Search

Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-specific manner. Interestingly, AXL is frequently overexpressed in GBM patients. Using commercially available GBM cell lines, we first show that cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not. Furthermore, inhibition of AXL kinase using R428 and antibody blockade of AXL receptor strongly attenuated virus entry in GBM cell lines. Additionally, CRISPR knockout of the AXL gene in GBM cell lines completely abolished ZIKV infection, significantly inhibited viral replication, and significantly reduced apoptosis compared with parental lines. Lastly, introduction of AXL receptor into non-expressing cell lines renders the cells susceptible to ZIKV infection. Together, these findings demonstrate that ZIKV entry into GBM cells in vitro is mediated by the AXL receptor and that following cell entry, productive infection is cytotoxic. Thus, ZIKV is a potential oncolytic virus for GBM., Graphical abstract, Zika virus (ZIKV) can infect glioblastoma (GBM) cells. We show that ZIKV entry and infection is mediated by the tyrosine kinase receptor AXL. AXL antibody blockade, CRISPR knockout, and kinase inhibition all mitigate ZIKV entry and infection. This receptor-mediated tropism suggests ZIKV as a candidate oncolytic virus for GBM.

Tumors in the posterior fossa can be situated either dorsal and lateral, ventral and medial, or occupying both regions in relation to the cranial nerves, with the latter position being especially challenging. In an effort to organize neurovascular complexes contained within, anatomically based triangles have been proposed to serve as guiding landmarks for locating critical neurovascular structures. The objectives of this study were to: (1) provide a review of historical anatomically based vascular-centric triangles of the posterior fossa based on respective neurovascular complexes; (2) introduce a more organized alternative system of triangles with the conceptualization of a projection system from superficial to deep; and (3) propose and describe two new triangles of the posterior fossa: Petrous-Acousticofacial and Acousticofacial-Trigeminal. Five cadavers were studied. Neurovascular complexes were described with the use of anatomically guided cranial nerve-centric triangles, each of which was formed by cranial nerves, petrous bone, brainstem, tentorium, and superior petrosal vein. All triangles were measured and anatomical boundaries confirmed by neuronavigation. Two circumferential frameworks were created to correlate superficial and deep anatomy: (1) Outer circumference and (2) Inner circumference. Posterior fossa was divided into the following: (1) Superior complex-corresponds to the sub-asterional region, which was projected to the trigeminal nerve; (2) Middle complex-corresponds to the mastoid emissary vein foramen, which was projected to the facial and vestibulocochlear nerves; and (3) Inferior complex-corresponds to the posterior condylar canal, which projects to the lower cranial nerves. Neuronavigation confirmed these landmarks. Two new triangles were proposed: (1) The Petrous-Acousticofacial triangle, and (2) The Acousticofacial-Trigeminal triangle. Triangles provide a useful anatomical guide to the posterior fossa. We have introduced an organized schema, as well as proposed two new triangles, with the intent to minimize manipulation of neurovascular structures.

Objective The aim of this study is to determine feasibility of incorporating three-dimensional (3D) tractography into routine skull base surgery planning and analyze our early clinical experience in a subset of anterior cranial base meningiomas (ACM). Methods Ninety-nine skull base endonasal and transcranial procedures were planned in 94 patients and retrospectively reviewed with a further analysis of the ACM subset. Main Outcome Measures (1) Automated generation of 3D tractography; (2) co-registration 3D tractography with computed tomography (CT), CT angiography (CTA), and magnetic resonance imaging (MRI); and (3) demonstration of real-time manipulation of 3D tractography intraoperatively. ACM subset: (1) pre- and postoperative cranial nerve function, (2) qualitative assessment of white matter tract preservation, and (3) frontal lobe fluid-attenuated inversion recovery (FLAIR) signal abnormality. Results Automated 3D tractography, with MRI, CT, and CTA overlay, was produced in all cases and was available intraoperatively. ACM subset: 8 (44%) procedures were performed via a ventral endoscopic endonasal approach (EEA) corridor and 12 (56%) via a dorsal anteromedial (DAM) transcranial corridor. Four cases (olfactory groove meningiomas) were managed with a combined, staged approach using ventral EEA and dorsal transcranial corridors. Average tumor volume reduction was 90.3 ± 15.0. Average FLAIR signal change was –30.9% ± 58.6. 11/12 (92%) patients (DAM subgroup) demonstrated preservation of, or improvement in, inferior fronto-occipital fasciculus volume. Functional cranial nerve recovery was 89% (all cases). Conclusion It is feasible to incorporate 3D tractography into the skull base surgical armamentarium. The utility of this tool in improving outcomes will require further study.

