Biological Insights and Radiation-Immuno-Oncology Developments in Primary and Secondary Brain Tumors.

Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient's survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation-immuno-oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients' survival.

DOTATATE PET/MR Imaging Differentiates Secondary-Progressive from de Novo World Health Organization Grade 3 Meningiomas.

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 (68Ga) 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 (68Ga) 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 (68Ga) 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.

neuroGPT-X: toward a clinic-ready large language model.

OBJECTIVE: The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to the management of vestibular schwannoma. Furthermore, another objective was to develop a chat-based platform incorporating in-text citations, references, and memory to enable accurate, relevant, and reliable information in real time. METHODS: The analysis involved 1) creating a data set through web scraping, 2) developing a chat-based platform called neuroGPT-X, 3) enlisting 8 expert neurosurgeons across international centers to independently create questions (n = 1) and to answer (n = 4) and evaluate responses (n = 3) while blinded, and 4) analyzing the evaluation results on the management of vestibular schwannoma. In the blinded phase, all answers were assessed for accuracy, coherence, relevance, thoroughness, speed, and overall rating. All experts were unblinded and provided their thoughts on the utility and limitations of the tool. In the unblinded phase, all neurosurgeons provided answers to a Likert scale survey and long-answer questions regarding the clinical utility, likelihood of use, and limitations of the tool. The tool was then evaluated on the basis of a set of 103 consensus statements on vestibular schwannoma care from the 8th Quadrennial International Conference on Vestibular Schwannoma. RESULTS: Responses from the naive and context-enriched Generative Pretrained Transformer (GPT) models were consistently rated not significantly different in terms of accuracy, coherence, relevance, thoroughness, and overall performance, and they were often rated significantly higher than expert responses. Both the naive and content-enriched GPT models provided faster responses to the standardized question set than expert neurosurgeon respondents (p < 0.01). The context-enriched GPT model agreed with 98 of the 103 (95%) consensus statements. Of interest, all expert surgeons expressed concerns about the reliability of GPT in accurately addressing the nuances and controversies surrounding the management of vestibular schwannoma. Furthermore, the authors developed neuroGPT-X, a chat-based platform designed to provide point-of-care clinical support and mitigate the limitations of human memory. neuroGPT-X incorporates features such as in-text citations and references to enable accurate, relevant, and reliable information in real time. CONCLUSIONS: The present study, with its subspecialist-level performance in generating written responses to complex neurosurgical problems for which evidence-based consensus for management is lacking, suggests that context-enriched LLMs show promise as a point-of-care medical resource. The authors anticipate that this work will be a springboard for expansion into more medical specialties, incorporating evidence-based clinical information and developing expert-level dialogue surrounding LLMs in healthcare.

A quantitative comparative surgical analysis of the endoscopic transorbital approach and frontotemporal-orbitozygomatic approach for extradural exposure of the cavernous sinus.

OBJECTIVE: Recently, the endoscopic superior eyelid transorbital approach (SETA) has emerged as a potential alternative to access the cavernous sinus (CS). Several previous studies have attempted to quantitatively compare the traditional open anterolateral skull base approaches with transorbital exposure; however, these comparisons have been limited to the area of exposure provided by the bone opening and trajectory, and fail to account for the main avenues of exposure provided by subsequent requisite surgical maneuvers. The authors quantitatively compare the surgical access provided by the frontotemporal-orbitozygomatic (FTOZ) approach and the SETA following applicable periclinoid surgical maneuvers, evaluate the surgical exposure of key structures in each, and discuss optimal approach selection. METHODS: SETA and FTOZ approaches were performed with subsequent applicable surgical maneuvers on 8 cadaveric heads. The lengths of exposure of cranial nerves (CNs) II-VI and the cavernous internal carotid artery; the areas of the space accessed within the supratrochlear, infratrochlear, and supramaxillary (anteromedial) triangles; the total area of exposure; and the angles of attack were measured and compared. RESULTS: Exposure of the extradural CS was comparable between approaches, whereas access was significantly greater in the FTOZ approach compared with the SETA. The lengths of extradural exposure of CN III, V1, V2, and V3 were comparable between approaches. The FTOZ approach provided marginally increased exposure of CNs IV (20.9 ± 2.36 mm vs 13.4 ± 3.97 mm, p = 0.023) and VI (14.1 ± 2.44 mm vs 9.22 ± 3.45 mm, p = 0.066). The FTOZ also provided significantly larger vertical (44.5° ± 6.15° vs 18.4° ± 1.65°, p = 0.002) and horizontal (41.5° ± 5.40° vs 15.3° ± 5.06°, p < 0.001) angles of attack, and thus significantly greater surgical freedom, and provided significantly greater access to the supratrochlear (p = 0.021) and infratrochlear (p = 0.007) triangles, and significantly greater exposure of the cavernous internal carotid artery (17.2 ± 1.70 mm vs 8.05 ± 2.37 mm, p = 0.001). Total area of exposure was also significantly larger in the FTOZ, which provided wide access to the lateral wall of the CS as well as the possibility for intradural access. CONCLUSIONS: This is the first study to quantitatively identify the relative advantages of the FTOZ and transorbital approaches at the target region following requisite surgical maneuvers. Understanding these data will aid in selecting an optimal approach and maneuver set based on target lesion size and location.

[Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas.

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 PFS was evaluated using Cox regression. RESULTS: 27 patients with 64 tumors (26% WHO-1, 41% WHO-2, 26% WHO-3, 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 < 0.0001). 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.

Trends in AVM-Associated Intracranial Hemorrhage in the United States, 2000-2019.

This cross-sectional study examines whether there has been a significant change in the annual incidence of arteriovenous malformation (AVM)­associated intracranial hemorrhage among US adults over the past 2 decades.

The complete anterior petrosectomy: an expanded extended-middle fossa approach with removal of the infratrigeminal petrous apex and drilling of the lateral clivus.

Intradural exposure in the extended middle fossa anterior transpetrosal approach is traditionally limited to the inferior petrosal sinus inferomedially. Expanding bone removal of the petrous apex around the petrous internal carotid artery (ICA), underneath the trigeminal ganglion/mandibular nerve, and into the lateral component of the clivus can significantly expand the limits of this approach beyond the inferior petrosal sinus and allows for exposure of the midline structures, aspects of the contralateral inferior clival region, and, when high riding, the vertebrobasilar junction. To date, no descriptive techniques for drilling into the lateral clivus in this approach have been published. The authors provide a detailed stepwise description of their complete anterior petrosectomy, in use at their institution, that involves skeletonization of the posteromedial petrous ICA, gentle elevation of the trigeminal ganglion/mandibular nerve, removal of the infratrigeminal petrous apex, and two techniques for drilling into the lateral clivus along the petroclival fissure. These techniques provide a direct and unobstructed corridor to the midpetroclival region and ventral brainstem with greater maneuverability and enhanced control of the midline structures, which is especially useful for resection of petroclival meningiomas, chondrosarcomas, and giant vascular lesions of the mid- and upper basilar artery and its proximal branches.

Quantitative analysis of external carotid artery bypass donor vessels by recipient and approach.

INTRODUCTION: Utilization an in-situ pedicle of the external carotid artery (ECA) as an arterial donor can allow for the successful augmentation or replacement of flow to a large vascular territory. We propose a mathematical model for quantitatively analyzing and grading the suitability of donor and recipient bypass vessels based on a set of anatomical and surgical variables in order to predict which pair has the greatest possibility for success. Using this method, we analyze all of the potential donor-recipient pairs for each ECA donor vessel-including the superficial temporal (STA), middle meningeal (MMA), and occipital (OA) arteries. METHODS: The ECA pedicles were dissected in frontotemporal, middle fossa, subtemporal, retrosigmoid, far lateral, suboccipital, supracerebellar, and occipital transtentorial approaches. For each approach, every potential donor-recipient pair was identified, and donor length and diameter were measured as well as depth of field, angle of exposure, ease of proximal control, maneuverability, and length and diameter of the recipient segment. Anastomotic pair scores were determined by adding the weighted donor and recipient. RESULTS: The best overall anastomotic pairs were OA-vertebral artery (V3, 17.1) and STA-insular (M2, 16.3) and STA-sylvian (M3, 15.9) segments of the middle cerebral artery. Other strong anastomotic combinations were OA- telovelotonsillar (15) and OA- tonsilomedullary (14.9) segments of the posterior inferior cerebellar artery, and MMA-lateral pontomesencephalic segment of the superior cerebellar artery (14.2). CONCLUSIONS: This novel model for anastamotic pair scoring can serve as a useful clinical tool for selecting the optimal donor, recipient, and approach combination that can help facilitate a successful bypass.

