Prediction of Neonatal Seizures in Hypoxic-Ischemic Encephalopathy Using Electroencephalograph Power Analyses.

BACKGROUND: The severity of the initial encephalopathy in neonatal hypoxic-ischemic encephalopathy correlates with seizure burden. Early electroencephalograph (EEG) background activity reflects the severity of encephalopathy. Thus, we hypothesized that early EEG background would be predictive of subsequent seizures in neonatal hypoxic-ischemic encephalopathy. METHODS: This study included infants undergoing therapeutic hypothermia at St. Louis Children's Hospital between January 2009 and April 2013. Two pediatric epilepsy specialists independently characterized EEG background qualitatively using amplitude-integrated EEG trends. Total EEG power in the 1-20 Hz frequency band was calculated for quantitative EEG background assessment. Seizures were identified on conventional full montage EEG. Statistical analysis was performed using logistic regression. RESULTS: Seventy-eight of the 93 eligible infants had artifact-free EEG data; 23 of 78 infants (29%) developed seizures, and of these, 11 developed status epilepticus. The best predictors of subsequent seizures during the first hour of EEG recording were a flat tracing pattern on amplitude-integrated EEG (sensitivity 26%, specificity 98%, likelihood ratio 13, positive predictive value 85%) and the total EEG power less than 10 µV2 (sensitivity 52%, specificity 98%, likelihood ratio 30, positive predictive value 92%). CONCLUSIONS: Early EEG biomarkers predict subsequent seizures in infants with hypoxic-ischemic encephalopathy. Compared with the qualitative amplitude-integrated EEG background, total EEG power improves our ability to identify high-risk infants from the first hour of EEG recording. Infants with a total EEG power of less than 10 µV2 have a 90% risk of subsequent seizures. Quantitative EEG measures could stratify cohorts while evaluating novel neuroprotective strategies in neonatal hypoxic-ischemic encephalopathy.

Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial.

BACKGROUND: The impact of treating electrographic seizures in hypoxic ischemic encephalopathy (HIE) is unknown. METHODS: Neonates ≥36 weeks with moderate or severe HIE were randomly assigned to either treatment of electrographic seizures alone (ESG) or treatment of clinical seizures (CSG). Conventional EEG video was monitored in both groups for up to 96 hours. Cumulative electrographic seizure burden (SB) was calculated in seconds and converted to log units for analysis. MRI scans were scored for severity of brain injury. Infants underwent neurodevelopmental evaluation at 18 to 24 months. Statistical analyses were performed by using SAS 9.3 version (SAS Institute, Inc, Cary, NC). RESULTS: Thirty-five of 69 neonates (51%) who were randomly assigned and included in the study developed seizures (15 in ESG and 20 in CSG). Excluding infants with status epilepticus, median SB (interquartile range) in seconds in ESG (n = 10) was lower than in CSG (n = 16) (449 [113-2070] vs 2226 [760-7654]; P = .02). ESG had fewer seizures with shorter time to treatment (P = .04). Twenty-four of 30 (80%) surviving infants with seizures underwent neurodevelopmental evaluation at 18 to 24 months. Increasing SB in the combined cohort was significantly associated with higher brain injury scores (P < .03) and lower performance scores across all 3 domains on BSID III (P = .03). CONCLUSIONS: In neonates with HIE, EEG monitoring and treatment of electrographic seizures results in significant reduction in SB. SB is associated with more severe brain injury and significantly lower performance scores across all domains on BSID III.

Therapeutic hypothermia in neonatal hypoxic ischemic encephalopathy: electrographic seizures and magnetic resonance imaging evidence of injury.

