The role of focused ultrasound for pediatric brain tumors: current insights and future implications on treatment strategies.

INTRODUCTION: Focused ultrasound (FUS) is an innovative and emerging technology for the treatment of adult and pediatric brain tumors and illustrates the intersection of various specialized fields, including neurosurgery, neuro-oncology, radiation oncology, and biomedical engineering. OBJECTIVE: The authors provide a comprehensive overview of the application and implications of FUS in treating pediatric brain tumors, with a special focus on pediatric low-grade gliomas (pLGGs) and the evolving landscape of this technology and its clinical utility. METHODS: The fundamental principles of FUS include its ability to induce thermal ablation or enhance drug delivery through transient blood-brain barrier (BBB) disruption, emphasizing the adaptability of high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) applications. RESULTS: Several ongoing clinical trials explore the potential of FUS in offering alternative therapeutic strategies for pathologies where conventional treatments fall short, specifically centrally-located benign CNS tumors and diffuse intrinsic pontine glioma (DIPG). A case illustration involving the use of HIFU for pilocytic astrocytoma is presented. CONCLUSION: Discussions regarding future applications of FUS for the treatment of gliomas include improved drug delivery, immunomodulation, radiosensitization, and other technological advancements.

Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

Focused ultrasound-mediated blood-brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma.

BACKGROUND: Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood-brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. METHODS: To establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53-/-). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI). RESULTS: FUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3-4 weeks post-RT. CONCLUSION: Repeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.

Socioeconomic Disparities Affecting the Presentation and Outcomes in Pediatric Subdural Empyema Patients.

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.

Medulloblastomas, CNS embryonal tumors, and cerebellar mutism syndrome: advances in care and future directions.

Central nervous system (CNS) embryonal tumors, commonly found in pediatric patients, represent a heterogeneous mix of lesions with an overall poor (though improving) prognosis. Medulloblastomas are by far the most frequently encountered and most widely studied subtype, though others include atypical teratoid/rhabdoid tumors (AT/RTs), embryonal tumor with multilayered rosettes (ETMRs), and CNS neuroblastomas, FOX-R2 activated. The classification, diagnosis, and treatment of these lesions have evolved drastically over the years as their molecular underpinnings have been elucidated. We describe the most recent 2021 WHO Classification system, discuss current understanding of the genetic basis, and demonstrate current thinking in treatment for these highly complex tumors. Since surgical resection continues to remain a mainstay of treatment, preventing and managing surgical complications, especially cerebellar mutism syndrome (CMS), is paramount. We describe the current theories for the etiology of CMS and two centers' experience in mitigating its risks. As our surgical toolbox continues to evolve along with our understanding of these tumors, we hope future patients can benefit from both improved overall survival and quality of life.

Primary Spinal Cord Astrocytomas: Two-Center Clinical Experience of Low- and High-Grade Lesions.

OBJECTIVE: Primary spinal cord astrocytomas are rare, fatal, and poorly studied. METHODS: This study included a 2-center, retrospective analysis of primary spinal cord astrocytoma patients from 1997 to 2020. Patients with drop metastases or without at least one follow-up were excluded. RESULTS: Seven World Health Organization grade I, 6 grade II, 7 grade III, and 4 grade IV astrocytoma patients were included. Older patients had higher grades (median 20 years in grade I vs. 36.5 in grade IV). The median follow-up was 15 months. Thirteen patients were discharged to rehabilitation. Eight patients demonstrated radiographic progression. Adjuvant therapy was utilized more in higher grades (5 of 13 grades III vs. all 11 grades IIIIV). Six patients died (1 death in grades III vs. 5 in grades IIIIV). Ten patients had worsened symptoms at the last follow-up. The median progression-free survival in grade I, II, III, and IV tumors was 116, 36, 8, and 8.5 months, respectively. The median overall survival in grade I, II, III, and IV tumors was 142, 69, 19, and 12 months, respectively. Thrombotic complications occurred in 2 patients, one with isocitrate dehydrogenasewild type glioblastoma. CONCLUSIONS: Outcomes worsen with higher grades and lead to difficult postoperative periods. Clinicians should be vigilant for thromboembolic complications. Further research is needed to understand these rare tumors.

