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OBJECTIVE: Strategies are needed to optimally deploy continuous EEG monitoring (CEEG) for electroencephalographic seizure (ES) identification and management due to resource limitations. We aimed to construct an efficient multi-stage prediction model guiding CEEG utilization to identify ES in critically ill children using clinical and EEG covariates. METHODS: The largest prospective single-center cohort of 1399 consecutive children undergoing CEEG was analyzed. A four-stage model was developed and trained to predict whether a subject required additional CEEG at the conclusion of each stage given their risk of ES. Logistic regression, elastic net, random forest, and CatBoost served as candidate methods for each stage and were evaluated using cross validation. An optimal multi-stage model consisting of the top-performing stage-specific models was constructed. RESULTS: When evaluated on a test set, the optimal multi-stage model achieved a cumulative specificity of 0.197 and cumulative F1 score of 0.326 while maintaining a high minimum cumulative sensitivity of 0.938. Overall, 11 % of test subjects with ES were removed from the model due to a predicted low risk of ES (falsely negative subjects). CEEG utilization would be reduced by 32 % and 47 % compared to performing 24 and 48 h of CEEG in all test subjects, respectively. We developed a web application called EEGLE (EEG Length Estimator) that enables straightforward implementation of the model. CONCLUSIONS: Application of the optimal multi-stage ES prediction model could either reduce CEEG utilization for patients at lower risk of ES or promote CEEG resource reallocation to patients at higher risk for ES.
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Estado Terminal , Eletroencefalografia , Convulsões , Humanos , Eletroencefalografia/métodos , Eletroencefalografia/normas , Convulsões/diagnóstico , Convulsões/fisiopatologia , Criança , Masculino , Feminino , Pré-Escolar , Lactente , Estudos Prospectivos , Adolescente , Monitorização Neurofisiológica/métodosRESUMO
PURPOSE: We aimed to characterize electrographic seizures (ES) and electrographic status epilepticus (ESE) and determine whether a model predicting ESE exclusively could effectively guide continuous EEG monitoring (CEEG) utilization in critically ill children. METHODS: This was a prospective observational study of consecutive critically ill children with encephalopathy who underwent CEEG. We used descriptive statistics to characterize ES and ESE, and we developed a model for ESE prediction. RESULTS: ES occurred in 25% of 1,399 subjects. Among subjects with ES, 23% had ESE, including 37% with continuous seizures lasting >30 minutes and 63% with recurrent seizures totaling 30 minutes within a 1-hour epoch. The median onset of ES and ESE occurred 1.8 and 0.18 hours after CEEG initiation, respectively. The optimal model for ESE prediction yielded an area under the receiver operating characteristic curves of 0.81. A cutoff selected to emphasize sensitivity (91%) yielded specificity of 56%. Given the 6% ESE incidence, positive predictive value was 11% and negative predictive value was 99%. If the model were applied to our cohort, then 53% of patients would not undergo CEEG and 8% of patients experiencing ESE would not be identified. CONCLUSIONS: ESE was common, but most patients with ESE had recurrent brief seizures rather than long individual seizures. A model predicting ESE might only slightly improve CEEG utilization over models aiming to identify patients at risk for ES but would fail to identify some patients with ESE. Models identifying ES might be more advantageous for preventing ES from evolving into ESE.
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PURPOSE: Electrographic seizures (ES) are common in critically ill children undergoing continuous EEG (CEEG) monitoring, and previous studies have aimed to target limited CEEG resources to children at highest risk of ES. However, previous studies have relied on observational data in which the duration of CEEG was clinically determined. Thus, the incidence of late occurring ES is unknown. The authors aimed to assess the incidence of ES for 24 hours after discontinuation of clinically indicated CEEG. METHODS: This was a single-center prospective study of nonconsecutive children with acute encephalopathy in the pediatric intensive care unit who underwent 24 hours of extended research EEG after the end of clinical CEEG. The authors assessed whether there were new findings that affected clinical management during the extended research EEG, including new-onset ES. RESULTS: Sixty-three subjects underwent extended research EEG. The median duration of the extended research EEG was 24.3 hours (interquartile range 24.0-25.3). Three subjects (5%) had an EEG change during the extended research EEG that resulted in a change in clinical management, including an increase in ES frequency, differential diagnosis of an event, and new interictal epileptiform discharges. No subjects had new-onset ES during the extended research EEG. CONCLUSIONS: No subjects experienced new-onset ES during the 24-hour extended research EEG period. This finding supports observational data that patients with late-onset ES are rare and suggests that ES prediction models derived from observational data are likely not substantially underrepresenting the incidence of late-onset ES after discontinuation of clinically indicated CEEG.
