A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

Posterior cervical foraminotomy versus anterior cervical discectomy for Cervical Brachialgia: the FORVAD RCT.

Background: Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective: The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design: This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting: National Health Service trusts. Participants: Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions: Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures: The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results: The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow-Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale - Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale - Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions: The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration: This trial is registered as ISRCTN10133661. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.

Cervical brachialgia is pain that starts in the neck and passes down into the arm. Although most people with cervical brachialgia recover quickly, in some patients pain persists, and in 15% of patients pain is so severe that they are unable to work. In the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial, we investigated two neck surgeries used to treat this problem: posterior cervical foraminotomy (surgery from the back of the neck) and anterior cervical discectomy (surgery from the front of the neck). This trial aimed to find out if one of them is better than the other at relieving pain and more cost-effective for the National Health Service. We assessed patients' quality of life 1 year after their surgery and how their pain changed over the course of the year. We also measured the number of complications patients had in the first 6 weeks after their operation. Recruitment was slow and so the trial was stopped early, after only 23 patients from 11 hospitals had been randomly allocated to the two surgery groups. We had planned to recruit 252 participants to the trial; the number of participants we were able to recruit in practice was too small to enable us to determine which surgery is better at relieving pain. To find out why the trial had struggled to recruit, we asked hospital staff and participants about their experiences. We found that hospital staff sometimes struggled to organise everything needed to randomise patients on the day of surgery. Some staff also found it difficult to randomise patients as they had an opinion on which surgery they thought the patient should receive. The data collected in the trial will still be useful to help design future research. Finding out which surgery is better at relieving pain remains important, and the data we have collected will support answering this question in future.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

Tumour treating fields therapy for glioblastoma: current advances and future directions.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.

External Validation of Scoring Models to Predict Shunt Insertion after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The current study is an external validation of 4 scoring models proposed in the literature for predicting ventriculoperitoneal shunt insertion after aneurysmal subarachnoid hemorrhage (aSAH) using retrospective patient data from Sheffield Teaching Hospital (STH). METHODS: Data were collected on various demographics, and patients were individually scored using the 4 scoring models. Models were compared with each other using receiver-operator characteristic curves. The best model had the highest area under the curve. RESULTS: A total of 301 aSAH patients were referred to the neurosurgery department in STH between 1 January 2014 and 31 December 2017. Scoring model 4 also had the largest area under the curve of 0.853 (P < 0.001), and scoring model 3 had the lowest area under the curve of 0.654 (P = 0.036). CONCLUSIONS: Scoring model 4 was found to be the best scoring model out of the 4 scoring models externally validated to predict shunt dependency after an aSAH in STH patients. Scoring model 4 is less applicable in modern practice due to a higher proportion of coiling and use of the Hunt and Hess scale grade. A new scoring model is needed to predict shunt insertion in modern practice.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

Thirty-Day Mortality and Survival in Elderly Patients Undergoing Neurosurgery.

OBJECTIVES: With an aging population and advances in neuroanesthesia and critical care, an increasing subgroup of elderly patients have been undergoing neurosurgery. Of particular relevance is the cohort aged >80 years. The aim of the present study was to investigate the 30-day mortality and survival in this cohort after emergency and elective neurosurgery. METHODS: We performed a retrospective cohort study of all patients aged ≥70 years who had undergone a neurosurgical procedure from 2015 to 2017. The patient demographic data were identified, and independent predictors were found using logistic regression analysis. RESULTS: A total of 796 patients were included, of whom 622 were aged <80 years (group A) and 174 were aged >80 years (group B). Overall survival was 86.3% in group A and 79.9% in group B. The 30-day mortality between the elective (0.8%) and emergency (10.1%) patients was significantly different statistically (P < 0.001). Of the patients in groups A and B, 84.7% and 68.9% were discharged back to their usual residence, respectively. Logistic regression found emergency surgery to be an independent predictor of mortality. CONCLUSIONS: The current model for accepting elderly patients has been associated with good overall outcomes. The elderly should not be refused neurosurgery on the basis of their age alone. However, we applied fairly strict criteria, especially for those with subarachnoid hemorrhage, which should be factored into our results.

Compartmentalisation of the inflammatory response following aneurysmal subarachnoid haemorrhage.