Background Due to its rarity, few studies have characterized the epidemiology of male breast cancer. The purpose of this study was to determine survival and risk factors for male breast cancer in a large U.S. population. Methods In this study, 19,795 male patients with breast cancer were identified from the National Cancer Database (2004–2014). Patient demographics, tumor characteristics and treatments were analyzed by using descriptive statistics. We used multivariate Cox regression and Kaplan Meier analysis. Results Over 10 years, the incidence of male breast cancer increased from 7.2% to 10.3%, while mortality decreased from 11% to 3.8%. Socioeconomic factors predicting mortality included income medium, and high vs low (HR = 0.78; 0.68), private vs no insurance (HR = 0.73) and the academic research facility vs community cancer center (HR = 0.79). Significant predictors of all-cause mortality included age (HR = 1.04), tumor size (HR = 1.01), hormone receptor expression (HR = 0.8) and cancer stage I vs II, III, and IV at the time of diagnosis (HR = 1.5, 2.7, 4.4, 9.9 respectively). Other predictors of mortality include surgery (HR = 0.4), chemotherapy (HR = 0.8), radiation (HR = 0.8), and hormonal therapy (HR-0.8). Conclusions Socioeconomic factors, cancer stage, tumor characteristics (size and grade), and high Charlson-Dayo score contributed to higher mortality among male patients diagnosed with breast cancer. Surgery was most effective, followed by radiation, chemotherapy, and hormonal therapy. Patients with positive ER or PR expression demonstrated better survival. Adjusting for socioeconomic factors, biomarker identification and timely, appropriately chosen treatment are likely to reduce the risk for mortality., Highlights 1 Mortality was higher among patients with Low income and with no insurance. 2 Patients with positive ER or PR expression demonstrated better survival. 3 Surgery, chemotherapy, radiation, and hormonal therapy improved survival.

The minimally invasive port-based trans-sulcal parafascicular surgical corridor (TPSC) has incrementally evolved to provide a safe, feasible, and effective alternative to access subcortical and intraventricular pathologies. A detailed anatomical foundation is important in mitigating cortical and white matter tract injury with this corridor. Thus, the aims of this study are (1) to provide a detailed anatomical construct and overview of TPSCs and (2) to translate an anatomical framework to early clinical experience. Based on regional anatomical constraints, suitable parafascicular entry points were identified and described. Fiber tracts at both minimal and increased risks for each corridor were analyzed. TPSC-managed cases for metastatic or primary brain tumors were retrospectively reviewed. Adult patients 18 years or older with Karnofsky Performance Status (KPS) ≥ 70 were included. Subcortical brain metastases between 2 and 6 cm or primary brain tumors between 2 and 5 cm were included. Patient-specific corridors and trajectories were determined using MRI-tractography. Anatomy: The following TPSCs were described and translated to clinical practice: superior frontal, inferior frontal, inferior temporal, intraparietal, and postcentral sulci. Clinical: Eleven patients (5 males, 6 females) were included (mean age = 52 years). Seven tumors were metastatic, and 4 were primary. Gross total, near total, and subtotal resection was achieved in 7, 3, and 1 patient(s), respectively. Three patients developed intraoperative complications; all recovered from their intraoperative deficits and returned to baseline in 30 days. A detailed TPSC anatomical framework is critical in conducting safe and effective port-based surgical access. This review may represent one of the few early translational TPSC studies bridging anatomical data to clinical subcortical and intraventricular surgical practice.

Background Frontal subcortical and intraventricular pathologies are traditionally accessed via transcortical or interhemispheric-transcallosal corridors. Objective To describe the microsurgical subcortical anatomy of the superior frontal sulcus (SFS) corridor. Methods Cadaveric dissections were undertaken and correlated with magnetic resonance imaging/diffusion-tensor imaging-Tractography. Surgical cases demonstrated clinical applicability. Results SFS was divided into the following divisions: proximal, precentral sulcus to coronal suture; middle, 3-cm anterior to coronal suture; and distal, middle division to the orbital crest. Anatomy was organized as layered circumferential rings projecting radially towards the ventricles: (1) outer ring: at the level of the SFS, the following lengths were measured: (A) precentral sulcus to coronal suture = 2.29 cm, (B) frontal bone projection of superior sagittal sinus (SSS) to SFS = 2.37 cm, (C) superior temporal line to SFS = 3.0 cm, and (D) orbital crest to distal part of SFS = 2.32 cm; and (2) inner ring: (a) medial to SFS, U-fibers, frontal aslant tract (FAT), superior longitudinal fasciculus I (SLF-I), and cingulum bundle, (b) lateral to SFS, U-fibers, (SLF-II), claustrocortical fibers (CCF), and inferior fronto-occipital fasciculus, and (c) intervening fibers, FAT, corona radiata, and CCF. The preferred SFS parafascicular entry point (SFSP-EP) also referred to as the Kassam-Monroy entry point (KM-EP) bisects the distance between the midpupillary line and the SSS and has the following coordinates: x = 2.3 cm (lateral to SSS), y ≥ 3.5 cm (anterior to CS), and z = parallel corona radiata and anterior limb of the internal capsule. Conclusion SFS corridor can be divided into lateral, medial, and intervening white matter tract segments. Based on morphometric assessment, the optimal SFSP-EP is y ≥ 3.5 cm, x = 2.3 cm, and z = parallel to corona radiata and anterior limb of the internal capsule.

