The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma.

Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM.

Examining barriers to care: a retrospective cohort analysis investigating the relationship between hospital volume and outcomes in pediatric patients with cerebral arteriovenous malformations.

OBJECTIVE: Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors' aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers. METHODS: Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids' Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed. RESULTS: Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06-0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02-0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals. CONCLUSIONS: In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.

Disparities in Indications and Outcomes Reporting for Spinal Column Shortening for Tethered Cord Syndrome: The Need for a Standardized Approach.

STUDY DESIGN: Systematic review. OBJECTIVE: To identify commonly reported indications and outcomes in spinal column shortening (SCS) procedures. BACKGROUND: SCS is a surgical procedure used in patients with tethered cord syndrome-characterized by abnormal attachment of neural components to surrounding tissues-to shorten the vertebral column, release tension on the spinal cord/neural elements, and alleviate associated symptoms. PATIENTS AND METHODS: PubMed and EMBASE searches captured SCS literature published between 1950 and 2023. Prospective/retrospective cohort studies and case series were included without age limit or required follow-up period. Review articles without new patient presentations, meta-analyses, systematic reviews, conference abstracts, and letters were excluded. Studies included adult and pediatric patients. RESULTS: The 29 identified studies represented 278 patients (aged 5-76 yr). In 24.1% of studies, patients underwent primary tethered cord syndrome intervention through SCS. In 41.4% of studies, patients underwent SCS after failed previous primary detethering (24.1% of studies were mixed and 10.3% were unspecified). The most commonly reported nongenitourinary/bowel surgical indications were back pain (55.2%), lower-extremity pain (48.3%), lower-extremity weakness (48.3%), lower-extremity numbness (34.5%), and lower-extremity motor dysfunction (34.5%). Genitourinary/bowel symptoms were most often described as nonspecific bladder dysfunction (58.6%), bladder incontinence (34.5%), and bowel dysfunction (31.0%). After SCS, nongenitourinary/bowel outcomes included lower-extremity pain (44.8%), back pain (31.0%), and lower-extremity sensory and motor function (both 31.0%). Bladder dysfunction (79.3%), bowel dysfunction (34.5%), and bladder incontinence (13.8%) were commonly reported genitourinary/bowel outcomes. In total, 40 presenting surgical indication categories and 33 unique outcome measures were reported across studies. Seventeen of the 278 patients (6.1%) experienced a complication. CONCLUSION: The SCS surgical literature displays variability in operative indications and postoperative outcomes. The lack of common reporting mechanisms impedes higher-level analysis. A standardized outcomes measurement tool, encompassing both patient-reported outcome measures and objective metrics, is necessary. LEVEL OF EVIDENCE: Level IV.

High-Value Epilepsy Care in the United States: Predictors of Increased Costs and Complications from the National Inpatient Sample Database 2016-2019.

BACKGROUND: For patients with medically refractory epilepsy, newer minimally invasive techniques such as laser interstitial thermal therapy (LITT) have been developed in recent years. This study aims to characterize trends in the utilization of surgical resection versus LITT to treat medically refractory epilepsy, characterize complications, and understand the cost of this innovative technique to the public. METHODS: The National Inpatient Sample database was queried from 2016 to 2019 for all patients admitted with a diagnosis of medically refractory epilepsy. Patient demographics, hospital length of stay, complications, and costs were tabulated for all patients who underwent LITT or surgical resection within these cohorts. RESULTS: A total of 6019 patients were included, 223 underwent LITT procedures, while 5796 underwent resection. Significant predictors of increased patient charges for both cohorts included diabetes (odds ratio: 1.7, confidence interval [CI]: 1.44-2.19), infection (odds ratio: 5.12, CI 2.73-9.58), and hemorrhage (odds ratio: 2.95, CI 2.04-4.12). Procedures performed at nonteaching hospitals had 1.54 greater odds (CI 1.02-2.33) of resulting in a complication compared to teaching hospitals. Insurance status did significantly differ (P = 0.001) between those receiving LITT (23.3% Medicare; 25.6% Medicaid; 44.4% private insurance; 6.7 Other) and those undergoing resection (35.3% Medicare; 22.5% Medicaid; 34.7% private Insurance; 7.5% other). When adjusting for patient demographics, LITT patients had shorter length of stay (2.3 vs. 8.9 days, P < 0.001), lower complication rate (1.9% vs. 3.1%, P = 0.385), and lower mean hospital ($139,412.79 vs. $233,120.99, P < 0.001) and patient ($55,394.34 vs. $37,756.66, P < 0.001) costs. CONCLUSIONS: The present study highlights LITT's advantages through its association with lower costs and shorter length of stay. The present study also highlights the associated predictors of LITT versus resection, such as that most LITT cases happen at academic centers for patients with private insurance. As the adoption of LITT continues, more data will become available to further understand these issues.

