Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients.

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.

Pediatric stroke associated with a sedentary lifestyle during the SARS-CoV-2 (COVID-19) pandemic: a case report on a 17-year-old.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic-associated quarantine has led to a more sedentary lifestyle in teenagers. This may increase the risk for venous thromboembolism and a subsequent source of an ischemic stroke through a patent foramen ovale (PFO). Here, we report a pediatric stroke case likely due to these factors.

Perspectives from neuro-oncology providers on patient access to electronic records: a survey study.

Aim: To evaluate the neuro-oncology providers' experience with patient online access to electronic records. Methods: Cross-sectional survey for physicians and advanced care providers within the field of neuro-oncology in the USA. Results: 65 providers completed the survey, from all major regions of the USA. 58% reported that at least once per month, patients contacted them outside of an office visit about provider notes or a laboratory or imaging finding accessed online. 54% of providers did not think that all laboratory results should be released automatically, and only 25% of providers thought that all radiology reads should be released immediately. 97% thought that some patients suffered substantial distress viewing test results prior to appointments. Qualitative responses aligned with the quantitative results. Conclusion: Most neuro-oncology providers are concerned about the immediate release of laboratory and imaging findings to patients without guidance.

Prior studies had investigated the perspectives of medical providers on patients having immediate access to medical records. However, almost none of them focus on neuro-oncology. In our study, we distributed a survey electronically to neuro-oncology providers across the USA to seek their perspectives. Our results show that most neuro-oncology providers found patients having immediate access to their records to be useful. However, they raised concerns about the immediate release of laboratory and imaging findings to patients without guidance. Our study also included free responses from the neuro-oncology providers that could help mitigate this concern.

Neurofilament light chain in serum of cancer patients with acute neurological complications.

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died during hospitalization.Conclusion: Serum NfL levels consistently corresponded to death, disease severity or recovery in this series.

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Therapeutic Strategies for Gliomas Associated With Cancer Predisposition Syndromes.

PURPOSE: The purpose of this article was to provide an overview of syndromic gliomas. DESIGN: The authors conducted a nonsystematic literature review. RESULTS: Cancer predisposition syndromes (CPSs) are genetic conditions that increase one's risk for certain types of cancer compared with the general population. Syndromes that can predispose one to developing gliomas include neurofibromatosis, Li-Fraumeni syndrome, Lynch syndrome, and tuberous sclerosis complex. The standard treatment for sporadic glioma may involve resection, radiation therapy, and/or alkylating chemotherapy. However, DNA-damaging approaches, such as radiation and alkylating agents, may increase the risk of secondary malignancies and other complications in patients with CPSs. In some cases, depending on genetic aberrations, targeted therapies or immunotherapeutic approaches may be considered. Data on clinical characteristics, therapeutic strategies, and prognosis of syndromic gliomas remain limited. CONCLUSION: In this review, we provide an overview of syndromic gliomas with a focus on management for patients with CPSs and the role of novel treatments that can be considered.

Current status of sinonasal cancer survivorship care.

Sinonasal cancer is a heterogeneous orphan disease of diverse histologies, each with distinct clinical, oncologic, and toxicity profiles. Because of the comparative rarity of these cancers, sinonasal cancers are treated as a grouped diagnosis despite their clinical and biological heterogeneity. Multimodality treatment with a combination of surgery, chemotherapy, and/or radiotherapy is the standard-of-care for advanced-stage patients but there are few surveillance or follow-up practice guidelines or formalized survivorship care pathways. A scoping literature review was conducted via PubMed, EMBASE, and Google Scholar. A total of 112 studies were included, which were grouped along the following topics: surveillance, second primary tumors, quality of life, and symptom burden. Sinonasal cancer tends to exhibit a higher rate of local failure and occur in a delayed fashion compared to mucosal malignancies of the head and neck. Moreover, the site of failure and time-varying risk of recurrence is histology-specific. Following multimodality treatment of the skull base, patients may experience endocrine, visual, auditory, sinonasal, olfactory, and neurocognitive deficits, as well as psychosocial impairments that impact multiple physical and neuropsychological domains, resulting in diminished quality of life. Sinonasal cancer patients would benefit from tailored, histology-specific survivorship programs to address the recurrence, second primary, and functional impairments resulting from disease and treatment toxicity.

Prognostic value of O 6-methylguanine-DNA methyltransferase methylation in isocitrate dehydrogenase mutant gliomas.

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 O 6 -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.

Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions.

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.

Vagus Nerve Stimulation for Tumor-Related Epilepsy: Does It Make Sense?

Seizure is a common presenting symptom for those with brain tumor due to its unique pathogenesis. Several choices of antiepileptic drug are available to use, but some patients can still go on to develop tumor-related refractory epilepsy. Vagus nerve stimulation is becoming a popular option for those with medical refractory epilepsy but no brain tumor due to its effectiveness. There are very few studies available that address the topic of using vagus nerve stimulation for tumor-related epilepsy. Here we discuss the evidence of using vagus nerve stimulation for refractory tumor-related epilepsy and its challenges and gaps moving forward.

Open Access Fees: A Barrier to Scholarly Activity Among Neurology Trainees.

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.

Clinical Outcome of Adult Spinal Muscular Atrophy Patients Treated with Nusinersen: A Case Series Review.

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.

Effective Connectivity of the Fronto-Parietal Network during the Tangram Task in a Natural Environment.

Although the neural basis underlying visuospatial reasoning has been widely explored by neuroimaging techniques, the brain activation patterns during naturalistic visuospatial reasoning such as tangram remains unclear. In this study, the directional functional connectivity of fronto-parietal networks during the tangram task was carefully inspected by using combined functional near-infrared spectroscopy (fNIRS) and conditional Granger causality analysis (GCA). Meanwhile, the causal networks during the traditional spatial reasoning task were also characterized to exhibit the differences with those during the tangram task. We discovered that the tangram task in a natural environment showed enhanced activation in the fronto-parietal regions, particularly the frontal cortex. In addition, a strong directional connectivity from the right prefrontal cortex to left angular gyrus was detected for the complex spatial reasoning condition of spatial reasoning task, whereas no effective connectivity was identified between the frontal and parietal cortices during the tangram task. Further correlation analyses showed that the behavioral performance in the spatial reasoning rather than the tangram task manifested the relationship with the connectivity between the frontal and parietal cortex. Our findings demonstrate that the tangram task measures a different aspect of the visuospatial reasoning ability which requires more trial-and-error strategies and creative thinking rather than inductive reasoning. In particular, the frontal cortex is mostly involved in tangram puzzle-solving, whereas the interaction between frontal and parietal cortices is regulated by the hands-on experience during the tangram task.

Causal Cortical Network for Arithmetic Problem-Solving Represents Brain's Planning Rather than Reasoning.

Arithmetic problem-solving whose components mainly involve the calculation, planning and reasoning, is an important mathematical skill. To date, the neural mechanism underlying arithmetic problem-solving remains unclear. In this study, a scheme that combined a novel 24 points game paradigm, conditional Granger causality analysis, and near-infrared spectroscopy (fNIRS) neuroimaging technique was developed to examine the differences in brain activation and effective connectivity between the calculation, planning, and reasoning. We discovered that the performance of planning was correlated with the activation in frontal cortex, whereas the performance of reasoning showed the relationship with the activation in parietal cortex. In addition, we also discovered that the directional effective connectivity between the anterior frontal and posterior parietal cortex was more closely related to planning rather than reasoning. It is expected that this work will pave a new avenue for an improved understanding of the neural underpinnings underlying arithmetic problem-solving, which also provides a novel indicator to evaluate the efficacy of mathematical education.