Background Endoscopic endonasal approaches to access the sellar and parasellar regions are challenging in the face of anatomical variations or pathologic conditions. We propose an anatomically-based model including the orbitosellar line (OSL), critical oblique foramen line (COFL), and paramedial anterior line (PAL) facilitating safe, superficial-to-deep dissection triangulating upon the medial opticocarotid recess. Methods Five cadaveric heads were dissected to systematically expose the OSL, COFL, and PAL, illustrated with image guidance. Application of the coordinate system and a 6-step dissection sequence is described. Results The coordinate system consists of 1) the OSL, connecting a) the anterior orbital point, junction of the anterior buttress of the middle turbinate with the agger nasi region, located 34.3 ± 0.9 mm above the intersection of the vertical plane of the lacrimal crest, and the orthogonal plane of the maxillo-ethmoidal suture; b) the posterior orbital point, junction of the optic canal with the lamina papyracea, located 4 ± 0.7 mm below the posterior ethmoidal artery; and c) the medial opticocarotid recess; 2) COFL (15 ± 2.8 mm), connecting the palatovaginal canal, vidian canal, and foramen rotundum; and 3) PAL (39 ± 0.06 mm), connecting the vidian canal with the posterior ethmoidal artery. Conclusions OSL, COFL, and PAL form an anatomically-based model for the systematic exposure when accessing the parasellar and sellar regions. Preliminary anatomical data suggest that this model may be of value when normal anatomy is distorted by pathology or anatomic variations.

Purpose Integrative medicine interventions are needed for awake craniotomies, as many patients experience anxiety. Lavender aromatherapy significantly reduces anxiety or pain in a variety of surgical procedures. This feasibility study used lavender aromatherapy during awake craniotomies to determine the number of patients who would consent and complete the study, the technicality of lavender aromatherapy use, and acceptance by operating room (OR) staff. Methods We approached 40 consecutive patients (≥18 years old). Exclusion criteria were pulmonary issues or sensitivity to lavender. Outcome measures in consented patients were enrollment and completion rates, anxiety and pain as measured by the Visual Analog Scale for Anxiety (VAS-A) and Visual Analog Scale for Pain (VAS-P), and satisfaction with pain control using the Patient Opinion of Pain Management (POPM) survey. Results Of the 40 patients approached, 4 declined participation or had their surgery cancelled. Of the remaining 36, 4 required increased sedation during surgery and 1 was unable to detect lavender. Thus, 31 patients (77.5%) completed the study. VAS-A and VAS-P scores trended lower after lavender inhalation, but the difference did not reach statistical significance. There was a slight increase in VAS-P score at the OR1 time point. Expectancy for reduction in both anxiety and pain were not significantly different. Improvement in anxiety also was not different, while improvement in pain trended lower (P=0.025). POPM results indicated the majority of patients were either "satisfied" or "very satisfied" with pain management. Conclusions This study demonstrated 77.5% completion and the ability to integrate lavender aromatherapy into the OR. Thus, we plan to conduct a randomized clinical trial to assess efficacy of lavender aromatherapy.

Background The use of vascularized flap to reconstruct the skull base defects has dramatically changed the postoperative cerebrospinal fluid (CSF) leak rates allowing the expansion of endoscopic skull base procedures. At present, there is insufficient scientific evidence to permit identification of the optimal reconstruction technique after the endoscopic endonasal approach (EEA). Objective The main purpose of this article is to establish the risk factors for failure in the reconstruction after EEA and whether the use of a surgical reconstruction protocol can improve the surgical results. Material and Methods A retrospective cohort study was conducted in our institution, selecting patients that underwent EEA with intraoperative CSF leak. Two reconstructive protocols were defined based on different reconstructive techniques; both were vascularized but one monolayer and the other multilayer. A multivariate analysis was performed with outcome variable presentation of postoperative leak. Results One hundred one patients were included in the study. Patients reconstructed with protocol 1, with the diagnosis different to the pituitary adenoma and older than 45 years old had higher risk of presenting postoperative leak, and with statistically significant differences when we adjusted for the remaining variables. Conclusion The vascularized reconstructions after endoscopic endonasal skull base approaches have demonstrated to be able to obtain a low rate of postoperative CSF leak. The multilayer vascularized technique may provide a more evolved technique, even reducing the postoperative leak rates comparing with the monolayer vascularized one. The reconstructive protocol employed in each case, as well as age and histological diagnosis, is independent risk factor for presenting postoperative leak.

