Second surgery for progressive glioblastoma: a multi-centre questionnaire and cohort-based review of clinical decision-making and patient outcomes in current practice.

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

Suspected cauda equina syndrome: no reduction in investigation, referral and treatment during the COVID-19 pandemic.

INTRODUCTION: Compression of the cauda equina can lead to bladder, bowel and sexual dysfunction with lower limb pain, numbness and weakness. Urgent surgical decompression aims to prevent progressive neurological deficit. Symptoms of cauda equina syndrome (CES), such as back pain, sciatica and bladder dysfunction are common in the population, but the majority of those investigated do not have radiological cauda equina compression. However, a missed diagnosis can have significant medical, social and legal consequences. We investigated the effect of the COVID-19 pandemic on presentation and management of suspected CES. METHODS: This retrospective cohort study analysed referral, investigation and treatment of CES in a regional neurosurgical centre during the initial COVID-19 surge between March and May 2020 compared with March to May 2019. RESULTS: Referrals for suspected CES were similar during the COVID-19 pandemic (n = 275) compared with 2019 (n = 261, p = 0.596) despite a significant (19%) decrease in total emergency neurosurgical referrals (1248 in 2020 vs 1544 in 2019, p < 0.001). Nineteen (7%) of the suspected CES referrals underwent decompression in 2020, similar to 16 (6%) in 2019 (p = 0.867). There were no differences in outcomes or complications and no evidence of delays in presentation or treatment. CONCLUSIONS: Unlike other emergency neurosurgical conditions, the number of referrals for suspected CES and the percentage of referrals with radiological cauda equina compression were unchanged during the COVID-19 pandemic. The persistence of CES referrals when many people stayed away from hospital highlights the distress and worry caused by suspected CES and its symptoms to both patients and healthcare providers.

Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

Chronic Subdural Haematoma in the Elderly: Is It Time for a New Paradigm in Management?

Chronic subdural haematoma (CSDH) is a common neurological condition that usually affects the elderly. The optimal treatment strategy remains uncertain, principally because there is a lack of a good evidence base. In this paper, we review the literature concerning the peri-operative and operative care of patients. In particular, we highlight the non-surgical aspects of care that might impact on patient outcomes and CSDH recurrence. We propose that an integrated approach to care in patients with CSDH, similar to care of fragility fractures in the elderly, may be an important strategy to improve patient care and outcomes.

Academic Productivity of Neurosurgeons Working in the United Kingdom: Insights from the H-Index and Its Variants.

OBJECTIVES: Academic metrics can be used to compare the productivity of researchers. We aimed to use a variety of bibliometric parameters to assess the productivity of neurosurgeons working in the United Kingdom. METHODS: Neurosurgical consultants working in the United Kingdom were identified using the Society of British Neurosurgeons' Audit Programme website. Baseline data collected included year of entry to specialist register, academic position and award of higher degree. Google Scholar was used to compute a range of academic metrics for each consultant including the h-index, hi-norm, e-index and g-index. Non-parametric tests were used to compare median results. RESULTS: Median metrics for the whole cohort were: h-index (5), hi-norm (3), g-index (10.4) and e-index (9). The top 3 units based on h-index were Addenbrookes (13), Great Ormond Street (12.5) and Queen's Square (11.5). The h-index correlated with academic position [Prof (17.5), Senior Lecturer (10.5) and non-academic (5); P < 0.0001], higher degree [PhD (10), MD (6) and none (4.5); P < 0.0001] and consultant experience [> 10 year (7), < 10 years (4); P < 0.0001]. No difference was found based on gender [male (5), female (4); P = 0.12]. The same trends were seen across the following other metrics: hi-norm, e-index and g-index. DISCUSSION: This study details the academic impact of United Kingdom-based neurosurgeons through the analysis of a number of citation metrics. It provides a benchmark bibliometric profile and we advocate future comparative assessments as a means to assess impact of and guide academic policy.

