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Peer reviewed: True, Funder: NIHR Brain Injury MedTech Co-operative, Glioblastoma and the surgery to remove it pose high risks to the cognitive function of patients. Little reliable data exist about these risks, especially postoperatively before radiotherapy. We hypothesized that cognitive deficit risks detected before surgery will be exacerbated by surgery in patients with glioblastoma undergoing maximal treatment regimens. We used longitudinal electronic cognitive testing perioperatively to perform a prospective, longitudinal, observational study of 49 participants with glioblastoma undergoing surgery. Before surgery (A1), the participant risk of deficit in 5/6 cognitive domains was increased compared to normative data. Of these, the risks to Attention (OR = 31.19), Memory (OR = 97.38), and Perception (OR = 213.75) were markedly increased. These risks significantly increased in the early period after surgery (A2) when patients were discharged home or seen in the clinic to discuss histology results. For participants tested at 4-6 weeks after surgery (A3) before starting radiotherapy, there was evidence of risk reduction towards A1. The observed risks of cognitive deficit were independent of patient-specific, tumour-specific, and surgery-specific co-variates. These results reveal a timeframe of natural recovery in the first 4-6 weeks after surgery based on personalized deficit profiles for each participant. Future research in this period could investigate personalized rehabilitation tools to aid the recovery process found.

Background To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis. Methods Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query ‘Pineal Cyst’ AND ‘Surgery’ as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria. Results All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4–63) with 77% females. Mean cyst size was 15 mm (5–35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0–228). Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), ‘psychiatric’ (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0–9). Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N = 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR = 5.76; 95% CI: 1.74–19.02) and resection over fenestration (OR = 12.64; 3.07–52.01). Age predicted worse outcomes (OR = 0.95; 0.91–0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1). Conclusions Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.

Background With increasing molecular analyses of meningiomas, there is a need to harmonize language used to capture clinical data across centers to ensure that molecular alterations are appropriately linked to clinical variables of interest. Here the International Consortium on Meningiomas presents a set of core and supplemental meningioma-specific common data elements (CDEs) to facilitate comparative and pooled analyses. Methods The generation of CDEs followed the 4-phase process similar to other National Institute of Neurological Disorders and Stroke (NINDS) CDE projects: discovery, internal validation, external validation, and distribution. Results The CDEs were organized into patient- and tumor-level modules. In total, 17 core CDEs (10 patient level and 7 tumor level) as well as 14 supplemental CDEs (7 patient level and 7 tumor level) were defined and described. These CDEs are now made publicly available for dissemination and adoption. Conclusions CDEs provide a framework for discussion in the neuro-oncology community that will facilitate data-sharing for collaborative research projects and aid in developing a common language for comparative and pooled analyses. The meningioma-specific CDEs presented here are intended to be dynamic parameters that evolve with time and The Consortium welcomes international feedback for further refinement and implementation of these CDEs.

Background Chronic subdural hematoma (CSDH) is one of the commonest neurosurgical pathologies with an increasing incidence. Observational studies of routine care have demonstrated high perioperative morbidity and approximately 10% mortality at one year. 20 The development, implementation, and evaluation of a potential care framework relies on an accurate and reproducible method of case identification and case ascertainment. With this manuscript, we report on the accuracy of diagnostic ICD codes for identifying patients with CSDH from retrospective electronic data and explore whether basic demographic data could improve the identification of CSDH. Methods: Data were collected retrospectively from the hospital administrative system between 2014–2018 of all patients coded with either S065 or I620. Analysis of the ICD codes in identifying patients with CSDH diagnosis was calculated using the caretR package in RStudioR .and stepwise logistic regression analysis was performed to evaluate the best predictive model for CSDH. Results: A total of 1861 patients were identified. Of these, 189 (10.2%) had a diagnosis of non-traumatic SDH (I620) and 1672 (89.8%) traumatic subdural haematomas (S065). Variables that identified CSDH as a diagnosis on univariate logistic regression included male sex (Odds Ratios (OR) − 1.606(1.197–2.161), elderly age (OR) − 1.023(1.015–1.032) per year for age (p

