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Many factors contribute to the conceptualization of health related quality of life. These same factors seem to influence the medical decision-making in a manner that reflects competing principles and interests. The overall trend, however, may appear to be skewed toward weighing "worthiness" of patients for treatment according to their current or expected quality of life. Such position is in contrast to the whole concept of health related quality of life, which was meant to help improve health care access and delivery rather than limit it based on prognosis. This article aims to reiterate the absolute value of life from my understanding of Islamic perspective, and argues against belittling the value of life based on poor health-related quality of life. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is a paucity of data directly comparing the outcome of surgical techniques available for the treatment of hypothalamic hamartomas (HHs). This study aims to evaluate the safety and efficacy of commonly used surgical approaches in the treatment of HH-related epilepsy., Methods: A systematic review and individual participant data (IPD) meta-analysis was conducted. The PubMed, Embase, and Scopus online databases were searched without any date restrictions for original studies with more than 1 participant reporting on patients with HH-related epilepsy who underwent surgical treatment. Random-effects modeling was used to calculate the pooled proportions of seizure freedom (Engel I) at the last follow-up. IPD were used to perform mixed-effects logistic regression to identify predictors of seizure freedom and major postoperative complications., Results: Sixty-four studies were included, and IPD on 517 patients were obtained. The overall quality of evidence was low. After the index procedure, the pooled proportion of overall seizure freedom was 50.0% (95% CI 42.7%-57.4%), which increased to 64.5% (95% CI 57.2%-71.5%) after multiple treatments. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) and radiofrequency thermocoagulation (RFTC) demonstrated the highest efficacy at the last follow-up, with seizure freedom rates of 74.5% (95% CI 66.8%-81.7%) and 78.5% (95% CI 71.6%-84.8%), respectively. Factors independently associated with a lower likelihood of seizure freedom included multiple seizure types (odds ratio [OR] 0.296, 95% CI 0.140-0.624, p = 0.001) and previous surgery (OR 0.418, 95% CI 0.198-0.884, p = 0.023). Stereotactic radiosurgery (SRS) was the safest approach, with a pooled proportion of major complications of 0.0% (95% CI 0.0%-1.4%). Only surgical technique emerged as an independent predictor of major complications, with SRS (OR 0.024, 95% CI 0.002-0.292, p = 0.004), RFTC (OR 0.133, 95% CI 0.026-0.692, p = 0.017), and MRgLITT (OR 0.234, 95% CI 0.056-0.968, p = 0.045) being associated with a lower likelihood of major complications., Discussion: MRgLITT and RFTC offer superior efficacy and safety compared with open microsurgery and should be considered as first-line options. Despite its lower efficacy, SRS is associated with few reported long-term complications, making it a viable alternative for select cases, such as small HHs with good baseline functioning. Direct comparisons between techniques are limited by short follow-up durations in RFTC and MRgLITT cohorts. Further large-scale, multicenter studies directly comparing these modalities are warranted.

Purpose: To explore the effects of telerehabilitation-based motor imagery (Tele-MI) training on motor imagery ability (MI), motor function, and performance in children with Duchenne muscular dystrophy (DMD)., Methods: The research involved twenty-three children with DMD and twelve healthy children. DMD cohort were randomized into two groups: treatment [Tele-MI training and telerehabilitation-based physiotherapy program (Tele-PTP), n  = 12] and control (Tele-PTP, n  = 11). MI ability [Kinesthetic and Visual Imagery Questionnaire-10 (KVIQ-10), Motor Imagery Questionnaire for Children (MIQ-C), mental chronometry tests], motor function [Motor Function Measure (MFM), North Star Ambulation Assessment, Four Square Step Test] and timed performance were assessed at baseline and after 8-week training., Results: MI ability scores of DMD cohort were lower than healthy children. A large interaction effect was found for KVIQ-10 visual and total, MIQ-C internal visual and kinesthetic scores, and delta time of 10-meter walk test of mental chronometry (η2 > 0.14). The small-medium interaction effect was found in motor function and ambulation results (η 2 <0.14)., Conclusions: This study demonstrated that Tele-MI training improved MI ability of DMD cohort. The small-to-medium effects of Tele-MI training on motor function, particularly those involving the trunk, have demonstrated its potential as a complementary approach in rehabilitation to improve motor functions in children with DMD., Clinical Trial Registration Number and Url: NCT06109103 (https://clinicaltrials.gov/study/NCT06109103?term=merve%20bora%20zereyak&rank=1).

Introduction: Nowadays, the diagnostic rate of childhood epilepsies is increasing rapidly in parallel with the advances in genetic technology. In this study, it was aimed to reveal the diagnostic yield of whole exome sequencing (WES) in children with epilepsy and neurodevelopmental disorders (NDDs). Methods: Children aged 1 to 17 years with epilepsy and NDD who underwent WES were included in this retrospective study. Demographic, epilepsy and NDD characteristics, and WES results were recorded. Results: WES was performed in 36.6% of cases. Various single nucleotide variants were detected in 86.3% of cases tested by WES, and the diagnostic yield on a case-by-case basis was found to be 50%. Discussion: The diagnostic yield of WES is quite high in children with epilepsy and NDDs without a definitive diagnosis. Revealing the genetic causes of childhood epilepsy brings up effective and individualized treatment options.

