Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies.This comprehensive review aims to provide valuable insights on present and future use of neuromodulation.

Extracorporeal life support (ECLS) serves as a rescue therapy for patients with congenital diaphragmatic hernia (CDH) and severe cardiopulmonary failure, and only half of these patients survive to discharge. This costly intervention has a significant complication risk and is reserved for patients with the most severe disease physiology refractory to maximal cardiopulmonary support. Some contraindications to ECLS do exist such as coagulopathy, lethal chromosomal or congenital anomaly, very preterm birth, or very low birth weight, but many of these limits are being evaluated through further research. Consensus guidelines from the past decade vary in recommendations for ECLS use in patients with CDH but this therapy appears to have a survival benefit in the most severe subset of patients. Improved outcomes have been observed for patients treated at high-volume centers. This review details the evolving literature surrounding management paradigms for timing of CDH repair for patients receiving preoperative ECLS. Most recent data support early repair following cannulation to avoid non-repair which is uniformly fatal in this population. Longer ECLS runs are associated with decreased survival, and patient physiology should guide ECLS weaning and eventual decannulation rather than limiting patients to arbitrary run lengths. Standardization of care across centers is a major focus to limit unnecessary costs and improve short-term and long-term outcomes for these complex patients.

Determination of language hemispheric dominance (HD) in patients undergoing evaluation for epilepsy surgery has traditionally relied on the sodium amobarbital (Wada) test. The emergence of non-invasive methods for determining language laterality has increasingly shown to be a viable alternative. In this study, we assessed the efficacy of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), compared to the Wada test, in determining language HD in a sample of 12 patients. TMS-induced speech errors were classified as speech arrest, semantic, or performance errors, and the HD was based on the total number of errors in each hemisphere with equal weighting of all errors (classic) and with a higher weighting of speech arrests and semantic errors (weighted). Using MEG, HD for language was based on the spatial extent of long-latency activity sources localized to receptive language regions. Based on the classic and weighted language laterality index (LI) in 12 patients, TMS was concordant with the Wada in 58.33% and 66.67% of patients, respectively. In eight patients, MEG language mapping was deemed conclusive, with a concordance rate of 75% with the Wada test. Our results indicate that TMS and MEG have moderate and strong agreement, respectively, with the Wada test, suggesting they could be used as non-invasive substitutes.

Infants presenting to pediatric emergency departments (EDs) after a choking episode, cyanotic event, or irregular breathing pattern are often diagnosed with a brief, resolved, unexplained event (BRUE). Social determinants of health may affect these patients; therefore, we aimed to define population demographics and determine significant demographic predictors between 2 cohorts-infants presenting with BRUE, and those admitted to the intensive care unit. Using data from the Pediatric Health Information System (Children's Hospital Association, Washington, DC, Lenexa, KS), this multicenter, retrospective study included children aged 0-1 year from 52 hospitals who presented with an International Classification of Diseases-10 coded primary diagnosis for BRUE/apparent life-threatening event (ALTE) between January 1, 2016, and June 30, 2021. Cohort 1 patients presented to the ED with BRUE; cohort 2 patients were admitted from the ED for BRUE. Univariate and multivariate logistic regression were performed for both cohorts to discover possible demographic predictors. Overall, 24,027 patients were evaluated. Patient sex did not affect admission rates (odds ratio [OR] = 1.034; 95% confidence interval [CI], 0.982-1.089; P = 0.2051). Black race (OR = 1.252; 95% CI, 1.177-1.332; P < 0.0001) and Medicaid insurance (OR = 1.126; 95% CI, 1.065-1.19; P < 0.0001) were significantly associated with an increased risk of admission. "Other" race (OR = 0.837; 95% CI, 0.777-0.902; P < 0.0001) and commercial insurance were significantly associated with a greater likelihood of discharge (OR = 0.888; 95% CI, 0.84-0.939; P < 0.0001). Black race and Medicaid insurance predicted admission in this patient population, but demographics did not play a role in intensive care unit admission overall. Social determinants of health and demographics therefore appeared to play a role in admission for patients presenting to the ED. Future research could evaluate the effect of focused interventions, such as providing additional resources to socially at-risk families through community outreach, on admission rates of patients with these specific at-risk demographics.

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine the proportion of second doses used within 24 h (ie, a proxy for effectiveness) and SEIVAL. Adverse events were recorded. Of 163 treated patients, 89 were female, and 74 were male. Approximately 16% of both sexes self-administered the study drug. A slightly higher proportion of seizure clusters was treated with a second dose in female (14.7%) than male (9.4%) patients. SEIVAL increased significantly and substantially over a year for all patients. The safety profile was generally similar between the sexes. These results suggest that potential sex differences in benzodiazepine pharmacokinetics do not meaningfully influence outcomes associated with diazepam nasal spray. PLAIN LANGUAGE SUMMARY: Some drugs may have differences in absorption and metabolism between genders that could translate into differences in safety and effectiveness. This safety study looked at diazepam nasal spray for treating seizure clusters in patients at least 6 years old. It found that safety was about the same for females and males. For both groups, most clusters stopped after only 1 dose of the drug, and the time between treated clusters got longer over a year.

