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Purpose: Lennox-Gastaut syndrome (LGS) is an epileptogenic disorder that arises in childhood and is typically characterized by multiple seizure types, slow spike-and-wave complexes on EEG and cognitive impairment. If medical treatment fails, patients can proceed to one of two palliative surgeries, vagus nerve stimulation (VNS) or corpus callosotomy (CC). Their relative seizure control rates in LGS have not been well studied. The purpose of this paper is to compare seizure reduction rates between VNS and CC in LGS using meta-analyses of published data.Methods: A systematic search of Pubmed, Ovidsp, and Cochrane was performed to find articles that met the following criteria: (1) prospective or retrospective study, (2) at least one patient diagnosed with Lennox-Gastaut syndrome, and (3) well-defined measure of seizure frequency reduction. Seizure reduction rates were divided into seizure subtypes, as well as total seizures, and categorized as 100%, >75%, and >50%. Patient groups were compared using chi-square tests for categorical variables and t-test for continuous measures. Pooled proportions with 95% confidence interval (95% CI) of seizure outcomes were estimated for total seizures and seizure subtypes using random effects methods.Results: 17 VNS and 9 CC studies met the criteria for inclusion. CC had a significantly better outcome than VNS for >50% atonic seizure reduction (80.0% [67.0-90.0%] vs. 54.1% [32.1-75.4%], p<0.05) and for >75% atonic seizure reduction (70.0% [48.05-87.0%] vs. 26.3% [5.8-54.7%], p<0.05). All other seizure types, as well as total number of seizures, showed no statistically significant difference between VNS and CC.Conclusions: CC may be more beneficial for LGS patients whose predominant disabling seizure type is atonic. For all other seizure types, VNS offers comparable rates to CC. [ABSTRACT FROM AUTHOR]

Abstract Background The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects. Methods A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies. Results A statistically significant difference in genotype frequency for the SLC6A4 intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for the DRD4 exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group. Conclusion An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder.

Objective: Our purpose was to describe our initial institutional experience using dedicated brain [18F]-Fluoroestradiol (FES) PET/CT or PET/MRI in the management of patients with estrogen-receptor-positive (ER+) breast cancer brain metastases (BCBM), and compare to [18F]-Fluorodeoxyglucose (FDG) PET and MRI., Materials & Methods: Patients with biopsy-proven ER+ disease and MRI findings of suspected new, progressive, or recurrent BCBM were included in this retrospective study. Clinical and demographic data were collected. Dedicated brain FES PET/CT or PET/MRI was performed for clinical purposes. Maximum standardized uptake value (SUV) in MRI-defined target lesions and SUV ratio (SUVR, referencing normal-appearing parenchyma) were obtained. Pathology and/or clinical and MRI follow-up data were used as gold standard to classify viable neoplasm versus post-radiotherapy (RT) sequelae. Mann-Whitney tests were performed to compare subgroups., Results: Seven patients met inclusion criteria. 15/16 (94 %) lesions classified as neoplasm were FES-positive. 4/4 (100 %) lesions classified as RT sequelae were FES-negative. Median tumor FES-SUVR were higher than median RT-sequelae FES-SUVR (6.0 (2.8-9.1) versus 0.5 (0.3-0.7), p < 0.01), and similarly, median tumor FES-SUV were higher than median RT-sequelae FES-SUV (4.8 (2.8-9.1) versus 0.6 (0.3-0.8), p < 0.01). Lesion-based analysis of FDG-SUV and -SUVR demonstrated a trend for higher FDG avidity in lesions characterized as neoplasm; however, this did not reach statistical significance., Conclusion: Dedicated FES brain PET represents a promising adjunct modality, noting limitations of small sample size, retrospective nature of our study, and the possibility of ER expression heterogeneity. Our findings merit future prospective clinical trials incorporating dedicated brain FES PET/CT and PET/MRI in the management of patients with ER-positive disease and BCBM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Papillary craniopharyngioma (PCP) is a rare type of tumor, comprising ∼20% of all craniopharyngioma (CP) cases. It is now recognized as a separate pathological entity from the adamantinomatous type. PCPs are benign tumors, classified as WHO grade 1, characterized by non-keratinizing squamous epithelium. They typically grow as solid and round papillomatous masses or as unilocular cysts with a cauliflower-like excrescence. PCPs primarily occur in adults (95%), with increased frequency in males (60%) and predominantly affect the hypothalamus. Over 80% of these tumors are located in the third ventricle, expanding either above an anatomically intact infundibulum (strictly third ventricle tumors) or within the infundibulo-tuberal region of the third ventricle floor. Clinical manifestations commonly include visual deficits and a wide range of psychiatric disturbances (45% of patients), such as memory deficits and odd behavior. MRI can identify up to 50% of PCPs by the presence of a basal duct-like recess. Surgical management is challenging, requiring complex approaches to the third ventricle and posing significant risk of hypothalamic injury. The endoscopic endonasal approach allows radical tumor resection and yields more favorable patient outcomes. Of intriguing pathogenesis, over 90% of PCPs harbor the somatic BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK/ERK) signaling pathway. A phase 2 clinical trial has demonstrated that PCPs respond well to BRAF/MEK inhibitors. This comprehensive review synthesizes information from a cohort of 560 well-described PCPs and 99 large CP series including PCP cases published from 1856-2023 and represents the most extensive collection of knowledge on PCPs to date., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach., Competing Interests: Declaration of competing interest The authors have no relevant financial interests in the manuscript and no other potential conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Developmental and Epileptic Encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, FGF13 were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because FGF13 is expressed in both excitatory and inhibitory neurons, FGF13 undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell type-specific conditional knockout mice. Interneuron-targeted deletion of Fgf13 led to perinatal mortality associated with extensive seizures and impaired the hippocampal inhibitory/excitatory balance while excitatory neuron-targeted deletion of Fgf13 caused no detectable seizures and no survival deficits. While best studied as a voltage-gated sodium channel (Na v ) regulator, we observed no effect of Fgf13 ablation in interneurons on Na v s but rather a marked reduction in K + channel currents. Re-expressing different Fgf13 splice isoforms could partially rescue deficits in interneuron excitability and restore K + channel current amplitude. These results enhance our understanding of the molecular mechanisms that drive the pathogenesis of Fgf13- related seizures and expand our understanding of FGF13 functions in different neuron subsets., Competing Interests: Conflicts of Interest. GSP is a scientific advisory board member for Tevard Biosciences. None of the other authors report any conflicts.