The sensitivity of limited-sequence magnetic resonance imaging in identifying pediatric cervical spine injury: A Western Pediatric Surgery Research Consortium multicenter retrospective cohort study.

INTRODUCTION: Clinical clearance of a child's cervical spine after trauma is often challenging because of impaired mental status or an unreliable neurologic examination. Magnetic resonance imaging (MRI) is the criterion standard for excluding ligamentous injury in children but is constrained by long image acquisition times and frequent need for anesthesia. Limited-sequence magnetic resonance imaging (LSMRI) is used in evaluating the evolution of traumatic brain injury and may also be useful for cervical spine clearance while potentially avoiding the need for anesthesia. The purpose of this study was to assess the sensitivity and negative predictive value of LSMRI as compared with criterion standard full-sequence MRI as a screening tool to rule out clinically significant ligamentous cervical spine injury. METHODS: We conducted a 10-center, 5-year retrospective cohort study (2017-2021) of all children (0-18 years) with a cervical spine MRI after blunt trauma. Magnetic resonance imaging images were rereviewed by a study pediatric radiologist at each site to determine if the presence of an injury could be identified on limited sequences alone. Unstable cervical spine injury was determined by study neurosurgeon review at each site. RESULTS: We identified 2,663 children younger than 18 years who underwent an MRI of the cervical spine with 1,008 injuries detected on full-sequence studies. The sensitivity and negative predictive value of LSMRI were both >99% for detecting any injury and 100% for detecting any unstable injury. Young children (younger than 5 years) were more likely to be electively intubated or sedated for cervical spine MRI. CONCLUSION: Limited-sequence magnetic resonance imaging is reliably detects clinically significant ligamentous injury in children after blunt trauma. To decrease anesthesia use and minimize MRI time, trauma centers should develop LSMRI screening protocols for children without a reliable neurologic examination. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level III.

Frequency and predictors of complication clustering within 30 days of spinal fusion surgery: a study of children with neuromuscular scoliosis.