A systematic review and meta-analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy?

BACKGROUND: The development of therapeutics is often characterized by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We tested the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in experimental glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a quality checklist. We calculated median survival ratios and used random effects meta-analysis to estimate efficacy. We explored effects of study design and quality and searched for evidence of publication bias. RESULTS: We identified 193 publications using gene therapy in experimental glioma, including 6,366 animals. Overall, gene therapy improved median survival by a factor of 1.60 (95% CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity. We observed similar findings in a data subset limited to the most common gene therapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment for glioma. Nevertheless, we have identified areas for improvement in conduct and reporting of studies, and we provide a basis for sample size calculations. Further work should focus on genes of interest in paradigms recapitulating human disease. This might improve the translation of such therapies into the clinic.

Surgical management of acute subdural haematomas: current practice patterns in the United Kingdom and the Republic of Ireland.

INTRODUCTION: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of acute subdural haematomas (ASDH). In 2011, a collaborative group was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of decompressive craniectomy, in comparison with craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multicentre, pragmatic, parallel group randomised trial of DC versus craniotomy for adult head-injured patients with an ASDH. In this study, we used an online questionnaire to assess the current practice patterns in the management of ASDH in the UK and the Republic of Ireland, and to gauge neurosurgical opinion regarding the proposed RESCUE-ASDH trial. MATERIALS AND METHODS: A questionnaire survey of full members of the Society of British Neurological Surgeons and members of the British Neurosurgical Trainees Association was undertaken between the beginning of May and the end of July 2012. RESULTS: The online questionnaire was answered by 95 neurosurgeons representing 31 of the 32 neurosurgical units managing adult head-injured patients in the UK and the Republic of Ireland. Forty-five percent of the respondents use primary DC in at least 25% of patients with ASDH. In addition, of the 22 neurosurgical units with at least two Consultant respondents, only three units (14%) showed intradepartmental agreement regarding the proportion of their patients receiving a primary DC for ASDH. CONCLUSION: The survey results demonstrate that there is significant uncertainty as to the optimal surgical technique for primary evacuation of ASDH. The fact that the majority of the respondents are willing to become collaborators in the planned RESCUE-ASDH trial highlights the relevance of this important subject to the neurosurgical community in the UK and Ireland.

Wide variation and systematic bias in expert clinicians' perceptions of prognosis following brain injury.

BACKGROUND: The heterogeneous nature of traumatic brain injury (TBI) makes outcome prediction difficult. Although a considerable evidence base exists in the form of well-validated predictive models, these models are not widely used. We hypothesised that this prognostic gap, between the availability and use of prognostic data, leads to inaccurate perceptions of patient outcome. We investigated whether outcome predictions in TBI made by expert clinicians were consistent and accurate when compared to a well-validated prognostic model (IMPACT). METHODS: Neurosurgeons and neurointensivists were asked to predict probability of death at 6 months for 12 case vignettes describing patients with isolated TBI. Predictions were compared to IMPACT prognosis for each vignette. To interrogate potential sources of bias in clinical predictions, respondents were given one of two sets of vignettes (A or B) identical apart from one critical factor known to make a large difference to outcome. RESULTS: 27 of 33 questionnaires were returned. Clinicians were consistently more pessimistic about outcomes than the IMPACT model, predicting a significantly greater probability of death (mean difference + 16.3%, 95% CI 13.3-19.4, p < 0.001). There was wide variation between clinicians predicting outcomes for any given vignette (mean range 68.3%), and within the predictions made by each individual: 30% of clinicians were both the most pessimistic respondent, and the most optimistic, for at least one vignette. Clinicians modified their predictions appropriately for most of the factors altered between corresponding vignettes. However when the reported blood glucose was changed, clinicians' predictions deviated widely from IMPACT predictions, indicating that clinicians systematically overlooked the prognostic relevance of this information. CONCLUSION: Clinical experts' predictions of outcome in TBI are widely variable and systematically pessimistic compared to IMPACT. Clinicians overlook important factors in formulating these predictions. Use of well-validated outcome models may add value and consistency to prognostication.