Affordability impacts therapeutic intensity of acute management of severe traumatic brain injury patients: An exploratory study in Tanzania.

Introduction: Quality health care in low and middle-income countries (LMICs) is constrained by financing of care. Research question: What is the effect of ability to pay on critical care management of patients with severe traumatic brain injury (sTBI)? Material and Methods: Data on sTBI patients admitted to a tertiary referral hospital in Dar-es-Salaam, Tanzania, were collected between 2016 and 2018, and included payor mechanisms for hospitalization costs. Patients were grouped as those who could afford care and those who were unable to pay. Results: Sixty-seven patients with sTBI were included. Of those enrolled, 44 (65.7%) were able to pay and 15 (22.3%) were unable to pay costs of care upfront. Eight (11.9%) patients did not have a documented source of payment (unknown identity or excluded from further analysis). Overall mechanical ventilation rates were 81% (n=36) in the affordable group and 100% (n=15) in the unaffordable group (p=0.08). Computed tomography (CT) rates were 71.6% (n=48) overall, 100% (n=44) and 0% respectively (p<0.01); Surgical rates were 16.4% (n=11) overall, 18.2% (n=8) vs. 13.3% (n=2) (p=0.67) respectively. Two-week mortality was 59.7% overall (n=40), 47.7% (n=21) in the affordable group and 73.3% (n=11) in the unaffordable group (p=0.09) (adjusted OR 0.4; 95% CI: 0.07-2.41, p=0.32). Discussion and Conclusion: Ability to pay appears to have a strong association with the use of head CT and a weak association with mechanical ventilation in the management of sTBI. Inability to pay increases redundant or sub-optimal care, and imposes a financial burden on patients and their relatives.

Safety and efficacy of Cesium-131 brachytherapy for brain tumors.

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.

Multidisciplinary management of carotid body tumors: a single-institution case series of 22 patients.

OBJECTIVE: Carotid body tumors (CBTs) are rare, slow-growing neoplasms derived from the parasympathetic paraganglia of the carotid bodies. Although inherently vascular lesions, the role of preoperative embolization prior to resection remains controversial. In this report, the authors describe an institutional series of patients with CBT successfully treated via resection following preoperative embolization and compare the results in this series to previously reported outcomes in the treatment of CBT. METHODS: All CBTs resected between 2013 and 2019 at a single institution were retrospectively identified. All patients had undergone preoperative embolization performed by interventional neuroradiologists, and all had been operated on by a combined team of cerebrovascular neurosurgeons and otolaryngology-head and neck surgeons. The clinical, radiographic, endovascular, and perioperative data were collected. All procedural complications were recorded. RESULTS: Among 22 patients with CBT, 63.6% were female and the median age was 55.5 years at the time of surgery. The most common presenting symptoms included a palpable neck mass (59.1%) and voice changes (22.7%). The average tumor volume was 15.01 ± 14.41 cm3. Most of the CBTs were Shamblin group 2 (95.5%). Blood was predominantly supplied from branches of the ascending pharyngeal artery, with an average of 2 vascular pedicles (range 1-4). Fifty percent of the tumors were embolized with more than one material: polyvinyl alcohol, 95.5%; Onyx, 50.0%; and N-butyl cyanoacrylate glue, 9.1%. The average reduction in tumor blush following embolization was 83% (range 40%-95%). No embolization procedural complications occurred. All resections were performed within 30 hours of embolization. The average operative time was 173.9 minutes, average estimated blood loss was 151.8 ml, and median length of hospital stay was 4 days. The rate of permanent postoperative complications was 0%; 2 patients experienced transient hoarseness, and 1 patient had medical complications related to alcohol withdrawal. CONCLUSIONS: This series reveals that endovascular embolization of CBT is a safe and effective technique for tumor devascularization, making preoperative angiography and embolization an important consideration in the management of CBT. Moreover, the successful management of CBT at the authors' institution rests on a multidisciplinary approach whereby endovascular surgeons, neurosurgeons, and ear, nose, and throat-head and neck surgeons work together to optimally manage each patient with CBT.

