Reliability and accuracy of EEG interpretation for estimating age in preterm infants.

OBJECTIVES: To determine the accuracy of, and agreement among, EEG and aEEG readers' estimation of maturity and a novel computational measure of functional brain age (FBA) in preterm infants. METHODS: Seven experts estimated the postmenstrual ages (PMA) in a cohort of recordings from preterm infants using cloud-based review software. The FBA was calculated using a machine learning-based algorithm. Error analysis was used to determine the accuracy of PMA assessments and intraclass correlation (ICC) was used to assess agreement between experts. RESULTS: EEG recordings from a PMA range 25 to 38 weeks were successfully interpreted. In 179 recordings from 62 infants interpreted by all human readers, there was moderate agreement between experts (aEEG ICC = 0.724; 95%CI:0.658-0.781 and EEG ICC = 0.517; 95%CI:0.311-0.664). In 149 recordings from 61 infants interpreted by all human readers and the FBA algorithm, random and systematic errors in visual interpretation of PMA were significantly higher than the computational FBA estimate. Tracking of maturation in individual infants showed stable FBA trajectories, but the trajectories of the experts' PMA estimate were more likely to be obscured by random errors. The accuracy of visual interpretation of PMA estimation was compromised by neurodevelopmental outcome for both aEEG and EEG review. INTERPRETATION: Visual assessment of infant maturity is possible from the EEG or aEEG, with an average of human experts providing the highest accuracy. Tracking PMA of individual infants was hampered by errors in experts' estimates. FBA provided the most accurate maturity assessment and has potential as a biomarker of early outcome.

Hearing Loss after Cardiac Surgery in Infancy: An Unintended Consequence of Life-Saving Care.

OBJECTIVES: To investigate the prevalence of hearing loss after cardiac surgery in infancy, patient and operative factors associated with hearing loss, and the relationship of hearing loss to neurodevelopmental outcomes. STUDY DESIGN: Audiologic and neurodevelopmental evaluations were conducted on 348 children who underwent repair of congenital heart disease at the Children's Hospital of Philadelphia as part of a prospective study evaluating neurodevelopmental outcomes at 4 years of age. A prevalence estimate was calculated based on presence and type of hearing loss. Potential risk factors and the impact of hearing loss on neurodevelopmental outcomes were evaluated. RESULTS: The prevalence of hearing loss was 21.6% (95% CI, 17.2-25.9). The prevalence of conductive hearing loss, sensorineural hearing loss, and indeterminate hearing loss were 12.4% (95% CI, 8.8-16.0), 6.9% (95% CI, 4.1-9.7), and 2.3% (95% CI, 0.6-4.0), respectively. Only 18 of 348 subjects (5.2%) had screened positive for hearing loss before this study and 10 used a hearing aid. After adjusting for patient and operative covariates, younger gestational age, longer postoperative duration of stay, and a confirmed genetic anomaly were associated with hearing loss (all P < .01). The presence of hearing loss was associated with worse language, cognition and attention (P <.01). CONCLUSIONS: These findings suggest that the prevalence of hearing loss in preschool children after heart surgery in infancy may be 20-fold higher than in the 1% prevalence seen in the general population. Younger gestational age, presence of a genetic anomaly, and longer postoperative duration of stay were associated with hearing loss. Hearing loss was associated with worse neurodevelopmental outcomes.

Effect of congenital heart disease on 4-year neurodevelopment within multiple-gestation births.

