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.

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.

Surgical Anatomy Applied to the Resection of Craniopharyngiomas: Anatomic Compartments and Surgical Classifications.

BACKGROUND: Resective surgery remains the main treatment option for most patients with craniopharyngiomas. Understanding of the microsurgical anatomy of the sella and suprasellar region and its relationship with these tumors is necessary to achieve effective surgical treatment and minimize complications. In this article, we review the surgical anatomy related to craniopharyngiomas and divide it in 5 compartments according to tumor extension. METHODS: Endoscopic and microsurgical dissection were performed in 3 freshly injected cadaver heads at the Weill Cornell Surgical Innovations Laboratory (New York, New York, USA) and at the Surgical Skills Center at Mount Sinai Hospital (Toronto, Ontario, Canada). Tumor extension was classified as 1) inferomedial or sellar, 2) superomedial or suprasellar, 3) lateral or sylvian, 4) posterior or interpeduncular/prepontine, and 5) intraventricular. The selection of surgical approaches is discussed based on the anatomic nuances of each these regions. In addition, we reviewed the literature regarding previous anatomic classifications for resection of craniopharyngiomas. RESULTS: Different approaches should be considered according to tumor extension into different compartments. Purely sellar tumors are amenable to endoscopic transsellar approaches, whereas those with a suprasellar extension require an extended transtuberculum approach. In some of those patients, a narrow chiasm-pituitary window may block access to the tumor and a transcranial translamina terminalis approach may be favored. Tumors occupying the interpeduncular fossa may pose a significant challenge for an endoscopic endonasal approach and transcranial approaches. Transcavernous approaches and anterior and posterior clinoidectomies may be required for adequate exposure in such patients. Translamina terminalis and/or transcallosal approaches are recommended for resection of purely intraventricular tumors. Tumors extending into the lateral compartment should be considered for transcranial frontotemporal approaches. CONCLUSIONS: The understanding of such anatomic nuances aids in the selection of the most appropriate surgical approach and in the prevention of potential complications. Because most craniopharyngiomas are midline lesions, the endoscopic endonasal approach represents an excellent approach for most of those tumors. However, transcranial approaches should be considered for tumors with extension into the lateral compartment and for selected tumors involving the ventricular compartment (purely intraventricular tumors and those with extension to the foramen of Monro and/or lateral ventricles).

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.

Temporal-plus epilepsy in children: A connectomic analysis in magnetoencephalography.

OBJECTIVE: Seizure recurrence following surgery for temporal lobe (TL) epilepsy may be related to extratemporal epileptogenic foci, so-called temporal-plus (TL+) epilepsy. Here, we sought to leverage whole brain connectomic profiling in magnetoencephalography (MEG) to identify neural networks indicative of TL+ epilepsy in children. METHODS: Clinical and MEG data were analyzed for 121 children with TL and TL+ epilepsy spanning 20 years at the Hospital for Sick Children. Resting-state connectomes were derived using the weighted phase lag index from neuromagnetic oscillations. Multidimensional associations between patient connectomes, TL versus TL+ epilepsy, seizure freedom, and clinical covariates were performed using a partial least squares (PLS) analysis. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A single significant latent variable representing 66% of the variance in the data was identified with significant contributions from extent of epilepsy (TL vs TL+), duration of illness, and underlying etiology. This component was associated with significant bitemporal and frontotemporal connectivity in the theta, alpha, and beta bands. By extracting a brain score, representative of the observed connectivity profile, patients with TL epilepsy were dissociated from those with TL+, independent of their postoperative seizure outcome. SIGNIFICANCE: By analyzing 121 connectomes derived from MEG data using a PLS approach, we find that connectomic profiling could dissociate TL from TL+ epilepsy. These findings may inform patient selection for resective procedures and guide decisions surrounding invasive monitoring.

Selective dorsal rhizotomy: an illustrated review of operative techniques.

OBJECTIVE: Selective dorsal rhizotomy (SDR) is a procedure primarily performed to improve function in a subset of children with limitations related to spasticity. There is substantial variability in operative techniques among centers and surgeons. Here, the authors provide a technical review of operative approaches for SDR. METHODS: Ovid MEDLINE, Embase, and PubMed databases were queried in accordance with PRISMA guidelines. All studies included described a novel surgical technique. The technical nuances of each approach were extracted, including extent of exposure, bone removal, and selection of appropriate nerve roots. The operative approach preferred at the authors' institution (the "2 × 3 exposure") is also detailed. RESULTS: Five full-text papers were identified from a total of 380 articles. Operative approaches to SDR varied significantly with regard to level of exposure, extent of laminectomy, and identification of nerve roots. The largest exposure involved a multilevel laminectomy, while the smallest exposure involved a keyhole interlaminar approach. At the Hospital for Sick Children, the authors utilize a two-level laminoplasty at the level of the conus medullaris. The benefits and disadvantages of the spectrum of techniques are discussed, and illustrative figures are provided. CONCLUSIONS: Surgical approaches to SDR vary considerably and are detailed and illustrated in this review as a guide for neurosurgeons. Future studies should address the long-term impact of these techniques on functional outcomes and complications such as spinal deformity.

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.

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.