Tailored Surgical Access to the Cavernous Sinus and Parasellar Region: Assessment of Cavernous Sinus Entry Corridors and the Periclinoid and Pericavernous Surgical Maneuvers.

BACKGROUND: Lesions involving the cavernous sinus (CS) represent some of the most challenging pathologies of the skull base owing to the dense traversing and surrounding neurovasculature. Extradural exposure and preparation of this region, whether as initial preparation for a combined intra-extradural approach or as the main avenue of surgical exposure, can enlarge surgical corridors and minimize the need for brain retraction in this very confined space. We provide a detailed assessment of the entry corridors to the CS that are available within each approach, the surgical exposure and freedom provided by each of these corridors, and demonstrate how extradural and intradural preparation of these corridors can be used to widen the available working space and facilitate surgery. METHODS: Pterional, frontotemporal-orbital, frontotemporal-orbitozygomatic, frontotemporal-zygomatic, perilabyrinthine transtentorial, and endoscopic transnasal transsphenoidal approaches were performed on cadaveric heads to access the perisellar and CS regions. Periclinoid maneuvers (extradural cutting of the meningo-orbital band, anterior clinoidectomy, unroofing of the optic canal, opening of the superior orbital fissure, displacement of the extra-annular structures, opening of the annulus of Zinn, and interdural dissection), pericavernous maneuvers (intradural cutting of the distal dural ring, mobilization of the supraclinoid internal carotid artery, opening of the oculomotor porus, and mobilization of cranial nerve (CN) III), peritrigeminal extensions (extradural mobilization of CN V2 [maxillary] and/or V3 [mandibular]), and other surgical maneuvers were performed and evaluated. The CS was divided into 8 anatomical compartments and 9 entry corridors were described, and exposure and freedom were assessed accordingly. RESULTS: Intradurally, the standard unextended pterional, frontotemporal-orbital, and frontotemporal orbitozygomatic transsylvian approaches provided access solely to the parasellar entry corridor into the superior wall of the CS. Expanding these approaches with extradural periclinoid maneuvers allowed for subsequent application of the intradural pericavernous maneuvers and enlargement of the parasellar corridor and exposure of the carotid cave. Extradurally, the frontotemporal-orbital approach could be expanded via application of periclinoid maneuvers, which provided access to the anterior portions of the main lateral wall entry corridors. The frontotemporal-orbitozygomatic approach could also be expanded with periclinoid maneuvers to provide extradural access to all 6 lateral wall entry corridors. The extradural frontotemporal-zygomatic approach only provided exposure following interdural dissection, which allowed for access to the inferolateral entry corridors into the lateral wall. Extradural peritrigeminal extension in the frontotemporal-orbitozygomatic and frontotemporal-zygomatic approaches allows for enlargement of the supramaxillary and pre- and postmandibular corridors. The perilabyrinthine approach to the posterior wall was enlarged with opening of Dorello's canal and the endoscopic transnasal transsphenoidal approach was enlarged with opening of the optic canal. CONCLUSIONS: Targeted extradural preparation optimizes exposure and significantly improves access to deep-seated targets by enhancing surgical maneuverability through the unlocking of neurovascular structures and widening of surgical corridors without the need for additional brain retraction.

A novel 3D surgical neuroanatomy course for medical students: Outcomes from a pilot 6-week elective.

BACKGROUND: Developing and maintaining a three-dimensional working knowledge of neuroanatomy is an essential skill in neurosurgery. However, conventional 2D head, neck, and neuroanatomy education is typically characterized by the separate rote learning of constituent tissues and often fails to provide learners with a contextual understanding of the relationships between these highly complex and interconnected structures. This can pose a significant challenge to medical students entering neurosurgery who lack a topographic understanding of intracranial anatomy. METHODS: We report on the design and efficacy of a novel 6-part 3D surgical neuroanatomy pilot elective for medical students that utilized a navigation-based pedagogical technique with the goal of providing students with a framework for developing a 3D mental map of the skull base, neurovasculature, ventricular system, and associated brain regions. Students took on the perspective of physically traveling along the paths of key structures with a 360-degree view of surrounding anatomy such that they could appreciate the integration and relative spatial relationships of the varying tissues within the cranium. Mental navigation exercises and pre- and post-course surveys were used to assess students' baseline and learned familiarity with the different anatomical regions covered. RESULTS: At the conclusion of the course, all students were able to successfully complete all of the multifaceted mental navigation exercises. Post-course survey data indicated that respondents perceived significant increases in their knowledge of cranial nerves; anterior, middle, and posterior skull base anatomy; anterior and posterior cranial circulation; and the ventricular system. CONCLUSION: 3D navigation-based fly-through instruction is a novel and effective technique for teaching complex anatomy and can provide learners with the foundational skills for developing and maintaining a 3D mental map of intracranial anatomy.

