A Novel Predictive Model Utilizing Retinal Microstructural Features for Estimating Survival Outcome in Patients with Glioblastoma.

Glioblastoma is a highly aggressive brain tumor with poor prognosis despite surgery and chemoradiation. The visual sequelae of glioblastoma have not been well characterized. This study assessed visual outcomes in glioblastoma patients through neuro-ophthalmic exams, imaging of the retinal microstructures/microvasculature, and perimetry. A total of 19 patients (9 male, 10 female, average age at diagnosis 69 years) were enrolled. Best-corrected visual acuity ranged from 20/20-20/50. Occipital tumors showed worse visual fields than frontal tumors (mean deviation - 14.9 and - 0.23, respectively, p < 0.0001). Those with overall survival (OS) < 15 months demonstrated thinner retinal nerve fiber layer and ganglion cell complex (p < 0.0001) and enlarged foveal avascular zone starting from 4 months post-diagnosis (p = 0.006). There was no significant difference between eyes ipsilateral and contralateral to radiation fields (average doses were 1370 cGy and 1180 cGy, respectively, p = 0.42). A machine learning algorithm using retinal microstructure and visual fields predicted patients with long (≥ 15 months) progression-free and overall survival with 78% accuracy. Glioblastoma patients frequently present with visual field defects despite normal visual acuity. Patients with poor survival duration demonstrated significant retinal thinning and decreased microvascular density. A machine learning algorithm predicted survival; further validation is warranted.

Diffuse Midline H3K27-Altered Gliomas in the Spinal Cord: A Systematic Review.

PURPOSE: To systematically review the clinical features, management, and outcomes of diffuse midline H3K27-altered gliomas of the spinal cord (DMG-SCs). METHODS: PubMed, Ovid EMBASE, Scopus, and Web of Science were searched from database inception to 23 September 2023 for histologically confirmed cases of DMG-SC. Patient demographics, tumor characteristics, management information, and survival outcomes were extracted and analyzed. RESULTS: A total of 279 patients from 39 studies were collected. Patients were mostly male (61%), with an average age of 32 years. Patients were treated with surgery, radiotherapy, and chemotherapy combined (31%) or surgery only (24%), and extent of resection was most often subtotal (38%). Temozolomide was the most common chemotherapeutic agent (81%). Radiation therapy was delivered with mean dose of 47 Gy in 23 fractions. At mean follow-up time of 21 months, 13% of patients were alive. Average median overall survival was 24 months (range of 13 to 40 months) with a median progression-free survival of 14 months. Historical WHO grades of 2 or 3 appeared to exhibit a longer average median overall survival time than that of grade 4 DMG-SCs (32 vs. 23 months, p = 0.009). CONCLUSIONS: Outcomes for DMG-SCs are poor overall but appear to be favorable compared to intracranial DMGs. Despite the recent WHO 2021 grade 4 classification for all DMGs, given the differences in overall survival reported based on historical grading systems, future studies on DMG-SCs are needed to further define if DMG-SCs may represent a heterogeneous group of tumors with different prognoses.

A Feasibility Study on a Portable Vision Device for Patients with Stroke and Brain Tumours.

This prospective, single-centre cohort study aimed to evaluate the impact of a portable vision reading device, OrCam Read, on vision-related quality-of-life and independent functional status in patients with low vision due to stroke or brain tumours. Six patients with poor visual acuity or visual field defects due to a stroke or a brain tumour were enrolled at a U.S. Ophthalmology Department. Participants were trained to use OrCam Read and given a loaner device for the 1 month duration of the study. Various assessments, including daily function tests, the National Eye Institute Visual Function Questionnaire-25, and the 10-item neuro-ophthalmic supplement, were administered at the first and last visits. Patients' experience with the device was evaluated with weekly telephone and end-of-study satisfaction surveys. The main outcome measures were the patient satisfaction with OrCam and the mean assessment scores between enrolment and final visits. The intervention with OrCam significantly improved patients' ability to complete daily tasks and participants reported good satisfaction with the device. The results also show non-significant improvement with distant activities, dependency, and role difficulties. Our findings demonstrate the feasibility of studying vision-related quality-of-life using a portable vision device in this patient population and pave the way for a larger study to validate the results of this study.

