain, there is a need for cooling devices for the transfer of these patients and their centralisation.     

Prediction of survival in severely asphyxiated infants

There is currently no set of evaluations that allows for the accurate prediction of survival or death following severe perinatal asphyxia and the development of hypoxic-ischemic encephalopathy. We hypothesized that low cerebral blood flow velocity, as determined by Doppler ultrasonography, may predict neurologic nonviability in a group of severely asphyxiated infants who exhibited signs of severe encephalopathy. Using the staging system of Sarnat and Sarnat, 11 infants who had had severe perinatal asphyxia were studied at the time that their neurologic examinations met the criteria for stage 3 encephalopathy. Apgar scores, cord or initial blood gases and pH, blood pressure, heart rate, and electroencephalographic findings were similar between those infants who survived (N = 8) and those who died due to cerebral injury (N = 3). Cerebral blood flow velocity, however, was significantly lower in those infants who died (3,288 ± 884 vs 1,051 ± 789 planimeter units/min; P < .005). All infants who died had retrograde diastolic blood flow in the common carotid artery. In the study group the combination of low cerebral blood flow velocity and retrograde diastolic blood flow in the common carotid artery allowed prediction of survival and death with sensitivity and specificity of 100% (P < .006). Following perinatal asphyxia and the development of severe encephalopathy, the finding of low cerebral blood flow velocity appears to be predictive of neurologic nonviability.     

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 6 h 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 12 h after birth, and deaths or outcomes at 18 months 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 20 s 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 10 min in term infants with HIE and a good correlation with short-term outcome.     

The localizing value of auditory event-related potentials (P300) in patients with medically intractable temporal lobe epilepsy

The localizing value of postictal versus interictal event-related potentials (ERPs) was studied in patients with medically intractable TLE admitted for long-term video EEG monitoring. Ten patients with partial seizures and secondary generalization underwent preictal (upon hospital admission), postictal (6 h after seizure), and interictal (7–48 h after seizure) ERP recordings of an auditory oddball paradigm. Preictal ERPs were compared to postictal and interictal recordings. Intraclass correlations, transformed into z scores, were utilized to analyze amplitude differences between electrodes placed on the hemisphere ipsilateral versus contralateral to the epileptogenic focus. The results showed that in 9 out of 10 patients the ERP amplitude was reduced in postictal compared to preictal recordings for electrodes placed ipsilateral to the epileptogenic focus (P<0.0001). However, there was no difference in amplitude between ipsilateral and contralateral electrodes in preictal and interictal recordings. These findings suggest that postictal ERPs are of localizing value in patients with TLE while interictal ERPs are not.     

The impact of Neonatal Resuscitation Program courses on mortality and morbidity of newborn infants with perinatal asphyxia

OBJECTIVE: Neonatal care provided within the first few minutes of life plays a major role in the reduction of neonatal morbidity and mortality. Neonatal Resuscitation Program (NRP) courses had been held since 1996. The aim of this study was to evaluate the impact of the NRP on morbidity and mortality of newborn infants with perinatal asphyxia. METHODS: This retrospective study comprised newborn infants who were born in hospitals at Trakya region of Turkey during the last 3 years and were diagnosed as perinatal asphyxia and were referred to our Neonatal Unit. Those patients who were referred before NRP course (pretraining period) were designated as Group 1, those who were referred after the first NRP course (transition period) as Group 2, and those who were referred after the second NRP course (post-training period) as Group 3. Chart review was performed with regard to gestational age, birth weight, Apgar scores, resuscitation type, stage of hypoxic ischemic encephalopathy (HIE), existence of meconium aspiration syndrome (MAS), progress of the disease, duration of hospitalization. RESULTS: The study comprised 66 patients; 35 in Group 1, 18 in Group 2 and 13 in Group 3. The number of cases who had not been resuscitated was 10 in the pretraining period, 3 in the transition period and 1 in the post-training period which decreased significantly. The first minute Apgar scores in three groups were as follows; 2.08+/-1.2, 2.2+/-1.1 and 3.7+/-1.4, and this increase was statistically significant. The fifth minute Apgar scores also increased from 5.43+/-1.5 in the pretraining period to 6.5+/-1.9 in the post-training period, but this increase was not statistically significant. The number of patients with Stage 1 and 2 HIE decreased more in Group 3 (n=11 in Stage 1 HIE, n=17 in Stage 2 HIE) compared to those in Group 1 (n=7 in Stage 1 HIE, n=5 in Stage 2 HIE) but the difference was not statistically significant. The duration of hospitalization decreased in post-training period (15.1+/-10.3 days in pretraining period, 12.0+/-8.9 days in transition period, 6.1+/-1.2 days in post-training period). CONCLUSIONS: After NRP courses, the number of patients with perinatal asphyxia and with no resuscitation and also the duration of hospitalization decreased significantly, whereas the first minute Apgar scores increased significantly.     

