Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111.

Dual mechanism underlying failure of neural tube closure in the Zic2 mutant mouse.

Understanding the molecular mechanisms that lead to birth defects is an important step towards improved primary prevention. Mouse embryos homozygous for the Kumba (Ku) mutant allele of Zic2 develop severe spina bifida with complete lack of dorsolateral hinge points (DLHPs) in the neuroepithelium. Bone morphogenetic protein (BMP) signalling is overactivated in Zic2Ku/Ku embryos, and the BMP inhibitor dorsomorphin partially rescues neural tube closure in cultured embryos. RhoA signalling is also overactivated, with accumulation of actomyosin in the Zic2Ku/Ku neuroepithelium, and the myosin inhibitor Blebbistatin partially normalises neural tube closure. However, dorsomorphin and Blebbistatin differ in their effects at tissue and cellular levels: DLHP formation is rescued by dorsomorphin but not Blebbistatin, whereas abnormal accumulation of actomyosin is rescued by Blebbistatin but not dorsomorphin. These findings suggest a dual mechanism of spina bifida origin in Zic2Ku/Ku embryos: faulty BMP-dependent formation of DLHPs and RhoA-dependent F-actin accumulation in the neuroepithelium. Hence, we identify a multi-pathway origin of spina bifida in a mammalian system that may provide a developmental basis for understanding the corresponding multifactorial human defects.

The Role of Endoscopy in the Resection of Sporadic Vestibular Schwannomas: A Systematic Review of Surgical Outcomes.

BACKGROUND: Vestibular schwannomas (VS) are benign intracranial tumors originating from the vestibular division of the eighth cranial nerve. Treatment options include microsurgery, radiotherapy, and surveillance. Endoscopy is becoming more widely used as an adjunct in skull base surgery and may influence outcomes in surgically managed VS. METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies involving endoscope-assisted and fully endoscopic procedures for sporadic VS resection were identified. Facial nerve function, hearing preservation, extent of resection, and complications were analyzed. RESULTS: Thirty-one studies were included (27 endoscope-assisted, four fully endoscopic). Subgroup analyses were performed to assess outcomes according to tumor size and surgical approach. Overall, endoscopic facial nerve preservation rates were comparable to microsurgical treatment. A subgroup analysis suggested that functional facial nerve preservation rates may be higher when endoscopic assistance is used for smaller (Koos I-II) tumors using the retrosigmoid or translabyrinthine approach. The gross total resection rate for small tumors was higher in retrosigmoid ES-assisted microsurgery (96.2%) compared to rates in the literature for the standard, open retrosigmoid approach. Hearing outcomes were more variable and were under-reported. CONCLUSIONS: Current data suggest that ES-assisted resection of sporadic VS is not inferior to microsurgical resection with respect to facial nerve outcomes and extent of resection. However, some ES series report poor hearing outcomes, which are under-reported in the literature. Further prospective studies are required to ascertain if endoscopic assistance can improve outcomes for VS resection, particularly for smaller (Koos I-II) tumors.

Women in neurosurgery in the United Kingdom: past, present and future.

Whilst a growing number of women in the United Kingdom (UK) are making a success of a career in medicine as a whole, a considerable gender imbalance persists in neurosurgery. The extent of this disparity and the factors that perpetuate it are difficult to assess. Furthermore, over the 70 years since the first female neurosurgeon in the UK commenced her postgraduate training, it is difficult to gauge the progress that has been made. In this article we present a snapshot of women who have played, and who are playing, a key role in UK neurosurgery, highlighting their diverse career paths. We also present the current training distribution and subspecialties of women in UK neurosurgery. We use these data to reflect upon the possible barriers to completion of neurosurgical training, obtaining a substantive consultant position, and reaching positions of academic and clinical leadership. We discuss potential interventions that may overcome these. Highlighting the role women play in UK neurosurgery's past, present and future should inspire more female neurosurgeons to become leaders in the coming years.

Neurosurgery activity levels in the United Kingdom and republic of Ireland during the first wave of the covid-19 pandemic - a retrospective cross-sectional cohort study.

The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April-June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 (n = 304) and 2019 (n = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.

Headache outcomes in children undergoing foramen magnum decompression for Chiari I malformation.

OBJECTIVE: A common symptom of Chiari I malformation (CIM) is headache, which is diagnosed using non-validated criteria from the International Headache Society (IHS). CIM-associated headaches should resolve following neurosurgical treatment of the malformation by foramen magnum decompression (FMD). We aimed to validate the IHS criteria and determine (1) the efficacy of FMD in treating headache and (2) whether duraplasty confers an advantage over simple bony decompression in the treatment of this symptom. METHODS: A retrospective review of CIM cases treated with FMD at Great Ormond Street Hospital from 1989 to 2014 was carried out. Clinical headache characteristics were compared against IHS criteria and correlated with outcome following FMD. RESULTS: Headache was a presenting symptom in 57/102 (55.9%) of patients. Of these, 42/57 (73.7%) could be classified as Chiari I-type headache. Following FMD, 42/57 (73.7%) of all presenting headaches showed a sustained improvement (>3 months) compared with 32/39 (82.1%) of Chiari I-type headaches. Duraplasty led to a sustained improvement in headache in 32/38 (84.2%) cases compared with 9/16 (56.3%) cases treated with bone-only decompression. CONCLUSIONS: Our data suggest that 80% of headaches classified as Chiari I-type will show a sustained improvement following FMD, and, as such, the IHS criteria are clinically useful in evaluating symptoms attributable to CIM. For all headaches associated with CIM, duraplasty may confer a benefit in terms of long-term improvement, compared with bone-only decompression.