Pediatric-Like Brain Tumors in Adults.

Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these tumors usually occur in childhood, they also rarely present in adult patients, either as a de novo diagnosis or as a delayed recurrence of a pediatric tumor in the setting of a patient that has transitioned into adult services.Due to the rarity of pediatric-like tumors in adults, the literature on these tumor types in adults is often limited to small case series, and treatment decisions are often based on the management plans taken from pediatric studies. However, the biology of these tumors is often different from the same tumors found in children. Likewise, adult patients are often unable to tolerate the side effects of the aggressive treatments used in children-for which there is little or no evidence of efficacy in adults. In this chapter, we review the literature and summarize the clinical, pathological, molecular profile, and response to treatment for the following pediatric tumor types-medulloblastoma, ependymoma, craniopharyngioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, germ cell tumors, choroid plexus tumors, midline glioma, and pleomorphic xanthoastrocytoma-with emphasis on the differences to the adult population.

Management of glioblastoma in elderly patients: A review of the literature.

High grade gliomas are the most common primary aggressive brain tumours with a very poor prognosis and a median survival of less than 2 years. The standard management protocol of newly diagnosed glioblastoma patients involves surgery followed by radiotherapy, chemotherapy in the form of temozolomide and further adjuvant temozolomide. The recent advances in molecular profiling of high-grade gliomas have further enhanced our understanding of the disease. Although the management of glioblastoma is standardised in newly diagnosed adult patients there is a lot of debate regarding the best treatment approach for the newly diagnosed elderly glioblastoma patients. In this review article we attempt to summarise the findings regarding surgery, radiotherapy, chemotherapy, and their combination in order to offer the best possible management modality for this group of patients. Elderly patients 65-70 with an excellent functional level could be considered as candidates for the standards treatment consisting of surgery, standard radiotherapy with concomitant and adjuvant temozolomide. Similarly, elderly patients above 70 with good functional status could receive the above with the exception of receiving a shorter course of radiotherapy instead of standard. In elderly GBM patients with poorer functional status and MGMT promoter methylation temozolomide chemotherapy can be considered. For elderly patients who cannot tolerate chemotherapy, hypofractionated radiotherapy is an option. In contrast to the younger adult patients, it seems that a careful individualised approach is a key element in deciding the best treatment options for this group of patients.

Motor seizures confer overall survival benefit in who grade 2 glioma.

OBJECTIVE: The prevalence of epilepsy in World Health Organization (WHO) grade 2 glioma is high, with seizures being the presenting symptom in 60%-90%. We explore the epidemiology of seizures in this patient population in a regional neurosurgical center. METHODS: Electronic health records of patients with histologically-proven WHO grade 2 glioma (n = 228) were reviewed between 1997 and 2021, with data collected including patient demographics, epilepsy prevalence, and seizure semiology. The influence of seizure type on overall survival was calculated using a Cox proportional hazards model. RESULTS: Overall, 197 of 228 patients (86.4%) were diagnosed with epilepsy-either at presentation or during the course of their disease. Male patients were more likely than female patients to be diagnosed with epilepsy (91.1% vs 77.1%, p = .003) and, in those with epilepsy, more likely to experience at least one focal to bilateral tonic-clonic seizure (69.4% vs 54.1%, p = .05). Patients with left-sided tumors were twice as likely to have experienced a focal to bilateral tonic-clonic seizure (p = .02, odds ratio [OR] = .47). Predominantly experiencing seizures with motor activity appeared to confer better overall survival, with a 65% decrease in the risk of death 10 years post diagnosis (hazard ratio [HR] = .35, p = .02). This is despite accounting for previously described prognostic markers including tumor histology/genetics, time from diagnosis to surgery, and the extent of tumor resection. SIGNIFICANCE: Motor seizure activity is a frequent feature in WHO grade 2 glioma and appears to confer a survival benefit regardless of histology or surgical factors. Seizures due to dominant hemisphere tumors may be more likely to propagate and cause bilateral tonic-clonic activity.

Feasibility and safety of a non-operative clinical strategy for radiologically diagnosed low grade anterior mesial temporal tumours in the absence of a histological diagnosis.

