The delicate nature of a constructive peer review: pearls from the editorial board.

Peer review stands as a cornerstone of academic publishing, especially in the era of evidence-based neurosurgery - the scientific literature relies on proficient peer reviewers. Providing a constructive peer review is an art and learned skill that requires knowledge of study design and expertise in the neurosurgical subspeciality. Peer reviewers guard against arbitrary decision-making and are essential in ensuring that published manuscripts are of the highest quality. However, there remains a scarcity in the formal training relating to the peer review process. The objective of this article is therefore to shed light on this process through the lens of the Editorial Board. We encourage our invited peer reviewers to make use of this guide when appraising potential manuscripts.

Systematic reviews and meta-analyses in neurosurgery part I: interpreting and critically appraising as a guide for clinical practice.

Neurosurgeons are inundated with the Herculean task to keep abreast with the rapid pace at which clinical research is proliferating. Systematic reviews and meta-analyses (SRMAs) have consequently surged in popularity because when executed properly, they constitute the highest level of evidence, and may save busy neurosurgeons many hours of combing the literature. Well-executed SRMAs may prove instructive for clinical practice, but poorly conducted reviews sow confusion and may potentially cause harm. Unfortunately, many SRMAs within neurosurgery are relatively lackluster in methodological rigor. When neurosurgeons apply the results of an SRMA to patient care, they should start by evaluating the extent to which the employed methods have likely protected against misleading results. The present article aims to educate the reader about how to interpret an SRMA, to assess the potential relevance of its results in the special context of the neurosurgical patient population.

Systematic reviews and meta-analyses in neurosurgery Part II: a guide to designing the protocol.

Despite clearly established guidelines, recent audits have found the conduct and reporting of systematic reviews and meta-analyses (SRMAs) within neurosurgery to be relatively lackluster in methodological rigor and compliance. Protocols of SRMAs allow for planning and documentation of review methods, guard against arbitrary decision-making during the review process, and enable readers to assess for the presence of selective reporting. To aid transparency, authors should provide sufficient detail in their protocol so that the readers could reproduce the study themselves. Development of our guideline drew heavily from the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P) initiative. The objective of this article is not to enumerate every detail of this checklist, but to provide guidance to authors preparing their protocol, with examples, for a systematic review in neurosurgery. Particularly, we emphasize on the PICO framework - population (P), interventions (I), comparators (C), outcomes (O) - which is central to constructing a clinical question, defining the scope of the systematic review, defining and prioritizing the primary outcome, to specifying the eligibility criteria, designing the search strategy, and identifying potential sources of heterogeneity. We encourage our readers to make use of this guideline alongside the PRISMA-P 2015 statement, when drafting and appraising systematic review protocols.

Diagnostic utility of Brain Injury Guidelines (BIG): systematic review and meta-analysis for prediction of neurosurgical intervention in traumatic brain injury.

BACKGROUND: The Brain Injury Guidelines (BIG) categorize the severity of Traumatic Brain Injury (TBI). The efficacy of BIG in predicting radiological deterioration and the necessity for neurosurgical intervention remains uncertain, as there is a lack of examination of pooled data from current literature despite validation in numerous single and multi-institutional studies. The aim of this study was to analyze existing studies to determine the diagnostic accuracy of BIG scoring criteria. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPEROID CRD42021277542). Three databases were searched, and articles published from 2000 to October 2022 were included (last search date: 25 November 2022). Pooled sensitivity and specificity were calculated using random effects meta-analysis. RESULTS: Of the 1130 articles identified, 13 were included in the analysis (9032 patients - 1433 BIG1, 2136 BIG2 & 3189 BIG3). A total of 2274 patients were not classified under either group. Pooled sensitivity for predicting neurosurgical intervention was 1.00 (95%CI:1.00-1.00), and 0.98 for radiological deterioration (95% CI: 0.927-0.996). The specificity in predicting radiological deterioration was 0.18 (95% CI: 0.16-0.21) and 0.05 for neurosurgical intervention (95% CI 0.05-0.05). CONCLUSIONS: The BIG score is highly sensitive at excluding TBI cases that do not require neurosurgical intervention; however, BIG-2 and BIG-3 might not be useful for ruling in TBI patients who require neurosurgical intervention.

Seniority of Surgeon in Chronic Subdural Hematoma Recurrence: A Systematic Review and Meta-analysis.

