Common Central Nervous System Research Articles

Transcranial near-infrared laser improves postoperative neurocognitive disorder in aged mice via SIRT3/AMPK/Nrf2 pathway.

Postoperative neurocognitive disorder (PND) is a common central nervous system (CNS) complication that might increase the morbidity and mortality of elderly patients after anesthesia/surgery. Neuroinflammation, oxidative stress, and synaptic dysfunction are closely related to cognitive dysfunction, an important clinical feature of PND. Transcranial near-infrared laser (TNIL) is regarded as an effective treatment for cognitive-related diseases by improving mitochondrial function and alleviating neuroinflammation and oxidative stress damage. Aged male C57BL/6 mice underwent a carotid artery exposure procedure under isoflurane anesthesia. We treated PND-aged mice for three consecutive days (4 h post-operation, 1-laser) with 810 nm continuous wave (CW) laser 18 J/cm2 at 120 mW/cm2. The post-treatment evaluation included behavioral tests, RTq-PCR, immunofluorescence, and Western blot. The results demonstrated that TNIL improved PND and the levels of synaptic function-associated proteins such as post-synaptic density protein 95 (PSD95), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Besides, neuroinflammatory cytokine levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as microglia activation and oxidative stress damage were attenuated after TNIL treatment in aged mice with PND. Further investigation suggested that TNIL relieved oxidative stress response by activating the SIRT3/AMPK/Nrf2 pathway. Transcranial near-infrared laser improved cognitive impairment in aged mice with PND, which may be a promising therapeutic for PND.

Clinical features and outcomes of pediatric intracranial gliomas: results from single center's 226 cases and corroborated with SEER database.

Pediatric gliomas are the most common central nervous system (CNS) tumors in children and adolescents and show different clinical and histopathological characteristics from the adult. The prognostic factors were poorly defined in pediatric intracranial gliomas. We collected pediatric intracranial glioma cases in our institution between February 2011 and June 2022. The patient clinical data, tumor growth characteristics, treatments, and follow-up data were analyzed by Cox regression analysis to identify impact factors on the prognosis of pediatric intracranial glioma patients. To corroborate our data, an independent cohort of pediatric intracranial glioma from the Surveillance, Epidemiology, and End Results Program (SEER) database was analyzed. A total of 181 cases of pediatric low-grade glioma (PLGG) and 45 cases of pediatric high-grade glioma (PHGG) were included. In multivariate Cox regression analysis, tumor size > 59.5mm (p = 0.006) and non-gross total resection (non-GTR; subtotal resection, STR, p = 0.042; biopsy, p = 0.012) were associated with decreased overall survival (OS) in PLGG patients. In PHGG patients, only chemotherapy (p = 0.023) was associated with OS while tumor size was marginally prognostic for OS (p = 0.051). Additional independent analysis of 2734 PLGG and 741 PHGG from the SEER database corroborated that larger tumor size was associated with decreased OS in LGG (p = 0.001) and HGG (p < 0.001) patients, separately. In this study, we found that tumor size was a significant prognostic factor for the OS of PLGG patients in our series. Besides the tumor size, the extent of resection also independently impacted the prognosis of PLGG patients. While in PHGG patients, only chemotherapy was associated with improved OS and tumor size was marginally prognostic.

Comprehensive analysis of the prognosis and immune infiltrates for the BET protein family reveals the significance of BRD4 in glioblastoma multiforme.

