Intracranial complications secondary to acute bacterial sinusitis requiring neurosurgical intervention before and after the onset of the COVID-19 pandemic.

OBJECTIVE: Intracranial complications of acute bacterial sinusitis are rare pathologies that occur in children, and are associated with significant neurological morbidity and mortality. There is a subjective concern among neurosurgeons that the incidence of this rare disease has increased since the onset of the novel COVID-19 pandemic. The primary objective of this study was to review the presentation and management of patients admitted at the authors' institution with intracranial extension of sinusitis, to better understand the local disease burden relative to the COVID-19 pandemic. METHODS: This is a single-center retrospective observational cohort study. The patients underwent neurosurgical intervention for intracranial extension of sinusitis between January 1, 2007, and March 1, 2023. The historical cohort was defined as those patients who presented prior to March 2020. Clinical covariates such as surgical and microbiological data were collected and analyzed. RESULTS: A total of 78 patients (55 historical, 23 new) were included; they had a median age of 11.7 years and a male predominance of 69.2%. There was a significant increase in the annual rate of neurosurgical intervention for suppurative intracranial extension of acute bacterial sinusitis after the onset of the COVID-19 pandemic, with an average of 4.2 cases per year prior to March 2020 compared to 7.7 cases per year after that date (p = 0.013). This increase was largely driven by the unprecedented case volume of 13 cases in 2022. Patients in the new cohort were older (p = 0.009) and more likely to have Pott's puffy tumor/frontal bone osteomyelitis (p = 0.003) at the time of presentation than patients in the historical cohort. Patients in the new cohort had lower rates of readmission within 30 days of discharge than those in the historical cohort (p = 0.047). In both cohorts, patients with seizure on presentation were more likely to have neurological sequelae at last follow-up (p = 0.004), which occurred at a median of 2.9 months after discharge. CONCLUSIONS: Clinicians encountering pediatric patients presenting with persistent symptoms of acute bacterial sinusitis must have a high index of suspicion for suppurative intracranial extension. Prompt neuroimaging and subsequent neurosurgical intervention are critical to ensure timely diagnosis and treatment. The results in this study show a significant increase in the number of neurosurgical interventions for suppurative intracranial extension of sinusitis per year after the onset of the COVID-19 pandemic. Further research is needed to understand the underlying pathophysiology of this clinical phenomenon.

Hypophysitis Secondary to Small Vessel ANCA Vasculitis Treated With Rituximab.

Background/Objective: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis is a rare small vessel vasculitis that can cause pituitary hypophysitis. Hypophysitis is difficult to treat, often requiring high doses of glucocorticoids with frequent flaring as glucocorticoids are tapered. We present a case of ANCA vasculitis involving the pituitary gland successfully treated with rituximab. Case Report: Fifty-one-year-old woman developed progressive frontal headaches, congestion, and epistaxis. Sinus computed tomography scan showed pituitary enlargement and chronic mucosal disease. Pituitary magnetic resonance imaging (MRI) confirmed a diffusely enlarged pituitary with a thickened pituitary stalk. Serologic evaluation revealed elevated inflammatory markers, positive perinuclear ANCA (p-ANCA), and an elevated serum anti-proteinase 3 (anti-PR3) antibody. The patient underwent pituitary biopsy, which showed adenohypophysitis with dense lymphoplasmacytic infiltration, some arranged perivascularly, compatible with involvement of the pituitary gland by ANCA vasculitis. The patient began rituximab and reported resolution of daily headaches, congestion, and epistaxis. Pituitary MRI scan 6 months after rituximab showed reduction in pituitary gland size and stalk thickening. Discussion: ANCA vasculitis is a rare etiology of pituitary hypophysitis, which can present a diagnostic and therapeutic challenge. Pituitary involvement of ANCA vasculitis can be identified through p-ANCA or cytoplasmic ANCA (c-ANCA) and biopsy of the involved tissue. Rituximab, a monoclonal antibody against CD20, has been successfully used to treat ANCA vasculitis and in this case, led to clinical improvements and reduction in the size of the pituitary gland. Conclusion: Pituitary biopsy enabled confirmation of ANCA hypophysitis and facilitated treatment with a steroid-sparing agent.

Near-infrared spectroscopy monitoring in severe pediatric abusive head trauma.

