Intraoperative Neurophysiological Monitoring for Endoscopic Endonasal Approaches to the Skull Base: A Technical Guide.

Intraoperative neurophysiological monitoring during endoscopic, endonasal approaches to the skull base is both feasible and safe. Numerous reports have recently emerged from the literature evaluating the efficacy of different neuromonitoring tests during endonasal procedures, making them relatively well-studied. The authors report on a comprehensive, multimodality approach to monitoring the functional integrity of at risk nervous system structures, including the cerebral cortex, brainstem, cranial nerves, corticospinal tract, corticobulbar tract, and the thalamocortical somatosensory system during endonasal surgery of the skull base. The modalities employed include electroencephalography, somatosensory evoked potentials, free-running and electrically triggered electromyography, transcranial electric motor evoked potentials, and auditory evoked potentials. Methodological considerations as well as benefits and limitations are discussed. The authors argue that, while individual modalities have their limitations, multimodality neuromonitoring provides a real-time, comprehensive assessment of nervous system function and allows for safer, more aggressive management of skull base tumors via the endonasal route

Potential for early warning of viral influenza activity in the community by monitoring clinical diagnoses of influenza in hospital emergency departments

<p>Abstract</p> <p>Background</p> <p>Although syndromic surveillance systems are gaining acceptance as useful tools in public health, doubts remain about whether the anticipated early warning benefits exist. Many assessments of this question do not adequately account for the confounding effects of autocorrelation and trend when comparing surveillance time series and few compare the syndromic data stream against a continuous laboratory-based standard. We used time series methods to assess whether monitoring of daily counts of Emergency Department (ED) visits assigned a clinical diagnosis of influenza could offer earlier warning of increased incidence of viral influenza in the population compared with surveillance of daily counts of positive influenza test results from laboratories.</p> <p>Methods</p> <p>For the five-year period 2001 to 2005, time series were assembled of ED visits assigned a provisional ED diagnosis of influenza and of laboratory-confirmed influenza cases in New South Wales (NSW), Australia. Poisson regression models were fitted to both time series to minimise the confounding effects of trend and autocorrelation and to control for other calendar influences. To assess the relative timeliness of the two series, cross-correlation analysis was performed on the model residuals. Modelling and cross-correlation analysis were repeated for each individual year.</p> <p>Results</p> <p>Using the full five-year time series, short-term changes in the ED time series were estimated to precede changes in the laboratory series by three days. For individual years, the estimate was between three and 18 days. The time advantage estimated for the individual years 2003–2005 was consistently between three and four days.</p> <p>Conclusion</p> <p>Monitoring time series of ED visits clinically diagnosed with influenza could potentially provide three days early warning compared with surveillance of laboratory-confirmed influenza. When current laboratory processing and reporting delays are taken into account this time advantage is even greater.</p

Pediatric primary intramedullary spinal cord glioblastoma

Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors. Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported. Both patients presented with rapid onset paraparesis and quadraparesis. Magnetic resonance imaging in both showed heterogeneously enhancing solitary mass lesions localized to lower cervical and upper thoracic spinal cord parenchyma. Histopathologic diagnosis was glioblastoma. Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245–88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples. Case #2 had relatively bland histomorphology and negligible p53 immunoreactivity. Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy. However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months.This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy. The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy. The differences in management with intracranial and low-grade spinal cord gliomas and current management issues are discussed

KIAA1549-BRAF Expression Establishes A Permissive Tumor Microenvironment Through Nfκb-Mediated CCL2 Production

KIAA1549-BRAF is the most frequently identified genetic mutation in sporadic pilocytic astrocytoma (PA), creating a fusion BRAF (f-BRAF) protein with increased BRAF activity. Fusion-BRAF-expressing neural stem cells (NSCs) exhibit increased cell growth and can generate glioma-like lesions following injection into the cerebella of naïve mice. Increased Iba1+ monocyte (microglia) infiltration is associated with murine f-BRAF-expressing NSC-induced glioma-like lesion formation, suggesting that f-BRAF-expressing NSCs attract microglia to establish a microenvironment supportive of tumorigenesis. Herein, we identify Ccl2 as the chemokine produced by f-BRAF-expressing NSCs, which is critical for creating a permissive stroma for gliomagenesis. In addition, f-BRAF regulation of Ccl2 production operates in an ERK- and NFκB-dependent manner in cerebellar NSCs. Finally, Ccr2-mediated microglia recruitment is required for glioma-like lesion formation in vivo, as tumor do not form in Ccr2-deficient mice following f-BRAF-expressing NSC injection. Collectively, these results demonstrate that f-BRAF expression creates a supportive tumor microenvironment through NFκB-mediated Ccl2 production and microglia recruitment

Low Grade Gliomas of Childhood: The Actual Management

Low grade gliomas (LGG) are the most common brain tumors of childhood and adolescence, consisting of a mixed group of grade I and grade II neoplasms. In general, their location and resectability are the most important predictors of outcome. Surgery is curative, usually for superficial tumors of the cerebral or cerebellar hemispheres, but has a more controversial role for deep-seated midline tumors. Where gross total resection is not feasible, LGG becomes a chronic disease of childhood, and adjuvant therapies must be tailored for each individual based on age and tumor location. Radiotherapy (RT) is effective but associated with neurological, cognitive, and endocrinological morbidity, prompting the use of chemotherapy regimens aimed at delaying RT, especially in younger children. Long-term surveillance imaging for up to five years after treatment is warranted even after gross total resection, and lifelong surveillance is warranted after RT because of iatrogenic effects. Despite a favorable prognosis for survival, LGG are associated with disability, decreased quality of life, and late effects of treatment, all requiring long-term specialty care through a multidisciplinary approach

