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This letter to the editor of Acta Neurochirurgica discusses a study by Tosi et al. on combined surgical repair and venous sinus stenting (VSS) for patients with skull base encephaloceles secondary to dural venous sinus stenosis. The study included 13 patients, mostly female, with cerebrospinal fluid (CSF) leaks and dural stenosis requiring VSS. The authors highlight the importance of previous literature on VSS for skull base CSF leaks and venous sinus stenosis, including studies by Owler et al., Iyer et al., and Labeyrie et al. They also mention the potential of VSS to resolve CSF leaks associated with transverse sinus stenoses. While not the first or largest study on VSS, the authors commend Tosi et al. for their contribution to the field. [Extracted from the article]

Purpose: Cushing Syndrome (CS) is a rare endocrine disorder associated with physical and mental symptoms that can drastically affect quality of life (QoL). This study characterizes QoL in patients with CS, describes their treatment experiences, and identifies patient subsets associated with decreased QoL or shared impressions of treatment. Methods: A 136-question survey addressing QoL factors and treatment experiences was completed by adult patients with CS from the Cushing Support and Research Foundation. Patient demographics, tumor characteristics, and treatment information were collected. Bivariate analyses were conducted to determine if patients' symptoms or treatment experiences were significantly associated with demographics or other variables. Results: A total of 178 patients, predominantly female (94%) with mean age 53 years, completed the survey. Anxiety and/or depression (n = 163, 94%), loss of physical strength (n = 164, 93%), loneliness (n = 156, 90%), fatigue from treatment (n = 142, 89%), memory loss (n = 153, 88%), insomnia (n = 144, 83%), and pain (n = 141, 83%) were symptoms most commonly experienced by respondents. Patients experiencing delay of diagnosis >10 years were more likely to have suicidal thoughts (p = 0.002). Younger patients were more likely to express concerns about hair loss (p = 0.007), loneliness (p = 0.025), pain (p = 0.004), or the impact of CS on their marriage (p = 0.039) or children (p = 0.024). Conclusion: This survey demonstrates CS impacts patients across many dimensions, emphasizing the need for holistic support. We identified patient subsets in which QoL may be improved with additional patient resources or provider attention. [ABSTRACT FROM AUTHOR]

Introduction: Gruber's ligament (GL), a surgical landmark, extends from the lateral upper clivus to the petrous apex (PA), forming the superior boundary of Dorello's canal (DC). It overlies the interdural segment of the abducens nerve (CN VI). High-resolution 3D skull base MRI (SB-MRI) demonstrates anatomic details visible to the surgeon, but not well seen on traditional cross-sectional imaging. The aim of this study was to demonstrate visualization of the GL and its relationship to CN VI utilizing contrast enhanced high-resolution SB-MRI. Methods: Two neuroradiologists retrospectively reviewed in consensus the SB-MRIs of 27 skull base sides, among 14 patients. GL detection rate, confidence of detection, and GL length were recorded. When GL was successfully identified, the position of the interdural segment of CN VI within DC was recorded. Results: GL was readily identified in 16 skull base sides (59%), identified with some difficulty in 2 skull base sides (7%), and failed to be identified in 9 skull base sides (33%). The mean GL length was 7.1 mm (4.5–9.3 mm). Among the 18 cases where GL was successfully identified, CN VI was readily identified in all cases (100%), coursing the lateral third of DC in 72% of sides, and middle third in the remaining 28% of sides. Conclusion: GL can be identified in approximately two-thirds of cases utilizing 3D high resolution SB-MRI. CN VI passes most commonly along the lateral third of DC. This is the first report demonstrating visualization of GL and its relation to CN VI, on imaging. [ABSTRACT FROM AUTHOR]