Infections of cerebrospinal fluid diversion devices in adults: the role of intraventricular antimicrobial therapy.

OBJECTIVES: The precise role for intraventricular (IVT) antimicrobials in combination with systemic antibiotics in management of cerebrospinal fluid (CSF) diversion device-associated infections is uncertain. We evaluated our current practice, comparing dual therapy against systemic antimicrobials alone. METHODS: All adult patients with at least two consecutive CSF isolates who were treated for CSF diversion device-related infection over a 5-year period (2005-2010) were identified retrospectively. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were analysed. RESULTS: Forty-eight patients were identified - 25 received IVT and systemic antibiotics (group A), and 23 systemic antibiotics alone (group B). Clinical features were similar between groups, as were causative organisms. CSF leucocyte counts differed slightly (A > B, p = 0.067) but no laboratory parameters differed significantly. Infected devices were generally revised (A = 92%, B = 91%). Mean times to CSF sterilisation and normalisation of CSF microscopy were significantly shorter for group A (p < 0.05 and p < 0.005 respectively), as was duration of hospital stay (p < 0.002) and required length of systemic antimicrobial therapy (p < 0.001). CONCLUSIONS: Our findings indicate that IVT antibiotics enhance clinical and microbiological recovery and should therefore be considered for patients with CSF infection associated with a CSF diversion device. We recommend further evaluation of this approach in a prospective, randomised, controlled trial.

Are we following the guiding SIGN when managing paediatric head injury?

BACKGROUND AND AIMS: The Scottish Intercollegiate Guidelines Network (SIGN) has published guidelines for the management of children with head injuries. The management of children with head injuries admitted to our local unit under the Paediatric Surgeons has been audited to determine whether or not current practice follows SIGN recommendations. METHODS: Data were collected retrospectively from the case records of patients admitted between January and December 2007. The SIGN guideline 'Early Management of Patients with a Head Injury' (Guideline 46) was published in 2000 and updated in 2009 (Guideline 110). Head injury admission practices were audited against both guidelines. RESULTS: The case records of 200 patients were analysed. According to SIGN Guideline 46 (2000), 146 Computed Tomography (CT) scans were indicated but only 24 were performed (16%). The updated Guideline 110 (2009) suggests a CT scan was indicated in 24 patients and should have been considered in a further 87. However, only 12 (50%) and 18 (21%) patients were imaged in these respective groups. Both guidelines indicated neurosurgical review in 13 patients but sought in only 4 (31%). 50 patients were deemed to have suffered a significant head injury warranting follow-up, but this was arranged in only 14 (28%). CONCLUSIONS: Our study has identified that management of paediatric head injuries in our unit is reliant on clinical acumen rather than the SIGN guidelines when making decisions regarding the need for imaging, neurosurgical review and follow-up. We suggest further investigation is required to determine whether greater awareness and closer adherence with the guidelines would alter clinical outcomes.

Chordoma masquerading as a nerve root tumour -- a clinical lesson.

Chordomas usually arise in bone and are most commonly found in the midline axial skeleton. An accurate pre-operative diagnosis of chordoma is crucial, as survival is optimal when radical en bloc resection is performed at primary surgery. We report a rare case of cervical chordoma masquerading radiologically as an extracranial nerve sheath tumour. A laterally situated chordoma (centred extra-osseously in the neural foramen) was diagnosed radiologically as a neurofibroma pre-operatively. We review the key radiological features for diagnosis of chordoma. We consider the importance of pre-operative diagnosis of chordoma in guiding management and in determining survival.

Intrathecal baclofen therapy for neurological disorders: a sound knowledge base but many challenges remain.

