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.

Natural history of mild trigonocephalic deformities.

OBJECTIVE: Ridging along the metopic suture line can be a common cause of concern for parents and has been theorized to represent a mild form of trigonocephaly, a cranial deformity associated with risks of negative cosmetic outcomes, if not surgically corrected. Yet the literature contains sparse reports of long-term cosmetic results or expectations for infants with isolated metopic ridging compared with those with severe trigonocephaly, or even what objective metrics discriminate isolated metopic ridging from severe trigonocephaly. Therefore, the authors' goals for this study were to 1) quantify the degree of frontal deformity among patients with metopic ridge, metopic craniosynostosis, and normocephalic head shapes; and 2) document the natural history of frontal deformities in isolated metopic ridge patients in the 1st year of life. METHODS: This was a retrospective cohort study of patients with normocephalic head shapes, metopic ridges, and metopic craniosynostoses who presented at < 1 year of age to the Connecticut Children's neurosurgery clinic from January 2019 to December 2021. Data were collected regarding demographics and photograph-based craniometrics. RESULTS: A total of 212 normocephalic, 34 metopic ridge, and 29 metopic craniosynostosis patients were included. Both the normocephalic and metopic ridge groups had a significantly higher anterior arc angle (AAA) value compared with the metopic craniosynostosis group (p < 0.0001). The AAA did not differ significantly among normocephalic patients and those with ridging. Over the course of 1 year of follow-up, patients with metopic ridging demonstrated a slight decrease in AAA values, but overall remained within the same range as normocephalic patients. CONCLUSIONS: Photograph-based craniometrics suggest that metopic ridge patients with frontal bone angulations > 2.2 radians have a mild degree of frontal constriction that does not significantly worsen over the 1st year of life.

Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature.

Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient's tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient's culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene's expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine.

Telemedicine Utilization in an Outpatient Pediatric Neurosurgical Clinic: A Prospective Survey of Patient and Family Preferences.

OBJECTIVE: After becoming widespread during the COVID-19 pandemic, telemedicine continues to play an important role in outpatient neurosurgical care. Nevertheless, the factors that influence individual decisions to choose telemedicine versus in-person appointments remain understudied. Here, we performed a prospective survey of pediatric neurosurgical patients and caregivers presenting for telemedicine or in-person outpatient visits, to identify factors associated with appointment choice. METHODS: All patients and caregivers with an outpatient pediatric neurosurgical encounter at Connecticut Children's between January 31st and May 20th, 2022, were invited to participate in this survey. Data related to demographics, socioeconomics, technological access, COVID-19 vaccination status, and appointment preferences were collected. RESULTS: During the study period, there were 858 unique pediatric neurosurgical outpatient encounters (86.1% in-person and 13.9% telemedicine). A total of 212 (24.7%) respondents completed the survey. Those with a telemedicine appointment were more likely to be white (P = 0.005), not Hispanic or Latino (P = 0.020), have private insurance (P = 0.003), be established patients (P < 0.001), have a household income >$80,000 (P = 0.005), and have caregivers who completed a 4-year college degree (P < 0.001). Those who were seen in-person cited the patient's condition, quality of care, and communication as important factors, whereas those who were seen via telemedicine cited time, travel, and convenience. CONCLUSIONS: While convenience influences some to choose telemedicine, concerns regarding the quality of care persist among those who prefer in-person encounters. Recognizing these factors will minimize barriers to care, better define the appropriate populations/contexts for each encounter type, and improve the integration of telemedicine within an outpatient neurosurgical setting.

Incorporation of a biparietal narrowing metric to improve the ability of machine learning models to detect sagittal craniosynostosis with 2D photographs.

