Profiling of circulating glial cells for accurate blood-based diagnosis of glial malignancies.

Here, we describe a blood test for the detection of glial malignancies (GLI-M) based on the identification of circulating glial cells (CGCs). The test is highly specific for GLI-M and can detect multiple grades (II-IV) and subtypes including gliomas, astrocytomas, oligodendrogliomas, oligoastrocytomas and glioblastomas, irrespective of gender and age. Analytical validation of the test was performed as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Real-world performance characteristics of the test were evaluated in four clinical (observational) studies. The test has high analytical sensitivity (95%), specificity (100%) and precision (coefficient of variation [CV] = 13.7% for repeatability and CV = 23.5% for within laboratory precision, both at the detection threshold) and is not prone to interference from common drugs and serum factors. The ability of the test to detect and differentiate GLI-M from non-malignant brain tumours (NBT), brain metastases from primary epithelial malignancies (EPI-M) and healthy individual donors (HD) was evaluated in four clinical cohorts. Across these clinical studies, the test showed 99.35% sensitivity (95% confidence interval [CI]: 96.44%-99.98%) and 100% specificity (95% CI: 99.37%-100%). The performance characteristics of this test support its clinical utility for diagnostic triaging of individuals presenting with intracranial space-occupying lesions (ICSOL).

The role of BCL2L13 in glioblastoma: turning a need into a target.

Glioblastoma (GBM) is the most common aggressive central nervous system cancer. GBM has a high mortality rate, with a median survival time of 12-15 months after diagnosis. A poor prognosis and a shorter life expectancy may result from resistance to standard treatments such as radiation and chemotherapy. Temozolomide has been the mainstay treatment for GBM, but unfortunately, there are high rates of resistance with GBM bypassing apoptosis. A proposed mechanism for bypassing apoptosis is decreased ceramide levels, and previous research has shown that within GBM cells, B cell lymphoma 2-like 13 (BCL2L13) can inhibit ceramide synthase. This review aims to discuss the causes of resistance in GBM cells, followed by a brief description of BCL2L13 and an explanation of its mechanism of action. Further, lipids, specifically ceramide, will be discussed concerning cancer and GBM cells, focusing on ceramide synthase and its role in developing GBM. By gathering all current information on BCL2L13 and ceramide synthase, this review seeks to enable an understanding of these pieces of GBM in the hope of finding an effective treatment for this disease.

Noise suppression of proton magnetic resonance spectroscopy improves paediatric brain tumour classification.

Proton magnetic resonance spectroscopy (1H-MRS) is increasingly used for clinical brain tumour diagnosis, but suffers from limited spectral quality. This retrospective and comparative study aims at improving paediatric brain tumour classification by performing noise suppression on clinical 1H-MRS. Eighty-three/forty-two children with either an ependymoma (ages 4.6 ± 5.3/9.3 ± 5.4), a medulloblastoma (ages 6.9 ± 3.5/6.5 ± 4.4), or a pilocytic astrocytoma (8.0 ± 3.6/6.3 ± 5.0), recruited from four centres across England, were scanned with 1.5T/3T short-echo-time point-resolved spectroscopy. The acquired raw 1H-MRS was quantified by using Totally Automatic Robust Quantitation in NMR (TARQUIN), assessed by experienced spectroscopists, and processed with adaptive wavelet noise suppression (AWNS). Metabolite concentrations were extracted as features, selected based on multiclass receiver operating characteristics, and finally used for identifying brain tumour types with supervised machine learning. The minority class was oversampled through the synthetic minority oversampling technique for comparison purposes. Post-noise-suppression 1H-MRS showed significantly elevated signal-to-noise ratios (P < .05, Wilcoxon signed-rank test), stable full width at half-maximum (P > .05, Wilcoxon signed-rank test), and significantly higher classification accuracy (P < .05, Wilcoxon signed-rank test). Specifically, the cross-validated overall and balanced classification accuracies can be improved from 81% to 88% overall and 76% to 86% balanced for the 1.5T cohort, whilst for the 3T cohort they can be improved from 62% to 76% overall and 46% to 56%, by applying Naïve Bayes on the oversampled 1H-MRS. The study shows that fitting-based signal-to-noise ratios of clinical 1H-MRS can be significantly improved by using AWNS with insignificantly altered line width, and the post-noise-suppression 1H-MRS may have better diagnostic performance for paediatric brain tumours.

