Natural language processing for identification of refractory status epilepticus in children.

OBJECTIVE: Pediatric status epilepticus is one of the most frequent pediatric emergencies, with high mortality and morbidity. Utilizing electronic health records (EHRs) permits analysis of care approaches and disease outcomes at a lower cost than prospective research. However, reviewing EHR manually is time intensive. We aimed to compare refractory status epilepticus (rSE) cases identified by human EHR review with a natural language processing (NLP)-assisted rSE screen followed by a manual review. METHODS: We used the NLP screening tool Document Review Tool (DrT) to generate regular expressions, trained a bag-of-words NLP classifier on EHRs from 2017 to 2019, and then tested our algorithm on data from February to December 2012. We compared results from manual review to NLP-assisted search followed by manual review. RESULTS: Our algorithm identified 1528 notes in the test set. After removing notes pertaining to the same event by DrT, the user reviewed a total number of 400 notes to find patients with rSE. Within these 400 notes, we identified 31 rSE cases, including 12 new cases not found in manual review, and 19 of the 20 previously identified cases. The NLP-assisted model found 31 of 32 cases, with a sensitivity of 96.88% (95% CI = 82%-99.84%), whereas manual review identified 20 of 32 cases, with a sensitivity of 62.5% (95% CI = 43.75%-78.34%). SIGNIFICANCE: DrT provided a highly sensitive model compared to human review and an increase in patient identification through EHRs. The use of DrT is a suitable application of NLP for identifying patients with a history of recent rSE, which ultimately contributes to the implementation of monitoring techniques and treatments in near real time.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

OBJECTIVE: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. METHODS: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. RESULTS: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. SIGNIFICANCE: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort).

PURPOSE: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE). METHODS: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS. RESULTS: We included 91 patients with a median (percentile25-percentile75) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001). CONCLUSION: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication.

Measuring Real-Time Medication Effects From Electroencephalography.

PURPOSE: Evaluating the effects of antiseizure medication (ASM) on patients with epilepsy remains a slow and challenging process. Quantifiable noninvasive markers that are measurable in real-time and provide objective and useful information could guide clinical decision-making. We examined whether the effect of ASM on patients with epilepsy can be quantitatively measured in real-time from EEGs. METHODS: This retrospective analysis was conducted on 67 patients in the long-term monitoring unit at Boston Children's Hospital. Two 30-second EEG segments were selected from each patient premedication and postmedication weaning for analysis. Nonlinear measures including entropy and recurrence quantitative analysis values were computed for each segment and compared before and after medication weaning. RESULTS: Our study found that ASM effects on the brain were measurable by nonlinear recurrence quantitative analysis on EEGs. Highly significant differences (P < 1e-11) were found in several nonlinear measures within the seizure zone in response to antiseizure medication. Moreover, the size of the medication effect correlated with a patient's seizure frequency, seizure localization, number of medications, and reported seizure frequency reduction on medication. CONCLUSIONS: Our findings show the promise of digital biomarkers to measure medication effects and epileptogenicity.