OBJECTIVE: Sagittal craniosynostosis is the most common form of craniosynostosis and typically results in scaphocephaly, which is characterized by biparietal narrowing, compensatory frontal bossing, and an occipital prominence. The cephalic index (CI) is a simple metric for quantifying the degree of cranial narrowing and is often used to diagnose sagittal craniosynostosis. However, patients with variant forms of sagittal craniosynostosis may present with a "normal" CI, depending on the part of the suture that is closed. As machine learning (ML) algorithms are developed to assist in the diagnosis of cranial deformities, metrics that reflect the other phenotypic features of sagittal craniosynostosis are needed. In this study the authors sought to describe the posterior arc angle (PAA), a measurement of biparietal narrowing that is obtained with 2D photographs, and elucidate the role of PAA as an adjuvant to the CI in characterizing scaphocephaly and the potential relevance of PAA in new ML model development. METHODS: The authors retrospectively reviewed 1013 craniofacial patients treated during the period from 2006 to 2021. Orthogonal top-down photographs were used to calculate the CI and PAA. Distribution densities, receiver operating characteristic (ROC) curves, and chi-square analyses were used to describe the relative predictive utility of each method for sagittal craniosynostosis. RESULTS: In total, 1001 patients underwent paired CI and PAA measurements and a clinical head shape diagnosis (sagittal craniosynostosis, n = 122; other cranial deformity, n = 565; normocephalic, n = 314). The area under the ROC curve (AUC) for the CI was 98.5% (95% confidence interval 97.8%-99.2%, p < 0.001), with an optimum specificity of 92.6% and sensitivity of 93.4%. The PAA had an AUC of 97.4% (95% confidence interval 96.0%-98.8%, p < 0.001) with an optimum specificity of 94.9% and sensitivity of 90.2%. In 6 of 122 (4.9%) cases of sagittal craniosynostosis, the PAA was abnormal while the CI was normal. This means that adding a PAA cutoff branch to a partition model increases the detection of sagittal craniosynostosis. CONCLUSIONS: Both CI and PAA are excellent discriminators for sagittal craniosynostosis. Using an accuracy-optimized partition model, the addition of the PAA to the CI increased model sensitivity compared to using the CI alone. Using a model that incorporates both CI and PAA could assist in the early identification and treatment of sagittal craniosynostosis via automated and semiautomated algorithms that utilize tree-based ML models.

Changes in the epidemiology of pediatric sinogenic and otogenic intracranial infections during the COVID-19 pandemic: a single-institution study.

OBJECTIVE: Focal intracranial infections (epidural abscesses, subdural empyemas, and intraparenchymal abscesses) are uncommon complications of sinusitis and otitis media but can be associated with significant morbidity. Treatment typically requires neurosurgical and otolaryngological interventions in combination with antibiotic treatment. Historically, children have presented to the authors' pediatric referral center with sinusitis- or otitis media-related intracranial infections in low numbers. However, since the onset of the COVID-19 pandemic, the incidence of intracranial pyogenic complications has increased at this center. The objective of this study was to compare the epidemiology, severity, microbial causes, and management of pediatric sinusitis- and otitis-related intracranial infections in the periods before and during the COVID-19 pandemic. 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 from January 2012 to December 2022 were retrospectively reviewed. Demographic, clinical, laboratory, and radiological data were systematically collated, and variables before and during COVID-19 were compared statistically. RESULTS: Overall, 18 patients were treated for sinusitis-related (n = 16) or otitis media-related (n = 2) intracranial infections during the study period. Ten patients (56%) presented from January 2012 to February 2020, none from March 2020 to June 2021, and 8 (44%) from July 2021 to December 2022. There were no significant demographic differences between the pre-COVID-19 and COVID-19 cohorts. The 10 patients in the pre-COVID-19 cohort underwent a total of 15 neurosurgical and 10 otolaryngological procedures, while the 8 patients in the COVID-19 cohort underwent a total of 12 neurosurgical and 10 otolaryngological procedures. Surgically obtained wound cultures yielded a variety of organisms; Streptococcus constellatus/S. anginosus/S. intermedius were more prevalent in the COVID-19 cohort (87.5% vs 0%, p < 0.001) as was Parvimonas micra (62.5% vs 0%, p = 0.007). CONCLUSIONS: At an institutional level, there has been an approximately threefold increase in cases of sinusitis- and otitis media-related intracranial infections during the COVID-19 pandemic. Multicenter studies are needed to confirm this observation and to investigate whether the mechanisms of infection are related directly to SARS-CoV-2, changes in the respiratory flora, or delayed care. The next steps will include expansion of this study to other pediatric centers throughout the United States and Canada.

Clinical metrics and tools for provider assessment and tracking of trigonocephaly.