BACKGROUND: Although resection of mesial temporal lobe lesions can be achieved with relatively low morbidity, resective surgery is not without risk. Whilst many lesions found in the anterior mesiotemporal lobe are low-grade entities, transforming and high-grade lesions have also been demonstrated. We investigate the feasibility of utilising serial quantitative volumetric imaging, to determine if a strategy of imaging surveillance can be safely employed for the management of radiologically diagnosed anterior mesial temporal low-grade tumours without a confirmed histological diagnosis. METHODS: A retrospective case-note and radiology review design were utilised. The primary presenting symptomatology was recorded together with the efficacy of symptomatic control. Volumetric analysis of MRI images was performed using Brainlab software. Pre- and post-operative neuropsychological data were analysed. RESULTS: 35 patients were identified with a radiological diagnosis of a low-grade anterior mesial temporal lobe tumour. Of these, 29% (n = 10) underwent surgical resection. For the whole cohort, the mean tumour volume at diagnosis was 6.5cm3, with a mean volumetric expansion of 1.4% per month. A significant difference was found between the volumetric expansion rate of those that underwent surgical treatment and those that did not (4.9% per month vs 0.06% per month, p < .01). Of those cases that did not undergo surgical resection, no significant difference was seen between the initial diagnostic volume and the volume at the time of their most recent interval surveillance scan (p = .97). New onset epilepsy was significantly associated with a requirement for eventual surgical tumour resection; relative risk = 6.25, 95% CI = 1.5-25.9, p = .0114. CONCLUSION: Where medical seizure control is adequate, we suggest that conservative management is feasible even in the absence of a confirmed histological diagnosis. However, in patients aged over 50 years with new onset epilepsy, a lower threshold for intervention should be considered.

Video article: the subtemporal extradural approach to cavernous sinus tumour.

OBJECTIVE: Here we demonstrate via operative video the subtemporal extradural approach to a tumour in the cavernous sinus. METHODS: The extradural approach is performed here in a paediatric patient (a 15-year-old child) via a right extended pterional osteoplastic craniotomy with removal of the zygomatic arch. The operative microscope is introduced, and the dura is divided at the superior orbital fissure into endosteal and meningeal layers using a diamond knife. The middle cranial fossa floor is drilled flat to increase access, and the plane is further developed towards the cavernous sinus. The tumour is seen bulging from within the cavernous sinus, and the cavernous sinus is opened in the anteromedial triangle between cranial nerves Vi and Vii. After biopsy, the tumour is debulked with an ultrasonic aspirator. Doppler is used to identify the internal carotid artery and preserve it. The bone flap is replaced, and the wound is closed in layers in standard fashion. RESULTS: The patient recovered well and was discharged on post-operative day 3. Persistent sixth nerve palsy (present pre-operatively) was present; however, otherwise, there was good recovery from surgery. Good resection of tumour is demonstrated on post-operative MR imaging. CONCLUSIONS: This approach is uncommon but important as it enables extradural access to the cavernous sinus, minimising the complications associated with an intradural approach such as cortical injury. In this video, we also demonstrate the fundamental anatomy using annotation and cadaveric images to enhance understanding required for the neurosurgeon to successfully complete this approach. The patient consented to the procedure in the standard fashion.

Do animal models of brain tumors replicate human peritumoral edema? a systematic literature search.

INTRODUCTION: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. METHODS: A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with "brain tumors", "brain edema" and "animal models". RESULTS: We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. CONCLUSION: No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.

Levetiracetam as a first-line antiseizure medication in WHO grade 2 glioma: Time to seizure freedom and rates of treatment failure.

OBJECTIVE: The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma. METHODS: This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line. RESULTS: Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates. SIGNIFICANCE: More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.

Progesterone as a Neuroprotective Agent in Neonatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review.

Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of progesterone (PROG) include anti-apoptotic, anti-inflammatory, and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema, and excitotoxicity. In pre-clinical studies of neonatal HIE, PROG has neuroprotective properties but has not been the subject of systematic review. Here, our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria. Population: human neonates with HIE/animal models of HIE; intervention: PROG +/- other agents; comparison: V.S. control; outcome: pathological, neurobehavioural, and mechanistic outcome measures. Medline, EMBASE, and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and keywords. Study inclusion, data extraction, and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG reduced neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) insult in 8 and 3 studies, respectively. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies, and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing, and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without TH.

Day 2 neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for prediction of delayed cerebral ischemia in subarachnoid hemorrhage.