Profile Characterization of Biogenic Amines in Glioblastoma Patients Undergoing Standard-of-Care Treatment.

INTRODUCTION: Biogenic amines play important roles throughout cellular metabolism. This study explores a role of biogenic amines in glioblastoma pathogenesis. Here, we characterize the plasma levels of biogenic amines in glioblastoma patients undergoing standard-of-care treatment. METHODS: We examined 138 plasma samples from 36 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma at multiple stages of treatment. Untargeted gas chromatography-time of flight mass spectrometry (GC-TOF MS) was used to measure metabolite levels. Machine learning approaches were then used to develop a predictive tool based on these datasets. RESULTS: Surgery was associated with increased levels of 12 metabolites and decreased levels of 11 metabolites. Chemoradiation was associated with increased levels of three metabolites and decreased levels of three other metabolites. Ensemble learning models, specifically random forest (RF) and AdaBoost (AB), accurately classified treatment phases with high accuracy (RF: 0.81 ± 0.04, AB: 0.78 ± 0.05). The metabolites sorbitol and N-methylisoleucine were identified as important predictive features and confirmed via SHAP. CONCLUSION: To our knowledge, this is the first study to describe plasma biogenic amine signatures throughout the treatment of patients with glioblastoma. A larger study is needed to confirm these results with hopes of developing a diagnostic algorithm.

In vivo characterization of the human glioblastoma infiltrative edge with label-free intraoperative fluorescence lifetime imaging.

Challenges in identifying a glioblastoma's infiltrative edge during neurosurgical procedures result in rapid recurrence. A label-free fluorescence lifetime imaging (FLIm) device was used to evaluate glioblastoma's infiltrative edge in vivo in 15 patients (89 samples). FLIm data were analyzed according to tumor cell density, infiltrating tissue type (gray and white matter), and diagnosis history (new or recurrent). Infiltrations in white matter from new glioblastomas showed decreasing lifetimes and a spectral red shift with increasing tumor cell density. Areas of high versus low tumor cell density were separated through a linear discriminant analysis with a ROC-AUC=0.74. Current results support the feasibility of intraoperative FLIm for real-time in vivo brain measurements and encourage refinement to predict glioblastoma infiltrative edge, underscoring the ability of FLIm to optimize neurosurgical outcomes.

A pilot study on metabolomic characterization of human glioblastomas and patient plasma.

Purpose: To determine whether recurrent GBMs are metabolically distinct from primary GBM, and whether patient plasma can be used as a liquid biopsy to reflect this difference. Methods: In a single center cohort study, tissue and blood samples from 15 patients with glioblastoma (9 glioblastoma tissues at diagnosis, 3 pairs of tissue, and 6 pairs of plasma specimens at diagnosis and at recurrence) were analyzed. Results: Several metabolites had significant alternations in both tumor and plasma specimens. In the tissue, the following representative metabolites had a significant increase in peak intensity at recurrence compared to diagnosis: N-alpha-methylhistamine (p = 0.037), glycerol-3-phosphate (p = 0.029), phosphocholine (p = 0.045), and succinic acid (p = 0.025). In patient plasma, metabolites that significantly increased at recurrence included: 2,4-difluorotoluene (p = 0.031), diatrizoic acid (p = 0.032), indole-3-acetate with (p = 0.029), urea (P = 0.025), pseudouridine (p = 0.042), and maltose (p = 0.035). Metabolites that significantly decreased in plasma at recurrence were: eicosenoic acid (p = 0.017), glucose-1-phosphate (p = 0.017), FA 18:2 (linoleic acid) (p = 0.017), arginine (p = 0.036), fatty acids 20:3 (homo-gamma-linolenic acid (p = 0.036), galactosamine (p = 0.007), and FA 18:3 (linolenic acid) (P = 0.012). Principal component analysis showed that the metabolomic profiles differ between tumor tissue and patient plasma. Conclusions: Our data suggest that metabolomic profiles of human GBM tissue and patient plasma differ at diagnosis and at recurrence. Many metabolites involved in tumorigenesis and metabolomic flexibility were identified. A larger study using targeted metabolomic assay is warranted to measure the levels of these metabolites, which will help identify the metabolomic signatures in both GBM tissue and patient plasma for risk stratification, clinical outcome prediction, and development of new adjuvant metabolomic-targeting therapy.