Continuous infusion of intrathecal baclofen (ITB) via a subcutaneously implanted pump has developed over the last 20 years as a powerful tool in the management of spasticity in various adult and paediatric neurological conditions. Acting more focally on spinal GABA receptors, ITB causes fewer systemic side effects than orally administered baclofen. The result is facilitation of daily caring, and symptomatic relief from painful spasm. With increasing experience of ITB use, novel applications and indications are emerging. These include the management of dystonia and chronic neuropathic pain. However, despite some recent authoritative reviews, there is still uncertainty about optimal use and evaluation of this therapy. Many challenges remain. How can efficacy of therapy best be assessed both at primary testing and after pump implantation? What is the precise mechanism of baclofen action in different brain and spinal disorders associated with spasticity and dystonia? Does placement of the spinal catheter tip influence efficacy? What is the cranio-caudal gradient of CSF baclofen levels at given pump flow rates and does this matter? What CSF baclofen levels are efficacious in various conditions? Why do some patients with the same primary condition require large differences in ITB dose? What are the relative merits of programmable versus constant infusion rate pumps? What are the implications of setting up multidisciplinary teams for long term follow up? This review evaluates these questions and highlights other areas for further investigation.

Endoscopic transpapillary stenting of pancreatic duct disruption.

BACKGROUND/AIMS: Endoscopic transpapillary stenting of the pancreatic duct is increasingly being used in the management of pancreatic duct disruption. In contrast to its more established role in pancreatic duct obstruction, little is reported on the spectrum of indications and outcome in management of pancreatic duct disruption. METHODS: The indication for and outcome of transpapillary pancreatic duct stenting was analysed retrospectively in a UK supra-regional specialist pancreatobiliary centre, between January 1998 and August 2004. RESULTS: Data were obtained on 30 patients (19 male, 11 female, median age 53 years). The main indications for pancreatic duct stenting were: pancreatic pseudocyst, pancreatic ascites, pancreatic duct leak following necrosectomy, and pancreaticopleural fistula. The median duration of stenting was 6 weeks for fistulae and 10 weeks for pseudocysts. Twenty-one patients (70%) had complete resolution. After a median follow-up of 45 months, no recurrence was noted in successfully treated patents. CONCLUSION: Endoscopic transpapillary pancreatic duct stenting is an increasingly valuable treatment option in the management of pancreatic fistulae and pseudocysts.

Avulsion of the gallbladder following trivial injury.

Traumatic cholecystectomy is a rare condition that has always been described in the context of major trauma and associated liver or biliary injuries. We present a case of isolated traumatic cholecystectomy following a trivial injury which resulted in both a delayed presentation and a difficult diagnosis.

Naphthyl- and quinolylluciferin: green and red light emitting firefly luciferin analogues.

In the course of investigations on the possible involvement of the CIEEL (chemically initiated electron-exchange luminescence) mechanism in firefly bioluminescence, we have synthesized two novel firefly luciferin substrate analogues. D-Naphthylluciferin and D-quinolylluciferin were prepared by condensing D-cysteine with 2-cyano-6-hydroxynaphthalene and 2-cyano-6-hydroxyquinoline, respectively. These analogues are the first examples of bioluminescent substrates for firefly luciferase that do not contain a benzothiazole moiety. Firefly luciferase-catalyzed bioluminescence emission spectra revealed that compared to the normal yellow-green light of luciferin (lambda max = 559 nm), the emission from naphthylluciferin is significantly blue-shifted (lambda max = 524 nm); whereas quinolylluciferin emits orange-red light (lambda max = 608 nm). The fluorescence emission spectra, reaction pH optima, relative light yields, light emission kinetics and KM values of the analogues also were measured and compared to those of luciferin. Neither of the analogues produced the characteristic flash kinetics observed for the natural substrate. Instead, slower rise times to peak emission intensity were recorded. It appears that the formation of an intermediate from the analogue adenylates prior to the addition of oxygen is responsible for the slow rise times. The synthetic substrate analogues described here should be useful for future mechanistic studies.