Bauman, Megan M. J.

OBJECTIVE Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. METHODS The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). RESULTS A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19–70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38–72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45–164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03–78.86, p = 0.007; HR 7.31, 95% CI 1.45–36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. CONCLUSIONS Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.

OBJECTIVE Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33–29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54–3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

Abstract White matter dissection (WMD) involves isolating bundles of myelinated axons in the brain and serves to gain insights into brain function and neural mechanisms underlying neurological disorders. While effective, cadaveric brain dissections pose certain challenges mainly due to availability of resources. Technological advancements, such as photogrammetry, have the potential to overcome these limitations by creating detailed three-dimensional (3D) models for immersive learning experiences in neuroanatomy. Objective: This study aimed to provide a detailed step-by-step WMD captured using two-dimensional (2D) images and 3D models (via photogrammetry) to serve as a comprehensive guide for studying white matter tracts of the brain. One formalin-fixed brain specimen was utilized to perform the WMD. The brain was divided in a sagittal plane and both cerebral hemispheres were stored in a freezer at -20°C for 10 days, then thawed under running water at room temperature. Micro-instruments under an operating microscope were used to perform a systematic lateral-to-medial and medial-to-lateral dissection, while 2D images were captured and 3D models were created through photogrammetry during each stage of the dissection. Dissection was performed with comprehensive examination of the location, main landmarks, connections, and functions of the white matter tracts of the brain. Furthermore, high-quality 3D models of the dissections were created and housed on SketchFab®, allowing for accessible and free of charge viewing for educational and research purposes. Our comprehensive dissection and 3D models have the potential to increase understanding of the intricate white matter anatomy and could provide an accessible platform for the teaching of neuroanatomy.

AbstractHemifacial spasm is a neuromuscular disorder caused by compression of the facial nerve at the nerve root entry zone, often due to ectatic or aberrant vasculature. Pathologic compression of the nerve–brainstem interface results in involuntary, paroxysmal contractions of ipsilateral facial muscles that may cause considerable impairments in quality of life. For those with severe symptoms, have positive imaging demonstrating vascular compression, or who fail other management modalities,1 2 3 4 microvascular decompression offers potential definitive treatment.5 6 Traditionally, nonabsorbable packing agent is used to pack between the nerve and offending vascular structure. However, for large and more complex arterial structures, simple nonabsorbable padding is often not sufficient.In this operative video, we demonstrate microvascular decompression for intractable hemifacial spasm in a 52-year-old female using a specialized sling tacked to the petrous dura for management of a large, ectatic vertebral artery. Following a standard left retrosigmoid craniotomy, an atheromatous ectatic vertebral artery was identified. We fashioned a bovine pericardium sling around the vessel and used a permanent aneurysm clip to secure it to an incision portion of petrous dura. We subsequently identified potential additional facial nerve root compression by anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery (PICA) branches, which were elevated and secured using Teflon felt packing. Following elevation of all three vessels, the lateral spread response resolved. At 2 weeks postoperatively, the patient reported substantial relief in her hemifacial spasms and endorsed highly improved quality of life.

Abstract OBJECTIVE This study aimed to analyze the hemorrhagic risk of melanoma brain metastases following SRS. METHODS A retrospective analysis was conducted using a prospective institutional database between 1990 and 2021. Lesional hemorrhage was categorized as definite or possible, and hemorrhage severity was graded using CTCAE. RESULTS The study identified 291 patients with 1083 lesions. The mean age of patients was 60 ± 15 years, with 61% being male. Median follow-up was 11 months, corresponding to 581 patient-years. Among the patients, 82 (28%) experienced 135 lesional hemorrhages (13%). Of these, 88 lesions in 61 patients were grade 1-2 hemorrhages, 42 lesions in 25 patients were grade 3, and five lesions in five patients progressed from grade 1 to 3. Surgical intervention was required for 17 lesions (2%) in 16 patients (5%). Lesional hemorrhage was associated with radiosurgery performed between 2015 and 2021 (OR, 0.373; 95% CI, 0.231-0.60; p &lt; 0.001), increasing marginal dose (OR, 0.89; 95% CI, 0.82-0.98; p = 0.017), antiplatelet use (OR, 0.192; 95% CI, 0.082-0.45; p &lt; 0.001), and WBRT (OR, 0.51; 95% CI, 0.330-0.77; p = 0.0017). The cumulative lesional hemorrhage risk reached 17–20% at 36 months following radiosurgery, with 95-96% of hemorrhages occurring within the initial year. Median OS was 11 months (95% CI, 9-13 months). Patients who received radiosurgery between 2015 and 2021 exhibited a median OS of 17 months (95% CI, 10-24 months; p &lt; 0.001), while those without hemorrhage had a median OS of 12 months (95% CI, 10-14 months; p = 0.054). CONCLUSIONS Definitive hemorrhage risk was 17% for melanoma brain metastases after SRS within the first three years, with 95% of lesional hemorrhages occurring within the initial year. Surgical intervention was necessary in 5% of patients. Hemorrhage risk and overall survival improved after 2015.