Application of Machine Learning to Metabolomic Profile Characterization in Glioblastoma Patients Undergoing Concurrent Chemoradiation.

We here characterize changes in metabolite patterns in glioblastoma patients undergoing surgery and concurrent chemoradiation using machine learning (ML) algorithms to characterize metabolic changes during different stages of the treatment protocol. We examined 105 plasma specimens (before surgery, 2 days after surgical resection, before starting concurrent chemoradiation, and immediately after chemoradiation) from 36 patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma. Untargeted GC-TOF mass spectrometry-based metabolomics was used given its superiority in identifying and quantitating small metabolites; this yielded 157 structurally identified metabolites. Using Multinomial Logistic Regression (MLR) and GradientBoostingClassifier (GB Classifier), ML models classified specimens based on metabolic changes. The classification performance of these models was evaluated using performance metrics and area under the curve (AUC) scores. Comparing post-radiation to pre-radiation showed increased levels of 15 metabolites: glycine, serine, threonine, oxoproline, 6-deoxyglucose, gluconic acid, glycerol-alpha-phosphate, ethanolamine, propyleneglycol, triethanolamine, xylitol, succinic acid, arachidonic acid, linoleic acid, and fumaric acid. After chemoradiation, a significant decrease was detected in 3-aminopiperidine 2,6-dione. An MLR classification of the treatment phases was performed with 78% accuracy and 75% precision (AUC = 0.89). The alternative GB Classifier algorithm achieved 75% accuracy and 77% precision (AUC = 0.91). Finally, we investigated specific patterns for metabolite changes in highly correlated metabolites. We identified metabolites with characteristic changing patterns between pre-surgery and post-surgery and post-radiation samples. To the best of our knowledge, this is the first study to describe blood metabolic signatures using ML algorithms during different treatment phases in patients with glioblastoma. A larger study is needed to validate the results and the potential application of this algorithm for the characterization of treatment responses.

NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

Intraoperative detection of IDH-mutant glioma using fluorescence lifetime imaging.

Identifying isocitrate dehydrogenase (IDH)-mutation and glioma subtype during surgery instead of days later can aid in modifying tumor resection strategies for better survival outcomes. We report intraoperative identification of IDH-mutant glioma (N = 12 patients) with a clinically compatible fluorescence lifetime imaging (FLIm) device (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm). The fluorescence-derived parameters were analyzed to study the optical contrast between IDH-mutant tumors and surrounding brain tissue. IDH-mutant oligodendrogliomas exhibited shorter lifetimes (3.3 ± 0.1 ns) than IDH-mutant astrocytomas (4.1 ± 0.1 ns). Both IDH-mutant glioma subtypes had shorter lifetimes than white matter (4.6 ± 0.4 ns) but had comparable lifetimes to cortex. Lifetimes also increased with malignancy grade within IDH-mutant oligodendrogliomas (grade 2: 2.96 ± 0.08 ns, grade 3: 3.4 ± 0.3 ns) but not within IDH-mutant astrocytomas. The current results support the feasibility of FLIm as a surgical adjuvant for identifying IDH-mutant glioma tissue.

Low-molecular-weight Heparin (enoxaparin) versus unfractionated heparin for venous thromboembolism prophylaxis in patients undergoing craniotomy.

