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Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h −5.7 ± 2.9 cmCSF (P = 0.048); 24 h −6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks −5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.

Insertion of cerebrospinal fluid (CSF) shunts in patients with idiopathic intracranial hypertension (IIH) is challenging mainly due to the small ventricles and phenotypical body habitus. In this report the authors present their surgical protocol for insertion of a ventriculoperitoneal shunt (VPS) in patients with IIH and the associated revision rates.The protocol comprises the following: shunt surgery by neurosurgeons with expertise in CSF disorders; a frontal VPS usually right sided but left sided if the left ventricle is bigger; use of the proGAV 2.0 valve with gravitational unit, set at 10 and the M.scio telemetric sensor; cannulation of the ventricle with StealthStation EM navigation system; and laparoscopic insertion of the peritoneal catheter. The authors describe the protocol and rationale and evidence behind each component and present the results of a prospective analysis on revision rates.The protocol has been implemented since 1 July, 2019, and by 28 February, 2022, sixty-two patients with IIH had undergone primary VPS insertion. The 30-day revision rate was 6.5%, and overall 11.3% of patients underwent revision during the study period, which compares favorably with the literature. The etiology for early failures was related to the surgical technique.The components of the Birmingham standardized IIH shunt protocol are evidence based and address the technical challenges of CSF diversion in patients with IIH. This protocol is associated with a low revision rate, and the authors recommend standardization for CSF shunting in IIH.

Infected Rathke's cleft cysts (RCC) are extremely rare with only a few published cases. We report the case of a 31-year-old man who presented with headaches, visual disturbance, and hypopituitarism secondary to an infected RCC with extension of abscesses along the optic tract. Magnetic resonance imaging showed ring enhancing cystic lesions within an expanded sella with suprasellar and intraparenchymal extension. The radiological appearance suggested a high-grade optic glioma, but an endoscopic transsphenoidal biopsy revealed frank pus in the pituitary fossa, which subsequently grew Staphylococcus aureus. Pathological examination of the cyst wall showed an inflamed RCC. Following a prolonged course of intravenous antibiotics, the infection resolved and vision improved. RCC abscesses are rare and the intracranial extension of the infection in our case makes it unique.

Although rare, injury to the internal carotid artery (ICA) during pituitary surgery may result in serious morbidity such as stroke or death. This case series explores a single centre's incidence and outcomes of ICA injury during endoscopic transsphenoidal pituitary surgery, discusses the current management options, and introduces the 'muscle wonton' (morcellised muscle wrapped in a single sheet of SurgicelAll patients undergoing pituitary operations from January 2010 to December 2019 at the Queen Elizabeth Hospital, Birmingham, UK were included. Primary outcome was number of internal carotid artery injuries during pituitary surgery. Secondary outcome measures included pre-operative (demographic, risk factors such as previous radiotherapy, number of previous operations, imaging available), operative (intra-operative image guidance, intra-operative doppler ultrasound, which side ICA was damaged, repair technique) and post-operative result (death, cranial nerve VI palsy, or stroke).7 out of 893 patients (0.8%) were identified as having an ICA injury. Four of the injuries were left sided. Average age was 54 years old, five were male. In four of the ICA injuries intra-operative navigation imaging was used, and a further two concurrently used ultrasound doppler. Three of the seven cases resulted in permanent morbidity (stroke). There were no other consistent demographic, pre-operative, operative, or post-operative similarities. The two patients with muscle wonton repair suffered no permanent serious complication of ICA injury (i.e. death, abducens nerve palsy, stroke).Our findings resemble the current literature, with left sided ICA injury being more common. Different methods for repairing ICA injury exist, however morcellised muscle patches have shown significant promise in animal models, and the perforated Surgicel

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Funder: Wellcome Trust, PurposeSurgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice.MethodsA mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached.ResultsThere was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured.ConclusionsThrough an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

Background With the advent of modern endoscopes and a better anatomic understanding of the skull base, the indications of endonasal approaches are increasing. These procedures may be complicated by high rates of postoperative cerebrospinal fluid (CSF) leak, and reconstruction of the defect remains challenging. In the anterior skull base, vascularized grafts have been reported as superior in preventing CSF leakage and infection. The Hadad-Bassagasteguy flap, being a pedicled flap, is our first line flap to reconstruct the skull base. When we were not successful with this flap, we resorted to different flaps. Objective We modified the originally described temporoparietal fascial flap by Fortes et al and applied clinically. The objective of this paper is to briefly describe the modification of the flap and to review the clinical outcome. Methods From 2014 to 2018, in 6 cases of CSF leak with the appropriate indication, we used the temporoparietal myofascial flap repair that is a modification of the temporoparietal fascial flap by Fortes et al. We took all the 6 patients in our study and followed them up. Results All of the 6 repairs were successful, and no CSF leak was found just after the operation in 6- to 48-month follow-up. Conclusion We recommend our modified novel temporoparietal myofascial flap as a very good option in case of failed cases of postoperative CSF leak.

