Use of a Suction-Monopolar Stimulator for Continuous Neurophysiology Monitoring During Endonasal Resection of a Cavernous Sinus Schwannoma: 2-Dimensional Operative Video.

Cavernous sinus schwannomas are exceptionally rare tumors.1,2 Although these tumors commonly originate from the trigeminal nerve, instances involving the oculomotor, abducens, trochlear nerves, and the carotid plexus have also been documented.2-7 In this operative video, we showcase a 44-year-old man with a medical history of acromegaly and schwannomatosis who presented with retro orbital pain and a growing cystic lesion in the left cavernous sinus. Genetic testing ruled out neurofibromatosis types 1 and 2. An endonasal resection was recommended considering the left side and extradural location of the lesion.8 The tumor was excised through an endonasal transpterygoid approach using 2 suctions, one of which was equipped with an electrode tip for continuous monitoring of extraocular nerves during the resection process. Imaging postoperatively demonstrated near-total resection. Institutional review board approval was not required; the patient agreed to undergo the procedure and to have his operative video published.

Use of a Monopolar Stimulator to Preserve the Frontotemporal Branches of the Facial Nerve During a Pterional Approach: 2-Dimensional Operative Video.

Preservation of the frontotemporal branches of the facial nerve is essential to obtain good cosmetic outcomes after anterolateral cranial base approaches.1,2 Since the description of the interfacial dissection, most nerve injuries are due to retraction of the nerve fibers and not direct transection.3-5 In this video, we showcase the use of a monopolar stimulator to guide the placement of hook retractors and assess no undue retraction is applied to the nerve fibers during a pterional craniotomy. This simple tool can help in preserving frontalis function after anterolateral skull base craniotomies. Institutional review board approval was not required; the patient consented to the procedure and to the publication of his/her image.

Use of Real-Time Superior Hypophyseal Artery Indocyanine Green Angiogram During Endoscopic Resection of a Third Ventricular Craniopharyngioma: 2-Dimensional Operative Video.

The endoscopic endonasal approach for resection of craniopharyngiomas has gained popularity because of its minimal need for retraction and superior visualization of and access to the optic chiasm.1-4 Despite these advantages, the proximity of craniopharyngiomas to the optic apparatus still challenges the preservation of visual function.5-10 Indocyanine green (ICG) angiography can evaluate the perfusion of the chiasm and can predict visual outcomes after endonasal approaches, in addition to known uses of the dye.3 ICG angiography may therefore hold promise in the real-time assessment of optic chiasm perfusion during resection of craniopharyngiomas by delineating details of the superior hypophyseal artery (SHA) system. Here, we present a case in which ICG angiogram was used to assess the perfusion of the chiasm before, during, and after tumor resection. This technique signaled thrombosis of the left principal SHA during tumor resection that was compensated by the anastomotic SHA system from the right. The case shows an endoscopic endonasal approach for the resection of a third ventricular craniopharyngioma in a 21-year-old woman presenting with unremitting headaches, endocrine dysfunction, and vision loss. Postoperatively, the patient's neurological examination remained unchanged and visual function improved within 2 weeks. This case underscores the potential for real-time intraoperative ICG angiography to assist in the careful resection of craniopharyngiomas while improving visual outcomes. Institutional review board approval was not required; the patient consented to the procedure and to publishing of the operative video.

Calcified Meningiomas Demonstrate Equivocal Grade, Proliferation, and Immediate Surgical Outcomes.