INTRODUCTION: There is some evidence to suggest that a systemic and central nervous system (CNS) inflammatory response occurs following aneurysmal subarachnoid haemorrhage (aSAH) which may be related to the pathophysiology of early brain injury and delayed ischaemic neurological deficit (DIND). The aim of this study was to measure inflammatory mediator levels in plasma and cerebrospinal fluid (CSF) in the days following aSAH and to determine their association with aSAH, DIND and clinical outcome. MATERIAL AND METHODS: Plasma and CSF samples were obtained prospectively from patients with aSAH on days 1-3, 5, 7 and 9 and profiled for interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17, IL-18, macrophage chemotactic protein (MCP)-1, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)-α. Plasma and CSF samples from non-aSAH patients undergoing spinal anaesthesia were used as controls. RESULTS: The CSF levels of all cytokines investigated except for IL-1α were significantly higher in aSAH compared to controls in the first seven days of ictus. CSF levels of IL-1α (p = 0.014), IL-18 (p = 0.016), IL-6 (p = 0.0006) and IL-8 (p = 0.006) showed significant increases in the days following aSAH. Conversely IL-17 demonstrated a decrease. In particular, IL-4 was higher in the CSF of patients who had DIND at all time-points (p = 0.032). Plasma IL-6 and IL-8 levels were higher, and IL-1α levels lower, than controls at most time-points. All mediators demonstrated persistent elevation in the CSF compared to plasma apart from IL-1α and IL-18 which followed the opposite trend. Day 3 plasma IL-6 levels predicted poor outcome at six months (Exp(B) 1.12 1.03-1.22, P = 0.012), although this association was lost in the second analysis incorporating Fisher grade, WFNS grade and age. CONCLUSION: The post aSAH inflammatory response peaks on days 5-7 post ictus and remains largely compartmentalised within the CNS. IL-4 may have a particular association with DIND although its precise role in the pathophysiology of the disorder remains unclear. IL-6 predicted poor outcome but not independently of clinical grade, suggesting that it may be a surrogate marker of early brain injury.

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.

The 'Ins and Outs' of Early Preclinical Models for Brain Tumor Research: Are They Valuable and Have We Been Doing It Wrong?

In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early translational in vitro brain tumor models-a perspective given limited emphasis in the Consensus Statement, despite in vitro models being widely used to prioritize candidate therapeutic strategies prior to in vivo studies and subsequent clinical trials. We argue that successful translation of effective novel treatments into the clinic will require investment into the development of more predictive early pre-clinical models. It is in the interest of researchers, clinicians, and ultimately, patients that the most promising therapeutic candidates are identified and translated toward use in the clinic. Highlighting the value of early pre-clinical brain tumor models and debating how such models can be improved is of the utmost importance to the neuro-oncology research community and cancer research more broadly.

Correction to: Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

After publication of the original article [1], the authors notified that that one of the BNTRC institutional collaborator names was misspelled.

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions. METHODS: Dex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis. DISCUSSION: This multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition. TRIAL REGISTRATION: ISRCTN, ISRCTN80782810 . Registered on 7 November 2014. EudraCT, 2014-004948-35 . Registered on 20 March 2015. Dex-CSDH trial protocol version 3, 27 Apr 2017. This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request.

Low-Grade Glioma with Foci of Early Transformation Does Not Necessarily Require Adjuvant Therapy After Radical Surgical Resection.

BACKGROUND: Low-grade glioma (LGG) is a slow-growing tumor often found in young adults with minimal or no symptoms. As opposed to true low-grade lesions such as dysembryoplastic neuroepithelial tumors, they are associated with continuous growth and inevitable malignant transformation. METHODS: Case series of patients who have had en bloc resection of LGG with foci of anaplasia found embedded within the tumor specimen and not at margins. Patients were offered and agreed to a conservative approach avoiding adjuvant therapy. RESULTS: In the current case series, we describe a small subset of LGG that have shown foci of high-grade glioma but have shown behavior and growth tendencies similar to LGG after radical surgical resection. No patient to date has shown recurrent disease requiring adjuvant therapy. CONCLUSIONS: This case series supports the use of early aggressive surgical treatment of grade II gliomas that are premalignant. It acts as proof of concept that after radical resection, the presence of small foci of transformation embedded within grade II tumor may be treated with close radiologic surveillance rather than immediate adjuvant therapy.

Safety of Superior Petrosal Vein Sacrifice During Microvascular Decompression of the Trigeminal Nerve.

