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1.  Neuroprognostication After Pediatric Cardiac Arrest 
Pediatric neurology  2014;51(5):663-668.e2.
Management decisions and parental counseling after pediatric cardiac arrest depend on the ability of physicians to make accurate and timely predictions regarding neurological recovery. We evaluated neurologists and intensivists performing neuroprognostication after cardiac arrest to determine prediction agreement, accuracy, and confidence.
Pediatric neurologists (n = 10) and intensivists (n = 9) reviewed 18 cases of children successfully resuscitated from a cardiac arrest and managed in the pediatric intensive care unit. Cases were sequentially presented (after arrest day 1, days 2–4, and days 5–7), with updated examinations, neurophysiologic data, and neuroimaging data. At each time period, physicians predicted outcome by Pediatric Cerebral Performance Category and specified prediction confidence.
Predicted discharge Pediatric Cerebral Performance Category versus actual hospital discharge Pediatric Cerebral Performance Category outcomes were compared. Exact (Predicted Pediatric Cerebral Performance Category – Actual Pediatric Cerebral Performance Category = 0) and close (Predicted Pediatric Cerebral Performance Category – Actual Pediatric Cerebral Performance Category = ±1) outcome prediction accuracies for all physicians improved over successive periods (P < 0.05). Prediction accuracy did not differ significantly between physician groups at any period or overall. Agreement improved over time among neurologists (day 1 Kappa [κ], 0.28; days 2–4 κ, 0.43; days 5–7 κ, 0.68) and among intensivists (day 1 κ, 0.30; days 2–4 κ, 0.44; days 5–7 κ, 0.57). Prediction confidence increased over time (P < 0.001) and did not differ between physician groups.
Inter-rater agreement among neurologists and among intensivists improved over time and reached moderate levels. For all physicians, prediction accuracy and confidence improved over time. Further prospective research is needed to better characterize how physicians objectively and subjectively estimate neurological recovery after acute brain injury.
PMCID: PMC4254345  PMID: 25193413
neuroprognostication; pediatric cardiac arrest; outcome prediction
2.  Telemedicine for genetic and neurologic evaluation in the Neonatal Intensive Care Unit 
Evaluate whether telemedicine can be used to perform dysmorphology and neurologic examinations in the neonatal intensive care unit (NICU) by determining the examination accuracy, limitations, and optimized procedures.
Study design
Prospective evaluation of NICU patients referred for subspecialty consultation for dysmorphic features (n=10) or encephalopathy (n=10). A physician at bedside (bedside clinician) performed an in-person examination which was viewed in real-time by a remote physician (remote consultant). Standardized examinations were recorded and compared. Subsequently, a qualitative approach established technique adjustments and optimization procedures necessary to improve visualization.
Telemedicine examinations identified 81 of 87 (93%) dysmorphology examination abnormalities and 37 of 39 (92%) neurologic examination abnormalities. Optimization of remote consultant visualization required an active bedside clinician assisting in camera and patient adjustments.
Telemedicine can be used to accurately perform many components of the dysmorphology or neurologic examinations in NICU patients, but physicians must be mindful of specific limitations.
PMCID: PMC3943754  PMID: 24406740
3.  Density Spectral Array for Seizure Identification in Critically Ill Children 
We evaluated the validity and inter-rater reliability of encephalographer interpretation of color density spectral array (CDSA) EEG for seizure identification in critically ill children and explored predictors of accurate seizure identification.
Conventional EEG tracings from 21 consecutive critically ill children were scored for electrographic seizures. Four two-hour long segments from each patient were converted to 8 channel CDSA displays, yielding 84 images. Eight encephalographers received CDSA training and circled elements thought to represent seizures. Images were reviewed in random order (Group A) or with information regarding seizure presence in the initial 30 minutes and with patient images in order (Group B). Sensitivity, specificity, and inter-rater reliability were calculated. Factors associated with CDSA seizure identification were assessed.
Seizure prevalence was 43% on conventional EEG. Specificity was significantly higher for Group A (92.3% versus 78.2%, p<0.00). Sensitivity was not significantly different between Groups A and B (64.8% versus 75%, p=0.22). Inter-rater reliability was moderate in both groups. Ten percent of images were falsely classified as containing a seizure. Seizure duration ≥2 minutes predicted identification (p<0.001).