Background: Glioblastoma multiforme (GBM) is the most common and invasive primary central nervous system tumor. The prognosis after surgery, radiation and chemotherapy is very poor. Bromodomain (BRD) proteins have been identified in oncogenic rearrangements, and play a key role in the development of multiple cancers. However, the relationship between BET proteins and prognosis of GBM are still worth exploring, and the distinct functions of BET proteins and tumor immunology in GBM have not been fully elucidated. Therefore, it is particularly important to develop effective biomarkers to predict the prognosis of GBM patients. Methods: Metascape, David, Kaplan-Meier Plotter, Oncomine, GEPIA, TCGA, TIMER, and LinkedOmics databases were used to assess the expression and prognosis for BET proteins in GBM. ROC analysis of risk model was established to identify the correlation between BET genes and overall survival in GBM patients. TIMER and GEPIA databases were used to comprehensively investigate the correlation between BET genes and tumor immune infiltration cells. Moreover, the image of immunohistochemistry staining of BET proteins in normal tissue and tumor tissue were retrived from the HPA database. In addition, differential analysis and pathway enrichment analysis of BRD4 gene expression profile were also carried out. Finally, immune-fluorescence and Western blot were used to clarify the expression of BRD4 in GBM cells. Results: Bioinformatics analysis showed that the expression levels of BET genes in GBM may play an important role in oncogenesis. Specifically, bioinformatic and immunohistochemistry analysis showed that BRD4 protein was more highly expressed in tumor tissues than that in normal tissues. The high expression of BRD4 was associated with poor prognosis in GBM. The expression of BET genes were closely related to the immune checkpoint in GBM. The correlation effect of BRD4 was significantly higher than other BET genes, which represented negative correlation with immune checkpoint. The expression of BRD4 was positively associated with tumor purity, and negatively associated with immune infiltration abundance of macrophage, neutrophil and CD8+ T-cell, respectively. Cox analysis showed that the model had good survival prediction and prognosis discrimination ability. In addition, the expression levels of BRD4 protein was significantly higher in U-251MGcells than that in normal cells, which was consistent with the results of bioinformatics data. Conclusion: This study implied that BRD4 could be hopeful prognostic biomarker in GBM. The increased expression of BRD4 may act as a molecular marker to identify GBM patients with high-risk subgroups. BRD4 may be a valuable prognostic biomarker, and a potential target of precision therapy against GBM.

Characterization of the lncRNA-miRNA-mRNA regulatory network to reveal potential functional competing endogenous RNAs in traumatic brain injury.

Traumatic brain injury (TBI) is one of the most common acute central nervous system injury diseases. Given the medical and socio-economic burdens of TBI patients, the pathogenesis in TBI and the latent intervention targets needed to be further illuminated. Long non-coding RNAs (lncRNAs) had been revealed to play a vital role in the regulation of pathogenesis after TBI. However, the mutual communication and adjustment of lncRNA associated competing for endogenous RNA (ceRNA) networks in TBI have not been explored to date. In this study, we systematically sequenced the whole transcriptome of lncRNAs, miRNAs, and mRNAs between sham and TBI groups and a total of 939 differentially expressed (DE) lncRNAs, 46 DE miRNAs, and 1,951 DE mRNAs were obtained. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein interaction relationship analyses were conducted for DE mRNAs to identify hub DE genes in TBI. Based on the criteria of bioinformatics prediction, the lncRNA associated ceRNA network covering 201 lncRNAs, 22 miRNAs, and 79 mRNAs was constructed. This study provides a novel perspective on the molecular mechanism of lncRNA in TBI and identifies certain lncRNAs as potential therapeutic targets against TBI.

Single-cell RNA sequencing reveals changes in glioma-associated macrophage polarization and cellular states of malignant gliomas with high AQP4 expression

Glioma is the most common primary central nervous system tumor in adults. Aquaporin-4, as a water channel protein encoded by AQP4 in the brain, is reported to alter its aggregation status to affect plasma membrane dynamics and provide the potential for metastasis of tumor cells and components of the tumor microenvironment. We performed single-cell RNA transcriptome sequencing of 53059 cells from 13 malignant glioma samples and spotted that the expression of AQP4 differed between samples. The same result was observed in the TCGA glioma database, showing poor overall survival and poor response to chemotherapy in AQP4 overexpressed populations. Concomitant with the overexpression of AQP4, genes related to the immune system were also over-expressed, such as CD74, HES1, CALD1, and HEBP2, indicating AQP4 may relate to immune factors of tumor progression. We also found that tumor-associated macrophages tended to polarize toward M2 macrophages in the high AQP4 group. In glioblastoma samples, we examined cell status differences and identified that cell status differs according to AQP4 expression levels. Briefly, our study revealed substantial heterogeneity within malignant gliomas with different AQP4 expression levels, indicating the intricate connection between tumor cells and the tumor immune environment.

Inflammatory Cerebral Amyloid Angiopathy: A Broad Clinical Spectrum.