Intracranial Venous Alteration in Patients With Aneurysmal Subarachnoid Hemorrhage: Protocol for the Prospective and Observational SAH Multicenter Study (SMS).

Background: Arterial vasospasm has been ascribed as the responsible etiology of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (aSAH), but other neurovascular structures may be involved. We present the protocol for a multicenter, prospective, observational study focused on analyzing morphological changes in cerebral veins of patients with aSAH. Methods and Analysis: In a retrospective arm, we will collect head arterial and venous CT angiograms (CTA) of 50 patients with aSAH and 50 matching healthy controls at days 0-2 and 7-10, comparing morphological venous changes. A multicenter prospective observational study will follow. Patients aged ≥18 years of any gender with aSAH will be enrolled at 9 participating centers based on the predetermined eligibility criteria. A sample size of 52 aSAH patients is expected, and 52 healthy controls matched per age, gender, and comorbidities will be identified. For each patient, sequential CTA will be conducted upon admission (day 0-2), at 7-10 days, and at 14-21 days after aSAH, evaluating volumes and morphology of the cerebral deep veins and main cortical veins. One specialized image collecting center will analyze all anonymized CTA scans, performing volumetric calculation of targeted veins. Morphological venous changes over time will be evaluated using the Dice coefficient and the Jaccard index and scored using the Boeckh-Behrens system. Morphological venous changes will be correlated to clinical outcomes and compared between patients with aSAH and healthy-controls, and among groups based on surgical/endovascular treatments for aSAH. Ethics and Dissemination: This protocol has been approved by the ethics committee and institutional review board of Ethikkommission, SALK, Salzburg, Austria, and will be approved at all participating sites. The study will comply with the Declaration of Helsinki. Written informed consent will be obtained from all enrolled patients or their legal tutors. We will present our findings at academic conferences and peer-reviewed journals. Approved Protocol Version and Registration: Version 2, 09 June 2021.

Familial colloid cysts: not a chance occurrence.

PURPOSE: Colloid cysts are rare, benign brain tumors of the third ventricle with an estimated population prevalence of 1 in 5800. Sudden deterioration and death secondary to obstructive hydrocephalus are well-described presentations in patients with a colloid cyst. Although historically conceptualized as driven by sporadic genetic events, a growing body of literature supports the possibility of an inherited predisposition. METHODS: A prospective registry of patients with colloid cysts was maintained between 1996 and 2021. Data pertaining to a family history of colloid cyst was collected retrospectively; self-reporting was validated in each case by medical record or imaging review. Frequency of patients with a documented first-degree family member with a colloid cyst based on self-reporting was calculated. The rate of familial co-occurrence within our series was then compared to a systematic literature review and aggregation of familial case studies, as well as population-based prevalence rates of sporadic colloid cysts. RESULTS: Thirteen cases with affected first-degree relatives were identified in our series. Of the entire cohort, 19/26 were symptomatic from the lesion (73%), 12/26 (46.2%) underwent resection, and 2/26 (7.7%) had sudden death from presumed obstructive hydrocephalus. The majority of transmission patterns were between mother and child (9/13). Compared with the estimated prevalence of colloid cysts, our FCC rate of 13 cases in 383 (3.4%) estimates a greater-than-chance rate of co-occurrence. CONCLUSION: Systematic screening for FCCs may facilitate early recognition and treatment of indolent cysts, thereby preventing the rapid deterioration that can occur with an unrecognized third ventricular tumor. Furthermore, identifying a transmission pattern may yield more insight into the molecular and genetic underpinnings of colloid cysts.