Double-blind, randomized, and placebo-controlled trial SP0967 (NCT02477839/2013-000717-20) did not demonstrate superior efficacy of lacosamide versus placebo in patients aged ≥1 month to <4 years with uncontrolled focal seizures, per ≤72 h video-electroencephalogram (video-EEG)-based primary endpoints (reduction in average daily frequency of focal seizures at end-of-maintenance [EOM] versus end-of-baseline [EOB], patients with ≥50% response). This was unexpected because randomized controlled trial SP0969 (NCT01921205) showed efficacy of lacosamide in patients aged ≥4 to <17 years with uncontrolled focal seizures. SP0969's primary endpoint was based on seizure diary instead of video-EEG, an issue with the latter being inter-reader variability. We evaluated inter-reader agreement in video-EEG interpretation in SP0967, which to our knowledge, are the first such data for very young children with focal seizures from a placebo-controlled trial. Local investigator and central reader agreement in video-EEG interpretation was analyzed post hoc. Analysis included 105 EOB and 98 EOM video-EEGs. Local investigators and central reader showed poor agreement based on ≥2 focal seizures at EOB (Kappa = 0.01), and fair agreement based on ≥2 focal seizures at EOM (Kappa = 0.23). Local investigator and central reader seizure count interpretations varied substantially, particularly for focal seizures, but also primary generalized and unclassified epileptic seizures, at both timepoints. High inter-reader variability and low inter-reader reliability of the interpretation of seizure types and counts prevent confident conclusion regarding the lack of efficacy of lacosamide in this population. We recommend studies in very young children do not employ video-EEGs exclusively for accurate study inclusion or as an efficacy measure.

The Mature Minor Doctrine Clarification Act, a Tennessee bill stating that a healthcare provider may not provide vaccination to a minor without the informed consent of a parent/legal guardian, poses significant challenges to pediatric immunization. We outline changes implemented to our processes in response to this bill.

Background: As thyroid cancer incidence rises, it is increasingly valuable to recognize disparities in treatment and diagnosis. Prior investigations into social determinants of health (SDoH) are limited to pediatric populations or studies looking at single factors such as race or environmental influences. Utilizing the CDC-social vulnerability index and SEER-patient database to assess the amalgamated, real-world influence of varied SDoH and their quantifiable impact on thyroid cancer disparities across the United States. Methods: In a retrospective cohort study, 199,340 adult thyroid cancer patients from 1975 to 2017 were assessed for significant regression trends in months of follow-up/surveillance, survival, late staging, and treatment receipt across thyroid cancer-subtypes with increasing overall social vulnerability, as well as in 15 SDoH variables regarding socioeconomic status, minority-language status, household composition, and housing-transportation across all the U.S. counties while accounting for sociodemographic regional differences. Results: With increasing overall social vulnerability, decreases in months of follow-up were observed with patients with papillary, follicular, medullary, oncocytic, and anaplastic thyroid cancer (p = 0.001). Comparing lowest with highest vulnerability cohorts, relative decreases in months of surveillance ranged from 55.6% (14.5-6.5 months) with anaplastic to 17% (108.6-90.2) with oncocytic. Socioeconomic status vulnerabilities, followed by vulnerabilities in household composition and housing-transportation type, contributed to these overall trends. Similar survival decreases occurred across all thyroid cancer patients, ranging from 55.9% (9.6-4.2) with anaplastic to 28.3% (97-69.5) with oncocytic. Minority-language status vulnerabilities and housing-transportation types largely contributed to these trends. Increasing overall vulnerability was associated with increased odds of advanced staging for papillary (odds ratio [OR] = 1.07 [confidence interval, CI 1.03-1.12]) and decreased odds of indicated treatment via surgery (lowest, medullary: 0.91 [CI 0.84-0.99]), radiation therapy (lowest, anaplastic: 0.88 [CI 0.82-0.93]), and chemotherapy (lowest, oncocytic: 0.81 [CI 0.67-0.98]) were observed. Vulnerabilities in minority-language status and housing-transportation, followed by socioeconomic status vulnerabilities, were differential contributors to these overall vulnerability trends. Conclusions: Our results show significant detriments in thyroid cancer care and prognosis in the United States with increasing overall social vulnerability while identifying which SDoH quantifiably contribute more to disparities in inter-relational, real-world-like contexts.

Skull base surgery is a young surgical subspecialty currently led by its second generation of surgeons. At present, there is no literature that narrates the connection of the present to the past. An extended interview was held with Dr Jon H. Robertson, who helped establish the subspecialty in Memphis, TN, to aid in identifying and connecting sentinel events and key figures in the development of the discipline. The field drastically evolved during his era of practice (1975-present), with the advent of advanced imaging and technology, as well as the emergence of multidisciplinary skull base surgical teams. The intersection of the careers of Jon H. Robertson, James T. Robertson, Gale Gardner, Edwin Cocke, John Shea, Jr., and Jerrall Crook in Memphis catalyzed the standardization of a multidisciplinary approach to cranial base pathology. We report the findings of Dr Jon H. Robertson's extended interview, told against the backdrop of the history of the subspecialty. The story of the development of skull base surgery is told from the unique perspective of one who lived and shaped a pivotal segment in this historical timeline.