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.

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.

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.

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.

Differences in Admission Blood Pressure Among Causes of Intracerebral Hemorrhage.

Background and Purpose- It is unknown whether admission systolic blood pressure (SBP) differs among causes of intracerebral hemorrhage (ICH). We sought to elucidate an association between admission BP and ICH cause. Methods- We compared admission SBP across ICH causes among patients in the Cornell Acute Stroke Academic Registry, which includes all adults with ICH at our center from 2011 through 2017. Trained analysts prospectively collected demographics, comorbidities, and admission SBP, defined as the first recorded value in the emergency department or on transfer from another hospital. ICH cause was adjudicated by a panel of neurologists using the SMASH-U criteria. We used ANOVA to compare mean admission SBP among ICH causes. We used multiple linear regression to adjust for age, sex, race, Glasgow Coma Scale score, and hematoma size. In secondary analyses, we compared hourly SBP measurements during the first 72 hours after admission, using mixed-effects linear models adjusted for the covariates above plus antihypertensive agents. Results- Among 484 patients with ICH, admission SBP varied significantly across ICH causes, ranging from 138 (±24) mm Hg in those with structural vascular lesions to 167 (±35) mm Hg in those with hypertensive ICH (P<0.001). The mean admission SBP in hypertensive ICH was 17 (95% CI, 11-24) mm Hg higher than in ICH of all other causes combined. These differences remained significant after adjustment for age, sex, race, Glasgow Coma Scale score, and hematoma size (P<0.001), and this persisted throughout the first 72 hours of hospitalization (P<0.001). Conclusions- In a single-center ICH registry, SBP varied significantly among ICH causes, both on admission and during hospitalization. Our results suggest that BP in the acute post-ICH setting is at least partly associated with ICH cause rather than simply representing a physiological reaction to the ICH itself.

Non-Traumatic Subdural Hemorrhage and Risk of Arterial Ischemic Events.

Background and Purpose- The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods- We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease, and venous thromboembolism). Results- Among 1.7 million Medicare beneficiaries, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients' risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9-5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients' risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1-7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2-1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions- Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.

Dynamic contrast-enhanced magnetic resonance imaging perfusion characteristics in meningiomas treated with resection and adjuvant radiosurgery.

OBJECTIVEThere is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.METHODSA retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (vp), extracellular volume (ve), volume transfer constant (Ktrans), rate constant (kep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.RESULTSThe mean patient age was 64 years (range 49-86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21-27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median vp (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec-1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between ve and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between Ktrans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).CONCLUSIONSThis study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.

Association of Seizure Occurrence with Aneurysm Treatment Modality in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Data on new-onset seizures after treatment of aneurysmal subarachnoid hemorrhage (aSAH) patients are limited and variable. We examined the association between new-onset seizures after aSAH and aneurysm treatment modality, as well their relationship with initial clinical severity of aSAH and outcomes. METHODS: This is a retrospective cohort study of all aSAH patients admitted to our institution over a 6-year period. 'Seizures' were defined as any observed clinical seizure or electrographic seizure on continuous electroencephalogram (cEEG) recordings, as determined by the reviewing neurophysiologist. Subgroup analyses were performed in low-grade (Hunt-Hess 1-3) and high-grade (Hunt-Hess 4-5) patients. Outcomes measures were Glasgow Coma Score (GCS) at intensive care unit (ICU) discharge and modified Rankin Scale (mRS) at outpatient follow-up. RESULTS: There were 282 patients with aSAH; 203 (72.0%) suffered low-grade and 79 (28%) high-grade aSAH. Patients were treated with endovascular coiling (N = 194, 68.8%) or surgical clipping (N = 66, 23.4%). Eighteen (6.4%) patients had seizures, of whom 10 (5.5%) had aneurysm coiling and 7 (10.6%) underwent clipping (p = 0.15). In low-grade patients, seizures occurred less frequently (p = 0.016) and were more common after surgical clipping (p = 0.0089). Seizures correlated with lower GCS upon ICU discharge (p < 0.001), in clipped (p = 0.011) and coiled (p < 0.001) patients and in low-grade aSAH (p < 0.001). Seizures correlated with higher mRS on follow-up (p < 0.001), in clipped (p = 0.032) and coiled (p = 0.004) patients and in low-grade aSAH (p = 0.003). CONCLUSIONS: New-onset seizures after aSAH occurred infrequently, and their incidence after aneurysm clipping versus coiling was not significantly different. However, in low-grade patients, new seizures were more frequently associated with clipping than coiling. Additionally, non-convulsive seizures did not occur in low-grade patients treated with coiling. These findings may explain, in part, previous work suggesting better outcomes in coiled patients and encourage physicians to have a lower threshold for cEEG utilization in low-grade patients suspected to have acute seizures after surgical clipping.

Neurocognitive function and quality of life in patients with newly diagnosed brain metastasis after treatment with intra-operative cesium-131 brachytherapy: a prospective trial.