Stereotactic radiosurgery for vestibular schwannomas in neurofibromatosis type 2 patients: a systematic review and meta-analysis.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is characterized by often bilateral vestibular schwannomas (VS) that result in progressive hearing loss and compression of nearby brainstem structures causing cranial nerve palsies. Treatment of these tumors remains challenging, as both surgical removal and expectant management can result in symptom progression. Stereotactic radiosurgery (SRS) has been investigated for the management of NF2-associated VS; however, the role, promises, and pitfalls of this treatment modality remain unclear. METHODS: Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Reviews were searched for studies assessing SRS outcome in NF2-associated VS only. Primary endpoints included tumor control, serviceable hearing, presence of tinnitus, and cranial nerve V and VII symptoms. RESULTS: A total of 16 studies (589 patients harboring 750 tumors) were analyzed. Clinical tumor control was achieved in 88% of cases (95% CI 80-95%); salvage surgery was needed in 8% (95% CI 4-13%) of cases. Treatment resulted in a worsening of pre-treatment serviceable hearing (OR = 0.26, p < 0.01), increased facial nerve (OR = 1.62, p < 0.01) and trigeminal nerve (OR = 1.42, p = 0.07) impairment. The incidence of vestibular symptoms and hydrocephalus were not consistently reported and thus could not be assessed. CONCLUSIONS: The treatment of NF2-associated VS continues to pose a challenge, as current SRS regimens result in impaired hearing and worse cranial nerve comorbidities, despite achieving high tumor control. It remains unclear if these findings have to be regarded as treatment complications or, rather, continued disease progression.

Transseptal interforniceal endoscopic removal of superiorly recessed colloid cysts.

OBJECTIVE: Transforaminal endoscopic colloid cyst resection is well described. However, some anatomical colloid cyst variants may warrant a modified approach. Rarely, colloid cysts separate the forniceal columns and grow superiorly within the leaflets of the septum pellucidum. Thus, the authors' goal was to characterize the imaging features, clinical presentation, surgical strategy, and outcomes of patients with this superiorly recessed colloid cyst variant. METHODS: A retrospective evaluation of patients who underwent endoscopic resection of colloid cysts from 1999 to 2020 was performed. The patients were dichotomized depending on whether the cyst was located predominately below the forniceal columns or was superiorly recessed (forniceal column separation with variable intraseptal extension). This comparative cohort study focused on clinical presentation, imaging features, operative technique, and patient outcome. RESULTS: In total, 182 patients were identified. Seventeen patients had colloid cysts that were defined as superiorly recessed and underwent transseptal interforniceal removal, and 165 patients underwent a standard transforaminal approach. Patients had similar demographic characteristics. However, transseptal cysts were on average larger (17.8 mm vs 11.4 mm, p < 0.0001), and these patients had a greater frontal-occipital horn ratio (0.45 vs 0.41, p = 0.012). They were also more likely to have undergone a previous resection (p = 0.02). The two cohorts had similar surgical outcomes, with no differences in extent of resection, recurrence, or complications. CONCLUSIONS: Superiorly recessed intraseptal colloid cysts are larger and tend to splay the bodies of the fornix, thus requiring a parasagittal transseptal interforniceal endoscopic approach. This achieves complete removal with comparatively negligible morbidity or rare recurrence (5.9%).

Corticothalamic Connectivity in Aneurysmal Subarachnoid Hemorrhage: Relationship with Disordered Consciousness and Clinical Outcomes.

BACKGROUND: We present an exploratory analysis of the occurrence of early corticothalamic connectivity disruption after aneurysmal subarachnoid hemorrhage (SAH) and its correlation with clinical outcomes. METHODS: We conducted a retrospective study of patients with acute SAH who underwent continuous electroencephalography (EEG) for impairment of consciousness. Only patients undergoing endovascular aneurysm treatment were included. Continuous EEG tracings were reviewed to obtain artifact-free segments. Power spectral analyses were performed, and segments were classified as A (only delta power), B (predominant delta and theta), C (predominant theta and beta), or D (predominant alpha and beta). Each incremental category from A to D implies greater preservation of corticothalamic connectivity. We dichotomized categories as AB for poor connectivity and CD for good connectivity. The modified Rankin Scale score at follow-up and in-hospital mortality were used as outcome measures. RESULTS: Sixty-nine patients were included, of whom 58 had good quality EEG segments for classification: 28 were AB and 30 were CD. Hunt and Hess and World Federation of Neurological Surgeons grades were higher and the initial Glasgow Coma Scale score was lower in the AB group compared with the CD group. AB classification was associated with an adjusted odds ratio of 5.71 (95% confidence interval 1.61-20.30; p < 0.01) for poor outcome (modified Rankin Scale score 4-6) at a median follow-up of 4 months (interquartile range 2-6) and an odds ratio of 5.6 (95% confidence interval 0.98-31.95; p = 0.03) for in-hospital mortality, compared with CD. CONCLUSIONS: EEG spectral-power-based classification demonstrates early corticothalamic connectivity disruption following aneurysmal SAH and may be a mechanism involved in early brain injury. Furthermore, the extent of this disruption appears to be associated with functional outcome and in-hospital mortality in patients with aneurysmal SAH and appears to be a potentially useful predictive tool that must be validated prospectively.

