The unseen impact - a deep dive into neurocognitive impairment among patients with intracranial meningiomas: a comprehensive systematic review of the literature.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life.

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.

Sex Differences in Adult Incarceration After Pediatric Traumatic Brain Injury.

Pediatric traumatic brain injury (pTBI) is a major risk factor associated with adulthood incarceration. Most research into the link between pTBI and adulthood incarceration has focused on incarcerated males, who comprise the vast majority of incarcerated adults, particularly in industrialized nations. In this review, we sought to identify sex-related differences in the incidence and pathophysiology of pTBI and subsequent risk of adulthood incarceration. A scoping review was undertaken using PubMed, Scopus, Ovid, and the Cochrane Library. Articles analyzing sex-related differences in pTBI and adult incarceration rates, studies conducted on an incarcerated population, and cohort studies, cross-sectional studies, clinical trials, systematic reviews, or meta-analyses were included in this review. Of the 85 unique results, 25 articles met our inclusion criteria. Male children are 1.5 times more likely to suffer a TBI than females; however, the prevalence of incarcerated adults with a history of pTBI is ∼35-45% for both sexes. Neurophysiologically, female sex hormones are implicated in neuroprotective roles, mitigating central nervous system (CNS) damage post-TBI, although this role may be more complex, given that injury severity and sequelae have been correlated with male sex whereas increased mortality has been correlated with female sex. Further investigation into the relationship between estrogen and subsequent clinical measurements of CNS function is needed to develop interventions that may alleviate the pathophysiological consequences of pTBI.

[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.

Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

Posterior cranial vault distraction in children with syndromic craniosynostosis: the era of biodegradable materials-a comprehensive review of the literature and proposed novel global application.

Distraction osteogenesis is utilized to increase intracranial volume in the treatment of restrictive pathologies, most commonly syndromic synostosis. Children too young for open calvarial vault expansion or other systemic or local contraindications to a direct reconstructive approach benefit greatly from distraction osteogenesis, typically addressing posterior vault expansion. Wound infection, cerebrospinal fluid (CSF) leak, device failure, need for a second surgery for removal, and cost, are issues that can limit the use of this approach. These challenges are more pronounced in low- and middle-income countries (LMICs) due to lack of access to the device, the financial burden of the need for a second surgery, and the severity of the implications of infection and CSF leak. Over the last five decades, there has been an increased acceptance of bioresorbable instrumentation in craniofacial surgery. Poly L-lactic acid, polyglycolic acid, and polydioxanone are the most commonly used polymers. New resorbable fixation tools such as ultrasound-activated pins and heat-activated pins are superior to conventional bioresorbable screws in allowing attachment to thinner bone plates. In this paper, we present a review of the literature on cranial vault distraction and the use of bioresorbable materials and propose a novel design of a fully absorbable cranial distractor system using external magnetic distraction control, eliminating the need for external activation ports and a second surgery to remove the hardware. The application of this technology in LMIC settings could advance access to care and treatment options for patients with syndromic synostosis.

Assessing the state of LGBTQ+ diversity and inclusion in neurosurgery.