Chronic subdural hematoma (CSDH) is increasingly common, particularly in the older and multimorbid population. Surgical proficiency in management is required in the early years of U.K. neurosurgical training with most cases performed by nonconsultant-grade surgeons. The aim of this systematic review was to examine the effect of surgeon seniority on recurrence for patients with CSDH. Full-text articles comparing surgical treatment for CSDH with a "senior" (consultant/attending level) or "junior" (resident/registrar or similar) lead surgeon were identified. MEDLine and EMBASE databases were searched. The primary outcome of this study was recurrence. Secondary outcomes included postoperative complications and mortality rate. A random effects meta-analysis was performed. The risk of bias was assessed using the National Institute of Health risk of bias toolkit. Five studies were included in the final analysis (n = 941 total patients). Individually, no study identified a significant difference in recurrence rate and postoperative complications between senior and junior neurosurgeons. On meta-analysis, junior-led evacuations had lower recurrence rates on pooled univariable analysis (12.0% vs. 17.9% [odds ratio 0.48, 95% confidence interval 0.29-0.78, I2 = 0%]) (3 studies). Seniority of surgeon was not associated with increased rates of recurrence patients undergoing CSDH surgery. Complexity of operation may be a confounding factor in observed lower recurrence rates with more junior operators.

Associated demographic factors for the recurrence and prognosis of stroke patients within a multiethnic Asian population.

OBJECTIVE: There is a paucity of studies investigating the outcomes among Asian stroke patients. Identifying subgroups of stroke patients at risk of poorer outcomes could identify patients who would benefit from targeted interventions. Therefore, the aim of this study was to identify which ischemic stroke patients at high risk of recurrent events and mortality. METHODS: This cohort study adhered to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. We obtained data from the Singapore Stroke Registry (SSR) from 2005 to 2016 and cross referenced to the Death Registry and the Myocardial Infarction Registry. Outcome measures included recurrent stroke, acute myocardial infarction (AMI), and all-cause and stroke-related deaths. Multivariable Cox proportional hazards regression models were performed to determine risk factors for recurrent stroke, AMI, and all-cause and stroke-related deaths. RESULTS: A total of 64,915 patients (6705 young, and 58,210 older) were included in our analysis. Older stroke patients were found to have an increased risk of recurrent stroke (hazard ratio (HR) = 1.21, 95% confidence interval (CI) = 1.12-1.30), AMI (HR = 1.73, 95% CI = 1.54-1.95), all-cause death (HR = 2.49, 95% CI = 2.34-2.64), and stroke-related death (HR = 176, 95% CI = 1.61-1.92). Among young stroke patients, males were at increased risk for recurrent stroke (HR = 1.18, 95% CI = 1.01-1.39) and AMI (HR = 1.41, 95% CI = 1.08-1.83), but at reduced risk for all-cause (HR = 0.78, 95% CI = 0.69-0.89) and stroke-related deaths (HR = 0.79, 95% CI = 0.67-0.94). Ethnicity appeared to influence outcomes, with Malay patients at increased risk of recurrent stroke (HR = 1.37, 95% CI = 1.14-1.65), AMI (HR = 2.45, 95% CI = 1.87-3.22), and all-cause (HR = 1.43, 95% CI = 1.24-1.66) and stroke-related deaths (HR = 1.34, 95% CI = 1.09-1.64). Indian patients were also at increased risk of AMI (HR = 1.96, 95% CI = 1.41-2.72). Similar findings were seen among the older stroke patients. CONCLUSION: This study found that older stroke patients are at risk of poorer outcomes. Within the young stroke population specifically, males were predisposed to recurrent stroke and AMI but were protected against all-cause and stroke-related deaths. Males were also at reduced risk of all-cause and stroke-related deaths in the older stroke population. In addition, Malay and Indian patients experience poorer outcomes after first stroke. Further optimization of risk factors targeting these high-priority populations are needed to achieve high-quality care.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Impact of antithrombotic agents on outcomes in patients requiring surgery for chronic subdural haematoma: a systematic review and meta-analysis.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

Incidence and Risk Factors of Surgical Site Infection After Cranial Surgery for Patients with Brain Tumors: A Systematic Review and Meta-analysis.