Objective: Neonatal seizures present significant treatment challenges, often requiring adjunctive antiseizure medications. This study aimed to evaluate the efficacy of lacosamide as an adjunctive antiseizure medication in managing refractory neonatal seizures., Methods: The study included neonates up to 44 weeks of corrected gestational age who received lacosamide treatment at a level 4 neonatal intensive care unit between January 2015 and December 2023. The collected data encompassed demographic features, birth history, perinatal/postnatal complications, seizure characteristics, and treatment details. The primary outcome was the response to lacosamide, assessed by changes in total seizure burden on electroencephalography (EEG). The cohort characteristics were compared between nonresponders and responders., Results: The final analysis was conducted on 18 neonates with available EEG data. Of all patients, 72% showed a favorable response to lacosamide treatment, as evidenced by a reduced seizure burden on EEG. The demographic and clinical characteristics of the neonates varied, including a range of seizure etiologies. Responder and nonresponder groups had no differences in clinical characteristics., Conclusion: This study suggests that lacosamide may be an effective adjunctive antiseizure medication in treating refractory neonatal seizures. Further prospective studies are warranted to confirm these findings and explore the long-term outcomes and safety profile of lacosamide in this vulnerable patient group.

Underrepresentation in clinical genomics research limits the generalizability of findings and the benefits of scientific discoveries. We describe the impact of patient-centered, data-driven recruitment and retention strategies in a pediatric genome sequencing study. We collaborated with a stakeholder board, conducted formative research with adults whose children had undergone genomic testing, and piloted and revised study approaches and materials. Our approaches included racially, ethnically, and linguistically congruent study staff, relational interactions, study visit flexibility, and data-informed quality improvement. Of 1,656 eligible children, only 6.5% declined. Their parents/legal guardians were 76.9% non-White, 65.6% had public health insurance for the child, 49.9% lived below the federal poverty level, and 52.8% resided in a medically underserved area. Among those enrolled, 87.3% completed all study procedures. There were no sociodemographic differences between those who enrolled and declined or between those retained and lost to follow-up. We outline stakeholder-engaged approaches that may have led to the successful enrollment and retention of diverse families. These approaches may inform future research initiatives aiming to engage and retain underrepresented populations in genomics medicine research., Competing Interests: Declaration of interests N.S.A.-H. is an employee and equity holder of 23andMe and serves as a scientific advisory board member for Allelica. E.E.K. received personal fees from Illumina, 23andMe, Allelica, and Regeneron Pharmaceuticals, received research funding from Allelica, and serves as a scientific advisory board member for Encompass, Bio, Overtone, and Galateo Bio. K.B. is an employee and stockholder of Illumina, Inc. M.P.W. receives consulting fees from Sanofi Genzyme and research funding from Abeona, Alexion, Ara Parseghian Medical Research Foundation, BioMarin Pharmaceutical, Cure Sanfilippo Foundation, Dana’s Angels Research Trust, Firefly Fund, Mirium Pharma, Noah’s Hope/Hope4Bridget, Orchard Therapeutics, PassageBio, Sanofi Genzyme, Sio Gene Therapies, Takeda Pharmaceutical, Travere Therapeutics, and Ultragenyx Pharmaceutical., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the use of nuclear medicine cerebral perfusion studies as an ancillary test for brain death/death by neurologic criteria (BD/DNC) in infants aged under 1 year., Design: Retrospective case series., Setting: Single-center, quaternary, academic children's hospital in the United States., Patients: Patients younger than 1 year of age whose evaluation for BD/DNC included a nuclear medicine cerebral perfusion study as an ancillary test, 2005-2022., Interventions: None., Measurements and Main Results: Ten infants were identified from local databases. Mechanisms of brain injury included hypoxic-ischemic injury (8/10), traumatic brain injury (1/10), and intracranial hemorrhage (1/10). Testable components of the first BD/DNC examination were consistent with BD/DNC in all patients. Apnea testing was consistent with BD/DNC in 5 of 10 patients and deferred or terminated prematurely in 5 of 10 patients. All patients underwent ancillary testing with a nuclear medicine scan to assess cerebral perfusion using 99mTc-ethyl cysteinate dimer (99mTc-ECD). Indications were inability to complete the apnea test (5/10), presence of a confounder to the clinical examination (3/10), and clinician discretion (2/10). Nine studies were consistent with BD/DNC. The patient whose ancillary test was inconsistent with BD/DNC had their examination limited by the inability to assess the pupillary reflex and subsequently underwent withdrawal of life-sustaining technology., Conclusions: Radionuclide cerebral perfusion studies using 99mTc-ECD were used in our setting to support the determination of BD/DNC in infants aged younger than 1 year of age., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Gut microbiota plays a role in epilepsy. However, current knowledge of how gut dysbiosis is associated with a response to anti-seizure medications (ASMs) in epileptic children is still limited. We aimed to characterize the gut microbiota profiles in epileptic children based on response to ASMs. Eighty-six children aged 3-18 years old with a regular oral diet were enrolled onto the study and divided into three groups in accordance with ILAE definitions: 26 healthy controls, 31 drug-sensitive epilepsy (DSE) patients, and 29 drug-resistant epilepsy (DRE) patients. Based on ASM responsiveness, defined as a reduction in seizure frequency of at least 75 % over one year, DRE individuals were subclassified into 13 drug responsive (DRE-DR) and 16 drug non-responsive (DRE-DNR) patients. Feces were collected at the time of enrollment for gut microbiota analysis using 16S rRNA sequencing. Epileptic patients exhibited distinctive gut dysbiotic profiles. Differential abundance investigation revealed that CAG-56 