Racial differences in patient expectations prior to resective epilepsy surgery

We assessed the nature and frequency of preoperative expectations among patients with refractory epilepsy who were enrolled in a seven-center observational study of epilepsy surgery outcomes. At enrollment, patients responded to open-ended questions about expectations for surgical outcome. With the use of an iterative cutting-and-sorting technique, expectation themes were identified and rank-ordered. Associations of expectations with race/ethnicity were evaluated. Among 391 respondents, the two most frequently endorsed expectations (any rank order) were driving (62%) and job/school (43%). When only the most important (first-ranked) expectation was analyzed, driving (53%) and cognition (17%) were most frequently offered. Nonwhites endorsed job/school and cognition more frequently and driving less frequently than whites (all P  0.05), whether expectations of any order or only first-ranked expectations were included. Elucidating the reason for these differences can aid in the clinical decision-making process for resective surgery and potentially address disparities in its utilization.     

Prevalence of dementia and associated risk factors in Middle Anatolia, Turkey

This study aimed to investigate the prevalence of various cognitive disorders in the older population (age 55 years and above) of Eskisehir, Turkey, by conducting a cluster sampled door-to-door survey. A total of 3100 inhabitants were screened with the Mini-Mental State Examination (MMSE) and a questionnaire concerning demographic, occupational and social data. Individuals (n = 320) with MMSE scores of 25 were assessed according to the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and were investigated in the more detailed phase 2 study. The overall prevalence of dementia was 8.4%, although it ranged from 2.2% among those aged 55–59 years to 5.3% among those aged 60–64 years, and to 30.4% among those aged 75 or above. Vascular dementia was the most common type (51.1%), followed by Alzheimer’s dementia (48.8%). In a very small proportion of individuals (0.1%), dementia was due to other causes such as B12 deficiency, a tumour or hydrocephalus. Significant risk factors for dementia were female sex, low education, age, living in a rural area and a family history of dementia.     

Cerebral blood flow regulation in neonatal rabbits is altered by chronic cocaine administration

Maternal cocaine abuse has several deleterious effects in the newborn, including perinatal asphyxia, hypoxia, and hypercapnia. We hypothesized that chronic cocaine exposure during development may alter cerebral blood flow (CBF) regulation. We studied 16 neonatal rabbits that had received cocaine (20 mg/kg, i.p. b.i.d.) or saline since birth. Changes in CBF were measured by laser doppler flowmetry before (baseline), and during hypercapnia (FiCO₂=7.5%), hypoxia (FiO₂=12%), and asphyxia (apnea for 1 min). During hypercapnia, CBF increased less in cocaine than in control animals (28±3% vs. 69±10%, P<0.05). During hypoxia, CBF increased similarly in both groups. During reventilation after asphyxia, CBF increased more in cocaine than in control animals (391±52% vs. 225±43%, P<0.05). Chronic cocaine exposure during brain development appears to alter CBF regulation to hypercapnia and asphyxia, which may put the drug exposed newborn at risk for neurologic injury around birth.     

Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia

Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morphine exposure of lumbar dorsal spinal cord caused significant increases in proinflammatory cytokine and chemokine release. Opposition of analgesia by proinflammatory cytokines is rapid, occurring 5 min after intrathecal (perispinal) opioid administration. We document that opposition of analgesia by proinflammatory cytokines cannot be accounted for by an alteration in spinal morphine concentrations. The acute anti-analgesic effects of proinflammatory cytokines occur in a p38 mitogen-activated protein kinase and nitric oxide dependent fashion. Chronic intrathecal morphine or methadone significantly increased spinal glial activation (toll-like receptor 4 mRNA and protein) and the expression of multiple chemokines and cytokines, combined with development of analgesic tolerance and pain enhancement (hyperalgesia, allodynia). Statistical analysis demonstrated that a cluster of cytokines and chemokines was linked with pain-related behavioral changes. Moreover, blockade of spinal proinflammatory cytokines during a stringent morphine regimen previously associated with altered neuronal function also attenuated enhanced pain, supportive that proinflammatory cytokines are importantly involved in tolerance induced by such regimens. These data implicate multiple opioid-induced spinal proinflammatory cytokines in opposing both acute and chronic opioid analgesia, and provide a novel mechanism for the opposition of acute opioid analgesia.     

