Intraoperative Augmented Reality for Complex Glioma Resection: A Case Report.

Augmented reality (AR) is an emerging technology that can display three-dimensional patient anatomy in the surgeons' field of view. The use of this technology has grown considerably for both presurgical and intraoperative guidance. A patient diagnosed with breast cancer started to experience numbness in the left hand, which progressed to weakness in the left hand and arm. An MRI was performed demonstrating a 2.9 cm X 1.8 cm lesion with extensive surrounding edema in the posterior fronto-parietal lobes. Surgery was recommended for presumed metastatic disease. Preoperatively, an AR system and Brainlab navigation were registered to the patient. AR, traditional navigation, and ultrasound were all used to localize the lesion and determine the craniotomy site and size. The tumor was removed along the direction of the lesion. Intraoperatively, we used AR to reexamine the tumor details and could appreciate that we had to redirect our surgical trajectory anteriorly and laterally in order to follow along the main axis of the tumor. In doing this, we were able to more confidently remain with the tumor, which by this time was poorly defined by 2D navigation and by direct vision. Postoperative MRI confirmed gross total removal of the tumor. The patient had an uneventful postoperative course with resolution of preoperative symptoms and the final surgical pathology was grade 4 glioblastoma. Here, we describe the valuable use of AR for the resection of a glioma. The system has a seamless registration process and provides the surgeon with a unique view of 3D anatomy overlaid onto the patient's head. This exciting technology can add tremendous value to complex cranial surgeries.

Integration of Augmented Reality Into Glioma Resection Surgery: A Case Report.

Augmented reality (AR) is an exciting technology that has garnered considerable attention in the field of neurosurgery. Despite this, clinical use of this technology is still in its infancy. An area of great potential for this technology is the ability to display 3D anatomy overlaid with the patient to assist with presurgical and intraoperative decision-making. A 39-year-old woman presented with headaches and was experiencing what was described as a whooshing sound. MRI revealed the presence of a large left frontal mass involving the genu of the corpus callosum, with heterogeneous enhancement and central hemorrhagic necrosis, confirmed to be a glioma. She underwent a craniotomy with intraoperative MRI for resection. An augmented reality system was used to superimpose 3D holographic anatomy onto the patient's head for surgical planning. This report highlights a new AR technology and its immediate application to cranial neurosurgery. It is critical to document new uses of this technology as the field continues to integrate AR as well as other next-generation technologies into practice.

Anatomic Review in 3D Augmented Reality Alters Craniotomy Planning Among Residents.

OBJECTIVE: Objectively examine the effect of 3D-Augmented Reality anatomic review on craniotomy planning among neurosurgical residents as it pertains to craniotomy size, skull positioning, and knowledge of significant anatomic relationships. METHODS: Postgraduate year 1-7 neurosurgery residents were instructed to review standard 2D radiographs, pin a skull, and tailor a craniotomy for 6 different lesions and case vignettes. Participants then reviewed the lesion in a 3D-augmented reality (AR) environment, followed by repeating the craniotomy station for a variety of lesion types and locations (superficial, subcortical, deep, skull base). Quiz with case-specific anatomic and surgical questions followed by an exit survey for qualitative impressions. RESULTS: Eleven of thirteen eligible residents participated. Skull position significantly changed in 5 out of 6 cases after 3D-AR view (P < 0.05, 20° angular adjustment). No significant change in incision length or craniotomy size. Subgroup analysis of junior versus senior residents revealed that craniotomy size was significantly altered in 2 out of 6 cases. Qualitative testimonials (Likert scale 5 = strongly agree) reported a change in craniotomy approach after 3D-review (3.5), improved appreciation of anatomy (4.2), increased confidence in surgical approach (4.33 junior residents, 3.5 senior residents), smaller incision (3.5 junior residents, 1.75 senior residents), better appreciation of white matter tracts (4.6). CONCLUSIONS: The augmented reality platform offers a medium to examine surgical planning skills. Residents uniformly appreciated 3D-AR as a valuable tool for improving appreciation of critical anatomic structures and their relationship to lesional pathology. 3D-AR review significantly altered skull positioning for various lesions and craniotomy approaches, particularly among junior residents.