CDSA may be a useful screening tool for seizure identification by encephalographers, but it does not identify all seizures and false positives occur.
PMCID: PMC3743420  PMID: 23912575
Critical Care; EEG; Pediatric; Seizure; EEG monitoring
4.  Electroencephalographic Monitoring in Critically Ill Children: Current Practice and Implications for Future Study Design 
Epilepsia  2013;54(8):1419-1427.
Survey data indicate that continuous EEG (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multi-center studies evaluating the impact of electrographic seizures on outcome.
Eleven North American centers retrospectively enrolled 550 consecutive critically ill children who underwent CEEG. We collected data regarding subject characteristics, CEEG indications, and CEEG findings.
Key Findings
CEEG indications were encephalopathy with possible seizures in 67% of subjects, event characterization in 38% of subjects, and management of refractory status epilepticus in 11% of subjects. CEEG was initiated outside routine work hours in 47% of subjects. CEEG duration was <12 hours in 16%, 12-24 hours in 34%, and >24 hours in 48%. Substantial variability existed among sites in CEEG indications and neurologic diagnoses, yet within each acute neurologic diagnosis category a similar proportion of subjects at each site had electrographic seizures. Electrographic seizure characteristics including distribution and duration varied across sites and neurologic diagnoses.
These data provide a systematic assessment of recent CEEG use in critically ill children and indicate variability in practice. The results suggest that multi-center studies are feasible if CEEG monitoring pathways can be standardized. However, the data also indicate that electrographic seizure variability must be considered when designing studies addressing the impact of electrographic seizures on outcome.
PMCID: PMC4062191  PMID: 23848569
EEG Monitoring; Seizure; Status Epilepticus; Pediatric; Non-Convulsive Seizure
5.  Nonconvulsive Electrographic Seizures are Common in Children With Abusive Head Trauma* 
To determine the prevalence of nonconvulsive seizures in children with abusive head trauma.
Retrospective study of children with abusive head trauma undergoing clinically indicated continuous electroencephalographic monitoring.
PICU of a tertiary care hospital.
Children less than or equal to 2 years old with evidence of abusive head trauma determined by neuroimaging, physical examination, and determination of abuse by the Child Protection Team.
Measurements and Main Results
Thirty-two children with abusive head trauma were identified with a median age of 4 months (interquartile range 3, 5.5 months). Twenty-one of 32 children (66%) underwent electroencephalographic monitoring. Those monitored were more likely to have a lower admission Glasgow Coma Scale (8 vs 15, p = 0.05) and be intubated (16 vs 2, p = 0.002). Electrographic seizures occurred in 12 of 21 children (57%) and constituted electrographic status epilepticus in 8 of 12 children (67%). Electrographic seizures were entirely nonconvulsive in 8 of 12 children (67%). Electroencephalographic background category (discontinuous and slow-disorganized) (p = 0.02) and neuroimaging evidence of ischemia were associated with the presence of electrographic seizures (p = 0.05). Subjects who had electrographic seizures were no more likely to have clinical seizures at admission (67% electrographic seizures vs 33% none, p = 0.6), parenchymal imaging abnormalities (61% electrographic seizures vs 39% none, p = 0.40), or extra-axial imaging abnormalities (56% electrographic seizures vs 44% none, p = 0.72). Four of 21 (19%) children died prior to discharge; none had electrographic seizures, but all had attenuated-featureless electroencephalographic backgrounds. Follow-up outcome data were available for 16 of 17 survivors at a median duration of 9.5 months following PICU admission, and the presence of electrographic seizures or electrographic status epilepticus was not associated with the Glasgow Outcome Scale score (p = 0.10).
Electrographic seizures and electrographic status epilepticus are common in children with abusive head trauma. Most seizures have no clinical correlate. Further study is needed to determine whether seizure identification and management improves outcome.
PMCID: PMC4082326  PMID: 23842589
abusive head trauma; electroencephalographic monitoring; electroencephalography; seizure; traumatic brain injury
6.  Current Treatment of Electrographic Seizures and Status Epilepticus in Critically Ill Children: a Single Center Experience 
Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in encephalopathic children in the pediatric intensive care unit (PICU) and associated with worse short-term outcome. Survey data indicate most physicians treat ES and ESE with antiepileptic drugs (AEDs), but few data are available regarding AED usage patterns. We aimed to describe AED usage for ES and ESE in critically ill children.
