Endovascular Rescue of Previously Treated Carotid Aneurysm: Higher Radial Force 48-Wire Flow Diverter for Salvage of Collapsed 64-Wire Device With Braid Deformation: 2-Dimensional Operative Video.

Aneurysm treatment presents various therapeutic options. Flow diverters (FD) stents are a revolutionizing endovascular technique for previously untreatable aneurysms.1 FD stents have documented success rates up to 95% and complication rates as low as 2.3%.2 This modality has proven its effectiveness and safety, but it is critical to consider potential complications. Complications include vascular-related problems such as perforation, occlusion, cerebral hyperperfusion, stent thrombosis, restenosis, and embolic events.3 To date, there is no standardized definition for braid collapse and fish-mouthing; however, braid collapse has been reported to occur at a rate of 1% and the latter at a rate of 3%.4 This technical video presents a case of a 51-year-old woman initially treated with a Surpass Evolve flow diverter (Stryker) for a right ophthalmic aneurysm. Secondary to device malapposition and collapse, she developed recurrent ischemic progressive neurologic impairment symptoms. The braid collapse was treated using a Pipeline Embolization device 3.25 × 20 mm (Medtronic) because this device exhibited a larger partial compressive force when compared with the 64-wire device.5 The procedure was uneventful and significantly improved the patient's neurologic symptoms. This technical video illustrates rescue stenting as a salvage intervention for FD collapse cases. The patient gave informed consent for surgery. Institutional review board approval was deemed unnecessary.

Post-Transplant Lymphoproliferative Disorder: A Rare Case of CNS Involvement following Renal Transplant.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare immunosuppression complications affecting 5% of transplant patients. Isolated central nervous system (CNS)-PTLD without nodal or extra-nodal organ involvement is rarely reported and is difficult to diagnose due to the non-specific clinical manifestations and imaging features overlapping with other common CNS lesions. CASE PRESENTATION: We present a case of a 72-year-old female subjected to a renal transplant 11 years ago with progressively worsening headaches and confusion. Imaging revealed vasogenic edema in the left frontal and bilateral temporal lobes. She was subjected to a craniotomy and excisional biopsy to obtain tissue for diagnostic and therapeutic interventions. Pathology examination showed atypical EBV-positive lymphoplasmacytic infiltrate, consistent with Polymorphic type PTLD. CONCLUSIONS: Patients diagnosed with PTLD need to have close monitoring of immunosuppressive medications while in the hospital. Early diagnosis is essential for patient survival with PTLD, as their health can deteriorate fast.

Upper Extremity Monoplegia following Prone Surrender Position for Spinal Surgery.

Background Secondary peripheral nerve injuries remain a significant perioperative problem due to patient positioning and contribute to reduced patient quality of life and exacerbated professional liability. Comorbidities and concomitant lesions can further elicit these injuries in patients undergoing spinal surgeries. Case Presentation We report a case of a 70-year-old male polytrauma patient presenting with a left first-rib fracture and an adjacent hematoma around the brachial plexus without preoperative deficits. Subsequent to a lumbar spinal fusion in the prone position, he developed a postoperative left upper extremity monoplegia. The postoperative magnetic resonance imaging revealed an enhanced asymmetric signal in the trunks and cords of the left brachial plexus. He progressively improved with rehabilitation, a year after the initial presentation, with a residual wrist drop. Conclusions Pan brachial plexus monoplegia, following spine surgery, is rare and under-reported pathology. To minimize the occurrence of this rare morbidity, appropriate considerations in preoperative evaluation and counseling, patient positioning, intraoperative anesthetic, and electrophysiological monitoring should be performed. We emphasize an unreported risk factor in polytrauma patients, predisposing this rare injury that is associated with prone spinal surgery positioning, SEPs being an extremely sensitive test intraoperatively and highlight the importance of counseling patients and families to the possibility of this rare occurrence.

Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone.