was significantly increased in epileptic patients compared to controls. Saccharimonadales and Peptoclostridium significantly increased in the DSE group, compared to the DRE group. Vibrionaceae, especially Grimontia, Rhodobacteraceae, and Enterobacter were significantly abundant in the DRE-DNR group, followed by abundance in the DRE-DR and DSE groups. Outcomes from PICRUSt2 analysis predicted that epileptic patients, especially those in the DRE group, had increased metabolic pathways responsible for vanillin and taurine degradation, compared to controls. These findings suggest that gut dysbiosis could play roles in epileptogenesis and ASM resistance. Notably, the identified gut microbes could serve as predictive biomarkers for the DRE condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: We systematically reviewed the existing literature on the efficacy of corpus callosotomy (CC) in children and adults with refractory epileptic spasms (ES) and analyzed clinical determinants of seizure outcomes., Methods: The Preferred Report Items for Systematic Reviews and Meta-Analysis Guidelines (PRISMA) were followed. We systematically searched MEDLINE, EMBASE and Cochrane databases up to December 2023 for original research articles on using CC to treat refractory ES. The primary outcome measure was the proportion of study participants who achieved seizure freedom following initial CC at the last follow-up. Meta-regression using mixed-effects models was performed to obtain clinical determinants of seizure outcomes., Results: A total of 12 studies were included (253 individuals). Initial complete total CC was most common (n = 218/253, 86%), followed by anterior CC (n = 29/253, 12%) and other forms of CC (i.e., anterior to posterior, posterior, staged total) (n = 6/253, 2%). The pooled proportion of patients achieving spasm freedom following CC was 0.31 (95% CI: 0.22, 0.42) (mean follow-up 47 months). Meta-regression showed that structural etiology and mean age at the time of CC were significant moderators of the pooled effect. For every 1% increase in the proportion of structural etiology, the proportion of spasm-free outcome was found to reduce by 0.45 (95% CI: -0.86, -0.03, p < 0.0001). In addition, increasing the mean age by 1 month led to a reduction in the proportion of spasms-free patients by 0.003 (95% CI: -0.005, -0.0006, p = 0.01). Sixty-two individuals (24%) from seven studies underwent further surgery for residual ES; 34 became spasm free (55%)., Conclusions: Corpus callosotomy may be an effective treatment option in selected individuals with refractory epileptic spasms. Structural aetiologies and increased age at the time of corpus callosotomy are important clinical determinants. In some cases, CC may lead to further epilepsy surgery., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Abusive Head Trauma (AHT) remains an important cause of acute seizures, morbidity, and mortality in children. We aimed to assess the clinical and electrographic seizure burden in children with AHT and to explore predictors of morbidity and mortality., Methods: We conducted a retrospective chart review of all children admitted with AHT who underwent continuous electroencephalographic monitoring (cEEG) between January 1st, 2015, and April 15th, 2021. Their clinical, EEG and imaging variables were extracted and summarized., Results: A total of 31 children (17 female) were included. The median age was 3 months (IQR 1.75-5). Forty-five percent of cases presented in the winter season (p = 0.024). In 25 cases out of 31, cEEG detected electrographic seizures, with 6 of these children not manifesting clinical seizures. A shorter time to first recorded seizure during cEEG was a significant predictor of in-hospital mortality (p = 0.012) and the maximum 1-hour seizure count was higher in children with worse cerebral outcomes (p = 0.008). A normal EEG background activity during cEEG was associated with favorable neurological outcomes (p = 0.008). The hospital mortality rate was 23 %., Conclusion: Almost 20 % of children with AHT had seizures recognized exclusively by cEEG. Normal cEEG background activity predicted a better outcome, while a shorter time to the first recorded seizure was associated with a higher in-hospital mortality. Corroborating prior reports, we found a significant clustering of cases during the winter. These results could enhance AHT prevention strategies and case prognostication., Competing Interests: Declaration of competing interest None of the authors have any relevant conflict of interest to disclose., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children., Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs. The proportion of patients receiving low first non-benzodiazepine ASM doses was calculated and a logistic regression model was used to evaluate risk factors for low dosing of the first non-benzodiazepine ASM., Results: Among 320 children, 170 (53.1 %) developed RSE, and 150 (46.9 %) responded to the first non-benzodiazepine ASM dose (non-RSE). One hundred thirty-seven (42.8 %) received a low total benzodiazepine dose, and 128 (40 %) received a low first non-benzodiazepine ASM dose. The odds of developing RSE were not higher after a low total benzodiazepine dose (OR=0.76, 95 %CI 0.47-1.23, p = 0.27) or low first non-benzodiazepine ASM dose (OR=0.85, 95 %CI 0.42-1.71, p = 0.65). Receiving a low first non-benzodiazepine ASM dose was independently associated with having received a low total benzodiazepine dose (OR=1.65, 95 %CI 1.01-2.70, p = 0.04)., Conclusion: For most patients, dosing variability in first and second-line medications for SE was not the sole clinical feature predicting progression to RSE in this cohort of benzodiazepine-resistant patients. Identification of additional modifiable clinical biomarkers that predict progression to RSE is needed. Though lower ASM doses did not predict RSE in this model, the administration of ASMs at doses likely to prevent RSE remains crucial in SE treatment., Competing Interests: Declaration of competig interest TL is part of pending patent applications to detect and predict seizures and to diagnose epilepsy. He receives research support from the NIH, the Epilepsy Research Fund, and Epitel. He received research grants from Sage, Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Pfizer, and MIKU in the past. He served as a consultant for Engage and Upsher Smith, in the past., (Copyright © 2024. Published by Elsevier Ltd.)