We performed an observational study of patients who underwent continuous electroencephalographic (cEEG) monitoring in the PICU of a single quaternary care children’s hospital. We collected data regarding age, clinical diagnoses, ES and ESE occurrence, and AEDs utilized.
200 subjects underwent cEEG. ES occurred in 21% (41/200) and ESE occurred in 22% (43/200). Of the 84 patients with ES or ESE, 80 received non-benzodiazepine AEDs including 48% (38 of 80) with ES and 52% (42 of 80) with ESE. The most commonly administered first AEDs were levetiracetam in 38% (30/80), phenobarbital in 31% (25/80), phenytoin-fosphenytoin in 28% (22/80), and valproate in 4% (3/80). Seizures terminated after administration of the first AED in 74% (28/38) with ES and 22% (9/41) with ESE.
Levetiracetam, phenobarbital, and phenytoin-fosphenytoin are commonly used to manage ES and ESE at our center. Over half of subjects received multiple AEDs.
PMCID: PMC3681868  PMID: 23601851
Seizure; Status Epilepticus; Pediatric; Critically Ill; Electroencephalogram; Anticonvulsant; Phenytoin; Fosphenytoin; Phenobarbital; Levetiracetam
7.  Pediatric ICU EEG Monitoring: Current Resources and Practice in the United States and Canada 
To describe current continuous EEG (cEEG) utilization in critically ill children.
An online survey of pediatric neurologists from 50 United States (U.S.) and 11 Canadian institutions was conducted in August 2011.
Responses were received from 58 of 61 (95%) surveyed institutions. Common cEEG indications are altered mental status after a seizure or status epilepticus (97%), altered mental status of unknown etiology (88%), or altered mental status with an acute primary neurological condition (88%). The median number of patients undergoing cEEG per month per center increased from August 2010 to August 2011 (6 to 10 per month in U.S., 2 to 3 per month in Canada). Few institutions have clinical pathways addressing cEEG use (31%). Physicians most commonly review cEEG twice per day (37%). There is variability regarding which services can order cEEG, the degree of neurology involvement, technologist availability, and whether technologists perform cEEG screening.
Among the surveyed institutions, which included primarily large academic centers, cEEG use in pediatric intensive care units is increasing and is often considered indicated for children with altered mental status at risk for non-convulsive seizures. However, there remains substantial variability in cEEG access and utilization among institutions.
PMCID: PMC3616267  PMID: 23545766
Critical Care; EEG; Pediatric; Survey; EEG monitoring
8.  A review of long-term EEG monitoring in critically ill children with hypoxic-ischemic encephalopathy, congenital heart disease, ECMO, and stroke 
PMCID: PMC3616335  PMID: 23545764
EEG monitoring; seizure; pediatric; hypoxia-ischemia; stroke; ECMO; cardiac arrest; congenital heart disease; status epilepticus
9.  Pediatric Intracerebral Hemorrhage: Acute Symptomatic Seizures and Epilepsy 
JAMA neurology  2013;70(4):448-454.
To define the incidence of and explore risk factors for seizures and epilepsy in children with spontaneous intracerebral hemorrhage (ICH).
Prospective cohort study.
Three tertiary care pediatric hospitals.
Seventy-three pediatric subjects with spontaneous ICH including 20 perinatal (≥37 weeks gestation to 28 days) and 53 childhood subjects (>28 days to <18 years at presentation).
Main outcome measures
Acute symptomatic seizures (clinically evident and electrographic-only within 7 days), remote symptomatic seizures, and epilepsy.
Acute symptomatic seizures occurred in 35 subjects (48%). Acute symptomatic seizures as a presenting symptom of ICH occurred in 12 (60%) perinatal and 19 (36%) childhood subjects, P=.07. Acute symptomatic seizures after presentation occurred in 7 children. Electrographic-only seizures were present in 9/32 (28%) with continuous EEG monitoring. One-and two-year remote symptomatic seizure-free survival were 82% (95% CI 68%–90%) and 67% (95% CI 46%–82%), respectively. One- and two-year epilepsy-free survival were 96% (95% CI 83%–99%) and 87% (95% CI 65%–95%), respectively. Elevated intracranial pressure requiring acute intervention was a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy (P=.014, P=.025 and P=.0365, respectively log-rank test).