OBJECTIVE: Quantitative measurements of trigonocephaly can be used to characterize and track this phenotype, which is associated with metopic craniosynostosis. Traditionally, trigonocephaly metrics were extracted from CT scans; however, this method exposes patients to ionizing radiation. Three-dimensional optical scans are another option but are not routinely available in most outpatient settings. Recently, the authors developed semiautomated artificial intelligence algorithms that extract craniometric data from orthogonal 2D photographs. Although 2D photographs are safe, inexpensive, and straightforward to obtain, the accuracy of photograph-based craniometrics in comparison to CT and 3D optical scan correlates has not been established. In this study the authors compared the classification power of 2D photograph-based metrics of trigonocephaly with four CT-based metrics and one 3D optical scan-based metric in a heterogeneous series of patients who presented to an outpatient craniofacial clinic. METHODS: In this study the authors performed retrospective craniometric analyses of patient 2D photographs, 3D optical scans, and CT scans. Imaging-derived craniometrics include the 2D photograph-based anterior arc angle (AAA2D-photo), anterior-posterior ratio (APR2D-photo), and anterior-middle ratio (AMR2D-photo); the CT-based anterior arc angle (AAACT), metopic index (MICT), endocranial-bifrontal angle (eBFACT), and interfrontal angle (IFACT); and the 3D optical scan-based anterior arc angle (AAA3D-optical). Receiver operating characteristics (ROCs) were used to identify craniometrics strongly descriptive of trigonocephaly. Interrater comparisons were made between paired trigonocephaly measurements obtained from photographs and either CT scans or 3D optical scans. RESULTS: There were 13 photograph-based and CT-based pairs and 22 paired measurements from 2D photographs and 3D optical scans. AAA displayed the strongest classification capacity across all three imaging modalities. Significant agreement was observed between AAACT and AAA2D-photo (intraclass correlation coefficient [ICC] = 0.68 [95% CI 0.24-0.89], p = 0.0035), and AAA3D-optical and AAA2D-photo (ICC = 0.70 [95% CI 0.41-0.87], p < 0.0001). There was no significant correlation between APR2D-photo or AMR2D-photo and conventional CT-based metrics describing longitudinal width ratios (MICT). CONCLUSIONS: Photograph-based craniometrics are powerful tools that can be used to quantify the severity of trigonocephaly and exhibit high concordance with standard measurements derived from CT scans and 3D optical scans. The authors developed and freely share a research-use application to calculate trigonocephaly metrics from 2D photographs. Given the availability of digital photography, lack of ionizing radiation, and low cost of photograph-based craniometric derivation, this technique may be useful to supplement routine ambulatory care and objectively track outcomes following treatment.

Middle Meningeal Artery Embolization for Primary Treatment of a Chronic Subdural Hematoma in a Pediatric Patient: A Systematic Review of the Literature and Case Report.

BACKGROUND: Middle meningeal artery (MMA) embolization is becoming increasingly studied as a safe, effective treatment for chronic subdural hematoma (cSDH) in adults. Among pediatric patients, however, MMA embolization for cSDH has been rarely described, and the potential benefit of this approach for pediatric patients remains unknown. OBJECTIVE: To systematically review the literature and identify cases of pediatric MMA embolization for cSDH. We also report our experience with pediatric MMA embolization. METHODS: A systematic review of the literature was performed to identify cases of pediatric MMA embolization for cSDH. Inclusion criteria included English language availability and pediatric age defined as less than 18 years. A pediatric patient treated with MMA embolization was also identified at our institution. RESULTS: Five cases of pediatric MMA embolization for cSDH were identified in the literature. Two were associated with arachnoid cysts, 2 with antiplatelet/anticoagulation therapy, and 1 with abusive head trauma. There were no adverse events, and all patients demonstrated clinical and radiological improvement on follow-up. At our institution, a previously healthy 8-year-old male was found to have a right-sided acute-on-chronic SDH during a headache evaluation. A diagnostic angiogram was performed to rule out a dural arteriovenous fistula, and right-sided MMA embolization was performed concurrently. Rapid clinical and radiological improvement was observed, with complete resolution by 6 months. CONCLUSION: MMA embolization may represent a treatment option for pediatric patients with cSDH.