Tuberous sclerosis Complex (TSC) is a genetic disorder characterized by multisystem involvement, with epilepsy affecting 80-90% of patients, often beginning in infancy. Early-life seizures in TSC are associated with poor neurodevelopmental outcomes, underscoring the importance of timely and effective management. This review explores the evolving treatment landscape for TSC-associated seizures in young children, focusing on three recently approved or license-expanded therapies: vigabatrin, everolimus, and cannabidiol. The efficacy and safety profiles of these treatments are examined based on clinical trials and real-world evidence, with a focus on their use in treating seizures in young children. The preemptive use of vigabatrin in clinical studies has also been carefully reviewed. A treatment algorithm is proposed, emphasizing early diagnosis, prompt initiation of appropriate therapy, and a stepwise approach to managing both infantile spasms and focal seizures. The algorithm incorporates these newer therapies alongside traditional antiseizure medications and non-pharmacological approaches. Challenges in optimizing treatment strategies, minimizing side effects, and improving long-term outcomes are discussed. This review aims to guide clinicians in navigating the complex landscape of early-life seizures associated with TSC, ultimately striving for improved seizure control and better developmental outcomes in this vulnerable population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Debopam Samanta collected the data, analyzed and interpreted them, and drafted and revised the manuscript for intellectual content.He declares no potential conflicts of interest with respect to this article's research, authorship, and/or publication.]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To evaluate the benefits of high-dose erythropoietin (EPO) combined with therapeutic hypothermia (TH) on brain magnetic resonance imaging (MRI) scores and neurodevelopmental outcomes in neonates with moderate to severe hypoxic-ischemic-ecephalopathy (HIE), especially in neonates who received TH between six to 12 hours of birth., Methods: This prospective, single-blind, randomized, placebo-controlled trial enrolled term newborns with moderate to severe HIE admitted to neonatal intensive care unit between April 2018 and April 2022. Hypothermia was started within 12 hours of birth. Infants were randomized to receive EPO 1000 U/kg or an equal volume of normal saline (placebo) on days 1, 2, 3, 5, and 7 of age in combination with hypothermia., Results: Fifty-seven neonates with moderate to severe HIE were recruited; 10 were excluded. Forty-seven patients were included: 32 received TH within six hours (group I) and in 15 TH was started within six to 12 hours of birth (group II). The clinical characteristics of mothers and infants, maternal complications, and resuscitations performed during the perinatal period showed no statistical differences between EPO group and placebo groups I and II. The MRI scores and brain injury patterns did not differ between the EPO and placebo groups. There is no statistical significance in either group's seizure and severe electroencephalography background (initial and after rewarming) between EPO and placebo in each group. There were no differences in developmental outcomes (abnormal Denver II > 2 area, Gross Motor Function Classification Score >1); Bayley Scales of Infant and Toddler Development, third edition (BSID-III) score (cognitive, language, and motor); or disability (hearing impairment and impaired vision) between the EPO and placebo groups I and II at 12 and 18 months., Conclusions: Among term infants with moderate to severe HIE, TH with EPO administration, compared with TH alone, did not reduce brain injury on MRI or the risk of neurological sequelae both in patients who received TH within six hours and in those who received TH later (six to 12 hours). Further studies on the benefit of EPO injection alone or before TH in situations where TH cannot be performed are required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Responsive neurostimulation (RNS) is used off-label in pediatric patients with drug-resistant epilepsy (DRE). Our study aims to assess the safety and efficacy of RNS in pediatric and young adult patients with focal, multifocal, and generalized DRE., Methods: All patients who underwent RNS implantation at Primary Children's Hospital in Salt Lake City, UT, between December 2017 and 2022., Results: A total of 47 patients were retrospectively identified, of which 32 patients were included in the final analysis. Patients ranged in age from five to 21 years (pediatric n = 22, young adult n = 10) at the time of RNS implantation with focal (20 [63%]), multifocal (8 [25%]), and generalized (4 [12%]) DRE. Operative complications (3 [9%]) and negative side effects (6 [19%]) were minor. At the time of most recent clinic visit (mean 18.6 months, S.D. 13.9), 19 of 32 patients (59%) were responders with ≥50% reduction in seizure frequency (pediatric n = 14, young adult n = 5). The rate of responders increased with prolonged activation of RNS stimulation, reaching 71% (five of seven patients) after 24 months. Antiseizure medication was reduced in five (16%) patients, and seizure rescue medication usage was reduced in 10 (31%) patients. Quality of life improved in 15 (47%) patients., Conclusions: RNS implantation resulted in a sustained reduction in seizure frequency with minimal side effects in a majority of patients. Taken together, our data suggest that RNS is an effective and safe treatment option for focal, multifocal, and potentially generalized DRE in the pediatric and young adult population., Competing Interests: Declaration of competing interest A.S.K. is supported by the Pediatric Epilepsy Research Foundation Elterman Research Grant. None of the other authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. This study was approved by the institutional review board of the University of Utah and the privacy board of Intermountain Healthcare (IH), IRB 00150886. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Published by Elsevier Inc.)