The understanding of raised intracranial pressure (ICP) is increasing with the directed use of intracranial telemetric ICP monitors. This case uniquely observed ICP changes by telemetric monitoring in a patient with idiopathic intracranial hypertension (IIH), who developed rapid sight-threatening disease. A lumbar drain was inserted, as a temporising measure, and was clamped prior to surgery. This resulted in a rapid rise in ICP, which normalised after insertion of a ventriculoperitoneal shunt. This case highlighted the utility of the ICP monitor and the lumbar drain as a temporising measure to control ICP prior to a definitive procedure as recommended by the IIH consensus guidelines.

Specific symptom outcomes after craniovertebral decompression for patients with Chiari type 1 malformation, without accompanying syringomyelia, are not well characterised and poorly reported. We performed a retrospective review of all patients diagnosed with Chiari type 1, without syringomyelia, who underwent craniovertebral decompression in our unit. We identified 129 individuals with a minimum of 2 years’ follow-up. The most common pre-operative symptoms were pressure dissociation headaches (78%), visual disturbances (33%), dizziness/balance disturbances (24%) and blackouts (17%). The symptoms most likely to respond to surgery included Valsalva-induced headache (74% response, p < 0.0001) and blackouts (86% response, p < 0.001). After successful craniovertebral decompression, most patients presenting with pressure dissociation headaches and blackouts will improve. However, the large variety of other symptoms patients often present with may not improve after surgery.

Craniovertebral decompression is performed for symptomatic Chiari malformation type 1, with or without syringomyelia. In a few patients the symptoms and/or syrinx persist or recur, in which case revision surgery may be offered. The aim of this study was to examine the cause of failure of primary surgery and to assess the outcomes for revision cranio-vertebral decompression.We retrospectively reviewed all revision cranio-vertebral decompressions performed in our centre over an eighteen-year period. A total of 35 patients were identified (23 females; 12 males). Twenty patients had isolated Chiari malformation type 1 and a further fifteen had associated syringomyelia. The mean follow up period was 4-years (range:1-12 years).The mean time to revision was 7 years after the primary surgery. The commonest operative finding was that of dense arachnoid scar tissue, obstructing movement of CSF across the craniovertebral junction. Overall, 32 of the 35 patients reported improvement after surgery, including all 15 patients with syringomyelia. Improvement was maintained in the longer term in more than two thirds of those patients who underwent revision craniovertebral decompression.Failure of primary craniovertebral decompression for Chiari malformation most often results from the formation dense scar tissue at the operation site, obstructing CSF movement. Revision cranio-vertebral decompression can provide early symptomatic relief in most patients and this benefit is sustained in at least two thirds of cases, in the medium term at least. Patients with concomitant syringomyelia appear to derive most benefit from revision surgery.

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.

With increasing incidence and prevalence of Idiopathic intracranial hypertension in the UK, the aim of this study was to explore emerging themes in Idiopathic intracranial hypertension using the Hospital Episode Statistics dataset and to quantify recent change in hospital admissions and surgeries performed within England. Methods: Hospital Episode Statistics national data was extracted between 1 April 2002 and 31 March 2019, and followed up until 31 March 2020. All those within England with a diagnosis of Idiopathic Intracranial Hypertension were included. Those with secondary causes of raised intracranial pressure such as tumors, hydrocephalus and cerebral venous sinus thrombosis were excluded. Results: 28,794 new IIH cases were diagnosed between 1 January 2002 and 31 December 2019. Incidence rose between 2002 to 2019 from 1.8 to 5.2 per 100,000 in the general population. Peak incidence occurred in females aged 25–29 years. Neurosurgical shunt was the commonest procedure performed (6.4%), followed by neovascular venous sinus stenting (1%), bariatric surgery (0.8%) and optic nerve sheath fenestration (0.5%). The portion of the total IIH population requiring a shunt fell from 10.8% in 2002/2003 to 2.46% in 2018/2019. The portion of the total IIH population requiring shunt revision also reduced over time from 4.84% in 2002/2003 to 0.44% in 2018/2019. The mean 30 days emergency readmissions for primary shunt, revision of shunt, bariatric surgery, neurovascular stent, and optic nerve sheath fenestration was 23.1%, 23.7%, 10.6%, 10.0% and 9.74%, respectively. There was a peak 30 days readmission rate following primary shunt in 2018/2019 of 41%. Recording of severe visual impairment fell to an all-time low of 1.38% in 2018/19. Conclusions: Increased awareness of the condition, specialist surgery and expert guidance may be changing admissions and surgical trends in IIH. The high 30 readmission following primary shunt surgery for IIH requires further investigation.

Background Endoscopic skull base surgery continues to push boundaries with increased complexity of work and subsequently larger defects requiring repair. Robust repair following endoscopic skull base surgery is essential to reduce significant postoperative complications such as cerebrospinal fluid leak, meningitis, and pneumocephalus. Objective To describe and further validate our novel technique of using a polydioxanone plate wrap used in large anterior skull base resections where brain herniation can be of concern. Method After large resections where there is obvious brain herniation, our PDS (polydioxanone) wrap can be deployed to provide rigid support to the brain. The PDS plate is wrapped in a dural graft material and sutured closed in order to allow deployment by releasing the sutures when in position under the bony ridge of the defect. Conclusion Till date we have successfully used this technique in 3 patients following large skull base resections of olfactory meningiomas, where there was herniation of the brain. Postoperatively, there was no evidence of cerebrospinal fluid leak. We therefore recommend the use of the PDS wrap to prevent brain herniation and provide additional support to the repair.

