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Purpose: Multiple surgical approaches have been described to maximize visualization and accessibility for resection while minimizing morbidity in the patient with orbital intraconal tumors. Transnasal endoscopic approaches have become increasingly standard in select orbital cavernous venous malformations but often require a partial septectomy. The purpose of this manuscript is to communicate a septal preserving modified transseptal approach., Methods: A 37-year old male was found to have an inferomedial intraconal orbital mass, measuring up to 2.6 cm on magnetic resonance imaging. Binarial transseptal access with septal preservation was obtained with a Killian incision on the right and a small incision in the midseptum on the left., Results: Successful tumor delivery through the nasal cavity resulted in orbital relaxation. Postoperative evaluation of the septum demonstrated an intact septum with nearly no evidence of septal trauma from surgical manipulation., Conclusion: This technique is easily performed and affords adequate visualization and freedom of movement as traditional binarial transseptal approaches without the disadvantages of partial septal loss such as increased crusting, olfactory disturbance, and loss of nasoseptal flaps., (Copyright © 2021. Published by Elsevier Inc.)

Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas., (Copyright © 2020 Wilson, Huang, Ramanathan, Lopez-Gonzalez, Pillai, De Los Reyes, Kumal and Boling.)

Background: Meningiomas are common intracranial neoplasms of undetermined etiology. Accelerated growth during episodes of elevated serum estrogen and progesterone have been demonstrated in pregnant patients, as exhibited by an overexpression of estrogen or progesterone on immunohistochemical analysis. This case report and literature review describe a case of complete meningioma regression in a postpartum patient., Case Description: A 23-year-old female presented at 37 weeks of pregnancy with 1-month history of fluctuating severe left-sided headaches, periodic blurry vision, nausea, and vomiting. She had 2 previous pregnancies without complication. Magnetic resonance imaging revealed a dural-based, heterogeneously enhancing mass along the left tentorium, just posterior to the transverse sinus, with supratentorial extension and surrounding edema. Differential diagnoses included meningioma versus hemangioma versus hemangiopericytoma. The patient followed up with neurosurgery 1 month after delivery. She had continued left-sided headaches but no longer complained of visual changes. A postpartum surgical resection via left occipital and suboccipital craniotomy was planned. Approximately 1 month later (now about 3 months after delivery) a repeat magnetic resonance imaging demonstrated a marked decrease in meningioma size, and the previously seen edema had resolved. In light of the sudden disappearance of the meningioma, no further surgical intervention was pursued., Conclusions: Because meningioma shrinkage or disappearance may occur after pregnancy, repeat imaging is advised as part of a preoperative evaluation. In addition, it is possible that an undetermined amount of meningioma removal surgeries may be avoided with further research into monitoring hormone levels connected to meningioma growth., (Published by Elsevier Inc.)

Background: Trigeminal neuralgia (TGN) causes severe unilateral facial pain. The etiology is hypothesized to be segmental demyelination of the trigeminal nerve root via compression by the superior cerebellar artery (SCA). Microvascular decompression (MVD) allows immediate and long-term pain relief. Preoperative evaluation includes magnetic resonance imaging (MRI) and/or magnetic resonance angiography of the brain. Having a pacemaker is a contraindication for MRI. There have been isolated reports of using computed tomography (CT) cisternography scans for radiation planning for TGN., Case Description: A 75-year-old male with a permanent pacemaker who had refractory TGN in the V2 (maxillary) distribution of the trigeminal nerve underwent CT cisternography to prepare for MVD. CT angiography with Isovue 370 intravenous contrast injection and 0.625-mm axial images were obtained from the skull base across the posterior fossa. An intrathecal injection of Isovue 180 was performed at the L2/3 level. Imaging revealed the right SCA abutting the medial margin of the proximal right trigeminal nerve. In surgery (K.D.), a standard retrosigmoid suboccipital craniotomy was performed to access the cerebellopontine angle and separate the abutting SCA and trigeminal nerve. The patient had immediate pain relief., Conclusions: MRI is the preferred method of evaluating for TGN because it offers excellent visualization of vasculature in relation to the trigeminal nerve without accompanying radiation exposure. However, for patients who have contraindications to MRI, CT cisternography is shown to also be an effective method for visualizing the trigeminal root entry zone and nearby vasculature in preparation for MVD of the trigeminal nerve., (Published by Elsevier Inc.)