OBJECTIVE: Recent evidence has suggested that an admission neutrophil-to-lymphocyte ratio (NLR) of ≥ 5.9 predicts delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH). The primary aims of this study were to assess reproducibility and to ascertain the predictive ability of NLR on subsequent days postictus. Secondary aims included identification of additional inflammatory markers. METHODS: A single-center, retrospective study of all patients aged ≥ 18 years with aSAH between May 2014 and July 2018 was performed. Patient characteristics, DCI incidence, operative features, and outcomes (on discharge and at 3 months postictus) were recorded. C-reactive protein (CRP) and full blood count differentials were recorded on admission and through day 8 postictus or at discharge. In total, 403 patients were included in the final analysis. RESULTS: Ninety-six patients (23.8%) developed DCI with a median time from ictus of 6 days (IQR 3.25-8 days). A platelet-to-lymphocyte ratio (PLR) cutoff ≥ 157 and CRP cutoff ≥ 27 was used in our cohort. In a multiple binary logistic regression model, after controlling for known DCI predictors, day 2 NLR ≥ 5.9 (OR 2.194, 95% CI 1.099-4.372; p = 0.026), day 1 PLR ≥ 157 (OR 2.398, 95% CI 1.1072-5.361; p = 0.033), day 2 PLR ≥ 157 (OR 2.676, 95% CI 1.344-5.329; p = 0.005), and CRP ≥ 27 on days 3, 4, and 5 were predictive of DCI. CONCLUSIONS: The results of this study have confirmed the association between NLR and DCI and have demonstrated the predictive potential of PLR and CRP, suggesting that NLR and PLR at day 2, and CRP from day 3 onward, may be better predictors of DCI than those measurements at the time of ictus.

ABO blood group in aneurysmal subarachnoid haemorrhage-a pilot study.

PURPOSE: To evaluate the distribution and impact of ABO blood group on the baseline characteristics and clinical outcomes of patients presenting with aneurysmal subarachnoid haemorrhage (aSAH). METHODS: Retrospective, single-centre study of patients admitted to a neurosurgical department in the UK, with a diagnosis of spontaneous subarachnoid haemorrhage between May 2014 and January 2020. Patients were categorised by ABO blood type and by Rhesus status. Clinical outcomes such as initial bleeding, rebleeding, delayed cerebral ischaemia (DIND) and venous thromboembolism were analysed in relation to the size of their association with ABO blood type. Hospital mortality rate, Glasgow Outcome Score (GOS) - at discharge and 3 months post-ictus, requirement for ventriculoperitoneal shunt insertion, discharge destination and inpatient length of stay were also considered. RESULTS: Four-hundred twelve adult patients admitted with aSAH were included in our analysis. The distribution of ABO group or Rhesus status in our cohort did not differ significantly from the general population in the UK. Blood group A patients had a significantly increased risk of developing DIND, compared with non-blood group A patients (OR, 1.88 [95% CI: 1.10-3.21]). CONCLUSIONS: ABO blood type appears to influence aSAH sequelae. Blood group A patients are at highest risk of DIND following aSAH.

The role of sex genotype in paediatric CNS tumour incidence and survival.

PURPOSE: Evidence exists, in CNS germinomas and medulloblastomas (MB), that patient sex significantly influences incidence and outcome. The role of sex genotype in other paediatric CNS tumours remains unclear. This study sought to examine the role of sex genotype in CNS tumour incidence and overall survival (OS). METHODS: Age-adjusted incidence and OS rates were collected from the Surveillance Epidemiology and End Result (SEER) registry between 2000 and 2011 for common paediatric (<=19 years) CNS tumours: pilocytic astrocytoma (PA), anaplastic astrocytoma, glioblastoma (GBM), medulloblastoma, supratentorial CNS embryonal tumour, ependymoma, and germinoma. All patients with histologically confirmed, ICD-03 coded, first tumours, were included. Kaplan-Meier and Cox regression analyses were used to calculate hazard ratios (HR). RESULTS: The total cases are as follows: males=3018 and females=2276. Highest incidence was seen in PA (n=2103). GBM displayed the worst OS, whilst PA displayed the best. Higher incidence was observed in males for all tumours, except PA. Females with ependymoma had significantly better OS compared to males, whereas males with germinomas had better OS compared to females. Females <1 year with AA had better OS than males. Increasing age significantly improved male and female survival in ependymoma and medulloblastoma. CONCLUSION: Interrogating population-based registries such as SEER minimises bias and provides credible data. Observed differences in incidence and OS between the sexes for different paediatric CNS tumours provide useful prognostic information for clinicians. Sex genotype was a significant independent prognostic factor in ependymomas and germinomas. Further investigation of possible epigenetic and hormonal differences may provide sex-specific vulnerabilities that may be exploitable for targeted therapy.

