A clinically applicable integrative molecular classification of meningiomas.

Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.

Biomarkers of seizure response to vagus nerve stimulation: A scoping review.

Although vagus nerve stimulation (VNS) is a common procedure, seizure outcomes are heterogeneous, with few available means to preoperatively identify the ideal surgical candidate. Here, we perform a scoping review of the literature to identify biomarkers of VNS response in patients with drug-resistant epilepsy. Several databases (Ovid MEDLINE, Ovid Embase, BIOSIS Previews, and Web of Science) were searched for all relevant articles that reported at least one biomarker of VNS response following implantation for intractable epilepsy. Patient demographics, seizure data, and details related to biomarkers were abstracted from all studies. From the 288 records screened, 28 articles reporting on 16 putative biomarkers were identified. These were grouped into four categories: network/connectomic-based biomarkers, electrophysiological signatures, structural findings on neuroimaging, and systemic assays. Differences in brain network organization, connectivity, and electrophysiological synchronicity demonstrated the most robust ability to identify VNS responders. Structural findings on neuroimaging yielded inconsistent associations with VNS responsiveness. With regard to systemic biomarkers, heart rate variability was shown to be an independent marker of VNS response, whereas inflammatory markers were not useful. There is an unmet need to preoperatively identify candidates who are likely to benefit from VNS. Several biomarkers demonstrate promise in predicting seizure responsiveness to VNS, particularly measures of brain network connectivity. Further efforts are required to validate existing biomarkers to inform clinical decision-making.

Cognitive Outcomes After Anterior Communicating Artery Aneurysm Repair.

Background The long-term cognitive and quality-of-life (QoL) outcomes after treatment of ruptured anterior communicating artery (ACoA) aneurysms are unknown. Methods Potential participants were all consecutive patients with ruptured ACoA aneurysms who were treated at one institution from July 1992 to December 2008. All potential participants were asked to complete the Cognitive Failures Questionnaire (CFQ), Center for Epidemiology Studies-Depression (CES-D) questionnaire, Short Form 36 (SF-36) questionnaire, and Telephone Interview for Cognitive Status-Modified (TICS-M). Patient charts were retrospectively reviewed for baseline demographics and clinical status, intra-operative details, and post-operative course. Reporting of cognitive and QoL assessment results was stratified by treatment method (endovascular coil embolization and surgical clipping by pterional craniotomy or orbitocranial craniotomy). Results In total, 82 patients (18 treated with coiling, 27 by orbitocranial craniotomy, and 37 by pterional craniotomy) were included in this study. In total, 32 patients (9 treated by coiling, 11 by orbitocranial craniotomy, and 16 by pterional craniotomy) completed follow-up cognitive and QoL questionnaires. The mean follow-up for patients who completed the questionnaires was 8.64±3.81 years. The three groups did not differ in questionnaires assessing cognitive status (TICS-M p=0.114, CFQ p=0.111). Moreover, there were no observed differences in QoL or depression scores between the three groups. Conclusions At long-term follow-up, QoL, cognitive, and depression test scores of patients with ruptured ACoA aneurysms are similar across open surgery and coiling modalities. Our results emphasize the importance of considering long-term outcomes with validated daily measures of functioning when reporting on outcomes after treatment for ruptured intracranial aneurysms. Larger prospective studies are required to further explore the results.

Detection of high-frequency oscillations in electroencephalography: A scoping review and an adaptable open-source framework.

PURPOSE: High frequency oscillations (HFOs) are putative biomarkers of epileptogenicity. These electrophysiological phenomena can be effectively detected in electroencephalography using automated methods. Nonetheless, the implementation of these methods into clinical practice remains challenging as significant variability exists between algorithms and their characterizations of HFOs. Here, we perform a scoping review of the literature pertaining to automated HFO detection methods. In addition, we propose a framework for defining and detecting HFOs based on a simplified single-stage time-frequency based detection algorithm with clinically-familiar parameters. METHODS: Several databases (OVID Medline, Web of Science, PubMed) were searched for articles presenting novel, automated HFO detection methods. Details related to the algorithm and various stages of data acquisition, pre-processing, and analysis were abstracted from included studies. RESULTS: From the 261 records screened, 57 articles presented novel, automated HFO detection methods and were included in the scoping review. These algorithms were categorized into 3 groups based on their most salient features: energy thresholding, time-frequency analysis, and data mining/machine learning. Algorithms were optimized for specific datasets and suffered from low specificity. A framework for user-constrained inputs is proposed to circumvent some of the weaknesses of highly performant detectors. CONCLUSIONS: Further efforts are required to optimize and validate existing automated HFO detection methods for clinical utility. The proposed framework may be applied to understand and standardize the variations in HFO definitions across institutions.

Twitter and traumatic brain injury: A content and sentiment analysis of tweets pertaining to sport-related brain injury.

OBJECTIVES: Sport-related traumatic brain injuries are a significant public health burden, with hundreds of thousands sustained annually in North America. While sports offer numerous physical and social health benefits, traumatic brain injuries such as concussion can seriously impact a player's life, athletic career, and sport enjoyment. The culture in many sports encourages winning at all costs, placing athletes at risk for traumatic brain injuries. As social media has become a central part of everyday life, the content of users' messages often reflects the prevailing culture related to a particular event or health issue. METHODS: We hypothesized that Twitter data might be useful for understanding public perceptions and misperceptions of sport-related traumatic brain injuries. We performed a content and sentiment analysis of 7483 Twitter® tweets related to traumatic brain injuries in sports collected during June and July 2013. RESULTS: We identified five major themes. Users tweeted about personal traumatic brain injuries experiences, reported traumatic brain injuries in professional athletes, shared research about sport-related concussions, and discussed policy and safety in injury prevention, such as helmet use. We identified mixed perceptions of and sentiment toward traumatic brain injuries in sports: both an understanding that brain injuries are serious and disregard for activities that might reduce the public burden of traumatic brain injuries were prevalent in our Twitter analysis. CONCLUSION: While the scientific and medical community considers a concussion a form of traumatic brain injuries, our study demonstrates a misunderstanding of this fact among the public. In our current digital age, social media can provide useful insight into the culture around a health issue, facilitating implementation of prevention and treatment strategies.