BackgroundNormal pressure hydrocephalus (NPH) is a disease that causes gait disturbance, urinary incontinence and dementia and is treated through ventriculoperitoneal shunting (VPS). Although CSF infusion studies are currently used to predict the likelihood of improvement following VPS, many see no benefit or deteriorate after initial improvement. It is currently unknown whether preoperative characteristics could predict the likelihood of postoperative improvement.AimsTo investigate associations between postoperative symptomatic improvement and patients’ mean baseline and plateau CSF pressures, the time between NPH diagnoses and performing VPS, and patients’ age at diagnosis.MethodsA retrospective audit was performed using data collected between 14/05/2018 and 18/06/2018 from 65 NPH patients treated with VPS at University Hospital Birmingham. Percentages of patients whose symptoms improved and did not improve postoperatively were calculated. Two-tailed unpaired t-tests were performed to analyse associations between the pre-operative factors studied and symptomatic improvement. The level of significance used was p = 0.05.Results69.0% of patients with gait disturbance, 52.9% with urinary incontinence and 56.4% with cognitive impairment at baseline showed improvement at their first postoperative follow up. Just 31.0% of patients with gait disturbance, 47.1% with urinary incontinence and 43.6% with cognitive impairment showed improvement at their last postoperative follow up. None of the pre-operative factors studied were associated with significant differences in the rates of symptomatic improvement at patients’ first or last recorded follow ups.ConclusionsThe majority of patients showed improved gait, incontinence, and cognition postoperatively at their first recorded follow up. The mean rates of improvement in all 3 symptoms studied at patients’ last recorded follow up were lower than at their first recorded follow up. There were no associations with symptomatic improvement with the number of weeks between diagnosis and VPS, age at diagnosis, baseline CSF pressure and plateau CSF pressure. saiju.jacob@uhb.nhs.uk

OBJECTIVE Cerebrospinal fluid (CSF) shunting in idiopathic intracranial hypertension (IIH) is associated with high complication rates, primarily because of the technical challenges that are related to small ventricles and a large body habitus. In this study, the authors report the benefits of a standardized protocol for CSF shunting in patients with IIH as relates to shunt revisions. METHODS This was a retrospective study of consecutive patients with IIH who had undergone primary insertion of a CSF shunt between January 2014 and December 2020 at the authors’ hospital. In July 2019, they implemented a surgical protocol for shunting in IIH. This protocol recommended IIH shunt insertion by neurosurgeons with expertise in CSF disorders, a frontal ventriculoperitoneal (VP) shunt with an adjustable gravitational valve and integrated intracranial pressure monitoring device, frameless stereotactic insertion of the ventricular catheter, and laparoscopic insertion of the peritoneal catheter. Thirty-day revision rates before and after implementation of the protocol were compared in order to assess the impact of standardizing shunting for IIH on shunt complications. RESULTS The 81 patients included in the study were predominantly female (93%), with a mean age of 31 years at primary surgery and mean body mass index (BMI) of 37 kg/m2. Forty-five patients underwent primary surgery prior to implementation of the protocol and 36 patients after. Overall, 12 (15%) of 81 patients needed CSF shunt revision in the first 30 days, 10 before and 2 after introduction of the protocol. This represented a significant reduction in the early revision rate from 22% to 6% after the protocol (p = 0.036). The most common cause of shunt revision for the whole cohort was migration or misplacement of the peritoneal catheter, occurring in 6 of the 12 patients. Patients with a higher BMI were significantly more likely to have a shunt revision within 30 days (p = 0.022). CONCLUSIONS The Birmingham standardized IIH shunt protocol resulted in a significant reduction in revisions within 30 days of primary shunt surgery in patients with IIH. The authors recommend standardization for shunting in IIH as a method for improving surgical outcomes. They support the notion of subspecialization for IIH shunts, the use of a frontal VP shunt with sophisticated technology, and laparoscopic insertion of the peritoneal end.