A systematic review of the impact of brain tumours on risk of motor vehicle crashes.

PURPOSE: Brain tumours are associated with neurocognitive impairments that are important for safe driving. Driving is vital to maintaining patient autonomy, despite this there is limited research on driving capacity amongst patients with brain tumours. The purpose of this review is to examine MVC risk in patients with brain tumours to inform development of clearer driving guidelines. METHODS: A systematic review was performed using Medline and EMBASE. Observational studies were included. The outcome of interest was MVC or measured risk of MVC in patients with benign or malignant brain tumours. Descriptive analysis and synthesis without meta-analysis were used to summarise findings. A narrative review of driving guidelines from Australia, United Kingdom and Canada was completed. RESULTS: Three studies were included in this review. One cohort study, one cross-sectional study and one case-control study were included (19,135 participants) across United States and Finland. One study evaluated the incidence of MVC in brain tumour patients, revealing no difference in MVC rates. Two studies measured MVC risk using driving simulation and cognitive testing. Patients found at higher risk of MVC had greater degrees of memory and visual attention impairments. However, predictive patient and tumour characteristics of MVC risk were heterogeneous across studies. Overall, driving guidelines had clear recommendations on selected conditions like seizures but were vague surrounding neurocognitive deficits. CONCLUSION: Limited data exists regarding driving behaviour and MVC incidence in brain tumour patients. Existing guidelines inadequately address neurocognitive complexities in this group. Future studies evaluating real-world data is required to inform development of more applicable driving guidelines. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2023 CRD42023434608.

Experiences of families post treatment for childhood brain tumours during medical clinic consultations regarding health-related quality of life, unmet needs and communication barriers: A qualitative exploration.

BACKGROUND: Many studies highlight poor health-related quality of life (HRQoL) in children treated for brain tumours and their parents. However, little is known about the extent to which their informational, healthcare and communication needs regarding HRQoL are met during medical outpatient consultations. AIM: To explore the experiences of families regarding communication with physicians about HRQoL issues during consultations after treatment for childhood brain tumours. METHODS: Interviews were conducted with 18 families of children and adolescents aged 8-17 years after completion of brain tumour treatment. Participants had completed treatment within the last 5 years and were receiving regular outpatient follow-up care. Thematic analysis was undertaken using the Framework Method. RESULTS: Five main themes were identified: (i) unmet emotional and mental health needs; (ii) double protection; (iii) unmet information needs; (iv) communication barriers within consultations; and (v) finding a new normal. CONCLUSION: There was a need to improve communication between clinicians and these families, improve information provision, and overcome barriers to conversing with children within these outpatient consultations. Children and their parents should be supported to voice their current needs and concerns regarding their HRQoL. These findings will inform further development of the UK version of the 'KLIK' patient- and parent-reported outcome (PROM) portal.

The anatomy of neuroepithelial tumours.