Background The decision to resume antithrombotic therapy after surgical evacuation of chronic subdural hematoma (CSDH) requires judicious weighing of the risk of bleeding against that of thromboembolism. This study aimed to investigate the impact of time to resumption of antithrombotic therapy on outcomes of patients after CSDH drainage. Methods Data were obtained retrospectively from three tertiary hospitals in Singapore from 2010 to 2017. Outcome measures analyzed were CSDH recurrence and any thromboembolic events. Logistic and Cox regression tests were used to identify associations between time to resumption and outcomes. Results A total of 621 patients underwent 761 CSDH surgeries. Preoperative antithrombotic therapy was used in 139 patients. 110 (79.1%) were on antiplatelets and 35 (25.2%) were on anticoagulants, with six patients (4.3%) being on both antiplatelet and anticoagulant therapy. Antithrombotic therapy was resumed in 84 patients (60.4%) after the surgery. Median time to resumption was 71 days (IQR 29 – 201). Recurrence requiring reoperation occurred in 15 patients (10.8%), of which 12 had recurrence before and three after resumption. Median time to recurrence was 35 days (IQR 27 – 47, range 4 – 82 days). Recurrence rates were similar between patients that were restarted on antithrombotic therapy before and after 14, 21, 28, 42, 56, 70 and 84 days, respectively. Thromboembolic events occurred in 12 patients (8.6%), of which five had the event prior to restarting antithrombosis. Conclusions Time to antithrombotic resumption did not significantly affect CSDH recurrence. Early resumption of antithrombotic therapy can be safe for patients with a high thromboembolic risk.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.

Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature. Indeed, GBM-derived CD11b+ microglia/macrophages were necessary and sufficient to protect progenitors against ZIKV infection in a non-cell autonomous manner. Using SOX2+ GBM cell lines, we found that CD11b+-conditioned medium containing type 1 interferon beta (IFNβ) promoted progenitor resistance to ZIKV, whereas inhibition of JAK1/2 signaling restored productive infection. Additionally, CD11b+ conditioned medium, and IFNβ treatment rendered HDB progenitor lines and explants refractory to ZIKV. These findings provide insight into neuroprotection for HDB progenitors as well as enhanced GBM oncolytic therapies.

The widespread use of MRI has led to the increasingly frequent diagnosis of pineal and colloid cysts. While most are small and incidental, do not require long-term monitoring and will never need treatment, they are a cause of patient anxiety and clinician uncertainty regarding the optimal management—particularly for larger cysts or those with an atypical appearance. Occasionally pineal cysts, and more commonly colloid cysts, cause hydrocephalus that requires urgent neurosurgical treatment. More recently the non-hydrocephalic symptomatic pineal cyst has been described in the neurosurgical literature but there is controversy over this entity and its management. This review addresses the difficulties in managing pineal and colloid cysts and provides a pragmatic framework for the practising clinician.

Medical students' perception of neuroanatomy as a challenging topic has implications for referrals and interaction with specialists in the clinical neurosciences. Given plans to introduce a standardised Medical Licensing Assessment by 2023, it is important to understand the current framework of neuroanatomy education. This study aims to describe how neuroanatomy is taught and assessed in the UK and Ireland.A structured questionnaire capturing data about the timing, methods, materials, assessment and content of the 2019/2020 neuroanatomy curriculum in the UK and Ireland medical schools.We received 24/34 responses. Lectures (96%) were the most widely used teaching method, followed by prosection (80%), e-learning (75%), tutorials/seminars (67%), problem-based learning (50%), case-based learning (38%), and dissection (30%). The mean amount of core neuroanatomy teaching was 29.3 hours. The most common formats of assessing neuroanatomical knowledge were multiple-choice exams, spot tests, and objective structured clinical exams. Only 37.5% schools required demonstration of core clinical competency relating to neuroanatomy.Our survey demonstrates variability in how undergraduate neuroanatomy is taught and assessed across the UK and Ireland. There is a role for development and standardisation of national undergraduate neuroanatomy curricula in order to improve confidence and attainment.

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two ‘Core Outcome Sets’ (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508

