The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Pediatric Postmortem Tissue Donation in the Confines of a Pandemic: A Model of Collaboration.

BACKGROUND: Obtaining postmortem tissue from pediatric oncology patients is critical to research and may help grieving families heal. Since 2019, the national Gift from a Child program has made significant progress in collecting postmortem tissue from pediatric patients with central nervous system tumors to advance research. This progress was at risk during the onset of the severe acute respiratory syndrome coronavirus 2 pandemic, when some autopsy programs came to a halt. METHODS: We retrospectively reviewed autopsies of four patients treated at Memorial Sloan Kettering Cancer Center who underwent postmortem examination at Weill Cornell Medicine from June 2020 to March 2021. We collected patient demographics, Do not resuscitate status, time of death and procedure, restrictions due to the coronavirus disease 2019 (COVID-19) pandemic, and results of the tissue analysis. RESULTS: Three of four specimens were processed within 12 hours of the time of death. Two families required interpreter services to obtain consent. In all cases, tumor aliquots were flash frozen for further study. Cell line generation was successful in one case. All families expressed gratitude both for the opportunity to participate and for the handling of the procedures. CONCLUSIONS: Despite the sensitive nature of these cases and the challenges presented by COVID-19 restrictions, clinicians should offer the option of a rapid autopsy to caregivers of pediatric patients based on the scientific need and the positive effect it has on grieving families. This article outlines the logistic efforts required for these donations to take place and provides a framework for providers to offer rapid autopsy as an option for families through this program.

The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

Cervical Instability and Quadriparesis Requiring Stabilization in Pediatric Patient Caused by a Mutation in COL2A1.

A 3-year-old male with no past medical history presented with flaccid plegia of his upper extremities and significant weakness in his lower extremities after wrestling with his brother. Cervical spine magnetic resonance imaging was consistent with cord edema and intraparenchymal hemorrhage at C1-C2. A nonossified tissue mass at the expected location of the upper dens created narrowing of the canal at the C1-2 level and mass effect on the cord. Head computed tomography showed periventricular leukomalacia. Initial findings favored dysplasia of the odontoid with associated soft tissue mass/pannus caused by a possible underlying genetic or metabolic bone dyscrasia. The patient underwent suboccipital craniotomy/C1 laminectomy and occiput to C4 fusion, for decompression and stabilization. Genetic testing showed a COL2A1 collagen disorder, with the child harboring a de novo mutation for c.3455 G>T (p.G1152V). The patient was discharged to inpatient acute rehabilitation, with gradual improvement in strength in all 4 extremities.

Leptomeningeal dissemination in pediatric brain tumors.

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors.

Predictors of extent of resection and recurrence following endoscopic endonasal resection of craniopharyngioma.

OBJECTIVE: Craniopharyngioma is a benign but surgically challenging brain tumor. Controversies exist regarding its ideal treatment strategy, goals of surgery, efficacy of radiation, and the long-term outcomes of these decisions. The authors of this study performed a detailed analysis of factors predictive of the extent of resection and recurrence in large series of craniopharyngiomas removed via an endoscopic endonasal approach (EEA) with long-term follow-up. METHODS: From a prospective database of all EEAs done at Weill Cornell Medical College by the senior author from 2004 to 2022, a consecutive series of histologically proven craniopharyngiomas were identified. Gross-total resection (GTR) was generally the goal of surgery. Radiation was often given if GTR had not been achieved. The stalk was preserved if not infiltrated with tumor but was sacrificed to achieve GTR. Intentional subtotal resection (STR) was performed in select cases to avoid hypothalamic injury. RESULTS: Among the 111 identified cases were 88 adults and 23 children. Newly diagnosed cases comprised 58.6% of the series. GTR was attempted in 77.5% of the patients and among those cases was achieved in 89.5% of treatment-naive tumors and 72.4% of recurrent tumors. An inability to achieve GTR was predicted by prior surgical treatment (OR 0.13, 95% CI 0.03-0.6, p = 0.009), tumor diameter ≥ 3.5 cm (OR 0.11, 95% CI 0.02-0.53, p = 0.006), and encasement of the optic nerve or a major artery (OR 0.11, 95% CI 0.01-0.8, p = 0.03). GTR with stalk preservation maintained some anterior pituitary function in 64.5% of cases and prevented diabetes insipidus in 25.8%. After a median follow-up of 51 months (IQR 17-80 months), the recurrence rate after GTR was 12.5% compared with 38.5% after non-GTR. The median recurrence-free survival was 5.5 years after STR, 8.3 years after near-total resection (≥ 98%), and not reached after GTR (p = 0.004, log-rank test). GTR was the strongest predictor of recurrence-free survival (OR 0.09, 95% CI 0.02-0.42, p = 0.002), whereas radiation did not show a statistically significant impact (OR 1.17, 95% CI 0.45-3.08). In GTR cases, the recurrence rate was higher if the stalk had been preserved (22.6%) as opposed to a sacrificed stalk (4.9%; OR 5.69, 95% CI 1.09-29.67). CONCLUSIONS: The study data show that GTR should be the goal of surgery in craniopharyngiomas if it can be achieved safely. Although stalk preservation can maintain some endocrine function, the risk of recurrence is higher in such cases. Radiation may not be as effective as previously reported.