BACKGROUND/OBJECTIVE: Meningioma calcification is thought to predict reduced growth potential and aggression. However, historical studies have primarily focused on correlating calcification in small meningiomas (diameter less than 2.5 cm) rather than analyzing characteristics of calcified meningiomas across all sizes. In this study, we investigate the pathologic and clinical implications of meningioma calcification. METHODS: We utilized a historical database of 342 consecutive newly diagnosed intracranial meningiomas with preoperative computed tomography and magnetic resonance imaging scans treated at a single institution from 2005 to 2019. We correlated the presence of calcification with patient demographics, grade, Mindbomb Homolog-1 index, location, volume, Simpson grade, and recurrence using both univariate and multivariate generalized linear models. RESULTS: On univariate analysis, no single variable correlated with tumor calcification. Notably, neither tumor 2021 World Health Organization grade (P = 0.91) nor Mindbomb Homolog-1 index (P = 0.62) predicted calcification. After accounting for demographic characteristics and tumor volume and location, there was no significant association between 2021 World Health Organization grade (P = 0.52) and Mindbomb Homolog-1 index (P = 0.54) and calcification. Calcification had no influence on resection grade (P = 0.59) or recurrence (P = 0.80). CONCLUSIONS: In this series, calcified meningiomas exhibited similar 2021 World Health Organization tumor grading distribution, proliferation indexes, and immediate surgical outcomes compared to their noncalcified counterparts. These findings question the historical role of using meningioma calcification as an independent guide to their management.

Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas.

BACKGROUND AND OBJECTIVES: Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas. METHODS: Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200). RESULTS: MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c2) or skull base location (62.5% vs 38.3%, P < .001, c2) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas (P < .05, t test). There was no association between MIH and histological World Health Organization grade (P = .32, c2). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group (P < .05). Somatic missense mutations in the WD-repeat-containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c2). CONCLUSION: In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.

Genomic alterations associated with postoperative nodular leptomeningeal disease after resection of brain metastases.

OBJECTIVE: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. This study examined genomic alterations found in brain metastases with the aim of identifying alterations associated with postoperative nLMD in the context of clinical and treatment factors. METHODS: A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of > 500 oncogenes was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD. RESULTS: The cohort comprised 101 patients with tumors originating from multiple cancer types. There were 15 patients with nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B codeletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazards analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (× 10 cm3; HR 1.2, 95% CI 1.01-1.5; p = 0.04), CDKN2A/B codeletion (HR 5.3, 95% CI 1.7-16.9; p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4; p = 0.04) were associated with a decreased time to postoperative nLMD. CONCLUSIONS: In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.

Association of CDKN2A alterations with increased postoperative seizure risk after resection of brain metastases.

OBJECTIVE: Seizures are common and significantly disabling for patients with brain metastases (BMs). Although resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Genomic BM characteristics may influence which patients are at risk for postoperative seizures. This work explores correlations between genomic alterations and risk of postoperative seizures following BM resection. METHODS: All patients underwent BM resection at a single institution, with available clinical and sequencing data on more than 500 oncogenes. Clinical seizures were documented pre- and postoperatively. A random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures by using Cox proportional hazards models. RESULTS: There were 112 patients with BMs who underwent 114 surgeries and had at least 1 month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). The Engel classification achieved at 6 months for those with preoperative seizures was class I in 13 (50%); class II in 6 (23.1%); class III in 5 (19.2%), and class IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively, and preoperative seizures were not a significant predictor of postoperative seizures (HR 1.84; 95% CI 0.79-4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR 3.22; 95% CI 1.27-8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other primary malignancies (HR 5.23; 95% CI 1.37-19.98; p = 0.016). Of 39 BMs with CDKN2A alteration, 35.9% (14/39) had postoperative seizures, compared to 14.7% (11/75) without CDKN2A alteration. The overall rate of postoperative seizures in melanoma BMs was 42.9% (15/35), compared with 12.7% (10/79) for all other primary malignancies. CONCLUSIONS: CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.

Genomic alterations associated with rapid progression of brain metastases.

OBJECTIVE: The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery. METHODS: This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses. RESULTS: The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039). CONCLUSIONS: Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.

A new perspective on an old method: gated SPECT imaging for left ventricular contractile function assessment.