PURPOSE: There is limited information on the clustering or co-occurrence of complications after spinal fusion surgery for neuromuscular disease in children. We aimed to identify the frequency and predictive factors of co-occurring perioperative complications in these children. METHODS: In this retrospective database cohort study, we identified children (ages 10-18 years) with neuromuscular scoliosis who underwent elective spinal fusion in 2012-2020 from the National Surgical Quality Improvement Program-Pediatric database. The rates of co-occurring complications within 30 days were calculated, and associated factors were identified by logistic regression analysis. Correlation between a number of complications and outcomes was assessed. RESULTS: Approximately 11% (709/6677 children with neuromuscular scoliosis undergoing spinal fusion had co-occurring complications: 7% experienced two complications and 4% experienced ≥ 3. The most common complication was bleeding/transfusion (80%), which most frequently co-occurred with pneumonia (24%) and reintubation (18%). Surgical time ≥ 400 min (odds ratio (OR) 1.49 [95% confidence interval (CI) 1.25-1.75]), fusion ≥ 13 levels (1.42 [1.13-1.79]), and pelvic fixation (OR 1.21 [1.01, 1.44]) were identified as procedural factors that independently predicted concurrent complications. Clinical risk factors for co-occurring complications included an American Society of Anesthesiologist physical status classification ≥ 3 (1.73 [1.27-2.37]), structural pulmonary/airway abnormalities (1.24 [1.01-1.52]), impaired cognitive status (1.80 [1.41-2.30]), seizure disorder (1.36 [1.12-1.67]), hematologic disorder (1.40 [1.03-1.91], preoperative nutritional support (1.34 [1.08-1.72]), and congenital malformations (1.20 [1.01-1.44]). Preoperative tracheostomy was protective against concurrent complications (0.62 [0.43-0.89]). Significant correlations were found between number of complications and length of stay, non-home discharge, readmissions, and death. CONCLUSION: Longer surgical time (≥ 400 min), fusion ≥ 13 levels and pelvic fixation are surgical risk factors independently associated with co-occurring complications, which were associated with poorer patient outcomes. Recognizing identified nonmodifiable risk factors might also be important for preoperative planning and risk stratification of children with neuromuscular scoliosis requiring spinal fusion. LEVEL OF EVIDENCE: Level IV evidence.

De novo cerebral pseudoaneurysm formation: a rare delayed complication of stereotactic electroencephalography in children.

OBJECTIVE: To describe the rare complication of cerebral pseudoaneurysm formation following stereotactic electroencephalography (sEEG) lead implantation in children. METHODS: A retrospective chart review of all pediatric patients undergoing sEEG procedures between 2015 and 2020 was performed. Cases of pseudoaneurysm were identified and reviewed. RESULTS: Cerebral pseudoaneurysms were identified in two of 58 total cases and 610 implanted electrodes. One lesion was detected 1 year after sEEG explantation and required craniotomy and clipping. The other was detected 3 months post-explantation and underwent coil embolization. Neither patient had any neurologic deficits associated with the pseudoaneurysm before or after treatment. CONCLUSIONS: Pseudoaneurysm formation post-sEEG explantation is rare and likely underreported. Routine, post-explantation/treatment imaging is warranted to detect this rare but potentially lethal complication.

Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties.

Brain tumors in children are a devastating disease in a high proportion of patients. Owing to inconsistent results in clinical trials in unstratified patients, the role of immunotherapy remains unclear. We performed an in-depth survey of the single-cell transcriptomes and clonal relationship of intra-tumoral T cells from children with brain tumors. Our results demonstrate that a large fraction of T cells in the tumor tissue are clonally expanded with the potential to recognize tumor antigens. Such clonally expanded T cells display enrichment of transcripts linked to effector function, tissue residency, immune checkpoints and signatures of neoantigen-specific T cells and immunotherapy response. We identify neoantigens in pediatric brain tumors and show that neoantigen-specific T cell gene signatures are linked to better survival outcomes. Notably, among the patients in our cohort, we observe substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response. Our findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, an approach that requires prospective validation in clinical trials.

Frequency and predictors of concurrent complications in multi-suture release for syndromic craniosynostosis.

PURPOSE: Understanding the complication profile of craniosynostosis surgery is important, yet little is known about complication co-occurrence in syndromic children after multi-suture craniosynostosis surgery. We examined concurrent perioperative complications and predictive factors in this population. METHODS: In this retrospective cohort study, children with syndromic diagnoses and multi-suture involvement who underwent craniosynostosis surgery in 2012-2020 were identified from the National Surgical Quality Improvement Program-Pediatric database. The primary outcome was concurrent complications; factors associated with concurrent complications were identified. Correlations between complications and patient outcomes were assessed. RESULTS: Among 5,848 children identified, 161 children (2.75%) had concurrent complications: 129 (2.21%) experienced two complications and 32 (0.55%) experienced ≥ 3. The most frequent complication was bleeding/transfusion (69.53%). The most common concurrent complications were transfusion/superficial infection (27.95%) and transfusion/deep incisional infection (13.04%) or transfusion/sepsis (13.04%). Two cardiac factors (major cardiac risk factors (odds ratio (OR) 3.50 [1.92-6.38]) and previous cardiac surgery (OR 4.87 [2.36-10.04])), two pulmonary factors (preoperative ventilator dependence (OR 3.27 [1.16-9.21]) and structural pulmonary/airway abnormalities (OR 2.89 [2.05-4.08])), and preoperative nutritional support (OR 4.05 [2.34-7.01]) were independently associated with concurrent complications. Children who received blood transfusion had higher odds of deep surgical site infection (OR 4.62 [1.08-19.73]; p = 0.04). CONCLUSIONS: Our results indicate that several cardiac and pulmonary risk factors, along with preoperative nutritional support, were independently associated with concurrent complications but procedural factors were not. This information can help inform presurgical counseling and preoperative risk stratification in this population.