Endoscopic odontoidectomy for brainstem compression in association with posterior fossa decompression and occipitocervical fusion.

OBJECTIVE: Endonasal endoscopic odontoidectomy (EEO) is an alternative to transoral surgery for symptomatic ventral compression of the anterior cervicomedullary junction (CMJ), allowing for earlier extubation and feeding. Because the procedure destabilizes the C1-2 ligamentous complex, posterior cervical fusion is often performed concomitantly. The authors' institutional experience was reviewed to describe the indications, outcomes, and complications in a large series of EEO surgical procedures in which EEO was combined with posterior decompression and fusion. METHODS: A consecutive, prospective series of patients who underwent EEO between 2011 and 2021 was studied. Demographic and outcome metrics, radiographic parameters, extent of ventral compression, extent of dens removal, and increase in CSF space ventral to the brainstem were measured on the preoperative and postoperative scans (first and most recent scans). RESULTS: Forty-two patients (26.2% pediatric) underwent EEO: 78.6% had basilar invagination, and 76.2% had Chiari type I malformation. The mean ± SD age was 33.6 ± 3.0 years, with a mean follow-up of 32.3 ± 4.0 months. The majority of patients (95.2%) underwent posterior decompression and fusion immediately before EEO. Two patients underwent prior fusion. There were 7 intraoperative CSF leaks but no postoperative CSF leaks. The inferior limit of decompression fell between the nasoaxial and rhinopalatine lines. The mean ± SD vertical height of dens resection was 11.98 ± 0.45 mm, equivalent to a mean ± SD resection of 74.18% ± 2.56%. The mean increase in ventral CSF space immediately postoperatively was 1.68 ± 0.17 mm (p < 0.0001), which increased to 2.75 ± 0.23 mm (p < 0.0001) at the most recent follow-up (p < 0.0001). The median (range) length of stay was 5 (2-33) days. The median time to extubation was 0 (0-3) days. The median time to oral feeding (defined as, at minimum, toleration of a clear liquid diet) was 1 (0-3) day. Symptoms improved in 97.6% of patients. Complications were rare and mostly associated with the cervical fusion portion of the combined surgical procedures. CONCLUSIONS: EEO is safe and effective for achieving anterior CMJ decompression and is often accompanied by posterior cervical stabilization. Ventral decompression improves over time. EEO should be considered for patients with appropriate indications.

Nucleolin promotes angiogenesis and endothelial metabolism along the oncofetal axis in the human brain vasculature.