Background CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) is a prospective multicenter observational study seeking to determine 1) the scope of skull base repair methods used and 2) corresponding rates of postoperative cerebrospinal fluid (CSF) rhinorrhea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull base tumors. We sought to pilot the project, assessing the feasibility and acceptability by gathering preliminary data. Methods A prospective observational cohort study was piloted at 12 tertiary neurosurgical units in the United Kingdom. Feedback regarding project positives and challenges were qualitatively analyzed. Results A total of 187 cases were included: 159 TSA (85%) and 28 EEA (15%). The most common diseases included pituitary adenomas (n = 142/187), craniopharyngiomas (n = 13/187). and skull base meningiomas (n = 4/187). The most common skull base repair techniques used were tissue glues (n = 132/187, most commonly Tisseel), grafts (n = 94/187, most commonly fat autograft or Spongostan) and vascularized flaps (n = 51/187, most commonly nasoseptal). These repairs were most frequently supported by nasal packs (n = 125/187) and lumbar drains (n = 20/187). Biochemically confirmed CSF rhinorrhea occurred in 6/159 patients undergoing TSA (3.8%) and 2/28 patients undergoing EEA (7.1%). Four patients undergoing TSA (2.5%) and 2 patients undergoing EEA (7.1%) required operative management for CSF rhinorrhea (CSF diversion or direct repair). Qualitative feedback was largely positive (themes included user-friendly and efficient data collection and strong support from senior team members), demonstrating acceptability. Conclusions Our pilot experience highlights the acceptability and feasibility of CRANIAL. There is a precedent for multicenter dissemination of this project, to establish a benchmark of contemporary practice in skull base neurosurgery, particularly with respect to patients undergoing EEA.

Investigating potential cerebrospinal fluid (CSF) shunt malfunction can be a challenge. Optical coherence tomography (OCT), a non-invasive imaging technique, is used to monitor changes at the optic nerve head in papilloedema. Conventional teaching suggests that in the presence of optic atrophy the optic nerve head may not re-swell in response to a relapse in raised intracranial pressure (ICP).A retrospective case series of three patients who had prior CSF diversion surgery for idiopathic intracranial cranial hypertension (IIH) is presented demonstrating the benefit of non-invasive OCT imaging confirming raised ICP.Recurrence of raised ICP, due to malfunctioning CSF shunt, was diagnosed in three patients requiring further surgical intervention. All re-presented acutely with headache and visual disturbances. All had a prior diagnosis of optic atrophy. In all patients, OCT peripapillary retinal nerve fibre layer qualitative image analysis and quantified progression analysis permitted easy detection of the recurrence of papilloedema.OCT imaging supports clinical decision making in shunt malfunction, even in the presence of established optic atrophy secondary to IIH.

Background: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. Methods: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. Ethics and dissemination: Formal institutional ethical board review was not required owing to the nature of the study–this was confirmed with the Health Research Authority, UK. Conclusions: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.

The coronavirus disease 2019 pandemic has presented a massive burden to most health care systems across the globe. The demand for intensive care unit capacity in particular has increased significantly, and hospitals in most affected regions have struggled to cope. The focus of health care activity has shifted to the pandemic, with a negative impact on the management of other conditions. Neurosurgery, like most specialties, has been drastically affected but, arguably, warrants special considerations because many of the treatments required are time-critical. Lack or delay of appropriate intervention may lead, for an individual patient, to permanent neurologic injury and a significant decline in function and quality of life, or even death. In this report, we consider the challenges that neurosurgeons currently face in relation to the pandemic and are likely to face in the foreseeable future. The challenges are multifaceted with practical, ethical, legal, and other implications. These include re-deployment of staff to areas outside neurosurgery, treatment priority setting, ethical decision-making and risk of moral injury, as well as medicolegal risks, financial uncertainties and implications for training, research, and global health work. As well as patients, these challenges will affect neurosurgeons as doctors and as humans. The international neurosurgical community has a moral duty to contribute to the global response to the COVID-19 crisis, but also to retain a duty to care for individual patients.

Purpose Highlight and characterize manifestations, diagnostic/management approaches and outcomes in a contemporary cohort of patients with pituitary metastases (PM) from a large European pituitary center—over 10 years. Methods Retrospective review of PM cases between 1/2009 and 12/2018. Clinical, laboratory, imaging data at PM detection and during follow-up were analysed. Results 18 cases were identified (14 females; median age at diagnosis 61.5 years). Most common primary malignancies were lung (39%) and breast (32%). Most frequent presenting manifestation was visual dysfunction (50%). Gonadotrophin, ACTH, TSH deficiency were diagnosed in 85%, 67%, 46% of cases, respectively; diabetes insipidus (DI) was present in 17%. 33% of cases were detected during investigation for symptoms unrelated to PM. PM management included radiotherapy (44%), transsphenoidal surgery (17%), transsphenoidal surgery and radiotherapy (6%) or monitoring only (33%). One-year survival was 49% with median survival from PM detection 11 months (range 2–47). Conclusions In our contemporary series, clinical presentation of PM has evolved; we found increased prevalence of anterior hypopituitarism, decreased rates of DI and longer survival compared with older literature. Increased availability of diagnostic imaging, improvements in screening and recognition of pituitary disease and longer survival of patients with metastatic cancer may be contributing factors.