Low Grade Gliomas of Childhood: The Actual Management

Low grade gliomas (LGG) are the most common brain tumors of childhood and adolescence, consisting of a mixed group of grade I and grade II neoplasms. In general, their location and resectability are the most important predictors of outcome. Surgery is curative, usually for superficial tumors of the cerebral or cerebellar hemispheres, but has a more controversial role for deep-seated midline tumors. Where gross total resection is not feasible, LGG becomes a chronic disease of childhood, and adjuvant therapies must be tailored for each individual based on age and tumor location. Radiotherapy (RT) is effective but associated with neurological, cognitive, and endocrinological morbidity, prompting the use of chemotherapy regimens aimed at delaying RT, especially in younger children. Long-term surveillance imaging for up to five years after treatment is warranted even after gross total resection, and lifelong surveillance is warranted after RT because of iatrogenic effects. Despite a favorable prognosis for survival, LGG are associated with disability, decreased quality of life, and late effects of treatment, all requiring long-term specialty care through a multidisciplinary approach

Maladjustment of Programmable Ventricular Shunt Valves by Inadvertent Exposure to a Common Hospital Device

Background: Programmable ventricular shunt valves are commonly used to treat hydrocephalus. They can be adjusted to allow for varying amounts of cerebrospinal fluid (CSF) flow using an external magnetic programming device, and are susceptible to maladjustment from inadvertent exposure to magnetic fields.Case Description: We describe the case of a 3‑month‑old girl treated for hydrocephalus with a programmable StrataTM II valve found at the incorrect setting on multiple occasions during her hospitalization despite frequent reprogramming and surveillance. We found that the Vocera badge, a common hands‑free wireless communication system worn by our nursing staff, had a strong enough magnetic field to unintentionally change the shunt setting. The device is worn on the chest bringing it into close proximity to the shunt valve when care providers hold the baby, resulting in the maladjustment.Conclusion: Some commonly used medical devices have a magnetic field strong enough to alter programmable shunt valve settings. Here, we report that the magnetic field from the Vocera hands‑free wireless communication system, combined with the worn position, results in shunt maladjustment for the StrataTMII valve. Healthcare facilities using the Vocera badges need to put protocols in place and properly educate staff members to ensure the safety of patients with StrataTM II valves

DIPG-30. Differential Hypoxic Response inHuman Dipg Cell Lines

BACKGROUND: Diffuse Intrinsic Pontine Glioma (DIPG) are rare and aggressive childhood tumors, with an abysmal prognosis and limited experimental models available for study. A recent report showed that DIPG are hypoperfused compared to surrounding brain tissue, suggesting that the tumor cells are exposed to a hypoxic microenvironment. This stimulus may induce widespread transcriptional changes through activation of Hypoxia-inducible Factors (HIF), which have been associated with invasion, metastasis, angiogenesis, and resistance to radiation therapy and chemotherapy. Therefore, in vitro models using DIPG cells cultured in conditions of normal oxygen tension may not be representative of in vivo tumors because of artificial differences in HIF activation. METHODS: To test cellular responses to hypoxia, human DIPG cell lines with H3.1 K27M and H3.3 K27M mutations were treated with the hypoxia-mimetic compound, cobalt (II) chloride, for 24 hours. Simulated hypoxic responses were assayed using Western blot analysis, proliferation assays, and extracellular flux analysis. RESULTS: The H3.3 K27M cell line increased expression of HIF1a with cobalt (II) chloride treatment and correlated with an increase in glycolytic rates and increased expression of proteins involved in glucose transport and glycolysis. The H3.1 K27M cell line increased expression of HIF2a and not HIF1a after cobalt (II) chloride treatment, correlating with an increase in some glycolysis-associated proteins but no change in glycolytic rate. CONCLUSION: These data suggest that the effects of a hypoxic microenvironment should be considered in experimental models using cultured DIPG cell lines to understand differences in cell behavior, patient prognosis, and predicted treatment responses. Activation of specific HIF isoforms may underlie differences in hypoxic responses among cell line

DIPG-30. Differential Hypoxic Response inHuman Dipg Cell Lines

BACKGROUND: Diffuse Intrinsic Pontine Glioma (DIPG) are rare and aggressive childhood tumors, with an abysmal prognosis and limited experimental models available for study. A recent report showed that DIPG are hypoperfused compared to surrounding brain tissue, suggesting that the tumor cells are exposed to a hypoxic microenvironment. This stimulus may induce widespread transcriptional changes through activation of Hypoxia-inducible Factors (HIF), which have been associated with invasion, metastasis, angiogenesis, and resistance to radiation therapy and chemotherapy. Therefore, in vitro models using DIPG cells cultured in conditions of normal oxygen tension may not be representative of in vivo tumors because of artificial differences in HIF activation. METHODS: To test cellular responses to hypoxia, human DIPG cell lines with H3.1 K27M and H3.3 K27M mutations were treated with the hypoxia-mimetic compound, cobalt (II) chloride, for 24 hours. Simulated hypoxic responses were assayed using Western blot analysis, proliferation assays, and extracellular flux analysis. RESULTS: The H3.3 K27M cell line increased expression of HIF1a with cobalt (II) chloride treatment and correlated with an increase in glycolytic rates and increased expression of proteins involved in glucose transport and glycolysis. The H3.1 K27M cell line increased expression of HIF2a and not HIF1a after cobalt (II) chloride treatment, correlating with an increase in some glycolysis-associated proteins but no change in glycolytic rate. CONCLUSION: These data suggest that the effects of a hypoxic microenvironment should be considered in experimental models using cultured DIPG cell lines to understand differences in cell behavior, patient prognosis, and predicted treatment responses. Activation of specific HIF isoforms may underlie differences in hypoxic responses among cell line