Glioblastomas are among the deadliest human cancers and are highly vascularized. Angiogenesis is dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies, including brain tumors. The oncofetal axis describes the reactivation of fetal programs in tumors, but its relevance in endothelial and perivascular cells of the human brain vasculature in glial brain tumors is unexplored. Nucleolin is a regulator of cell proliferation and angiogenesis, but its roles in the brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit in human fetal brains, adult brains, and human gliomas in vivo as well as its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression correlated with glioma malignancy in vivo. In culture, siRNA-mediated Nucleolin knockdown reduced human brain endothelial cell (HCMEC) and HUVEC sprouting angiogenesis, proliferation, filopodia extension, and glucose metabolism. Furthermore, inhibition of Nucleolin with the aptamer AS1411 decreased brain endothelial cell proliferation in vitro. Mechanistically, Nucleolin knockdown in HCMECs and HUVECs uncovered regulation of angiogenesis involving VEGFR2 and of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that promotes sprouting angiogenesis and endothelial metabolism, characterizing Nucleolin as an oncofetal protein. Our findings have potential implications in the therapeutic targeting of glioma.

Fourth ventricular subarachnoid stent for Chiari malformation type I-associated persistent syringomyelia.

OBJECTIVE: Syringomyelia (syrinx) associated with Chiari malformation type I (CM-I) is commonly managed with posterior fossa decompression, which can lead to resolution in most cases. A persistent syrinx postdecompression is therefore uncommon and challenging to address. In the setting of radiographically adequate decompression with persistent syrinx, the authors prefer placing fourth ventricular subarachnoid stents that span the craniocervical junction particularly when intraoperative observation reveals arachnoid plane scarring. The objective of this study was to evaluate the safety and efficacy of a fourth ventricle stent for CM-I-associated persistent syringomyelia, assess dynamic changes in syrinx dimensions, and report stent-reduction durability, clinical outcomes, and procedure-associated complications. METHODS: The authors performed a single-institution, retrospective review of patients who underwent fourth ventricular subarachnoid stent placement for persistent CM-I-associated syringomyelia following a prior posterior fossa decompression. The authors' institutional Chiari database contains 600 cases with 149 decompressions for CM-I-associated syringomyelia, of which 13 met criteria for inclusion. Data on patient demographics, clinical presentation and outcomes, and MRI findings were collected. The maximal syrinx diameter was estimated by calculating the area of an elliptical cross-section in the largest axial plane from preoperative, immediately postoperative, and late postoperative T2-weighted MR images. RESULTS: All 13 patients experienced a significant decrease in mean syrinx area from the preoperative to the late postoperative MRI (mean syrinx diameter 114.1 ± 81.8 mm2 vs 24.5 ± 23.8 mm2, p < 0.001). The mean time until late postoperative MRI was 19.7 months (range 2.0-70.7 months). The syrinx area reduced on average by 75.0% ± 23.9% at the time of the last postoperative scan. Syrinx resolution was variable, with 4 patients (30.8%) achieving near-complete resolution (> 90%, grade III reduction), 7 patients (50%) having 50%-90% reduction (grade II), and 2 patients (14.3%) having < 50% decrease (grade I). One patient experienced catheter migration into the left brachium pontis with an associated cyst at the tip of the catheter that decreased in size on follow-up imaging. CONCLUSIONS: Placement of fourth ventricular subarachnoid stents spanning the craniocervical junction in patients with persistent CM-I-associated syringomyelia after posterior fossa decompression is a safe therapeutic option and significantly reduced the mean syrinx area, with a greater reductive effect seen over longer follow-up periods.

Defining Occult High-Risk Cysts of the Pineal Region: A Case Series.