Effects of brain radiotherapy on cognitive performance in adult low-grade glioma patients: A systematic review.

Grade II gliomas are slow growing tumours that usually affect younger patients. The mainstream treatment modality at present is surgical. The role of radiation therapy in the management of grade II gliomas has been the subject of considerable debate. Radiation therapy has a proven potential to prolong progression free and overall survival in high-risk patients, but may also produce long-term cognitive deficits. Since grade II glioma patients are expected to live several years, retention of cognitive capacity and quality of life is an equally important endpoint as prolonging progression free survival. Our overarching goal is to critically review the available evidence on the possible neuropsychological effects of postoperative radiotherapy in adult grade II glioma patients. We performed a systematic literature search in Medline, Embase and Cochrane databases up to 1st of May 2020 for studies assessing the cognitive effects of radiation therapy on grade II glioma patients. Eleven studies meeting our inclusion criteria provide either negative or contradictory data regarding the cognitive domains affected, while major confounding variables remain incompletely addressed. The available evidence does not adequately support the notion that current radiation therapy protocols independently produce substantial cognitive decline in grade II glioma patients and therefore it would be premature to argue that radiation associated cognitive morbidity outweighs the benefit of prolonged survival. A large prospective study incorporating a full battery of neuropsychological testing, sufficiently long-term follow-up period and tight control of confounders is due to provide high quality data.

A comparison of the extent of resection in pineal region tumours via the occipital transtentorial and supracerebellar infratentorial approaches.

PURPOSE: To perform a single unit review of surgical approaches to the pineal region, looking to ascertain if trends were identifiable regarding the extent of resection and the rate of post-operative complications between approaches. We hypothesised that each approach would offer different exposure of the pineal region which may result in poor access to certain areas of the tumour. This may lead to residual tumour in reliable and predictable locations, and an awareness of these regions could help with pre-operative planning and lead to higher levels of suspicion when inspecting these regions intraoperatively. MATERIALS AND METHODS: We performed a single centre, retrospective review of all adult and paediatric patients who underwent surgical debulking of pineal region tumours between 2008 and 2019. Patient demographics, pre- and post- operative radiological tumour volume data, histology and complication rates were compared between the two groups. RESULTS AND CONCLUSIONS: The occipital transtentorial approach resulted in a significantly lower extent of resection when compared to the supracerebellar infratentorial approach (p = 0.04), even after multivariate analysis (p = 0.006). There was no significant difference between the location of residual tumour relative to the superior colliculi between the two approaches (p = 1.00). There was a significant incidence of radiological occipital lobe ischaemia from the occipital transtentorial approach (p = 0.04). Within our series, we did not demonstrate a consistent location of residual tumour relative to the surgical approach chosen. Whilst there was a significant difference with regards to the extent of resection between approaches, in the context of small comparative groups this is difficult to draw far-reaching conclusions from.

Intramedullary spinal cord tumours - a single Centre, 10-year review of clinical and pathological outcomes.

BACKGROUND: Intramedullary spinal cord tumours are relatively rare tumours of the central nervous system. Surgical outcomes are affected by many variables, including pre-operative neurological function, tumour histology and extent of resection. Emphasis remains on surgical treatment due to limited adjunctive therapeutic options and poor drug penetration. OBJECTIVE: To identify clinically relevant predictors of progression free survival by retrospectively analysing the extent of resection, pre- and post-operative neurological function and histology in intramedullary spinal cord tumours from a single neurosurgical centre over 10 years. METHODS: Forty-three adult cases were identified from a surgical database. Variables collected included pre-and post-operative Frankel Grade and Modified McCormick Scale assessments, tumour histology, extent of resection and length of follow up. Chi-Squared, Kaplan-Mier Survival and Mann-Whitney U-tests were completed. RESULTS: Ependymoma (41.9%) and haemangioblastoma (14.0%) were the commonest tumour histologies. In total, 17 different histological tumours were identified in the series. There was a statistically significant relationship between identification of the tumour plane and extent of resection (p < 0.01), along with the extent of resection and recurrence (p = 0.04). Compared to the other histological subtypes, ependymoma's demonstrated a significantly greater extent of resection (p = 0.01). There was a significant relationship between the grade of tumour and progression-free survival (p < 0.01). CONCLUSION: Tumour plane and the extent of tumour resection are significant determinants of progression-free survival. Ependymoma, whilst being the commonest histology in our series were also the most resectable. Whilst complete resection reduces the rate of recurrence, tumour grade is the most important predictor of outcome. Given the importance of the extent of resection, and following a similar trend to other low volume pathologies, these tumours should only be tackled by neurosurgeons with experience in their resection.

