The role of microRNAs in brain metastasis.

Brain metastasis (BM) is the most common type of brain tumor and frequently foreshadows disease progression and poor overall survival with patients having a median survival of 6 months. 70,000 new cases of BM are diagnosed each year in the United States (US) and the incidence rate for BM is increasing with improved detection. MicroRNAs (miRNAs) are small non-coding RNAs that serve as critical regulators of gene expression and can act as powerful oncogenes and tumor suppressors. MiRNAs have been heavily implicated in cancer and proposed as biomarkers or therapeutic targets or agents. In this review, we summarize an extensive body of scientific work investigating the role of microRNAs in BM. We discuss miRNA dysregulation, functions, targets, and mechanisms of action in BM and present the current standing of miRNAs as biomarkers and potential therapeutics for BM. We conclude with future directions of miRNA basic and clinical research in BM.

Use of rituximab, temozolomide, and radiation in recurrent and refractory primary central nervous system lymphoma in the Philippines: a retrospective analysis.

Background: Refractory disease in primary central nervous system lymphoma (PCNSL) may occur despite adequate initial treatment. There is currently no standard of care for relapsed and recurrent PCSNL. No study to date documents using a combined regimen of radiotherapy, temozolomide, and rituximab. This study aimed to present the clinical course and outcomes of patients with recurrent or refractory disease who were given a combination of radiation, temozolomide, and rituximab. Methods: Retrospective analysis was employed to evaluate data from recurrent or refractory PCNSL patients who were treated with radiation, temozolomide, and rituximab in two tertiary hospitals in the Philippines. Baseline demographics, treatment regimen, and outcomes were analyzed. Results: Fifteen patients with a median age of 56 years were included, 11 with refractory disease and 4 with recurrent disease. Patients with bulky disease received either whole brain radiotherapy or partial field radiotherapy with rituximab and temozolomide given during radiation and for 6 months after radiation. Overall response rate to salvage therapy was 93.3% (14/15). Median overall survival from initial diagnosis was not reached (median follow-up: 84 months). Mortality rate was 33.3% (5/15), but only 2 out of 5 mortalities were from disease progression. There were only two reported cases of mild allergic reactions to rituximab, which did not result in treatment interruption. Conclusion: Rituximab, temozolomide, and radiotherapy can be considered as an effective and safe salvage therapy for relapsed and recurrent central nervous system lymphoma.

Brain Tumor Infodemiology: Worldwide Online Health-Seeking Behavior Using Google Trends and Wikipedia Pageviews.

Background: Searching the internet for information on common neurologic symptoms and diseases has been increasing in recent times. It is postulated that online search volume data could be utilized to gauge public awareness and real-world epidemiological data regarding brain tumors. Objectives: The goal of this study was to describe the pattern of online search queries of keywords related to neoplasms of the central nervous system (CNS). Methods: Using Google Trends, search activity from January 2004 - January 2021 was quantified using relative search volume (RSV). The average RSV for the first 3 years was compared with the final 3 years to account for percent change. Wikipedia article views from July 2007 - January 2021 were generated using Pageviews. Peaks in RSV and page views were then matched for related news. Results: "Brain tumor", "brain cancer", "glioblastoma", and "glioma" had the highest search volume. RSV from Google Trends and views of Wikipedia pages reflected comparable data in terms of known prevalence rankings of tumor subtypes. There were no observable trends that could correlate to the rising numbers of brain tumor cases worldwide. However, headlines of personalities being diagnosed with glioblastomas were mostly responsible for temporary increases in public interest. Conclusions: Transient rises in online search volume mirror public awareness of more aggressive CNS neoplasms that have a high burden of disease. Worldwide interest in brain tumors may not necessarily correspond to clinical occurrence, but may signify an unmet gap in providing accurate online information to neuro-oncologic patients.

Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection.

Purpose: Epithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor. Methods: Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies. Results: An epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85-90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts from myeloid cells as well as M1 and M2 macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section. Conclusion: Epithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different.

Neuro-oncology in the Philippines: a scoping review on the state of medical practice, deterrents to care and therapeutic gaps.

BACKGROUND: Neoplasms of the brain and spine are relatively uncommon compared to breast, lung and gastrointestinal tumours, which occur at higher rates in the Asian population. Updated guidelines in diagnosis and treatment of neuro-oncologic diseases recommend advanced molecular-based precision-medicine; thus the need for increasingly individualised regimens. It is, therefore, necessary to determine whether there are areas of improvement in the provision of care to these patients, especially in low- to middle-income economies like the Philippines. METHODS: In this study, we identified gaps in the delivery of medical care to Filipino patients with tumours of the central nervous system. We performed a scoping review on the available literature on clinical experience with treatment of neuro-oncologic cases from the Philippines and performed qualitative analysis viewed through the lens of the existing healthcare system. RESULTS: The medical practice of neuro-oncology in the Philippines lacks robust local data on epidemiology and treatment outcomes. There are existing legislative frameworks to support adequate healthcare delivery and financing to brain tumour patients. However, inequities in the geographic distribution of infrastructure, manpower and medications are roadblocks for accessibility to neuro-oncologic services like specialised molecular markers, neurosurgical procedures, sustained chemotherapy and radiation therapy centres. CONCLUSION: There are significant treatment gaps in the care of neuro-oncologic patients in the Philippines that need to be addressed. Early detection and initiation of prognosis-changing therapeutics through reduction of out-of-pocket expenses, access to readily available diagnostic tools and sustainability of management regimens are the main areas that necessitate strengthened partnership between the public and private sectors of Philippine society.