OBJECTIVE: The aim of this study was to assess the diversity of neurosurgeons in terms of lesbian, gay, bisexual, transgender, and/or queer (LGBTQ+) gender and sexual minority status using the Graduation Questionnaire (GQ) as the single nationalized source of LGBTQ+ identification. Additionally, inclusivity was assessed through interviews by residents and attendings in the field. METHODS: First, a PRISMA literature review was conducted and independently reviewed by two authors on studies involving LGBTQ+ representation in neurosurgery from PubMed, Web of Science, and Google Scholar. Then, aggregate responses of 16,901 participants' sexual and gender identities from the GQ administered between 2016 and 2022 were compiled. To statistically analyze the response frequencies, the authors performed a chi-square analysis. Finally, interviews were conducted with individuals who identify as LGBTQ+ and are currently neurosurgical residents or attendings. Direct invitations were extended to participate in interviews, and all participants gave informed consent prior to the interview. Interviews were conducted using standardized questions and were video recorded. RESULTS: Two studies were identified by literature review that referenced the LGBTQ+ community in neurosurgery. A GQ chi-square analysis comparing neurosurgical with nonneurosurgical LGBTQ+ identification proved statistically insignificant (p = 0.65). More broad analysis of majority sexual and gender identification (heterosexual and cisgendered) compared with the total gender and sexual minority group also proved statistically insignificant (p = 0.32) in response frequency. Five interviews, including 4 residents and 1 attending, provided several overarching themes including self-identification as an invisible minority, self-limiting behavior to ensure inclusion, and LGBTQ+ status as a direct departure from the stereotypical neurosurgeon. CONCLUSIONS: Results from the GQ analysis indicate that neurosurgery is achieving LGBTQ+ diversity of its incoming members comparable to that of other fields in medicine. However, qualitative data from the interviews and a lack of specific literature indicate that despite obtaining diversity, inclusion of LGBTQ+ neurosurgeons and trainees is lacking.

[68 Ga]-DOTATATE PET/MR-based evaluation of physiologic somatostatin receptor 2 expression in the adult pituitary gland as a function of age and sex in a prospective cohort.

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.

Concurrent immunotherapy and re-irradiation utilizing stereotactic body radiotherapy for recurrent high-grade gliomas.

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.

Shared Objective Mentorship via Virtual Research and Education Initiatives for Medical Students and Residents in Neurosurgery: A Systematic Review and Methodological Discussion of the Neurosurgery Education and Research Virtual Group Experience.

OBJECTIVE: Virtual mentorship and research programs are becoming increasingly popular to facilitate education and career development for students and residents. We review virtual research initiatives for early trainees in neurosurgery and describe our effort to expand access to resources and shared objective mentorship (SOM) via the novel Neurosurgery Education and Research Virtual Group (NERVE). METHODS: A systematic review of neurosurgical programming delivered via a virtual platform was conducted using PubMed, Embase, and Scopus databases. Identified articles were screened. Those meeting prespecified inclusion criteria were reviewed in full and examined for relevant data. Data analysis was performed using Microsoft Excel, and means and standard deviations were calculated. Descriptive analysis of NERVE characteristics was also performed. RESULTS: Of the 2438 identified articles, 10 were included. The most common (70%) implementation style was a webinar-based lecture series. The least common (10%) was a longitudinal curricular interest group. Of the total NERVE cohort, 90% were first generation medical students and 82% attended institutions without home programs. Survey results indicated 73.8% had contributed to at least 2 research projects throughout the year. CONCLUSIONS: There is a scarcity of virtual neurosurgical resources which facilitate SOM opportunities for trainees. In our systematic review, NERVE is the only multi-institutional virtual initiative aimed at increasing access to neurosurgical education and research opportunities for the purpose of SOM among early trainees from disadvantaged backgrounds. This highlights the group's niche and potential impact on increasing diversity in neurosurgery, improving trainees' career development, and facilitating future resident research productivity.

The use of mixed reality for the treatment planning of unruptured intracranial aneurysms.

BACKGROUND: A thorough comprehension of topographic neuroanatomy is paramount in neurosurgery. In recent years, great attention has been raised towards extended reality, which comprises virtual, augmented, and mixed reality (MR) as an aid for surgery. In this paper, we describe our preliminary experience with the use of a new MR platform, aiming to assess its reliability and usefulness in the planning of surgical treatment of unruptured intracranial aneurysms. METHODS: We prospectively enrolled 5 patients, harboring a total of 8 intracranial unruptured aneurysms, undergoing elective surgical clipping. A wearable mixed-reality device (HoloLens; Microsoft Corp., Redmond, WA, USA) was used to display and interact with a holographic model during surgical planning. Afterward, a total of 10 among surgeons and residents filled in a 5-point Likert-Scale evaluation questionnaire. RESULTS: According to the participants' feedback, the main MR platform advantages were considered the educational value, its utility during patients positioning and craniotomy planning, as well as the anatomical and imaging interpretation during surgery. The graphic performance was also deemed very satisfactory. On the other hand, the device was evaluated as not easy to use and pretty uncomfortable when worn for a long time. CONCLUSIONS: We demonstrated that MR could play important role in planning the surgical treatment of intracranial aneurysms by enhancing the visualization and understanding of the patient-specific anatomy.