BACKGROUND: Absence of hydrocephalus on neuroimaging may impart a false sense of security for patients with pineal cysts. In this case series, we characterize a subset of patients with pineal cysts having an occult presentation. Unifying features of worsening paroxysmal headaches suggesting intermittent obstructive hydrocephalus and radiographic evidence of third ventricular invagination characterize these patients as high risk. OBJECTIVE: To define features of occult, high-risk pineal cysts and outcomes of endoscopic cyst fenestration. METHODS: Charts were retrospectively reviewed for patients with pineal cysts evaluated at our institution between 2018 and 2021 who underwent endoscopic cyst fenestration. To capture cysts presenting as occult, patients were excluded if hydrocephalus was noted at presentation. Relevant clinical history, imaging, operative data, and clinical outcomes were reviewed. RESULTS: Of 50 pineal cyst patients, 4 satisfied inclusion criteria. All patients presented with worsening paroxysmal headaches. In addition, 75% (3/4) also experienced intermittent syncope. Patients exhibited no hydrocephalus (n = 3) or fluctuating ventricular size on longitudinal imaging (n = 1). In all cases, high-resolution sagittal 3-dimensional T2 magnetic resonance imaging demonstrated invagination of the cyst anteriorly into the posterior third ventricle. All patients underwent endoscopic cyst fenestration with complete symptom resolution (mean follow-up of 20.6 months; range 3.5-37.4 months). CONCLUSION: The clinical history for occult, high-risk pineal cysts is notable for worsening paroxysmal headaches and episodic alterations of consciousness suggesting intermittent obstructive hydrocephalus. Because ventricular size can appear normal on standard imaging protocols, clinical suspicion should trigger workup with high-resolution magnetic resonance imaging designed to detect these cysts. Endoscopic cyst fenestration is a safe and efficacious management strategy.

Intraoperative occipital to C2 angle and external acoustic meatus-to-axis angular measurements for optimizing alignment during posterior fossa decompression and occipitocervical fusion for complex Chiari malformation.

Background: Excess flexion or extension during occipitocervical fusion (OCF) can lead to postoperative complications, such as dysphagia, respiratory problems, line of sight issues, and neck pain, but posterior fossa decompression (PFD) and OCF require different positions that require intraoperative manipulation. Objective: The objective of this study was to describe quantitative fluoroscopic morphometrics in Chiari malformation (CM) patients with symptoms of craniocervical instability (CCI) and demonstrate the intraoperative application of these measurements to achieve neutral craniocervical alignment while leveraging a single axis of motion with the Mayfield head clamp locking mechanism. Methods: A retrospective cohort study of patients with CM 1 and 1.5 and features of CCI who underwent PFD and OCF at a single-center institution from March 2015 to October 2020 was performed. Patient demographics, preoperative presentation, radiographic morphometrics, operative details, complications, and clinical outcomes were analyzed. Results: A total of 39 patients met the inclusion criteria, of which 37 patients (94.9%) did not require additional revision surgery after PFD and OCF. In this nonrevision cohort, preoperative to postoperative occipital to C2 angle (O-C2a) (13.5° ± 10.4° vs. 17.5° ± 10.1°, P = 0.047) and narrowest oropharyngeal airway space (nPAS) (10.9 ± 3.4 mm vs. 13.1 ± 4.8 mm, P = 0.007) increased significantly. These measurements were decreased in the two patients who required revision surgery due to postoperative dysphagia (mean difference - 16.6°° in O C2a and 12.8°° in occipital and external acoustic meatus to axis angle). Based on these results, these fluoroscopic morphometrics are intraoperatively assessed, utilizing a locking Mayfield head clamp repositioning maneuver to optimize craniocervical alignment prior to rod placement from the occipital plate to cervical screws. Conclusion: Establishing a preoperative baseline of reliable fluoroscopic morphometrics can guide surgeons intraoperatively in appropriate patient realignment during combined PFD and OCF, and may prevent postoperative complications.

Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies.