Many neurological conditions conceal specific anatomical patterns. Their study contributes to the understanding of disease biology and to tailored diagnostics and therapy. Neuroepithelial tumours exhibit distinct anatomical phenotypes and spatiotemporal dynamics that differ from those of other brain tumours. Brain metastases display a preference for the cortico-subcortical boundaries of watershed areas and have a predominantly spherical growth. Primary CNS lymphomas localize to the white matter and generally invade along fibre tracts. In neuroepithelial tumours, topographic probability mapping and unsupervised topological clustering have identified an inherent radial anatomy and adherence to ventriculopial configurations of specific hierarchical orders. Spatiotemporal probability and multivariate survival analyses have identified a temporal and prognostic sequence underlying the anatomical phenotypes of neuroepithelial tumours. Gradual neuroepithelial de-differentiation and declining prognosis follow (i) an expansion into higher order radial units; (ii) a subventricular spread; and (iii) the presence of mesenchymal patterns (expansion along white matter tracts, leptomeningeal or perivascular invasion, CSF spread). While different pathophysiological hypotheses have been proposed, the cellular and molecular mechanisms dictating this anatomical behaviour remain largely unknown. Here we adopt an ontogenetic approach towards the understanding of neuroepithelial tumour anatomy. Contemporary perception of histo- and morphogenetic processes during neurodevelopment permit us to conceptualize the architecture of the brain into hierarchically organized radial units. The anatomical phenotypes in neuroepithelial tumours and their temporal and prognostic sequences share remarkable similarities with the ontogenetic organization of the brain and the anatomical specifications that occur during neurodevelopment. This macroscopic coherence is reinforced by cellular and molecular observations that the initiation of various neuroepithelial tumours, their intratumoural hierarchy and tumour progression are associated with the aberrant reactivation of surprisingly normal ontogenetic programs. Generalizable topological phenotypes could provide the basis for an anatomical refinement of the current classification of neuroepithelial tumours. In addition, we have proposed a staging system for adult-type diffuse gliomas that is based on the prognostically critical steps along the sequence of anatomical tumour progression. Considering the parallels in anatomical behaviour between different neuroepithelial tumours, analogous staging systems may be implemented for other neuroepithelial tumour types and subtypes. Both the anatomical stage of a neuroepithelial tumour and the spatial configuration of its hosting radial unit harbour the potential to stratify treatment decisions at diagnosis and during follow-up. More data on specific neuroepithelial tumour types and subtypes are needed to increase the anatomical granularity in their classification and to determine the clinical impact of stage-adapted and anatomically tailored therapy and surveillance.

Approaches to supratentorial brain tumours in children.

The differential diagnosis of supratentorial brain tumours in children can be challenging, especially considering the recent changes to the WHO classification of CNS tumours published in 2021. Many new tumour types have been proposed which frequently present in children and young adults and their imaging features are currently being described by the neuroradiology community. The purpose of this article is to provide guidance to residents and fellows new to the field of paediatric neuroradiology on how to evaluate an MRI of a patient with a newly diagnosed supratentorial tumour. Six different approaches are discussed including: 1. Tumour types, briefly discussing the main changes to the recent WHO classification of CNS tumours, 2. Patient age and its influence on incidence rates of specific tumour types, 3. Growth patterns, 4. Tumour location and how defining the correct location helps in narrowing down the differential diagnoses and 5. Imaging features of the tumour on DWI, SWI, FLAIR and post contrast sequences.

Goal-directed therapeutic exercise for paediatric posterior fossa brain tumour survivors: a qualitative analysis of experiences.

PURPOSE: To explore child and parent experiences of a 12-week goal-directed therapeutic exercise intervention in paediatric posterior fossa brain tumours survivors and to identify features of the program that influenced program adherence and acceptability. METHODS: Eleven interviews were conducted; five parent-child dyads (mothers = 83%) and one parent only (mean child age = 10.6 ± 3.0 years; 83% male). Posterior fossa brain tumour survivors, who participated in a weekly goal-directed exercise program for 12 weeks, completed semi-structured interviews to discuss their experience of the program. An inductive content analysis was undertaken. Interviews were transcribed, imported into NVivo and independently coded by two reviewers. Code and content categories were iteratively discussed and refined. RESULTS: Five content categories were generated: (1) perceived improvements, (2) program logistics, (3) activity selection, (4) connection with the therapist and (5) options for technology. All participants valued the tailored exercise program and described improvements in movement competence. Children and their parents discussed preferring home- and community-based locations and favoured face-to-face delivery. Occasionally, parents reported difficulty completing the home program due to low child motivation or family time restrictions. Multiple families suggested an interactive digital application would be an effective delivery channel for the supplemental home-based program. CONCLUSION: A goal-directed exercise program delivered at home and in community-based locations was considered valuable and helpful for improving movement competence in paediatric survivors of posterior fossa brain tumour. TRIAL REGISTRATION: ACTRN12619000841178 June 12, 2019.

A robust genetic algorithm-based optimal feature predictor model for brain tumour classification from MRI data.