BACKGROUND: Glioblastoma (GBM) is the most aggressive and common type of primary brain tumor in adults. Tumor location plays a role in patient prognosis, with tumors proximal to the lateral ventricles (LVs) presenting with worse overall survival, increased expression of stem cell genes, and increased incidence of distal tumor recurrence. This may be due in part to interaction of GBM with factors of the subventricular zone (SVZ), including those contained within the cerebrospinal fluid (CSF). However, direct interaction of GBM tumors with CSF has not been proved and would be hindered in the presence of an intact ependymal cell layer. METHODS: Here, we investigate the ependymal cell barrier and its derived extracellular matrix (ECM) fractones in the vicinity of a GBM tumor. Patient-derived GBM cells were orthotopically implanted into immunosuppressed athymic mice in locations distal and proximal to the LV. A PBS vehicle injection in the proximal location was included as a control. At four weeks post-xenograft, brain tissue was examined for alterations in ependymal cell health via immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. RESULTS: We identified local invading GBM cells within the LV wall and increased influx of CSF into the LV-proximal GBM tumor bulk compared to controls. In addition to the physical disruption of the ependymal cell barrier, we also identified increased signs of compromised ependymal cell health in LV-proximal tumor-bearing mice. These signs include increased accumulation of lipid droplets, decreased cilia length and number, and decreased expression of cell channel proteins. We additionally identified elevated numbers of small fractones in the SVZ within this group, suggesting increased indirect CSF-contained molecule signaling to tumor cells. CONCLUSIONS: Our data is the first to show that LV-proximal GBMs physically disrupt the ependymal cell barrier in animal models, resulting in disruptions in ependymal cell biology and increased CSF interaction with the tumor bulk. These findings point to ependymal cell health and CSF-contained molecules as potential axes for therapeutic targeting in the treatment of GBM.

Diffuse Intrinsic Pontine Glioma: Molecular Landscape, Evolving Treatment Strategies and Emerging Clinical Trials.

Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population of cells with multiple genetic mutations and high infiltrative capacity. The most common mutation seen in this group is a lysine to methionine point mutation seen at position 27 (K27M) within histone 3 (H3). Tumors with the H3 K27M mutation, are considered grade 4 and are now categorized within the H3 K27-altered diffuse midline glioma category by World Health Organization classification. Due to its critical location and aggressive nature, DIPG is resistant to the most eradicative treatment and is universally fatal; however, modern advances in the surgical techniques resulting in safe biopsy of the lesion have significantly improved our understanding of this disease at the molecular level. Genomic analysis has shown several mutations that play a role in the pathophysiology of the disease and can be targeted therapeutically. In this review, we will elaborate on DIPG from general aspects and the evolving molecular landscape. We will also review innovative therapeutic options that have been trialed along with new promising treatments on the horizon.

Current Advances in the Management of Adult Craniopharyngiomas.

Craniopharyngiomas (CPs) are slow growing, histologically benign intracranial tumors located in the sellar-suprasellar region. Although known to have low mortality, their location and relationship to the adjacent neural structures results in patients having significant neurologic, endocrine, and visual comorbidities. The invasive nature of this tumor makes complete resection a challenge and contributes to its recurrence. Additionally, these tumors are bimodally distributed, being treated with surgery, and are followed by other adjuncts, such as focused radiation therapy, e.g., Gamma knife. Advances in surgical techniques, imaging tools, and instrumentations have resulted in the evolution of surgery using endoscopic techniques, with residual components being treated by radiotherapy to target the residual tumor. Advances in molecular biology have elucidated the main pathways involved in tumor development and recurrence, but presently, no other treatments are offered to patients, besides surgery, radiation, and endocrine management, as the disease and tumor evolve. We review the contemporary management of these tumors, from the evolution of surgical treatments, utilizing standard open microscopic approaches to the more recent endoscopic surgery, and discuss the current recommendations for care of these patients. We discuss the developments in radiation therapy, such as radiosurgery, being used as treatment strategies for craniopharyngioma, highlighting their beneficial effects on tumor resections while decreasing the rates of adverse outcomes. We also outline the recent chemotherapy modalities, which help control tumor growth, and the immune landscape on craniopharyngiomas that allow the development of novel immunotherapies.

Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance.