Sudden Unexpected Death in Epilepsy (SUDEP) poses a significant risk to life expectancy for individuals with epilepsy. Mechanistic insight, while incomplete, has advanced through clinical observational studies and animal models. Yet we lack preventative therapies, which will depend on understanding SUDEP mechanisms. Recurrent convulsive seizures are the major SUDEP risk factor. Cardiorespiratory dysfunction precedes SUDEP, but whether cardiac arrhythmias are major proximate culprits for SUDEP remains to be determined. Here, we highlight recent data from mouse models and clinical studies that provide increasing support for respiratory depression and decreasing evidence for tachyarrhythmia-induced SUDEP. Further, we review data from genetic and chemoconvulsant mouse models that have enabled a deeper understanding for how seizures initiated in the central nervous system propagate to the autonomic nervous system and drive seizure-induced respiratory depression and subsequent SUDEP, rather than supporting a proximate cardiac arrhythmia cause. Ongoing research will continue to identify predictive SUDEP biomarkers, improve animal models, and translate basic research into precision medicine approaches. Identifying and understanding the brainstem circuits vulnerable in seizure-induced apnea will enable therapeutic interventions, to enhance the quality of life and life expectancy for individuals with epilepsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery., Methods: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post-radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and progression-free survival (PFS) was evaluated using Cox regression., Results: Twenty-seven patients with 64 tumors (26% World Health Organization [WHO]-1, 41% WHO-2, 26% WHO-3, and 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT; mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (P < .0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort., Conclusions: DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post-radiosurgery. Lesion size decrease was statistically significant; however, it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery., Clinicaltrials.gov Identifier: NCT04081701., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20-µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cerebrospinal fluid (CSF) leaks may occur at the skull base or along the spinal column and can cause a variety of debilitating neurological symptoms for patients. Recognizing the potential presence of a CSF leak and then identifying its source are necessary for accurate diagnosis and definitive treatment. A standardized workflow can be followed for successful leak localization, which often requires several diagnostic studies, and for definitive leak treatment, which can range from minimally invasive, needle-based approaches to a variety of surgical corrections. This review paper provides an overview of epidemiology, pathophysiology, and diagnostic workup for CSF leaks and introduces available treatment options. An illustrative case of a skull base CSF leak demonstrating diagnosis and surgical correction is provided., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cerebrospinal fluid leak after endoscopic skull base surgery remains a significant complication. Several investigators have suggested Hydroset cranioplasty to reduce leak rates. We investigated our early experience with Hydroset and compared the rate of nasal complications and CSF leak rates with case-controlled historic controls., Methods: We queried a prospective database of patients undergoing first time endoscopic, endonasal resection of suprasellar meningiomas and craniopharyngiomas from 2015 to 2023. We compared cases closed with a gasket seal, Hydroset, and a nasoseptal flap with those closed with only a gasket seal and nasoseptal flap. Demographics, technical considerations and postoperative outcomes (SNOT-22) were compared., Results: Seventy patients met inclusion criteria, twenty patients in the Hydroset group (meningioma n = 12; craniopharyngioma n = 8) and 50 control patients (meningioma n = 25; craniopharyngioma n = 25). CSF diversion was used in fewer Hydroset patients (75%, 15/20) compared with control group (94%, 47/50; p = 0.02). CSF leak was less frequent in the Hydroset than the control group (5% versus 12%, p = 0.38). One Hydroset patient required delayed nasal debridement. SNOT-22 responses demonstrated no significant difference in sinonasal complaints between groups (Hydroset average SNOT-22 score 22.45, control average SNOT-22 score 25.90; p = 0.58)., Conclusions: We demonstrate that hydroxyapatite reconstruction leads to improved CSF leak control above that provided by the gasket-seal and nasoseptal flap, without significant associated morbidity as long as the cement is fully covered with vascularized tissue., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Purpose: WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 ( 68 Ga) DOTATATE PET/MR imaging., Materials and Methods: Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of ( 68 Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included. We stratified patients by de novo-versus-secondary-progressive status and evaluated the differences in the PET standard uptake value, molecular profiles, and clinical outcomes., Results: Patients met the inclusion criteria (secondary-progressive: 7/14; de novo: 7/14). The secondary-progressive cohort had a significantly higher per-patient number of surgeries (4.1 versus 1.6; P  = .011) and trended toward a higher number of radiation therapy courses (2.4 versus 1.6; P  = .23) and cumulative radiation therapy doses (106Gy versus 68.3Gy; P  = .31). The secondary-progressive cohort had a significantly lower progression-free survival compared with the de novo cohort (4.8 versus 37.7 months; P  = .004). Secondary-progressive tumors had distinct molecular pathology profiles with higher numbers of mutations (3.5 versus 1.2; P  = .024). Secondary-progressive tumors demonstrated higher PET standard uptake values (17.1 versus 12.4; P  = .0021)., Conclusions: Our study confirms prior work illustrating distinct clinical outcomes in secondary-progressive and de novo World Health Organization grade 3 meningiomas. Furthermore, our findings support ( 68 Ga) DOTATATE PET/MR imaging as a useful management strategy in World Health Organization grade 3 meningiomas and provide insight into meningioma biology, as well as clinical management implications., (© 2024 by American Journal of Neuroradiology.)