Background: For patients diagnosed with breast cancer treatment plans are usually determined by biomarkers such as ER, PR and HER2, the absence or presence of which determines molecular subtype of the tumor (luminal A, luminal B, triple-negative, and HER2-enriched). However, it is unclear to what extent each treatment plan contributes to overall survival across these four molecular types of breast cancer (as determined by the presence or combination of biomarkers). Objective: Assuming inherent heterogeneity among breast cancer patients, we sought to determine the benefit of any one or combination of treatment methods among surgery, chemotherapy, radiation, immunotherapy, and hormonal therapy and whether differences exist among various subgroups for predicting mortality risk. Methods: A total of 827,888 patients diagnosed with breast cancer from the National Cancer Database were analyzed. The patient population was 99.1% female, 0.9% male, 75.5% white, 11.2% black, 0.8% Hispanic, and 12.5% other races. Most of the patients (97.1%) were diagnosed with invasive breast cancer; the remaining 2.9% were diagnosed with in situ and/or carcinoma in situ. For molecular subtypes, the distribution of patients was 72.7% with luminal A, 10.4% luminal B, 4.7% HER2-enriched and 12.2% triple-negative. Results: Overall, patients who did not receive treatment were 6.9 times more likely to die (95% confidence interval [CI]: 6.7–7.0) than those who did. Within molecular subtypes, hazards ratios [HR] were for dying without treatment were7.0 (95% CI: 6.8–7.1) for luminal A, 7.8 (95% CI: 7.3–8.3) for luminal B, 6.9 (95% CI: 6.6–7.2) for triple-negative, and 8.9 (95% CI: 8.2–9.7) for HER2-enriched tumor. Overall survival was best for luminal A, followed by luminal B, HER2-enriched and triple-negative (p Conclusion: Despite recent suggestions of over diagnoses and unnecessary treatment for certain types of tumor, this retrospective study suggested that treatment remains highly beneficial for breast cancer patients. Among treatments, surgery remains a strong predictor of survival across the board; however, for luminal B, HER2-enriched, and for triple negative subtype chemotherapy along with surgery provides additional survival benefit. Overall survival was better for luminal A, followed by luminal B, HER2 and triple negative breast cancer. These results can provide guidance for clinicians as well as for patients. Citation Format: Konduri SD, Singh M, Bobustuc GC, Rovin RA, Kassam AB. Treatment across the four molecular types of breast cancer: Insight from the national cancer database, 2010–2014 (N=827,888) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-35.

Background Endoscopic and microneurosurgical approaches to third ventricular lesions are commonly performed under general anesthesia. Objective To report our initial experience with awake transsulcal parafascicular corridor surgery (TPCS) of the third ventricle and its safety, feasibility, and limitations. Methods A total of 12 cases are reviewed: 6 colloid cysts, 2 central neurocytomas, 1 papillary craniopharyngioma, 1 basal ganglia glioblastoma, 1 thalamic glioblastoma, and 1 ependymal cyst. Lesions were approached using TPCS through the superior frontal sulcus. Pre-, intra-, and postoperative neurocognitive (NC) testing were performed on all patients. Results No cases required conversion to general anesthesia. Awake anesthesia changed intraoperative management in 4/12 cases with intraoperative cognitive changes that required port re-positioning; 3/4 recovered. Average length of stay (LOS) was 6.1 d ± 6.6. Excluding 3 outliers who had preoperative NC impairment, the average LOS was 2.5 d ± 1.2. Average operative time was 3.00 h ± 0.44. Average awake anesthesia time was 5.05 h ± 0.54. There were no mortalities. Conclusion This report demonstrated the feasibility and safety of awake third ventricular surgery, and was not limited by pathology, size, or vascularity. The most significant factor impacting LOS was preoperative NC deficit. The most significant risk factor predicting a permanent NC deficit was preoperative 2/3 domain impairment combined with radiologic evidence of invasion of limbic structures - defined as a "NC resilience/reserve" in our surgical algorithm. Larger efficacy studies will be required to demonstrate the validity of the algorithm and impact on long-term cognitive outcomes, as well as generalizability of awake TPCS for third ventricular surgery.