Background Glioma is the most common intrinsic brain tumor and also occurs in the spinal cord. Activating EGFR mutations are common in IDH1 wild-type gliomas. However, the cooperative partners of EGFR driving gliomagenesis remain poorly understood. Results We explore EGFR-mutant glioma evolution in conditional mutant mice by whole-exome sequencing, transposon mutagenesis forward genetic screening, and transcriptomics. We show mutant EGFR is sufficient to initiate gliomagenesis in vivo, both in the brain and spinal cord. We identify significantly recurrent somatic alterations in these gliomas including mutant EGFR amplifications and Sub1, Trp53, and Tead2 loss-of-function mutations. Comprehensive functional characterization of 96 gliomas by genome-wide piggyBac insertional mutagenesis in vivo identifies 281 known and novel EGFR-cooperating driver genes, including Cdkn2a, Nf1, Spred1, and Nav3. Transcriptomics confirms transposon-mediated effects on expression of these genes. We validate the clinical relevance of new putative tumor suppressors by showing these are frequently altered in patients’ gliomas, with prognostic implications. We discover shared and distinct driver mutations in brain and spinal gliomas and confirm in vivo differential tumor suppressive effects of Pten between these tumors. Functional validation with CRISPR-Cas9-induced mutations in novel genes Tead2, Spred1, and Nav3 demonstrates heightened EGFRvIII-glioma cell proliferation. Chemogenomic analysis of mutated glioma genes reveals potential drug targets, with several investigational drugs showing efficacy in vitro. Conclusion Our work elucidates functional driver landscapes of EGFR-mutant gliomas, uncovering potential therapeutic strategies, and provides new tools for functional interrogation of gliomagenesis.

Introduction: The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between “gross total removal” and “subtotal removal,” while the latter comprises a five-tiered differentiation of the surgeon’s impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas. Objective: To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose “Copenhagen Grading” for meningiomas. Results: Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen. Conclusion: Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively.Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up.One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups.Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.

Background Resorbable hemostatic agents are commonly used to control bleeding intra- and post- operatively. Once left behind, these agents can occasionally trigger pathological, granulomatous reactions, resulting in space-occupying lesions known as gossypibomas. Here we report a case of an intracranial gossypiboma. These are notoriously difficult to diagnose as they are exceedingly rare and frequently radiologically indistinguishable from other lesions (tumors, abscess etc). Case Presentation A 35-year-old woman presented with a generalized tonic-clonic seizure and subsequent left-sided hemiparesis. MRI demonstrated an enhancing lobulated lesion subjacent to a right frontal burr hole, surrounded by vasogenic edema with mass effect and midline shift. Nine years ago, she had a triple bolt inserted to monitor intracranial pressure after sustaining traumatic brain injury in a road traffic accident. Surgicel was used to control bleeding during insertion. She made a full recovery. Co-location of the lesion with the position of triple bolt nine years ago raised a suspicion for gossypiboma. However, the minor nature of the surgery, and the length of time since surgery to presentation were placing this case well outside range of cases reported in the literature. The lesion was resected en bloc, with no recurrence 18 months later. Histological examination revealed presence of foreign material, confirming the suspicion of Surgicel-elicited gossypiboma. Conclusions We show here that gossypibomas can occur following a relatively minor procedure and remain clinically and radiologically silent for much longer than what was previously reported. Thus, they should be included in differential diagnoses despite being remarkably rare.

In neurosurgery, tumour-infiltrated cortex is generally assumed to be non-functional. While prior studies have suggested integration of tumour-infiltrated tissue in relatively local circuits responsible for language and motor function, it is unknown whether such tissue can participate in distributed networks important for higher-order cognitive abilities like executive function. We tested the hypothesis that diffuse low-grade gliomas integrate into large-scale cognitive circuits using intracranial electrocorticography and resting-state functional magnetic resonance imaging of four patients. To identify brain areas recruited for executive function, electrocorticography recordings were acquired from tumour-infiltrated tissue under three conditions: i) baseline (rest), ii) simple counting (1-20; “easy”), and iii) switch counting (1-a-2-b-3-c etc.; “hard”). In each patient, we observed significant task-based high gamma power modulations in tumour-infiltrated cortex in response to increasing cognitive effort (p < 0.05), implying preserved functionality of neoplastic tissue for complex tasks. Additionally, tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in higher-order cognitive processing (p < 0.05). Finally, dorsal attention network connectivity in tumour-infiltrated cortex correlated with high gamma power elevations during increased cognitive demand (χ 2(1) = 5.14; p = 0.023), establishing a concordance between both techniques. Overall, this study contributes convergent evidence that tumour-infiltrated cortex can participate in large-scale neurocognitive circuits, prompting a reconsideration of traditional notions of neoplastic brain tissue.