BACKGROUND: Surgical site infections after craniotomy (SSI-CRANs) are a serious adverse event given the proximity of the wound to the central nervous system. SSI-CRANs are associated with substantial patient morbidity and mortality. Despite the importance and recognition of this event in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to SSI-CRAN specifically in patients after brain tumor surgery. METHODS: Systematic searches of Medline, Embase, and Cochrane Central were undertaken. The primary outcome was the incidence of SSI-CRAN at 30 and 90 days. Secondary outcomes were risk factors for SSI-CRAN. RESULTS: Thirty-seven studies reporting 91,907 patients with brain tumors who underwent cranial surgery were included in the meta-analysis. Pooled incidence of SSI-CRAN at 30 and 90 days was 4.03% (95% CI: 2.94%-5.28%, I2 = 97.3) and 6.17% (95% CI: 3.16%-10.07%, I2 = 97.3), respectively. Specifically, incidence of SSI-CRAN following surgery for posterior fossa tumors was the highest at 9.67% (95% CI: 5.98%-14.09%, I2 = 75.5). Overall pooled incidence of readmission within 30 days and reoperation due to SSI-CRAN were 13.9% (95% CI: 12.5%-15.5%, I2 = 0.0) and 16.3% (95% CI: 5.4%-31.3%, I2 = 72.9), respectively. Risk factors for SSI-CRAN included reintervention (risk ratio [RR] 1.58, 95% CI: 1.22-2.04, I2 = 0.0), previous radiotherapy (RR 1.69, 95% CI: 1.20-2.38, I2 = 0.0), longer duration of operation (mean difference 64.18, 95% CI: 3.96-124.40 minutes, I2 = 90.3) and cerebrospinal fluid (CSF) leaks (RR 14.26, 95% CI: 2.14-94.90, I2 = 73.2). CONCLUSIONS: SSI-CRAN affects up to 1 in 14 patients with brain tumors. High-risk groups include those with reintervention, previous radiotherapy, longer duration of operation, and CSF leaks. Further prospective studies should focus on bundles of care that will reduce SSI-CRAN.

Endovascular coiling versus neurosurgical clipping in the management of aneurysmal subarachnoid haemorrhage in the elderly: a multicenter cohort study.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores.

Awake brain mapping paradigms for nondominant hemisphere gliomas.

OBJECTIVE: Traditionally, resection of nondominant hemisphere brain tumors was performed under general anesthesia. An improved understanding of right-lateralized neural networks has led to a paradigm shift in recent decades, where the right or nondominant hemisphere is no longer perceived as "functionally silent." There is an increasing interest in awake brain mapping for nondominant hemisphere resections. The objective of this study was to perform a comprehensive review of the existing brain mapping paradigms for patients with nondominant hemisphere gliomas undergoing awake craniotomies. METHODS: In accordance with PRISMA guidelines, systematic searches of the Medline, Embase, and American Psychological Association PsycInfo databases were undertaken from database inception to July 1, 2023. Studies providing a description of the intraoperative mapping paradigm used to assess cognition during an awake craniotomy for resection of a nondominant hemisphere glioma were included. RESULTS: The search yielded 1084 potentially eligible articles. Thirty-nine unique studies reporting on 788 patients were included in the systematic review. The most frequently tested cognitive domains in patients with nondominant hemisphere tumors were spatial attention/neglect (17/39 studies, 43.6%), speech-motor/language (17/39 studies, 43.6%), and social cognition (9/39 studies, 23.1%). Within the frontal lobe, the highest number of positive mapping sites was identified for speech-motor/language, spatial attention/neglect, dual tasking assessing motor and language function, working memory, and social cognition. Within the parietal lobe, eloquence was most frequently found upon testing spatial attention/neglect, speech-motor/language, and calculation. Within the temporal lobe, the assessment of spatial attention/neglect yielded the highest number of positive mapping sites. CONCLUSIONS: Cognitive testing in the nondominant hemisphere is predominantly focused on evaluating two domains: spatial attention/neglect and the motor aspects of speech/language. Multidisciplinary teams involved in awake brain mapping should consider testing an extended range of functions to minimize the risk of postoperative deficits and provide valuable information about anatomo-functional organization of cognitive networks.