Cerebral amyloid angiopathy (CAA) is a common central nervous system (CNS) vasculopathy, which in some cases is associated with subacute encephalopathy, seizures, headaches, or strokes due to vascular inflammation directed against vascular amyloid accumulation. The pathological subtypes of inflammatory CAA include CAA-related inflammation (CAAri) with mostly perivascular lymphocytic infiltrates, or amyloid-beta (Aβ)-related angiitis (ABRA) with transmural granulomatous inflammation. CAAri and ABRA probably represent part of the spectrum of CNS vasculopathies, intermediate between CAA and primary CNS vasculitis, and they are closely related to Aβ-related imaging abnormalities and other manifestations of an inflammatory response directed against Aβ in the leptomeninges and cerebral parenchyma. As treatment strategies in Alzheimer's disease shift toward potentially effective antiamyloid immunotherapy, the incidence rate of inflammatory CAA (which is probably an underrecognized condition) is likely to increase. Its clinical features are varied and include subacute encephalopathy, behavioral symptoms, headaches, seizures, and focal neurological deficits, which necessitate a high degree of suspicion for this disorder that often responds to treatment. The recent definition of the typical clinical and radiological syndrome has increased its recognition and may eliminate the need for invasive histological sampling in at least some affected patients. Here we review the pathophysiology, clinical spectrum, and approach to diagnosis, and discuss illustrative cases that highlight the wide range of clinical presentations.

Isocitrate Dehydrogenase (IDH1) and p53 Mutations in Gliomas: A Cross-sectional Study from a Tertiary Care Hospital, Karnataka, India

Introduction: Gliomas, being the most common Central Nervous System (CNS) neoplasms, are broadly divided into astrocytomas, oligodendrogliomas and ependymomas. World Health Organisation (WHO) 2016 criteria incorporated Immunohistochemistry (IHC), molecular diagnostic techniques and histological tumour grading into its diagnostic criteria. Isocitrate Dehydrogenase (IDH1) mutations are commonly seen in young people with good prognostic implications. The detection of Tumor Protein53 (p53) mutations in gliomas and its association with the grade of the tumour can be used as a diagnostic, prognostic and therapeutic tool for better survival in affected individuals. IHC can be used as surrogate markers in detecting the mutational status of IDH1 and p53. Aim: To study the expression of IDH1 and p53 mutations in gliomas and to evaluate its association with known clinicopathological variables. Materials and Methods: This cross-sectional, retrospective, analytical study was conducted in the Department of Pathology at JSSAHER, Mysuru, Karnataka, India. The duration of the study was three years and 11 months, from October 2018 to September 2022. All histopathologically diagnosed glioma cases, who underwent surgery, were appropriately reviewed and graded. IHC was performed for the detection of IDH1mutational status and p53 expression. The tumour was labelled as, IDH1 positive with cytoplasmic staining and p53 positive when nuclear staining was observed in more than 5% of tumour cells. The p53 expression was further quantified in scores as low ≤8 and high &gt;8 score. The associations of clinicopathological variables and the comparison of the scores of p53 mutation across various categories of gliomas were analysed statistically. The data was analysed using Statistical package for Social Sciences (SPSS) version 26.0. Results: The mean age of the study participants was 15.3 years. A total of 35 cases (20 males and 15 females) were analysed. The maximum number of cases was in the age group of 31-40 years (n=13) followed by 41-50 years of age group (n=11). Three of them were seen in age less than 20 years. The male: female ratio was 1.33:1. Out of total cases, 20 cases showed IDH1 positivity, 12 cases showed high p53 expression and six cases demonstrated both, IDH1 positivity and high expression of p53. A statistically significant association (p-value=0.014) was seen between the grade of the tumour and p53 immunoreaction. Conclusion: The present study of the detection of IDH1 and p53 mutations, could provide reliable information for improved tailoring of patient therapy as study revealed that, there was a significant association of p53 expression with the grade of the tumour with low expression in low grade gliomas and high p53 expression in high grade gliomas.

Combination of Caffeic Acid Phenethyl Ester and Crocin Realign Potential Molecular Markers in U87-MG Glioma Cells

Glial tumors are the most common primary malignant central nervous system tumors. They are hard to treat, not only because of the deregulation in multiple pathways but also because they are not contained in a well-defined mass with clear borders. The use of a single therapeutic agent to target gliomas has yielded unsatisfactory results. A combination of molecules targeting multiple pathways may prove to be a better alternative. The effect of caffeic acid phenethyl ester and crocin on the proliferation and death of U87-MG cells over a concentration range was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. A colony formation assay was used to measure the effect of caffeic acid phenethyl ester and crocin on contact inhibition and anchorage independence ability of U87-MG cells. Furthermore, apoptosis in U87-MG cells was analyzed by propidium iodide assay. Real-time polymerase chain reaction and Western blotting were performed to determine the expression level of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen. Caffeic acid phenethyl ester and crocin when used in combination present an anticancer potential for glioma. These molecules, in combination, inhibit proliferation and induce apoptosis in U87-MG glioma cells. Our results provide evidence that combination treatment realigns the expression paradigm of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen in cotreated U87-MG cells. The combination of caffeic acid phenethyl ester and crocin led to inhibition in glioma cell proliferation and might prove to be an effective adjunct to the therapies in vogue.