Abstract INTRODUCTION Extracellular Vesicles (EVs) are lipid bilayer particles present in almost all biofluids and carry tumor-specific molecular cargo. Plasma EVs are promising sources of biomarker discovery for glioblastoma (GBM). The clinical relevance of non-neoplastic plasma EVs in GBM remains unclear. In this study, we determine if associations exist between plasma EV subpopulation frequencies in GBM and clinical factors. METHODS Platelet-free plasma samples of 63 GBM, 43 Grade 2 glioma, and 45 healthy donors were included. All glioma plasma samples were collected before surgery. Plasma EV subpopulation frequency based on surface expression of EV-associated tetraspanins (CD9/CD81/CD63) and markers of cell origin (CD45/CD41a/CD11b/CD31) was determined by spectral flow cytometry. Clinical information including age, surgery, MGMT methylation status, corticosteroid usage, tumor volume, and overall survival data was recorded. RESULTS Compared to normal donors, GBM patients had increased CD9+, CD63+, CD81+, and CD11b+ EVs but decreased CD41a+ EVs. GBM patients also had the highest frequency of myeloid-derived CD9+CD11b+ EVs (20.17%) followed by grade 2 gliomas (13.78%) and normal donors (2.76%, p&lt; 0.001). More GBM patients (29/63, 46.0%) received preoperative corticosteroids than grade 2 glioma patients (9/43, 20.9%; p = 0.008). Corticosteroid use was not associated with differences in EV subpopulation frequencies in GBM or grade 2 glioma patients. Pearson correlation analysis showed weak but statistically significant correlations between GBM total tumor volume and CD9+ EVs (p = 0.014), CD41a+ EVs (p = 0.037), and CD9+/CD63-/CD81- EVs (p = 0.007). In GBM patients, younger age (&lt; 60 yrs, p = 0.01), gross total resection (p = 0.02), MGMT methylation (p = 0.002), high CD9+ EV expression (p = 0.011), low CD9+CD63-CD81- EV expression (p = 0.009) and low CD9+CD11b+ EV expression (p = 0.006) correlated with longer overall survival. CONCLUSION Differentially expressed non-neoplastic plasma EV subpopulations have significant clinical relevance in GBM including association with tumor volume and predicting survival. Validation of those markers in larger cohorts could reveal new prognostic biomarkers for GBM.

BACKGROUND AND OBJECTIVES: Schwannomas originating from the lower cranial nerves (LCNS) are rare and pose a significant surgical challenge. Resection is the mainstay treatment; however, risk of treatment morbidity is considerable, and the available literature regarding differential treatment outcomes in this vulnerable population is sparse. METHODS: A single-institution cohort study and systematic literature review of LCNS were performed. RESULTS: Fifty-eight patients were included: 34 underwent surgical resection and 24 underwent stereotactic radiosurgery (SRS). The median age at diagnosis was 48 years (range 17-74). Presenting symptoms were dysphagia (63%), dysarthria/hypophonia (47%), imbalance (33%), and hearing loss/tinnitus (30%). Tumor size was associated with surgical resection, as compared with initial SRS (4.1 cm vs 1.5 cm, P = .0001). Gross total resection was obtained in 52%, with tumor remnants predominantly localized to the jugular foramen (62%). Post-treatment worsening of symptoms occurred in 68% of surgical and 29% of SRS patients ( P = .003). Postoperative symptoms were mostly commonly hypophonia/hoarseness (63%) and dysphagia (59%). Seven patients (29%) had new neurological issues after SRS treatment, but symptoms were overall milder. The median follow-up was 60 months (range 12-252); 98% demonstrated meaningful clinical improvement. Eighteen surgical patients (53%) underwent adjuvant radiation at a median of 5 months after resection (range 2-32). At follow-up, tumor control was 97% in the surgical cohort and 96% among SRS patients. CONCLUSION: Although LCNS resection is potentially morbid, most postoperative deficits are transient, and patients achieve excellent tumor control—particularly when paired with adjuvant SRS. For minimally symptomatic patients undergoing surgical intervention, we advise maximally safe resection with intracapsular dissection to preserve nerve integrity where possible. For residual or as a primary treatment modality, SRS is associated with low morbidity and high rates of long-term tumor control.

OBJECTIVE The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists’ readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0–214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266–0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83–0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083–0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344–0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%–20% at 36 months from GKRS, with 95%–96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9–13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45–0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26–0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02–1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04–1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.