Imaging hemodynamic responses to interictal spikes holds promise for presurgical epilepsy evaluations. Understanding the hemodynamic response function is crucial for accurate interpretation. Prior interictal neurovascular coupling data primarily come from anesthetized animals, impacting reliability. We simultaneously monitored calcium fluctuations in excitatory neurons, hemodynamics, and local field potentials (LFP) during bicuculline-induced interictal events in both isoflurane-anesthetized and awake mice. Isoflurane significantly affected LFP amplitude but had little impact on the amplitude and area of the calcium signal. Anesthesia also dramatically blunted the amplitude and latency of the hemodynamic response, although not its area of spread. Cerebral blood volume change provided the best spatial estimation of excitatory neuronal activity in both states. Targeted silencing of the thalamus in awake mice failed to recapitulate the impact of anesthesia on hemodynamic responses suggesting that isoflurane's interruption of the thalamocortical loop did not contribute either to the dissociation between the LFP and the calcium signal nor to the alterations in interictal neurovascular coupling. The blood volume increase associated with interictal spikes represents a promising mapping signal in both the awake and anesthetized states., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pituitary adenomas are slow-growing, benign intracranial tumors that can be characterized as functional (hormone-producing) or non-functional (non-hormone producing). Symptoms therefore arise from either endocrinologic abnormalities or mass effect on surrounding structures resulting in symptoms such as visual impairment and headache. In the last two decades, technical innovations have shifted surgical resection of such adenomas to endoscopic endonasal approaches. In this review, we describe the evolving approach to pituitary adenomas in the modern endoscopic era, including preoperative multidisciplinary review, relevant surgical anatomy, and a description of the technical nuances of standard and expanded approaches to the anterior skull base., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: The endoscopic lateral transorbital approach (eLTOA) is a relatively new approach to the skull base that has only recently been applied in vivo in the management of complex skull base pathology. Most meningiomas removed with this approach have been in the spheno-orbital location. We present a series of select purely sphenoid wing and middle fossa meningiomas removed through eLTOA. The objective here was to describe the selection criteria and results of eLTOA for a subset of sphenoid wing and middle fossa meningiomas., Methods: This is a retrospective study based on a prospectively maintained database of consecutive cases of eLTOA operated on at our institution by the lead author. The cohort's clinical and radiographic characteristics and outcome are presented., Results: Five patients underwent eLTOA to remove 3 sphenoid wing and 2 middle fossa meningiomas. The mean tumor volume was 11.9 cm 3 . Gross total resection was achieved in all cases. There were no intraoperative complications. Postoperatively, there was one case of subretinal hemorrhage, which was corrected by open vitrectomy repair, and one case of cerebrospinal fluid leak, which resolved with lumbar drainage. Three patients presented with visual impairment, 1 improved, 1 remained stable, and 1 worsened, but returned to stable after vitrectomy repair. All patients have been free of disease at a median follow-up of 8.9 months., Conclusion: eLTOA provides a direct minimal access corridor to certain well-selected sphenoid wing and middle fossa meningiomas. eLTOA minimizes brain retraction and provides a high rate of gross total resection. Meningiomas appropriately selected based on size, type, and location of dural attachment, and the eLTOA is a safe, rapid, and highly effective procedure with acceptable morbidity., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: Olfactory groove meningiomas (OGMs) often require surgical removal. The introduction of recent keyhole approaches raises the question of whether these tumors may be better treated through a smaller cranial opening. One such approach, the supraorbital keyhole craniotomy, has never been compared with more traditional open transcranial approaches with regard to outcome. In this study, the authors compared clinical, radiographic, and functional quality of life (QOL) outcomes between the keyhole supraorbital approach (SOA) and traditional transcranial approach (TTA) for OGMs. They sought to examine the potential advantages and disadvantages of open/TTA versus keyhole SOA for the resection of OGMs in a relatively case-matched series of patients., Methods: A retrospective, single-institution review of 57 patients undergoing a keyhole SOA or larger traditional transcranial (frontotemporal, pterional, or bifrontal) craniotomy for newly diagnosed OGMs between 2005 and 2023 was performed. Extent of resection, olfaction, length of stay (LOS), radiographic volumetric assessment of postoperative vasogenic and cytotoxic edema, and QOL (using the Anterior Skull Base Questionnaire) were assessed., Results: Thirty-two SOA and 25 TTA patients were included. The mean EOR was not significantly different by approach (TTA: 99.1% vs SOA: 98.4%, p = 0.91). Olfaction was preserved or improved at similar rates (TTA: 47% vs SOA: 43%, p = 0.99). The mean LOS was significantly shorter for SOA patients (4.1 ± 2.8 days) than for TTA patients (9.4 ± 11.2 days) (p = 0.002). The authors found an association between an increase in postoperative FLAIR cerebral edema and TTA (p = 0.031). QOL as assessed by the ASQB at last follow-up did not differ significantly between groups (p = 0.74)., Conclusions: The keyhole SOA was associated with a statistically significant decrease in LOS and less postoperative edema relative to traditional open approaches.