OBJECTIVEMultiple meningiomas account for 1%–10% of meningiomas. This study describes epidemiological aspects of the disease and its management, which is more challenging than for single tumors.METHODSA consecutive series of adult patients with ≥ 2 spatially separated meningiomas was reviewed. Patients with neurofibromatosis Type 2 were excluded. The authors collected clinical, imaging, histological, and treatment data to obtain information on epidemiology, management options, and outcomes of active treatment and surveillance.RESULTSA total of 133 consecutive patients were included over 25 years, with a total of 395 synchronous and 53 metachronous meningiomas, and a median of 2 tumors per patient. One hundred six patients had sporadic disease, 26 had radiation-induced disease, and 1 had familial meningiomatosis. At presentation, half of the patients were asymptomatic. In terms of their maximum cross-sectional diameter, the tumors were small (≤ 2 cm) in 67% and large (> 4 cm) in 11% of the meningiomas. Fifty-four patients had upfront treatment, and 31 had delayed treatment after an observation period (mean 4 years). One in 4 patients had ≥ 2 meningiomas treated. Overall, 64% of patients had treatment for 142 tumors—67 with surgery and 18 with radiotherapy alone. The mean follow-up was 7 years, with 13% of treated patients receiving salvage therapy. Approximately 1 in 4 patients who underwent surgery had ≥ 1 WHO Grade II or III meningioma. Meningiomas of different histological subtypes and grades in the same patient were not uncommon.CONCLUSIONSMultiple meningiomas are often asymptomatic, probably because the majority are small and a significant proportion are induced by radiation. Approximately two-thirds of patients with multiple meningiomas require therapy, but only one-third of all meningiomas need active treatment. The authors recommend surveillance for stable and asymptomatic meningiomas and therapy for those that are symptomatic or growing.

Craniopharyngiomas are rare epithelial tumours situated primarily in the sellar/parasellar region, occurring along the path of the craniopharyngeal duct. Whilst classed as histologically benign tumours, their unpredictable growth pattern and proximity to vital structures including the optic chiasm, hypothalamus, and pituitary gland renders them a considerable threat, with significant associated morbidity and increase in mortality. Occurring both in child and adulthood, their clinical manifestations are broad, commonly with symptoms/signs secondary to hypothalamic-pituitary dysfunction, raised intracranial pressure and visual compromise. They have two distinct histological subtypes (adamantinomatous and papillary), with unique patterns of age distribution, and genetic and molecular make-up. With increasing understanding of their genetic pathogenesis including BRAF V600E mutations in the papillary subtype, and β-catenin mutations in the adamantinomatous, further research provides hope for the discovery of targeted medical therapy that can exploit molecular changes occurring as a result of such alterations. Until then, primary treatment consists of surgery with or without radiotherapy, with intracystic aspiration, chemotherapy or irradiation being alternative options in selected patients. Long term management by an experienced multidisciplinary team is essential, given the breadth of complications, including hypothalamic morbidity, visual compromise, cognitive and neuropsychological sequelae and impairment to quality of life.

IntroductionRaised intracranial pressure (ICP) causes significant morbidity and mortality in a range of conditions including idiopathic intracranial hypertension (IIH) and traumatic brain injury (TBI). Exenatide is a GLP-1 receptor agonist; pre-clinical data demonstrates its ability to reduce ICP. GLP-1R agonists have also been shown to have neuro-protective properties in pre-clinical models of TBI. The objectives of this study are to assess the biological effect of a Glucagon-like Peptide 1 (GLP-1) agonist on ICP in a cohort of participants with IIH, a raised ICP model.MethodsRandomised, placebo controlled, double-blind physiology study of Exenatide in women with active IIH (>25 cmCSF lumbar puncture opening pressure and papilloedema). Telemetric, intraparenchymal ICP monitors were implanted to enable gold standard, long-term ICP monitoring (Raumedic p-Tel, Helmbrechts, Germany). Participants were randomised 1:1 to receive Exenatide (10 mcg BD sub-cutaneous) or placebo for 12 weeks. ICP was recorded over a 24-hour baseline visit, at two weeks and 12 weeks. Monthly headache diaries were completed at baseline and 8–12 weeks. Significance was set at pResultsOf the 16 participants recruited, 15 were randomised and completed the study: age 29.5 ±9.5 years, BMI 38.1 ±6.2 kg/m2, ICP 30.6±5.1 cmCSF. All ICP monitor implants were well tolerated and allowed successful ICP quantification. A significant reduction in ICP was noted at all timepoints: at 2.5 hours -5.7 cm CSF (p=0.031), at 24 hours -6.3 cmCSF (p=0.095), and at 12 weeks -5.6 cmCSF (p=0.064).ConclusionsWe report the first human study to assess the biological effect of the GLP-1 agonist Exenatide on ICP in IIH utilising highly accurate implantable telemetric ICP monitors. Exenatide reduced ICP at all timepoints including acutely at 2.5 hrs and during chronic dosing. New therapies for ICP modulation are a significant un-met need in both military and civilian spheres.

Degenerative cervical spinal disease refers to neck pain, myelopathy, and/or radiculopathy. It is a common problem with increased prevalence above the age of 55 years. Understanding the natural history and pathophysiology is crucial in selecting patients for surgery. The degenerative pathological processes that can occur in the cervical spine include degenerative disc disease, degenerative cervical myelopathy, ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF). There are also systemic diseases affecting the cervical spine and these include rheumatoid disease, sero-negative spondyloarthropathies and diffuse idiopathic skeletal hyperostosis (DISH). This section describes the pathology of cervical spinal disease, the clinical management, surgical approaches, and controversies in the field.