BACKGROUND: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies. PATIENTS AND METHODS: We conducted a phase I trial of intraventricular 131I-omburtamab using a standard 3 + 3 design. Eligibility criteria included adequate cerebrospinal fluid (CSF) flow, no major organ toxicity, and for patients > dose level 6, availability of autologous stem cells. Patients initially received 74 MBq radioiodinated omburtamab to evaluate dosimetry and biodistribution followed by therapeutic 131I-omburtamab dose-escalated from 370 to 2960 MBq. Patients were monitored clinically and biochemically for toxicity graded using CTCAEv 3.0. Dosimetry was evaluated using serial CSF and blood sampling, and serial PET or gamma-camera scans. Patients could receive a second cycle in the absence of grade 3/4 non-hematologic toxicity or progressive disease. RESULTS: Thirty-eight patients received 100 radioiodinated omburtamab injections. Diagnoses included metastatic neuroblastoma (n = 16) and other B7H3-expressing solid tumors (n = 22). Thirty-five patients received at least 1 cycle of treatment with both dosimetry and therapy doses. Acute toxicities included < grade 4 self-limited headache, vomiting or fever, and biochemical abnormalities. Grade 3/4 thrombocytopenia was the most common hematologic toxicity. Recommended phase 2 dose was 1850 MBq/injection. The median radiation dose to the CSF and blood by sampling was 1.01 and 0.04 mGy/MBq, respectively, showing a consistently high therapeutic advantage for CSF. Major organ exposure was well below maximum tolerated levels. In patients developing antidrug antibodies, blood clearance, and therefore therapeutic index, was significantly increased. In patients receiving cRIT for neuroblastoma, survival was markedly increased (median PFS 7.5 years) compared to historical data. CONCLUSIONS: cRIT with 131I-omburtamab is safe, has favorable dosimetry and may have a therapeutic benefit as adjuvant therapy for B7-H3-expressing leptomeningeal metastases. TRIAL REGISTRATION: clinicaltrials.gov NCT00089245, August 5, 2004.

Intracranial hypotension due to ventral thoracic dural tear secondary to osteophyte complex: resolution after transdural thoracic microdiscectomy with dural repair. Illustrative case.

BACKGROUND: Intracranial hypotension (IH) manifests with orthostatic headaches secondary to cerebrospinal fluid (CSF) hypovolemia. Common iatrogenic etiologies include lumbar punctures and spinal surgery. Although much rarer, structural defects such as osteophytes and herniated calcified discs can violate dural integrity, resulting in CSF leak. OBSERVATIONS: The authors reported the case of a 32-year-old woman who presented with progressively worsening orthostatic headaches. During an extensive examination, magnetic resonance imaging of her thoracic spine revealed a cervicothoracic ventral epidural collection of CSF, prompting a dynamic computed tomography myelogram, which not only helped to confirm severe cerebral hypotension but also suggested underlying pathology of a dorsally projecting disc osteophyte complex at T2-3. Conservative and medical management failed to alleviate symptoms, and a permanent surgical cure was eventually sought. The patient underwent a transdural thoracic discectomy with dural repair, which resulted in resolution of her symptoms. LESSONS: Clear guidelines regarding the management strategy of IH secondary to disc osteophyte complexes are yet to be established. A thorough literature review noted only 24 reported cases between 1998 and 2019, in which 13 patients received surgery. There is a 46% symptom resolution rate with conservative management, lower than that for iatrogenic etiologies. For patients in whom conservative management failed, surgical intervention proved effective in resolving symptoms, with a success rate of 92.3%.

Reevaluating Innovations in Medical Student Neurosurgery Education: Lessons Learned Today from Data Collected Before COVID-19.

OBJECTIVE: Virtual learning has made neurosurgery education more available to medical students (MSs) of all stages than ever before. We aimed to evaluate the impact of on-site learning in order to assess whether a return to this method of teaching, when safe, is warranted for MSs of all years. METHODS: Registrants of the 2019 MS Neurosurgery Training Camps were sent precourse and postcourse surveys to assess changes in self-assessed confidence in concrete neurosurgical skills. Data were analyzed using a 2-tailed paired Student's t-test for continuous variables. A P value <0.05 was considered significant. RESULTS: The 2019 Training Camp had 105 attendees, of whom 94 (89.5%) completed both surveys. Students reported statistically significant improvements in every surveyed skill area, except for understanding what is and is not sterile in an operating room. The cohort of MS 3/4 students indicated a postcourse decrease in confidence in their ability to understand what is and is not sterile in an operating room (93.69 ± 16.41 vs. 86.20 ± 21.18; P < 0.05). MS 3/4 students did not benefit in their ability to perform a neurologic examination or tie knots using a 1-handed technique. CONCLUSIONS: Neurosurgical education initiatives for MSs should continue to be developed. Hands-on neurosurgical training experiences for MSs serve as a valuable educational experience. Improvement in training models will lead to capitalizing on MS education to better improve readiness for neurosurgical residency without concern for patient safety.