Background and Objectives: Tuberculum sellae meningiomas are resected via an expanded endonasal (EEA) or transcranial approach (TCA). Which approach provides superior outcomes is debated. The Magill-McDermott (M-M) grading scale evaluating tumor size, optic canal invasion, and arterial involvement remains to be validated for outcome prediction. The objective of this study was to validate the M-M scale for predicting visual outcome, extent of resection (EOR), and recurrence, and to use propensity matching by M-M scale to determine whether visual outcome, EOR, or recurrence differ between EEA and TCA., Methods: Forty-site retrospective study of 947 patients undergoing tuberculum sellae meningiomas resection. Standard statistical methods and propensity matching were used., Results: The M-M scale predicted visual worsening (odds ratio [OR]/point: 1.22, 95% CI: 1.02-1.46, P = .0271) and gross total resection (GTR) (OR/point: 0.71, 95% CI: 0.62-0.81, P < .0001), but not recurrence ( P = .4695). The scale was simplified and validated in an independent cohort for predicting visual worsening (OR/point: 2.34, 95% CI: 1.33-4.14, P = .0032) and GTR (OR/point: 0.73, 95% CI: 0.57-0.93, P = .0127), but not recurrence ( P = .2572). In propensity-matched samples, there was no difference in visual worsening ( P = .8757) or recurrence ( P = .5678) between TCA and EEA, but GTR was more likely with TCA (OR: 1.49, 95% CI: 1.02-2.18, P = .0409). Matched patients with preoperative visual deficits who had an EEA were more likely to have visual improvement than those undergoing TCA (72.9% vs 58.4%, P = .0010) with equal rates of visual worsening (EEA 8.0% vs TCA 8.6%, P = .8018)., Conclusion: The refined M-M scale predicts visual worsening and EOR preoperatively. Preoperative visual deficits are more likely to improve after EEA; however, individual tumor features must be considered during nuanced approach selection by experienced neurosurgeons., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Objectives: Tuberculum sellae meningiomas (TSMs) can be resected through transcranial (TCA) or expanded endonasal approach (EEA). The objective of this study was to report TSM management trends and outcomes in a large multicenter cohort., Methods: This is a 40-site retrospective study using standard statistical methods., Results: In 947 cases, TCA was used 66.4% and EEA 33.6%. The median maximum diameter was 2.5 cm for TCA and 2.1 cm for EEA ( P < .0001). The median follow-up was 26 months. Gross total resection (GTR) was achieved in 70.2% and did not differ between EEA and TCA ( P = .5395). Vision was the same or better in 87.5%. Vision improved in 73.0% of EEA patients with preoperative visual deficits compared with 57.1% of TCA patients ( P < .0001). On multivariate analysis, a TCA (odds ratio [OR] 1.78, P = .0258) was associated with vision worsening, while GTR was protective (OR 0.37, P < .0001). GTR decreased with increased diameter (OR: 0.80 per cm, P = .0036) and preoperative visual deficits (OR 0.56, P = .0075). Mortality was 0.5%. Complications occurred in 23.9%. New unilateral or bilateral blindness occurred in 3.3% and 0.4%, respectively. The cerebrospinal fluid leak rate was 17.3% for EEA and 2.2% for TCA (OR 9.1, P < .0001). The recurrence rate was 10.9% (n = 103). Longer follow-up (OR 1.01 per month, P < .0001), World Health Organization II/III (OR 2.20, P = .0262), and GTR (OR: 0.33, P < .0001) were associated with recurrence. The recurrence rate after GTR was lower after EEA compared with TCA (OR 0.33, P = .0027)., Conclusion: EEA for appropriately selected TSM may lead to better visual outcomes and decreased recurrence rates after GTR, but cerebrospinal fluid leak rates are high, and longer follow-up is needed. Tumors were smaller in the EEA group, and follow-up was shorter, reflecting selection, and observation bias. Nevertheless, EEA may be superior to TCA for appropriately selected TSM., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Objectives: Surgical access to the cavernous sinus (CS) poses a unique challenge to the neurosurgeon given the concentration of delicate structures in the confines of a very small anatomic space. The lateral transorbital approach (LTOA) is a minimally invasive, keyhole approach that can provide direct access to the lateral CS., Methods: A retrospective review of CS lesions treated by a LTOA at a single institution was performed between 2020 and 2023. Patient indications, surgical outcomes, and complications are described., Results: Six patients underwent a LTOA for a variety of pathologies including a dermoid cyst, schwannoma, prolactinoma, craniopharyngioma, and solitary fibrous tumor. The goals of surgery (ie, drainage of cyst, debulking, and pathological diagnosis) were achieved in all cases. The mean extent of resection was 64.6% (±34%). Half of the patients with preoperative cranial neuropathies (n = 4) improved postoperatively. There were no new permanent cranial neuropathies. One patient had a vascular injury repaired endovascularly with no neurological deficits., Conclusion: The LTOA provides a minimal access corridor to the lateral CS. Careful case selection and reasonable goals of surgery are critical to successful outcome., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: Encephaloceles of the lateral sphenoid sinus are rare. Originally believed to be due to defects in a patent lateral craniopharyngeal canal (Sternberg canal), they are now thought to originate more commonly from idiopathic intracranial hypertension, not unlike encephaloceles elsewhere in the skull base. A new classification of these encephaloceles was recently introduced, which divided them in relation to the foramen rotundum. Whether this classification can be applied to a larger cohort from multiple institutions and whether it might be useful in predicting outcome is unknown. Thus, the authors' goal was to divide a multiinstitutional cohort of patients with lateral sphenoid encephaloceles into four subtypes to determine their incidence and any correlation with surgical outcome., Methods: A multicenter retrospective review of prospectively acquired databases was carried out across three institutions. Cases were categorized into one of four subtypes (type I, Sternberg canal; type II, medial to rotundum; type III, lateral to rotundum; and type IV, both medial and lateral with rotundum enlargement). Demographic and outcome metrics were collected. Kaplan-Meyer curves were used to determine the rate of recurrence after surgical repair., Results: A total of 49 patients (71% female) were included. The average BMI was 32.8. All encephaloceles fell within the classification scheme. Type III was the most common (71.4%), followed by type IV (16.3%), type II (10.2%), and type I (2%). Cases were repaired endonasally, via a transpterygoidal approach. Lumbar drains were placed in 78% of cases. A variety of materials was used for closure, with a nasoseptal flap used in 65%. After a mean follow-up of 47 months, there were 4 (8%) CSF leak recurrences, all in patients with type III or type IV leaks and all within 1 year of the first repair. Two leaks were fixed with ventriculoperitoneal shunt and reoperation, 1 with ventriculoperitoneal shunt only, and 1 with a lumbar drain only. Of 45 patients in whom detailed information was available, there were 12 (26.7%) with postoperative dry eye or facial numbness, with facial numbness occurring in type III or type IV defects only., Conclusions: Endoscopic endonasal repair of lateral sphenoid wing encephaloceles is highly successful, but repair may lead to dry eye or facial numbness. True Sternberg (type I) leaks were uncommon. Failures and facial numbness occurred only in patients with type III and type IV leaks.