Objective: To evaluate the etiology-specific diagnosis of early-onset developmental epileptic encephalopathies (EO-DEEs) in a nationwide Turkish cohort to determine the implications for therapeutic management., Methods: The cohort comprised 1450 patients who underwent EO-DEE. The utility of genetic testing was assessed with respect to the initial phases of next generation sequencing (NGS) (2005-2013) and the current NGS era (2014-2022). A predefined four-stepwise diagnostic model was evaluated using cost-effectiveness analysis. The diagnostic and potential therapeutic yields of the genetic tests were subsequently determined., Results: Gene-related EO-DEEs were identified in 48.3 % (n = 701) of the cohort: non-structural genetic (62.6 %), metabolic genetic (15.1 %), and structural genetic (14.1 %). The most common nonstructural genetic variants were SCN1A (n = 132, 18.8 %), CDKL5 (n = 30, 4.2 %), STXBP1 (n = 21, 2.9 %), KCNQ2 (n = 21, 2.9 %), and PCDH19 (n = 17, 2.4 %). The rate of ultra-rare variants (< 0.5 %) was higher in the NGS era (52 %) than that in the initial phase (36 %). The potential therapeutic yields with precision therapy and antiseizure drug modification were defined in 34.5 % and 56.2 % in genetic-EO-DEEs, respectively. The diagnostic model provided an etiology-specific diagnosis at a rate of 78.7 %: structural (nongenetic) (31.4 %), genetic (38.5 %), metabolic (6.1 %), and immune-infectious (2.8 %). Based on a cost-effectiveness analysis, the presented diagnostic model indicated the early implementation of whole-exome sequencing for EO-DEEs., Significance: In the present cohort, the higher rate (48.3 %) of gene-related EO-DEE diagnoses in the NGS era provides a potential therapeutic management plan for more patients., Competing Interests: Declaration of competing interest There are no conflicts of interest that require disclosure by any of the authors. This article does not contain any pertinent financial information that the authors are required to disclose. This manuscript does not receive any external funding., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Providing accurate prenatal prognostication for expectant parents is challenging due to limited literature on factors impacting outcomes in children with congenital aqueductal stenosis (CAS). This study stratified CAS patients into isolated or complex categories (presence of additional intra- or extra-cranial anomalies or genetic syndromes) and evaluated both short- and long-term outcomes. Additionally, the role of ventricular rupture was assessed., Methods: This was a single center retrospective-cohort study of CAS patients who underwent fetal MRI over a 10-year period., Results: Of 140 patients with CAS, 107 (76%) were complex and 33 (24%) were isolated. There were no differences in the size of ventricular enlargement or incidence of ventricular rupture between the two groups. 14 pregnancies were terminated, 9 experienced fetal demise/stillbirth, and there were 21 post-natal deaths. Outcomes at the time of hospital discharge were available for 86 patients and long-term follow-up data for 64. CSF diversion (via ventriculoperitoneal shunt) was performed in 95% of complex and 71% of isolated CAS patients. Acutely, no differences were noted in seizures (complex: 10%; isolated: 18%) or respiratory support but there was an increased risk for feeding support. Risks for non-ambulatory status (complex: 32% vs. isolated: 0%), epilepsy (complex: 56% vs. isolated: 19%) and long-term gastrostomy tube assisted feeding (complex: 25.5% vs. isolated: 0%) were significantly greater with complex CAS. The presence of rupture did not impact clinical outcome., Conclusion: Poor clinical outcome was associated with complex CAS. Ventricular rupture alone did not portend a poor outcome. Prenatal counseling can tailor prognostication by CAS type., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Only 5% of aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) cases emerge during childhood. Poorer outcomes have been suggested in black/African American (AA) adults with NMOSD; however, conflicting and limited data exist for pediatric-onset NMOSD. This study evaluates racial, ethnic, and socioeconomic disparities in pediatric AQP4+ NMOSD outcomes., Methods: Thirty-eight pediatric patients with AQP4+ NMOSD cared for at three pediatric tertiary care centers between 2009 and 2021 were identified. Patient addresses connected to socioeconomic measures available from the US Census. Demographic characteristics, pertinent clinical outcomes, and health care utilization in the two years following diagnosis were captured., Results: Compared with non-Hispanic White children, Black/AA children had a significantly higher Expanded Disability Status Scale (EDSS) (2.46 vs 0.33, P = 0.003), 2.37 more hospital admissions (P = 0.002), and 28.40 additional inpatient days (P = 0.002) in the two years following their NMOSD diagnosis. Additionally, children with public insurance had higher relapse rates than those with private insurance (P = 0.046). At two years and at the most recent follow-up, a significantly higher EDSS was correlated with children living in census tracts with a lower median income, higher deprivation index, and higher proportion of population on assisted income, in poverty, and with vacant housing (all P < 0.05)., Conclusions: We identified racial, ethnic, and socioeconomic disparities in clinical outcomes and health care utilization in pediatric AQP4+ NMOSD. Further prospective and household-level data are needed to dissect the interplay of genetics, structural racism, and social determinants of health so that interventions to optimize care and outcomes for this population may be developed., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke., Methods: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular thrombectomy plus best medical practice or best medical treatment alone. Intravenous thrombolysis was considered part of best medical treatment and therefore permitted in both groups. The primary outcome was the difference in median modified Rankin Scale (mRS) score between baseline (pre-stroke) and 90 days (±10 days) post-stroke, assessed by the Wilcoxon rank test (α=0·05). Efficacy outcomes in the endovascular thrombectomy and best medical treatment groups were compared in sensitivity analyses using propensity score matching. The Save ChildS Pro study is registered at the German Clinical Trials Registry, DRKS00018960., Findings: Between Jan 1, 2020, and Aug 31, 2023, of the 241 patients in the Save ChildS Pro registry, 208 were included in the analysis (115 [55%] boys and 93 [45%] girls). 117 patients underwent endovascular thrombectomy (median age 11 years [IQR 6-14]), and 91 patients received best medical treatment (6 years [3-12]; p<0·0001). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score on admission was 14 (IQR 10-19) in the endovascular thrombectomy group and 9 (5-13) in the best medical treatment group (p<0·0001). Both treatment groups had a median pre-stroke mRS score of 0 (IQR 0-0) at baseline. The change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·020). One (1%) patient developed a symptomatic intracranial haemorrhage (this patient was in the endovascular thrombectomy group). Six (5%) patients in the endovascular thrombectomy group and four (5%) patients in the best medical treatment group had died by day 90 (p=0·89). After propensity score matching for age, sex, and PedNIHSS score at hospital admission (n=79 from each group), the change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·029). Regarding the primary outcome for patients with suspected focal cerebral arteriopathy, endovascular thrombectomy (n=18) and best medical treatment (n=33) showed no difference in 90-day median mRS scores (2 [IQR 1-3] vs 2 [1-4]; p=0·074)., Interpretation: Clinical centres tended to select children with more severe strokes (higher PedNIHSS score) for endovascular thrombectomy. Nevertheless, endovascular thrombectomy was associated with improved functional outcomes in paediatric patients with large-vessel or medium-vessel occlusions compared with best medical treatment. Future studies need to investigate whether the positive effect of endovascular thrombectomy is confined to older and more severely affected children., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared with TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected., Methods: We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant., Results: Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3-diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4-diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis., Conclusions: This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur., Competing Interests: Declaration of Competing Interest Dr. Whitney previously received clinical consulting fees from Jazz and Takeda Pharmaceuticals. Dr. Marques previously received consulting fees from Jazz Pharmaceuticals. None of the other authors have any conflict of interest to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: Autoimmune encephalitis (AE) can present as first-episode psychosis (FEP) in children. An FEP diagnostic algorithm has been proposed, but how this algorithm applies to children is unknown. We assess the FEP diagnostic algorithm in children with FEP., Methods: The FEP algorithm was applied to a retrospective cohort of children with FEP without other neurological symptoms., Results: Twenty-four patients were included, with five AE (anti-N-methyl-d-aspartate receptor encephalitis) and 19 non-AE patients (12 primary psychiatric, two headaches, mycoplasma-related encephalitis, post-coronavirus disease 2019 encephalitis, drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome, cobalamin C deficiency, and two unknown). Some non-AE patients (five of 19 = 26%) received immunotherapies, with symptom resolution in one of five (20%) with immunotherapy and in four of 14 (29%) without immunotherapy. The FEP algorithm recommended cerebrospinal fluid (CSF) testing in all (five of five = 100%) patients with AE and in six of 19 (32%) non-AE patients, resulting in 100% sensitivity (95% confidence interval [CI]: 100% to 100%) and 45.5% specificity (95% CI: 16% to 75%), with a negative predictive value of 100% (95% CI: 100% to 100%)., Conclusions: FEP can occur in children from different causes, including AE and metabolic conditions. Evaluation of FEP should be broad, especially without CSF evidence of inflammation. The FEP algorithm is useful to assess patients who would benefit from CSF testing and should be assessed in larger cohorts., Competing Interests: Declaration of competing interest G.T., L.B., and R.H. have nothing to declare. G.G. receives part time salary support from the Centers for Disease Control and Prevention for acute flaccid myelitis surveillance and an honorarium as a Media Editor for Pediatric Neurology, but this is not relevant to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Positional plagiocephaly (PP) is an asymmetric deformation of the skull as a consequence of external forces acting on a normal and pliable skull. The prevalence of PP ranges between 19.6% and 46.6%. Treatment options for PP include repositioning, physical therapy, and helmet orthoses. Consensus regarding the treatment of PP remains elusive due to the condition's imprecise natural history, dissimilar diagnostic strategies, and unreliable data asserting treatments' efficacy. Our aim was to conduct a systematic review of the tools used to diagnose, suggest treatment strategies, and assess outcomes for PP., Methods: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to query a variety of databases. A total of 444 articles were imported into Covidence, a screening and data extraction tool for conducting systematic reviews., Results: After a series of screenings, 60 articles met inclusion criteria and were reviewed in detail. The information was entered into a data extraction list consisting of 16 variables in the categories of general information, diagnostic strategies, treatment modalities, and treatment outcomes. Most articles reported retrospective case series, which yielded level 4 evidence. Only one article reported the results of a randomized and blinded outcomes assessment trial. Such article yielded level 1 evidence and was rated as high quality for allocation, concealment, and blinding of personnel., Conclusion: The strategies used to diagnose and classify PP are a disparate list of measures most of which have no parallels making it impossible to offer treatment recommendations and generate generalizable knowledge., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Neonatal seizures (NS) represent an important clinical manifestation among critically ill infants and are often the first sign of underlying brain injury. Early recognition and treatment are essential to reduce morbidity and mortality. The present study investigated the NS management and treatment approaches employed by level II/III neonatal intensive care units (NICUs) across the United States to identify areas of consensus and variability., Methods: Personnel associated with level II/III NICUs were directly surveyed with an electronic questionnaire. Access to neurology specialists, on-site electroencephalography (EEG) monitoring, and use of antiseizure medications was directly queried. A total of 51 NICUs participated in this survey., Results: Twenty-five percent of the surveyed NICUs reported having an established clinical practice pathway available for treating NS. Twenty-four percent endorsed having written guidelines that provided a formal definition for the concept of "neonatal seizures." Although the majority of NICUs reported having phenobarbital available for rapid seizure management, most NICUs lacked access to additional antiseizure medications for treatment escalation. Twenty-four percent of the surveyed NICUs had no access to EEG monitoring available to them on-site. Daytime and overnight access to neurology consultants was limited and variable., Conclusions: Findings were consistent with a lack of equitable access for NS treatment. Areas of potential improvement include development and implementation of a protocol for rapidly treating NS that emphasizes enhanced access to EEG and rapid neurology consultation, acknowledging and improving upon resource limitations. These developments may eventually provide earlier detection, evaluation, and treatment of seizures in newborns, contributing to improved long-term outcomes., Competing Interests: Declaration of competing interest The authors declare no known conflicts of interest associated with this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Transitional care (TC) is increasingly crucial, particularly in