Presenting seizures are common in perinatal and childhood ICH. Continuous EEG may detect electrographic seizures in some subjects. Single remote symptomatic seizures occur in many, and development of epilepsy is estimated to occur in 13% at two-years. Elevated intracranial pressure requiring acute intervention is a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy.
PMCID: PMC3640376  PMID: 23392319
10.  Electroencephalographic Monitoring in the Pediatric Intensive Care Unit 
Continuous EEG monitoring is used with increasing frequency in critically ill children to provide insight into brain function and to identify electrographic seizures. EEG monitoring use often impacts clinical management, most often by identifying electrographic seizures and status epilepticus. Most electrographic seizures have no clinical correlate, and thus would not be identified without EEG monitoring. There is increasing data that electrographic seizures and electrographic status epilepticus are associated with worse outcome. Seizure identification efficiency may be improved by further development of quantitative EEG trends. This review describes the clinical impact of EEG data, the epidemiology of electrographic seizures and status epilepticus, the impact of electrographic seizures on outcome, the utility of quantitative EEG trends for seizure identification, and practical considerations regarding EEG monitoring.
PMCID: PMC3569710  PMID: 23335026
EEG; EEG monitoring; seizure; status epilepticus; intensive care unit; critical care
11.  Electrographic seizures in pediatric ICU patients 
Neurology  2013;81(4):383-391.
We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality.
Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality.
Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category.
Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality.
PMCID: PMC3772834  PMID: 23794680
12.  Electrographic Status Epilepticus is Associated with Mortality and Worse Short-Term Outcome in Critically Ill Children 
Critical care medicine  2013;41(1):210-218.
Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in critically ill children. We aimed to determine whether ES and ESE are associated with higher mortality or worse short-term neurologic outcome.
Prospective observational study.
Pediatric intensive care unit of a tertiary children’s hospital.
Non-neonatal children admitted to a pediatric intensive care unit (PICU) with acute encephalopathy underwent continuous electroencephalographic (cEEG) monitoring. EEGs were scored as (1) no seizures, (2) ES, or (3) ESE. Covariates included age, acute neurologic disorder category, prior neurodevelopmental status, sex, and EEG background category. Outcomes were mortality and worsening of Pediatric Cerebral Performance Category (PCPC) from pre-admission to PICU discharge. Chi-squared analysis, Fisher’s exact test, and multivariable logistic regression were used to evaluate the associations between ES or ESE and mortality or short-term neurologic outcome, using odds ratios (OR) and 95% confidence intervals (95%CI).
Main Results
Two hundred children underwent cEEG. Eighty-four (42%) had seizures which were categorized as ES in 41 (20.5%) and ESE in 43 (21.5%). Thirty-six subjects (18%) died and 88 subjects (44%) had PCPC worsening. In multivariable analysis ESE was associated with an increased risk of mortality (OR 5.1; 95%CI 1.4, 18, p=0.01) and PCPC worsening (OR 17.3; 95%CI 3.7, 80, p<0.001) while ES was not associated with an increased risk of mortality (OR 1.3; 95%CI 0.3, 5.1; p=0.74) or PCPC worsening (OR 1.2; 95%CI 0.4, 3.9; p=0.77).
ESE, but not ES, is associated with mortality and worse short-term neurologic outcome in critically ill children with acute encephalopathy.
PMCID: PMC3531581  PMID: 23164815
EEG Monitoring; Seizure; Status Epilepticus; Pediatric; Outcome; Non-Convulsive Seizure
13.  Neonatal Seizures and Status Epilepticus 
Neonatal seizures are common, often require electroencephalographic (EEG) monitoring for diagnosis and management, may be associated with worse neurodevelopmental outcome, and can often be treated with existing anticonvulsants. A neonatal electrographic seizure is defined as a sudden, repetitive, evolving and stereotyped event of abnormal electrographic pattern with amplitude of at least two microvolts and a minimum duration of ten seconds. The diagnosis of neonatal seizures relies heavily on the neurophysiologist’s interpretation of EEG. Consideration of specific criteria for the definition of a neonatal seizure, including seizure duration, location, morphology, evolution, semiology, and overall seizure burden, have utility for both the clinician and researcher. We review the importance of EEG in the diagnosis and management of neonatal seizures, the electrographic characteristics of neonatal seizures, the impact of neonatal seizures on outcome, and tools to aid in the identification of neonatal seizures.