Objective: The lateral transorbital approach (LTOA) is a relatively new minimal access skull base approach suited for addressing paramedian pathology of the anterior and middle fossa. The authors define target zones for this approach and describe a series of cases with detailed measurements of visual outcomes, including those obtained with exophthalmometry., Methods: The authors performed a retrospective analysis of a consecutive series of LTOA patients. Seven target zones were identified: 1) the orbit, 2) the lesser sphenoid wing and anterior clinoid, 3) the middle fossa, 4) the lateral wall of the cavernous sinus and Meckel's cave, 5) the infratemporal fossa, 6) the petrous apex, and 7) the anterior fossa. The authors used volumetric analyses of preoperative and postoperative MR and CT imaging data to calculate the volume of bone and tumor removed and to provide detailed ophthalmological, neurological, and cosmetic outcomes., Results: Of the 20 patients in this cohort, pathology was in zone 2 (n = 10), zone 4 (n = 6), zone 3 (n = 2), zone 1 (n = 1), and zone 5 (n = 1). Pathology was meningioma (n = 10), schwannoma (n = 2), metastasis (n = 2), epidermoid (n = 1), dermoid (n = 1), encephalocele (n = 1), adenoma (n = 1), glioblastoma (n = 1), and inflammatory lesion (n = 1). The goal was gross-total resection (GTR) in 9 patients, all of whom achieved GTR. Subtotal resection (STR) was the goal in 8 patients (5 spheno-orbital meningiomas, 1 giant cavernous sinus/Meckel's cave schwannoma, 1 cavernous sinus prolactinoma, and 1 cavernous sinus dermoid), 7 of whom achieved STR and 1 of whom achieved GTR. The goal was biopsy in 2 patient and repair of encephalocele in 1. Visual acuity was stable or improved in 18 patients and worse in 2. Transient early postoperative diplopia, ptosis, eyelid swelling, and peri-orbital numbness were common. All 9 patients with preoperative diplopia improved at their last follow-up. Seven of 8 patients with preoperative exophthalmos improved after surgery (average correction of 64%). There were no cases of clinically significant (> 2 mm) postoperative enophthalmos. The most frequent postoperative complaint was peri-orbital numbness (40%). There was 1 CSF leak. Most patients were satisfied with their ocular (84%-100% of patients provided positive satisfaction-related responses) and cosmetic (75%-100%) outcomes., Conclusions: The LTOA is a safe minimal access approach to a variety of paramedian anterior skull base pathologies in several locations. Early follow-up revealed excellent resolution of exophthalmos with little risk of clinically significant enophthalmos. Transient diplopia, ptosis, and peri-orbital numbness were common but improved. Careful case selection is critical to ensure good outcome.

Introduction  Pedicled nasoseptal flap (NSF) placement is a critical component of skull base reconstruction after endoscopic endonasal approaches (EEAs). The effectiveness of NSF reuse has not been thoroughly studied. Prior reports using flaps harvested at one center and reused at another may have technical variability bias. Methods  We identified patients who underwent both their initial and NSF-reused surgeries at Weill Cornell Medical College from 2004 to 2022 using a prospective database of all EEAs. Surgical pathology, intraoperative leak grade, use of cerebrospinal fluid (CSF) diversion and skull base coverage were examined. The primary outcome measure was occurrence of CSF leak. Results  Fourteen patients (six women, eight men) underwent 14 first time and 14 revision operations with median age of 36.6 years (interquartile range [IQR]: 23.9-61.3) at the time of the NSF reuse. The median interval between the first NSF use and reuse was 70.6 months (IQR: 16.6-87). Eight patients were operated on for pituitary adenoma. Nonadenomas included three craniopharyngiomas and one case each of epidermoid, ependymoma, and chordoma. There were 16 high-flow, 8 low-flow intraoperative leaks, and 4 with no leak. CSF diversion was used in 24 operations. There were three postoperative leaks, one after a first operation and two after NSF reuse. All postoperative CSF leaks, whether first or second operations, occurred in cases with both high-flow intraoperative CSF leak and incomplete NSF coverage ( p  = 0.006). Conclusion  NSF reuse is effective at preventing postoperative CSF leak. The primary predictors of leak are high-flow intraoperative leak and inadequate defect coverage with NSF, regardless of the operation number., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: The repair of lateral sphenoid sinus cerebrospinal fluid leaks is routinely accomplished through the use of the endonasal endoscopic approach (EEA) with a transpterygoidal extension. This approach can incur sinus morbidity, damage to the vidian, palatine and trigeminal nerves, and the contents of the pterygopalatine fossa, particularly if the encephalocele is lateral to the foramen rotundum (FR) and V2., Objective: To investigate the use of the lateral transorbital approach (LTOA) as an alternative approach for repair of lateral sphenoid sinus encephaloceles that avoids the potential morbidity of EEA., Methods: We performed cadaveric dissections of 2 specimens (4 sides) and present one of the first cases of a lateral sphenoid sinus encephalocele repair lateral to the FR in a patient through an ipsilateral LTOA., Results: We find that the LTOA provides a shorter distance to target compared with the EEA (56 vs 89.5 mm, P = .002). The LTOA field of view also affords excellent visualization of both the medial and lateral aspects of V2, whereas the EEA is less effective at exposing lateral to V2, even after sacrifice of the vidian nerve and maximal pterygopalatine fossa content retraction. We report a case of LTOA to repair a meningoencephalocele lateral to V2 in the sphenoid sinus., Conclusion: The LTOA to the foramen rotundum is a more direct approach that minimizes the morbidity associated with EEA to repair meningoencephaloceles both medial and lateral to foramen rotundum., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Chronically elevated intracranial pressure (ICP) seen in idiopathic intracranial hypertension (IIH) can cause the development of skull base encephaloceles and cerebrospinal fluid (CSF) leaks. Surgical repair and ventriculoperitoneal shunt (VPS) placement are mainstays of treatment. Venous sinus stenting (VSS) is a newly accepted treatment modality. The goal of this study was thus to determine if VSS can be used to treat symptoms and prevent recurrence after