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.

Awake craniotomy for high-grade gliomas - a prospective cohort study in a UK tertiary-centre.

BACKGROUND: Studies from the UK reporting on awake craniotomy (AC) include a heterogenous group of patients which limit the evaluation of the true impact of AC in high-grade glioma (HGG) patients. This study aims to report solely the experience and outcomes of AC for HGG surgery from our centre. METHODS: A prospective review of all patients who underwent AC for HGG from 2013 to 2019 were performed. Data on patient characteristics including but not limited to demographics, pre- and post-operative Karnofsky performance status (KPS), tumour location and volume, type of surgery, extent of resection (EOR), tumour histopathology, intra- and post-operative complications, morbidity, mortality, disease recurrence, progression-free survival (PFS) and overall survival (OS) from the time of surgery were collected. RESULTS: Fifteen patients (6 males; 9 females; 17 surgeries) underwent AC for HGG (median age = 55 years). Two patients underwent repeat surgeries due to disease recurrence. Median pre- and post-operative KPS score was 90 (range:80-100) and 90 (range:60-100), respectively. The EOR ranges from 60 to 100 % with a minimum of 80 % achieved in 81.3 % cases. Post-operative complications include focal seizures (17.6 %), transient aphasia/dysphasia (17.6 %), permanent motor deficit (11.8 %), transient motor deficit (5.9 %) and transient sensory disturbance (5.9 %). There were no surgery-related mortality or post-operative infection. The median PFS and OS were 13 (95%CI 5-78) and 30 (95%CI 21-78) months, respectively. CONCLUSION: This is the first study in the UK to solely report outcomes of AC for HGG surgery. Our data demonstrates that AC for HGG in eloquent region is safe, feasible and provides comparable outcomes to those reported in the literature.

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.

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.

Benchmarking short-term postoperative mortality across neurosurgery units: is hospital administrative data good enough for risk-adjustment?

BACKGROUND: Surgical mortality indicators should be risk-adjusted when evaluating the performance of organisations. This study evaluated the performance of risk-adjustment models that used English hospital administrative data for 30-day mortality after neurosurgery. METHODS: This retrospective cohort study used Hospital Episode Statistics (HES) data from 1 April 2013 to 31 March 2018. Organisational-level 30-day mortality was calculated for selected subspecialties (neuro-oncology, neurovascular and trauma neurosurgery) and the overall cohort. Risk adjustment models were developed using multivariable logistic regression and incorporated various patient variables: age, sex, admission method, social deprivation, comorbidity and frailty indices. Performance was assessed in terms of discrimination and calibration. RESULTS: The cohort included 49,044 patients. Overall, 30-day mortality rate was 4.9%, with unadjusted organisational rates ranging from 3.2 to 9.3%. The variables in the best performing models varied for the subspecialties; for trauma neurosurgery, a model that included deprivation and frailty had the best calibration, while for neuro-oncology a model with these variables plus comorbidity performed best. For neurovascular surgery, a simple model of age, sex and admission method performed best. Levels of discrimination varied for the subspecialties (range: 0.583 for trauma and 0.740 for neurovascular). The models were generally well calibrated. Application of the models to the organisation figures produced an average (median) absolute change in mortality of 0.33% (interquartile range (IQR) 0.15-0.72) for the overall cohort model. Median changes for the subspecialty models were 0.29% (neuro-oncology, IQR 0.15-0.42), 0.40% (neurovascular, IQR 0.24-0.78) and 0.49% (trauma neurosurgery, IQR 0.23-1.68). CONCLUSIONS: Reasonable risk-adjustment models for 30-day mortality after neurosurgery procedures were possible using variables from HES, although the models for trauma neurosurgery performed less well. Including a measure of frailty often improved model performance.

Assessing national patterns and outcomes of pituitary surgery: is hospital administrative data good enough?

PURPOSE: Patterns of surgical care, outcomes, and quality of care can be assessed using hospital administrative databases but this requires accurate and complete data. The aim of this study was to explore whether the quality of hospital administrative data was sufficient to assess pituitary surgery practice in England. METHODS: The study analysed Hospital Episode Statistics (HES) data from April 2013 to March 2018 on all adult patients undergoing pituitary surgery in England. A series of data quality indicators examined the attribution of cases to consultants, the coding of sellar and parasellar lesions, associated endocrine and visual disorders, and surgical procedures. Differences in data quality over time and between neurosurgical units were examined. RESULTS: A total of 5613 records describing pituitary procedures were identified. Overall, 97.3% had a diagnostic code for the tumour or lesion treated, with 29.7% (n = 1669) and 17.8% (n = 1000) describing endocrine and visual disorders, respectively. There was a significant reduction from the first to the fifth year in records that only contained a pituitary tumour code (63.7%-47.0%, p < .001). The use of procedure codes that attracted the highest tariff increased over time (66.4%-82.4%, p < .001). Patterns of coding varied widely between the 24 neurosurgical units. CONCLUSION: The quality of HES data on pituitary surgery has improved over time but there is wide variation in the quality of data between neurosurgical units. Research studies and quality improvement programmes using these data need to check it is of sufficient quality to not invalidate their results.

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.

Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells.

Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo-induced cellular network (iNet) 'webs', which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.

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.

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.