Early experience with targeted therapy as a first-line adjuvant treatment for pediatric low-grade glioma.

OBJECTIVE: Pediatric low-grade gliomas (pLGGs) frequently exhibit dysregulation of the mitogen-activated protein kinase (MAPK) pathway. Targeted therapies, including mutant BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib), have shown promise in patients in whom conventional chemotherapy has failed. However, few studies have investigated the use of targeted therapy as a first-line treatment for pLGG. Here, the authors reviewed their institutional experience with using a personalized medicine approach to patients with newly diagnosed pLGGs. METHODS: All pediatric patients at the authors' institution who had been treated with dabrafenib or trametinib for pLGG without first receiving conventional chemotherapy or radiation were retrospectively reviewed. Demographic, clinical, and radiological data were collected. RESULTS: Eight patients underwent targeted therapy as a first-line treatment for pLGG. Five patients had a BRAF alteration (1 with a BRAFV600E mutation, 4 with a KIAA1549:BRAF fusion), and 3 patients had an NF1 mutation. One of the 8 patients was initially treated with dabrafenib, and trametinib was added later. Seven patients were initially treated with trametinib; of these, 2 later transitioned to dual therapy, whereas 5 continued with trametinib monotherapy. Six patients (75%) demonstrated a partial response to therapy during their treatment course, whereas stable disease was identified in the remaining 2 patients (25%). One patient experienced mild disease progression after completing a course of trametinib monotherapy, but ultimately stabilized after a period of close observation. Another patient experienced tumor progression while on dabrafenib, but subsequently responded to dual therapy with dabrafenib and trametinib. The most common adverse reactions to targeted therapy were cutaneous toxicity (100%) and diarrhea (50%). CONCLUSIONS: Targeted therapies have the potential to become a standard treatment option for pLGG due to their favorable toxicity profile and oral route of administration. This case series provides preliminary evidence that targeted therapies can induce an early disease response as a first-line adjuvant treatment; however, large-scale studies are required to assess long-term durability and safety.

Family-acquired photographs for the evaluation of pediatric head shape via telemedicine: an analysis of photograph quality.

OBJECTIVE: Telemedicine can be an effective tool for the evaluation of the pediatric patient with a cranial deformity, but it increases the reliance of neurosurgical providers on data provided by patients and families. Family-acquired photographs, in particular, can be used to augment the evaluation of pediatric head shape abnormalities via telemedicine, but photographs of sufficient quality are necessary. Here, the authors systematically reviewed the quality and utility of family-acquired photographs for patients referred to their pediatric neurosurgery clinic for telemedicine-based head shape evaluations. METHODS: All telemedicine encounters that were completed for head shape abnormalities at the authors' institution between May 2020 and December 2021 were retrospectively reviewed. Instructions were sent to families prior to each visit with examples of ideal photographs. Three orthogonal views of the patient's head-frontal, lateral, and vertex-were requested. Data were collected regarding demographics, diagnosis, follow-up, and photograph quality. Quality variables included orthogonality of each requested view, appropriate distance, appropriate lighting, presence of distracting elements, and whether hair obscured the head shape. RESULTS: Overall, 565 patients had 892 visits during the study period. A total of 1846 photograph requests were made, and 3335 photographs were received for 829 visits. Of 2676 requested orthogonal views, 1875 (70%) were received. Of these, 1826 (97%) had adequate lighting, 1801 (96%) had appropriate distance, and 1826 (97%) had no distracting features. Hair did not obscure the head shape on the vertex view in 557 visits with orthogonal vertex views (82%). In-person follow-up was requested for further medical evaluation in 40 visits (5%). CONCLUSIONS: The family-acquired photographs in this series demonstrated high rates of adequate lighting and distance, without distracting features. Lack of orthogonality and obscuration of the head shape by hair, however, were more common issues. Family education prior to the visit may improve the quality of family-acquired photographs but requires an investment of time by medical staff. Efforts to further improve photographic quality will facilitate efforts to perform craniometric evaluations through telemedicine visits.

3D patient-derived tumor models to recapitulate pediatric brain tumors In Vitro.

Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular subtypes. Here, we adapted a previously established brain tissue-model to fresh patient tumor cells with the goal of establishing3D in vitro culture conditions for each tumor type.Wereported our findings from 11 pediatric tumor cases, consisting of three medulloblastoma (MB) patients, three ependymoma (EPN) patients, one glioblastoma (GBM) patient, and four juvenile pilocytic astrocytoma (Ast) patients. Chemically defined media consisting of a mixture of pro-neural and pro-endothelial cell culture medium was found to support better growth than serum-containing medium for all the tumor cases we tested. 3D scaffold alone was found to support cell heterogeneity and tumor type-dependent spheroid-forming ability; both properties were lost in 2D or gel-only control cultures. Limited in vitro models showed that the number of differentially expressed genes between in vitro vs. primary tissues, are 104 (0.6%) of medulloblastoma, 3,392 (20.2%) of ependymoma, and 576 (3.4%) of astrocytoma, out of total 16,795 protein-coding genes and lincRNAs. Two models derived from a same medulloblastoma patient clustered together with the patient-matched primary tumor tissue; both models were 3D scaffold-only in Neurobasal and EGM 1:1 (v/v) mixture and differed by a 1-mo gap in culture (i.e., 6wk versus 10wk). The genes underlying the in vitrovs. in vivo tissue differences may provide mechanistic insights into the tumor microenvironment. This study is the first step towards establishing a pipeline from patient cells to models to personalized drug testing for brain cancer.

Machine Learning-Driven Clinical Image Analysis to Identify Craniosynostosis: A Pilot Study of Telemedicine and Clinic Patients.

BACKGROUND: The authors have developed pretrained machine learning (ML) models to evaluate neonatal head shape deformities using top-down and facial orthogonal photographs of the patient's head. In previous preliminary analysis, this approach was tested with images from an open-source data bank. OBJECTIVE: To determine the accuracy of pretrained ML models in identifying craniosynostosis among patients seen in our outpatient neurosurgery clinic. METHODS: We retrospectively reviewed top-down and facial orthogonal images of each patient's head and provider clinical diagnosis from the same encounters. Head shape classifications generated from 3 pretrained ML models (random forest, classification and regression tree, and linear discriminant analysis) were applied to each patient's photograph data set after craniometric extraction using a predefined image processing algorithm. Diagnoses were codified into a binary scheme of craniosynostosis vs noncraniosynostosis. Sensitivity, specificity, and Matthew correlation coefficient were calculated for software vs provider classifications. RESULTS: A total of 174 patients seen for abnormal head shape between May 2020 and February 2021 were included in the analysis. One hundred seven patients (61%) were seen in-person and 67 (39%) through telemedicine. Twenty-three patients (13%) were diagnosed with craniosynostosis. The best-performing model identified craniosynostosis with an accuracy of 94.8% (95% CI 90.4-97.6), sensitivity of 87.0% (95% CI 66.4-97.2), specificity of 96.0% (95% CI 91.6-98.5), and Matthew correlation coefficient of 0.788 (95% CI 0.725-0.839). CONCLUSION: Machine learning-driven image analysis represents a promising strategy for the identification of craniosynostosis in a real-world practice setting. This approach has potential to reduce the need for imaging and facilitate referral by primary care providers.

Solid-variant aneurysmal bone cysts in the craniofacial skeleton: the role of genomic analysis.

BACKGROUND: Solid variant aneurysmal bone cysts (SVABCs) are a rare but well-described subtype of ABCs. While classic ABCs are readily identified radiographically, SVABCs lack these characteristic radiographic features and thus have a wide differential diagnosis on presentation (including Ewing sarcoma, Langerhans cell histiocytosis, osteosarcoma, metastasis, and giant cell tumor). Genomic/molecular analyses are often necessary for the diagnosis of SVABCs, with USP6 rearrangements being a characteristic finding. We present two cases in which genomic analysis was critical in the diagnosis of SVABCs and revealed unique gene fusions that may provide insight into SVABC pathogenesis. CASE DESCRIPTIONS: Two 13-year old male children presented to our institution with new mass lesions involving the craniofacial skeleton. Magnetic resonance imaging (MRI) in both cases revealed predominantly solid, avidly enhancing masses, one of the squamous portion of the temporal bone, and the other arising from the sphenopalatine foramen with extension into the ipsilateral maxillary and ethmoid sinuses. Histopathology displayed predominantly solid morphology, and next generation sequencing (NGS) revealed a FAT1-USP6 gene fusion in the temporal lesion, and a MIR22HG-USP6 gene fusion in the maxillofacial lesion, the latter of which was not identified on fluorescence in situ hybridization (FISH). These findings were most consistent with a diagnosis of SVABC in each case. CONCLUSIONS: These two cases highlight novel gene fusions in atypically located SVABCs and emphasize the ability of NGS to more accurately and consistently identify USP6 gene fusions, particularly in SVABCs that may otherwise be indistinguishable from alternative pathologies.