Disparities in indications and outcomes reporting for pediatric tethered cord surgery: The need for a standardized outcome assessment tool.

PURPOSE: Tethered cord syndrome (TCS) is characterized by abnormal attachment of the spinal cord neural elements to surrounding tissues. The most common symptoms include pain, motor or sensory dysfunction, and urologic deficits. Although TCS is common in children, there is a significant heterogeneity in outcomes reporting. We systematically reviewed surgical indications and postoperative outcomes to assess the need for a grading/classification system. METHODS: PubMed and EMBASE searches identified pediatric TCS literature published between 1950 and 2023. Studies reporting surgical interventions, ≥ 6-month follow-up, and ≥ 5 patients were included. RESULTS: Fifty-five studies representing 3798 patients were included. The most commonly reported non-urologic symptoms were nonspecific lower-extremity motor disturbances (36.4% of studies), lower-extremity/back pain (32.7%), nonspecific lower-extremity sensory disturbances (29.1%), gait abnormalities (29.1%), and nonspecific bowel dysfunction/fecal incontinence (25.5%). Urologic symptoms were most commonly reported as nonspecific complaints (40.0%). After detethering surgery, retethering was the most widely reported non-urologic outcome (40.0%), followed by other nonspecific findings: motor deficits (32.7%), lower-extremity/back/perianal pain (18.2%), gait/ambulation function (18.2%), sensory deficits (12.7%), and bowel deficits/fecal incontinence (12.7%). Commonly reported urologic outcomes included nonspecific bladder/urinary deficits (27.3%), bladder capacity (20.0%), bladder compliance (18.2%), urinary incontinence/enuresis/neurogenic bladder (18.2%), and nonspecific urodynamics/urodynamics score change (16.4%). CONCLUSION: TCS surgical literature is highly variable regarding surgical indications and reporting of postsurgical outcomes. The lack of common data elements and consistent quantitative measures inhibits higher-level analysis. The development and validation of a standardized outcomes measurement tool-ideally encompassing both patient-reported outcome and objective measures-would significantly benefit future TCS research and surgical management.

Anterolateral Thoracic Myelomeningocele With Split Cord Malformation.

We present a case of a two-year-old male with a history of congenital scoliosis and anterolateral thoracic meningocele. He was able to walk and run, but his parents reported left leg weakness and a frequent cough. The patient had normal neurological examination findings. Magnetic resonance imaging (MRI) of the spine without contrast showed left convex upper thoracic congenital scoliosis and rightward anterolateral meningocele inferiorly to T3, with the spinal cord tethered at this location. Neurosurgical cord detethering and repair of the meningocele were performed simultaneously with scoliosis repair by orthopedics. During the dissection of the meningocele, the bulging neural tissue was found to be a split cord ending in a blind stump. The split cord was determined to be nonfunctional via Prass probe (Medtronic, Minneapolis, MN) stimulation and was subsequently dissected. Detethering of the spinal cord was followed by repair of the dural outpouching and dural closure. The patient was stable post-surgery, but long-term results remain to be seen.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

Human microglia maturation is underpinned by specific gene regulatory networks.

Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.

Challenging, giant occipital encephalocele in a pediatric saipanese male.