According to classical dogma, the central nervous system (CNS) is defined as an immune privileged space. The basis of this theory was rooted in an incomplete understanding of the CNS microenvironment, however, recent advances such as the identification of resident dendritic cells (DC) in the brain and the presence of CNS lymphatics have deepened our understanding of the neuro-immune axis and revolutionized the field of neuroimmunology. It is now understood that many pathological conditions induce an immune response in the CNS, and that in many ways, the CNS is an immunologically distinct organ. Hyperactivity of neuro-immune axis can lead to primary neuroinflammatory diseases such as multiple sclerosis and antibody-mediated encephalitis, whereas immunosuppressive mechanisms promote the development and survival of primary brain tumors. On the therapeutic front, attempts are being made to target CNS pathologies using various forms of immunotherapy. One of the most actively investigated areas of CNS immunotherapy is for the treatment of glioblastoma (GBM), the most common primary brain tumor in adults. In this review, we provide an up to date overview of the neuro-immune axis in steady state and discuss the mechanisms underlying neuroinflammation in autoimmune neuroinflammatory disease as well as in the development and progression of brain tumors. In addition, we detail the current understanding of the interactions that characterize the primary brain tumor microenvironment and the implications of the neuro-immune axis on the development of successful therapeutic strategies for the treatment of CNS malignancies.

Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone.

Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ.

MR1 overexpression correlates with poor clinical prognosis in glioma patients.

BACKGROUND: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma. METHODS: Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression. RESULTS: MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma. CONCLUSIONS: Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.

A Comparison Between Chemo-Radiotherapy Combined With Immunotherapy and Chemo-Radiotherapy Alone for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Immunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates. OBJECTIVE: To perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM. METHODS: A literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher. RESULTS: Nine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group's 1-year OS [80.6% (95% CI: 68.6%-90.2%) vs. 72.6% (95% CI: 65.7%-78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%-48.2%) vs. 30.4% (95% CI: 25.4%-35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8-74.6%, vs 43.8%, 95% CI: 8.7-83.1, p = 0.81), but this effect also failed to reach statistical significance. CONCLUSION: Our results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.

Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy.

Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.

Alpha 1-antichymotrypsin contributes to stem cell characteristics and enhances tumorigenicity of glioblastoma.

BACKGROUND: Glioblastomas (GBMs) are the main primary brain tumors in adults with almost 100% recurrence rate. Patients with lateral ventricle proximal GBMs (LV-GBMs) exhibit worse survival compared to distal locations for unknown reasons. One hypothesis is the proximity of these tumors to the cerebrospinal fluid (CSF) and its chemical cues that can regulate cellular phenotype. We therefore investigated the role of CSF on GBM gene expression and the role of a CSF-induced gene, SERPINA3, in GBM malignancy in vitro and in vivo. METHODS: We utilized human CSF and GBM brain tumor-initiating cells (BTICs). We determined the impact of SERPINA3 expression in glioma patients using The Cancer Genome Atlas (TCGA) database. SERPINA3 expression changes were evaluated at mRNA and protein levels. The effects of knockdown (KD) and overexpression (OE) of SERPINA3 on cell migration, viability and cell proliferation were evaluated. Stem cell characteristics on KD cells were evaluated by differentiation and colony formation experiments. Tumor growth was studied by intracranial and flank injections. RESULTS: GBM-CSF increased BTIC migration accompanied by upregulation of the SERPINA3 gene. In patient samples and TCGA data, we observed SERPINA3 to correlate directly with brain tumor grade and indirectly with GBM patient survival. SERPINA3 KD induced a decrease in cell proliferation, migration, invasion, and stem cell characteristics, while SERPINA3 OE increased cell migration. In vivo, SERPINA3 KD BTICs showed increased survival in a murine model. CONCLUSIONS: SERPINA3 plays a key role in GBM malignancy and its inhibition results in a better outcome using GBM preclinical models.

Ankylosing spondylitis traumatic subaxial cervical fractures - An updated treatment algorithm.

Ankylosing spondylitis (AS) is a rheumatologic disease characterized by ankylosis and ligament ossification of the spine with an elevated risk of vertebrae fractures at the cervical level or cervicothoracic junction. AS related cervical fractures (ASCFs) require early diagnosis and a treatment plan that considers the high risk for additional fractures to avoid neurological complications or death. We present the case of a patient with an ASCF and a review of the literature with key recommendations that shape our algorithm for the proper diagnosis and treatment of ASCFs. We present the case of a 29-year-old male with an ASCF at C5-C6 treated initially with a short segment instrumented arthrodesis that required an additional operation to properly stabilize and protect his spine. Based on our experience with this case and a review of the literature, we discuss three recommendations to improve ASCF management. These include the need for early computed tomography/magnetic resonance image for proper diagnoses, combined surgical approach with long-segment stabilization for maximum stability. Delayed diagnosis or revision surgery, both of which are common in these patients who present with a stiffened and osteoporotic spine, may lead to spinal cord injury or neurologic deficits. Our recommendations based on the most recent evidence can help surgeons better manage these patients and decrease their overall morbidity and mortality.