Effectiveness of Cerebrospinal Fluid Lumbar Drainage Among Patients with Aneurysmal Subarachnoid Hemorrhage: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science research. The removal of blood and its degradation products from the subarachnoid space through prophylactic lumbar drainage (LD) is a favorable option. However, several studies have delivered conflicting conclusions on its efficacy after aSAH. METHODS: Systematic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were performed. The primary outcome was a good functional outcome (modified Rankin scale score, 0-2). Secondary outcomes included symptomatic vasospasm, secondary cerebral infarction, and mortality. RESULTS: A total of 14 studies reporting on 2473 patients with aSAH were included in the meta-analysis. Compared with the non-LD group, no significant differences were found in the rates of good functional outcomes in the LD group at discharge to 1 month (risk ratio [RR], 1.28; 95% confidence interval [CI], 0.64-2.58) or at 6 months (RR, 1.12; 95% CI, 0.97-1.41). These findings were consistent in the subgroup analyses of only randomized controlled trials or observational studies. LD was associated with lower rates of symptomatic vasospasm (RR, 0.61; 95% CI, 0.48-0.77), secondary cerebral infarction (RR, 0.59; 95% CI, 0.45-0.79), and mortality at discharge to 1 month (RR, 0.58; 95% CI, 0.41-0.82). The effect on mortality diminished at 6 months (RR, 0.70; 95% CI, 0.34-1.45). However, when analyzing only randomized controlled trials, the benefit of LD on lower rates of mortality continued even at 6 months (RR, 0.75; 95% CI, 0.58-0.99). CONCLUSIONS: For aSAH patients, the use of LD is associated with benefits in the rates of vasospasm, secondary cerebral infarctions, and mortality, without an increased risk of adverse events.

Patient-specific automated cerebrospinal fluid pressure control to augment spinal wound closure: a case series using the LiquoGuard®.

OBJECTIVE: Spinal cerebrospinal fluid (CSF) leaks are common, and their management is heterogeneous. For high-flow leaks, numerous studies advocate for primary dural repair and CSF diversion. The LiquoGuard7® allows automated and precise pressure and volume control, and calculation of patient-specific CSF production rate (prCSF), which is hypothesized to be increased in the context of durotomies and CSF leaks. METHODS: This single-centre illustrative case series included patients undergoing complex spinal surgery where: 1) a high flow intra-operative and/or post-operative CSF leak was expected and 2) lumbar CSF drainage was performed using a LiquoGuard7®. CSF diversion was tailored to prCSF for each patient, combined with layered spinal wound closure. RESULTS: Three patients were included, with a variety of pathologies: T7/T8 disc prolapse, T8-T9 meningioma, and T4-T5 metastatic spinal cord compression. The first two patients underwent CSF diversion to prevent post-op CSF leak, whilst the third required this in response to post-op CSF leak. CSF hyperproduction was evident in all cases (mean >/=140ml/hr). With patient-specific CSF diversion regimes, no cases required further intervention for CSF fistulae repair (including for pleural CSF effusion), wound breakdown or infection. CONCLUSIONS: Patient-specific cerebrospinal fluid drainage may be a useful tool in the management of high-flow intra-operative and post-operative CSF leaks during complex spinal surgery. These systems may reduce post-operative CSF leakage from the wound or into adjacent body cavities. Further larger studies are needed to evaluate the comparative benefits and cost-effectiveness of this approach.

Brain MRI changes in degenerative cervical myelopathy: a systematic review.

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction globally. Associated neurological symptoms and signs have historically been explained by pathobiology within the cervical spine. However, recent advances in imaging have shed light on numerous brain changes in patients with DCM, and it is hypothesised that these changes contribute to DCM pathogenesis. The aetiology, significance, and distribution of these supraspinal changes is currently unknown. The objective was therefore to synthesise all current evidence on brain changes in DCM. METHODS: A systematic review was performed. Cross-sectional and longitudinal studies with magnetic resonance imaging on a cohort of patients with DCM were eligible. PRISMA guidelines were followed. MEDLINE and Embase were searched to 28th August 2023. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. A qualitative synthesis of the literature is presented as per the Synthesis Without Meta-Analysis (SWiM) reporting guideline. The review was registered with PROSPERO (ID: CRD42022298538). FINDINGS: Of the 2014 studies that were screened, 47 studies were identified that used MRI to investigate brain changes in DCM. In total, 1500 patients with DCM were included in the synthesis, with a mean age of 53 years. Brain alterations on MRI were associated with DCM both before and after surgery, particularly within the sensorimotor network, visual network, default mode network, thalamus and cerebellum. Associations were commonly reported between brain MRI alterations and clinical measures, particularly the Japanese orthopaedic association (JOA) score. Risk of bias of included studies was low to moderate. INTERPRETATION: The rapidly expanding literature provides mounting evidence for brain changes in DCM. We have identified key structures and pathways that are altered, although there remains uncertainty regarding the directionality and clinical significance of these changes. Future studies with greater sample sizes, more detailed phenotyping and longer follow-up are now needed. FUNDING: ODM is supported by an Academic Clinical Fellowship at the University of Cambridge. BMD is supported by an NIHR Clinical Doctoral Fellowship at the University of Cambridge (NIHR300696). VFJN is supported by an NIHR Rosetrees Trust Advanced Fellowship (NIHR302544). This project was supported by an award from the Rosetrees Foundation with the Storygate Trust (A2844).