Outcomes following upfront radiation versus monitoring in atypical meningiomas: 16-year experience at a tertiary medical center.

BACKGROUND: The role of postoperative upfront radiotherapy (RT) in the management of gross totally resected atypical meningiomas remains unclear. This single-center retrospective review of newly diagnosed histologically confirmed cases of World Health Organization (WHO) Grade II atypical meningioma at Weill Cornell Medicine from 2004 to 2020 aims to compare overall survival (OS) and progression-free survival (PFS) of postoperative upfront RT versus observation, stratified by resection status (gross total resection [GTR] vs subtotal resection [STR]). METHODS: Ninety cases of atypical meningioma were reviewed (56% women; median age 61 years; median follow-up 41 months). RESULTS: In patients with GTR, hazard ratio (HR) of PFS was 0.09 for postoperative upfront RT versus observation alone (95% confidence interval [CI] 0.01-0.68; P = .02), though HR for OS was not significant (HR 0.46; 95% CI 0.05-4.45; P = .5). With RT, PFS was 100% at 12 and 36 months (compared to 84% and 63%, respectively, with observation); OS at 36 months (OS36) was 100% (compared to 94% with observation). In patients with STR, though PFS at 36 months was higher for RT arm versus observation (84% vs 74%), OS36 was 100% in both arms. HR was not significant (HR 0.76; 95% CI 0.16-3.5; P = .73). CONCLUSIONS: This retrospective study suggests postoperative upfront RT following GTR of atypical meningioma is associated with improved PFS compared to observation. Further studies are required to draw conclusions about OS.

Efficacy and comorbidities of hypofractionated and single-dose radiosurgery for vestibular schwannomas: a systematic review and meta-analysis.

BACKGROUND: Vestibular schwannomas (VS) are tumors of the cerebellopontine angle with significant morbidity, causing hearing loss, tinnitus, and trigeminal and facial nerve compromise. An effective alternative to microsurgical resection is stereotactic radiosurgery (SRS), which can be delivered in either single-fraction (SRS) or hypofractionated stereotactic radiotherapy (hSRT) (3-5 treatments) regimens. It remains unclear which fractionation regimen provides superior outcomes. METHODS: Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Reviews were searched for studies either comparing hSRT with SRS or focusing on hSRT alone in treating VS. Primary endpoints included tumor control, serviceable hearing, tinnitus, and cranial nerve V and VII symptoms. A random-effects analysis was employed to compare pre- and post-treatment effects (hSRT alone) or SRS and hSRT outcomes (two-arm studies). RESULTS: This analysis included 21 studies focusing on hSRT alone and 13 studies comparing SRS and hSRT. Significant heterogeneity was observed. Overall, when hSRT was analyzed alone, crude tumor control was achieved in 94% (95% CI: 88%, 99%) of 1571 patients. There was no difference between pre- and post-treatment odds ratios (OR) of tinnitus, facial, or trigeminal impairment. Serviceable hearing was diminished following hSRT (OR = 0.60, 95% CI: 0.44, 0.83). Comparison with SRS showed no difference with respect to tumor control, serviceable hearing, trigeminal or facial nerve impairment. CONCLUSIONS: hSRT achieved excellent tumor control and, with the exception of serviceable hearing, did not result in worse post-treatment cranial nerve symptomatology. Analysis of comparative studies between hSRT and SRS did not reveal any significant difference in either tumor control or treatment morbidities.