BACKGROUND Resorbable hemostatic agents left behind postoperatively occasionally result in granulomatous space-occupying lesions known as “gossypibomas.” The authors report a case of an intracranial gossypiboma, which is exceedingly rare and frequently radiologically indistinguishable from other lesions. OBSERVATIONS A 35-year-old woman presented with a generalized tonic-clonic seizure and subsequent left-sided hemiparesis. Magnetic resonance imaging showed an enhancing lobulated lesion subjacent to a right frontal burr hole, surrounded by vasogenic edema with mass effect and midline shift. Nine years earlier, she had had a triple bolt inserted to monitor intracranial pressure after sustaining a traumatic brain injury. Surgicel was used to control bleeding during insertion. Colocation of the lesion with the position of triple bolt 9 years earlier raised suspicion for gossypiboma. However, the minor nature of the surgery and the length of time since surgery to presentation placed this case well outside the range of cases reported in the literature. The lesion was resected en bloc with no recurrence 18 months later. Histological examination revealed the presence of foreign material. However, given its minute size, confirming its nature was not possible. Lessons The authors show that gossypibomas can occur following a relatively minor procedure and remain clinically and radiologically silent for much longer than previously reported.

How the frontal cortex is anatomically and functionally organized to control cognition remains puzzling. Numerous non-invasive brain imaging studies relate cognitive control to a localized set of frontal regions, part of a wider fronto-parietal network (FPN), that show increases in functional MRI (fMRI) signal during the performance of multiple cognitively demanding tasks. Lesions implicating frontal control regions lead to disorganized behaviour. However, the fMRI BOLD signal is an indirect measure of neuronal activity and represents evidence from a single modality. This has led to limited clinical translation of fMRI findings e.g. to guide the surgical resection of brain tumours. Here we sought supporting evidence for lateral frontal control regions using electrocorticography (ECoG). We recorded electrophysiological activity from electrodes placed on the lateral frontal cortex in patients undergoing awake craniotomy for glioma resection. During surgery, patients performed two verbal executive-related counting tasks with a difficulty level manipulation, closely adapting difficulty manipulations in fMRI studies of cognitive control. We performed spectral analysis focusing on the gamma range (30-250 Hz) due to mounting evidence of its value as an index of local cortical processing. Comparing hard versus easy demands revealed circumscribed frontal regions with power increases in the gamma range. This contrasted with spatially distributed power decreases in the beta range (12-30 Hz). Further, electrodes showing significant gamma power increases were more likely to occur within a canonical fMRI-defined FPN and showed stronger gamma power increases compared to electrodes outside the FPN, even at the single patient level. Reinforcing the need for careful task manipulation, an easy versus baseline comparison, which includes factors such as speech output, produced gamma changes over a wider area. Thus, using similar task difficulty manipulations, ECoG and fMRI signals converged on delineating lateral frontal control regions. These findings open the door for extending clinical functional mapping to the domain of cognitive control during awake neurosurgery.

The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between "gross total removal" and "subtotal removal," while the latter comprises a five-tiered differentiation of the surgeon's impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging withTo develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance ofCopenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen.Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.

Background Although the use of a postoperative drain after burr-hole evacuation of chronic subdural hematoma (CSDH) is known to improve surgical outcomes, the superiority of subdural over subperiosteal drains has not been firmly established. Evidence comparing these 2 drain types is largely restricted to single-center series with limited numbers. Using a multicenter cohort study, we aimed to show noninferiority of subperiosteal drains vis-a-vis subdural drains after burr-hole evacuation of CSDH. Methods We performed a retrospective analysis of all consecutive patients with CSDH aged 21 years and older who had undergone burr-hole craniostomy across 3 tertiary hospitals from 2010 to 2017. Primary outcome measures included CSDH recurrence and modified Rankin Scale (mRS) score at 6 months. Outcomes of patients in the subdural and subperiosteal drain groups were analyzed and confounders were adjusted for using multivariate logistic regression. Results Of the 570 cases analyzed, 329 (57.7%) received a subdural drain and 241 (42.3%) received a subperiosteal drain. There was no significant difference between the 2 drain groups in CSDH recurrence (13.1% in the subdural group vs. 11.2% in the subperiosteal group; P = 0.502) or 6-month mRS score (27.2% with mRS 4–6 in the subdural group vs. 20.4% in the subperiosteal group; P = 0.188). Independent predictors of CSDH recurrence identified on multivariate analysis included premorbid mRS score 0–3 (P = 0.021), separated CSDH type on preoperative computed tomography scan (P = 0.002), and postoperative pneumocephalus of ≥15 mm (P = 0.005). Conclusions Outcomes of subdural and subperiosteal drains after burr-hole craniostomy for CSDH are largely equivalent based on our findings.