The ejection fraction (LVEF) is a commonly used marker of left ventricular function. However, because it is strongly influenced by loading conditions, it can be inaccurate in representing cardiac contractility. We therefore evaluated a gated SPECT based tool to simultaneously assess preload, afterload, and contractility. Using gated SPECT-determined ventricular volumes and arterial tension measurements, we calculated ventricular and arterial elastance (Ev and Ea), as well as end-diastolic volumes, which are surrogates for contractility, afterload, and preload, respectively. We applied this protocol to 1462 consecutive patients and assessed the ventricular function in patients with and without myocardial infarction. The median LVEF was 68% (IQR 62-74%). Patients with infarction exhibited decreased contractility (ventricular elastance of 3 mmHg/ml vs. 6 mmHg/ml), compensated by an increase of preload (end-diastolic volume of 100 ml vs. 78 ml) and a decrease in afterload (arterial elastance of 1.8 mmHg/ml vs. 2.2 ml/mmHg). These interactions yielded a preserved ejection fraction in both groups. Gated SPECT-measured volumes were consistent with values reported in the literature. In addition, the combination of nuclear imaging and arterial tension measurement accounted for not only the ejection fraction but also the loading context, providing a more accurate representation of cardiac contractility.

Heterogeneous growth of the insula shapes the human brain.

The human cerebrum consists of a precise and stereotyped arrangement of lobes, primary gyri, and connectivity that underlies human cognition [P. Rakic, Nat. Rev. Neurosci. 10, 724-735 (2009)]. The development of this arrangement is less clear. Current models explain individual primary gyrification but largely do not account for the global configuration of the cerebral lobes [T. Tallinen, J. Y. Chung, J. S. Biggins, L. Mahadevan, Proc. Natl. Acad. Sci. U.S.A. 111, 12667-12672 (2014) and D. C. Van Essen, Nature 385, 313-318 (1997)]. The insula, buried in the depths of the Sylvian fissure, is unique in terms of gyral anatomy and size. Here, we quantitatively show that the insula has unique morphology and location in the cerebrum and that these key differences emerge during fetal development. Finally, we identify quantitative differences in developmental migration patterns to the insula that may underlie these differences. We calculated morphologic data in the insula and other lobes in adults (N = 107) and in an in utero fetal brain atlas (N = 81 healthy fetuses). In utero, the insula grows an order of magnitude slower than the other lobes and demonstrates shallower sulci, less curvature, and less surface complexity both in adults and progressively throughout fetal development. Spherical projection analysis demonstrates that the lenticular nuclei obstruct 60 to 70% of radial pathways from the ventricular zone (VZ) to the insula, forcing a curved migration to the insula in contrast to a direct radial pathway. Using fetal diffusion tractography, we identify radial glial fascicles that originate from the VZ and curve around the lenticular nuclei to form the insula. These results confirm existing models of radial migration to the cortex and illustrate findings that suggest differential insular and cerebral development, laying the groundwork to understand cerebral malformations and insular function and pathologies.

Superior Hypophyseal Artery Intraoperative Indocyanine Green Angiogram as a Predictor of Postoperative Visual Function After Endoscopic Endonasal Surgery.

BACKGROUND AND OBJECTIVES: To date, there are no tools to intraoperatively predict postoperative visual function after endoscopic endonasal surgery (EES) for suprasellar lesions. The objective of this study was to retrospectively evaluate the utility of indocyanine green (ICG) angiography as an intraoperative tool to measure optic chiasm perfusion and determine its relationship with postoperative visual function. METHODS: Videos of patients undergoing EES for resection of suprasellar lesions were reviewed, where 5 mg of ICG was diluted in 10 mL of saline and administered. Time between luminescence of the anterior cerebral artery and the superior hypophyseal artery branches supplying the optic chiasm was noted, and the percentage of optic chiasm vessels that luminesced was recorded. Postoperative examinations and imaging studies were used to assess visual function. Patients with and without new deficits were compared with examination of trends in ICG findings. RESULTS: A total of 7 trials were reviewed on 6 patients, with no complications occurring from ICG administration. Mean time to chiasm peak luminescence was 3.8 seconds, and 81.8% of chiasm vessels luminesced. Patients with stable or improved vision after resection demonstrated over 90% chiasm luminescence in every case, and mean chiasm time in these postresection ICG administrations was 4.0 seconds. One patient experienced new postoperative visual deficits; on review of their ICG administration, 11.5% of chiasm vessels luminesced, and the chiasm itself failed to display robust luminescence after 30 seconds of direct observation. CONCLUSION: This pilot study showed the capability of intraoperative ICG angiography to demonstrate perfusion of the optic chiasm during EES for resection of suprasellar lesions. While larger studies are required, preliminary results suggest chiasm times under 5 seconds and over 90% chiasm vessel illumination may reflect adequate chiasm perfusion, while those with delayed or absent chiasm luminescence may have compromised chiasm perfusion.

CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases.

Background: While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types. Methods: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence. Results: A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status. Conclusions: CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.

Risk Factors for Significant Postoperative Hemorrhage After Pituitary Neuroendocrine Tumor Resection: A Case-Control Study of 1066 Surgeries.

BACKGROUND: Postoperative hemorrhage is a rare but potentially serious complication after pituitary surgery. The risk factors for this complication are mostly unknown, and further knowledge would help guide postoperative management. OBJECTIVE: To investigate the perioperative risks and clinical presentation of significant postoperative hemorrhage (SPH) after endonasal surgery for pituitary neuroendocrine tumors. METHODS: A population of 1066 patients undergoing endonasal (microscopic and endoscopic) surgery for pituitary neuroendocrine tumor resection at a high-volume academic center was reviewed. SPH cases were defined as postoperative hematoma evident on imaging requiring return to the operating room for evacuation. Patient and tumor characteristics were analyzed with uni- and multivariable logistic regression, and postoperative courses were descriptively examined. RESULTS: Ten patients were found to have SPH. On univariable analysis, these cases were significantly more likely to present with apoplexy ( P = .004), have larger tumors ( P < .001), and lower gross total resection rates ( P = .019). A multivariate regression analysis showed that tumor size (odds ratio 1.94, P = .008) and apoplexy at presentation (odds ratio 6.00, P = .018) were significantly associated with higher odds of SPH. The most common symptoms for patients with SPH were vision deficits and headache, and the median time for symptom onset was 1 day after surgery. CONCLUSION: Larger tumor size and presentation with apoplexy were associated with clinically significant postoperative hemorrhage. Patients presenting with pituitary apoplexy are more likely to experience a significant postoperative hemorrhage and should be carefully monitored for headache and vision changes in the days after surgery.

Identification of risk factors associated with leptomeningeal disease after resection of brain metastases.

OBJECTIVE: Resection of brain metastases (BMs) may be associated with increased risk of leptomeningeal disease (LMD). This study examined rates and predictors of LMD, including imaging subtypes, in patients who underwent resection of a BM followed by postoperative radiation. METHODS: A retrospective, single-center study was conducted examining overall LMD, classic LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression, Cox proportional hazards, and random forest analyses were performed to identify risk factors associated with LMD. RESULTS: Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD, with 19 cases (8.8%) of cLMD and 28 cases (12.9%) of nLMD. Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from the date of LMD diagnosis compared with nLMD (median 2.4 vs 6.9 months, p = 0.02, log-rank test). Cox proportional hazards analysis identified cerebellar/insular/occipital location (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.73-6.11, p = 0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27-4.88, p = 0.008), and ventricle contact (HR 2.82, 95% CI 1.5-5.3, p = 0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an area under the receiver operating characteristic curve of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. CONCLUSIONS: Tumor location, absence of extracranial disease at the time of surgery, ventricle contact, and increased tumor volume were associated with LMD. Further work is needed to determine whether escalating therapies in patients at risk of LMD prevents disease dissemination.

Gender Diversity in Hand Surgery Leadership.

BACKGROUND: Diversity in leadership drives innovation; however, women are underrepresented in leadership positions across academic medicine. The aim of this study was to assess the current gender representation in hand surgery leadership positions. METHODS: This was a cross-sectional analysis of leaders in hand surgery. Leaders were defined as President, Board and Committee members of the American Society for Surgery of the Hand and the American Association for Hand Surgery, as well as hand surgery fellowship program directors and physician lead editors of peer-reviewed hand journals. The representation of women in leadership was compared to the percentage of female hand fellows over the same period. Years in practice, academic rank, additional degrees, h-index, m-index, National Institutes of Health (NIH) funding, publications, and citations were compared between male and female leaders. RESULTS: Twenty-nine of 213 leadership positions (13.6%) are held by women which is fewer than would be expected based on hand surgery fellowship composition. Female leaders were earlier in practice than their male counterparts (13.5 ± 5.7 versus 20.8 ± 11.1 years, P < .01). Women were more likely to hold position of assistant professor and less likely to be full professors (P < .05). There was no gender difference in NIH funding, h-index, m-index, publications, or citations. The greatest gender disparity was at the level of National Society President, which is a title held by only 2 women and 119 men. CONCLUSIONS: Gender disparities in hand surgery exist and are accentuated at the leadership level. Further work is needed to decrease leadership promotion disparities between men and women.