A 56-year-old woman with a 3-year history of hydrocephalus and ventriculo-peritoneal shunt placement, presented with worsening altered level of consciousness for 2 days. Imaging studies showed severe ventriculomegaly involving the lateral and third ventricles with multiple septated cysts noted in the lateral ventricles predominantly near the frontal horns. Histopathologic examination of the excised brain lesion revealed choroid plexus tissue and adjacent cerebral parenchyma with several non-caseating granulomas. Granulomatous inflammation was also identified in mediastinal lymph nodes. By using specific monoclonal antibodies, Propionibacterium acnes (P. acnes) were detected in non-caseating granulomas of both the brain and mediastinal lymph nodes. No acid-fast bacilli or fungal elements were present. To the best of our knowledge, this is the first demonstration of P. acnes in sarcoid granulomas of cerebral tissue, and it reinforces the possible link between P. acnes and sarcoidosis., (© 2017 Japanese Society of Neuropathology.)

IgG4-related pachymeningitis is a serious inflammatory condition that can present with symptoms of mass effect and focal deficits. The first-line therapy is steroids and second-line is chemotherapy (methotrexate, azathioprine, etc.). We describe a patient with IgG4-related pachymeningitis in whom steroid use was contraindicated and methotrexate was ineffective. During the course of treatment, the patient presented to the emergency department with receptive and expressive aphasia, slurred speech, right-sided neglect, and loss of sensation. After a single infusion of rituximab and anticonvulsants, her symptoms resolved. Our unique case suggests that patients with IgG4-related pachymeningitis might benefit from early initiation of rituximab., (Copyright © 2016 Elsevier B.V. All rights reserved.)

OBJECT Approximately 250 million surgical procedures are performed annually worldwide, and data suggest that major complications occur in 3%-17% of them. Many of these complications can be classified as avoidable, and previous studies have demonstrated that preoperative checklists improve operating room teamwork and decrease complication rates. Although the authors' institution has instituted a general preoperative "time-out" designed to streamline communication, flatten vertical authority gradients, and decrease procedural errors, there is no specific checklist for transnasal transsphenoidal anterior skull base surgery, with or without endoscopy. Such minimally invasive cranial surgery uses a completely different conceptual approach, set-up, instrumentation, and operative procedure. Therefore, it can be associated with different types of complications as compared with open cranial surgery. The authors hypothesized that a detailed, procedure-specific, preoperative checklist would be useful to reduce errors, improve outcomes, decrease delays, and maximize both teambuilding and operational efficiency. Thus, the object of this study was to develop such a checklist for endonasal transsphenoidal anterior skull base surgery. METHODS An expert panel was convened that consisted of all members of the typical surgical team for transsphenoidal endoscopic cases: neurosurgeons, anesthesiologists, circulating nurses, scrub technicians, surgical operations managers, and technical assistants. Beginning with a general checklist, procedure-specific items were added and categorized into 4 pauses: Anesthesia Pause, Surgical Pause, Equipment Pause, and Closure Pause. RESULTS The final endonasal transsphenoidal anterior skull base surgery checklist is composed of the following 4 pauses. The Anesthesia Pause consists of patient identification, diagnosis, pertinent laboratory studies, medications, surgical preparation, patient positioning, intravenous/arterial access, fluid management, monitoring, and other special considerations (e.g., Valsalva, jugular compression, lumbar drain, and so on). The Surgical Pause is composed of personnel introductions, planned procedural elements, estimation of duration of surgery, anticipated blood loss and fluid management, imaging, specimen collection, and questions of a surgical nature. The Equipment Pause assures proper function and availability of the microscope, endoscope, cameras and recorders, guidance systems, special instruments, ultrasonic microdoppler, microdebrider, drills, and other adjunctive supplies (e.g., Avitene, cotton balls, nasal packs, and so on). The Closure Pause is dedicated to issues of immediate postoperative patient disposition, orders, and management. CONCLUSIONS Surgical complications are a considerable cause of death and disability worldwide. Checklists have been shown to be an effective tool for reducing preventable errors surrounding surgery and decreasing associated complications. Although general checklists are already in place in most institutions, a specific checklist for endonasal transsphenoidal anterior skull base surgery was developed to help safeguard patients, improve outcomes, and enhance teambuilding.