Intraoperative permanent Cesium-131 (Cs-131) brachytherapy can provide a viable alternative to WBRT with excellent response rates and minimal toxicity. This study reports the results of the prospective trial of the impact of intraoperative Cs-131 on neurocognitive function and quality of life (QoL) in patients with resected brain metastases. Between 2010 and 2012, 24 patients with newly diagnosed metastasis to the brain were accrued on a prospective protocol and treated with Cs-131 brachytherapy seeds after surgical resection. Physicians administered the mini-mental status examination (MMSE) and functional assessment of cancer therapy-brain (FACT-Br) questionnaire to all patients before treatment and again every 2 months for the duration of 6 months with additional follow-up again at 12 months. Wilcoxon rank sum test was used to analyze statistically significant changes in MMSE over time and paired t test was used to analyze changes in FACT-BR. There was a statistical improvement in overall FACT-BR score at 4 and 6 months of follow-up when compared to baseline (162 vs. 143, P = 0.004; 164 vs. 143, P = 0.005 respectively) with a non-significant trend toward improvement at 2 and 12 months (154 vs. 143, P = 0.067; 159 vs. 149, P = 0.4). MMSE score was statistically improved at 4 and up to 12 months compared to pre-treatment MMSE (30 vs. 29, P = 0.017; 30 vs. 29, P = 0.001 respectively). Patients with brain metastasis who received intra-operative permanent Cs-131 brachytherapy implants saw an improvement of their neurocognitive status and self-assessment of QoL. In addition to the excellent local control of metastasis, this approach may contribute to the improvements in cognitive function and QOL.

Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the incidence of wound complications in previously-operated patients treated with bevacizumab (Avastin®) and radiation.

Neurosurgical craniotomy, craniectomy, or other trans-galeal interventions are performed for a variety of indications, including the resection of benign or malignant tumors, hematoma evacuation, and for the management of intractable seizure disorders. Despite an overall low complication rate of intervention, wound healing complications such as dehiscence, surgical site infection, and cerebrospinal fluid leak are not uncommon. A retrospective review was performed of all patients who underwent scalp incision closure at a single institution by a single plastic surgeon between 2006 and 2013. Sixty patients (83 procedures) were included in the study. Fifty-seven patients (95.0 %) underwent previous craniotomy, craniectomy, or other trans-galeal procedure. Of the total 60 patients, 35 patients received preoperative radiation. Sixteen patients received bevacizumab prior to their index case, while 12 received bevacizumab postoperatively. Ten patients (16.7 %) required additional plastic surgical intervention for wound complications after their index plastic surgery procedure. Plastic surgery was consulted prophylactically in 34 patients (38 procedures). When plastic surgery was consulted prophylactically, 4 patients (11.8 %) required further wound revision. None of the 14 patients who underwent prophylactic plastic surgery closure for previous scalp incision, preoperative bevacizumab, and XRT administration required re-intervention. Plastic surgery closure of complex scalp incisions reduces the incidence of wound complications among patients who underwent previous neurosurgical intervention, XRT administration, and preoperative bevacizumab administration. This is particularly true when plastic surgery closure is performed "prophylactically." Further collaboration between the neurosurgical and plastic surgery teams is therefore warranted, particularly in the setting of these high-risk cases.

A combined dual-port endoscope-assisted pre- and retrosigmoid approach to the cerebellopontine angle: an extensive anatomo-surgical study.

The use of the endoscope in the cerebellopontine angle (CPA) has been suggested to minimize cerebellar retraction and reduce the size of the craniotomy. 3D endoscopy combines the benefits of conventional 2D endoscopy with the added benefit of stereoscopic perception, though improved visualization alone does not guarantee improved surgical maneuverability and a better surgical outcome. We propose a new combined dual-port endoscope-assisted pre- and retrosigmoid approach to improve visualization and accessibility of the CPA with shortened distances and increased surgical maneuverability of neurovascular structures. We analyze surgical exposure and maneuverability of this approach and compare it with the surgical microscopic and a conventional single-port endoscope-assisted retrosigmoid approach. This combined pre- and retrosigmoid approach was performed on eight cadaveric heads (16 sides). The endoscopic probe was inserted through the presigmoid surgical port while surgical manipulation was performed through the retrosigmoid corridor. The CPA was divided into three compartments, from medial to lateral, the anteromedial, and the middle and the posterolateral. The microscope provided good visualization of the posterolateral and middle compartments, whereas poor visualization was offered of the anteromedial compartment. The dual-port endoscopic approach dramatically improved visualization and surgical maneuverability of the anteromedial compartments, clivus, and related neurovascular structures. Additionally, the 3D endoscope allowed for a better understanding of the surgical anatomy of the CPA and improved visualization of structures located in the anteromedial compartments towards the midline. This approach allowed for full realization of the benefits of endoscopic-assisted technique by improving surgical access and maneuverability.

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.

Innovations in the Treatment of Spinal Cerebrospinal Fluid Leaks.

Spontaneous spinal cerebrospinal fluid (CSF) leaks are uncommon but can be neurologically debilitating. When initial treatments fail, definitive repair or closure of the leak is indicated. Depending upon the type of leak present, innovative strategies for their treatment have been developed. Among them are open surgical techniques using a transdural approach for the closure of ventral CSF leaks, minimally invasive tubular techniques for the reduction and repair of lateral meningeal diverticula, and endovascular embolization of CSF-venous fistulas. Illustrative cases demonstrating the indications for and implementation of these techniques are provided.

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.

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.

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.

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.

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.