OBJECTIVES: We sought to assess the effect of congenital heart disease requiring infant surgery with cardiopulmonary bypass on neurodevelopmental outcomes and growth at 4 years of age, while matching for gestational age, socioeconomic status, maternal gestational conditions, home environment, and parental intelligence by studying multiple-gestation births. METHODS: We performed within-family comparison of 14 multiple-gestation births in which 1 child had congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age. Between 4 and 5 years of age, a comprehensive neurodevelopmental assessment was performed. Paired comparisons were conducted between siblings with and without heart defects using a series of nonparametric tests. RESULTS: On average, the children qualified as late preterm (mean gestational age 35.4 ± 2.6 weeks). At an average age of 4.8 ± 0.1 years, children with congenital heart disease weighed less than their siblings (median weight for age z score -0.4 vs 0.1, P = .02) and had worse performance for cognition (median full-scale IQ 99 vs 109, P = .02) and fine motor skills (median Wide Range Assessment of Visual Motor Ability, Fine Motor score 94.5 vs 107.5, P < .01). CONCLUSIONS: After controlling for socioeconomic status, home environment, parental intelligence, and gestational factors by using multiple-gestation births, congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age is associated with lower weight, cognitive abilities and fine motor skills at 4 years of age.

Rates of autism and potential risk factors in children with congenital heart defects.

OBJECTIVE: Atypical development, behavioral difficulties, and academic underachievement are common morbidities in children with a history of congenital heart defects and impact quality of life. Language and social-cognitive deficits have been described, which are associated with autism spectrum disorders. The current study aimed to assess the rates of autism spectrum disorders in a large sample of children with a history of congenital heart defects and to assess medical, behavioral, and individual factors that may be associated with the risk of autism spectrum disorders. DESIGN: Participants included 195 children with a history of congenital heart defects, who are followed in a large-scale longitudinal study. Measures included behavioral data from 4-year-old neurodevelopmental evaluations and parent-report data from a later annual follow-up. RESULTS: Using established cutoffs on an autism spectrum disorder screener, children with congenital heart defects showed higher rates of "possible" autism spectrum disorders than national rates, (Chi-square Test of Equal Proportions), all Ps < .05. A stepwise variable selection method was used to create a "best prediction model" and multivariable logistic regression was used to identify variables predicting diagnostic status. Factors associated with diagnostic risk included medical (delayed sternal closure, prematurity, positive genetic findings), behavioral (cognitive, language, attention issues), and individual (socioeconomic, cultural/racial) variables. ROC analyses identified a cutoff of 7 to maximize sensitivity/specificity based on parent-reported diagnosis. CONCLUSIONS: Risk of autism spectrum disorder screening status in children with congenital heart defects was higher than expected from population rates. Findings highlight the need for referral to a specialist to assess the presence and severity of social-communication issues and congenital heart defects population-specific screening thresholds for children with concern for autism spectrum disorders.

Measuring the Severity of Neonatal Seizures: Temporal-Spatial Burden.

PURPOSE: The American Clinical Neurophysiology Society recommends measuring neonatal seizures' severity by their frequency (number of seizures-anywhere per hour), burden (percentage of time with seizures-anywhere), or on a region-by-region, temporal-spatial basis. This study compares two reduced-channel montages for temporal-spatial seizure burden analyses and examines the agreement of seizures' quantification among these three methodologies. METHODS: A convenience sample of 10 neonatal electroencephalograms was annotated for the beginnings and ends of seizures, which appeared anywhere in the full neonatal montage, then repeated on a more precise, region-by-region basis using 2 reduced-channel montages A and B. Seizure severity was measured by seizures-anywhere frequency, seizures-anywhere burden, and temporal-spatial seizure burdens using montages A and B. The results were compared by measuring their correlation and by linear regression modeling. RESULTS: Seizures-anywhere frequency was correlated with seizures-anywhere burden (ρ = 0.77). However, a narrow range of seizures-anywhere frequencies corresponded with a broad range of seizures-anywhere burdens. Although there was high correlation between seizures-anywhere burdens and temporal-spatial seizure burdens (ρ = 0.92 montage A, ρ = 0.90 montage B), seizures-anywhere burdens were insensitive to variations in the spatial aspects of seizures, which were highly prevalent even in this small sample set. After adjusting for intrareader variability, the temporal-spatial seizure burdens measured by montages A and B were not significantly different (P = 0.56). CONCLUSIONS: The severity of neonatal seizures is poorly represented by simple measures such as seizures-anywhere frequencies or burdens. The use of temporal-spatial seizure burden measurements is supported in work where great precision in quantifying neonatal seizures is required.

Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome.

OBJECTIVES: Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. METHODS: Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. RESULTS: Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores (P's < .05) alone and after adjusting for relevant covariates. CONCLUSIONS: Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants.

Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy.

OBJECT: Mutations in the sodium channel alpha 1 subunit gene (SCN1A) have been associated with a wide range of epilepsy phenotypes including Dravet syndrome. There currently exist few histopathological and surgical outcome reports in patients with this disease. In this case series, the authors describe the clinical features, surgical pathology, and outcomes in 6 patients with SCN1A mutations and refractory epilepsy who underwent focal cortical resection prior to uncovering the genetic basis of their epilepsy. METHODS: Medical records of SCN1A mutation-positive children with treatment-resistant epilepsy who had undergone resective epilepsy surgery were reviewed retrospectively. Surgical pathology specimens were reviewed. RESULTS: All 6 patients identified carried diagnoses of intractable epilepsy with mixed seizure types. Age at surgery ranged from 18 months to 20 years. Seizures were refractory to surgery in every case. Surgical histopathology showed evidence of subtle cortical dysplasia in 4 of 6 patients, with more neurons in the molecular layer of the cortex and white matter. CONCLUSIONS: Cortical resection is unlikely to be beneficial in these children due to the genetic defect and the unexpected neuropathological finding of mild diffuse malformations of cortical development. Together, these findings suggest a diffuse pathophysiological mechanism of the patients' epilepsy which will not respond to focal resective surgery.

Subclinical seizures identified by postoperative electroencephalographic monitoring are common after neonatal cardiac surgery.

OBJECTIVES: The American Clinical Neurophysiology Society recommends continuous electroencephalographic monitoring after neonatal cardiac surgery because seizures are common, often subclinical, and associated with worse neurocognitive outcomes. We performed a quality improvement project to monitor for postoperative seizures in neonates with congenital heart disease after surgery with cardiopulmonary bypass. METHODS: We implemented routine continuous electroencephalographic monitoring and reviewed the results for an 18-month period. Clinical data were collected by chart review, and continuous electroencephalographic tracings were interpreted using standardized American Clinical Neurophysiology Society terminology. Electrographic seizures were classified as electroencephalogram-only or electroclinical seizures. Multiple logistic regression was used to assess associations between seizures and potential clinical and electroencephalogram predictors. RESULTS: A total of 161 of 172 eligible neonates (94%) underwent continuous electroencephalographic monitoring. Electrographic seizures occurred in 13 neonates (8%) beginning at a median of 20 hours after return to the intensive care unit after surgery. Neonates with all types of congenital heart disease had seizures. Seizures were electroencephalogram only in 11 neonates (85%). Status epilepticus occurred in 8 neonates (62%). In separate multivariate models, delayed sternal closure or longer deep hypothermic circulatory arrest duration was associated with an increased risk for seizures. Mortality was higher among neonates with than without seizures (38% vs 3%, P < .001). CONCLUSIONS: Continuous electroencephalographic monitoring identified seizures in 8% of neonates after cardiac surgery with cardiopulmonary bypass. The majority of seizures had no clinical correlate and would not have been otherwise identified. Seizure occurrence is a marker of greater illness severity and increased mortality. Further study is needed to determine whether seizure identification and management lead to improved outcomes.

Interobserver agreement for neonatal seizure detection using multichannel EEG.