surgical encephalocele repair., Methods: Retrospective chart review of patients that had surgical repair of encephaloceles followed by VSS for symptomatic stenosis with elevated pressure gradient., Results: A total of 13 patients underwent a combined encephalocele repair and VSS. Seventy-two percent were female; 46% had headaches, 69% pulsatile tinnitus, and 92% CSF rhinorrhea or otorrhea. One had seizures. Mean lumbar opening pressure was 23.3 ± 2.6 cm H 2 O; the average sagittal-to-jugular pressure gradient was 12.7 ± 1.8 cmH 2 O and was elevated in all patients. Four patients had middle fossa craniotomy for repair of tegmen defect (one bilateral); one had a retrosigmoid craniotomy for repair of a sigmoid plate defect. Eight had an endoscopic endonasal repair for sphenoid or cribriform plate encephalocele. There were no VSS procedural complications or complications associated with dual antiplatelet therapy. One patient had meningitis after endoscopic repair that was treated with antibiotics. One patient had recurrence of both CSF leak and venous stenosis adjacent to the stent requiring repeat repair and VSS. There was no further recurrence., Conclusion: In patients with dural sinus stenosis and encephaloceles requiring repair, VSS can be performed safely within weeks of surgery for relief of symptoms, resolution of underlying pathology, and prevention of CSF leak recurrence., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: The pituitary gland has the fourth highest physiologic avidity of [68 Ga]-DOTATATE. In order to guide our understanding of [68 Ga]-DOTATATE PET in clinical contexts, accurate characterization of the normal pituitary gland is first required. This study aimed to characterize the normal pituitary gland using dedicated brain [68 Ga]-DOTATATE PET/MRI as a function of age and sex., Methods: A total of 95 patients with a normal pituitary gland underwent brain [68 Ga]-DOTATATE PET examinations for the purpose of diagnosing CNS SSTR2 positive tumors (mean age: 58.9, 73% female). Maximum SUV of the pituitary gland was obtained in each patient. SUV of superior sagittal sinus was obtained to calculate normalized SUV score (SUVR) of the gland. The anatomic size of the gland was collected as maximum sagittal height (MSH). Correlations with age and sex were analyzed., Results: The mean SUV and SUVR of the pituitary gland were 17.6 (range: 7-59.5, SD = 7.1) and 13.8 (range: 3.3-52.6, SD = 7.2), respectively. Older females had significantly higher SUV of the pituitary gland compared to younger females. When stratified by age and sex, both older and younger females had significantly higher pituitary SUV than older males. SUVR did not differ significantly by age or sex. MSH of the pituitary gland in younger females was significantly greater than in younger males at all age cutoffs., Conclusion: This study provides an empiric profiling of the physiological [68 Ga]-DOTATATE avidity of the pituitary gland. The findings suggest that SUV may vary by age and sex and can help guide the use of [68 Ga]-DOTATATE PET/MRI in clinical and research settings. Future studies can build on these findings to investigate further the relationship between pituitary biology and demographic factors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The most common presenting symptom in patients with both small and large Rathke cleft cysts (RCC) is headache (H/A). It is well established that patients with large RCC can have significant symptomatic improvement after cyst drainage. However, patients with small RCC (≤ 1 cm) are rarely operated on, even if they present with debilitating H/A. It is not well understood whether resection of these smaller RCCs can lead to durable H/A resolution., Methods: A retrospective search of our institutional database for sub-centimeter RCCs presenting with intractable H/A and treated with an endoscopic endonasal approach was carried out. A detailed H/A questionnaire as well as patient chart review was conducted to assess the long-term outcome of these patients after surgical intervention., Results: Ten consecutive patients with 11 endonasal surgeries met inclusion criteria. Eight responded to the questionnaire. The median cyst diameter was 6 mm (IQR 3-9). Median preoperative H/A duration was 12 months (range 2 months-15 years). H/As occurred on average for 20 days per month and all required analgesics for symptomatic control for more than 15 of these 20 days. Half of the patients also had to miss work because of H/A. Average preoperative H/A intensity was 8.7 (scale 0-10) compared with postoperative scores of 2.9 at one month, 1.6 at 3 months, and 0.9 at 1 year. There were no permanent endocrinological or other surgical complications. After a median follow-up of 2 years, one patient had radiographic and symptomatic recurrence which resolved after re-operation., Conclusions: Endoscopic fenestration of sub-centimeter RCCs provides a safe and durable treatment for patients with intractable H/A., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood., Methods: We injected bicuculline into the S1 barrel cortex and employed multisite local field potential and Thy-1 and parvalbumin (PV) cell mesoscopic calcium imaging during IISs to monitor excitatory and inhibitory cells in two monosynaptically connected nodes and one disynaptically connected node: ipsilateral secondary motor area (iM2), contralateral S1 (cS1), and contralateral secondary motor area (cM2). Node participation was analyzed with spike-triggered coactivity maps. Experiments were repeated with 4-aminopyridine as an epileptic agent., Results: We found that each IIS reverberated throughout the network, differentially recruiting both excitatory and inhibitory cells in all connected nodes. The strongest response was found in iM2. Paradoxically, node cM2, which was connected disynaptically to the focus, was recruited more intensely than node cS1, which was connected monosynaptically. The explanation for this effect could be found in node-specific excitatory/inhibitory (E/I) balance, as cS1 demonstrated greater PV inhibitory cell activation compared with cM2, where Thy-1 excitatory cells were more heavily recruited., Significance: Our data show that IISs spread noncontiguously by exploiting fiber pathways that connect nodes in a distributed network and that E/I balance plays a critical role in node recruitment. This multinodal IIS network model can be used to investigate cell-specific dynamics in the spatial propagation of epileptiform activity., (© 2023 International League Against Epilepsy.)