Venous thromboembolism in the setting of pediatric central diabetes insipidus: a systematic review of the literature and report of 2 cases.

OBJECTIVE: Central diabetes insipidus (DI) is frequently identified preoperatively and/or postoperatively in patients with sellar or parasellar lesions. Early diagnosis and effective perioperative management of central DI is critical to minimize disruptions in fluid homeostasis. In particular, although venous thromboembolism (VTE) is generally less common in pediatric patients than their adult counterparts, isolated reports suggest that VTE occurs at a higher frequency in pediatric patients with central DI. METHODS: Using the PubMed, Scopus, and Springer Link databases, the authors performed a systematic review of the literature with regard to the incidence of VTE in pediatric patients with central DI. Inclusion criteria were availability of the full text in English, diagnosis of central DI and VTE in the same patient, and pediatric age defined as ≤ 21 years. Data were reported as median and interquartile range for continuous variables and as frequencies and percentages for categorical variables. Risk of bias assessments of the individual studies were performed using the Joanna Briggs Institute Critical Appraisal Checklists for case series and case reports. RESULTS: Of 2094 search results, 12 articles met the inclusion criteria and described a total of 17 cases of VTE in pediatric patients with central DI. Two additional patients from the authors' institution were added to this cohort. The underlying pathologies included craniopharyngioma (n = 6), suprasellar germinoma (n = 4), epileptic encephalopathy (n = 2), pilocytic astrocytoma (n = 2), prolactinoma (n = 2), Cushing disease (n = 1), failure to thrive (n = 1), and congenital hypothalamic syndrome (n = 1). Thrombotic complications included deep vein thrombosis (n = 10 [53%]), cerebral venous sinus thrombosis (n = 6 [32%]), pulmonary embolism (n = 4 [21%]), inferior vena cava thrombosis (n = 2 [11%]), and disseminated intravascular coagulation (n = 1 [5%]). There was a 26% mortality rate. CONCLUSIONS: VTE is a rare but potentially devastating postoperative complication that appears to have a higher incidence among patients with central DI. Although this review was limited by heterogeneous information across limited reports, pediatric neurosurgical patients with DI may benefit from more aggressive VTE surveillance and prophylaxis.

Rate of craniometric change following suture release in patients with metopic and sagittal craniosynostosis.

OBJECTIVE: Craniosynostosis is a congenital disorder resulting from the premature fusion of cranial sutures in the infant skull. This condition results in significant cosmetic deformity and can impede neurodevelopment, if left untreated. Currently, rates of craniometric change following minimally invasive surgery have only been examined for sagittal craniosynostosis. A better understanding of postoperative skull adaptations in other craniosynostosis subtypes is needed to objectively categorize surgical outcomes and guide length of cranial orthosis therapy. METHODS: Eleven patients with sagittal and 8 with metopic craniosynostosis treated using endoscopic strip craniectomy and postoperative helmet orthoses were retrospectively reviewed. Using semiautomated image analysis of top-down orthogonal 2D photographs, the following craniometrics were recorded before surgery and at postoperative visits: cephalic index (CI), cranial vault asymmetry index (CVAI), anterior arc angle (AAA), posterior arc angle (PAA), anterior-middle width ratio (AMWR), anterior-posterior width ratio (APWR), left-right height ratio (LRHR), sagittal Hu moment (Sag-Hu), and brachycephaly Hu moment (Brachy-Hu). These craniometrics were then normalized to photograph-based measurements of normocephalic patients and the rates of change between metopic and sagittal craniosynostoses were compared. RESULTS: Patients with sagittal craniosynostosis exhibited significantly lower CI, lower PAA, higher AMWR, higher APWR, lower Sag-Hu, and higher Brachy-Hu preoperatively compared to patients with normocephalic craniosynostosis. Patients with metopic craniosynostosis exhibited lower AAA and AMWR preoperatively compared to normocephalic subjects. Sagittal and metopic patients had a rapid initial change in normalized CI or AAA, respectively. Craniometric rates of change that significantly differed between metopic and sagittal patients were found in AAA (p < 0.001), AMWR (p < 0.001), and APWR (p < 0.0001). Metopic patients had a prolonged AAA change with a significantly different rate of change up to 6 months postoperatively (median at 3 months = 0.027 normalized units/day, median at 6 months = 0.017 normalized units/day, and median at > 6 months = 0.007 normalized units/day), while sagittal CI rate of change at these time points was not significantly different. CONCLUSIONS: Patients with metopic craniosynostosis have a prolonged rate of change compared to patients with sagittal craniosynostosis and may benefit from longer helmet use and extended postoperative follow-up. Categorizing craniometric changes for other craniosynostosis subtypes will be important for evaluating current treatment guidelines.