The incorporation of DTI and 3D tractography into the surgical planning workflow has increased awareness of the impact of resection of subcortical pathology as well as extra-axial anterior skull base lesions on the neural network. The 3D perspective that tractography affords in understanding neural anatomy, preoperative planning, and intraoperative navigation has provided unprecedented focus on neural network (both white matter tract and cranial nerve) preservation. The 3D-rendered neural network fused with CTA, structural MRI, and fMRI has prompted reanalysis of both subcortical and skull base surgical algorithms and refinement of conventional surgical approaches. Increased conspicuity of the neural network and integration of tractography in subcortical and skull base surgery aids in corridor choice, intraoperative navigation, and resection with the goal of minimizing the surgical footprint and maximizing patients’ quality of life.

Meckel’s diverticulum, or the quadrangular space, is one of the most anatomically complex regions in the skull base and one of the most difficult regions to access surgically from a ventral endoscopic endonasal perspective. Much of this is due to the tight anatomical confines of this space, which is hidden with critical neurovascular elements. One of the primary drivers of safe skull base surgery is attempting to minimize cranial nerve morbidity. Therefore, the primary effort is to develop a more understandable and organized modular system to access the skull base. In this chapter, we attempt to organize the ventral endonasal access to the Meckel’s diverticulum, from both an anatomical and surgical perspective. Specifically, we will organize the anatomical boundaries based on a concentric circumferential corridor model. We have also proposed, or reclassified, three anatomically-based surgical routes to Meckel’s diverticulum based on the relative position of neurovascular structures: retrocarotid (medial), transpterygopalatine-vidian nerve (anterior), and transpterygopalatine-mandibular strut (lateral).

Due to regional complexity and intimacy of osseous, vascular, and neural structures, access to the skull base has evolved to include numerous corridors and surgical approaches. The objective of the chapter is to create and organize a more simplified, generalizable, and reproducible surgical algorithm for accessing the skull base with the implementation of a novel 3-vector circumferential-radial coordinate system. The cadaveric dissections were undertaken to describe, in detail, the anatomic radial corridor system. Clinical case examples were described to apply this system in practice. We have effectively organized and consolidated all surgical approaches to the skull base and organized them into a 3-vector circumferential-radial coordinate system, based strictly on regional anatomical frameworks and boundaries. Appropriate selection of the corridor is based on the relative location of critical anatomy, more specifically the neural network, which defines the 3-vector algorithm. We hope that this system may be applied when deciding the appropriate corridor in relation to anatomy.

White matter tracts (WMTs) are located in the subcortical region and are the primary drivers of connectivity of vital functions of the human cerebrum. In order to better conceptualize WMT anatomy, we have previously organized this system into a surgical scaffolding or framework, referred to as the “Chassis”, in order to develop a tool to create WMT-centered trajectories. WMTs can be generally classified into three categories, based on their location and primary function: commissural (coronal plane), association (sagittal plane), and projection (axial/craniocaudal). The corpus callosum is the largest commissural tract bundle in the brain, connecting both hemispheres, and is composed of the rostrum, genu, body, isthmus and splenium. Other important fibers include the anterior, posterior, and hippocampal commissural fibers. The thalamic peduncles communicate the cortex with subcortical centers. The cingulum bundle is located above the corpus callosum on the medial surface of the hemisphere and forms part of the limbic system along with the fornix, which is the main fiber system of the hippocampus. The visual pathway consists of the optic nerve, chiasm, optic tract, and optic radiations. The most important association fibers are the superior longitudinal fasciculus, which interconnect the frontal and parietal lobes, the inferior longitudinal fasciculus, which communicates with the temporal and occipital poles, and the inferior fronto-occipital fasciculus, which connects the frontal lobe to the parietal lobe. The most recent tracts which have been described in literature are the frontal aslant tract, which links the supplementary motor area with the language motor area, the sledge runner fasciculus, which is located on the medial surface of the occipitoparietal region, and the middle longitudinal fasciculus, which interconnects the temporal lobe with the parietal lobe. In this chapter, we will provide a detailed description of WMT anatomy according to the organization schema provided by the “Chassis”.

The skull base represents one of most complex anatomical structures in the human body; as such, it has been the subject of significant anatomical and clinical research and discussion for centuries. The skull base consists of both an intracranial surface, which is related to the brain, and an extracranial or craniofacial surface, which is related to the nasal cavity sinuses, orbits, infra-temporal and pterygopalatine fossae, and the parapharyngeal and infrapetrosal spaces. In addition, the osseous segment (skull) is divided into the cranium and the facial skeleton. The cranium is further subdivided into the calvarium and the cranial base. In this chapter, through cadaveric anatomy, we will particularly focus on developing a comprehensive 360-degree perspective of the skull base, integrating the intracranial (dorsal) and extracranial (ventral) views.