Using Ipratropium Bromide Nasal Spray Response as a Screening Tool in the Diagnostic Workup of Cerebrospinal Fluid Rhinorrhea.

OBJECTIVES: Unilateral clear thin rhinorrhea (UCTR) can be concerning for a nasal cerebrospinal fluid (CSF) leak. Beta-2 transferrin electrophoresis has been the gold standard for initial non-invasive confirmatory testing for CSF rhinorrhea, but there can be issues with fluid collection and testing errors. Ipratropium bromide nasal spray (IBNS) is highly effective at reducing rhinitis-related rhinorrhea, and should presumably not resolve CSF rhinorrhea. This study assessed whether different clinical features and IBNS response helped predict presence or absence of CSF rhinorrhea. METHODS: A prospective cohort study was conducted where all patients with UCTR had nasal fluid tested for beta-2 transferrin, and were prescribed 0.06% IBNS. Patients were diagnosed with CSF rhinorrhea or other rhinologic conditions. Clinical variables like IBNS response (rhinorrhea reduction), positional worsening, salty taste, postoperative state, female gender, and body-mass index were assessed for their ability to predict CSF rhinorrhea. Sensitivity, specificity, and predictive values and odds ratios were calculated for all clinical variables. RESULTS: Twenty patients had CSF rhinorrhea, and 53 had non-CSF etiologies. Amongst clinical variables assessed for predicting CSF absence or presence, significant associations were shown for IBNS response (OR = 844.66, p = 0.001), positional rhinorrhea worsening (OR = 8.22, p = 0.049), and body-mass index ≥30 (OR = 2.92, p = 0.048). IBNS response demonstrated 96% sensitivity and 100% specificity, and 100% positive and 91% negative predictive values for predicting CSF rhinorrhea. CONCLUSIONS: In patients with UCTR, 0.06% IBNS response is an excellent screening tool for excluding CSF rhinorrhea, and should be considered in the diagnostic workup of CSF rhinorrhea. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:56-61, 2024.

Augmented Reality Registration System for Visualization of Skull Landmarks.

BACKGROUND: Augmented reality (AR) is an emerging technology in neurosurgery with the potential to become a strategic tool in the delivery of care and education for trainees. Advances in technology have demonstrated promising use for improving visualization and spatial awareness of critical neuroanatomic structures. In this report, we employ a novel AR registration system for the visualization and targeting of skull landmarks. METHODS: A markerless AR system was used to register 3-dimensional reconstructions of suture lines onto the head via a head-mounted display. Participants were required to identify craniometric points with and without AR assistance. Targeting error was measured as the Euclidian distance between the user-defined location and the true craniometric point on the subjects' heads. RESULTS: All participants successfully registered 3-dimensional reconstructions onto the subjects' heads. Targeting accuracy was significantly improved with AR (3.59 ± 1.29 mm). Across all target points, AR increased accuracy by an average of 19.96 ± 3.80 mm. Posttest surveys revealed that participants felt the technology increased their confidence in identifying landmarks (4.6/5) and that the technology will be useful for clinical care (4.2/5). CONCLUSIONS: While several areas of improvement and innovation can further enhance the use of AR in neurosurgery, this report demonstrates the feasibility of a markerless headset-based AR system for visualizing craniometric points on the skull. As the technology continues to advance, AR is expected to play an increasingly significant role in neurosurgery, transforming how surgeries are performed and improving patient care.

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.

Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair.

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.

Prolactinoma: Medical and Surgical Considerations.

Prolactinomas are the most common secretory tumor of the pituitary gland. Clinical symptoms may be due to prolactin oversecretion, localized mass effect, or a combination of both. Although the mainstay of prolactinoma management is medical therapy with dopamine agonists, endoscopic endonasal or transcranial surgery, radiation therapy, or a combination of these is an important treatment option in select cases. This article discusses prolactinoma phenotypes, clinical presentations, and clinically pertinent medical and surgical considerations when managing these tumors.

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

Radiomics for precision medicine in glioblastoma.