Key Clinical Message: Giant occipital encephalocele is a rare form of congenital anomaly that involves protrusion of brain tissue (greater in size than the patient's cranial cavity) from a defect in the skull. This case reports illustrates repair of a giant encephalocele and emphasizes important methods to reduce risk for blood loss and other complications. Abstract: A rare form of congenital anomaly, giant occipital encephalocele involves protrusion of brain tissue from a defect in the skull (in this case from the occiput). While encephalocele itself is a fairly rare entity, those qualifying as "giant"-defined by size of the deformity exceeding that of the skull itself - require very technically challenging surgery.

An Initial Experience of Completion Hemispherotomy via Magnetic Resonance-Guided Laser Interstitial Therapy.

INTRODUCTION: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. METHODS: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. RESULTS: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342-1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2-3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246-475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0-5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384-918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. CONCLUSION: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

OBJECTIVE: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS: A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS: SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Predictive Factors for Delayed Surgical Intervention in Children With Epidural Hematomas.

BACKGROUND: Optimal treatment of children with traumatic intracranial epidural hematomas (EDHs) is unknown. We sought to identify clinical and radiographic predictors of delayed surgical intervention among children with EDH admitted for observation. METHODS: We retrospectively identified patients younger than 15 years with acute traumatic EDHs evaluated at our level 1 pediatric trauma center. We excluded patients with penetrating head injuries, recent surgical evacuation of EDH, or depressed skull fracture requiring surgical repair and assigned the remaining subjects to the immediate surgery group if they underwent immediate surgical evacuation, to the supportive-therapy-only group if they underwent observation only, and to the delayed surgery group if they underwent surgery after observation. We abstracted clinical and laboratory findings, surgical interventions, and neurological outcome and measured EDH dimensions and volumes, adjusting for cranial size. We compared clinical and radiographic characteristics among groups and performed receiver-operator characteristic analyses of predictors of delayed surgery. RESULTS: Of 172 patients with EDH, 103 patients met the inclusion criteria, with 6 (6%) in the immediate surgery group, 87 (84%) in the supportive-therapy-only group, and 10 (10%) in the delayed surgery group. Headache, prothrombin time of >14 seconds, EDH maximal thickness of ≥1.1 cm, volume of ≥14 mL, EDH thickness/cranial width index of ≥0.08 and EDH volume/cranial volume index of ≥0.18, and mass effect were associated with delayed surgical intervention. There was no difference in length of stay or functional impairment between the immediate and delayed surgery groups. However, patients in delayed surgery group were more likely to have subjective symptoms at discharge than those in immediate surgery group. CONCLUSIONS: Among patients with EDH admitted for observation, larger EDH, mass effect, headaches, and prothrombin time of >14 seconds were associated with delayed surgical intervention. A larger-scale study is warranted to identify independent predictors of delayed surgery in children under observation for EDH.

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.

Shunt freedom in slit ventricle syndrome: using paradoxical ventriculomegaly following lumbar shunting to our advantage. Illustrative cases.

BACKGROUND: The authors present two cases of paradoxical ventriculomegaly after lumboperitoneal (LP) shunting in patients with slit ventricle syndrome (SVS). OBSERVATIONS: After placement of an LP shunt, both patients rapidly developed radiographic and clinically symptomatic ventricular enlargement. The then generous ventricular corridors allowed both patients to be treated by endoscopic third ventriculostomy (ETV) with concurrent removal of their LP shunt. The patients then underwent staged increases in their shunt resistance to the maximum setting and remain asymptomatic. LESSONS: The authors suggest that this paradoxical ventriculomegaly may have resulted from a pressure gradient between the shunt systems in the intra- and extraventricular spaces due to a noncommunicating etiology of their hydrocephalus. ETV may successfully exploit this newfound obstructive hydrocephalus and provide resolution of the radiographic and clinical hydrocephalus through allowing for improved communication between the cranial and lumbar cerebrospinal fluid spaces in SVS.