Fetal Neurosurgical Interventions for Spinal Malformations, Cerebral Malformations, and Hydrocephalus: Past, Present, and Future.

In this article we review the last 40 years of progress in fetal neurosurgery with special attention to current controversies and upcoming challenges in the field. We surveyed the published literature describing prenatal interventions for spinal malformations, cerebral malformations, and hydrocephalus. Even the most mature treatment paradigm, intrauterine repair of myelomeningocele, stands to benefit from advances in imaging and therapeutic modalities to improve patient selection, refine surgical techniques, validate novel biologic therapies, and streamline postoperative patient care. Other conditions under evaluation include congenital cerebral malformations, such as encephalocele, cerebrovascular malformations, and hydrocephalus. We describe cross-cutting needs for advances in fetal neuroimaging, basic disease models and new therapeutic devices to support further progress across various neurosurgical conditions affecting patients during the fetal period.

Neurosurgery Subspecialty Practice During a Pandemic: A Multicenter Analysis of Operative Practice in 7 U.S. Neurosurgery Departments During Coronavirus Disease 2019.

OBJECTIVE: Changes to neurosurgical practices during the coronavirus disease 2019 (COVID-19) pandemic have not been thoroughly analyzed. We report the effects of operative restrictions imposed under variable local COVID-19 infection rates and health care policies using a retrospective multicenter cohort study and highlight shifts in operative volumes and subspecialty practice. METHODS: Seven academic neurosurgery departments' neurosurgical case logs were collected; procedures in April 2020 (COVID-19 surge) and April 2019 (historical control) were analyzed overall and by 6 subspecialties. Patient acuity, surgical scheduling policies, and local surge levels were assessed. RESULTS: Operative volume during the COVID-19 surge decreased 58.5% from the previous year (602 vs. 1449, P = 0.001). COVID-19 infection rates within departments' counties correlated with decreased operative volume (r = 0.695, P = 0.04) and increased patient categorical acuity (P = 0.001). Spine procedure volume decreased by 63.9% (220 vs. 609, P = 0.002), for a significantly smaller proportion of overall practice during the COVID-19 surge (36.5%) versus the control period (42.0%) (P = 0.02). Vascular volume decreased by 39.5% (72 vs. 119, P = 0.01) but increased as a percentage of caseload (8.2% in 2019 vs. 12.0% in 2020, P = 0.04). Neuro-oncology procedure volume decreased by 45.5% (174 vs. 318, P = 0.04) but maintained a consistent proportion of all neurosurgeries (28.9% in 2020 vs. 21.9% in 2019, P = 0.09). Functional neurosurgery volume, which declined by 81.4% (41 vs. 220, P = 0.008), represented only 6.8% of cases during the pandemic versus 15.2% in 2019 (P = 0.02). CONCLUSIONS: Operative restrictions during the COVID-19 surge led to distinct shifts in neurosurgical practice, and local infective burden played a significant role in operative volume and patient acuity.

Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics.

As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.

Bone grafting and biologics for spinal fusion in the pediatric population: current understanding and future perspective.

Pediatric spinal fusions have been associated with nonunion rates of approximately 25%, putting patients at risk for neurological complications while simultaneously incurring significant costs for revision surgery. In an effort to decrease nonunion rates, various bone grafts and biologics have been developed to increase osseous formation and arthrosis. The current gold-standard bone graft is autologous bone taken from the iliac crest or ribs, but this procedure is associated with significant morbidity and postoperative pain due to an additional graft harvesting procedure. Other bone graft substitutes and biologics include allografts, demineralized bone matrix, bone morphogenetic protein, and bioactive glass. Ultimately, these substitutes have been studied more extensively in the adult population, and there is a paucity of strong evidence for the use of these agents within the pediatric population. In this review, the authors will discuss in detail the characteristics of the various bone graft substitutes, their fusion efficacy, and their safety profile in this subpopulation.

