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Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field.

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Background Patients with isocitrate dehydrogenase (IDH) mutant gliomas have been associated with longer survival time than those that are IDH wild-type. Previous studies have shown the prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for glioblastoma multiforme (GBM), which are predominantly IDH wild-type. Little is known of the prognostic value of MGMT methylation status for IDH mutant gliomas. Methods We retrospectively identified IDH mutant gliomas patients between 2011 and 2020 that were tested for MGMT promoter methylation. We generated Kaplan–Meier estimator curves and performed Cox proportional hazard models for overall survival (OS) and progression-free survival (PFS) to compare the outcomes of MGMT promoter methylated versus MGMT unmethylated patients. Results Of 419 IDH mutant gliomas with MGMT promoter methylation testing, we identified 54 GBMs, 223 astrocytomas, and 142 oligodendrogliomas. 62.3% patients had MGMT methylated tumors while 37.7% were MGMT unmethylated. On Kaplan–Meier analysis, median OS for all MGMT methylated patients was 17.7 years and 14.6 years for unmethylated patients. Median PFS for all MGMT methylated patients was 7.0 years and for unmethylated patients 5.2 years. After univariate subgroup analysis, MGMT methylation is only prognostic for OS and PFS in GBM, and for OS in anaplastic oligodendroglioma and anaplastic oligodendroglioma for OS. In multivariate analysis, MGMT unmethylated GBM patients carry a higher risk of death (HR 7.72, 95% CI 2.10–28.33) and recurrence (HR 3.85, 95% CI 1.35–10.96). Conclusions MGMT promoter methylation is associated with better OS and PFS for IDH mutant GBM. MGMT promoter methylation testing for other IDH mutant glioma subtypes may not provide additional information on prognostication.

The open access publishing model provides readers of all backgrounds access to articles free of charge. To cover the costs of open access, however, many journals now charge substantial article processing fees. This has inadvertently created yet another barrier for trainees to engage in scholarly activity. Herein, we describe the issue, review the literature, and provide suggestions for addressing this barrier with the focus on the neurology specialty.

A 53-year-old man was admitted to hospital for elective repair of a descending aortic dissection and type B intramural haematoma. He had a history of stage 3 chronic kidney disease and took aspirin for paroxysmal atrial fibrillation. At 07:00 on the morning of the operation he was awake, alert and moving all limbs. His surgery began at 09:10. He received various anaesthetic medications, including rocuronium 50 mg (0.5 mg/kg); last dose at 17:20. The surgical repair ended at 16:15, and left the operating theatre at around 20:00 after an uneventful surgery. At midnight, he was still unresponsive despite receiving naloxone. His observations were: temperature 37°C, blood pressure 158/100 mmHg, heart rate 80/min, intubated and breathing at set respiratory rate 14/min, and oxygen saturation 100% on pressor support of 8 cmH2O, tidal volume 580 mL (8 mL/kg of his ideal body weight), FiO2 45%, and positive end-expiratory pressure of 5 cmH2O. He was not on sedation. His pupils were …

Introduction Nusinersen is an antisense oligonucleotide drug that was developed for treatment of spinal muscular atrophy (SMA). Its effectiveness for adults is limited; therefore, more clinical data are needed to guide adult SMA patients who are considering this treatment. Methods Through case series review, we retrospectively reviewed charts of Kaiser Permanente Southern California members who were already receiving nusinersen treatment, which has been available since August 2017. Patients were evaluated by physical therapy using the Hammersmith Functional Motor Scale (out of highest possible score of 40). Results We identified 4 adult patients who met our study criteria as of February 1, 2020. All patients were mobility device dependent. Patient age ranged from 23 to 56 years. A generalized linear model was used to assess trendlines for repeated measures within subjects. In this small sample, there appears to a significant increase in scores on repeated measures (p = 0.0027). Conclusion Based on this small study, some adult SMA patients may benefit from treatment with nusinersen.

We report our experience treating 20 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 65 y; 8 patients were men and 12 were women. Eighteen had cerebral mass lesions, 1 had a paraspinal mass, and 1 leptomeningeal disease. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 3.5 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 5 mg/kg followed by autologous bone marrow transplantation. Four patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received only 2 initial cycles including cytarabine and thiotepa. Overall, 14 patients completed initial chemotherapy. Twelve of these 14 went on to transplantation; one patient had early disease progression, and in one no stem cells could be collected. All 4 patients over 70 y died early after 1-2 cycles; the median age of these was 80 y, and the causes of early death were neutropenic fever, septic thrombophlebitis, and cardiac arrest. One patient who completed the entire regimen including transplantation died of fungal pneumonia; the other 13 experienced no serious acute toxicity. One patient had late disease progression; one developed symptomatic leukoencephalopathy. Thirteen of the 20 patients remain alive. Median OS for the cohort is 698 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high incidence of early death in patients over 70 y suggests that the regimen may be too toxic for elderly individuals.