OBJECTIVE: To determine the interobserver agreement (IOA) of neonatal seizure detection using the gold standard of conventional, multichannel EEG. METHODS: A cohort of full-term neonates at risk of acute encephalopathy was included in this prospective study. The EEG recordings of these neonates were independently reviewed for seizures by three international experts. The IOA was estimated using statistical measures including Fleiss' kappa and percentage agreement assessed over seizure events (event basis) and seizure duration (temporal basis). RESULTS: A total of 4066 h of EEG recordings from 70 neonates were reviewed with an average of 2555 seizures detected. The IOA was high with temporal assessment resulting in a kappa of 0.827 (95% CI: 0.769-0.865; n = 70). The median agreement was 83.0% (interquartile range [IQR]: 76.6-89.5%; n = 33) for seizure and 99.7% (IQR: 98.9-99.8%; n = 70) for nonseizure EEG. Analysis of events showed a median agreement of 83.0% (IQR: 72.9-86.6%; n = 33) for seizures with 0.018 disagreements per hour (IQR: 0.000-0.090 per hour; n = 70). Observers were more likely to disagree when a seizure was less than 30 sec. Overall, 33 neonates were diagnosed with seizures and 28 neonates were not, by all three observers. Of the remaining nine neonates with contradictory EEG detections, seven presented with low total seizure burden. INTERPRETATION: The IOA is high among experts for the detection of neonatal seizures using conventional, multichannel EEG. Agreement is reduced when seizures are rare or have short duration. These findings support EEG-based decision making in the neonatal intensive care unit, inform EEG interpretation guidelines, and provide benchmarks for seizure detection algorithms.

Neurodevelopmental outcomes in preschool survivors of the Fontan procedure.

OBJECTIVES: The study objectives were to compare the neurodevelopmental outcomes of preschool survivors of the Fontan procedure with those of children with congenital heart disease undergoing biventricular repair and to investigate predictors of neurodevelopmental outcome for those with single ventricle congenital heart disease, including hypoplastic left heart syndrome. METHODS: Neurodevelopmental outcomes were assessed at 4 years of age, including cognition, visual-motor integration, behavior, social skills, and academic achievement. Unadjusted outcomes were compared between patients with biventricular circulation and patients with single ventricles. Predictors of neurodevelopmental outcome were assessed in the patients with single ventricles. Multiple covariate models were evaluated using patient-related, operative, and postoperative covariates. RESULTS: Neurodevelopmental evaluation was performed in 365 children, 112 after the Fontan procedure (hypoplastic left heart syndrome, n = 91; other single ventricle, n = 21) and 253 after biventricular repair. Compared with patients with biventricular circulation, patients with single ventricles performed worse in terms of processing speed, inattention, and impulsivity. Otherwise, there were no significant differences between the groups for any domain. There was a trend toward lower performance for patients with single ventricles on visual motor integration. Outcomes for patients with hypoplastic left heart syndrome were not worse than for other forms of functional single ventricle. Patient factors were more important predictors of neurodevelopmental outcomes than were operative management variables. CONCLUSIONS: In this cohort, unadjusted neurodevelopmental outcomes for preschool survivors of the Fontan procedure are similar to those for children with congenital heart disease undergoing biventricular repair for most domains. Among the patients undergoing the Fontan procedure, hypoplastic left heart syndrome was not associated with worse outcomes compared with other forms of single ventricle.

Postoperative electroencephalographic seizures are associated with deficits in executive function and social behaviors at 4 years of age following cardiac surgery in infancy.