neurosurgery, where optimal follow-through of patients' care is paramount. Challenges of transition are exacerbated by the complexity of neurosurgical conditions, with pediatric and adult neurosurgery often managed separately by different attending neurosurgeons or in different institutions. While numerous models for transitioning have been proposed, several barriers persist, impeding successful transfer from pediatric to adult settings. Our review focuses on important roles neurosurgeons can play in facilitating successful transition, exploring some existing TC models, with emphasis on the benefits of maintaining a single provider., Methods: Clinic visits data between 2019 to 2023 of patients between the ages of 16 to 26 was compiled retrospectively. Successful transition was defined as continued follow-up moving from pediatric to adulthood with lost to follow-up being that of unsuccessful transition. Age, diagnosis and whether patients were successfully transitioned or lost to follow-up were documented., Results: 1829 neurosurgical patients between the ages of 16 to 26 were identified over 5 years. A snapshot review identified 78 adolescent patients deemed to require follow-up into adulthood. 13 patients had epilepsy, 32 central nervous system (CNS) tumors, 17 congenital conditions, 14 neurovascular, and 2 patients had idiopathic intracranial hypertension. All 78 were noted to have successfully transited into their adulthood (age 21 and beyond). Having the same providers; having pediatric and adult neurosurgery within the same institution, was the single most important factor in facilitating successful transition., Conclusion: Neurosurgeons in institutions, particularly those with experience and competencies in both pediatric and adult care, can serve as crucial anchors during the transitional period. At our institution, the implementation of this continuity of care model has demonstrated remarkable success. Institutions with both pediatric and adult services would be uniquely positioned to develop and implement effective transitional care., Competing Interests: Declarations. Ethical approval: All authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Consent for publication: Consent is given should the article be published. Conflict of interest: There was no conflict of interests among all authors. No financial or non-financial interests exist. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Several randomized controlled trials (RCT) have been conducted in the past to determine the optimum dose of iron supplementation during pregnancy, but there is a lack of consensus among different guidelines regarding the appropriate dosage of iron for prophylaxis during pregnancy., Methods: Relevant electronic databases were searched to identify publications describing RCTs comparing different daily dosages of iron supplementation during pregnancy. Meta-analysis for various efficacy and safety outcomes such as changes in blood hemoglobin, serum ferritin, serum iron, and serum transferrin saturation, as well as the frequency of adverse effects, was performed using random and fixed effect models suitably depending on the degree of heterogeneity. Two groups were compared: those receiving 60 mg elemental iron or less and those receiving more than 60 mg elemental iron per day. Additionally, the efficacy of those receiving 30 mg elemental iron per day and those receiving 60 mg elemental iron per day were also compared., Results: A to total of 15 RCTs comprising 2726 participants were included in the meta-analysis. Change in blood hemoglobin levels was comparable between the ≤60 mg/day and >60 mg/day group (pooled estimate for mean difference, 0.01 [-0.11, 0.09], p = 0.86, I 2  = 96 %), but serum ferritin, iron level, and serum transferrin saturation change were higher in the >60 mg group (p < 0.0001, 0.008, and 0.02, respectively). Change in blood hemoglobin level was better in the 60 mg/day group compared to the 30 mg/day group (pooled estimate for mean difference, -0.11 [-0.21, 0.00], p = 0.04, I 2  = 90 %), as well as changes in serum ferritin and serum transferrin saturations (p = 0.004 and 0.0004, respectively)., Conclusion: Daily supplementation of 60 mg elemental iron is more efficacious than daily supplementation of 30 mg elemental iron for the prophylaxis of anemia in pregnant women (certainty of evidence-moderate), and daily supplementation of ≤60 mg elemental iron is equally efficacious compared to daily supplementation of >60 mg elemental iron for the prophylaxis of anemia in pregnant women (certainty of evidence-moderate)., Proespero Registration No: CRD42023455485., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Parents of neonates with seizures report persistent symptoms of depression, anxiety, and posttraumatic stress. We aimed to characterize the parent experience of caring for children impacted by neonatal seizures, including longitudinal assessment across childhood., Methods: This prospective, observational, multicenter study was conducted at Neonatal Seizure Registry (NSR) sites in partnership with the NSR Parent Advisory Panel. Parents completed surveys at discharge; 12, 18, and 24 months; and 3, 4, 5, 7, and 8 years. Surveys included demographic information and open-ended questions targeting parent experience. A conventional content analysis approach was used., Results: A total of 320 caregivers completed at least one open-ended question, with the majority of respondents at discharge (n = 142), 12 months (n = 169), 18 months (n = 208), and 24 months (n = 245). We identified the following three primary themes. (1) Personal Burden of Care: Parents experienced emotional distress, financial strain, physical demands, and fears for their child's unknown outcome; (2) Managing Day-to-Day Life: Parents described difficulties navigating their parenting role, including managing their child's challenging behaviors and understanding their child's needs amid neurodevelopmental impairment; (3) My Joys as a Parent: Parents valued bonding with their child, being a caregiver, and watching their child's personality grow., Conclusions: Parents of children impacted by neonatal seizures face persistent challenges, which are interwoven with the joys of being a parent. Our findings suggest that future interventions should promote resiliency, address caregivers' psychosocial needs longitudinally, and provide enhanced support for parents caring for children with medical complexity., Competing Interests: Declaration of Competing Interest Dr. Monica Lemmon receives funding from NIH (K23NS116453). Dr. Reneé Shellhaas receives royalties from UpToDate for authorship on topics related to neonatal seizures and serves as a consultant for the Epilepsy Study Consortium. Betsy Pilon is the Executive Director of Hope for HIE. The other authors have no disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Epilepsy with genetic etiology is high prevalence of DRE, which is reported responsive to ketogenic diet therapy (KDT). Our retrospective cohort study attempted to investigate the KD responsiveness between DRE with genetic and non-genetic etiology., Method: Non-fasting gradual KD initiation protocol (GRAD-KD) and five-day diet program was implemented. Participants were categorized into genetic epilepsy or non-genetic epilepsy groups based on genetic tests. Monthly seizure frequencies and seizure reduction rate after KDT 3 months