The brainstem is located in the posterior fossa and is a critical center that regulates vital autonomic functions and relays motor and sensory information between the brain and spinal cord. The midbrain is located between the diencephalon and the pons. In an axial view of the midbrain, three structures can be visualized, from anterior to posterior: cerebral peduncles, tegmentum and tectum or quadrigeminal plate. The pons is cubic-shaped and is located between the midbrain and the medulla. In addition, is formed by a ventral part and a tegmental part, and constituted the superior part of the fourth ventricle. The medulla is located between spinal cord and the pons. The inferior limit constitutes the ventral root of the first cervical spinal nerve and the pyramidal decussation and the superior limit constitutes the pontomedullary sulcus. The floor of the fourth ventricle is divided into three parts: (1) the superior or pontine part; (2) the intermediate or junctional part; and (3) the inferior or medullary part. The cerebellum is located in the posterior cranial fossa behind the fourth ventricle, the pons, and the medulla oblongata and is formed for two hemispheres and a medial structure named vermis. From a surgical perspective, Prof. Rhoton divided the cerebellum into three faces: the tentorial surface, suboccipital surface and petrosal surface. A complete understanding of the tridimensional view of the microsurgical anatomy of the brainstem can greatly aid the surgeon in selecting the most appropriate surgical corridor.

Since the beginning of modern neurosurgery, technological advancements have paved the way for a more thorough and enhanced understanding of cerebral form and function to more effectively treat complex pathologies affecting patients. Through the power of optical modalities, functional neurosurgery and instrumentation, neurosurgery, and neuro-oncology as a whole, has transformed. The chapter will briefly review the current technological advances in neurosurgery, in the form of optics, imaging, intraoperative functional analysis, and access.

Functional MRI (fMRI) and Diffusion Tensor Imaging (DTI) are now considered mainstays of preoperative neurosurgical assessment. The strength of clinical fMRI as a noninvasive brain mapping technique lies in its ability to localize key regions of cortical/subcortical neurovascular activity subserving functions pertinent to patient-specific surgical/anatomical concerns. In complementary fashion, DTI offers the ability to create detailed maps of a patient’s individual white matter fascicular anatomy, crucial in the noninvasive planning of atraumatic parafascicular trajectories. In this chapter, we introduce the concept of a 5-point, imaging-based Target-Trajectory Complex (TTC) based on fused fMRI and DTI, and we discuss its applications to designing nearly zero-footprint, transsulcal, access points and individualized parafascicular subcortical white matter trajectories for the resection of brain tumors and vascular malformations. We demonstrated the synergistic manner in which fMRI and DTI may be used to provide simultaneous cortical and subcortical anatomic data for robust multimodal assessment of the TTC. The use of co-registered fMRI and DTI within an integrated neuronavigation system can inform precise individualized trajectories, ideally suited to emerging parafascicular, robotically guided techniques for effecting maximal safe resection of intracranial neoplasms.

Introduction: Greenspace, both residential and public, is associated with improved outcomes for a variety of medical conditions. Its effect on stroke incidence is not as well established. In this study, we sought answers to three questions: Does an increase in residential greenspace, as measured by the Normalized Difference in Vegetation Index (NDVI), lessen the odds of stroke? Is socioeconomic status (SES), as measured by the Area Deprivation Index (ADI), correlated with NDVI? Is proximity to a public park a risk factor for stroke? Methods: This is a matched (1:4) case-controlled study. The cohort was adult patients admitted to Aurora St Luke’s Medical Center in Milwaukee, WI between 2016 and 2018. Non-stroke controls (N=328,868) were matched to stroke cases (N=2336) on known cardiovascular risk factors after excluding patients with prior stroke, addresses outside of Milwaukee County, and residences within 250 meters of a water feature. The matched study sample included 5870 patients (stroke cases=1174 and non-stroke controls = 4696). The mean NDVI within a 250 meter radius around the patients’ residence and distance to a public park were calculated using satellite imagery and geographical information systems (GIS) software. State decile and national percentile ADI were obtained from the Neighborhood Atlas. A Spearman’s rank-order correlation determined the relationship between the NDVI, state and national ADI, and proximity to parks. Conditional logistic regression was used to examine the relationship between a stroke event and NDVI, ADI, and proximity to public parks. Results: We found a protective association between higher NDVI values and stroke (OR = 0.33, 95% CI = 0.111-0.975, p = 0.045). There was a negative correlation between NDVI and national (rs(5870) = -.548, p < .001) and state (rs(5870) = -.550, p < .001) ADI, both statistically significant. There was no association between proximity to parks and stroke (OR = 1.00, 95% CI = 1.000 – 1.000, p = 0.456). Conclusion: An increase in residential NDVI significantly decreases the odds of stroke. Distance to a public park did not impact the odds of stroke. These findings have implications for city planning and mitigation of social disparities in health.