Antiplatelet therapy in aneurysmal subarachnoid hemorrhage: an updated meta-analysis.

Antiplatelet therapy (AT) may serve to reduce the effects of aneurysmal subarachnoid hemorrhage (aSAH)-induced pro-coagulant state in the cerebral circulation. Several studies, however, have delivered conflicting conclusions on the efficacy of AT post aSAH. Systematic searches of Medline, Embase, and Cochrane Central were undertaken on 27th March 2023. The primary outcome was delayed cerebral ischaemia (DCI). Secondary outcomes were symptomatic and angiographic vasospasm, good functional outcome (modified Rankin Scale [mRS] with scores 0-2), hemorrhagic events, and in-hospital mortality. Twenty-two studies reporting 4378 patients with aSAH were included in the meta-analysis. AT was associated with lower rates of DCI (RR=0.62, 95% CI: 0.43; 0.89), symptomatic vasospasm (RR=0.63, 95% CI: 0.46; 0.86), and moderate/severe angiographic vasospasm (RR=0.74, 95% CI: 0.65; 0.84), with no effect on hemorrhagic complications (RR=1.36, 95% CI: 0.77; 2.41). When analyzing only post-ictal use of AT, AT additionally favored rates of good functional outcomes (RR=1.18, 95% CI: 1.10; 1.26) and in-hospital mortality (RR=0.56, 95% CI: 0.39; 0.80). In the subgroup treated with cilostazol, AT was associated with lower rates of DCI (RR=0.40, 95% CI: 0.32), symptomatic vasospasm (RR=0.47, 95% CI: 0.33; 0.65), moderate/severe angiographic vasospasm (RR=0.75, 95% CI: 0.57; 0.98) and good functional outcome (RR=1.24, 95% CI: 1.08; 1.43). In the surgically treated aSAH subgroup, AT favored rates of symptomatic vasospasm (RR=0.55, 95% CI: 0.30; 0.98), moderate/severe angiographic vasospasm (RR=0.70, 95% CI: 0.54; 0.90) and good functional outcome (RR=1.23, 95% CI: 1.09; 1.41). In the endovascularly treated aSAH subgroup, AT was associated with lower rates of in-hospital mortality (RR=0.60, 95% CI: 0.41; 0.88). In aSAH patients, post-ictal AT is associated with benefits in terms of rates of DCI, vasospasm, good functional outcomes, and in-hospital mortality without an increased risk of hemorrhagic events.

Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis.

INTRODUCTION: Brain metastases (BMs) in patients with advanced and metastatic NSCLC are linked to poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations. METHODS: A systematic review and meta-analysis compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were conducted (PROSPERO identification CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000 and May 2022 were included. Prevalence at diagnosis and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models. RESULTS: A total of 64 unique articles were included (24,784 patients with NSCLC with prevalence data from 45 studies and 9058 patients with NSCLC having incidence data from 40 studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% confidence interval [CI]: 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, the per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI: 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI: 0.11-0.21), 0.17 in the ALK group (five studies, 95% CI: 0.10-0.27), 0.10 in the KRAS group (four studies, 95% CI: 0.06-0.17), 0.13 in the ROS1 group (three studies, 95% CI: 0.06-0.28), and 0.12 in the RET group (two studies, 95% CI: 0.08-0.17). CONCLUSIONS: Comprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance.

Current landscape of academic neurosurgical training in the United Kingdom: analysis by the Society of British Neurological Surgeons.