OBJECTIVE: To explore the difference in post-operative DVT, PE, and ICH complications following administration of prophylactic UFH or enoxaparin in patients undergoing craniotomy. METHODS: A retrospective chart review was conducted for 542 patients at our institution receiving either 5000units/0.5 mL UFH (BID or TID; 180 patients) or single daily 40 mg/0.4 mL enoxaparin (362 patients) following craniotomy. Multivariate linear regression models were developed comparing rates of postoperative DVT, PE, and reoperation for bleeding in patients given enoxaparin versus UFH prophylaxis while controlling for age at surgery, history of VTE, surgery duration, number of post-operative hospital days, reoperation, post-operative infections, and reason for surgery (tumor type, genetics, etc.). Mann Whitney U tests were subsequently performed comparing rates of postoperative DVT, PE, and ICH for each group. RESULTS: Patients receiving prophylactic enoxaparin, when compared to UFH, exhibited similar rates of postoperative DVT (22 % vs 20.6 %, p = 0.86), PE (9.7 % vs 8.9 %, p = 0.86), and reoperation for bleeding (0.4 % vs 0.2 %, p = 0.58), while controlling for the factors described above. CONCLUSION: In patients undergoing craniotomy, rates for DVT, PE, and ICH were similar between patients treated with either prophylactic enoxaparin or UFH. Further studies are needed to understand whether a certain subset of patients demonstrate improved benefit from either prophylactic anticoagulant.

First in patient assessment of brain tumor infiltrative margins using simultaneous time-resolved measurements of 5-ALA-induced PpIX fluorescence and tissue autofluorescence.

SIGNIFICANCE: 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is currently used for image-guided glioma resection. Typically, this widefield imaging method highlights the bulk of high-grade gliomas, but it underperforms at the infiltrating edge where PpIX fluorescence is not visible to the eyes. Fluorescence lifetime imaging (FLIm) has the potential to detect PpIX fluorescence below the visible detection threshold. Moreover, simultaneous acquisition of time-resolved nicotinamide adenine (phosphate) dinucleotide [NAD(P)H] fluorescence may provide metabolic information from the tumor environment to further improve overall tumor detection. AIM: We investigate the ability of pulse sampling, fiber-based FLIm to simultaneously image PpIX and NAD(P)H fluorescence of glioma infiltrative margins in patients. APPROACH: A mesoscopic fiber-based point-scanning FLIm device (355 nm pulses) was used to simultaneously resolve the fluorescence decay of PpIX (629/53 nm) and NAD(P)H (470/28 nm). The FLIm device enabled data acquisition at room light and rapid (<33 ms) augmentation of FLIm parameters on the surgical field-of-view. FLIm measurements from superficial tumors and tissue areas around the resection margins were performed on three glioblastoma patients in vivo following inspection of PpIX visible fluorescence with a conventional neurosurgical microscope. Microbiopsies were collected from FLIm imaged areas for histopathological evaluation. RESULTS: The average lifetime from PpIX and NAD(P)H fluorescence distinguished between tumor and surrounding tissue. FLIm measurements of resection margins presented a range of PpIX and NAD(P)H lifetime values (τPpIX   ∼ 3 to 14 ns, τNAD(P)H = 3 to 6 ns) associated with unaffected tissue and areas of low-density tumor infiltration. CONCLUSIONS: Intraoperative FLIm could simultaneously detect the emission of PpIX and NAD(P)H from patients in vivo during craniotomy procedures. This approach doubles as a clinical tool to identify tumor areas while performing tissue resection and as a research tool to study tumor microenvironmental changes in vivo. Intraoperative FLIm of 5-ALA-induced PpIX and tissue autofluorescence makes a promising surgical adjunct to guide tumor resection surgery.

Correlation between social media utilization by academic neurosurgery departments and higher online patient ratings.