Purpose: Frailty is known to influence cost-related surgical outcomes in neurosurgery, but quantifying frailty is often challenging. Therefore, we investigated the predictive value of the 5-factor modified frailty index (mFI-5) on total hospital charges, LOS, and 90-day readmission for patients undergoing pituitary surgery. Methods: The medical records of all patients undergoing endoscopic endonasal resection of pituitary adenomas at an academic medical center between January 2017 and December 2018 were retrospectively reviewed. Bivariate statistical analyses were conducted using Fisher's exact test, chi-square test, and independent samples t-test. Linear and logistic regression models were used for multivariate analysis. Results: Our cohort (n = 234) had a mean age of 53.8 years (standard deviation 14.6 years). Sex distributions were equal, and most patients were Caucasian (59%). On multivariate linear regression, with each one-point increase in mFI-5, total LOS increased by 0.64 days in the overall cohort (p < 0.001), 1.08 days in the Cushing disease cohort (p = 0.045), and 0.59 days in non-functioning tumors cohort (p = 0.004). Total charges increased by $3954 in the whole cohort (p < 0.001), $10,652 in the Cushing disease cohort (p = 0.033), and $2902 in the non-functioning tumors cohort (p = 0.007) with each one-point increase in mFI-5. Greater mFI-5 scores were associated with greater odds of 90-day readmission in both overall and Cushing disease cohorts, but these associations did not reach statistical significance. Conclusion: A patient's mFI-5 score is significantly associated with increased length of stay and hospital charges for patients undergoing pituitary surgery. The mFI-5 may hold peri-operative value in patient counseling for pituitary adenoma surgery. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Manijeh Goldberg, Aaron Manzi. Author list, affiliations, author contributions and competing interests sections have now been updated in both the PDF and HTML versions of the Article. [Extracted from the article]

A correction is presented to the article "High resolution 3D magnetic resonance imaging of Gruber's ligament: a pilot study" which appeared in the previous issue of the periodical.

Imatinib, an orally administered tyrosine kinase inhibitor of PDGF receptor, c-abl and c-kit, is currently in clinical trials to assess its efficacy in malignant gliomas. Although imatinib does not readily penetrate an intact blood–brain barrier (BBB), the extent to which it distributes into regions of high grade gliomas where the BBB is compromised has not been determined. Patients with recurrent high-grade gliomas for whom repeat surgical tumor debulking was clinically indicated received imatinib mesylate 600 mg orally once a day for seven days prior to surgery. Tissue samples were collected from different regions of the tumor and the approximate location of these samples was determined using frameless stereotactic neuronavigation. Plasma samples were obtained immediately before and after the resection. The concentration of imatinib in the plasma and tumor samples was determined using high performance liquid chromatography with mass spectrometric detection. Eleven tumor samples were obtained from three patients with recurrent glioblastoma multiforme. The median concentration of imatinib in these 11 tumor specimens was 1.34 μg/g (range 0.21–4.31 μg/g) and the median tumor-to-plasma ratio was 0.71 (range 0.28–3.03). These findings suggest that imatinib can reach intratumoral concentrations similar to those or higher than in plasma in regions of glioblastoma where the BBB is disrupted as indicated by contrast enhancement on magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

The Fibroblast Growth Factor (FGF) signaling pathway is reported to stimulate glioblastoma (GBM) growth. In this work we evaluated the effect of FGF2, FGF receptor (FGFR), and small molecule inhibition on GBM cells grown in traditional media, or cultured directly in stem-cell media. These lines each expressed the FGFR1, FGFR3 and FGFR4 receptors. Addition of FGF2 ligand showed significant growth stimulation in 8 of 10 cell lines. Disruption of FGF signaling by a neutralizing FGF2 monoclonal antibody and FGFR1 suppression by RNA interference both partially inhibited cell proliferation. Growth inhibition was temporally correlated with a reduction in MAPK signaling. A receptor tyrosine kinase inhibitor with known FGFR/VEGFR activity, PD173074, showed reproducible growth inhibition. Possible mechanisms of growth suppression by PD173074 were implicated by reduced phosphorylation of AKT and MAPK, known oncogenic signal transducers. Subsequent reduction in the cyclin D1, cyclin D2 and CDK4 cell cycle regulators was also observed. Our results indicate that FGF signaling pathway inhibition as a monotherapy will slow, but not arrest growth of glioblastoma cells. [ABSTRACT FROM AUTHOR]

Frameless stereotaxy, while most commonly applied to intracranial surgery, has seen an increasing number of applications in spinal surgery. Its use in the spine has been described to a greater degree in posterior rather than anterior surgical approaches, presumably due to the relative paucity of anatomical landmarks appropriate for frameless stereotactic registration in the anterior spine. This technical note illustrates the previously undescribed, successful use of frameless stereotaxy to the transmandibular, circumglossal, retropharyngeal surgical approach in a patient with Klippel-Feil syndrome. [ABSTRACT FROM AUTHOR]

Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed genome-wide or targeted sequencing on 50 cases. Sixteen MPNSTs but none of the neurofibromas tested were found to have somatic mutations in SUZ12, implicating it as having a central role in malignant transformation. [ABSTRACT FROM AUTHOR]

Protein-protein interaction can play an important role in the control of several biological events including gene transcription, replication and cell proliferation. E2F-1 is a DNA-binding transcription factor which, upon interaction with its target DNA sequence, induces expression of several S phase specific genes allowing progression of the cell cycle. Evidently, the activity of this protein is modulated by its cellular partner, pRb, which in the hypophosphorylated form, binds to E2F-1 and inactivates its transcriptional ability. In this study, we have demonstrated that expression of a sequence-specific single-stranded DNA binding protein, Purα, in cells decreases the ability of E2F-1 to exert its transcriptional activity upon the responsive promoter derived from DHFR. Results from band shift experiments revealed that while Purα does not recognize the double-stranded DNA fragment containing the E2F-1 binding site, it has the ability to inhibit E2F-1 interaction with its target DNA sequence. Results from GST pull-down assays and the combined immunoprecipitation/Western blot analysis of nuclear extracts revealed a direct association of E2F-1 with Purα in the absence of the DNA molecule containing the E2F-1 binding site. The association of Purα with E2F-1 may increase the stability of E2F-1, as a higher level of E2F-1 was detected in cells co-expressing Purα and E2F-1. The importance of these observations with respect to the role of Purα in the control of cell cycle progression is discussed. [ABSTRACT FROM AUTHOR]

Tetracycline controlled gene expression systems have become powerful tools in the analysis of gene function in mammalian cell culture as well as transgenic animals and plants. The original description of a tetracycline-regulated gene expression system is based on two plasmids, one of which constitutively expresses a tetracycline-controlled transactivator protein (tTA), a fusion protein between the tetracycline repressor of E. coli and the transcriptional activation domain of the VP16 protein of herpes simplex virus. The second plasmid contains the gene to be regulated by tTA under the control of an inducible promoter which consists of seven copies of the tetracycline resistance operator (tetO). Since this original description, many modifications have been described. In this report, we evaluate an autoregulatory tetracycline controlled system, in which the tTA is itself under the control of the tetO. We demonstrate that this autoregulatory tetracycline system produces adverse effects including cellular morphologic changes, growth rate attenuation and alterations in cell cycle distribution. [ABSTRACT FROM AUTHOR]

Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising in the upper portion of the sinonasal cavity. To better understand the genetic bases for ONB, here we perform whole exome and whole genome sequencing as well as single nucleotide polymorphism array analyses in a series of ONB patient samples. Deletions involving the dystrophin (DMD) locus are found in 12 of 14 (86%) tumors. Interestingly, one of the remaining tumors has a deletion in LAMA2, bringing the number of ONBs with deletions of genes involved in the development of muscular dystrophies to 13 or 93%. This high prevalence implicates an unexpected functional role for genes causing hereditary muscular dystrophies in ONB. Olfactory neuroblastoma (ONB) is a rare malignant tumor whose genetic basis is poorly understood. Here the authors identify recurrent deletions involving dystrophin in the majority of ONB patient tumors examined. [ABSTRACT FROM AUTHOR]

Most applications of nanotechnology in cancer have focused on systemic delivery of cytotoxic drugs. Systemic delivery relies on accumulation of nanoparticles in a target tissue through enhanced permeability of leaky vasculature and retention effect of poor lymphatic drainage to increase the therapeutic index. Systemic delivery is limited, however, by toxicity and difficulty crossing natural obstructions, like the blood spine barrier. Magnetic drug targeting (MDT) is a new technique to reach tumors of the central nervous system. Here, we describe a novel therapeutic approach for high-grade intramedullary spinal cord tumors using magnetic nanoparticles (MNP). Using biocompatible compounds to form a superparamagnetic carrier and magnetism as a physical stimulus, MNP-conjugated with doxorubicin were successfully localized to a xenografted tumor in a rat model. This study demonstrates proof-of-concept that MDT may provide a novel technique for effective, concentrated delivery of chemotherapeutic agents to intramedullary spinal cord tumors without the toxicity of systemic administration. [ABSTRACT FROM AUTHOR]

A correction to the article "Glioblastoma cell growth is suppressed by disruption of fibroblast growth factor pathway signaling" which was published in a previous issue is presented.