BACKGROUND: Microvascular decompression (MVD) is a safe and effective treatment for trigeminal neuralgia. Cerebellar venous infarction is a complication associated with surgical sacrifice of the superior petrosal vein (SPV). The SPV intervenes between the trigeminal nerve and the surgeon. Optimal exposure of the cisternal trigeminal nerve, particularly at the brainstem, can be achieved by sacrificing the SPV. We analyzed a cohort of 224 patients to determine the frequency of cerebellar venous infarction. METHODS: Retrospective analysis of records and neuroradiology for patients undergoing trigeminal MVD at the Manchester Skull Base Unit between August 1st 2008 and July 31st 2015. RESULTS: A total of 184 of 224 (82%) patients had coagulation and division of the main stem of the SPV. There were no cases of venous infarction. There was one case of mild, transient, cerebellar symptoms and signs, with no radiologic evidence of venous infarction. This patient had SPV sacrifice at surgery but also had postoperative thrombosis of the transverse sinus. Venous sinus thrombosis affected 5 of 184 (2.7%) patients. A total of 208 of 224 (93%) patients had a good outcome with improvement or resolution of their trigeminal neuralgia at 3 months. CONCLUSIONS: The overall rate of venous complications in this study was 2.7%; however, we had no cases of venous infarction in 184 patients who had sacrifice of the SPV. The incidence of venous infarction associated with SPV obliteration during MVD surgery is therefore <0.5%. SPV sacrifice may be used where necessary to optimize visualization of the root entry zone and maximize the chance of effective decompression of the trigeminal nerve.

Self-perceived health status following aneurysmal subarachnoid haemorrhage: a cohort study.

OBJECTIVE: The objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet. DESIGN: A two-cohort study. SETTING: A regional tertiary neurosurgical centre. PARTICIPANTS: 2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year. INTERVENTIONS: Routine care. PRIMARY AND SECONDARY OUTCOMES: A range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score. RESULTS: 214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximately 90% of aneurysms of the anterior circulation. Of those previously in full or part-time employment, 48.9% were unemployed at follow-up. All summated scales satisfied the Rasch measurement model requirements, such that their summed scores were a sufficient statistic. Given this, one-third of patients were noted to have a significant mood disorder and 25% had significant dysexecutive function. Patients with an MRS of 3, 4 or 5 had significantly worse scores on most outcome measures, but a significant minority of those with a score of zero had failed to return to work and displayed significant mood disorder. CONCLUSIONS: A range of self-reported cognitive and physical deficits have been highlighted in a cohort of patients with ASAH. While the MRS has been shown to provide a reasonable indication of outcome, in routine clinical follow-up it requires supplementation by instruments assessing dysexecutive function, memory and mood.

Fracture through fused cervical segments following trauma in a patient with Klippel-Feil syndrome.

Klippel-Feil syndrome (KPS) is a congenital spinal deformity characterised by the presence of at least one fused cervical segment. We report an unusual case of a fracture through fused cervical segment in a patient with KPS, who presented with quadriparesis and progressed on to develop respiratory failure and quadriplegia and who had a successful outcome following surgery. To the best of our knowledge, fracture through fused cervical segments in a Klippel-Feil patient has not been reported previously and this case report extends the spectrum of injuries seen in patients with KPS.

Ventriculoperitoneal shunt 30-day failure rate: a retrospective international cohort study.

BACKGROUND: With the need for transparency of surgical results, 30-day outcome measures have become increasingly important. Ventriculoperitoneal (VP) shunt failure is a substantial burden to patients and health care systems. OBJECTIVE: This study introduces the 30-day VP shunt failure rate as a possible barometer of surgical outcome and demonstrates its use in a national (United Kingdom [UK]) study and makes comparison with 2 published randomized, controlled trials (RCT). METHODS: A cohort study of all (except 1) pediatric neurosurgical centers in the UK and Ireland. All new and revision VP shunt operations were recorded for 2008 and 2009. Both newly placed and revised VP shunts were subject to Kaplan-Meier analysis, and 30-day failure rate was obtained. Data from 2 RCTs investigating new VP shunt technology were analyzed, and the 30-day failure rate was extracted for comparative purposes. RESULTS: The overall 30-day and 1-year failure rates for new shunts were 12.9% and 28.8%, respectively. The 30-day failure rate from 2 RCTs was comparable (14% and 16%, respectively). The failure rate of the subsequent revision of those new shunts was 20.7% at 30 days and 40.4% at 1 year. According to these data, shunt survival appears to be better if performed by a consultant pediatric neurosurgeon for revision surgery only. CONCLUSION: VP shunt survival in the UK is comparable to the published multicenter data investigating shunt survival. The 30-day failure rate may represent a better barometer of surgical outcome and should be used as a separate outcome measure in the design of future trials.

Identifying patient report outcomes relevant to aneurysmal subarachnoid hemorrhage follow-up.

Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunction using postal questionnaires. We assessed 214 patients using various tests of memory, mood and strategic thinking. Patients in good outcome categories (modified Rankin Scale [mRS] 0-1) nevertheless exhibited mood disorder (28%), memory deficit and executive dysfunction (20%). Return to work (49%) was most influenced by previous employment status, Rankin scale and mood.