Clinical characteristics and long-term outcomes for patients who undergo cytoreductive surgery for thoracic meningiomas: a retrospective analysis.

OBJECTIVE: Primary spinal meningiomas represent a rare indolent neoplasm usually situated in the intradural-extramedullary compartment. They have a predilection for afflicting the thoracic spine and most frequently present with sensory and/or motor symptoms. Resection is the first-line treatment for symptomatic tumors, whereas other clinical factors will determine the need for adjuvant therapy. In this study, the authors aimed to elucidate clinical presentation, functional outcomes, and long-term outcomes in this population in order to better equip clinicians with the tools to counsel their patients. METHODS: This is a retrospective analysis of patients treated at the authors' institution between 1998 and 2018. All patients with thoracic meningiomas who underwent resection and completed at least one follow-up appointment were included. Multiple preoperative clinical variables, hospitalization details, and long-term outcomes were collected for the cohort. RESULTS: Forty-six patients who underwent resection for thoracic meningiomas were included. The average age of the cohort was 59 years, and the median follow-up was 53 months. Persistent sensory and motor symptoms were present in 29 patients (63%). Fifteen lesions were ventrally positioned. There were 43 WHO grade I tumors, 2 WHO grade II tumors, and 1 WHO grade III tumor; the grade III tumor was the only case of recurrence. The median length of hospitalization was 4 days. Seventeen patients (37%) were discharged to rehabilitation facilities. Thirty patients (65.2%) experienced resolution or improvement of symptoms, and there were no deaths within 30 days of surgery. Only 1 patient developed painful kyphosis and was managed medically. Ventral tumor position, new postoperative deficits, and length of stay did not correlate with disposition to a facility. Age, ventral position, blood loss, and increasing WHO grade did not correlate with length of stay. CONCLUSIONS: Outcomes are overall favorable for patients who undergo resection of thoracic meningiomas. Symptomatic patients often experience improvement, and patients generally do not require significant future operations. Tumors located ventrally, while anatomically challenging, do not necessarily herald a significantly worse prognosis or limit the extent of resection.

Three-dimensional printing and craniosynostosis surgery.

OVERVIEW: The goal of this study was to review the current application and status of three-dimensional printing for craniosynostosis surgery. METHODS: A literature review was performed using the PubMed/MEDLINE databases for studies published between 2010 and 2020. All studies demonstrating the utilization of three-dimensional printing for craniosynostosis surgery were included. RESULTS: A total of 15 studies were ultimately selected. This includes studies demonstrating novel three-dimensional simulation and printing workflows, studies utilizing three-dimensional printing for surgical simulation, as well as case reports describing prior experiences. CONCLUSION: The incorporation of three-dimensional printing into the domain of craniosynostosis surgery has many potential benefits. This includes streamlining surgical planning, developing patient-specific template guides, enhancing residency training, as well as aiding in patient counseling. However, the current state of the literature remains in the validation stage. Further study with larger case series, direct comparisons with control groups, and prolonged follow-up times is necessary before more widespread implementation is justified.

Diagnostic, Surgical, and Technical Considerations for Lumbar Interbody Fusion in Patients with Osteopenia and Osteoporosis: A Systematic Review.