Simple Summary This reseach explored the safety and feasibility of combining local chemotherapy with fluorescence-guided resection in patients with a brain cancer, glioblastoma. The aim was to determine if the combination of fluorescence-guided surgery using 5-aminolevulinic acid and BCNU wafers left in the tumour cavity at the end of the operation was safe and did not prevent patients getting subsequent chemo-radiotherapy. The results showed that combining local chemotherapy with fluorescence-guided resection was tolerable in terms of surgical morbidity and overall toxicity. However, any potential therapeutic benefit requires further investigation, preferably with improved local delivery technologies. Abstract Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (n = 3), death (n = 3), lost to follow-up/withdrew (n = 3), clinical decision (n = 1), poor performance status (n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4–9.8) and median overall survival was 14.7 months (95% CI: 11.7–16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.

Purpose Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is important in preventing CSFR. We sought to systematically review the current literature of available skull base repair techniques. Methods Pubmed and Embase databases were searched for studies (2000–2020) that (a) reported on the endonasal resection of pituitary and skull base tumours, (b) focussed on skull base repair techniques and/or postoperative CSFR risk factors, and (c) included CSFR data. Roles, advantages and disadvantages of each repair method were detailed. Random-effects meta-analyses were performed where possible. Results 193 studies were included. Repair methods were categorised based on function and anatomical level. There was absolute heterogeneity in repair methods used, with no independent studies sharing the same repair protocol. Techniques most commonly used for low CSFR risk cases were fat grafts, fascia lata grafts and synthetic grafts. For cases with higher CSFR risk, multilayer regimes were utilized with vascularized flaps, gasket sealing and lumbar drains. Lumbar drain use for high CSFR risk cases was supported by a randomised study (Oxford CEBM: Grade B recommendation), but otherwise there was limited high-level evidence. Pooled CSFR incidence by approach was 3.7% (CI 3–4.5%) for transsphenoidal, 9% (CI 7.2–11.3%) for expanded endonasal, and 5.3% (CI 3.4–7%) for studies describing both. Further meaningful meta-analyses of repair methods were not performed due to significant repair protocol heterogeneity. Conclusions Modern reconstructive protocols are heterogeneous and there is limited evidence to suggest the optimal repair technique after pituitary and skull base tumour resection. Further studies are needed to guide practice.

Background During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised regarding the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, especially during endonasal neurosurgical operations. The Pituitary Society has produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the effects of COVID-19. Methods A multicenter prospective observational cohort study was conducted at 12 tertiary neurosurgical units (United Kingdom and Ireland). Data were collected from March 23 to July 31, 2020, inclusive. The data points collected included patient demographics, preoperative COVID-19 test results, operative modifications, and 30-day COVID-19 infection rates. Results A total of 124 patients were included. Of the 124 patients, 116 (94%) had undergone COVID-19 testing preoperatively (transsphenoidal approach, 97 of 105 [92%]; expanded endoscopic endonasal approach, 19 of 19 [100%]). One patient (1 of 116 [0.9%]) had tested positive for COVID-19 preoperatively, requiring a delay in surgery until the infection had been confirmed as resolved. Other than transient diabetes insipidus, no other complications were reported for this patient. All operating room staff had worn at least level 2 personal protective equipment. Adaptations to surgical techniques included minimizing drilling, draping modifications, and the use of a nasal iodine wash. At 30 days postoperatively, no evidence of COVID-19 infection (symptoms or positive formal testing results) were found in our cohort and no mortality had occurred. Conclusions Preoperative screening protocols and operative modifications have facilitated endonasal neurosurgery during the COVID-19 pandemic, with the Pituitary Society guidelines followed for most of these operations. We found no evidence of COVID-19 infection in our cohort and no mortality, supporting the use of risk mitigation strategies to continue endonasal neurosurgery in subsequent pandemic waves.