OBJECTIVE: The occurrence of an electroencephalographic (EEG) seizure after surgery for complex congenital heart defects has been associated with worse neurodevelopmental (ND) outcomes. We previously identified postoperative seizures documented by 48-hour EEG monitoring in 11% of 178 neonates and infants. Evaluation at 1 year of age did not identify an adverse effect of an EEG seizure on ND outcomes. The current study was undertaken to determine if testing in the preschool period would identify deficits that become apparent as children develop. METHODS: The ND outcomes assessed at 4 years of age included cognition, language, attention, impulsivity, executive function, behavior problems, academic achievement, and visual and fine motor skills. RESULTS: Developmental evaluations were performed in 132 (87%) of 151 survivors. For the entire cohort, the Full-Scale IQ was 95.0 ± 18.5. IQ was 95.1 ± 18.7 for patients without a history of seizure and 93.6 ± 16.7 for those with a history of seizure. After covariate adjustment, occurrence of an EEG seizure was associated with worse executive function (P = .037) and impaired social interactions/restricted behavior (P = .05). Seizures were not significantly associated with worse performance for cognition, language, attention, impulsivity, academic achievement, or motor skills (all P > .1). CONCLUSIONS: The occurrence of a postoperative seizure is a biomarker of brain injury. This study confirms that postoperative EEG seizures are associated with worse ND outcomes, characterized by impairments of executive function and a higher prevalence of deficits in social interactions and repetitive/restricted behaviors in preschool survivors of cardiac surgery in infancy. However, EEG seizures were not associated with worse cognitive, language, or motor skills.

A review of long-term EEG monitoring in critically ill children with hypoxic-ischemic encephalopathy, congenital heart disease, ECMO, and stroke.

Continuous EEG monitoring is being used with increasing frequency in critically ill children with hypoxic ischemic encephalopathy, congenital heart disease, stroke, and extracorporeal membrane oxygenation (ECMO). The primary indication for EEG monitoring is to identify electrographic seizures and electrographic status epilepticus, which have been associated with worse outcome in some populations. A secondary indication is to provide prognostic information. This review summarizes the available data regarding continuous EEG monitoring in critically ill children with special attention to hypoxic ischemic encephalopathy, congenital heart disease, stroke, and children undergoing ECMO.

Plasma topiramate concentrations resulting from doses associated with neuroprotection against white matter injury and stroke in two strains of rat pups.

BACKGROUND: Cerebral white matter (WM) injury and stroke are common neuropathological injuries in newborns with congenital heart defects (CHDs) requiring surgery. Previous investigations in Long Evans rat pups subjected to hypoxia-ischemia found that intraperitoneal (i.p.) topiramate (TPM) at 30 mg/kg, but not 50 mg/kg, conferred neuroprotection. In Sprague-Dawley pups, a dose of 30 mg/kg protected against stroke. Concentrations associated with neuroprotective doses were not measured. The aims of this investigation were to determine concentrations associated with neuroprotective doses and to investigate the pharmacokinetics (PK) of i.p. TPM. METHODS: Concentration-time data following administration of 30 and 50 mg/kg doses were analyzed using nonlinear mixed-effect modeling. RESULTS: Mean predicted steady-state maximum and average concentrations following 30 mg/kg TPM were 31.3 and 16.8 µg/ml in Long Evans and 39.9 and 24.4 µg/ml in Sprague-Dawley pups. Mean predicted steady-state maximum and average concentrations following 50 mg/kg TPM were 52.1 and 28.1 µg/ml in Long Evans and 66.5 and 40.6 µg/ml in Sprague-Dawley pups. The apparent clearance (CL/F) and apparent volume of distribution (V/F) were 0.0470 ml/min and 22.2 ml, respectively, for Long Evans and 0.0325 ml/min and 19.7 ml, respectively, for Sprague-Dawley pups. CONCLUSION: TPM concentrations associated with neuroprotective doses were determined. Body size and strain were significant covariates on CL/F and V/F. Results provide targets for future neuroprotection studies.

Results of genome-wide analyses on neurodevelopmental phenotypes at four-year follow-up following cardiac surgery in infancy.