OBJECTIVE: Abusive head trauma (AHT) is one of the most devastating forms of pediatric traumatic brain injury (TBI). It commonly presents with seizures, which may contribute to poor neurological outcome following trauma. Noninvasive near-infrared spectroscopy (NIRS) neuromonitoring may provide information on cerebral oxygenation and perfusion. In this study, the authors evaluated whether NIRS regional cerebral oxygen saturation (rSO2) values were associated with seizure activity confirmed by electroencephalography (EEG) and whether NIRS neuromonitoring could aid in seizure detection in patients with severe AHT. METHODS: The authors retrospectively analyzed pediatric patients aged ≤ 18 years who were admitted to a quaternary urban pediatric hospital from 2016 to 2022 with severe AHT, who received NIRS and EEG monitoring during their hospital course. They evaluated clinical presentation and hospital course, including imaging findings, EEG findings, and NIRS rSO2 values. RESULTS: Nineteen patients with severe AHT were monitored with both EEG and NIRS. The median age was 3.4 months, and 14 patients experienced seizures confirmed by EEG. On average, rSO2 values before, during, and after seizure did not differ significantly. However, within individual patients, bilateral regional NIRS rSO2 (bilateral forehead region) was seen to rise in the hour preceding seizure activity and during periods of frequent seizure activity, confirmed by EEG in the bilateral frontal-midline brain regions. CONCLUSIONS: To the best of the authors' knowledge, this is the largest study to analyze NIRS and seizures confirmed by EEG in the severe AHT population. The relationship between NIRS values and seizures in this series of pediatric patients with severe AHT suggests that, overall, regional NIRS cannot predict early seizures. However, increased cerebral oxygenation preceding seizure activity and during seizure activity may be detected by regional NIRS in certain patients with local seizure activity. Future studies with larger sample sizes may help elucidate the relationship between seizures and cerebral oxygenation in different regions in severe pediatric AHT.

Pediatric Cerebral Sinovenous Thrombosis and Risk for Epilepsy.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) is a rare form of pediatric stroke with significant morbidity. We determined cumulative incidence and predictors of acute seizures, remote seizures, and epilepsy after pediatric CSVT. METHODS: Retrospective analysis of 131 neonates and children with neuroimaging-confirmed CSVT enrolled between 2008 and 2020 from a single-center prospective consecutive cohort. Acute seizures occurred within 7 days of CSVT. Remote seizures occurred >7 days after CSVT. Epilepsy was defined as 2 or more remote seizures at least 24 hours apart. Survival methods determined the incidence of and risk factors for remote seizures and epilepsy. RESULTS: Acute seizures occurred in 14/33 neonates (42%) and 19/98 children (19%). Among children, hemorrhage predicted acute seizures (OR 6.6, 95% CI 1.9 to 22.4, P = 0.003). Remote seizures occurred in six neonates; five developed epilepsy. Remote seizures occurred in 14 children; 10 developed epilepsy. In neonates, 1- and 3-year epilepsy-free survival were 86% (95% CI 62% to 95%) and 66% (95% CI 32% to 87%). One- and 3-year epilepsy-free survival in children were 88% (95% CI 76% to 92%) and 84% (95% CI 59% to 86%). In multivariable analysis for children, acute seizures predicted epilepsy (HR 3.8, 95% CI 1.1-13.3, P = 0.039). In both cohorts, Pediatric Stroke Outcome Measure scores at last follow-up were worse in those with epilepsy compared to those without. CONCLUSIONS: Acute seizures occurred in approximately one quarter of our cohort and are an epilepsy risk factor in children with CSVT. Neonates and children with epilepsy had worse outcomes than those without.

Invasive brain tissue oxygen and intracranial pressure (ICP) monitoring versus ICP-only monitoring in pediatric severe traumatic brain injury.