Rare case of intramedullary spinal cord metastasis from nasopharyngeal carcinoma.

INTRODUCTION: Central nervous system (CNS) metastasis from nasopharyngeal carcinoma (NPC) is rare and presents with high morbidity and mortality. As a rare entity, a few patients with CNS metastasis from NPC have been reported, and no studies were available on treatment and prognosis. Based on our clinical experience, early diagnosis with incorporation of a clear palliative plan is imperative in providing holistic care for patients with locally-invasive and metastatic nasopharyngeal carcinoma. CASE REPORT: Our study reports a case of a 48-year-old Filipino male with known NPC Stage IVB who developed acute symptoms of constipation, urinary retention, and bilateral lower limb weakness and numbness. Magnetic resonance imaging showed intramedullary lesions in multiple segments of the spinal cord. Steroid and radiotherapy of the spine were initiated with noted transient improvement of the motor strength. Subsequently, he developed cancer-related stroke. The patient progressively deteriorated despite best medical care.

Primary Brain Tumor Research Productivity in Southeast Asia and Its Association With Socioeconomic Determinants and Burden of Disease.

BACKGROUND: There is an unmet need to assess research productivity from southeast Asia (SEA) regarding primary central nervous system (CNS) tumors. The country's economy, landscape of neurology practice, and disease burden are hypothesized to correlate with scientific output. This study aimed to objectively measure the impact of published studies on primary brain tumors in SEA and to assess for correlation with socioeconomic determinants and burden of disease. METHODS: We systematically searched electronic databases for relevant articles from SEA on primary CNS tumor until July 31, 2020. Bibliometric indices were reported and subjected to correlational analysis with population size, gross domestic product (GDP) per capita, percentage (%) GDP for research and development (R&D), total number of neurologists, disease incidence, deaths, and disability-adjusted life years. RESULTS: A total of 549 articles were included, consisting primarily of case reports (n=187, 34.06%) and discussed gliomas (n=195, 35.52%). Singapore published the most number of the articles (n=246, 44.8%). Statistical analysis showed a positive correlation between %GDP for R&D and total publication. Additionally, negative relationships were noted between burden of disease and total neurologist with most bibliometric indices. However, GDP per capita was not correlated with measures for research productivity. CONCLUSION: The low impact of scientific output on primary CNS tumors in SEA does not address the growing epidemiology and burden of this disease. An increase in the GDP growth and financial and manpower investment to R&D may significantly improve research productivity in SEA.

Acute hemorrhagic leukoencephalitis of Weston Hurst secondary to herpes encephalitis presenting as status epilepticus: A case report and review of literature.

Acute hemorrhagic leukoencephalitis (AHL) is a rare and mostly fatal fulminant demyelinating disease. This case describes a 63-year old male in status epilepticus associated with an intracerebral hemorrhage following a one week viral prodrome with rapid decline to coma. He exhibited peripheral leukocytosis, neutrophilic pleocytosis with normal glucose and high protein in cerebrospinal fluid (CSF). Additionally, CSF was positive for herpes simplex virus (HSV) polymerase chain reaction (PCR). Medical decompression, low-dose dexamethasone, antibiotics and acyclovir were initially given. Magnetic resonance imaging (MRI) was suggestive of AHL, thus he was treated with methylprednisolone 1 g/day for 5 days. The patient improved and was discharged with significant neurologic morbidity. This is the first reported case of AHL in the Philippines presenting as a diagnostic dilemma with a protracted clinical course who responded to high dose intravenous steroids.

Corrigendum: Validation of a Questionnaire for Distinguishing X-Linked Dystonia Parkinsonism From Its Mimics.

[This corrects the article DOI: 10.3389/fneur.2018.00830.].

Validation of a Questionnaire for Distinguishing X-Linked Dystonia Parkinsonism From Its Mimics.

Objectives: X-linked dystonia parkinsonism (XDP) is a neurodegenerative movement disorder endemic to the island of Panay in the Philippines. We undertook a population-based prevalence study to enumerate all cases of XDP in Panay. We first developed a 4-item questionnaire to distinguish XDP suspects from the general population. In the present study we aimed to revalidate this questionnaire to distinguish XDP from similar conditions so as to give it greater utility in the clinical setting. Patients and Methods: A total of 306 subjects (114 cases and 192 controls) were screened in from the 16 towns and 1 city of Capiz province. Their responses to the previously developed 4-item questionnaire were collected and multivariable logistic regression was performed to develop a predictive model. The accuracy of the model was determined by using it on a subset of patients; then, a scoring system based on the model coefficients was established. Results: With a cut-off score of 6, the questionnaire had an accuracy of 70.7% (95% CI 0.57-0.82), a sensitivity of 84.6 % (95% CI 0.65-0.96) and a specificity of 59.4 % (95% CI 0.41-0.76). The item on "shuffling of feet" was the strongest predictor in distinguishing XDP from its common mimics. Conclusion: We were able to revalidate a simple, four-item questionnaire that could distinguish XDP from its common mimics with fair accuracy. The questionnaire along with other clinical features can be used to determine which patients need specialty evaluation and genetic testing to verify a diagnosis of XDP.