BACKGROUND: Adverse neurodevelopmental sequelae are reported among children who undergo early cardiac surgery to repair congenital heart defects (CHD). APOE genotype has previously been determined to contribute to the prediction of these outcomes. Understanding further genetic causes for the development of poor neurobehavioral outcomes should enhance patient risk stratification and improve both prevention and treatment strategies. METHODS: We performed a prospective observational study of children who underwent cardiac surgery before six months of age; this included a neurodevelopmental evaluation between their fourth and fifth birthdays. Attention and behavioral skills were assessed through parental report utilizing the Attention Deficit-Hyperactivity Disorder-IV scale preschool edition (ADHD-IV), and Child Behavior Checklist (CBCL/1.5-5), respectively. Of the seven investigated, three neurodevelopmental phenotypes met genomic quality control criteria. Linear regression was performed to determine the effect of genome-wide genetic variation on these three neurodevelopmental measures in 316 subjects. RESULTS: This genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with three neurobehavioral phenotypes in the postoperative children ADHD-IV Impulsivity/Hyperactivity, CBCL/1.5-5 PDPs, and CBCL/1.5-5 Total Problems. The most predictive SNPs for each phenotype were: a LGALS8 intronic SNP, rs4659682, associated with ADHD-IV Impulsivity (P=1.03 × 10(-6)); a PCSK5 intronic SNP, rs2261722, associated with CBCL/1.5-5 PDPs (P=1.11 × 10(-6)); and an intergenic SNP, rs11617488, 50 kb from FGF9, associated with CBCL/1.5-5 Total Problems (P=3.47 × 10(-7)). 10 SNPs (3 for ADHD-IV Impulsivity, 5 for CBCL/1.5-5 PDPs, and 2 for CBCL/1.5-5 Total Problems) had p<10(-5). CONCLUSIONS: No SNPs met genome-wide significance for our three neurobehavioral phenotypes; however, 10 SNPs reached a threshold for suggestive significance (p<10(-5)). Given the unique nature of this cohort, larger studies and/or replication are not possible. Studies to further investigate the mechanisms through which these newly identified genes may influence neurodevelopment dysfunction are warranted.

Younger gestational age is associated with worse neurodevelopmental outcomes after cardiac surgery in infancy.

OBJECTIVE: Evaluate the impact of near-term delivery on neurodevelopmental (ND) outcomes in children with congenital heart disease (CHD). METHODS: Secondary analysis of data from a study of genetic polymorphisms and ND outcomes after cardiac surgery in infants. The effect of gestational age (GA) as a continuous variable on ND outcomes was evaluated using general linear regression models. GA was also evaluated as a categorical variable to seek a threshold for better outcomes. ND domains tested at 4 years of age included cognition, language skills, attention, impulsivity, memory, executive function, social competence, visual-motor, and fine-motor skills. RESULTS: ND outcomes and GA were available for 378 infants. Median GA was 39 weeks (range, 28-42 weeks) with 351 born at 36 weeks or more (near-term/term). In univariate analysis of the near-term/term subgroup, older GA predicted better performance for cognition, visual-motor, and fine-motor skills. After covariate adjustment, older GA predicted better performance for fine-motor skills (P = .018). Performance for cognition, language, executive function, social skills, visual-motor, and fine-motor skills was better for those born at 39 to 40 weeks of GA or more versus those born at less than 39 weeks (all P < .05). CONCLUSIONS: These findings are consistent with the hypothesis that delivery before 39 to 40 weeks of GA is associated with worse outcomes in patients with CHD. Early delivery of a child with CHD is often indicated because of maternal or fetal health issues. In the absence of these concerns, these data suggest that elective (or spontaneous) delivery at 39 to 40 weeks of GA is associated with better ND outcomes.

Outcome prediction by motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest.