A multidisciplinary management algorithm for brain metastases.

The incidence of brain metastases continues to present a management issue despite the advent of improved systemic control and overall survival. While the management of oligometastatic disease (ie, 1-4 brain metastases) with surgery and radiation has become fairly straightforward in the era of radiosurgery, the management of patients with multiple metastatic brain lesions can be challenging. Here we review the available evidence and provide a multidisciplinary management algorithm for brain metastases that incorporates the latest advances in surgery, radiation therapy, and systemic therapy while taking into account the latest in precision medicine-guided therapies. In particular, we argue that whole-brain radiation therapy can likely be omitted in most patients as up-front therapy.

Challenges in the Diagnosis and Management of Low-Grade Gliomas.

Low-grade gliomas are clinically challenging entities. Patients with these tumors tend to be relatively young at presentation, and lesions are often incidental findings or are identified because the patient presents with a seizure. Rapidly emerging and evolving molecular classifications of gliomas have influenced treatment paradigms. Importantly, low-grade gliomas can be classified on the basis of IDH mutation status, whereby low-grade astrocytomas harbor the IDH mutation, while oligodendrogliomas are defined by both IDH mutant status and 1p/19q co-deletion. Given the importance of molecular classification for diagnosis, treatment planning, and prognostication, tissue samples are necessary for proper management. Literature supports improved overall survival and outcomes with increased extent of resection for low-grade glioma. Awake craniotomies and resection of insular low-grade gliomas both have been demonstrated as safe and improve outcomes for patients with lesions located in eloquent areas. Given the younger age at diagnosis of these lesions compared with higher-grade gliomas, fertility, fertility preservation, and potential malignant transformation should be discussed with patients of childbearing age.

Evaluating diagnostic accuracy and determining optimal diagnostic thresholds of different approaches to [68Ga]-DOTATATE PET/MRI analysis in patients with meningioma.

Multiple approaches with [68Ga]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of different approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method. Patients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), using follow-up pathology and MRI as reference standard. Lesions were reclassified using the following methods: absolute maximum SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), SUVR to the pituitary gland (SUVRpit), and SUVR to the normal brain parenchyma (SUVRnorm). Diagnostic performance of the four methods was compared using contingency tables and McNemar's test. Previously published pre-determined thresholds were assessed where applicable. The optimal thresholds for each method were identified using Youden's J statistics. 166 meningiomas and 41 PTC lesions were identified across 62 patients. SUV, SUVRsss, SUVRpit, and SUVRnorm of meningioma were significantly higher than those of PTC (P < 0.0001). The optimal thresholds for SUV, SUVRsss, SUVRpit, and SUVRnorm were 4.7, 3.2, 0.3, and 62.6, respectively. At the optimal thresholds, SUV had the highest specificity (97.6%) and SUVRsss had the highest sensitivity (86.1%). An ROC analysis of SUV, SUVRsss, SUVRpit, and SUVRnorm revealed AUC of 0.932, 0.910, 0.915, and 0.800, respectively (P < 0.0001). Developing a diagnostic threshold is key to wider clinical translation of [68Ga]-DOTATATE PET/MRI in meningioma evaluation. We found that the SUVRsss method may have the most robust combination of sensitivity and specificity in the diagnosis of meningioma in the post-treatment setting, with the optimal threshold of 3.2. Future studies validating our findings in different patient populations are needed to continue optimizing the diagnostic performance of [68Ga]-DOTATATE PET/MRI in meningioma patients.Trial registration: ClinicalTrials.gov Identifier: NCT04081701. Registered 9 September 2019. https://clinicaltrials.gov/ct2/show/NCT04081701 .