OBJECTIVE: Little is known about the impact of academic training on Neurosurgery in the United Kingdom (UK). The aim was to understand the early career clinical and research training journeys of potential future clinical academics, with a view to informing future policy and strategy to improve career development for academic neurosurgical trainees and consultants in the UK. METHODS: An online survey from the Society of British Neurological Surgeons (SBNS) academic committee was distributed to both the SBNS and British Neurosurgical Trainee Association (BNTA) mailing lists in early 2022. Neurosurgical trainees for any period between 2007 and 2022 or who had done any dedicated academic or clinical academic placement were encouraged to complete the survey. RESULTS: Sixty responses were received. Six (10%) were females and fifty-four (90%) were males. At the time of response, nine (15.0%) were clinical trainees, four (6.7%) were Academic Clinical Fellows (ACF), six (10.0%) were Academic Clinical Lecturers (ACL), four (6.7%) were post-CCT fellows, eight (13.3%) were NHS consultants, eight (13.3%) were academic consultants, eighteen (30.0%) were out of the programme (OOP) pursuing a PhD potentially returning to training, whilst three (5.0%) had left neurosurgery training entirely and no longer performing clinical neurosurgery. The mentorship was sought in most programmes, which tended to be informal. Self-reported success on a scale of 0 to 10 with 10 being the most successful, was greatest in the MD and the "Other research degree/fellowship group" which does not include a PhD. There was a significant positive association between completing a PhD and having an academic consultant appointment (Pearson Chi-Square = 5.33, p = 0.021). CONCLUSIONS: This study provides a snapshot to better understand the opinions of academic training in neurosurgery within the UK. Establishing clear, modifiable, and achievable goals, as well as providing tools for research success, may contribute to the success of this nationwide academic training.

AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins.

We previously reported that kenpaullone, which inhibits GSK-3a/b and CDKs inhibited CCCP mediated mitochondrial depolarisation and augments the mitochondrial network. To investigate the actions of this class of drug further, we compared the ability of kenpaullone, alsterpaullone, 1-azakenapaullone, AZD5438, AT7519 (CDK and GSK-3a/b inhibitors) and dexpramipexole and olesoxime (mitochondrial permeability transition pore inhibitors) to prevent CCCP mediated mitochondrial depolarisation and found that AZD5438 and AT7519, were the most effective. Furthermore, treatment with AZD5438 alone increased the complexity of the mitochondrial network. We also found that AZD5438 prevented the rotenone induced decrease in PGC-1alpha and TOM20 levels and that it mediated powerful anti-apoptotic effects and promoted glycolytic respiration. Importantly, experiments in human iPSC derived cortical and midbrain neurons showed AZD5438 mediated significant protective effects, preventing the neuronal cell death, and collapse in the neurite and mitochondrial network associated with rotenone treatment. These results suggest drugs that target GSK-3a/b and CDKs should be developed and assessed further as they may have significant therapeutic potential.

Accuracy of robot-assisted stereotactic MRI-guided laser ablation in children with epilepsy.

OBJECTIVE: Robot-assisted (RA) stereotactic MRI-guided laser ablation has been reported to be a safe and effective technique for the treatment of epileptogenic foci in children and adults. In this study the authors aimed to assess the accuracy of RA stereotactic MRI-guided laser fiber placement in children and to identify factors that might increase the risk of misplacement. METHODS: A retrospective single-institution review of all children from 2019 to 2022 who underwent RA stereotactic MRI-guided laser ablation for epilepsy was undertaken. Placement error was calculated at the target by measuring the Euclidean distance between the implanted laser fiber position and the preoperatively planned position. Collected data included age at surgery, sex, pathology, date of robot calibration, number of catheters, entry position, entry angle, extracranial soft-tissue thickness, bone thickness, and intracranial catheter length. A systematic review of the literature was also performed using Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. RESULTS: In 28 children with epilepsy, the authors assessed 35 RA stereotactic MRI-guided laser ablation fiber placements. Twenty (71.4%) children had undergone ablation for hypothalamic hamartoma, 7 children (25.0%) for presumed insular focal cortical dysplasia, and 1 patient (3.6%) for periventricular nodular heterotopia. Nineteen children were male (67.9.%) and 9 were female (32.1%). The median age at the time of the procedure was 7.67 years (IQR 4.58-12.26 years). The median target point localization error (TPLE) was 1.27 mm (IQR 0.76-1.71 mm). The median offset error between the planned and actual trajectories was 1.04° (IQR 0.73°-1.46°). Patient age, sex, pathology and the time interval between date of surgery and robot calibration, entry position, entry angle, soft-tissue thickness, bone thickness, and intracranial length were not associated with the placement accuracy of the implanted laser fibers. However, the number of catheters placed did correlate with the offset angle error on univariate analysis (ρ = 0.387, p = 0.022). There were no immediate surgical complications. Meta-analysis indicated that the overall pooled mean TPLE was 1.46 mm (95% CI -0.58 to 3.49 mm). CONCLUSIONS: RA stereotactic MRI-guided laser ablation for epilepsy in children is highly accurate. These data will aid surgical planning.