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BACKGROUND AND OBJECTIVES: Biochemical testing of CSF for neurotransmitter metabolites and their cofactors is often used in the diagnostic evaluation of infants with neurologic disorders but requires an invasive, labor-intensive procedure with many potential sources of error. Our aim was to determine the diagnostic yield of CSF testing for biogenic amines (serotonin, norepinephrine, epinephrine, and dopamine) and their cofactors in identifying inborn errors of neurotransmitter metabolism among infants. METHODS: We evaluated all infants aged 1 year or younger who underwent CSF biogenic amine neurotransmitter (CSFNT) testing at Children's Hospital of Philadelphia (CHOP) and Boston Children's Hospital (BCH) between 2008 and 2017 in this cross-sectional study. The primary outcome was the proportion of individuals who received a diagnostic result from CSFNT testing. Secondary assessments included the proportion of infants who obtained a diagnostic result from other types of diagnostic testing. RESULTS: The cohort included 323 individuals (191 from CHOP and 232 from BCH). The median age at presentation was 110 days (range 36-193). The most common presenting features were seizures (71%), hypotonia (47%), and developmental delay (43%). The diagnostic yield of CSFNT testing was zero. When CSF pyridoxal-5-phosphate level was assayed with CSFNT testing, 1 patient had a diagnostic result. An etiologic diagnosis was identified in 163 patients (50%) of the cohort, with genetic testing having the highest yield (120 individuals, 37%). DISCUSSION: Our findings support the case for deimplementation of CSFNT testing as a standard diagnostic test of etiology in infants aged 1 year or younger presenting with neurologic disorders.
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Aminas Biogênicas , Dopamina , Criança , Lactente , Humanos , Estudos Transversais , Dopamina/metabolismo , Convulsões , NeurotransmissoresRESUMO
BACKGROUND AND OBJECTIVES: EEG and MRI features are independently associated with pediatric cardiac arrest (CA) outcomes, but it is unclear whether their combination improves outcome prediction. We aimed to assess the association of early EEG background category with MRI ischemia after pediatric CA and determine whether addition of MRI ischemia to EEG background features and clinical variables improves short-term outcome prediction. METHODS: This was a single-center retrospective cohort study of pediatric CA with EEG initiated ≤24 hours and MRI obtained ≤7 days of return of spontaneous circulation. Initial EEG background was categorized as normal, slow/disorganized, discontinuous/burst-suppression, or attenuated-featureless. MRI ischemia was defined as percentage of brain tissue with apparent diffusion coefficient (ADC) <650 × 10-6 mm2/s and categorized as high (≥10%) or low (<10%). Outcomes were mortality and unfavorable neurologic outcome (Pediatric Cerebral Performance Category increase ≥1 from baseline resulting in ICU discharge score ≥3). The Kruskal-Wallis test evaluated the association of EEG with MRI. Area under the receiver operating characteristic (AUROC) curve evaluated predictive accuracy. Logistic regression and likelihood ratio tests assessed multivariable outcome prediction. RESULTS: We evaluated 90 individuals. EEG background was normal in 16 (18%), slow/disorganized in 42 (47%), discontinuous/burst-suppressed in 12 (13%), and attenuated-featureless in 20 (22%) individuals. The median percentage of MRI ischemia was 5% (interquartile range 1-18); 32 (36%) individuals had high MRI ischemia burden. Twenty-eight (31%) individuals died, and 58 (64%) had unfavorable neurologic outcome. Worse EEG background category was associated with more MRI ischemia (p < 0.001). The combination of EEG background and MRI ischemia burden had higher predictive accuracy than EEG alone (AUROC: mortality: 0.92 vs 0.87, p = 0.03) or MRI alone (AUROC: mortality: 0.92 vs 0.84, p = 0.02; unfavorable: 0.83 vs 0.73, p < 0.01). Addition of percentage of MRI ischemia to clinical variables and EEG background category improved prediction for mortality (χ2 = 19.1, p < 0.001) and unfavorable neurologic outcome (χ2 = 4.8, p = 0.03) and achieved high predictive accuracy (AUROC: mortality: 0.97; unfavorable: 0.92). DISCUSSION: Early EEG background category was associated with MRI ischemia after pediatric CA. Combining EEG and MRI data yielded higher outcome predictive accuracy than either modality alone. The addition of MRI ischemia to clinical variables and EEG background improved short-term outcome prediction.