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.

Prognostic factors following resection of intracranial metastases.

Background: The aim of this study was to identify prognostic factors associated with resection of intracranial metastases. Methods: A retrospective case series including patients who underwent resection of cranial metastases from March 2014 to April 2021 at a single center. This identified 112 patients who underwent 124 resections. The median age was 65 years old (24-84) and the most frequent primary cancers were nonsmall cell lung cancer (56%), breast adenocarcinoma (13%), melanoma (6%), and colorectal adenocarcinoma (6%). Postoperative MRI with contrast was performed within 48 hours in 56% of patients and radiation treatment was administered in 41%. GraphPad Prism 9.2.0 was used for the survival analysis. Results: At the time of data collection, 23% were still alive with a median follow-up of 1070 days (68-2484). The 30- and 90-day, and 1- and 5-year overall survival rates were 93%, 83%, 35%, and 17%, respectively. The most common causes of death within 90 days were as follows: unknown (32%), systemic or intracranial disease progression (26%), and pneumonia (21%). Age and extent of neurosurgical resection were associated with overall survival (P < 0.05). Patients aged >70 had a median survival of 5.4 months compared with 9.7, 11.4, and 11.4 for patients <50, 50-59, and 60-69, respectively. Gross-total resection achieved an overall survival of 11.8 months whereas sub-total, debulking, and unclear extent of resection led to a median survival of 5.7, 7.0, and 9.0 months, respectively. Conclusion: Age and extent of resection are potential predictors of long-term survival.

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.

The Sensor Reservoir-does it change management?

BACKGROUND: The Miethke Sensor Reservoir sits within a ventriculoperitoneal shunt system to give a reading of the pressure within the shunt. This information can guide the management of hydrocephalus patients who present frequently with headaches. METHODS: We reviewed a cohort of 12 patients who underwent implantation of a Sensor Reservoir to assess how the management of their symptoms changed over a 4-year period. RESULTS: When comparing the group before the Sensor Reservoir and after the Sensor Reservoir insertion, there was a 75% reduction in number of CT head scans (P<0.05), 100% reduction in episodes of ICP monitoring (P<0.05), 55% reduction in number of X-ray shunt series, and a 50% reduction in acute presentation to hospital with shunt-related symptoms. The number of clinic attendances increased by 44%. In addition, cost analysis showed a saving of £6952 per patients over the 2-year period following Sensor Reservoir insertion as a result of reduced admissions and investigations. Complications were seen in 3 patients-two patients developed shunt-related infections, and 1 patient underwent shunt revision due to a proximal shunt obstruction. Seventy-five percent of patients showed an improvement in their symptoms at the end of the 4-year period. CONCLUSION: Implantation of a Sensor Reservoir in shunt patients with chronic headaches can reduce the number of investigations and hospital admissions and guide management resulting in a clinical improvement.

A case series of early and late cranioplasty-comparison of surgical outcomes.

BACKGROUND: Cranioplasty is an increasingly common procedure performed in neurosurgical centres following a decompressive craniectomy (DC), however, timing of the procedure varies greatly. OBJECTIVES: The aim of this study is to compare the surgical outcomes of an early compared to a late cranioplasty procedure. METHODS: Ninety adult patients who underwent a prosthetic cranioplasty between 2014 and 2017 were studied retrospectively. Timing of operation, perioperative complications and length of stay were assessed. Early and late cranioplasties were defined as less or more than 3 months since craniectomy respectively. RESULTS: Of the 90 patients, 73% received a late cranioplasty and 27% received an early cranioplasty. The median interval between craniectomy and cranioplasty was 13 months [range 3-84] in late group versus 54 days [range 33-90] in early group. Twenty-two patients in the early group (91%) received a cranioplasty during the original admission while undergoing rehabilitation. Complications were seen in 25 patients (28%). These included wound or cranioplasty infection, hydrocephalus, symptomatic pneumocephalus, post-operative haematoma and cosmetic issues. The complication rate was 21% in the early group and 30% in the late group (P value 0.46). There was no significant difference in the rate of infection or hydrocephalus between the two groups. Length of stay was not significantly increased in patients who received an early cranioplasty during their initial admission (median length of stay 77 days versus 63 days, P value 0.28). CONCLUSION: We have demonstrated the potential for early cranioplasty to be a safe and viable option, when compared to delayed cranioplasty.

Ventriculo-peritoneal shunting is a safe and effective treatment for idiopathic intracranial hypertension.

PURPOSE: To determine the outcome of ventriculo-peritoneal shunts as a treatment for idiopathic intracranial hypertension (IIH) Materials and Methods: Retrospective case series of 28 patients with IIH and evidence of raised intracranial pressure (ICP) who underwent shunt insertion. Patients were identified from a prospectively updated operative database. A case-notes review was performed and data on type of shunt, pre- and post-operative symptoms, ophthalmological findings and post-operative complications were recorded. RESULTS: All patients had symptoms of IIH that had failed medical management. Twelve patients had previous lumbo-peritoneal shunts and 2 patients had previous venous sinus stents. All patients had evidence of raised ICP as papilloedema and raised CSF pressure on lumbar puncture. Twenty-seven patients received a ventriculo-peritoneal shunt and 1 patient a ventriculo-atrial shunt. Twenty-six patients received Orbis Sigma Valves and 2 patients Strata valves. At follow-up all patients (100%) had improvement/resolution of papilloedema, 93% had improved visual acuity and 84% had improved headaches. Mean time to last follow-up was 15 (range 4-96) months. Complications occurred in 3 patients (11%): 2 patients required revision of their peritoneal catheters and 1 patient had an anti-siphon device inserted. CONCLUSIONS: Previous literature reported a ventricular shunt revision rate of 22-42% in the management of IIH. We demonstrate ventriculo-peritoneal shunts to be an effective treatment with a revision rate of 11% compared to the previously reported 22-42%.