Background Intraoperative functional mapping with direct electrical stimulation during awake surgery for patients with diffuse low-grade glioma has been used in recent years to optimize the balance between surgical resection and quality of life following surgery. Mapping of executive functions is particularly challenging because of their complex nature, with only a handful of reports published so far. Here, we propose the recording of neural activity directly from the surface of the brain using electrocorticography to map executive functions and demonstrate its feasibility and potential utility. Methods To track a neural signature of executive function, we recorded neural activity using electrocorticography during awake surgery from the frontal cortex of three patients judged to have an appearance of diffuse low-grade glioma. Based on existing functional magnetic resonance imaging (fMRI) evidence from healthy participants for the recruitment of areas associated with executive function with increased task demands, we employed a task difficulty manipulation in two counting tasks performed intraoperatively. Following surgery, the data were extracted and analyzed offline to identify increases in broadband high-gamma power with increased task difficulty, equivalent to fMRI findings, as a signature of activity related to executive function. Results All three patients performed the tasks well. Data were recorded from five electrode strips, resulting in data from 15 channels overall. Eleven out of the 15 channels (73.3%) showed significant increases in high-gamma power with increased task difficulty, 26.6% of the channels (4/15) showed no change in power, and none of the channels showed power decrease. High-gamma power increases with increased task difficulty were more likely in areas that are within the canonical frontoparietal network template. Conclusions These results are the first step toward developing electrocorticography as a tool for mapping of executive function complementarily to direct electrical stimulation to guide resection. Further studies are required to establish this approach for clinical use.

Tumors around the cervicomedullary junction are rare and constitute 5% of spinal tumors and 1% of cranial tumors. The approach to these lesions is difficult because of the close proximity of the medulla and cervical spinal cord, lower cranial nerves, and vertebral artery (VA) as well as the complex articulation between occipital condyle, C1 and C2. Cervicomedullary junction meningiomas are commonly classified based on their origin in relation to the dentate ligament, but the relationship to the VA typically plays an important role in deciding the surgical approach. For lesions located dorsal to the dentate ligament and not involving the VA, a midline approach is typically sufficient. However, when the VA is involved a far lateral approach is preferred as it offers better access to the V4 segment. We describe a case of a 55-yr-old man who presented with accessory nerve palsy and mild upper motor neuron signs and was found to have a C1 meningioma encasing and narrowing the VA at the V3/V4 segment. Informed consent was obtained. The patient was treated with a right far lateral approach with limited condylectomy to gain access to the V4 segment. We described the steps used for safe resection of the tumor around the VA from distal to proximal. We demonstrate the relationship of the tumor to the VA and the need to completely skeletonize the VA to achieve a gross total resection. We supplement the discussion with a 3D surgical video.

Glioma, a type of brain tumour, affects not only the function of immediately adjacent brain tissue but also that in more distant areas, potentially impacting cognitive function after its surgical removal. Here, 17 patients with glioma had brain scans and tests of cognitive function during treatment and recovery. We investigated the effects of glioma on the brain, and what happens during recovery, using the brain’s “global signal” detected with magnetic resonance imaging (MRI). We found that the signal from gliomas was synchronised with the global signal in all patients and that this synchronisation was associated with the recovery of cognition after surgery. Specifically, patients with a greater reduction in glioma–global signal synchronisation following surgery were more likely to have a larger number of newly acquired cognitive difficulties. Together, these results suggest that the interaction between gliomas and the brain can predict how patients recover their cognitive abilities, which is important for their quality of life., Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk factors of cognitive recovery or deterioration. Seventeen patients with diffuse non-enhancing glioma (aged 22–56 years) were longitudinally MRI scanned and cognitively assessed before and after surgery and during a 12-month recovery period (55 MRI scans in total after exclusions). We initially found, and then replicated in an independent dataset, that the spatial correlation pattern between regional and global BOLD signals (also known as global signal topography) was associated with tumour occurrence. We then estimated the coupling between the BOLD signal from within the tumour and the signal extracted from different brain tissues. We observed that the normative global signal topography is reorganised in glioma patients during the recovery period. Moreover, we found that the BOLD signal within the tumour and lesioned brain was coupled with the global signal and that this coupling was associated with cognitive recovery. Nevertheless, patients did not show any apparent disruption of functional connectivity within canonical functional networks. Understanding how tumour infiltration and coupling are related to patients’ recovery represents a major step forward in prognostic development., Guarantors of Brain, Cancer Research UK Cambridge Centre, The Brain Tumour Charity, EMERGIA Junta de Andalucia program, Royal Society Dorothy Hodgkin Research Fellowship (DHF130100), e Ciencia e Innovación (España)/FEDER under the RTI2018-098913-B100 project, by the Consejería de Economía, Innovación, Ciencia y Empleo (Junta de Andalucía) and FEDER under CV20-45250, A-TIC-080-UGR18, B-TIC-586-UGR20 and P20-00525 projects, Cambridge Trust—Yousef Jameel Scholarship, NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), National Institute for Health Research (NIHR)