PMCID: PMC3463810  PMID: 23027101
seizures; neonate; electroencephalography; status epilepticus
14.  Induction and Maintenance of Therapeutic Hypothermia After Pediatric Cardiac Arrest: Efficacy of a Surface Cooling Protocol 
Induced therapeutic hypothermia after pediatric cardiac arrest is an important intervention. We assessed the feasibility, effectiveness, side effects, and adverse events associated with a standardized surface cooling protocol.
Prospective intervention trial
Urban, tertiary care children’s hospital
12 Pediatric cardiac arrest survivors
Standardized surface cooling protocol
Measurements and Main Results
Patients (age: median 1.5 years, IQR[0.5, 6.25], CPR duration: median 18 min, IQR [10, 45]) were cooled by a standard surface cooling protocol for rapid induction and maintenance of goal rectal Temperature (T) 32–34°C for 24 hours, with prospectively defined rescue protocols. Side effects and clinical interventions were recorded. Median time to rectal T ≤34°C was 1.5 [1, 1.5] hours from cooling initiation and 6 [5, 6.5] hours from arrest. T was documented every 30 minutes. Maintenance target T 32–34°C was attained in 78% (414/531) of measurements, overshoot hypothermia <32°C in 15% (81/531), and overshoot hyperthermia >34°C in 7% (36/531). Mean bias between rectal vs esophageal T was −0.42 °C [95%CI, −0.49 to −0.35], and between rectal and bladder T was 0.16 °C [95%CI, 0.11 to 0.22]. Side effects observed included: hypokalemia <3.0mEq/L in 67% of patients and bradycardia < 2%ile for age in 58%. There were no episodes of bleeding or ventricular tachyarrhythmia that required treatment. Six of 12 (50%) patients survived to discharge.
A standard surface cooling protocol achieved rapid induction of hypothermia after pediatric cardiac arrest. During maintenance of hypothermia, 78% of measures were within target T 32–34°C. Commonly employed temperature sites (esophageal, rectal and bladder) were similar. Overshoot hypothermia and associated side effects were common, but there were no serious adverse events attributable to induced therapeutic hypothermia in this case series. Surface cooling protocols to induce and maintain therapeutic hypothermia after pediatric cardiac arrest are potentially feasible.
PMCID: PMC3740551  PMID: 20431502
induced hypothermia; heart arrest; children
15.  EEG Monitoring in Critically Ill Children: Indications and Strategies 
Pediatric Neurology  2012;46(3):158-161.
Continuous electroencephalographic monitoring often detects non-convulsive seizures in critically ill children, but is resource intense and has not been shown to improve outcome. As institutions develop clinical pathways for monitoring, it is important to consider how seemingly minor variations may have a substantial impact on resource utilization and cost. We performed a one month prospective observational study in which each patient in a 45-bed pediatric intensive care unit was screened for potential monitoring indications. 247 patients were screened. Minor differences in monitoring indications would have a substantial impact on resource utilization. We then calculated the number of monitoring days that would be required each month based on two strategies that differed in monitoring duration. The prolonged-targeted and brief-targeted strategies would have required 106 and 33 monitoring days, respectively. Based on published non-convulsive seizure occurrence data, these strategies would detect 0.14, and 0.43 patients with seizures per monitoring day performed, respectively. A brief-targeted strategy provides a high yield for non-convulsive seizure identification, but would fail to diagnose some patients with seizures.
PMCID: PMC3286021  PMID: 22353290
EEG Monitoring; Non-Convulsive Seizure; Pediatric
16.  Common Data Elements for Pediatric Traumatic Brain Injury: Recommendations from the Working Group on Demographics and Clinical Assessment 
Journal of Neurotrauma  2012;29(4):639-653.
