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Objectives. A previous study performed at Children's Hospital Boston describing the natural history of intracerebral abscess between 1945 and 1980 demonstrated a decline in mortality after 1970. This current study examines the occurrence of intracerebral abscess at Children's Hospital Boston between 1981 and 2000, inclusive, and compares the results with the previous study. Our objectives were to determine whether there had been a change in the predisposing factors, whether there were changes in the microbiology of intracerebral abscesses, and whether mortality rate had continued to decline. Methods. To ensure that all occurrences of intracerebral abscess treated at Children's Hospital Boston between 1981 and 2000 were identified, we searched 4 separately maintained databases for the keywords "brain" or "abscess" or the International Classification of Diseases, Ninth Revision code 324.x. This search yielded the names of 386 patients. Of these 386 patients, a solitary intracerebral abscess or multiple noncontiguous intracerebral abscesses could be confirmed in 54 patients on the basis of cranial imaging (computed tomography or magnetic resonance imaging) or autopsy reports. The complete retrospective review of the medical records of these 54 patients constitutes the basis for this study. Results. Congenital heart disease was the most common predisposing factor during both eras. Compared with the previous era, important historical trends identified include a reduction in the number of abscesses that occurred in the settings of sinus or otitic infection (11% during 1981-2000 vs 26% during 1945-1980), an increase in number of intracranial abscesses in infants (18% vs 7%) and in the setting of immunosuppression (16% vs 1%), an increase in the number of children who were treated with antibiotics alone (22% vs 1%), a stable over-all mortality rate (24% vs 27%), and the identification of Citrobacter and fungus as causes of intracranial abscess not observed during the previous era of 1945-1980. Citrobacter was observed only during the neonatal period. Fungi were the causative organisms predominantly in the setting of immunosuppression. Conclusions. Intracerebral abscess in children continues to be associated with high rates of neurologic impairment and death. Because earlier detection may reduce morbidity and mortality, intracranial abscess should be considered when evaluating children with new-onset neurologic signs or symptoms, especially in children who have acute immunosuppression and disseminated fungal disease or fungemia, abscess, brain, children., ABBREVIATIONS. VP, ventriculoperitoneal; CT, computed tomography; MRI, magnetic resonance imaging; CI, confidence interval. Intracerebral abscesses result from the invasion of infectious organisms into the parenchyma of the brain as a [...]

Objective: Pediatric epilepsy is often associated with diminished health‐related quality of life (HRQOL). Our aim was to establish the validity of the Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS‐QOL‐2) questions, a novel two‐item HRQOL prompt for children with epilepsy, primarily for use in clinical care. Methods: We performed a multicenter cross‐sectional study to validate the PELHS‐QOL‐2. Construct validity was established through bivariate comparisons with four comparator measures and known drivers of quality of life in children with epilepsy, as well as by creating an a priori multivariable model to predict the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE‐55). Validity generalization was established through bivariate comparisons with demographic and clinical information. Content validity and clinical utility were established by assessing how well the PELHS‐QOL‐2 met eight design criteria for an HRQOL prompt established by a multistakeholder group of experts. Results: The final participant sample included 154 English‐speaking caregivers of children with epilepsy (mean age = 9.7 years, range =.5–18, 49% female, 70% White). The PELHS‐QOL‐2 correlated with the four comparator instruments (ρ =.44–.56), was significantly associated with several known drivers of quality of life in children with epilepsy (p <.05), and predicted QOLCE‐55 scores in the multivariate model (adjusted R2 =.54). The PELHS‐QOL‐2 item was not associated with the age, sex, and ethnicity of the children nor with the setting and location of data collection, although PELHS‐QOL‐Medications was significantly associated with race (worse for White race). Following both quantitative and qualitative analysis, the PELHS‐QOL‐2 met seven of eight design criteria. Significance: The PELHS‐QOL‐2 is a valid HRQOL prompt and is well suited for use in clinical care as a mechanism to routinely initiate conversations with caregivers about quality of life in children with epilepsy. The association of PELHS‐QOL‐Medications with race merits further study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We 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). Methods: Patients 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. Results: Of 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. Significance: Among 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. [ABSTRACT FROM AUTHOR]

Infantile spasms (IS) is a devastating epilepsy syndrome that typically begins in the first year of life. Symptoms consist of stereotypical spasms, developmental delay, and electroencephalogram (EEG) that may demonstrate Hypsarhythmia. Current therapeutic approaches are not always effective, and there is no reliable way to predict which patient will respond to therapy. Given this disorder's complexity and the potential impact of a disease‐modifying approach, Citizens United for Research in Epilepsy (CURE) employed a "team science" approach to advance the understanding of IS pathology and explore therapeutic modalities that might lead to the development of new ways to potentially prevent spasms and Hypsarhythmia. This approach was a first‐of‐its‐kind collaborative initiative in epilepsy. The IS initiative funded 8 investigative teams over the course of 1‐3 years. Projects included the following: discovery on the basic biology of IS, discovery of novel therapeutic targets, cross‐validation of targets, discovery of biomarkers, and prognosis and treatment of IS. The combined efforts of a strong investigative team led to numerous advances in understanding the neural pathways underlying IS, testing of small molecules in preclinical models of IS and generated preliminary data on potential biomarkers. Thus far, the initiative has resulted in over 19 publications and subsequent funding for several investigators. Investigators reported that the IS initiative generally affected their research positively due to its collaborative and iterative nature. It also provided a unique opportunity to mentor junior investigators with an interest in translational research. Learnings included the need for a dedicated project manager and more transparent and real‐time communication with investigators. The CURE IS initiative represents a unique approach to fund scientific discoveries on epilepsy. It brought together an interdisciplinary group of investigators—who otherwise would not have collaborated—to find transformative therapies for IS. Learnings from this initiative are being utilized for subsequent initiatives at CURE. [ABSTRACT FROM AUTHOR]