Background: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7%-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS., Aims: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy/fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy., Methods and Results: Patients ≥18-years-old with rHGG (WHO grade III and IV) receiving ICI + SBRT or ICI monotherapy between January 1, 2016 and January 1, 2019 were included. Adverse events, 6-month PFS and overall survival (OS) were assessed. Log-rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast-enhanced magnetic resonance perfusion metrics were performed. Twenty-one patients with rHGG (ICI + SBRT: 16; ICI: 5) were included. The ICI + SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3-5 AEs in the ICI + SBRT group, and four grade 1 and no grade 2-5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI + SBRT and ICI groups; median OS was 7 and 6 months among ICI + SBRT and ICI groups, respectively. There were significant differences in pre and posttreatment tumor volume in the cohort (12.35 vs. 20.51; p = .03), but not between treatment groups., Conclusions: In this heavily pretreated cohort, ICI with re-irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re-irradiation with ICI + SBRT in rHGG., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background and Purpose: While contrast-enhanced MR imaging is the criterion standard in meningioma diagnosis and treatment response assessment, gallium 68 Ga-DOTATATE PET/MR imaging has increasingly demonstrated utility in meningioma diagnosis and management. Integrating 68 Ga-DOTATATE PET/MR imaging in postsurgical radiation planning reduces the planning target volume and organ-at-risk dose. However, 68 Ga-DOTATATE PET/MR imaging is not widely implemented in clinical practice due to higher perceived costs. Our study analyzes the cost-effectiveness of 68 Ga-DOTATATE PET/MR imaging for postresection radiation therapy planning in patients with intermediate-risk meningioma., Materials and Methods: We developed a decision-analytical model based on both recommended guidelines on meningioma management and our institutional experience. Markov models were implemented to estimate quality-adjusted life-years (QALY). Cost-effectiveness analyses with willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were performed from a societal perspective. Sensitivity analyses were conducted to validate the results. Model input values were based on published literature., Results: The cost-effectiveness results demonstrated that 68 Ga-DOTATATE PET/MR imaging yields higher QALY (5.47 versus 5.05) at a higher cost ($404,260 versus $395,535) compared with MR imaging alone. The incremental cost-effectiveness ratio analysis determined that 68 Ga-DOTATATE PET/MR imaging is cost-effective at a willingness to pay of $50,000/QALY and $100,000/QALY. Furthermore, sensitivity analyses showed that 68 Ga-DOTATATE PET/MR imaging is cost-effective at $50,000/QALY ($100,000/QALY) for specificity and sensitivity values above 76% (58%) and 53% (44%), respectively., Conclusions: 68 Ga-DOTATATE PET/MR imaging as an adjunct imaging technique is cost-effective in postoperative treatment planning in patients with meningiomas. Most important, the model results show that the sensitivity and specificity cost-effective thresholds of 68 Ga-DOTATATE PET/MR imaging could be attained in clinical practice., (© 2023 by American Journal of Neuroradiology.)

Objective: Minimally invasive endoscope-assisted approaches to the anterior skull base offer an alternative to traditional open craniotomies. Given the restrictive operative corridor, appropriate case selection is critical for success. In this paper, the authors present the results of three different minimal access approaches to meningiomas of the anterior and middle fossae and examine the differences in the target areas considered appropriate for each approach, as well as the outcomes, to determine whether the surgical goals were achieved., Methods: A consecutive series of the endoscopic endonasal approach (EEA), supraorbital approach (SOA), or transorbital approach (TOA) for newly diagnosed meningiomas of the anterior and middle fossa skull base between 2007 and 2022 were examined. Probabilistic heat maps were created to display the distribution of tumor volumes for each approach. Gross-total resection (GTR), extent of resection, visual and olfactory outcomes, and postoperative complications were assessed., Results: Of 525 patients who had meningioma resection, 88 (16.7%) were included in this study. EEA was performed for planum sphenoidale and tuberculum sellae meningiomas (n = 44), SOA for olfactory groove and anterior clinoid meningiomas (n = 36), and TOA for spheno-orbital and middle fossa meningiomas (n = 8). The largest tumors were treated using SOA (mean volume 28 ± 29 cm3), followed by TOA (mean volume 10 ± 10 cm3) and EEA (mean volume 9 ± 8 cm3) (p = 0.024). Most cases (91%) were WHO grade I. GTR was achieved in 84% of patients (n = 74), which was similar to the rates for EEA (84%) and SOA (92%), but lower than that for TOA (50%) (p = 0.002), the latter attributable to spheno-orbital (GTR: 33%) not middle fossa (GTR: 100%) tumors. There were 7 (8%) CSF leaks: 5 (11%) from EEA, 1 (3%) from SOA, and 1 (13%) from TOA (p = 0.326). All resolved with lumbar drainage except for 1 EEA leak that required a reoperation., Conclusions: Minimally invasive approaches for anterior and middle fossa skull base meningiomas require careful case selection. GTR rates are equally high for all approaches except for spheno-orbital meningiomas, where alleviation of proptosis and not GTR is the primary goal of surgery. New anosmia was most common after EEA.