Myosin 10 Regulates Invasion, Mitosis, and Metabolic Signaling in Glioblastoma.

Invasion and proliferation are defining phenotypes of cancer, and in glioblastoma blocking one stimulates the other, implying that effective therapy must inhibit both, ideally through a single target that is also dispensable for normal tissue function. The molecular motor myosin 10 meets these criteria. Myosin 10 knockout mice can survive to adulthood, implying that normal cells can compensate for its loss; its deletion impairs invasion, slows proliferation, and prolongs survival in murine models of glioblastoma. Myosin 10 deletion also enhances tumor dependency on the DNA damage and the metabolic stress responses and induces synthetic lethality when combined with inhibitors of these processes. Our results thus demonstrate that targeting myosin 10 is active against glioblastoma by itself, synergizes with other clinically available therapeutics, may have acceptable side effects in normal tissues, and has potential as a heretofore unexplored therapeutic approach for this disease.

Chitosan-Based Non-viral Gene and Drug Delivery Systems for Brain Cancer.

Central nervous system (CNS) tumors are a leading source of morbidity and mortality worldwide. Today, different strategies have been developed to allow targeted and controlled drug delivery into the brain. Gene therapy is a system based on the modification of patient's cells through the introduction of genetic material to exert a specific action. Administration of the foreign genetic material can be done through viral-mediated delivery or non-viral delivery via physical or mechanical systems. For brain cancer specifically, gene therapy can overcome the actual challenge of blood brain barrier penetration, the main reason for therapeutic failure. Chitosan (CS), a natural based biodegradable polymer obtained from the exoskeleton of crustaceans such as crab, shrimp, and lobster, has been used as a delivery vehicle in several non-viral modification strategies. This cationic polysaccharide is highly suitable for gene delivery mainly due to its chemical properties, its non-toxic nature, its capacity to protect nucleic acids through the formation of complexes with the genetic material, and its ease of degradation in organic environments. Recent evidence supports the use of CS as an alternative gene delivery system for cancer treatment. This review will describe multiple studies highlighting the advantages and challenges of CS-based delivery structures for the treatment of brain tumors. Furthermore, this review will provide insight on the translational potential of various CS based-strategies in current clinical cancer studies. Specifically, CS-based nanostructures including nanocapsules, nanospheres, solid-gel formulations, and nanoemulsions, also microshperes and micelles will be evaluated.

Inflammatory Mediators in Glioma Microenvironment Play a Dual Role in Gliomagenesis and Mesenchymal Stem Cell Homing: Implication for Cellular Therapy.

Glioblastoma is the most aggressive malignant primary brain tumor, with a dismal prognosis and a devastating overall survival. Despite aggressive surgical resection and adjuvant treatment, average survival remains approximately 14.6 months. The brain tumor microenvironment is heterogeneous, comprising multiple populations of tumor, stromal, and immune cells. Tumor cells evade the immune system by suppressing several immune functions to enable survival. Gliomas release immunosuppressive and tumor-supportive soluble factors into the microenvironment, leading to accelerated cancer proliferation, invasion, and immune escape. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, or umbilical cord are a promising tool for cell-based therapies. One crucial mechanism mediating the therapeutic outcomes often seen in MSC application is their tropism to sites of injury. Furthermore, MSCs interact with host immune cells to regulate the inflammatory response, and data points to the possibility of using MSCs to achieve immunomodulation in solid tumors. Interleukin 1ß, interleukin 6, tumor necrosis factor α, transforming growth factor ß, and stromal cell-derived factor 1 are notably up-regulated in glioblastoma and dually promote immune and MSC trafficking. Mesenchymal stem cells have widely been regarded as hypoimmunogenic, enabling this cell-based administration across major histocompatibility barriers. In this review, we will highlight (1) the bidirectional communication of glioma cells and tumor-associated immune cells, (2) the inflammatory mediators enabling leukocytes and transplantable MSC migration, and (3) review preclinical and human clinical trials using MSCs as delivery vehicles. Mesenchymal stem cells possess innate abilities to migrate great distances, cross the blood-brain barrier, and communicate with surrounding cells, all of which make them desirable "Trojan horses" for brain cancer therapy.

Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model.

Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain cancer. Despite surgery and chemo/radiation therapy, recurrence often takes place and leads to patient death. We report here on the development of a camptothecin (CPT)-based self-assembling prodrug (SAPD) hydrogel that can be used as an adjunct therapy for local treatment of GBM following maximal tumor resection. When dispersed in aqueous solution, the designed CPT prodrug spontaneously assembles into supramolecular filaments with a 100% CPT loading. In both in vitro and ex vivo assays, we show that the designed CPT prodrug can be steadily released from its supramolecular filament hydrogel, effectively killing primary GBM cells derived from patients. We also found that the solution containing self-assembling CPT filaments can be directly applied to the tumor cavity after surgical removal, and forms a gel immediately upon contact with the brain tissue. Our in vivo studies with a resection and recurrence mouse model suggest that this prodrug hydrogel can release cancer therapeutics into brain parenchyma over a long period of time, suppressing tumor recurrence and leading to prolonged survival. We believe that the simplicity in prodrug design and the high efficacy in suppressing GBM growth enable the unique potential of this SAPD hydrogels for clinical translation as an adjunct therapy for GBM treatment.

The Study of Brain Tumor Stem Cell Migration.

Despite many advancements in brain cancer therapeutics, brain cancer remains one of the most elusive diseases with high migratory capacity and a dismal prognosis. It is well established that tumor stem cells utilize the same available migratory machinery that normal cells employ. Some of the major determinants of brain tumor stem cell migration are their cytoskeletal rearrangements and adhesion dynamics. This phenomenon allows brain tumor stem cells to perpetually migrate, invade, and repopulate in a vicious cycle leading to tumor expansion and invasion at tumor boundaries. In order to dissect the enabling factors that allow for this process to be hijacked, we have identified relevant assays to enable measurements of neoplastic migration such as Boyden Chamber, 3D chemogradient chamber, Nanopattern, and wound healing assays. Our purpose is to report the complex experimental platforms seen in the literature today and provide an optimal platform to kick off your studies in this field.

The Study of Brain Tumor Stem Cell Invasion.

Ninety percent of deaths from solid tumors have been ascribed to the invasion and metastatic dissemination of cancer cells. One of the most fundamental prerequisites of brain tumor stem cell invasion is their ability to penetrate and traverse through the basement membrane and stromal compartments displacing from their original point of origin and repopulating at a distant site and adjacent tissue. In order to propose a successful clinical strategy, the investigation of the molecular determinants of invasion must factor in measurements and predictors of the complexity of brain tumor invasion potential accounting for the physiological scenarios encountered in the tumor niche. This chapter will highlight some laboratory approaches such as: spot assay, 3D chemogradient chambers, Fluoroblok™ tumor invasion, organotypics, and 3D tumor spheroid assays that could help mitigate the investigation of a tumor stem cell's invasion capacity through restrictive 3D environments otherwise seen in vivo.

Challenges of Managing Patients with Symptomatic Large Traumatic Cervical Pseudomeningoceles.

BACKGROUND: Traumatic cervical pseudomeningoceles (TCPs) occur secondary to traction of the cervical nerve roots resulting in violation of the dura. Surgical repair is not necessary in most cases because pseudomeningoceles have a high propensity to spontaneously resolve with conservative management alone. Currently, there are a limited number of cases of large TCPs (large is defined as ≥6 cm in greatest diameter), and there is no established guideline for the management of such lesions. CASE DESCRIPTION: We describe the cases of 2 young men in their 20s who were involved in a motor vehicle accident. Both patients suffered a brachial plexus injury and developed large TCPs. Patient 1 was treated surgically for TCP using a combined intra-/extradural approach using a fascia lata graft. Patient 2 was ultimately treated nonsurgically because a spontaneous resolution of the pseudomeningocele was achieved over the period of 7 months after the accident. Both patients underwent brachial plexus repair surgery consisting of spinal accessory nerve transfer to the suprascapular nerve and intercostal nerve transfer to the musculocutaneous nerve. CONCLUSIONS: Disease progression of TCPs is a dynamic process, and even large lesions may spontaneously resolve without surgical intervention. When surgery is indicated, a definitive dural repair using a fascia lata graft to cover the dural tear intra- and extradurally is an effective method. Surgery must be planned carefully on a case-by-case basis, and close follow-up with thorough physical examination and serial imaging is critical to monitor disease progression.