OBJECTIVE: Patients increasingly utilize online physician review websites (PRWs) and social media to inform healthcare-related decisions. This provides neurosurgeons with opportunities for increased patient engagement. And despite the growing use of social media among neurosurgeons, the relationship between social media utilization and online reviews remains unknown. The goal of this study was to characterize the relationship between social media utilization and PRW ratings across academic neurosurgery departments. METHODS: Social media accounts (Twitter, Facebook, YouTube, Instagram) of academic neurosurgery departments were identified. Online reviews for individual faculty were obtained from Healthgrades, Vitals, WebMD, and Google. Reviews were aggregated to identify the total number of reviews per department, to generate a composite departmental rating, and to calculate a summed departmental score. US News & World Report (USNWR) and Doximity rankings were recorded for each department. Social media utilization by individual neurosurgeons and associated ratings were investigated within the departments with the highest social media utilization. RESULTS: Seventy-eight percent of academic neurosurgery departments utilized social media. The most prevalent platform was YouTube (49.1%), followed by Twitter (46.5%), Facebook (38.6%), and Instagram (16.7%). Higher patient ratings on PRWs were associated with the utilization of YouTube (p = 0.048) or Twitter (p = 0.02). The number of social media platforms utilized demonstrated a significant, positive correlation with patient ratings (p = 0.006) and summed patient ratings (p = 0.048). Although USNWR (p = 0.02) and Doximity (p = 0.0008) rankings correlated with patient ratings, only the number of social media platforms utilized remained a significant predictor of patient ratings on multivariate analysis (p = 0.0001). Thirty-one percent of academic neurosurgeons from departments with high social media utilization were active on social media. The most prevalent social media platform among individual neurosurgeons was Twitter (27.4%), followed by Instagram (8.4%), Facebook (4.9%), and YouTube (2.2%). Higher summed patient scores were associated with individual neurosurgeon utilization of YouTube (p = 0.04), Facebook (p < 0.0001), and Instagram (p = 0.01). Increased social media utilization among neurosurgeons was correlated with a greater number of patient reviews (p = 0.006) and higher summed patient scores (p = 0.003). On multivariate analysis, only Facebook use remained a significant predictor of the number of patient reviews received (p = 0.002) and summed patient satisfaction scores (p < 0.001). CONCLUSIONS: An increased social media presence is associated with higher ratings on PRWs. As neurosurgeons continue to expand their online presence, they should be aware of the possible impact of social media on online patient reviews.

Unfractionated Heparin TID Dosing Regimen Is Associated With a Lower Rate of Pulmonary Embolism When Compared With BID Dosing in Patients Undergoing Craniotomy.

BACKGROUND: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and intracranial hemorrhage (ICH) may complicate the post-operative course of patients undergoing craniotomy. While prophylaxis with unfractionated heparin (UFH) has been shown to reduce VTE rates, twice-daily (BID) and three-times-daily (TID) UFH dosing regimens have not been compared in neurosurgical procedures. The objective of this study was to explore the association between UFH dosing regimen and rates of VTE and ICH in craniotomy patients. METHODS: A retrospective chart review was conducted for 159 patients at Northwestern University receiving 5000 units/0.5 mL UFH injections either BID (n = 132) or TID (n = 27). General linear regression models were run to predict rates of DVT, PE, and reoperation due to bleeding from UFH dosing regimen while controlling for age at surgery, sex, VTE history, craniotomy for tumor resection, surgery duration, length of stay, reoperation, infections, and IDH/MGMT mutations. RESULTS: Receiving UFH TID was significantly associated with a lower rate of PE when compared with receiving UFH BID (ß = -0.121, P = 0.044; TID rate = 0%, BID rate = 10.6%). UFH TID also showed a trend toward lower rates of DVT (ß = -0.0893, P = 0.295; TID rate = 18.5%, BID rate = 21.2%) when compared with UFH BID. UFH TID showed no significant difference in rate of reoperation for bleeding when compared to UFH BID (ß = -0.00623, P = 0.725; TID rate = 0%, BID rate = 0.8%). CONCLUSIONS: UFH TID dosing is associated with lower rates of PE when compared with BID dosing in patients undergoing craniotomy.

A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma.

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference-based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial (NCT03020017) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment-related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129-treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

Lumboperitoneal shunts for the treatment of idiopathic normal pressure hydrocephalus.