The Common Data Elements (CDEs) initiative is a National Institutes of Health (NIH) interagency effort to standardize naming, definitions, and data structure for clinical research variables. Comparisons of the results of clinical studies of neurological disorders have been hampered by variability in data coding, definitions, and procedures for sample collection. The CDE project objective is to enable comparison of future clinical trials results in major neurological disorders, including traumatic brain injury (TBI), stroke, multiple sclerosis, and epilepsy. As part of this effort, recommendations for CDEs for research on TBI were developed through a 2009 multi-agency initiative. Following the initial recommendations of the Working Group on Demographics and Clinical Assessment, a separate workgroup developed recommendations on the coding of clinical and demographic variables specific to pediatric TBI studies for subjects younger than 18 years. This article summarizes the selection of measures by the Pediatric TBI Demographics and Clinical Assessment Working Group. The variables are grouped into modules which are grouped into categories. For consistency with other CDE working groups, each variable was classified by priority (core, supplemental, and emerging). Templates were produced to summarize coding formats, guide selection of data points, and provide procedural recommendations. This proposed standardization, together with the products of the other pediatric TBI working groups in imaging, biomarkers, and outcome assessment, will facilitate multi-center studies, comparison of results across studies, and high-quality meta-analyses of individual patient data.
PMCID: PMC3289844  PMID: 21939389
clinical studies; common data elements; data coding; data collection; pediatric; standardization; traumatic brain injury
17.  Outcome prediction by motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest 
Clinical neurologic signs considered predictive of adverse outcome after pediatric cardiac arrest (CA) may have a different prognostic value in the setting of therapeutic hypothermia (TH). We aimed to determine the prognostic value of motor and pupillary responses in children treated with TH after CA.
Prospective cohort study.
Pediatric ICU in tertiary care hospital.
Children treated with TH after CA.
Measurements and Main Results
Thirty-five children treated with TH after CA were prospectively enrolled. Examinations were performed by emergency medicine physicians and intensive care unit bedside nurses. Examinations were performed after resuscitation, 1 hour after achievement of hypothermia, during the last hour of hypothermia, 1 hour after achievement of normothermia, after 24 hours of normothermia, and after 72 hours of normothermia. The primary outcome was unfavorable outcome at ICU discharge, defined as a Pediatric Cerebral Performance Category (PCPC) score of 4–6 at hospital discharge. The secondary outcome was death (PCPC = 6). The associations between exam responses and unfavorable outcomes (as both PCPC 4,5,6 and PCPC 6) are presented as positive predictive values (PPV), 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 PPV is higher for the unfavorable outcome PCPC 4,5,6 than PCPC 6. By normothermia hour 24, absent motor and pupil responses were highly predictive of unfavorable outcome (PCPC 4,5,6) (PPV 100% and p<0.03 for all categories), while at earlier times the predictive value was lower.
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.
PMCID: PMC3264396  PMID: 21499174
Therapeutic Hypothermia; Neurological Examination; Pediatric; Hypoxic Ischemic Encephalopathy; Cardiac Arrest; Prognosis
18.  SIRPIDs in a 13 year old following overdose and respiratory arrest 
Pediatric neurology  2011;45(5):350-351.
PMCID: PMC3201738  PMID: 22000321
19.  Strain-Specific Differences in Perinatal Rodent Oligodendrocyte Lineage Progression and Its Correlation with Human 
Developmental Neuroscience  2011;33(3-4):251-260.
Progress in the development of rat models of human periventricular white matter injury (WMI) has been hampered by uncertainty about the developmental window in different rodent strains that coincides with cerebral white matter development in human premature infants. To define strain-specific differences in rat cerebral white matter maturation, we analyzed oligodendrocyte (OL) lineage maturation between postnatal days (P)2 and P14 in three widely studied strains of rat: Sprague-Dawley, Long-Evans and Wistar (W). We previously reported that late OL progenitors (preOL) are the major vulnerable cell type in human periventricular WMI. Strain-specific differences in preOL maturation were found at P2, such that the W rat had the highest percentage and density of preOL relative to the other strains. Overall, at P2, the state of OL maturation was similar to preterm human cerebral white matter. However, by P5, all three strains displayed a similar magnitude and extent of OL maturation that persisted with progressive myelination between P7 and P14. PreOL were the predominant OL lineage stage present in the cerebral cortex through P14, and thus OL lineage maturation occurred latter than in white matter. The hippocampus also displayed a later onset of preOL maturation in all three strains, such that OL lineage maturation and early myelination was not observed to occur until about P14. This timing of preOL maturation in rat cortical gray matter coincided with a similar timing in human cerebral cortex, where preOL also predominated until at least 8 months after full-term birth. These studies support that strain-specific differences in OL lineage immaturity were present in the early perinatal period at about P2, and they define a narrow window of preterm equivalence with human that diminishes by P5. Later developmental onset of preOL maturation in both cerebral cortex and hippocampus coincides with an extended window of potential vulnerability of the OL lineage to hypoxia-ischemia in these gray matter regions.