Hemorrhagic vestibular schwannoma: a case example of vestibular apoplexy syndrome. Illustrative case.

BACKGROUND: Acute intratumoral hemorrhage within a vestibular schwannoma, or vestibular apoplexy, is a rare condition. Unlike the typical insidious vestibulopathy typically caused by vestibular schwannoma growth, patients with vestibular apoplexy have an acute and severe presentation with nausea and emesis in addition to severe vertigo and hearing loss. Here, the authors present an illustrative case demonstrating this rare clinical condition and an operative video detailing the surgical management. OBSERVATIONS: A 76-year-old man presented to the emergency department with acute-onset dizziness, left-ear fullness, double vision, gait ataxia, emesis, and facial numbness. Imaging revealed a 2.8-cm hemorrhagic left cerebellopontine angle lesion extending into the left internal auditory canal, consistent with hemorrhagic vestibular schwannoma. The patient subsequently underwent a retrosigmoid craniotomy for resection of the hemorrhagic mass, and by 1 month after surgery, all his presenting symptoms had resolved, allowing his return to daily activities. LESSONS: Vestibular schwannomas typically present with decreased hearing and chronic vestibulopathy. Acute presentation should raise the suspicion for an apoplectic event, and surgical debulking may lead to improvement in most vestibular symptoms.

Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.

Comparison of Shunt Outcomes for Nonbacterial Infection Hydrocephalus with Common Hydrocephalus Etiologies: A Retrospective Case-Control Study.

BACKGROUND: Shunting is an established treatment for hydrocephalus, yet reports on shunt outcomes for nonbacterial infection (NBI) hydrocephalus are limited. Furthermore, comparison of mechanisms and rates of failure for shunted NBI hydrocephalus versus more typical etiologies remains undetermined. METHODS: Patients who underwent shunting for hydrocephalus at 2 centers (1995-2020) were included. Indications for shunting were grouped as "typical" (congenital, posthemorrhagic, normal pressure hydrocephalus, malignancy-related, trauma, and idiopathic) and NBI hydrocephalus (coccidioidomycosis, cryptococcosis, and neurocysticercosis). Rates of shunt malfunction were compared. RESULTS: There were 261 patients shunted for typical hydrocephalus (48.7% male; age = 50.7 ± 21.7) and 93 patients for NBI hydrocephalus (72.0% male; age = 41.8 ± 13.2). For patients with typical hydrocephalus, 29.5% required ≥1 shunt revision, compared with 64.5% with NBI hydrocephalus (P < 1E-5). Of those with malfunction, NBI shunts required more revision operations (median = 3.0; max = 21) than typical shunts (median = 2.0; max = 6; P < 0.05). The censored median time to shunt failure for NBI hydrocephalus was 26.9 months and was not reached for typical etiologies by 180 months. Multivariate analysis showed shunts for NBI hydrocephalus were significantly more likely to fail (hazard ratio = 2.25; 95% confidence interval = 1.58-3.19). A distal pseudocyst was implicated in 30.0% and 2.6% of shunt failures for NBI and typical hydrocephalus, respectively (P < 1E-5). Sixteen (26.7%) NBI shunt failures required revision to lower-resistance systems compared to 6 (7.8%) typical failures (P < 0.05). CONCLUSIONS: Shunts placed for hydrocephalus secondary to nonbacterial infections are complicated by significantly higher rates of malfunction. These patients are prone to develop distal abdominal pseudocysts and often require revision to low-resistance systems.