The standard of care for idiopathic normal pressure hydrocephalus (iNPH) is placement of a ventriculoperitoneal (VP) shunt. However, VP shunts require intracranial intervention and are associated with notable postoperative complications, with some groups reporting complication rates for VP shunts ranging from 17 to 33%, along with failure rates up to 17.7%. Lumboperitoneal (LP) shunts are an alternative for cerebrospinal fluid diversion that do not require intracranial surgery, thus providing utility in patients where intracranial surgery is not possible or preferred. Here we retrospectively reviewed our 25 patients with LP horizontal-vertical (LP-HV) shunts placement for initial treatment for iNPH from 2014 to 2019. All patients had preoperative gait dysfunction, 16 (64%) had urinary incontinence, and 21 (84%) exhibited cognitive insufficiency. Two weeks post-shunt placement, 23/25 (92%) patients demonstrated improvement in gait, 11/16 (68%) had improvement in incontinence, and 14/21 (66%) had improvement cognitive insufficiency. At six months or greater follow up 13/20 (65%) had improvement in gait, 7/15 (47%) showed improvement in incontinence, and 11/15 (73%) demonstrated improvement in cognitive function. Six patients (24%) required at least one revision of the LP shunt. Shunt malfunctions resulted from CSF leak in one patient, shunt catheter migration in two patients, peritoneal catheter pain in one patient, and clinical symptoms for overdrainage in two patients. Thus, we demonstrate that LP-HV shunt placement is safe and efficacious alternative to VP shunting for iNPH, resulting in notable symptomatic improvement and low risk of overdrainage, and may be considered for patients where cranial approaches should be avoided.

Diffuse astrocytic glioma, IDH-Wildtype, with molecular features of glioblastoma, WHO grade IV: A single-institution case series and review.

OBJECTIVE: In 2018, cIMPACT-NOW update 3 concluded that WHO grade II/III IDH-wildtype diffuse astrocytomas that contain TERT promoter mutations, chromosome 7 gain/10 loss, and/or EGFR amplification, correspond to a WHO grade IV diagnosis and should be classified as Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV (DAG-G). We present a single-institution series of patients with DAG-G and IDH-mutant astrocytomas and compare their clinical, molecular, and radiographic characteristics. METHODS: Patient data was retrospectively extracted from the EMR for all patients undergoing surgical biopsy/resection of a diffuse astrocytoma at our institution from 2018 to 2020. Clinical presentation, molecular alterations, radiographic appearance, surgery, and survival were reviewed for each patient. RESULTS: Six DAG-G patients were identified in our cohort. All patients had diffuse disease, and presented with expansile, T2 hyperintense lesions with minimal enhancement. Compared to patients with classic IDH-mutant astrocytomas, mean age for DAG-G patients was older (68 vs 33 years, p < 0.0001), tumors were more diffuse (p = 0.02), with patients more likely to present with focal deficits and receive a biopsy only (p = 0.005). Overall survival was significantly shorter for DAG-G patients (p = 0.03). CONCLUSION: Patients with DAG-G are more likely to be older than typical IDH-mutant diffuse astrocytoma patients. They are more likely to present with tumors in a diffuse pattern with focal deficits. When such patients are encountered, prompt biopsy/resection to confirm the diagnosis and immediate initiation of adjuvant therapy is recommended, as the disease progression and overall prognosis is similar to glioblastoma.

Brain Metastasis Recurrence Versus Radiation Necrosis: Evaluation and Treatment.

Radiation necrosis (RN) occurs in 5% to 25% of patients with brain metastases treated with stereotactic radiosurgery. RN must be distinguished from recurrent tumor to determine appropriate treatment. Stereotactic biopsy remains the gold standard for identifying RN. Initial treatment of RN often involves management of edema using corticosteroids, antiangiogenic therapies, and hyperbaric oxygen therapy. For refractory symptoms, surgical resection can be considered. Minimally invasive stereotactic laser ablation has the benefit of providing tissue diagnosis and treating RN or recurrent tumor with similar efficacy. Laser ablation should be considered for lesions in need of intervention where the diagnosis requires tissue confirmation.

Intraventricular adult Taenia solium causing hydrocephalus: A case report.