The neurological complications of SARS-CoV-2 infection are increasingly being recognised, as is the impact of enforced lockdown on both acute admissions and those with pre-existing neurological conditions. Papilloedema is a medical emergency requiring correct identification, timely investigations and a multidisciplinary approach.1 During the first National lockdown, access to optometric and hospital services, in the UK, was limited to absolute emergencies. The aim of this study was to evaluate the impact of lockdown on those presenting with new onset papilloedema and those with existing idiopathic intracranial hypertension (IIH) at a neuroscience centre in the UK. A 10-week prospective evaluation (15 May 2020 to 30 July 2020) of emergency papilloedema and IIH clinics. Patients seen were referred urgently with new papilloedema or potential exacerbation of existing IIH. IIH follow-up appointments, cancelled due to enforced national lockdown and deployment of staff to frontline services, were also seen. Data collected included demographics, final diagnosis, weight, visual acuity (logarithm of the minimum angle of resolution (logMAR)), perimetric mean deviation (MD) (Humphrey 24–2 (Swedish Interactive Testing Algorithm (SITA)) central threshold) and papilloedema (optical coherence tomography (OCT), average global peripapillary retinal nerve fibre layer (RNFL)). Headache frequency (days per month) and the headache impact test-6 questionnaire (HIT-6) were noted. Depression and anxiety were evaluated (Hospital Anxiety and Depression Scale (HADS) scores: 0–7 normal, 8–10 mild, 11–14 moderate, 15–21 severe). Cerebrospinal fluid (CSF) shunt data for IIH from 2019 were recorded retrospectively. Mean and SD have been reported. Worst eye data were reported. Changes were evaluated using the χ2 test with the significance set at p

Cranial trepanation is the oldest neurosurgical operation and its roots date back to prehistory. For many centuries, religion and mysticism were strongly linked to the cause of diseases, and trepanation was associated with superstitions such as releasing evil spirits from inside the skull. The Hippocratic treatise “On injuries of the head” was therefore a revolutionary work, as it presented a systematic approach to the management of cranial trauma, one that was devoid of spiritual elements. Unfortunately, there are only a limited number of skeletal findings that confirm that the practice of trepanation was performed as part of Hippocratic medicine. In this historical vignette, the authors present a trepanned skull that was found in Chios, Greece, as evidence of the procedure having been performed in accordance with the Hippocratic teaching. The skull bears a parietal bur hole in association with a linear fracture, and it is clear that the patient survived the procedure. In this analysis, the authors examine the application of the original Hippocratic teaching to the skull of Chios. The rationalization of trepanation was clearly a significant achievement in the evolution of neurosurgery.

Introduction With the advent of skull base endoscopy, tuberculum sellae meningiomas (TSMs) are currently operated both from the traditional transcranial (TC) route as well as the extended endonasal endoscopic trasns-sphenoidal approach (EETS). The aim of this study was to conduct a systematic review of TSMs excised via the TC route in the modern era when the EETS excision is gaining popularity. Evidence acquisition We performed a systematic review in the medical literature following the PRISMA guidelines. A medical librarian retrieved a list of 3443 articles published from 2006-2016 from the Medline, Embase and Cochrane Central databases. Two of the authors independently screened for titles and abstracts and excluded 3340 of them. We reviewed the full text of the remaining 103 articles and included in our analysis 31 that met the following inclusion criteria: 1) 5 or more cases reported; and 2) report of the extent of resection, visual outcomes and complications specifically for TSMs were documented. Evidence synthesis Thirty-one articles were selected for this systematic review with a total number of 983 patients with TSM. The mean age was 54.1±4.6 years, 75% of them being female. The follow-up was 43.9±20.7 months. The mean tumor diameter was 27.8±4.9 mm. Gross total resection was achieved in 84% while subtotal or near total resection was 14%. Vision improved, worsened and remained unchanged in 65.5%, 10.4%, and 24.7% respectively. The CSF leak rate was 3.4%. Transient or permanent pituitary dysfunction was reported in 6.9% of patients. There was a vascular injury in 5.1% of the patients with the majority (4.3%) being symptomatic. The recurrence rate was 3.8% and mortality 1.1%. Conclusions In the past decade, the ETTS excision of TSMs has gained popularity and in some centers has become the approach of choice. However the TC route still remains the most common approach for most TSMs meningiomas and for the majority of neurosurgeons. The evolution of transcranial surgery including the use of minimally invasive techniques, such as endoscope-assisted transcranial resection are associated with relatively high resection rates and improved visual outcomes with low morbidity and mortality. A direct comparison with TS approaches was not done for the purpose of this review analysis. Given the limited availability and heterogeneity of comparative observational studies, a meta-analysis was deemed inappropriate.