PMCID: PMC3225247  PMID: 21865655
Oligodendrocytes; Glia; White matter
20.  Seizures as a presenting symptom of acute arterial ischemic stroke in childhood 
The Journal of pediatrics  2011;159(3):479-483.
To define incidence of seizures as a presenting symptom of acute arterial ischemic stroke (AIS) in children and to determine whether younger age, infarct location, or AIS etiology were risk factors for seizure at AIS presentation.
Study design
Children aged 2 months to 18 years presenting with AIS from January 2005 to December 2008 were identified from a single center prospective pediatric stroke registry. Clinical data were abstracted, and a neuroradiologist reviewed imaging studies.
Among 60 children who met inclusion criteria, seizures occurred at stroke presentation in 13 (22%). Median age was significantly younger in children who presented with seizures than in those who did not (1.1 versus 10 years, p=0.0009). Seizures were accompanied by hemiparesis in all patients. Three of four children with clinically overt seizures at presentation also had non-convulsive seizures on continuous EEG monitoring.
About one-fifth of children with acute AIS present with seizures. Seizures were always accompanied by focal neurologic deficits. Younger age was a risk factor for seizures at presentation. Seizure at presentation was not associated with infarct location or etiology. Non-convulsive seizures may occur during the acute period.
PMCID: PMC3134612  PMID: 21429519
EEG; non-convulsive seizures; hemiparesis
21.  EEG Monitoring during Therapeutic Hypothermia in Neonates, Children, and Adults 
Therapeutic hypothermia is being utilized as a neuro-protective strategy in neonates, children, and adults. The most common indications are hypoxic ischemic encephalopathy in neonates and post cardiac arrest in adults. Electroencephalographic monitoring use is increasing in critical care units, and is sometimes a component of therapeutic hypothermia clinical pathways. Monitoring may detect non-convulsive seizures or non-convulsive status epilepticus, and it may provide prognostic information. We review data regarding indications for therapeutic hypothermia and electroencephalographic monitoring in neonatal, pediatric, and adult critical care units, and discuss technical aspects related to such monitoring.
PMCID: PMC3422126  PMID: 21988034
Cardiac arrest; EEG; neonatal hypoxic ischemic encephalopathy; non-convulsive seizures; seizures; therapeutic hypothermia; traumatic brain injury
22.  Impact of Continuous EEG Monitoring on Clinical Management in Critically Ill Children 
Neurocritical care  2011;15(1):70-75.
Continuous EEG (cEEG) monitoring is being used with increasing frequency in critically ill patients, most often to detect non-convulsive seizures. While cEEG is non-invasive and feasible in the critical care setting, it is also expensive and labor intensive, and there has been little study of its impact on clinical care. We aimed to determine prospectively the impact of cEEG on clinical management in critically ill children.
Critically ill children (non-neonates) with acute encephalopathy underwent cEEG. Study enrollment and data collection were prospective.
100 children were studied. EEG monitoring led to specific clinical management changes in 59 children. These included initiating or escalating anti-seizure medications in 43 due to seizure detection, demonstrating that a specific event (subtle movement or vital sign change) was not a seizure in 21, or obtaining urgent neuroimaging that led to a clinical change in 3. In the remaining 41 children, cEEG ruled out the presence of non-convulsive seizures but did not lead to a specific change in clinical management.
EEG monitoring led to changes in clinical management in the majority of patients, suggesting it may have an important role in management of critically ill children. Further study is needed to determine whether the management changes elicited by cEEG improve outcome.