Brain tumour can be cured if it is initially screened and given timely treatment to the patients. This proposed idea suggests a transform- and windowing-based optimization strategy for exposing and segmenting the tumour region in brain pictures. The processes of image processing that are included in the proposed idea include preprocessing, transformation, feature extraction, feature optimization, classification, and segmentation. In order to convert the pixels connected to the spatial domain into a multi-resolution domain, the Gabor transform is first applied to the brain test image. The Gabor converted brain image is then used to extract the parameters of the multi-level features. After that, the Genetic Algorithm (GA) is used to optimize the extracted features, and Neuro Fuzzy System (NFS) is used to classify the optimistic prominent section. Finally, the tumour region in brain images is found and segmented using the normalized segmentation algorithm. The effective detection and classification of brain tumours by the characteristics of sensitivity, specificity, and accuracy are described by the suggested GA-based NFS classification approach. The trial findings are displayed with an average of 99.37% sensitivity, 98.9% specificity, 99.21% accuracy, 97.8% PPV, 91.8% NPV, 96.8% FPR, and 90.4% FNR.

DTDO: Driving Training Development Optimization enabled deep learning approach for brain tumour classification using MRI.

A brain tumour is an abnormal mass of tissue. Brain tumours vary in size, from tiny to large. Moreover, they display variations in location, shape, and size, which add complexity to their detection. The accurate delineation of tumour regions poses a challenge due to their irregular boundaries. In this research, these issues are overcome by introducing the DTDO-ZFNet for detection of brain tumour. The input Magnetic Resonance Imaging (MRI) image is fed to the pre-processing stage. Tumour areas are segmented by utilizing SegNet in which the factors of SegNet are biased using DTDO. The image augmentation is carried out using eminent techniques, such as geometric transformation and colour space transformation. Here, features such as GIST descriptor, PCA-NGIST, statistical feature and Haralick features, SLBT feature, and CNN features are extricated. Finally, the categorization of the tumour is accomplished based on ZFNet, which is trained by utilizing DTDO. The devised DTDO is a consolidation of DTBO and CDDO. The comparison of proposed DTDO-ZFNet with the existing methods, which results in highest accuracy of 0.944, a positive predictive value (PPV) of 0.936, a true positive rate (TPR) of 0.939, a negative predictive value (NPV) of 0.937, and a minimal false-negative rate (FNR) of 0.061%.

Cerebrospinal fluid cytology in a case of epithelioid glioblastoma.

Epithelioid glioblastoma (eGB) is a rare GB subtype exhibiting characteristic morphology and genetic alterations. The efficacy of BRAF and MEK-1/2 inhibitors is demonstrated in eGB treatment, and therefore, considering eGB is important to enhance patient care and prognosis.

An attempt to identify brain tumour tissue in neurosurgery by mechanical indentation measurements.

BACKGROUND: The intraoperative differentiation between tumour tissue, healthy brain tissue, and any sensitive structure of the central nervous system is carried out in modern neurosurgery using various multimodal technologies such as neuronavigation, fluorescent dyes, intraoperative ultrasound or the use of intraoperative MRI, but also the haptic experience of the neurosurgeon. Supporting the surgeon by developing instruments with integrated haptics could provide a further objective dimension in the intraoperative recognition of healthy and diseased tissue. METHODS: In this study, we describe intraoperative mechanical indentation measurements of human brain tissue samples of different tumours taken during neurosurgical operation and measured directly in the operating theatre, in a time frame of maximum five minutes. We present an overview of the Young's modulus for the different brain tumour entities and potentially differentiation between them. RESULTS: We examined 238 samples of 75 tumour removals. Neither a clear distinction of tumour tissue against healthy brain tissue, nor differentiation of different tumour entities was possible on solely the Young's modulus. Correlation between the stiffness grading of the surgeon and our measurements could be found. CONCLUSION: The mechanical behaviour of brain tumours given by the measured Young's modulus corresponds well to the stiffness assessment of the neurosurgeon and can be a great tool for further information on mechanical characteristics of brain tumour tissue. Nevertheless, our findings imply that the information gained through indentation is limited.

Paediatric Rhabdoid Meningioma: Clinical and Therapeutic Features Findings - Case Series of 3 Patients.