OBJECTIVE: To evaluate the electrographic seizure burden in neonates with hypoxic ischemic encephalopathy (HIE) treated with or without therapeutic hypothermia and stratified results by severity of HIE and severity of injury as assessed by magnetic resonance imaging (MRI). STUDY DESIGN: Between 2007 and 2011, video-electroencephalography (EEG) monitoring was initiated in neonates with moderate to severe HIE. Seizure burden (in seconds) was calculated, and brain MRI scans were quantitatively scored. Data were analyzed by ANOVA, the Student t test, and the χ(2) test. RESULTS: Sixty-nine neonates with moderate or severe HIE were prospectively enrolled, including 51 who received therapeutic hypothermia and 18 who did not. The mean duration of video-EEG monitoring was longer in the therapeutic hypothermia group (72 ± 34 hours vs 48 ± 34 hours; P = .01). The therapeutic hypothermia group had a lower electrographic seizure burden (log units) after controlling for injury, as assessed by MRI (2.9 ± 0.6 vs 6.2 ± 0.9; P = .003). A reduction in seizure burden was seen in neonates with moderate HIE (P = .0001), but not in those with severe HIE (P = .80). Among neonates with injury assessed by MRI, seizure burden was lower in those with mild (P = .0004) and moderate (P = .02) injury, but not in those with severe injury (P = .90). CONCLUSION: Therapeutic hypothermia was associated with reduced electrographic seizure burden in neonatal HIE. This effect was detected on video-EEG in infants with moderate HIE, but not in those with severe HIE. When stratified by injury as assessed by MRI, therapeutic hypothermia was associated with a reduced seizure burden in infants with mild and moderate injury, but not in those with severe injury.

Posthemorrhagic ventricular dilatation-impact on early neurodevelopmental outcome.

OBJECTIVE: This study evaluates the impact of ventricular dilatation following severe (grades III or IV) intraventricular hemorrhage (IVH) in preterm neonates and the current practice of neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) and early neurodevelopmental outcome. STUDY DESIGN: Premature neonates born at ≤34 weeks' gestational ages with severe IVH were identified retrospectively over a 5-year period (2005 to 2009). Standard measures of ventricular dilatation on head ultrasound (HUS) were recorded. The treatment of PHVD, timing of surgery including the type of temporizing neurosurgical procedure (TNP)-either a ventricular reservoir or a subgaleal shunt-and the subsequent need for ventriculoperitoneal (VP) shunt were evaluated. Patients were retrospectively stratified to an "early" versus "late" intervention group based on HUS measures. Early intervention was defined as TNP performed when the ventricular index (VI) was >97th percentile but <97th percentile + 4 mm. Late intervention was defined as TNP performed when VI was ≥97th percentile + 4 mm. Neurodevelopmental outcomes were evaluated at 18 to 24 months. Infants followed up for neurodevelopmental testing were stratified as group A (progressive PHVD with TNP), group B (PHVD without TNP), and group C (severe IVH without PHVD). RESULTS: One hundred seventy-three preterm neonates with severe IVH were identified during the study period, of whom 139/173 (80%) developed PHVD. Of these, 54 (54/139, 39%) received TNP either early (4/54, 7%) or late (50/54, 93%). Of those who received TNP, 32/54 (59%) required subsequent VP shunt placement. Neurodevelopmental testing was available in 39/109 (36%) infants who survived to discharge. The mean ± standard deviation cognitive, motor, and language composite scores were 77 ± 14.8, 67 ± 15.2, 70 ± 13.8 for group A (n = 16/39), 90 ± 7.8, 84 ± 9.6, 82 ± 18.2 for group B (n = 12/39), and 95 ± 14.3, 86 ± 10.7, 94 ± 15.8 for group C (n = 11/39), respectively (p < 0.006 for group A versus group B and p < 0.004 for group A versus group C across all domains). Increasing ventricular dilatation was associated with adverse motor, cognitive, and language outcomes (p = 0.002) and neonates with progressive PHVD requiring a TNP were most adversely affected (p = 0.0006). There were no differences in any outcome measures between the two types of TNPs. Clinical and demographic characteristics of infants lost to follow-up were not significantly different than those available for follow-up. CONCLUSION: Increasing ventricular size adversely affects neurodevelopmental outcome in infants with PHVD.