Objective: Endoscopic skull base surgery has become increasingly popular among the skull base surgery community, with improved illumination and angled visualization potentially improving tumor resection rates. Intraoperative MRI (iMRI) is used to detect residual disease during the course of the resection. This study is an investigation of the utility of 3-T iMRI in combination with transnasal endoscopy with regard to gross-total resection (GTR) of pituitary macroadenomas., Methods: The authors retrospectively reviewed all endoscopic transsphenoidal operations performed in the Advanced Multimodality Image Guided Operating (AMIGO) suite from November 2011 to December 2014. Inclusion criteria were patients harboring presumed pituitary macroadenomas with optic nerve or chiasmal compression and visual loss, operated on by a single surgeon., Results: Of the 27 patients who underwent transsphenoidal resection in the AMIGO suite, 20 patients met the inclusion criteria. The endoscope alone, without the use of iMRI, would have correctly predicted extent of resection in 13 (65%) of 20 cases. Gross-total resection was achieved in 12 patients (60%) prior to MRI. Intraoperative MRI helped convert 1 STR and 4 NTRs to GTRs, increasing the number of GTRs from 12 (60%) to 16 (80%)., Conclusions: Despite advances in visualization provided by the endoscope, the incidence of residual disease can potentially place the patient at risk for additional surgery. The authors found that iMRI can be useful in detecting unexpected residual tumor. The cost-effectiveness of this tool is yet to be determined., Competing Interests: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Background: Retrochiasmatic, retroinfundibular craniopharyngiomas are surgically challenging tumors. Anterolateral, posterolateral, and endoscopic endonasal approaches represent the most commonly used techniques to access these tumors, but all require an extensive exposure time, and each has its own risks and limitations. The subtemporal approach is a well-known neurosurgical approach that is rarely described for craniopharyngiomas., Objective: To assess the feasibility, advantages, and disadvantages of a subtemporal approach for craniopharyngiomas., Methods: Five patients with retrochiasmatic craniopharyngiomas where the majority of the tumor extended behind the dorsal clival line underwent a subtemporal approach for resection. Extent of resection, degree of temporal lobe injury, visual and endocrine outcomes, and time to recurrence were analyzed., Results: Average tumor volume was 6.4 cm3. Near-total resection was achieved in 80% (4/5) and subtotal in 20% (1/5). All patients had stable or improved vision. There was 1 new permanent endocrine deficiency. Minimal temporal lobe edema was observed in 80% (4/5) of patients. Three patients required postoperative radiation., Conclusion: The subtemporal approach represents a feasible approach for retrochiasmatic, retroinfundibular craniopharyngiomas when gross total resection is not mandatory. It provides rapid access to the tumor and a caudal-to-cranial visualization that promotes minimal manipulation of critical neurovascular structures, particularly the optic apparatus.