Genomic markers of recurrence risk in atypical meningioma following gross total resection.

Meningiomas are the most common primary central nervous system (CNS) tumor in adults and CNS World Health Organization grade 2 (atypical) meningiomas show an intermediate risk of recurrence/progression. Molecular parameters are needed to better inform management following gross total resection (GTR). We performed comprehensive genomic analysis of tumor tissue from 63 patients who underwent radiologically confirmed GTR of a primary grade 2 meningioma, including a CLIA-certified target next-generation sequencing panel (n = 61), chromosomal microarray (n = 63), genome-wide methylation profiling (n = 62), H3K27me3 immunohistochemistry (n = 62), and RNA-sequencing (n = 19). Genomic features were correlated with long-term clinical outcomes (median follow-up: 10 years) using Cox proportional hazards regression modeling and published molecular prognostic signatures were evaluated. The presence of specific copy number variants (CNVs), including -1p, -10q, -7p, and -4p, was the strongest predictor of decreased recurrence-free survival (RFS) within our cohort (P < .05). NF2 mutations were frequent (51%) but did not show a significant association with RFS. DNA methylation-based classification assigned tumors to DKFZ Heidelberg benign (52%) or intermediate (47%) meningioma subclasses and was not associated with RFS. H3K27 trimethylation (H3K27me3) was unequivocally lost in 4 tumors, insufficient for RFS analysis. Application of published integrated histologic/molecular grading systems did not improve prediction of recurrence risk over the presence of -1p or -10q alone. CNVs are strong predictors of RFS in grade 2 meningiomas following GTR. Our study supports incorporation of CNV profiling into clinical evaluation to better guide postoperative patient management, which can be readily implemented using existing, clinically validated technologies.

Systemic therapy use for the treatment of meningioma: A systematic review

Purpose: Meningiomas are the most common primary central nervous system tumor. Many studies have investigated systemic therapy agents for treating meningiomas, but no study has systematically evaluated these agents in a comparative or comprehensive manner. Our goal was to investigate the recent systemic therapy agents used to treat meningioma and to compare outcomes such as progression-free survival and overall survival. Methods: A systematic literature review was performed to investigate systemic therapy agents that are being used to treat meningioma tumors. The PubMed database was used for this review and articles published from 7/4/2011 to 7/4/2021 were evaluated. The exclusion criteria were animal and cell line studies, case reports, review articles, articles in a foreign language, and articles not related to meningioma or to systemic therapy agents. Results: 163 articles were initially evaluated. After excluding 152 articles that did not fit the inclusion criteria, 11 articles exploring 14 different systemic therapy agents were included and compared, focusing on the outcomes of progression[1]free survival and overall survival. According to our findings, Bevacizumab has the most promising results as it is associated with reducing peri-tumoral edema and has the highest progression-free survival at six months of 86%. Conclusion: This article evaluated systemic therapy agents used to treat meningioma tumors. Bevacizumab has the most promising results overall. However, further studies are needed to evaluate its efficacy and possible side effects among a larger population of patients with different grades, locations, and responses of the meningioma tumors to Bevacizumab.

Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas.

Background: Glioblastomas are the most common and malignant central nervous system (CNS) tumors that occupied a highly heterogeneous tumor microenvironment (TIME). Long noncoding RNAs (lncRNAs), whose expression can be modified by DNA methylation, are emerging as critical regulators in the immune system. However, knowledge about the epigenetic changes in lncRNAs and their contribution to the immune heterogeneity of glioma is still lacking. Methods: In this study, we integrated paired methylome and transcriptome datasets of glioblastomas and identified 2 robust immune subtypes based on lncRNA methylation features. The immune characteristics of glioma subtypes were compared. Furthermore, immune-related lncRNAs were identified and their relationships with immune evasion were evaluated. Results: Glioma immunophenotypes exhibited distinct immune-related characteristics as well as clinical and epigenetic features. 149 epigenetically regulated (ER) lncRNAs were recognized that possessed inverse variation in epigenetic and transcriptional levels between glioma subtypes. Immune-related lncRNAs were further identified through the investigation of their correlation with immune cell infiltrations and immune-related pathways. In particular, the 'Hot' glioma subtype with higher immunoactivity while a worse survival outcome was found to character immune evasion features. We finally prioritized candidate ER lncRNAs associated with immune evasion markers and response to glioma immunotherapy. Among them, CD109-AS1 and LINC02447 were validated as novel immunoevasive biomarkers for glioma through in vitro experiments. Conclusion: In summary, our study systematically reveals the crosstalk among DNA methylation, lncRNA, and immune regulation in glioblastomas, and will facilitate the development of epigenetic immunotherapy approaches.