PMCID: PMC3134111  PMID: 20499208
Seizure; Status epilepticus; Pediatric; Critically Ill; Electroencephalogram; EEG monitoring
23.  Electrographic Seizures During Therapeutic Hypothermia for Neonatal Hypoxic-ischemic Encephalopathy 
Journal of child neurology  2011;26(6):724-728.
Electrographic seizures are common in neonates with hypoxic-ischemic encephalopathy, but detailed data are not available regarding seizure incidence during therapeutic hypothermia. The objective of this prospective study was to determine the incidence and timing of electrographic seizures in term neonates undergoing whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy as detected by conventional full-array electroencephalography for 72 hours of therapeutic hypothermia and 24 hours of normothermia. Clinical and electroencephalography data were collected from 26 consecutive neonates. Electroencephalograms were reviewed by 2 pediatric neurophysiologists. Electrographic seizures occurred in 17 of 26 (65%) patients. Seizures were entirely nonconvulsive in 8 of 17 (47%), status epilepticus occurred in 4 of 17 (23%), and seizure onset was in the first 48 hours in 13 of 17 (76%) patients. Electrographic seizures were common, were often nonconvulsive, and had onset over a broad range of times in the first days of life.
PMCID: PMC3102150  PMID: 21447810
hypothermia; induced; infant; seizures; electroencephalography; hypoxia-ischemia; brain
24.  Levetiracetam for Treatment of Neonatal Seizures 
Journal of child neurology  2011;26(4):465-470.
Neonatal seizures are often refractory to treatment with initial antiseizure medications. Consequently, clinicians turn to alternatives such as levetiracetam, despite the lack of published data regarding its safety, tolerability, or efficacy in the neonatal population. We report a retrospectively identified cohort of 23 neonates with electroencephalographically confirmed seizures who received levetiracetam. Levetiracetam was considered effective if administration was associated with a greater than 50% seizure reduction within 24 hours. Levetiracetam was initiated at a mean conceptional age of 41 weeks. The mean initial dose was 16 ± 6 mg/kg and the mean maximum dose was 45 ± 19 mg/kg/day. No respiratory or cardiovascular adverse effects were reported or detected. Levetiracetam was associated with a greater than 50% seizure reduction in 35% (8 of 23), including seizure termination in 7. Further study is warranted to determine optimal levetiracetam dosing in neonates and to compare efficacy with other antiseizure medications.
PMCID: PMC3082578  PMID: 21233461
neonatal seizures; status epilepticus; levetiracetam; anticonvulsant
25.  Short-Term Outcome Prediction by Electroencephalographic Features in Children Treated with Therapeutic Hypothermia After Cardiac Arrest 
Neurocritical care  2011;14(1):37-43.
Electroencephalographic (EEG) features may provide objective data regarding prognosis in children resuscitated from cardiac arrest (CA), but therapeutic hypothermia (TH) may impact its predictive value. We aimed to determine whether specific EEG features were predictive of short-term outcome in children treated with TH after CA, both during hypothermia and after return to normothermia.
Thirty-five children managed with a standard clinical TH algorithm after CA were prospectively enrolled. EEG recordings were scored in a standardized manner and categorized. EEG category 1 consisted of continuous and reactive tracings. EEG category 2 consisted of continuous but unreactive tracings. EEG category 3 included those with any degree of discontinuity, burst suppression, or lack of cerebral activity. The primary outcome was unfavorable short-term outcome defined as Pediatric Cerebral Performance Category score of 4–6 (severe disability, vegetative, death) at hospital discharge. Univariate analyses of the association between EEG category and outcome was performed using logistic regression.
For tracings obtained during hypothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcome than those in category 1 (OR 10.7, P = 0.023 and OR 35, P = 0.004, respectively). Similarly, for tracings obtained during normothermia, patients with EEGs in categories 2 or 3 were far more likely to have poor outcomes than those in category 1 (OR 27, P = 0.006 and OR 18, P = 0.02, respectively).
A simple EEG classification scheme has predictive value for short-term outcome in children undergoing TH after CA.
PMCID: PMC3086560  PMID: 20890677
Therapeutic hypothermia; Outcome; Pediatric; Hypoxic ischemic encephalopathy; Heart arrest; Prognosis

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