OBJECTIVE The treatment of recurrent and residual craniopharyngiomas is challenging. In this study the authors describe their experience with these tumors and make recommendations on their management. METHODS The authors performed an observational study of adult patients (≥ 18 years) with recurrent or residual craniopharyngiomas that were managed at their tertiary center. Retrospective data were collected on demographics and clinical, imaging, and treatment characteristics from patients who had a minimum 2-year follow-up. Descriptive statistics were used and the data were analyzed. RESULTS There were 42 patients (27 male, 15 female) with a mean age of 46.3 ± 14.3 years. The average tumor size was 3.1 ± 1.1 cm. The average time to first recurrence was 3.6 ± 5.5 years (range 0.2–27 years). One in 5 patients (8/42) with residual/recurrent tumors did not require any active treatment. Of the 34 patients who underwent repeat treatment, 12 (35.3%) had surgery only (transcranial, endoscopic, or both), 9 (26.5%) underwent surgery followed by adjuvant radiation therapy (RT), and 13 (38.2%) received RT alone. Eighty-six percent (18/21) had a gross-total (n = 4) or near-total (n = 14) resection of the recurrent/residual tumors and had good local control at last follow-up. One of 5 patients (7/34) who underwent repeat treatment had further treatment for a second recurrence. The total duration of follow-up was 8.6 ± 7.1 years. The average Karnofsky Performance Scale score at last follow-up was 80 (range 40–90). There was 1 death. CONCLUSIONS Based on this experience and in the absence of guidelines, the authors recommend an individualized approach for the treatment of symptomatic or growing tumors. This study has shown that 1 in 5 patients does not require repeat treatment of their recurrent/residual disease and can be managed with a “scan and watch” approach. On the other hand, 1 in 5 patients who had repeat treatment for their recurrence in the form of surgery and/or radiation will require further additional treatment. More studies are needed to best characterize these patients and predict the natural history of this disease and response to treatment.

Objective Subarachnoid haemorrhage (SAH) may present with coma and this is known to be associated with aneurysmal origin and blood load. Aneurysmal origin is associated with increased blood load and existing data do not allow us to determine if the association between coma and aneurysmal SAH is wholly due to blood load or if aneurysmal origin has an additional independent effect. The objective of our study is to find if an aneurysmal origin is a predictor of acute onset of coma independent of blood load. Methods A series of consecutive patients with spontaneous SAH were divided into two groups: aneurysmal (aSAH) and non-aneurysmal – angiographically negative SAH (naSAH). Blood load was quantified so that the effect of aneurysmal origin could be resolved from the effect of the amount of blood spilled. Non-parametric regression was used to relate blood load to coma and poor outcome rates for aneurysmal bleeds. Results We analysed a total of 421 patients presenting during the period 2009–2011. Ninety aneurysmal cases presented with coma, seventy immediately in the early phase and seven shortly after rebleeding. None of the naSAH cases presented with immediate coma and 1 developed delayed coma. Delayed coma was associated with acute hydrocephalus in both groups. Aneurysmal origin was found to be an independent determinant of immediate coma (p = 0.02) and poor outcome (p Conclusion Immediate coma and poor outcome in SAH are associated with an aneurysmal origin and do not characterize naSAH.

The endonasal endoscopic approach (EEA) for the resection of tuberculum sellae meningiomas (TSMs) has, more recently, been advocated as an alternative approach to deal with this challenging tumor. The aim of this study was to conduct a systematic review of publications of TSMs excised through the transsphenoidal route in the past 10 years and review data on the extent of excision, visual outcomes and complication rates.We performed a thorough systematic review of the medical literature following the PRISMA guidelines. A medical librarian retrieved a list of 3443 articles published from 2006-2015 from the MEDLINE, EMBASE and Cochrane Central databases. Two of the authors independently screened for titles and abstracts and excluded 3340 of them. We reviewed the full text of the remaining 103 articles and included in our analysis 12 that met the following inclusion criteria: 1) 5 or more cases reported; 2) the extent of resection, visual outcomes and complication rates that were specifically documented for TSMs excised through the transsphenoidal route.Twelve studies that included 150 patients were analyzed. The mean age was 55 years. The mean tumor volume, reported in 2 studies, was 6.6 cc and mean maximum diameter, reported in 11 studies, was 25 mm. The gross total resection rate was 77.2%. Vision improved in 79.5% of cases and deteriorated in 7.3%. CSF leak postoperatively occurred in 15.3% of patients. In the 11 studies that reported hormonal outcomes, there was a 9.4% transient hyponatremia or diabetes insipidus and 2.2% of patients developed a new permanent endocrine dysfunction. A symptomatic vascular injury was reported in 2.6% of patients. There was one mortality (0.6%).The endonasal endoscopic transsphenoidal excision of TSMs is a feasible, safe and effective surgical option with a low morbidity and mortality. The use of this approach has evolved in the last 10 years and in some centers has replaced the transcranial route for selected cases. Given the limited availability and heterogeneity of comparative observational studies, a direct comparison with transcranial approaches was not performed for the purpose of this review analysis. Likewise, from an epidemiological and statistical perspective a meta-analysis was deemed inappropriate.

