The ex vivo expansion of stem cells is making major contribution to biomedical research. The multipotent nature of neural precursors acutely isolated from the developing central nervous system has been established in a series of studies. Understanding the mechanisms regulating cell expansion in tissue culture would support their expanded use either in cell therapies or to define disease mechanisms. Basic fibroblast growth factor (FGF2) and insulin, ligands for tyrosine kinase receptors, are sufficient to sustain neural stem cells (NSCs) in culture. Interestingly, real-time imaging shows that these cells become multipotent every time they are passaged. Here, we analyze the role of FGF2 and insulin in the brief period when multipotent cells are present. FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c-Fos and c-Jun that lead to elevated cyclin D mRNA levels. Insulin signals through the PI3k/Akt pathway to regulate cyclins at the posttranscriptional level. This precise Boolean regulation extends our understanding of the proliferation of multipotent NSCs and provides a basis for further analysis of proliferation control in the cell states defined by real-time mapping of the cell lineages that form the central nervous system.

OBJECTIVESkull fracture is associated with several intracranial injuries. The object of this study was to determine the rate of fracture associated with venous thrombosis, intracranial arterial dissection (ICAD), and cerebrospinal fluid (CSF) leakage in pediatric patients. Further, the authors aimed to highlight the features of pediatric skull fracture that predict poor neurological outcomes.METHODIn this retrospective study, the authors evaluated the records of 258 pediatric patients who had incurred a traumatic skull fracture in the period from 2009 to 2015. All the patients had undergone CT imaging, which was used to characterize the type of skull fracture and other important features, including intracranial hemorrhage. Patients with fracture extending to a dural sinus or proximal to major intracranial vessels had undergone vascular imaging to evaluate for venous thrombosis or arterial dissection. Clinical data were also reviewed for patients who had CSF leakage.RESULTSTwo hundred fifty-eight patients had 302 skull fractures, with 11.6% having multiple fractures. Falling was the most common mechanism of injury (52.3%), and the parietal bone was most frequently involved in the fracture (43.4%). Diastatic fracture was associated with increased intracranial hemorrhage (p < 0.05). The rate of venous thrombosis was 0.4%, and the rate of ICAD was also 0.4%. The rate of CSF leakage was 2.3%. Skull base fracture was the only significant risk factor associated with an increased risk of CSF leakage (p < 0.05). There was a significant difference in fracture-related morbidity in patients younger than versus older than 2 years of age. Patients younger than 2 years had fewer intracranial hemorrhages (21.8% vs 38.8%) and fewer neurosurgical interventions (3.0% vs 12.7%) than the patients older than 2 years (p < 0.001). Moreover, skull fracture in the younger group was mostly caused by falling (81.2% vs 33.1%); in the older group, fracture was most often caused by vehicle-related accidents (35.7% vs 4.0%) and being struck by or against an object (19.1% vs 7.9%). Additionally, skull fracture location was analyzed based on the mechanism of injury. Parietal bone fracture was closely associated with falling, and temporal bone fracture was associated with being struck by or against an object (p < 0.05). Frontal bone fracture was more associated with being struck by or against an object and vehicle-related injury (p < 0.05) than with falling. Vehicle-related accidents and being struck by or against an object, as opposed to falling, were associated with increased surgical intervention (13.3% vs 16.2% vs 3.7%, respectively).CONCLUSIONSPediatric skull fracture usually has a benign outcome in patients who fall and are younger than 2 years of age. Poor prognostic factors include diastasis, an age > 2 years, and fracture caused by vehicle-related accidents or being struck by or against an object. In this series, the rates of venous thrombosis and ICAD were low, and the authors do not advocate vascular imaging unless these disease entities are clinically suspected. Patients with skull base fracture should be closely monitored for CSF leakage.

Background: Because of the commonality of diagnostic magnetic resonance imaging (MRI), MRI conditional technology has increased throughout the device industry. It is often difficult to be aware of MRI specifications for each device. Objectives: We provide a review of the clinical experience with MRI and spinal cord stimulation (SCS) devices and develop a general reference of current device/MRI specifications. Methods: We reviewed the available literature on the clinical experience with SCS devices and examined its specifications. Results: We developed a user-friendly table of the specific compatibility of SCS devices in the USA and the European Union, and examined the existing literature on the clinical experience with MRI and SCS devices. We share our experience with obtaining spine MRI with MRI conditional SCS leads. Conclusion: By describing SCS device specifications and reviewing the literature, we provide a guide to implanting and treating physicians on obtaining MRIs in patients who have SCS devices.

Introduction: Although endonasal endoscopic approaches (EEA) to the orbit have been previously reported, a didactic resource for educating neurosurgery and otolaryngology trainees regarding the pertinent anatomy, techniques, and decision-making pearls is lacking. Methods: Six sides of three formalin-fixed, color latex-injected cadaveric specimens were dissected using 4-mm 0º and 30º rigid endoscopes, as well as standard endoscopic equipment, and a high-speed surgical drill. The anatomical dissection was documented in stepwise 3-D endoscopic images. Following dissection, representative case applications were reviewed. Results: EEA to the orbit provides excellent access to the medial and inferior orbital regions. Key steps include positioning and preoperative considerations, middle turbinate medialization, uncinate process and ethmoid bulla removal, complete ethmoidectomy, sphenoidotomy, maxillary antrostomy, lamina papyracea resection, orbital apex and optic canal decompression, orbital floor resection, periorbita opening, dissection of the extraconal fat, and final exposure of the orbit contents via the medial-inferior recti corridor. Conclusion: EEA to the orbit is challenging, in particular for trainees unfamiliar with nasal and paranasal sinus anatomy. Operatively oriented neuroanatomy dissections are crucial didactic resources in preparation for practical endonasal applications in the OR. This approach provides optimal exposure to the inferior and medial orbit to treat a wide variety of pathologies. We describe a comprehensive step-by-step curriculum directed to any audience willing to master this endoscopic skull base approach.

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