Myofascial Flap Closure Decreases Complications in Complex Surgery of the Craniocervical Junction in Ehlers-Danlos Patients.

INTRODUCTION: Patients with Ehlers-Danlos syndrome (EDS) are at elevated risk for soft tissue complications when undergoing decompression with or without fusion of the craniocervical junction. We have previously shown that muscle flap closure can decrease reoperative rates. This study investigated whether myofascial flap closure improved clinical outcomes after simple or complex surgery of the craniocervical junction in EDS patients specifically. METHODS: We performed a retrospective chart review of EDS patients who had undergone surgery for Chiari malformation at the Weill Cornell Medical Center between 2013 and 2020. Postoperative complications were recorded, including infection, wound dehiscence, seroma, hematoma, hardware removal, cerebrospinal fluid (CSF) leak, reoperation, and pseudomeningocele. Patients were stratified by type of closure and type of surgery. Fisher exact test was used for statistical comparison. RESULTS: Between 2013 and 2020, 62 EDS patients who had surgery of the cervicocranial junction were reviewed. Of these, 31 patients had complex surgery with myofascial flap closure and 22 had simple surgery with traditional closure. The mean age at the time of surgery was 21.3 years. There were no significant differences in wound complications or reoperation rates between the simple surgery and complex surgery groups. In addition, there were no significant differences in complications between complex surgery with flap closure and simple surgery with traditional closure. Our CSF cutaneous fistula rate was 0%, considerably lower than rates reported in the literature, and, in one case, a patient developed a postoperative pseudomeningocele secondary to a dural leak, but the myofascial flap closure prevented its progression. CONCLUSIONS: Patients with EDS undergoing surgery of the cervicocranial junction may benefit from myofascial flap closure. Flap closure reduced complications after complex surgery of the craniocervical junction to the level of simple surgery. Our CSF leak rate was exceptionally low and only one patient experienced pseudomeningocele. Myofascial flaps are safe to perform in the EDS cohort and prevented CSF cutaneous fistula formation.

Utility of multimodality molecular profiling for pediatric patients with central nervous system tumors.

Background: As our molecular understanding of pediatric central nervous system (CNS) tumors evolves, so too do diagnostic criteria, prognostic biomarkers, and clinical management decision making algorithms. Here, we explore the clinical utility of wide-breadth assays, including whole-exome sequencing (WES), RNA sequencing (RNA-seq), and methylation array profiling as an addition to more conventional diagnostic tools for pediatric CNS tumors. Methods: This study comprises an observational, prospective cohort followed at a single academic medical center over 3 years. Paired tumor and normal control specimens from 53 enrolled pediatric patients with CNS tumors underwent WES. A subset of cases also underwent RNA-seq (n = 28) and/or methylation array analysis (n = 27). Results: RNA-seq identified the driver and/or targetable fusions in 7/28 cases, including potentially targetable NTRK fusions, and uncovered possible rationalized treatment options based on outlier gene expression in 23/28 cases. Methylation profiling added diagnostic confidence (8/27 cases) or diagnostic subclassification endorsed by the WHO (10/27 cases). WES detected clinically pertinent tier 1 or tier 2 variants in 36/53 patients. Of these, 16/17 SNVs/INDELs and 10/19 copy number alterations would have been detected by current in-house conventional tests including targeted sequencing panels. Conclusions: Over a heterogeneous set of pediatric tumors, RNA-seq and methylation profiling frequently yielded clinically relevant information orthogonal to conventional methods while WES demonstrated clinically relevant added value primarily via copy number assessment. Longitudinal cohorts comparing targeted molecular pathology workup vs broader genomic approaches including therapeutic selection based on RNA expression data will be necessary to further evaluate the clinical benefits of these modalities in practice.