Objective In surgery for acute subdural hematoma (ASDH), the bone flap can be fixed onto the skull, left riding to provide partial skull decompression, or removed. This study assessed whether removing the bone flap improved outcome. Methods We conducted an observational study on consecutive patients who were operated for ASDH in our hospital from July 2011 to June 2014. We retrospectively collected data on demographics, injury severity, and predicted and observed outcomes at 6 months. The cohort was divided into 2 groups based on whether the bone flap was replaced (fixed and riding flap craniotomy) or removed (decompressive craniectomy). The differences in functional status, postoperative control of intracranial hypertension, and number of cranial reoperations were analyzed. A subgroup analysis compared decompressive craniectomy with riding flap craniotomy alone. Results Data were obtained for 99 patients; 69 had decompressive craniectomy, 17 had riding flap craniotomy, and 13 had fixed flap craniotomy. The decompressive craniectomy group had statistically worse injuries, more predicted poor outcomes (69% vs. 57%, P = 0.013), more observed poor outcomes (59% vs. 37%, P = 0.037), equivalent control of intracranial hypertension, and a similar number of reoperations compared with the craniotomy groups. Subgroup analysis between decompressive craniectomy and riding flap craniotomy showed no significant difference in baseline characteristics and outcomes. Conclusions Our study concluded that removing the bone flap after ASDH evacuation was not associated with a better outcome. We recommend replacing the bone flap if brain conditions allow. Further research is required to evaluate the role of skull decompression in surgery for ASDH.

We analyse the factors that are associated with the diagnostic yield of needle brain biopsy.We present a retrospective series of 124 consecutive biopsies in a 30-month period. Patients' demographics (age, gender), lesion topography (side, location, depth), lesion characteristics (histology, volume, radiological enhancement), type of biopsy procedure (freehand, ultrasound guided, frameless and frame-based stereotactic) and the use of intraoperative histologic examination were correlated with the diagnostic rate. Descriptive statistics and a nominal logistic regression model were used to evaluate the factors influencing diagnostic yield.63 men and 61 women were included in the study with mean age 59.2 (range: 16-86). 55 were frame-based stereotactic biopsies, 33 were frameless stereotactic biopsies, 29 biopsies were performed under ultrasound guidance and 7 freehand. The diagnostic yield in our series is 93.5%. The gender, lesion topography, biopsy method, use of intraoperative histology and enhancement did not correlate with the diagnostic yield. Younger age had a negative impact on diagnostic yield. 6 out of 8 inconclusive biopsies were in non-glial lesions (p0.05). The odds of obtaining a positive diagnosis increased sevenfold with every cc increase in lesion volume.The age of the patient, the volume and the histology of the brain lesion had an impact on the diagnostic yield of needle biopsy. None of the other factors significantly influenced the diagnostic rate.

We present a case of anterior migration of prosthesis that presented acutely several weeks following cervical arthroplasty. The implant was subsequently removed and the level fused. The cause of this unusual complication is speculated.

We report the case of a young woman who developed brain swelling during an ultrasound-guided craniotomy for tumour. A contralateral acute extradural haematoma was identified with the ultrasound and removed. No cause for the extradural was found.

IMPORTANCE: There is an unmet need for noninvasive biomarkers of intracranial pressure (ICP), which manifests as papilledema that can be quantified by optical coherence tomography (OCT) imaging. OBJECTIVE: To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study used data collected from 3 randomized clinical trials that were conducted between April 1, 2014, and August 1, 2019. Participants who were female and had active idiopathic intracranial hypertension were enrolled from 5 National Health Service hospitals in the UK. Automated perimetry and OCT imaging were followed immediately by ICP measurement on the same day. Cohort 1 used continuous sitting telemetric ICP monitoring (Raumedic Neurovent P-tel device) on 1 visit. Cohort 2 was evaluated at baseline and after 3, 12, and 24 months and underwent lumbar puncture assessment of ICP. MAIN OUTCOMES AND MEASURES: Optical coherence tomography measures of the optic nerve head and macula were correlated with ICP levels, Frisén grading, and perimetric mean deviation. The OCT protocol included peripapillary retinal nerve fiber layer, optic nerve head, and macular volume scans (Spectralis [Heidelberg Engineering]). All scans were validated for quality and resegmented manually when required. RESULTS: A total of 104 women were recruited. Among cohort 1 (n = 15; mean [SD] age, 28.2 [9.4] years), the range of OCT protocols was evaluated, and optic nerve head central thickness was found to be most closely associated with ICP (right eye: r = 0.60; P = .02; left eye: r = 0.73; P = .002). Subsequently, findings from cohort 2 (n = 89; mean [SD] age, 31.8 [7.5] years) confirmed the correlation between central thickness and ICP longitudinally (12 and 24 months). Finally, bootstrap surrogacy analysis noted a positive association between central thickness and change in ICP at all points (eg, at 12 months, a decrease in central thickness of 50 μm was associated with a decrease in ICP of 5 cm H(2)O). CONCLUSIONS AND RELEVANCE: In this study, optic nerve head volume measures on OCT (particularly central thickness) reproducibly correlated with ICP and surrogacy analysis demonstrated its ability to inform ICP changes. These data suggest that OCT has the utility to not only monitor papilledema but also noninvasively prognosticate ICP levels in idiopathic intracranial hypertension.