TERM INFANTS WITH HYPOXIC-ISCHEMIC ENCEPHALOPATHY: OUTCOME AT 3.5 YEARS

A total of 167 term neonates with a diagnosis of hypoxic-ischemic encephalopathy (HIE) had detailed neurodevelopmental follow-up at 3.5 years of age. All 66 children with mild HIE were free from handicap; all seven with severe HIE were severely handicapped; and of the 94 with moderate HIE at birth, 21.3 per cent were handicapped. Mean IQ was significantly related to the category of HIE. Within the moderate HIE category, the neurological examination at discharge from the Neonatal Intensive Care Unit was more useful than the presence of neonatal convulsions in identifying children with subsequent developmental delay. Abnormalities on this examination related significantly to an increased number of handicapped children, decreased motor and language skills, and lower IQs. Although neonatal convulsions were associated with an increased number of handicapped children, they did not significantly affect most other developmental outcome measures. In term infants with documented HIE at birth, major neurodevelopmental dysfunction at 3.5 years depended more on prospectively established category of HIE than on other perinatal or social factors.     

The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia

BackgroundThe Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed.ObjectiveThe purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia.MethodsThe study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the “PharmaCool” multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied.ResultsData of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (interquartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score ≥12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8).ConclusionThe Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated newborns. A score ≥12 is associated with adverse outcomes (death before discharge and development of severe epilepsy). The Thompson encephalopathy score is not associated with the development of multiple organ failure.     

Nucleated red blood cell counts: An early predictor of brain injury and 2-year outcome in neonates with hypoxic–ischemic encephalopathy in the era of cooling-based treatment

Background: Raised nucleated red blood cell (NRBC) counts in neonates may indicate in utero hypoxia and brain damage. Objective: The study aimed to examine the use of NRBC counts as a predictor of brain injury and neurodevelopmental outcomes in neonates with hypoxic–ischemic encephalopathy (HIE) treated under current cooling-based strategy. Methods: Forty-three neonates with asphyxia between 2004 and 2010 were retrospectively investigated. Twenty neonates with moderate/severe HIE underwent hypothermia (HT), and 23 with mild HIE were treated in normothermia (NT). Neonates were divided into groups according to the presence of cerebral parenchymal lesions on magnetic resonance imaging (MRI) at 2 weeks after birth. All patients were followed-up neurologically for ?24 months. NRBC counts during the first 3 days were compared between groups. Results: Eleven HT (HT-N) and 21 NT (NT-N) neonates had normal MRI, and 9 HT (HT-L) and 2 NT (NT-L) neonates had parenchymal lesions. NRBC counts, both absolute and /100 white blood cells (WBC) counts, during the first 3 days in HT-L and NT-L were significantly higher than those in HT-N and NT-N, particularly within 6 hours after birth (HT-N: 502 [0–3060]/mm³ vs HT-L: 2765 [496–6192]; 0 [0–3417] vs NT-L: 4384 [3978–4789], median [range]). Neonates with /100 white blood cells ?6/mm³ and absolute NRBC counts ?1324/mm³ within 6 hours of birth had high risks of abnormal MRIs and 2-year outcomes. Conclusions: NRBC counts can predict brain injury and neurological outcomes in cooled and non-cooled asphyxiated neonates.     

EEG,evoked potentials and pulsed Doppler in asphyxiated term infants

ObjectiveTo evaluate electroencephalograms (EEG), evoked potentials (EPs) and Doppler findings in the cerebral arteries as predictors of a 1-year outcome in asphyxiated newborn infants.MethodsEEG and EPs (brain stem auditory (BAEP), somatosensory (SEP), visual (VEP) evoked potentials) were assessed in 30 asphyxiated and 30 healthy term infants during the first days (range 1–8). Cerebral blood flow velocities (CBFV) were measured from the cerebral arteries using pulsed Doppler at ∼24 h of age. EEG, EPs, Doppler findings, symptoms of hypoxic ischemic encephalopathy (HIE) and their combination were evaluated in predicting a 1-year outcome.ResultsAn abnormal EEG background predicted poor outcome in the asphyxia group with a sensitivity of 67% and 81% specificity, and an abnormal SEP with 75% and 79%, respectively. Combining increased systolic CBFV (mean + 3SD) with abnormal EEG or SEP improved the specificity, but not the sensitivity. The predictive values of abnormal BAEP and VEP were poor. Normal EEG and SEP predicted good outcome in the asphyxia group with sensitivities from 79% to 81%. The combination of normal EEG, normal SEP and systolic CBFV < 3SD predicted good outcome with a sensitivity of 74% and 100% specificity.ConclusionsCombining abnormal EEG or EPs findings with increased systolic CBFV did not improve prediction of a poor 1-year outcome of asphyxiated infants. Normal EEG and normal SEP combined with systolic CBFV < 3SD at about 24 h can be valuable in the prediction of normal 1-year outcome.SignificanceCombining systolic CBFV at 24 h with EEG and SEP examinations can be of use in the prediction of normal 1-year outcome among asphyxiated infants.     