Quantifying intraventricular drug delivery utilizing programmable ventriculoperitoneal shunts as the intraventricular access device.

PURPOSE: Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of drug concentrations in the thecal space with minimization in the peritoneum. This report assesses the success of the pVP shunt as an access device for intraventricular therapies. Quantifying intrathecal drug delivery using scintigraphy by pVP shunt model has not been previously reported. METHODS: We performed a single-institution, retrospective analysis on patients with CNS tumors and pVP shunts from 2003 to 2020, noting shunt model. pVP flow was evaluated for consideration of compartmental radioimmunotherapy (cRIT) using In-111-DTPA scintigraphy. Scintigraphy studies at 2-4 h and at 24 h quantified ventricular-thecal and peritoneal drug activity. RESULTS: Twenty-two CSF flow studies were administered to 15 patients (N = 15) with diagnoses including medulloblastoma, metastatic neuroblastoma, pineoblastoma, and choroid plexus carcinoma. Six different types of pVP models were noted. 100% of the studies demonstrated ventriculo-thecal drug activity. 27% (6 of 22) of the studies had no peritoneal uptake visible by imaging. 73% (16 of 22) of the studies had minimal relative peritoneal uptake (< 12%). 27% (6 of 22) of the studies demonstrated moderate relative peritoneal uptake (12-37%). No studies demonstrated peritoneal uptake above 37%. CONCLUSIONS: All patients had successful drug delivery of In-111-DTPA to the ventriculo-thecal space. 73% of the patients had minimal relative (< 12%) peritoneal drug uptake. Though efficacy varies by shunt model, low numbers preclude conclusions regarding model superiority. CSF flow scintigraphy studies assesses drug distribution of In-111-DTPA, informing CSF flow for delivery of intraventricular therapies.

Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent and young adult brain tumor patients.

BACKGROUND: Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests. METHODS: We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. RESULTS: We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient's disease course. CONCLUSIONS: We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care.

Pediatric pituitary adenomas are more aggressive, more likely to be hormone producing and are more difficult to cure than adult pituitary adenomas: case series and systematic literature review.

PURPOSE: Pediatric pituitary adenomas (pPAs) are uncommon. Thus, their presentation and outcomes after treatment are less well-understood than those of pituitary adenomas in adulthood (aPAs). METHODS: A retrospective chart review was conducted for all patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for pPA at NewYork-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) from 2005-2020. Eleven patients were identified, and information pertaining to age, sex, adenoma characteristics, procedural details, and outcomes was reviewed. A systematic review of the literature was also performed to compare outcomes of EETS versus microscopic endonasal transsphenoidal surgery (METS) for pPA. RESULTS: From 2005-2020, 11 patients underwent EETS for pPA at NYP/WCM. Mean age at operation was 14.9 ± 2.7 years, and 5 patients (45.5%) were male. 10 adenomas (90.9%) were hormone-producing. Of the functional adenomas, 8 (80.0%) were PRL-secreting and 2 (20.0%) were GH-secreting. Maximum adenoma diameter (MAD) ranged from 1.2-5.1 cm, with a median of 1.55 cm. Cavernous sinus invasion (CSI) occurred in 2 patients with macroprolactinoma. Gross total resection (GTR) was achieved in 10 (90.9%). Biochemical remission occurred in 5/10 (50.0%). Post-operative complications were documented in 8 cases (72.7%) and included diabetes insipidus, hypopituitarism, sinusitis, weight gain, cerebrospinal fluid leak, meningitis, and hydrocephalus. Systematic literature review of 105 microscopic and 175 endoscopic cases revealed high frequency of hormone-producing tumors (83.6%) and similar rates of GTR (82.4% vs 85.1%) and biochemical cure (75.8% vs 64.3%). CONCLUSIONS: pPAs are more likely to be hormone producing and may be more aggressive and difficult to cure than aPAs. EETS is an effective treatment, although complication rates may be higher than in adult populations.