INTRODUCTION: Being the most common primary brain tumor, glioblastoma presents as an extremely challenging malignancy to treat with dismal outcomes despite treatment. Varying molecular epidemiology of glioblastoma between patients and intra-tumoral heterogeneity explains the failure of current one-size-fits-all treatment modalities. Radiomics uses machine learning to identify salient features of the tumor on brain imaging and promises patient-specific management in glioblastoma patients. METHODS: We performed a comprehensive review of the available literature on studies investigating the role of radiomics and radiogenomics models for the diagnosis, stratification, prognostication as well as treatment planning and monitoring of glioblastoma. RESULTS: Classifiers based on a combination of various MRI sequences, genetic information and clinical data can predict non-invasive tumor diagnosis, overall survival and treatment response with reasonable accuracy. However, the use of radiomics for glioblastoma treatment remains in infancy as larger sample sizes, standardized image acquisition and data extraction techniques are needed to develop machine learning models that can be translated effectively into clinical practice. CONCLUSION: Radiomics has the potential to transform the scope of glioblastoma management through personalized medicine.

Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs.

BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P < .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns.

DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features.

BACKGROUND: Distinct genome-wide methylation patterns cluster pituitary neuroendocrine tumors (PitNETs) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize, and validate methylation signatures that objectively classify PitNET into clinicopathological groups. METHODS: Combining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumors (Panpit cohort) and 20 nontumor specimens from the pituitary gland. We also retrieved methylome data from an independent PitNET cohort (N = 86) to validate our findings. RESULTS: We identified three methylation clusters associated with adenohypophyseal cell lineages and functional status using an unsupervised approach. Differentially methylated probes (DMP) significantly distinguished the Panpit clusters and accurately assigned the samples of the validation cohort to their corresponding lineage and functional subtypes memberships. The DMPs were annotated in regulatory regions enriched with enhancer elements, associated with pathways and genes involved in pituitary cell identity, function, tumorigenesis, and invasiveness. Some DMPs correlated with genes with prognostic and therapeutic values in other intra- or extracranial tumors. CONCLUSIONS: We identified and validated methylation signatures, mainly annotated in enhancer regions that distinguished PitNETs by distinct adenohypophyseal cell lineages and functional status. These signatures provide the groundwork to develop an unbiased approach to classifying PitNETs according to the most recent classification recommended by the 2017 WHO and to explore their biological and clinical relevance in these tumors.

A serum-based DNA methylation assay provides accurate detection of glioma.

BACKGROUND: The detection of somatic mutations in cell-free DNA (cfDNA) from liquid biopsy has emerged as a noninvasive tool to monitor the follow-up of cancer patients. However, the significance of cfDNA clinical utility remains uncertain in patients with brain tumors, primarily because of the limited sensitivity cfDNA has to detect real tumor-specific somatic mutations. This unresolved challenge has prevented accurate follow-up of glioma patients with noninvasive approaches. METHODS: Genome-wide DNA methylation profiling of tumor tissue and serum cfDNA of glioma patients. RESULTS: Here, we developed a noninvasive approach to profile the DNA methylation status in the serum of patients with gliomas and identified a cfDNA-derived methylation signature that is associated with the presence of gliomas and related immune features. By testing the signature in an independent discovery and validation cohorts, we developed and verified a score metric (the "glioma-epigenetic liquid biopsy score" or GeLB) that optimally distinguished patients with or without glioma (sensitivity: 100%, specificity: 97.78%). Furthermore, we found that changes in GeLB score reflected clinicopathological changes during surveillance (eg, progression, pseudoprogression, and response to standard or experimental treatment). CONCLUSIONS: Our results suggest that the GeLB score can be used as a complementary approach to diagnose and follow up patients with glioma.

The Effect of Antithrombotics on Hematoma Expansion in Small- to Moderate-Sized Traumatic Intraparenchymal Hemorrhages.