BACKGROUND: Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system worldwide and is caused by the larval form of the tapeworm Taenia solium. In general, T. solium larval form may be located in the neuraxis, resulting in pathology. Here, we report a rare case of female with a history of adult onset seizures presenting with adult form T. solium in the fourth ventricle, causing hydrocephalus. CASE DESCRIPTION: A 36-year-old female patient with a known history of adult onset seizures presented with a 1-year history of progressively worsening bilateral headaches with vertigo and intermittent nausea. A computerized tomography scan revealed ventriculomegaly and transependymal flow, with an obstruction at the level of the fourth ventricle. Outpatient magnetic resonance imaging demonstrated obstructive hydrocephalus secondary to a lobulated cystic mass within the fourth ventricle, demonstrating a gross appearance consistent with racemose NCC. The patient underwent endoscopic third ventriculostomy, and gross examination of the resected cyst revealed a mature T. solium larvae encased in a cystic membrane. Given that our patient was born and raised in Mexico but had not returned since the age of 8, NCC was an unexpected finding. CONCLUSION: The present case highlights the importance of maintaining high suspicion for NCC in all patients presenting with seizures or hydrocephalus of unknown cause. Even in patients with a very remote history of residence in an endemic country, NCC can be an overlooked, underlying cause of both chronic neurologic symptoms, as well as acute, life-threatening neurologic emergencies.

The Practical Application of Emerging Technologies Influencing the Diagnosis and Care of Patients With Primary Brain Tumors.

Over the past decade, a variety of new and innovative technologies has led to important advances in the diagnosis and management of patients with primary malignant brain tumors. New approaches to surgical navigation and tumor localization, advanced imaging to define tumor biology and treatment response, and the widespread adoption of a molecularly defined integrated diagnostic paradigm that complements traditional histopathologic diagnosis continue to impact the day-to-day care of these patients. In the neuro-oncology clinic, discussions with patients about the role of tumor treating fields (TTFields) and the incorporation of next-generation sequencing (NGS) data into therapeutic decision-making are now a standard practice. This article summarizes newer applications of technology influencing the pathologic, neuroimaging, neurosurgical, and medical management of patients with malignant primary brain tumors.

Tumor-induced peripheral immunosuppression promotes brain metastasis in patients with non-small cell lung cancer.

INTRODUCTION: Brain metastases are a significant source of morbidity and mortality for patients with lung cancer. Lung cancer can induce local and systemic immunosuppression, promoting tumor growth and dissemination. One mechanism of immunosuppression is tumor-induced expansion of programmed death-ligand 1 (PD-L1) expressing myeloid cells. Here, we investigate peripheral blood immune phenotype in NSCLC patients with or without brain metastasis. METHODS: Peripheral blood was collected from patients with lung metastatic brain tumors and pre-metastatic lung cancer. Immunosuppressive monocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were quantified through flow cytometry. T cell reactivity was analyzed via ELISpot. Brain metastasis conditioned media was collected from tumor-derived cell cultures and analyzed for cytokines by ELISA. Naïve monocytes were stimulated with brain metastasis conditioned media to evaluate PD-L1 stimulation. RESULTS: Patients with brain metastatic lung carcinoma demonstrated increased peripheral monocyte PD-L1, MDSC abundance, and Treg percentage compared to early stage pre-metastatic patients and healthy controls. Patients with elevated peripheral monocyte PD-L1 had less reactive T cells and worse survival. Brain metastasis conditioned media stimulation increased monocyte PD-L1, and conditioned media IL-6 levels correlated with PD-L1 induction. Treatment with anti-IL-6 or anti-IL-6 receptor antibodies reduced PD-L1 expression. In summary, patients with lung cancer and brain metastases exhibit multiple markers of peripheral immunosuppression. CONCLUSIONS: The frequency of PD-L1+ myeloid cells correlated with the presence of brain metastases. Tumor-derived IL-6 was capable of inducing PD-L1+ myeloid cells in vitro, suggesting that monitoring of immunosuppressive factors in peripheral blood may identify new targets for therapeutic intervention in selected patients.