The DNA damage repair enzyme, O6-methylguanine DNA methyltransferase (MGMT) is overexpressed in breast cancer, correlating directly with estrogen receptor (ER) expression and function. In ER negative breast cancer the MGMT promoter is frequently methylated. In ER positive breast cancer MGMT is upregulated and modulates ER function. Here, we evaluate MGMT's role in control of other clinically relevant targets involved in cell cycle regulation during breast cancer oncogenesis. We show that O6-benzylguanine (BG), an MGMT inhibitor decreases CDC2, CDC20, TOP2A, AURKB, KIF20A, cyclin B2, A2, D1, ERα and survivin and induces c-PARP and p21 and sensitizes ER positive breast cancer to temozolomide (TMZ). Further, siRNA inhibition of MGMT inhibits CDC2, TOP2A, AURKB, KIF20A, Cyclin B2, A2 and survivin and induces p21. Combination of BG+TMZ decreases CDC2, CDC20, TOP2A, AURKB, KIF20A, Cyclin A2, B2, D1, ERα and survivin. Temozolomide alone inhibits MGMT expression in a dose and time dependent manner and increases p21 and cytochrome c. Temozolomide inhibits transcription of TOP2A, AURKB, KIF20A and does not have any effect on CDC2 and CDC20 and induces p21. BG+/-TMZ inhibits breast cancer growth. In our orthotopic ER positive breast cancer xenografts, BG+/-TMZ decreases ki-67, CDC2, CDC20, TOP2A, AURKB and induces p21 expression. In the same model, BG+TMZ combination inhibits breast tumor growth in vivo compared to single agent (TMZ or BG) or control. Our results show that MGMT inhibition is relevant for inhibition of multiple downstream targets involved in tumorigenesis. We also show that MGMT inhibition increases ER positive breast cancer sensitivity to alkylator based chemotherapy.

BACKGROUND A number of vertical prolongations of the superior longitudinal fasciculus, which we refer to as the vertical rami (Vr), arise at the level of the supramarginal gyrus, directed vertically toward the parietal lobe. OBJECTIVE To provide the first published complete description of the white matter tracts (WMT) of the Vr, their relationship to the intraparietal and parieto-occipital sulci (IPS-POS complex), and their importance in neurosurgical approaches to the parietal lobe. METHODS Subcortical dissections of the Vr and WMT of the IPS were performed. Findings were correlated with a virtual dissection using high-resolution diffusion tensor imaging (DTI) tractography data derived from the Human Connectome Project. Example planning of a transparietal, transsulcal operative corridor is demonstrated using an integrated neuronavigation and optical platform. RESULTS The Vr were shown to contain component fibers of the superior longitudinal fasciculus (SLF)-II and SLF-III, with contributions from the middle longitudinal fasciculus merging into the medial bank of the IPS. The anatomic findings correlated well with DTI tractography. The line extending from the lateral extent of the POS to the IPS marks an ideal sulcal entry point that we have termed the IPS-POS Kassam-Monroy (KM) Point, which can be used to permit a safe parafascicular surgical trajectory to the trigone. CONCLUSION The Vr are a newly conceptualized group of tracts merging along the banks of the IPS, mediating connectivity between the parietal lobe and dorsal stream/SLF. We suggest a refined surgical trajectory to the ventricular atrium utilizing the posterior third of the IPS, at or posterior to the IPS-POS Point, in order to mitigate risk to the Vr and its considerable potential for postsurgical morbidity.