Unlabelled: Recombinant trimeric mimics of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike should expose as many epitopes as possible for broadly neutralizing antibodies (bNAbs) but few, if any, for nonneutralizing antibodies (non-NAbs). Soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A strain BG505 approach this ideal and are therefore plausible vaccine candidates. Here, we report on the production and in vitro properties of a new SOSIP.664 trimer derived from a subtype B env gene, B41, including how to make this protein in low-serum media without proteolytic damage (clipping) to the V3 region. We also show that nonclipped trimers can be purified successfully via a positive-selection affinity column using the bNAb PGT145, which recognizes a quaternary structure-dependent epitope at the trimer apex. Negative-stain electron microscopy imaging shows that the purified, nonclipped, native-like B41 SOSIP.664 trimers contain two subpopulations, which we propose represent an equilibrium between the fully closed and a more open conformation. The latter is different from the fully open, CD4 receptor-bound conformation and may represent an intermediate state of the trimer. This new subtype B trimer adds to the repertoire of native-like Env proteins that are suitable for immunogenicity and structural studies., Importance: The cleaved, trimeric envelope protein complex is the only neutralizing antibody target on the HIV-1 surface. Many vaccine strategies are based on inducing neutralizing antibodies. For HIV-1, one approach involves using recombinant, soluble protein mimics of the native trimer. At present, the only reliable way to make native-like, soluble trimers in practical amounts is via the introduction of specific sequence changes that confer stability on the cleaved form of Env. The resulting proteins are known as SOSIP.664 gp140 trimers, and the current paradigm is based on the BG505 subtype A env gene. Here, we describe the production and characterization of a SOSIP.664 protein derived from a subtype B gene (B41), together with a simple, one-step method to purify native-like trimers by affinity chromatography with a trimer-specific bNAb, PGT145. The resulting trimers will be useful for structural and immunogenicity experiments aimed at devising ways to make an effective HIV-1 vaccine., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Laboratory-based testing does not reach many individuals in lower-resource settings who could benefit from access to appropriate tests for diagnosis and therapy. A critical issue is laboratory-based testing often requires an environment with a high level of resources and supporting infrastructure that is not available in many areas of the world. The current report describes the conversion of a laboratory-based test for phenylalanine detection to a simple paper-based test appropriate for use in low-resource settings. The paper-based test is easy to operate, with all reagents stored dry on the card, is compatible with visible detection for clinically relevant concentrations of phenylalanine, and has a time to result of 10 minutes. Next steps for test development are discussed in the context of the potential for the paper-based Phe test to be used as a newborn PKU screening test in settings that are not well served by existing screening approaches.

Background: Recombinant soluble, cleaved HIV-1 envelope glycoprotein SOSIP.664 gp140 trimers based on the subtype A BG505 sequence are being studied structurally and tested as immunogens in animals. For these trimers to become a vaccine candidate for human trials, they would need to be made in appropriate amounts at an acceptable quality. Accomplishing such tasks by transient transfection is likely to be challenging. The traditional way to express recombinant proteins in large amounts is via a permanent cell line, usually of mammalian origin. Making cell lines that produce BG505 SOSIP.664 trimers requires the co-expression of the Furin protease to ensure that the cleavage site between the gp120 and gp41 subunits is fully utilized., Results: We designed a vector capable of expressing Env and Furin, and used it to create Stable 293 T and CHO Flp-In™ cell lines through site-specific recombination. Both lines produce high quality, cleaved trimers at yields of up to 12-15 mg per 1 × 109 cells. Trimer expression at such levels was maintained for up to 30 days (10 passages) after initial seeding and was consistently superior to what could be achieved by transient transfection. Electron microscopy studies confirm that the purified trimers have the same native-like appearance as those derived by transient transfection and used to generate high-resolution structures. They also have appropriate antigenic properties, including the presentation of the quaternary epitope for the broadly neutralizing antibody PGT145., Conclusions: The BG505 SOSIP.664 trimer-expressing cell lines yield proteins of an appropriate quality for structural studies and animal immunogenicity experiments. The methodology is suitable for making similar lines under Good Manufacturing Practice conditions, to produce trimers for human clinical trials. Moreover, any env gene can be incorporated into this vector system, allowing the manufacture of SOSIP trimers from multiple genotypes, either by transient transfection or from stable cell lines.