OBJECTIVE: Clinical neurologic signs considered predictive of adverse outcome after pediatric cardiac arrest may have a different prognostic value in the setting of therapeutic hypothermia. We aimed to determine the prognostic value of motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit in tertiary care hospital. PATIENTS: Children treated with therapeutic hypothermia after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Thirty-five children treated with therapeutic hypothermia after cardiac arrest were prospectively enrolled. Examinations were performed by emergency medicine physicians and intensive care unit bedside nurses. Examinations were performed after resuscitation, 1 hr after achievement of hypothermia, during the last hour of hypothermia, 1 hr after achievement of normothermia, after 24 hrs of normothermia, and after 72 hrs of normothermia. The primary outcome was unfavorable outcome at intensive care unit discharge, defined as a pediatric cerebral performance category score of 4-6 at hospital discharge. The secondary outcome was death (pediatric cerebral performance category = 6). The associations between exam responses and unfavorable outcomes (as both pediatric cerebral performance category 4, 5, 6 and pediatric cerebral performance category 6) are presented as positive predictive values, for both all subjects and subjects not receiving paralytics. Statistical significance for these comparisons was determined using Fisher's exact test. At all examination times and examination categories, positive predictive values were higher for the unfavorable outcome pediatric cerebral performance category 4, 5, 6 than the pediatric cerebral performance category 6. By normothermia hour 24, absent motor and pupil responses were highly predictive of unfavorable outcome (pediatric cerebral performance category 4, 5, 6) (positive predictive value 100% and p < .03 for all categories), while at earlier times the predictive value was lower. CONCLUSIONS: Absent motor and pupil responses are more predictive of unfavorable outcome when defined more broadly than when defined as only death. Absent motor and pupil responses during hypothermia and soon after return of spontaneous circulation were not predictive of unfavorable outcome while absent motor and pupil responses once normothermic were predictive of unfavorable short-term outcome. Further study is needed using more robust short-term and long-term outcome measures.

Early EEG improvement after ketogenic diet initiation.

PURPOSE: This study examines electroencephalographic (EEG) changes in children with medication resistant epilepsy treated with the ketogenic diet (KD). METHODS: Routine EEGs were obtained prior to KD initiation, then one month and three months later. Changes in EEG background slowing and frequency of interictal epileptiform discharges (IEDs) were evaluated using power spectrum analysis and manual determination of spike index. KD responders were compared to non-responders to determine if baseline or early EEG characteristics predicted treatment response (>50% seizure reduction) at three months. RESULTS: Thirty-seven patients were evaluated. No differences in baseline EEG features were found between responder groups. Frequency of IEDs declined in 65% of patients as early as one month, by a median of 13.6% (IQR 2-33). Those with a ten percent or greater improvement in IED frequency at one month were greater than six times more likely to be KD responders (OR 6.5 95% CI 0.85-75 p=0.03). Qualitative and quantitative measures of EEG background slowing improved in the whole cohort, but did not predict responder status. CONCLUSION: Baseline predictors of KD response remain elusive. Most patients experienced a reduction in IEDs and improvement in EEG background slowing after KD initiation. Reduction of IEDs at one month strongly predicted KD responder status at three months.

Interobserver reproducibility of electroencephalogram interpretation in critically ill children.

Correct outcome prediction after cardiac arrest in children may improve clinical decision making and family counseling. Investigators have used EEG to predict outcome with varying success, but a limiting issue is the potential lack of reproducibility of EEG interpretation. Therefore, the authors aimed to evaluate interobserver agreement using standardized terminology in the interpretation of EEG tracings obtained from critically ill children after cardiac arrest. Three pediatric neurophysiologists scored 74 EEG samples using standardized categories, terminology, and interpretation rules. Interobserver agreement was evaluated using kappa and intraclass correlation coefficients. Agreement was substantial for the categories of continuity, burst suppression, sleep architecture, and overall rating. Agreement was moderate for seizure occurrence and interictal epileptiform discharge type. Agreement was fair for interictal epileptiform discharge presence, beta activity, predominant frequency, and fastest frequency. Agreement was slight for maximum voltage and focal slowing presence. The variability of interrater agreement suggests that some EEG features are superior to others for use in a predictive algorithm. Using only reproducible EEG features is needed to ensure the most accurate and consistent predictions. Because even seizure identification had only moderate agreement, studies of nonconvulsive seizures in critically ill patients must be conducted and interpreted cautiously.