Glioblastoma (GBM) is the most common and highly lethal primary malignant brain tumor in adults. There is a dire need for easily accessible, noninvasive biomarkers that can delineate underlying molecular activities and predict response to therapy. To this end, we sought to identify subtypes of GBM, differentiated solely by quantitative MR imaging features, that could be used for better management of GBM patients. Quantitative image features capturing the shape, texture, and edge sharpness of each lesion were extracted from MR images of 121 patients with de novo, solitary, unilateral GBM. Three distinct phenotypic “clusters” emerged in the development cohort using consensus clustering with 10,000 iterations on these image features. These three clusters—pre-multifocal, spherical, and rim-enhancing, names reflecting their image features—were validated in an independent cohort consisting of 144 multi-institution patients with similar tumor characteristics from The Cancer Genome Atlas (TCGA). Each cluster mapped to a unique set of molecular signaling pathways using pathway activity estimates derived from analysis of TCGA tumor copy number and gene expression data with the PARADIGM algorithm. Distinct pathways, such as c-Kit and FOXA, were enriched in each cluster, indicating differential molecular activities as determined by image features. Each cluster also demonstrated differential probabilities of survival, indicating prognostic importance. Our imaging method offers a noninvasive approach to stratify GBM patients and also provides unique sets of molecular signatures to inform targeted therapy and personalized treatment of GBM.

Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension-associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.

Background and Purpose Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma (GBM). The purpose of this study is to characterize GBM lesions by identifying MRI voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics and clinical outcomes. Materials and Methods Preoperative T1 anatomic MR images of 384 GBM patients were obtained from two independent cohorts (N=253 from our local (name withheld to preserve anonymity) Medical Center for training and N=131 from the Cancer Genome Atlas (TCGA) for validation). An automated computational image analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival (OS) > 17 months) and poor (OS < 11 months) survival groups identified in the training cohort were used to classify patients in the TCGA cohort into two brain location groups, for which clinical features, mRNA expression, and copy number changes were compared to elucidate the biological basis of tumors located in different brain regions. Results Tumors in the right occipito-temporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both log-rank P < 0.05) and had larger tumor volume compared to tumors in other locations. Tumors in the right peri-atrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies. Conclusion Voxel-based location in GBM is associated with patient outcome and may have a potential role for guiding personalized treatment.

Background: There are currently no clear guidelines for the management and radiological monitoring of pediatric patients with epidural hematomas (EDH). We aim to compare clinical and radiographic characteristics of pediatric EDH patients managed with observation alone versus surgical evacuation and to describe results of repeat head imaging in both groups. Methods: We performed a retrospective observational study of pediatric patients diagnosed with traumatic EDH at a level II trauma center. Results: Forty-seven cases of EDH were analyzed. Sixty-two percent were managed by observation alone. Patients undergoing surgery were more likely to have an altered mental status (17 vs. 72%, p < 0.001), but there were no other significant clinical differences between the groups. The mean initial EDH thickness and volume were 8.0 mm and 8.6 ml in the observed group and 15.5 mm and 35 ml in the surgery group, respectively (p < 0.001 for both comparisons). Eighty-six percent of the observed and all surgery patients underwent repeat CT imaging. The initial repeat CT scan results led to surgery in 1 patient who was initially treated with observation. Conclusions: Most pediatric patients with EDH can be managed with observation. Mental status and radiographic findings should guide the need for surgical intervention. Multiple repeat CT scans have minimal utility in changing management.

Medical and surgical graduate medical education has historically used a halstedian approach of "see one, do one, teach one." Increased public demand for safety, quality, and accountability in the setting of regulated resident work hours and limited resources is driving the development of innovative educational tools. The use of simulation in nonmedical, medical, and neurosurgical disciplines is reviewed in this article. Simulation has been validated as an educational tool in nonmedical fields such as aviation and the military. Across most medical and surgical subspecialties, simulation is recognized as a valuable tool that will shape the next era of medical education, postgraduate training, and maintenance of certification.

Objective. Primary intramedullary spinal germ cell tumors are exceedingly rare. As such, there are no established treatment paradigms. We describe our management for spinal germ cell tumors and a review of the literature. Clinical Presentation. We describe the case of a 45-year-old man with progressive lower extremity weakness and sensory deficits. He was found to have enhancing intramedullary mass lesions in the thoracic spinal cord, and pathology was consistent with an intramedullary germ cell tumor. A video presentation of the case and surgical approach is provided. Conclusion. As spinal cord germinomas are highly sensitive to radiation and chemotherapy, a patient can be spared radical surgery. Diverse treatment approaches exist across institutions. We advocate biopsy followed by local radiation, with or without adjuvant chemotherapy, as the optimal treatment for these tumors. Histological findings have prognostic value if syncytiotrophoblastic giant cells (STGCs) are found, which are associated with a higher rate of recurrence. The recurrence rate in STGC-positive spinal germinomas is 33% (2/6), whereas it is only 8% in STGC-negative tumors (2/24). We advocate limited volume radiotherapy combined with systemic chemotherapy in patients with high risk of recurrence. To reduce endocrine and neurocognitive side effects, cranio-spinal radiation should be used as a last resort in patients with recurrence.

Single position lateral fusion reduces the need for a secondary surgery and robotic guidance allows for potentially higher accuracy of screw placement. We expand the role of robotics with a simultaneous workflow where 2 surgeons can work in single position surgery and discuss the technical feasibility of placement of S2-alar-iliac (S2AI) screws in the lateral position. A 70-year-old male presented with chronic back pain and bilateral leg pain with the left side worse than the right. He subsequently underwent an L3-S1 oblique lumbar interbody fusion (OLIF) with a minimally invasive L3-ilium robotic posterior spinal fixation simultaneously in single lateral position with S2AI screws. The software planning requisite of robotics allowed for a preoperative plan where lumbar cortical screws were used to line up with bilateral S2AI screws. Intraoperatively, the OLIF was performed anterior to the patient which allowed for a second surgeon to perform the posterior stage of screw placement simultaneously in overlapping fashion during OLIF exposure. Once all screws were placed, the OLIF discectomy and cage placement were completed. As the OLIF incision is closed, rodding proceeds posteriorly with subsequent closure simultaneously as well. Operative time from skin incision to skin closure was 3 hours and 47 minutes. We present here a novel technical report on the recommended workflow of simultaneous robotic single position surgery OLIF and demonstrate the feasibility of placement of sacroiliac fixation in the lateral decubitus position. We believe this technique to be minimally invasive, effective, with the benefit of shortening valuable operating room case time.

Management of high-grade gliomas (HGGs) remains a complex challenge with an overall poor prognosis despite aggressive multimodal treatment. New translational research has focused on maximizing tumor cell eradication through improved tumor cell targeting while minimizing collateral systemic side effects. In particular, biological intratumoral therapies have been the focus of novel translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two part review will provide an overview of biological intratumoral therapies that have been evaluated in human clinical trials in HGGs, and summarize key advances and remaining challenges in the development of these therapies as a potential new paradigm in the management of HGGs. Part II discusses vector-based therapies, cell-based therapies and radioimmunotherapy.