and 6 months were compared between two groups., Results: Forty-six patients with genetic epilepsy and ninety-four patients with non-genetic epilepsy were recruited. Among 46 patients with genetic epilepsy, 12 patients withdrew from diet before 3 months of KDT, and 7 patients withdrew from diet before 6 months of KDT, thus, 27 patients retained the diet. Among 94 patients with non-genetic epilepsy, 20 patients withdrew from diet before 3 months of KDT, and 21 patients withdrew from diet before 6 months of KDT, 53 patients retained the diet. For the 46 patients with genetic epilepsy, 12 patients had pathogenic variants related to developmental and epileptic encephalopathy (DEE), whereas other 34 patients had disease-causing variants other than DEE. The mean monthly seizure frequencies showed significantly decreased both in patient with genetic-and non-genetic epilepsy after 6 months of KDT, however, the seizure reduction rate was significantly higher in patients with genetic epilepsy than patients with non-genetic epilepsy after 6 months of KDT. In addition, our data demonstrated that KDT could significantly reduce seizure burden in patients with non-DEE than patients with DEE. In addition, the patients with non-DEE significantly achieved greater seizure reduction rate than patients with DEE after 6 months of KDT., Interpretation: Our data highlighted that KD effectiveness is more outstanding in decreasing seizure burdens for epileptic patients with genetic etiology than those without causative gene mutation. Additionally, KDT is also significantly effective for decreasing more seizure burdens for non-DEE patients than for DEE patients. We suggested epileptic patients caused by genetic mutation should implement KDT as early as possible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Critically ill children are at risk of neurologic dysfunction and acquiring primary and secondary brain injury. Close monitoring of cerebral function is crucial to prevent, detect, and treat these complications., Recent Findings: A variety of neuromonitoring modalities are currently used in pediatric and neonatal ICUs. These include noninvasive modalities, such as electroencephalography, transcranial Doppler, and near-infrared spectroscopy, as well as invasive methods including intracranial pressure monitoring, brain tissue oxygen measurement, and cerebral microdialysis. Each modality offers unique insights into neurologic function, cerebral circulation, or metabolism to support individualized neurologic care based on a patient's own physiology. Utilization of these modalities in ICUs results in reduced neurologic injury and mortality and improved neurodevelopmental outcomes., Summary: Monitoring of neurologic function can significantly improve care of critically ill children. Additional research is needed to establish normative values in pediatric patients and to standardize the use of these modalities., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: A growing number of gene therapies are getting FDA-approved for pediatric rare disorders to treat once incurable diseases. Opportunities for preventing lifetime illness and improving quality of life for these patients is now becoming a reality. Challenges exist in navigating the complexities of determining which patients will benefit from these new gene therapies and how to effectively deliver them as a standard of care., Recent Findings: Gene therapies have been approved for pediatric hematological, neuromuscular, cancer, and other disorders that have improved the quality of life for rare disease patients. FDA approval of these drugs has been on a case-by-case basis leading towards gaps in drug approval, physician and patient knowledge of new gene therapies, and ultimate delivery of these drugs. Identifying patients that would benefit from these drugs and other coordination of care issues have arisen with each unique gene therapy product. These gene therapies have unique requirements and patient indications that require a knowledgeable group of physicians and hospital administrators to incorporate their use as a standard of care. With more gene therapies on the near horizon for FDA approval, multidisciplinary teams may improve patient access to these drugs by streamlining approaches towards adapting gene therapies into clinical use., Summary: The rapid increase in the number of FDA-approved gene therapies has not only created a number of challenges but also opportunities to improve the lives of pediatric patients with rare disorders. The adaptability of physicians, hospitals, and governmental regulatory boards is essential for delivering these new gene therapies safely and efficiently to these rare disease patients. Challenges still remain as to future requirements for additional gene therapy dosing and how to best manage financial burdens placed on the patient and providing institution., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe the changes in Food and Drug Administration (FDA)-approved non-intravenous rescue benzodiazepine (non-IV-rBZD) use and cost after the introduction of intranasal midazolam and intranasal diazepam., Methods: Retrospective descriptive study using the MarketScan Database between the years 2016 and 2022. We considered patients who had at least one non-IV-rBZD prescription before the introduction of intranasal rescue medications and at least one non-IV-rBZD prescription after the introduction of intranasal rescue medications., Results: There were 4,444 patients (45.8 % female, median (p 25 -p 75 ) age of 10.0 (5.0-15.0) years). 2,255 of 4,444 (50.7 %) patients switched from rectal diazepam to either intranasal midazolam (1,110 (25.0 %)) or intranasal diazepam (1,145 (25.8 %)) as their last non-IV-rBZD. The change from rectal to intranasal non-IV-rBZDs has been increasing over the years from 2019 to 2022. On multivariable analysis, having a non-IV-rBZD for epilepsy (rather than for other reasons including febrile seizures), the year of the last rescue medication, urban (non-rural) patient's residence, and certain regions of the United States were the factors most strongly associated with a change from rectal diazepam to intranasal non-IV-rBZDs. After adjusting for inflation, the median (p 25 -p 75 ) average wholesale price (AWP) of the last non-IV-rBZD was higher than that of the first non-IV-rBZD [702 (406-748) versus 417 (406-426), Wilcoxon signed rank test p < 0.0001)]. This difference was mainly driven by the patients who changed from rectal diazepam to intranasal non-IV-rBZD [748 (714-755) versus 417 (406-426), Wilcoxon signed rank test p < 0.0001)]. After adjusting for inflation, the median (p 25 -p 75 ) patient cost of the last non-IV-rBZD was higher than that of the first non-IV-rBZD [16 (3-55) versus 12 (6-31), Wilcoxon signed rank test p < 0.0001)]. This difference was mainly driven by the patients who changed from rectal diazepam to intranasal non-IV-rBZD [41 (6-83) versus 12 (6-30), Wilcoxon signed rank test p < 0.0001)]., Conclusion: Approximately half of patients changed from rectal diazepam to intranasal midazolam or intranasal diazepam and that transition has been progressively increasing from the year 2019 to the year 2022. The inflation-adjusted AWP and patient cost increased, especially among those patients who changed from rectal to intranasal rescue medication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)