BACKGROUND Patients with isocitrate dehydrogenase (IDH) mutant gliomas have been associated with longer survival time than those with IDH wildtype. Previous studies have also shown the predictive value of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for glioblastoma. However, little is known in the prognostic value of MGMT methylation status for IDH mutant gliomas. METHODS We retrospectively identified IDH mutant gliomas patients from University of California Los Angeles and Kaiser Permanente Los Angeles that had been tested for MGMT methylation status. We performed Kaplan-Meier and Cox regression analyses of overall survival (OS) to compare the MGMT methylated versus MGMT unmethylated patients. RESULTS We identified a total of 375 IDH mutant gliomas with MGMT testing. Subgroups include 52 glioblastoma, 191 astrocytoma, and 132 oligodendroglioma. The median OS for all MGMT methylated patients was 20.0 years and for unmethylated patients 14.3 years (log-rank P=0.008). Cox regression analysis also confirmed patients with MGMT methylated to have better survival than those with MGMT unmethylated (hazard ratio of 0.47, P= 0.005). During subgroup analysis, MGMT methylated glioblastoma patients have a median OS of 13.7 years compared to MGMT unmethylated patients 3.2 years (log-rank P=0.004) with a hazard ratio of 0.14 (P=0.005). However, we see no difference yet for astrocytoma (hazard ratio of 1.09, P= 0.81) and oligodendrogliomas (hazard ratio of 0.36, P= 0.193), possibly as a result of immature survival data. CONCLUSIONS MGMT promoter methylation is associated with better outcomes in IDH mutant glioblastoma patients. Progression free survival will be analyzed to determine predictive benefit of MGMT methylation for other glioma subtypes.

Thin-film crystalline photovoltaic (PV) cell is a trend for future PV with its potential to achieve low cost and high efficiency. Concerning material utilization efficiency, we propose a method with a fast manufacturing method of thin crystalline Si by chemical solution. To obtain the highest efficiency of material utilization, experiments with different H 2 O 2 /HF ratio are conducted, where related mechanisms are discussed. Moreover, large-area (87.7 mm2) thin film transferred to glass is demonstrated, and with embedded nanohole structure, lowest optical reflectance of 0.26% is measured. These characteristics show that the fabricated thin film has potential for large-area crystalline thin film PV.

Crystalline Si photovoltaic modules still have high production cost due to significant consumption of the Si wafer. Reducing the large amount of Si material consumption is thus a critical issue. Here we deve lop a two-step metal-assisted etching technique for forming vertically-aligned Si nanohole thin films from bulk Si wafers. The formation of Si nanohole thin films includes a series of solution processes: deposition of Ag nanoparticles in an AgNO 3 / HF aqueous solution, formation of Si nanohole arrays at the first-step metal-assisted etching, and side etching of the roots of the nanohole structure at the second-step meta l-assisted etching. All th e processes can proceed at around room temperature. A Si nanohole thin film with an averag e hole-size of 100 nm and a thickness of 5 m-20 m was hence formed at the top of the wafer. Afterwards, the Si nanohole thin film was tran sferred onto alien substrates. The Si nanohole thin film has the crystal quality similar to the bulk Si wafer. The above bul k Si substrate can be reused. With similar processes, other Si nanohole thin films can be formed fr om the above recycled Si wafer. The hole size and thickness are similar. The Si wafers recycled will significan tly reduce the material consumption of Si. Thus, such technique is promising for lowering the cost of Si solar cells. Keywords: Si nanohole, metal-assisted etching, transfer, lithium battery anode, Si nanohole powder, photovoltaic, Si wafer recycling.

Si nanostructures are promising materials for future photovoltaic applications. To date the Si nanostructures are mainly formed on particular substrates or at high temperatures, greatly limiting their application flexibility. Here we report a two-step metal-assisted etching technique for forming vertically aligned Si nanohole thin films on bulk Si wafers at room temperature. The Si nanohole thin films with a thickness of 5µm can be easily transferred to alien substrates. Because of the low temperature transfer process, it enables a large variety of alien substrates such as glass and plastics to be used. In addition, we demonstrate that the bulk Si substrate can be reused to fabricate Si nanohole thin films. The consumption of bulk Si materials is significantly reduced.

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