Validation of Davson's equation in patients suffering from idiopathic normal pressure hydrocephalus.

INTRODUCTION: The so-called Davson's equation relates baseline intracranial pressure (ICP) to resistance to cerebrospinal fluid outflow (Rout), formation of cerebrospinal fluid (If) and sagittal sinus pressure (PSS) There is a controversy over whether this fundamental equation is applicable in patients with normal pressure hydrocephalus (NPH). We investigated the relationship between Rout and ICP and also other compensatory, clinical and demographic parameters in NPH patients. METHOD: We carried out a retrospective study of 229 patients with primary NPH who had undergone constant-rate infusion studies in our hospital. Data was recorded and processed using ICM+ software. Relationships between variables were sought by calculating Pearson product correlation coefficients and p values. RESULTS: We found a significant, albeit weak, relationship between ICP and Rout (R = 0.17, p = 0.0049), Rout and peak-to-peak amplitude of ICP (AMP) (R = 0.27, p = 3.577e-05) and Rout and age (R = 0.16, p = 0.01306). CONCLUSIONS: The relationship found between ICP and Rout provides indirect evidence to support disturbed Cerebrospinal fluid circulation as a key factor in disturbed CSF dynamics in NPH. Weak correlation may indicate that other factors-variable PSS and formation of CSF outflow-contribute heavily to linear model expressed by Davson's equation.

A new method for monitoring nitric oxide production using Teflon membrane microdialysis.

The measurement of nitric oxide (NO) by electron spin resonance (ESR) is complicated by potentially toxic spin-trapping agents, which may affect the NO-producing cells per se and/or cause artifacts and systemic side effects. These problems can be addressed by preventing direct interaction between the agent and the biological system. In the present study, we utilized Teflon as a barrier between the spin trap and the living cell, since the material is permeable to gas only. Our aim was to investigate if NO could diffuse across the membrane in sufficient amounts to be trapped and quantified by ESR. We used standard microdialysis equipment and specially designed dialysis probes, or tubing, with Teflon membranes. Sodium nitroprusside was used as a NO donor and Fe-N-dithiocarboxysarcosine (Fe(DTCS)2) as a spin trap. NO readily diffuses through Teflon and could be quantified in concentrations considerably below 50 nM in a reproducible and accurate manner. In cell cultures of activated murine macrophages, NO synthesis from iNOS could be monitored and we noted a huge increase in NO concentration by superoxide dismutase. We conclude that spin trapping of NO by Fe(DTCS)2 across Teflon membranes is an attractive approach for quantifying and monitoring nitric oxide production without interfering with cell viability.

Primary human glomerular endothelial cells produce proteoglycans, and puromycin affects their posttranslational modification.

This article describes the possible role of the endothelial cell-surface coat, containing proteoglycans (PGs) with connected glycosaminoglycans (GAGs), in maintaining glomerular permselectivity. Primary human glomerular endothelial cells (HGEC) in culture were treated with the nephrosis-inducing agent puromycin aminonucleoside (PAN). Analysis was made by TaqMan real-time PCR, Western blot analysis, and by metabolic labeling with [(35)S]sulfate. The HGECs express several PGs: syndecan, versican, glypican, perlecan, decorin, and biglycan, which may contribute to the glomerular charge barrier. PAN treatment downregulated both the protein expression (by 25%) and the mRNA expression (by 37 +/- 6%, P < 0.001, n = 8) of versican compared with control. Transferases important for chondroitin and heparan sulfate biosynthesis were also significantly downregulated by PAN, resulting in less sulfate groups, shorter GAG chains, and reduced PG net-negative charge. Moreover, analysis of the cell media after PAN treatment revealed a reduced content of [(35)S]sulfate-labeled PGs (40% of control). We conclude that PAN may cause proteinuria by affecting the endothelial cell-surface layer and not only by disrupting the foot process arrangement of the podocytes. Thus the endothelium may be a more important component of the glomerular barrier than hitherto acknowledged.

Synthesis of sulfated proteoglycans by bovine glomerular endothelial cells in culture.

It has been suggested that proteinuria is caused by alterations of the charge selectivity of the basement membrane and/or the epithelial cell layer (podocytes). However, recent findings suggest that the endothelial luminal surface coat, consisting of proteoglycans with their connected glycosaminoglycan (GAG) branches and glycoproteins, may contribute to the permselectivity. Therefore, we wanted to investigate the effects on endothelial GAG synthesis during normal and pathological conditions. We treated glomerular endothelial cell cultures with puromycin aminonucleoside (PAN, a nephrosis-inducing agent) or interleukin-1beta (IL-1beta) for a total of 72 h and compared the metabolic turnover and incorporation of [(35)S]sulfate during the last 2 days. In control cultures, the GAG content in the media supernatants increased 66 +/- 6% (mean +/- SE) between 12 and 42 h of incubation with radioactivity (P < 0.01, n = 8). The content of (35)S-labeled GAGs in the media was reduced by 31 +/- 1% by PAN (P < 0.001, n = 8) and increased by 141 +/- 15% by 10 U/ml IL-1beta (P < 0.01, n = 8). Treatment with enzymes revealed a dominance of heparan, chondroitin, and dermatan sulfate GAGs. Thus the glomerular endothelial cell production of GAGs was increased by IL-1beta and reduced by PAN. Therefore, it is conceivable that certain nephrotic conditions may be due to endothelial dysfunction, rather than other renal causes.