Postnatal diagnosis of single-suture craniosynostosis with cranial ultrasound: a systematic review.

INTRODUCTION: The optimal protocol for diagnostic workup of craniosynostosis and the role of specific imaging modalities remain controversial. Skull X-rays and 3-dimensional head CTs are options when physical exam is equivocal but involve ionizing radiation. Ultrasound has emerged as an alternative modality for visualization of cranial sutures, but its use is not widespread. METHODS: The authors performed a systematic review of the literature on the use of ultrasound for the diagnosis of craniosynostosis. RESULTS: A total of 12 studies involving 1062 patients were included. Overall, 300 patients (28.2%) were diagnosed with craniosynostosis. A total of 369 (34.7%) patients had their diagnosis (craniosynostosis vs. patent sutures) confirmed with another imaging modality in addition to ultrasound. Among studies, the specificity of ultrasound ranged from 86 to 100%, and the sensitivity from 71 to 100%. CONCLUSIONS: Ultrasonography of cranial sutures is a feasible and accurate tool for the diagnosis of single-suture craniosynostosis when physical exam findings are insufficient. Although technical aspects of ultrasonography and its interpretation have an associated learning curve, ultrasound can achieve high sensitivity and specificity among patients with suspected craniosynostosis.

Predictors of Telemedicine Utilization in a Pediatric Neurosurgical Population During the COVID-19 Pandemic.

OBJECTIVE: In the wake of the COVID-19 pandemic, telemedicine has become rapidly adopted by the neurosurgical community; however, few studies have examined predictors of telemedicine utilization. Here, we analyze patient variables associated with the acceptance of a telemedicine encounter by a pediatric neurosurgical population during the early phases of the COVID-19 pandemic. METHODS: All patients seen in a single institution's outpatient pediatric neurosurgery clinic between April 1, 2020 and July 31, 2020 were retrospectively reviewed. Demographic variables were collected for each patient's first completed encounter. Patients participating in telemedicine were compared with those seen in person. Univariate analysis was performed using the Wilcoxon rank sum test for continuous variables and Fischer exact test for categorical variables. A logistic regression multivariable analysis was then performed. RESULTS: We included 682 patients (374 telemedicine and 308 in person). Univariate analysis demonstrated that telemedicine visits were more likely to occur at earlier study dates (P < 0.001) and that patients participating in telemedicine visits were more likely to be established rather than new patients (P < 0.001), White or Caucasian (P < 0.001), not Hispanic or Latino (P < 0.001), English-speaking (P < 0.001), non-Medicare/Medicaid recipients (P < 0.001), have lower no-show rates (P = 0.006), and live farther from the hospital (P = 0.005). Multivariable analysis demonstrated older age (P = 0.031), earlier appointment date (P < 0.01), established patient status (P < 0.001), English-speaking (P < 0.02), and non-Medicare/Medicaid insurance (P < 0.05) were significant predictors of telemedicine utilization. CONCLUSIONS: Significant demographic differences exist among pediatric patients who participated in telemedicine versus those who requested an in-person visit at our institution. Addressing barriers to access will be crucial for promoting health equity in continued utilization of telemedicine.