A desirable but as yet unachieved property of a human immunodeficiency virus type 1 (HIV-1) vaccine candidate is the ability to induce broadly neutralizing antibodies (bNAbs). One approach to the problem is to create trimeric mimics of the native envelope glycoprotein (Env) spike that expose as many bNAb epitopes as possible, while occluding those for non-neutralizing antibodies (non-NAbs). Here, we describe the design and properties of soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A transmitted/founder strain, BG505. These trimers are highly stable, more so even than the corresponding gp120 monomer, as judged by differential scanning calorimetry. They are also homogenous and closely resemble native virus spikes when visualized by negative stain electron microscopy (EM). We used several techniques, including ELISA and surface plasmon resonance (SPR), to determine the relationship between the ability of monoclonal antibodies (MAbs) to bind the soluble trimers and neutralize the corresponding virus. In general, the concordance was excellent, in that virtually all bNAbs against multiple neutralizing epitopes on HIV-1 Env were highly reactive with the BG505 SOSIP.664 gp140 trimers, including quaternary epitopes (CH01, PG9, PG16 and PGT145). Conversely, non-NAbs to the CD4-binding site, CD4-induced epitopes or gp41ECTO did not react with the trimers, even when their epitopes were present on simpler forms of Env (e.g. gp120 monomers or dissociated gp41 subunits). Three non-neutralizing MAbs to V3 epitopes did, however, react strongly with the trimers but only by ELISA, and not at all by SPR and to only a limited extent by EM. These new soluble trimers are useful for structural studies and are being assessed for their performance as immunogens.

Ommaya reservoirs are routinely placed for the administration of intrathecal chemotherapy or antibiotics. There is scant literature that addresses the functionality of an Ommaya catheter placed exclusively within a cavum septum pellucidum (CSP). In this case, the authors placed an Ommaya reservoir in a 30-year-old man with Burkitt lymphoma in the CNS for intrathecal chemotherapy. The catheter tip was placed within a large CSP. The authors demonstrated failure of the system by injecting contrast agent into the reservoir and obtaining immediate and delayed CT scans that failed to demonstrate contrast dissemination into the ventricular system. An Ommaya reservoir placed exclusively within a CSP is potentially not functional, and can be dangerous if used for intrathecal drug therapy.

Background: Aneurysmal subarachnoid hemorrhage (SAH) with associated intracerebral hemorrhage (ICH) is often treated with concomitant surgical clipping and ICH evacuation. The aim of this study was to determine if aneurysm coiling followed by ICH evacuation is a viable alternative treatment., Methods: A retrospective review was conducted between July 2000 and March 2009 of patients with aneurysmal SAH plus ICH (>30 ml or with midline shift >5 mm) who underwent aneurysm repair (either coiling or clipping) and craniotomy for ICH evacuation. Demographic and radiographic criteria, time to aneurysm protection, length of stay (LOS), treatment complications, discharge disposition and 3 month functional outcome were compared between groups., Results: Of 18 SAH+ICH patients, 10 underwent aneurysm coiling followed by ICH evacuation and eight underwent clipping with ICH evacuation. Compared with clipped patients, coiled patients had a lower Glasgow Coma Scale score (median 5.5 vs 7.5), higher ICH score (median 3 vs 2), worse modified Fisher score (median 4 vs 3) and higher rate of herniation at presentation (50% vs 25%). Median time to aneurysm protection was shorter in coiled patients (299 vs 885 min, p<0.001). Comparing coiled with clipped patients, rates of death (30% vs 25%), poor outcome (70% vs 50%), median ICU LOS (20 vs 22 days), median hospital LOS (27 vs 29 days) and total median direct costs ($64,537 vs $61,243) were similar, as were complication rates (all p>0.05)., Conclusions: Coiling followed by ICH evacuation is associated with faster time to aneurysm protection and similar outcome, LOS and cost as clipping and evacuation. This may be a viable alternative to clipping and ICH evacuation.