OBJECTIVE: Severe traumatic brain injury (TBI) is a leading cause of disability and death in the pediatric population. While intracranial pressure (ICP) monitoring is the gold standard in acute neurocritical care following pediatric severe TBI, brain tissue oxygen tension (PbtO2) monitoring may also help limit secondary brain injury and improve outcomes. The authors hypothesized that pediatric patients with severe TBI and ICP + PbtO2 monitoring and treatment would have better outcomes than those who underwent ICP-only monitoring and treatment. METHODS: Patients ≤ 18 years of age with severe TBI who received ICP ± PbtO2 monitoring at a quaternary children's hospital between 1998 and 2021 were retrospectively reviewed. The relationships between conventional measurements of TBI were evaluated, i.e., ICP, cerebral perfusion pressure (CPP), and PbtO2. Differences were analyzed between patients with ICP + PbtO2 versus ICP-only monitoring on hospital and pediatric intensive care unit (PICU) length of stay (LOS), length of intubation, Pediatric Intensity Level of Therapy scale score, and functional outcome using the Glasgow Outcome Score-Extended (GOS-E) scale at 6 months postinjury. RESULTS: Forty-nine patients, including 19 with ICP + PbtO2 and 30 with ICP only, were analyzed. There was a weak negative association between ICP and PbtO2 (ß = -0.04). Conversely, there was a strong positive correlation between CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm Hg (ß = 0.30 and ß = 0.29, p < 0.001, respectively). An increased number of events of cerebral PbtO2 < 15 mm Hg or < 20 mm Hg were associated with longer hospital (p = 0.01 and p = 0.022, respectively) and PICU (p = 0.015 and p = 0.007, respectively) LOS, increased duration of mechanical ventilation (p = 0.015 when PbtO2 < 15 mm Hg), and an unfavorable 6-month GOS-E score (p = 0.045 and p = 0.022, respectively). An increased number of intracranial hypertension episodes (ICP ≥ 20 mm Hg) were associated with longer hospital (p = 0.007) and PICU (p < 0.001) LOS and longer duration of mechanical ventilation (p < 0.001). Lower minimum hourly and average daily ICP values predicted favorable GOS-E scores (p < 0.001 for both). Patients with ICP + PbtO2 monitoring experienced longer PICU LOS (p = 0.018) compared to patients with ICP-only monitoring, with no significant GOS-E score difference between groups (p = 0.733). CONCLUSIONS: An increased number of cerebral hypoxic episodes and an increased number of intracranial hypertension episodes resulted in longer hospital LOS and longer duration of mechanical ventilator support. An increased number of cerebral hypoxic episodes also correlated with less favorable functional outcomes. In contrast, lower minimum hourly and average daily ICP values, but not the number of intracranial hypertension episodes, were associated with more favorable functional outcomes. There was a weak correlation between ICP and PbtO2, supporting the importance of multimodal invasive neuromonitoring in pediatric severe TBI.

Neurotrophic tyrosine receptor kinase fusion in pediatric central nervous system tumors.

Neurotrophins and their related tyrosine kinase receptors (TRKs), encoded by the neurotrophic tyrosine receptor kinase genes NTRKs, play a crucial role in central nervous system development. Oncogenic NTRK gene fusion events have been identified in several cancer subtypes and cause constitutive activation of the TRK receptor, promoting tumorigenesis. While NTRK fusions are rare in cancers overall, they have been identified in appreciable frequency in certain CNS tumors subtypes recently. In other non-CNS neoplasms, the development of NTRK fusion directed therapies has been developed with TRK inhibitors showing promise in clinical trials. Given the difficulty in treating certain pediatric CNS tumors such as high grade gliomas, understanding NTRK fusions in pediatric CNS tumors may lead to more directed treatment and subsequent therapeutic benefit. This review examines the biology of NTRK fusions, the frequency and clinical significance in pediatric CNS tumors, and methods for detection of NTRK fusion in CNS tumors.

Otitis Media Middle Ear Effusion Identification and Characterization Using an Optical Coherence Tomography Otoscope.

OBJECTIVE: To determine the feasibility of detecting and differentiating middle ear effusions (MEEs) using an optical coherence tomography (OCT) otoscope. STUDY DESIGN: Cross-sectional study. SETTING: US tertiary care children's hospital. SUBJECTS AND METHODS: Seventy pediatric patients undergoing tympanostomy tube placement were preoperatively imaged using an OCT otoscope. A blinded reader quiz was conducted using 24 readers from 4 groups of tiered medical expertise. The primary outcome assessed was reader ability to detect presence/absence of MEE. A secondary outcome assessed was reader ability to differentiate serous vs nonserous MEE. RESULTS: OCT image data sets were analyzed from 45 of 70 total subjects. Blinded reader analysis of an OCT data subset for detection of MEE resulted in 90.6% accuracy, 90.9% sensitivity, 90.2% specificity, and intra/interreader agreement of 92.9% and 87.1%, respectively. Differentiating MEE type, reader identification of nonserous MEE had 70.8% accuracy, 53.6% sensitivity, 80.1% specificity, and intra/interreader agreement of 82.9% and 75.1%, respectively. Multivariate analysis revealed that age was the strongest predictor of OCT quality. The mean age of subjects with quality OCT was 5.01 years (n = 45), compared to 2.54 years (n = 25) in the remaining subjects imaged (P = .0028). The ability to capture quality images improved over time, from 50% to 69.4% over the study period. CONCLUSION: OCT otoscopy shows promise for facilitating accurate MEE detection. The imageability with the prototype device was affected by age, with older children being easier to image, similar to current ear diagnostic technologies.