Increased neurogenesis after hypoxic-ischemic encephalopathy in humans is age related

The leading cause of morbidity and mortality after successful resuscitation is hypoxic-ischemic encephalopathy (HIE), which results in neuronal loss within the neocortex and the hippocampal formation. This study focuses on the impact of HIE on adult neurogenesis in the human hippocampal dentate gyrus as a potential intrinsic regenerative mechanism in response to neuronal damage. Brain sections of 22 autopsy cases with HIE and of 19 age-matched controls without neuropathological abnormalities were investigated by means of immunohistochemistry. The densities of immature granule cells during axon guidance and outgrowth (assessed by TUC-4 immunohistochemistry) and of young calretinin-expressing postmitotic neurons were increased in the granule cell layer of cases who had suffered from HIE (P = 0.0002 and P = 0.0001, respectively). Similarly, the density of apoptotic granule cells, as detected by in situ tailing and morphological criteria, was increased in HIE (P = 0.014). In cases with HIE, the increase in the density of TUC-4-labeled cells inversely correlated with age (P = 0.027). In contrast, neither the density of proliferating nor that of apoptotic cells was substantially influenced by age within the control group. Taken together, both an increase in adult neurogenesis and in neuronal apoptosis was observed in the human dentate gyrus in response to HIE. The data suggest a decrease of adult neurogenesis in older-aged cases. Whether neurogenesis can contribute to recovery after HIE remains to be determined. The stimulation of adult neurogenesis may be less efficient in older victims of HIE. W.-R. C. Mattiesen and S. C. Tauber have equally contributed to this work.     

Reduction in cerebral blood flow volume in infants complicated with hypoxic ischemic encephalopathy resulting in cerebral palsy

Hypoxic ischemic brain can result in cerebral palsy, mental retardation, and learning disabilities in surviving children. The purpose of this study was to elucidate the cerebral blood flow volume in infants complicated with brain damage after the birth. Nine term infants with hypoxic ischemic encephalopathy and 41 normal term infants were studied. Four infants with HIE suffered from CP or mental retardation, and the other five infants exhibited normal neurodevelopment. The mean blood flow velocity and diameter of the internal carotid artery and the vertebral artery were measured for 28 days. The intravascular flow volume was determined by calculating the flow velocity and the cross-sectional area. The ejection fraction and cardiac output were obtained, and the mean blood pressures were recorded. The summed flow volumes in both the ICA and VA, and the total CBFV increased after the birth in both the normal infants and the infants diagnosed with HIE with no disability complications. The total blood flow volume was significantly lower in infants with HIE and CP than in normal infants on days 0, 2, 5, 7, 10, 21, and 28, and significantly lower in infants with HIE and CP than in normal infants with HIE on days 2, 4, and 7. The ejection fraction was significantly lower in infants with HIE than in normal infants only on day 0. Our results suggest that the total cerebral blood supply is decreased in infants with HIE in those complicated with brain damage.     

Perinatal ischemic brain damages and apoptosis

Perinatal brain damages are caused mainly by circulation insufficiency due to intrauterine or birth asphyxia. Hypoxic-ischemic encephalopathy (HIE) and pontosubicular neuronal necrosis (PSN) are typical perinatal ischemic diseases. We investigated the expression of apoptosis in these diseases, using TdT-mediated dUTP nick end labeling (TUNEL) method and immunohistochemistry with Bcl-2, Bcl-x, Bak and caspase 3 (CPP 32). In HIE, Purkinje cells showed overexpression of Bcl-2 and CPP 32, and some karyorrhectic cells were positive for TUNEL. In PSN, neurons of the pontine nuclei showed overexpression of Bcl-x and CPP 32, and most karyorrhectic neurons were positive for TUNEL. Immature neurons were susceptible to these changes. Apoptosis may play an important role in the pathomechanism of perinatal ischemic brain damages.     

Severe fetal acidemia and subsequent neonatal encephalopathy in the larger premature infant

The contribution of intrapartum hypoxia-ischemia to neonatal encephalopathy in the larger preterm infant remains poorly defined. Such infants could become potential candidates for neuroprotective strategies. The objective of this study was to determine in preterm infants of gestation 31 to 36 weeks, with severe fetal acidemia (i.e., cord arterial pH < 7.00) the incidence of moderate to severe neonatal encephalopathy as well as the perinatal characteristics that may facilitate early identification. The data of 61 preterm infants of mean birth weight 1998 gm and mean gestation of 33.6 weeks were retrieved. Short-term abnormal neurologic outcome measures included evidence of encephalopathy with or without seizures or neuroimaging abnormalities. Eight (13%) of 61 infants developed an abnormal neonatal neurologic outcome. More infants with abnormal vs normal outcome had 1-minute Apgar of 0, i.e., 4/8 vs 3/53, 5-minute Apgar score 相似文献