Chapman, Kevin

Objective Epilepsy surgery is vital in managing of children with drug-resistant epilepsy. Noninvasive and invasive testing modalities allow for evaluation and treatment of children with drug-resistant epilepsy. Evidence-based algorithms for this process do not exist. This study examines expert response to a vignette of pediatric nonlesional epilepsy to assess associations in evaluation and treatment choices. Methods We analyzed annual report data and an epilepsy practice survey reported in 2020 from 135 pediatric epilepsy center directors in the United States. Characteristics of centers along with noninvasive and invasive testing and surgical treatment strategies were collected. Multivariable logistic regression modeling was performed. Results The response rate was 100% with 135 responses included in the analyses. Most used noninvasive testing modalities included Neuropsychology evaluation (90%), interictal brain fluorodeoxyglucose-positron emission tomography (85%), and functional magnetic resonance imaging (MRI) (72%) with nearly half obtaining genetic testing. Choosing functional MRI was associated with stereo electroencephalography (EEG) ( P = .025) and selecting Wada with subdural grid/strips ( P = .038). Directors from pediatric-only centers were more likely to choose stereo EEG as opposed to combined centers ( P = .042). Laser interstitial thermal therapy was almost 7 times as likely to be chosen as a treatment modality compared with open resection in dedicated pediatric centers (OR 6.96, P = .002). Significance In a vignette of nonlesional childhood drug-resistant epilepsy, epilepsy center directors’ patterns of noninvasive testing, invasive testing, and treatment were examined. Management choices were associated with pediatric versus combined pediatric/adult center characteristics. Expert opinions demonstrated equipoise in evaluation and management of children with drug-resistant epilepsy and the need for evidence-based management strategies.

Abstract Objective The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug‐resistant epilepsy (DRE) is not uniform. Many non‐invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice. Methods We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non‐invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi‐square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables. Results The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly ( p < .001). Associations between non‐invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo‐electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose–positron emission tomography (FDG‐PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06–3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60–5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27–6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19–4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28–3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24–7.89; p = .016). Significance In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non‐invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE.

Abstract Objective Persons with drug‐resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy. Methods We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank‐sum, Kruskal–Wallis, and chi‐squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables. Results The response rate was 100% with individual element missingness < 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval [CI] = 1.2–6.86; p = .018) and fluorodeoxyglucose–positron emission tomography (OR = 2.74, 95% CI = = 1.14–6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23–.93; p = .031) and West (OR = .41, 95% CI = .19–.87; p = .022), odds of performing single‐photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates. Significance Presurgical testing for drug‐resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment.

Abstract 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.

AbstractObjectiveThis 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.MethodsWe 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.ResultsFollow‐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.SignificanceAbout 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.

OBJECTIVES: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. DESIGN: Retrospective cohort study with prospectively collected data between June 2011 and January 2019. SETTING: Seventeen academic hospitals in the United States. PATIENTS: We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 281 patients (157 males) with a median age of 4.1 years (1.3–9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55–491.5 min] vs 62 min [33.3–120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5–1,255 min] vs 150 min [90–318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58–368 hr] vs 3 hr [1.4–5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5–40 d] vs [1.8–8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. CONCLUSIONS: Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

AbstractObjectiveWe aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE).MethodsPatients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever.ResultsOf 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function.SignificanceAmong pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection‐related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

Purpose: We aimed to determine whether clinical EEG reports obtained from children in the intensive care unit with refractory status epilepticus could provide data for comparative effectiveness research studies. Methods: We conducted a retrospective descriptive study to assess the documentation of key variables within clinical continuous EEG monitoring reports based on the American Clinical Neurophysiology Society's standardized EEG terminology for children with refractory status epilepticus from 10 academic centers. Two pediatric electroencephalographers reviewed the EEG reports. We compared reports generated using free text or templates. Results: We reviewed 191 EEG reports. Agreement between the electroencephalographers regarding whether a variable was described in the report ranged from fair to very good. The presence of electrographic seizures (ES) was documented in 46% (87/191) of reports, and these reports documented the time of first ES in 64% (56/87), ES duration in 72% (63/85), and ES frequency in 68% (59/87). Reactivity was documented in 16% (31/191) of reports, and it was more often documented in template than in free-text reports (40% vs. 14%, P = 0.006). Other variables were not differentially reported in template versus free-text reports. Conclusions: Many key EEG features are not documented consistently in clinical continuous EEG monitoring reports, including ES characteristics and reactivity assessment. Standardization may be needed for clinical EEG reports to provide informative data for large multicenter observational studies.