Background Treatment of intrinsic lesions of the ventral brainstem is a surgical challenge that requires complex skull base antero- and posterolateral approaches. More recently, endoscopic endonasal transclival approach (EETA) has been reported in the treatment of selected ventral brainstem lesions. Objective In this study we explored the endoscopic ventral brainstem anatomy with the aim to describe the degree of exposure of the ventral safe entry zones. In addition, we used a newly developed method combining traditional white matter dissection with high-resolution 7T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system. Methods Eight fresh-frozen latex-injected cadaver heads underwent EETA. Additional 8 formalin-fixed brainstems were dissected using Klingler technique guided by ultra-high resolution MRI. Results The EETA allows a wide exposure of different safe entry zones located on the ventral brainstem: the exposure of perioculomotor zone requires pituitary transposition and can be hindered by superior cerebellar artery. The peritrigeminal zone was barely visible and its exposure required an extradural anterior petrosectomy. The anterolateral sulcus of the medulla was visible in most of specimens, although its close relationship with the corticospinal tract makes it suboptimal as an entry point for intrinsic lesions. In all cases, the use of 7T-MRI allowed the identification of tiny fiber bundles, improving the quality of the dissection. Conclusion Exposure of the ventral brainstem with EETA requires mastering surgical maneuvers, including pituitary transposition and extradural petrosectomy. The correlation of fiber dissection with 7T-MRI neuronavigation significantly improves the understanding of the brainstem anatomy.

Background: Endoscopic endonasal approach (EEA) for skull base surgery (SBS) is a significant modification of the current practice. Methods: We reviewed our experience at the University of Pittsburgh with EEAs for 800 patients from 1998 to July 2007. Results: Modular approaches to multiple pathologies of the skull base were designed totally based on intrinsic anatomy. Stages of training were established based on the level of technical difficulty and potential risk of vascular and neural injury. Five levels were defined in an incremental manner. Conclusions: Practice standardization with modular, incremental training is projected to facilitate the gaining of knowledge and skills to safely master EEAs for SBS in an organized manner. We suggest adherence to the systematic acquisition of endoscopic skills, to work as an integrated team of surgeons and to have a thorough perspective of conventional SBS and endoscopic surgery. Therefore, the choice of approach must be a specific function of the anatomy and pathology rather than the surgeon’s bias or lack of experience with alternative approaches.

Objective The endoscopic endonasal odontoidectomy (EEO) is emerging as a feasible surgical alternative to conventional microscopic transoral approach. In this article, we show EEO in the basilar invagination (BI) and describe in detail the technical aspects, advantages, and disadvantages of this approach (Fig. 1). Methods We describe EEO using audiovisual material from the neurosurgical department of Hospital Universitari i Politècnic La Fe Valencia database. Results We present the case of a 61-year-old male patient with BI. Initially, we performed suboccipital decompression and occipitocervical fusion. Subsequently, after a no significant neurological improvement and persistent anterior compression, EEO was performed. The postoperative evolution was uneventful and the preoperative neurological deficits were recovered rapidly after surgery Discussion EEO technique enables complete odontoid resection, preventing invasion of aggressive oral bacterial flora, and it is not limited by the mouth opening. As well, it avoids manipulation of the soft palate, therefore evades the risk of velopalatal insufficiency, facilitates immediate oral tolerance, and early extubation. The rostral position of C1–C2 complex in BI could suppose a great advantage in favor the endonasal approaches. Mucoperichondrial vascularized flaps could be obtained to avoid a postoperative cerebrospinal fluid (CSF) leak and facilitate the reepithelization process of the surgical bed. Conclusion EEO may provide a significant anatomic and technical advantage over the trans-oral approach.The link to the video can be found at: https://youtu.be/Td6MDcjCNKk.

The success of expanded endoscopic endonasal approaches (EEAs) to the anterior skull base, sellar, and parasellar regions has been greatly aided by the advancement in reconstructive techniques. In particular, the pedicled vascularized flaps have been developed and effectively cover skull base defects of varying sizes with a significant reduction in postoperative CSF leaks. There are two aims to this review: (1) We will provide our current, simplified reconstruction algorithm. (2) We will describe, in detail, the relevant anatomy, indications/contraindications, and surgical technique, with a particular emphasis on the nasoseptal flap (NSF). The inferior turbinate flap (ITF), middle turbinate flap (MTF), pericranial flap (PCF), and temporoparietal fascial flap (TPFF) will also be described. The NSF should be the primary option for reconstruction of majority of skull base defects following endonasal endoscopic surgery. In general, for the planum, cribriform, and upper two-thirds of the clivus, the NSF is ideal. For the lower-third of the clivus, the NSF may not be adequate and may require additional reconstructive options. Although limited in reach or more technically challenging, these reconstructive flaps should still be considered and kept in the surgical algorithm.

Technological advancement in the operating room is evolving into a dynamic system mirroring that of the aeronautics industry. Through data visualization, information is continuously being captured, collected, and stored on a scalable informatics platform for rapid, intuitive, iterative learning. The authors believe this philosophy (paradigm) will feed into an intelligent informatics domain fully accessible to all and geared toward precision, cell-based therapy in which tissue can be targeted and interrogated in situ. In the future, the operating room will be a venue that facilitates this real-time tissue interrogation, which will guide in situ therapeutics to restore the state of health.