HIV-1 can infect T cells by cell-free virus or by direct virion transfer between cells through cell contact-induced structures called virological synapses (VS). During VS-mediated infection, virions accumulate within target cell endosomes. We show that after crossing the VS, the transferred virus undergoes both maturation and viral membrane fusion. Following VS transfer, viral membrane fusion occurs with delayed kinetics and transferred virions display reduced sensitivity to patient antisera compared to mature, cell-free virus. Furthermore, particle fusion requires that the transferred virions undergo proteolytic maturation within acceptor cell endosomes, which occurs over several hours. Rapid, live cell confocal microscopy demonstrated that viral fusion can occur in compartments that have moved away from the VS. Thus, HIV particle maturation activates viral fusion in target CD4+ T cell endosomes following transfer across the VS and may represent a pathway by which HIV evades antibody neutralization., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Little current data exists regarding outcome, cost, and length of stay (LOS) after subdural hemorrhage (SDH). We sought to examine predictors of discharge disposition, ICU and hospital LOS and direct, indirect, ICU, surgical, and diagnostic costs for SDH., Methods: A retrospective review was conducted of 216 SDH patients, aged >18 years admitted to our hospital between 1/2001 and 12/2008. Discharge disposition was characterized as dead, poor or good. Multivariable logistic regression analysis was performed to identify predictors of disposition, LOS, and cost., Results: Of 216 SDH patients, the median age was 74 (19-95), and the median admission Glasgow Coma Scale (GCS) was 14 (3-15). The SDH was characterized as acute in 14%, subacute in 44%, chronic in 12%, and mixed in 30%. Surgical evacuation was performed in 139 (64%) patients. Death occurred in 29 (13%) patients and poor disposition in 43 (20%). Significant predictors of death included age, admission GCS, and hospital LOS (P < 0.05). Longer hospital LOS was associated with poor disposition, while shorter ICU LOS was associated with good disposition (P < 0.01). Median hospital LOS was 8 (1-99) days. Median total direct costs for hospitalization were $10,670 ($907-238,856). ICU and hospital LOS were significant predictors of all measures of cost (P < 0.05). SDH size, chronicity, and surgical intervention were not predictors of any outcome. There was no significant change in any outcome variable between 2001 and 2008., Conclusions: Despite good admission neurological status, death or poor discharge disposition is common after SDH. LOS and costs remain high and have not improved in the last decade.

Objective: Deep brain stimulation (DBS) has become routine for the treatment of Parkinson's disease and essential tremor. Because both of these disorders are common in patients older than the age of 60, neurosurgeons are likely to encounter increasing numbers of patients who require DBS surgery but who already have another electronic medical implant such as a cardiac pacemaker/defibrillator or intrathecal infusion pump, raising the concern that one device might interfere with the performance of the other., Clinical Presentation: Herein we report a modification of surgical technique resulting in the successful use of thalamic DBS to treat disabling essential tremor in a man with a previously implanted cochlear implant., Intervention and Technique: The presence of the cochlear implant necessitated a number of modifications to our standard surgical technique including surgical removal of the subgaleal magnet that holds the receiver to the scalp and the use of computed tomography instead of magnetic resonance imaging to target the thalamus. More than a year after surgery, the patient is enjoying continued tremor suppression and an enhanced quality of life. The presence of the DBS device has not interfered with the proper functioning of his cochlear implant., Conclusion: DBS can be used successfully in patients with a previously implanted cochlear implant. The operating neurosurgeon should be aware of the limitations of intraoperative imaging and the need to coordinate with an otologic surgeon for maximum patient benefit.