'Possible shunt malfunction' pathway for paediatric hydrocephalus-a study of clinical outcomes and cost implications.

BACKGROUND: Shunt insertion for hydrocephalus is a common paediatric neurosurgery procedure. Shunt complications are frequent with an estimated 20-40% failure rate within the first year, and 4.5% per year subsequently. We have an open-door 'possible shunt malfunction' pathway for children treated with a shunt or endoscopic third ventriculostomy, providing direct ward access to ensure rapid assessment and timely management of children. OBJECTIVE: To audit the 'possible shunt malfunction' pathway in terms of clinical outcomes (percentage-confirmed shunt dysfunction and number of re-attendances) and costs. METHODS: Clinical data for patients attending the triage service were prospectively recorded over 7 months-including the number of attendances, previous shunt revisions, shunt type, investigations performed (CT, x-rays), and outcome. Costings (e.g. costs of physician, inpatient stay, investigations) were obtained from the hospital's procurement department. RESULTS: In the study period, there were 81 attendances by 62 patients and only 16% of attendances resulted in surgical management (either shunt revision or ETV). Approximately 17% of patients re-attended at least once. The average cost per attendance in our pathway was £765.57 ($969.63; €858.73). The total expenditure for the pathway over 7 months was £62,011.03 ($78,540.07; €69,556.81), with inpatient stay making up the biggest percentage of cost (49.2%). CONCLUSION: Only 16% (13 attendances) of those attending through our pathway required neurosurgical intervention. Investigations for possible blocked shunt come at significant health, social, and financial cost. High rates of shunt failure, re-attendance, investigations, and inpatient stays incur a sizable financial burden to the healthcare system.

Prognostic value of leukocytosis in pediatric traumatic brain injury.

OBJECTIVE: The purpose of this study was to assess leukocytosis and its prognostic value in pediatric isolated traumatic brain injury (TBI). METHODS: Two hundred one children with isolated TBI admitted to the authors' institution between June 2006 and June 2018 were prospectively followed and their data retrospectively analyzed. Initial blood leukocyte count (i.e., white cell count [WCC]), Glasgow Coma Scale (GCS) score, CT scans, duration of hospital stay, and Pediatric Cerebral Performance Category Scale (PCPCS) scores were analyzed. RESULTS: The mean age was 4.2 years (range 0.2-16 years). Seventy-four, 70, and 57 patients had severe (GCS score 3-8), moderate (GCS score 9-13), and mild (GCS score 14-15) TBI, respectively, with associated WCC of 20, 15.9, and 10.7 × 109/L and neutrophil counts of 15.6, 11.3, and 6.1 × 109/L, respectively (p < 0.01). Higher WCC and neutrophil counts were demonstrated in patients with increased intracranial mass effect on CT, longer hospital stay, and worse 6-month PCPCS score (p < 0.05). Multivariate regression revealed a cutoff leukocyte count of 16.1 × 109/L, neutrophil count of 11.9 × 109/L, and neutrophil-to-lymphocyte ratio (NLR) of 5.2, above which length of hospital stay and PCPCS scores were less favorable. Furthermore, NLR was the second most important independent risk factor for a poor outcome (after GCS score). The IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) adult TBI prediction model applied to this pediatric cohort demonstrated increased accuracy when WCC was incorporated as a risk factor. CONCLUSIONS: In the largest and first prospective study of isolated pediatric head injury to date, the authors have demonstrated that WCC > 16.1 × 109/L, neutrophil count > 11.9 × 109/L and NLR > 5.2 each have predictive value for lengthy hospital stay and poor PCPCS scores, and NLR is an independent risk factor for poor outcome. Incorporating the initial leukocyte count into TBI prediction models may improve prognostication.