Background: The introduction of Cesium-131 (Cs-131) as a radiation source has led to a resurgence of brachytherapy for central nervous system (CNS) tumors. The aim of this study was to evaluate the safety and efficacy of the largest cohort of Cs-131 patients to-date., Methods: A retrospective review of all CNS tumors treated with resection and adjuvant Cs-131 brachytherapy at New York-Presbyterian/Weill Cornell from 2010 to 2021 was performed. Overall survival (OS) and local control (LC) were assessed with Kaplan-Meier methodology. Univariable analysis was conducted to identify patient factors associated with local recurrence or radiation necrosis., Results: Adjuvant Cs-131 brachytherapy following resection was performed in 119 patients with a median follow-up time of 11.8 (IQR 4.7-23.6) months and a mean of 22.3 +/-30.3 months. 1-year survival rates were 53.3% (95%CI 41.9-64.6%) for brain metastases (BrM), 45.9% (95%CI 24.8-67.0%) for gliomas, and 73.3% (95%CI 50.9-95.7%) for meningiomas. 1-year local control rates were 84.7% for BrM, 34.1% for gliomas, and 83.3% for meningiomas (p < 0.001). For BrM, local control was superior in NSCLC relative to other BrM pathologies (90.8% versus 76.5%, p = 0.039). Radiographic radiation necrosis (RN) was identified in 10 (8.4%) cases and demonstrated an association with smaller median tumor size (2.4 [IQR 1.8-2.7 cm] versus 3.1 [IQR 2.4-3.8 cm], p = 0.034). Wound complications occurred in 14 (11.8%) patients., Conclusions: Cs-131 brachytherapy demonstrated a favorable safety and efficacy profile characterized by high rates of local control for all treated pathologies. The concept of brachytherapy has seen a resurgence given the excellent results when Cs-131 is used as a source., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Purpose: This study seeks to expound upon risk factor etiologies for surgical site infection (SSI) and investigate their combinatorial effects on infection rate following craniotomy for neuro-oncologic pathology., Methods: Patients who underwent neuro-oncologic craniotomy between 2006 and 2020 were included. Medical records were reviewed to identify the occurrence of wound infection at ≤ 3 months postoperatively. Potential risk factors for infection included tumor pathology, location, anesthesia type, indication, ventricular entry, foreign body, brachytherapy, lumbar drain, prior operation, prior cranial radiation, prior infection, bevacizumab, and medical comorbidities (hypertension, obesity, diabetes, hyperlipidemia, other cancer, cirrhosis). Logistic regression was implemented to determine risk factors for SSI. Chi-square tests were used to assess whether the number of risk factors (e.g., 0, ≥ 1, ≥2, ≥ 3, ≥4) increases the risk of SSI compared to patients with fewer risk factors. The relative increase with each additional risk factor was also evaluated., Results: A total of 1209 patients were included. SSI occurred in 42 patients (3.5%) by 90 days after surgery. Significant risk factors on multivariate logistic regression were bevacizumab (OR 40.84; p < 0.001), cirrhosis (OR 14.20, p = 0.03), foreign body placement (OR 4.06; P < 0.0001), prior radiation (OR 2.20; p = 0.03), and prior operation (OR 1.92; p = 0.04). Infection rates in the combinatorial analysis were as follows: ≥1 risk factor = 5.9% (OR 2.74; p = 0.001), ≥ 2 = 6.7% (OR 2.28; p = 0.01), ≥ 3 = 19.0% (OR 6.5; p < 0.0001), ≥ 4 = 100% (OR 30.2; p < 0.0001)., Conclusions: Risk factors in aggregate incrementally increase the risk of postoperative SSI after craniotomy for tumor., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Adjuvant radiotherapy is often necessary following surgical resection of brain metastases to improve local tumor control and survival. Brachytherapy using cesium-131 offers a novel method for loco-regional radiotherapy. We reviewed the current literature reporting the use of cesium-131 brachytherapy for the treatment of brain metastases. Published studies and ongoing trials were reviewed to identify treatment protocols and clinical outcomes of cesium-131 brachytherapy for brain metastases. Cesium-131 brachytherapy was further compared to current outcomes for iodine-125 brachytherapy and stereotactic radiosurgery. Intraoperative brachytherapy allows patients to receive two treatment modalities in one setting while minimizing tumor cell repopulation. After initial interest, the use of iodine-125 brachytherapy has declined due to unfavorable rates of radiation necrosis without survival improvement. Recent data on intracavitary cesium-131 brachytherapy in brain metastases have demonstrated improved locoregional tumor control with low risks of radiation necrosis, with associated improvements in patients compliance and satisfaction. Cesium-131 isotope has a short half-life, delivers 90% of its dose within a month, shortens the time to initiation of systemic therapy compared to iodine-125 or external radiotherapy, and has an excellent radiation safety profile. Further analyses have demonstrated superior cost-effectiveness and quality-of-life improvement ratios of cesium-131 brachytherapy than adjuvant stereotactic radiosurgery. Cesium-131 brachytherapy is a safe and effective post-surgical treatment option for brain metastases with associated clinical and cost-effectiveness benefits in appropriately selected patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection of high-grade gliomas (HGG) increases the extent of resection (EOR) and progression-free survival. The headlamp/loupe combination has been introduced as a method of performing fluorescent-guided surgery. This study aims to understand the correlation between fluorescent intensity and histology and between residual fluorescence and radiographic EOR utilizing the headlamp/loupe device., Methods: Intraoperative samples resected using the headlamp/loupe device from 14 patients were labeled as PINK, VAGUE, or NEGATIVE depending on the degree of fluorescence. Histological assessment of microvascular proliferation, necrosis, and cell density was performed, and samples were classified as histologically consistent with glioblastoma (GBM), high-grade infiltrating glioma (HGIG), IG, or non-diagnostic (NDX). The presence of intraoperative residual fluorescence was compared to EOR on post-operative MRI., Results: There was a significant difference in cell density comparing PINK, VAGUE, and NEGATIVE specimens (ANOVA, p < 0.00001). The PPV of PINK for GBM or HGIG was 88.4% (38/43). The NPV of NEGATIVE for IG or NDX was 74.4% (29/39). The relationship between the degree of fluorescence determination and histological results was significant (X 2 (6 degrees of freedom, N = 101) = 42.57, p < 0.00001). The PPV of intraoperative GTR for post-operative GTR on MRI was 100%, while the NPV of intraoperative STR for post-operative STR on MRI was 60%., Conclusion: The headlamp/loupe device provides information about histology, cell density, and necrosis with similar PPV for tumor to the operative microscope. Safe complete resection of florescence has a PPV of 100% for radiographic GTR and should be the goal of surgery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)