INTRODUCTION: Paediatric rhabdoid meningioma (RM) is the rarest but most aggressive subtype of meningioma, related to a severe prognosis. They account for 1-3% of all intracranial meningiomas. CASE PRESENTATIONS: We report an institutional experience of 3 cases through which we discuss clinical, histological, and therapeutic features of this tumour. Two of our patients were female-gendered (3 years old and 1 year and 6 months old), and one was male-gendered (16 years old). Revealing symptoms were related to intracranial hypertension, cerebellar syndrome, cranial nerve palsy, and skull tumefaction. Imaging showed extra-axial tumour located in the right ponto-cerebellar angle in the first case, in the left occipital region in the second case, left parietal tumour in the third case. All patients underwent a surgical intervention with a gross total resection. Histological evaluation supported by immunohistochemistry confirmed the diagnosis of RM. Tumour recurrence was observed at 45 days in the first case with a fatal outcome. Despite adjuvant radiotherapy, both second and third cases had local recurrence after a mean follow-up of 1 month following the radiotherapy. CONCLUSIONS: RM is very aggressive tumours. Standardized therapeutic guidelines are still under debate as actual approaches are still inefficient to prevent quick recurrence and fatal outcome.

Individuals' perceptions of health and well-being in the context of stereotactic radiosurgery for benign brain tumour: A longitudinal qualitative investigation.

BACKGROUND AND OBJECTIVES: Treatment-related outcomes after Gamma Knife Stereotactic Radiosurgery (GKSRS) for benign brain tumour are well-established; yet patient reported outcomes have been largely overlooked. This study explored individuals' perspectives of their health and well-being prior to and following GKSRS. METHOD: Twenty adults (65% female) aged 24-71 years with benign brain tumour were recruited from a major metropolitan hospital and assessed approximately one week prior to, two weeks after, and at three months following GKSRS. They completed telephone-based interviews focusing on general health, symptoms, and well-being. Interviews were transcribed and analysed using thematic analysis. RESULTS: Three major themes characterized individuals' perceptions of their health and well-being. "Understanding my Illness and Treatment" reflected individuals' efforts to make sense of their illness and symptoms to reduce ambiguity and increase sense of control. "Experiencing Gamma Knife" related to expectations of the procedure, outcomes, daily impacts, and emotional reactions. "Adjusting one's Mindset and Coping" characterised how peoples' approaches to coping with their illness were altered over time. CONCLUSIONS: Coping and adjustment is highly individualistic in the context of GKSRS. Over time, most individuals were able to make sense of their illness, adjust their mindset and utilize behavioural strategies and support systems to cope with the long-term effects.

Interventions facilitating the involvement of relatives of patients with acquired brain injury or malignant brain tumour: A scoping review.

AIM: To identify and map the evidence on interventions facilitating the involvement of relatives of patients with an acquired brain injury (ABI) or a malignant brain tumour (MBT). BACKGROUND: An ABI or a MBT are severe diseases that have profound impact on the lives of patients and their relatives. The well-being of the patient may be deteriorated, and relatives may experience a new role and changing caregiving tasks. Involvement of relatives seems essential, and there is a need for identifying interventions facilitating the involvement. DESIGN: Scoping review. METHODS: The Joanna Briggs Institute methodology was used in this review and the review was reported in accordance with the PRISMA extension for scoping reviews. DATA SOURCES: The literature search was conducted in MEDLINE, Embase, CINAHL and Cochrane Library. Reference lists of included studies, Google Scholar and Web of Science were also searched. RESULTS: In total, 46 studies were included of which 36 (78%) involved patients with stroke. Median duration of study interventions were 8 weeks, and nurses were involved as providers of the intervention in 23 (50%) studies. Thirty (65%) studies used a multicomponent intervention. Thirty-five unique outcomes were identified using 60 unique outcome measurements. CONCLUSION: Interventions facilitating the involvement of relatives differed importantly in key characteristics of study interventions, and in relation to the context in which they were used. There was no consensus regarding choice of outcomes and outcome measurements. Our results highlight the complexity of interventions in this field. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: To our knowledge this is the first scoping review examining interventions facilitating the involvement of relatives of patients with an acquired brain injury or a malignant brain tumour. This review suggests a clear definition of 'involvement' in future research and there is a need of development of a core outcome set for use in interventions facilitating the involvement. REPORTING METHOD: The scoping review was reported in accordance with the PRISMA extension for scoping reviews. NO PATIENT OR PUBLIC CONTRIBUTION: The authors decided to undertake this scoping review without patient and public contribution. However, the protocol was published prior to review conduct and available to the public but we did not receive any comments on it.