OBJECTIVE: Osteoporosis is increasing in incidence as the ageing population continues to grow. Decreased bone mineral density poses a challenge for the spine surgeon. In patients requiring lumbar interbody fusion, differences in diagnostics and surgical approaches may be warranted. In this systematic review, the authors examine studies performing lumbar interbody fusion in patients with osteopenia or osteoporosis and suggest avenues for future study. METHODS: A systematic literature review of the PubMed and MEDLINE databases was performed for studies published between 1986 and 2020. Studies evaluating diagnostics, surgical approaches, and other technical considerations were included. RESULTS: A total of 13 articles were ultimately selected for qualitative analysis. This includes studies demonstrating the utility of Hounsfield units in diagnosis, a survey of surgical approaches, as well as exploring the use of vertebral augmentation and cortical bone screw trajectory. CONCLUSIONS: This systematic review provides a summary of preliminary findings with respect to the use of Hounsfield units as a diagnostic tool, the benefit or lack thereof with respect to minimally invasive approaches, and the question of whether or not cement augmentation or cortical bone trajectory confers benefit in osteoporotic patients undergoing lumbar interbody fusion. While the findings of these studies are promising, the current state of the literature is limited in scope and, for this reason, definitive conclusions cannot be drawn from these data. The authors highlight gaps in the literature and the need for further exploration and study of lumbar interbody fusion in the osteoporotic spine.

Inadvertent intrathecal administration of daunomycin resulting in fatality: Case report and therapeutic considerations.

BACKGROUND: Daunomycin is a chemotherapeutic agent of the anthracycline family that is administered intravenously, most commonly in combination therapy. The authors report the first known adult case of inadvertently administered daunomycin directly into the human central nervous system and the neurologic manifestations and therapeutic interventions that followed. CLINICAL DESCRIPTION: A 53-year-old male presenting to the hospital for his second cycle of consolidation therapy for acute promyelocytic leukemia t(15;17) was accidentally administered 93 mg of intrathecal (IT) daunomycin. Within several hours of injection, the patient subsequently developed bilateral lower extremity pain, ascending paresthesias, headache, and left cranial nerve (CN) III palsy. Immediately following these neurologic sequalae, a subarachnoid lumbar drain was placed at the L4-5 interspace for the initial irrigation and drainage of cerebrospinal fluid (CSF). By hospital day 2, the patient's mental status significantly declined requiring an external ventricular drain (EVD) for hydrocephalus. Despite therapeutic interventions, the patient developed an ascending radiculomyeloencephalopathy with deterioration in clinical status. Eighteen days after the inadvertent injection of IT daunomycin, the patient became comatose and lost all cranial nerve function. CONCLUSIONS: Accidental IT injection of daunomycin is a neurosurgical emergency and warrants prompt intervention. Symptoms can mimic other medical conditions, making it imperative an accurate diagnosis is made so that appropriate therapies are implemented. At this time, therapies include rapid removal of the chemotherapeutic agent from the IT compartment by aspiration and irrigation; however, it is unclear if neuroprotective agents may provide added benefit.

Compressive epidural collection as an unusual complication of FESS for a pediatric mycetoma.

Functional endoscopic sinus surgery (FESS) is a treatment of choice for fungal sinus ball (mycetoma), which is considered safe with a very low major complication rate. We present an unusual case of a 12-year-old female, who underwent FESS for a sphenoid sinus mycetoma and which was complicated by an acute, compressive epidural fluid collection. This presumably resulted from sinus irrigation in the setting of an under-appreciated skull base and mucosal defects causing a ball-valve effect. Our patient had a temporary neurologic deficit with complete recovery, however, similar complications can have fatal consequences.

Dural Convexity Chondroma Mimicking Meningioma in a Young Female.

Intracranial meningeal convexity chondroma is a rare benign lesion hypothesized to stem from remnant chondrocyte precursors of embryonic origin. This lesion often masquerades as meningioma given the similar dural-based attachment and pattern of calcification. We describe the case of a 26-year-old female with incidentally discovered convexity meningeal chondroma, originally presumed to be a meningioma. In this case, we share our diagnostic and operative intervention and outcome and discuss the unique pathologic findings in this lesion that differentiate it from similar appearing lesions. To the authors' knowledge, there are fewer than 20 cases of convexity meningeal chondroma in the literature; thus, we also provide a brief review of the literature regarding this rare pathology.