BACKGROUND: Although pre-injury antithrombotic agents, including antiplatelets and anticoagulants, are historically associated with expansion of traumatic intraparenchymal hemorrhage (tIPH), the literature has poorly elucidated the actual risk of hematoma expansion on repeat computed tomography (CT). The objective was to determine the effect of antithrombotic agents on hematoma expansion in tIPH by comparing patients with and without pre-injury antithrombotic medication. METHODS: The volume of all tIPHs over a 5-year period at an academic Level 1 trauma center was measured retrospectively. The initial tIPH was divided into 3 equally sized quantiles. The third tercile, representing the largest subset of tIPH, was then removed from the study population because these patients reflect a different pathophysiologic mechanism that may require a more acute and aggressive level of care with reversal agents and/or operative management. Per institutional policy, all patients with small- to moderate-sized hemorrhages received a 24-hour stability CT scan. Patients who received reversal agents were excluded. RESULTS: Of the 105 patients with a tIPH on the initial head CT scan, small- to moderate-sized hemorrhages were <5 cm3. The size of tIPH on initial imaging did not statistically significantly differ between the antithrombotic cohort (0.7 ± 0.1 cm3) and the non-antithrombotic cohort (0.5 ± 0.1 cm3) (P = 0.091). Similarly, the volume of tIPH failed to differ on 24-hour repeat imaging (1.0 ± 0.2 cm3 vs. 0.6 ± 0.1 cm3, respectively, P = 0.172). Following a multiple linear regression, only history of stroke, not antithrombotic medications, predicted increased tIPH on 24-hour repeat imaging. CONCLUSIONS: In small- to moderate-sized tIPH, withholding antithrombotic agents without reversal may be sufficient.

Cranial angiomatoid fibrous histiocytoma: A case report and review of literature.

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare low-grade soft-tissue tumor that typically arises from the deep dermal and subcutaneous tissue of the extremities in children and young adults. Intracranial AFH is exceedingly rare, and only four cases of primary AFH tumors have been reported to date. CASE DESCRIPTION: A 43-year-old male presented to our hospital with headaches, vision changes, and a known brain tumor suspected to be an atypical meningioma. After undergoing craniotomy for resection of the mass, the immunomorphologic features of the resected tumor showed typical features of AFH with ESWR1 (exon7) - ATF1 (exon 5) fusion. CONCLUSION: AFH is a difficult tumor to diagnose with imaging and histologic studies. Thus, further knowledge is necessary - particularly of intracranial cases - to aid clinicians in its diagnosis and management.

Risk Factors Associated with Symptomatic Deep Vein Thrombosis Following Elective Spine Surgery: A Case-Control Study.

BACKGROUND: Few studies provide insight into risk factors (RFs) associated with postoperative deep vein thrombosis (DVT) following elective spinal surgery. DVTs are detrimental in this population because of the risk of pulmonary embolization or surgical site hemorrhage with treatment. OBJECTIVE: Elective spine surgery patients have a low incidence of DVT, thus a case-control study was selected to investigate RFs associated with postoperative, symptomatic DVT. METHODS: Cases were matched to controls in a 1:2 ratio based on surgery type. Risk of having a prior DVT and choice of subcutaneous heparin dosing following surgery was analyzed in a multivariate regression model with other potentially confounding variables. RESULTS: A total of 195 patients were included in this study. Independent of patient age, history of DVT was associated with postoperative symptomatic DVT (odds ratio [OR], 4.09; 95% confidence interval [CI], 1.22-13.78). Two versus 3 times daily postoperative heparin dosing (OR, 1.56; 95% CI, 0.32-7.56), surgery length (OR, 1.32; 95% CI, 0.98-1.79), and patient age (OR, 1.04; 95% CI, 1.0-1.08) were not statistically significant, independent RFs. Older age and longer length of surgery trended toward association with DVT without reaching significance. Length of stay was increased from 3-5 days (P < 0.001) in DVT patients compared with controls. CONCLUSIONS: These results suggest that patients with a history of DVT undergoing elective spinal surgery are at higher risk of developing symptomatic DVT postoperatively resulting in significantly increased length of stay. Further studies on additional preoperative screening and medical optimization in elective spine surgery patients may help reduce the rate of symptomatic, postoperative DVT.