Can quantifying the extent of 'high grade' features help explain prognostic variability in anaplastic astrocytoma?

PURPOSE: Both phenotypic and genotypic variations now underpin glioma classification, thus helping to more accurately guide their clinical management. However, WHO Grade III anaplastic astrocytoma (AA) remains an unpredictable, heterogeneous entity; displaying a variable prognosis, clinical course and treatment response. This study aims to examine whether additional tumour characteristics influence either overall survival (OS) or 3-year survival in AA. MATERIALS AND METHODS: Data were collected on all newly diagnosed cases of AA between 2003 and 2014, followed up for a minimum of 3 years. Molecular information was obtained from case records and if missing, was re-analysed. Histological slides were independently examined for Ki-67 proliferation index, cellularity and number of mitotic figures. Kaplan-Meier and Cox regression analyses were used to assess OS. RESULTS: In total, 50 cases were included with a median OS of 14.5 months (range: 1-150 months). Cumulative 3-year survival was 31.5%. Median age was 50 years (range: 24 - 77). Age, IDH1 mutation status, lobar location, oncological therapy and surgical resection were significant independent prognostic indicators for OS. In cases demonstrating an OS ≥ 3 years (n = 15), Ki-67 index, number of mitotic figures and percentage areas of 'high cellularity' were significantly reduced, i.e. more characteristic of lower-grade/WHO Grade II glioma. CONCLUSIONS: IDH1 status, age, treatment and location remain the most significant prognostic indicators for patients with AA. However, Ki-67 index, mitotic figures and cellularity may help identify AA cases more likely to survive < 3 years, i.e. AA cases more similar to glioblastoma and those cases more likely to survive > 3 years, i.e. more similar to a low-grade glioma.

Recovery of major cognitive deficits following awake surgery for insular glioma: a case report.

BACKGROUND: Resection of insular tumours utilising modern neurosurgical techniques has become commonplace since its safety and reduced morbidity was first established. Interest has grown in the cognitive consequences of insula neurosurgery and studies have largely shown postoperative stability or minor decline. Major or widespread improvements in cognitive functioning following resection of insular tumours have not previously been reported. CASE DESCRIPTION: A 34-year-old, left-handed man with a right insular low-grade glioma (LGG) presented with seizures, nausea, altered sensation, poor balance and extensive cognitive decline. Comprehensive neuropsychological assessment highlighted a striking left hemispatial neglect and impairments in attention, working memory, verbal learning and fluency. During an awake craniotomy with functional cortical mapping, he reported intraoperative improvements in hand function and processing speed. Resolution of the neglect and significant improvements in cognition, mood and functioning were observed at follow-up and sustained over several years. CONCLUSIONS: This case highlights that right insular LGGs can cause significant cognitive and functional deficits and that neurosurgery has the potential to alleviate these difficulties to an extent beyond those documented in the extant literature.

Fronto-orbital advancement and reconstruction using reverse frontal bone graft without the use of orbital bar: a technical note.

INTRODUCTION: We describe our technique of using reverse frontal bone graft for FOAR for patients with metopic or coronal synostosis and present our complications using the Leeds classification system for complications in craniosynostosis surgery. METHODS: Since April 2015, seventeen patients have been operated using this technique. We perform a frontal bone graft that is then reversed, and supraorbital margins are drilled out. The orbital bar is then removed and drilled down to make bone dust and on-lay bone grafts which are then used to fill gaps on exposed dura and fill in around the temporal region. RESULTS: All 17 patients who underwent this technique have good cosmetic results. We report 5 (29%) complications and 8 (47%) blood transfusions (7 exposures, 1 cell salvage).

Is surgery more about doing than thinking?

Detailed thought, knowledge, complex analysis, reasoned judgment and professionalism all fundamentally underpin a surgeon's work and training, yet there is a popularly held view that accomplished surgeons are primarily concerned with performing procedures. A review of pedagogical, social and medical literature, together with personal reflections from the authors, shows that a surgeon's work is multi-faceted. This article discusses the technical skills of operating as a reflection of the 'tip of the iceberg' of a surgeon's cognition, the increasingly multidisciplinary strategic approach of surgeons today, the importance of surgical decision making, the influence of robotics, the role of non-medically trained staff, surgeons' role in postoperative care, adaptive expertise and the formation of professional identity. In so doing, a much wider view of a surgeon than simply 'doing' or 'thinking' is presented with implications for surgical training.