Molecular and Pathological Features of Paediatric High-Grade Gliomas.

Paediatric high-grade gliomas are among the most common malignancies found in children. Despite morphological similarities to their adult counterparts, there are profound biological and molecular differences. Furthermore, and thanks to molecular biology, the diagnostic pathology of paediatric high-grade gliomas has experimented a dramatic shift towards molecular classification, with important prognostic implications, as is appropriately reflected in both the current WHO Classification of Tumours of the Central Nervous System and the WHO Classification of Paediatric Tumours. Emphasis is placed on histone 3, IDH1, and IDH2 alterations, and on Receptor of Tyrosine Kinase fusions. In this review we present the current diagnostic categories from the diagnostic pathology perspective including molecular features.

A fast transition: A case study of patients' experiences during the diagnostic and surgical treatment phase of an accelerated brain cancer pathway.

BACKGROUND: Patients receiving a brain cancer diagnosis may face cognitive decline and a poor prognosis. In addition, they suffer from a high symptom burden in a complex cancer pathway. The aim of this study was to investigate the early hospital experiences of brain tumour patients during the diagnostic and surgical treatment phase. METHODS: A descriptive longitudinal single-case study design was used, and data were analysed via systematic text condensation. RESULTS: The patients' experiences of being diagnosed with and treated for brain cancer were interpreted in terms of the central theme: a fast transition into an unknown journey. This theme consisted of the following subthemes: emotionally overwhelmed, putting life on hold and an unfamiliar dependency. CONCLUSIONS: Patients diagnosed with brain cancer struggle with overwhelming emotions due to this sudden life-threatening diagnosis, their fear of brain surgery and their progressing dependence. Patients did not voice their feelings, fears or needs, so these may easily be overlooked and unmet. A proactive and continuous care approach throughout the diagnostic phase is needed to support these patients.

Photodynamic Therapy in Adult Intra-axial Brain Tumours.

The management of high-grade gliomas is challenging considering their infiltrative nature, involvement of the eloquent cortex, and high recurrence rate. Photodynamic therapy (PDT) is an emerging modality that selectively destroys tumour cells while preserving normal brain tissue. Its safety, and the concurrent use with surgery, radiation, and chemotherapy, is some of its appealing tenets. Here, we present a review of the literature regarding the mechanism, safety, and efficacy of PDT.

Evolution of RANO in Assessing Brain Tumour Outcomes.

Assessing treatment response is extremely important in management of brain tumours. Response assessment in neuro-oncology (RANO) was introduced in 2008 for the purpose of making recommendations for it by addressing and countering the limitations in previously reported response criteriae. Subsequently, multiple RANO working groups have been formed to cater to different tumour types and to update their previous recommendations to counter the limitations in their criteria. Herein we have a summarized list of RANO criteria for adult brain tumours.

Socio-demographic characteristics of children and young people with primary brain tumours: comparison between a public and private sector tertiary hospital in Karachi, Pakistan.

Primary brain tumours (PBTs) are the commonest solid tumours in children and young people (CYP). A study was conducted at a private and a public sector hospital in Karachi, Pakistan, to determine the socio-demographic and tumour-related characteristics of CYP with PBTs between those presenting to the public and private hospitals. A total of 49 patients were included. The commonest PBT was pilocytic astrocytoma (29%). There were no differences in tumour-related characteristics between the two groups. However, parents of CYP with PBTs presenting to the public sector hospital were significantly less educated and had lower household incomes. No significant differences in age, gender, educational status, and ethnicity of CYP with PBTs were observed. Since CYP with PBTs presenting at the public sector hospital were from significantly lower socioeconomic backgrounds and their parents were less educated, it suggests socio-economic disparities in PBT care for CYPs in Karachi, Pakistan.