Diagnosis of neuroborreliosis in the context of local seroprevalence: A chart review study and a methodological overview.

In neuroborreliosis (NB) serology might objectively differentiate ongoing from past infection when the intrathecal space is involved. The hierarchy of the parallel serum-CSF (cerebrospinal fluid) methods is seldom discussed and remains elusive in daily practice. We compared the efficacy of certain methods and assessed the prevalence of anti-Borrelia antibodies in the local population. We summarized standard two-tier test results in all ELISA-reactive samples of patients with suspected NB (n=152) since 2017 and tested 122 unrelated sera for anti-Borrelia antibodies from central Hungary. The most common central nervous system symptom was a cranial nerve palsy (27.6% of all subjects). CSF was available in 25 cases. A serum-CSF IgG-matched line immunoassay (LIA) detected intrathecal antibody production correctly in 6 of 8 samples when compared to the ELISA-based antibody-index (AI). Among the 122 random sera the prevalence of specific anti-Borrelia IgG antibodies (on LIA, not including anti-p41) were 6.8% above 30 and 10% above 60 years. Our results enable us to assume the predictive values of serological results according to the pretest probability of neuroborreliosis. Our results suggest that recombinant antigen-based two-tier serology from solely the sera might have sufficient positive predictive value to verify NB in young individuals with characteristic anamnestic data in our region. When parallel serum-CSF testing is warranted, AI should have priority. IgG and albumin concentrations in the both serum and the CSF, the potential time of exposure and the nature and duration of symptoms form the bare minimal set of data for conclusive testing.

Microbial signatures of neonatal bacterial meningitis from multiple body sites.

As a common central nervous system infection in newborns, neonatal bacterial meningitis (NBM) can seriously affect their health and growth. However, although metagenomic approaches are being applied in clinical diagnostic practice, there are some limitations for whole metagenome sequencing and amplicon sequencing in handling low microbial biomass samples. Through a newly developed ultra-sensitive metagenomic sequencing method named 2bRAD-M, we investigated the microbial signatures of central nervous system infections in neonates admitted to the neonatal intensive care unit. Particularly, we recruited a total of 23 neonates suspected of having NBM and collected their blood, cerebrospinal fluid, and skin samples for 2bRAD-M sequencing. Then we developed a novel decontamination method (Reads Level Decontamination, RLD) for 2bRAD-M by which we efficiently denoised the sequencing data and found some potential biomarkers that have significantly different relative abundance between 12 patients that were diagnosed as NBM and 11 Non-NBM based on their cerebrospinal fluid (CSF) examination results. Specifically, we discovered 11 and 8 potential biomarkers for NBM in blood and CSF separately and further identified 16 and 35 microbial species that highly correlated with the physiological indicators in blood and CSF. Our study not only provide microbiological evidence to aid in the diagnosis of NBM but also demonstrated the application of an ultra-sensitive metagenomic sequencing method in pathogenesis study.

A study on the safety and tolerability of antiretroviral drugs prescribed in ART center of a rural-based tertiary care hospital

Background: Human immunodeficiency virus (HIV) is a serious health problem worldwide. The mainstay treatment of HIV infected individuals is antiretroviral therapy (ART). Although ART is effective, it has its drawbacks as it is causes various adverse drug reactions (ADRs) which negatively affects patient compliance resulting in treatment failure. Various studies have been conducted in western population to study the adverse effects of ART, but such study in Eastern India is scanty. This study was conducted to fill the void and to help optimize treatment in this area. Aim and Objectives: The aim of the study was to find the incidence and type of ADRs among patients on antiretroviral drugs and to evaluate the severity assessment of the ADRs caused by them. Materials and Methods: Pre-structured case record form was used to collect information regarding demography, disease, treatment, etc., of 188 patients who came to the ART center after taking consent. ADRs were noted on the basis of patient complaints and changes diagnosed by the physician (if any) during routine visit. Descriptive statistical analysis was performed and inference drawn. Results: Most of the subjects followed Tenofovir-Lamivudine-Efavirenz regimen of whom 89% experienced at least one ADR, central nervous system (CNS) being the most affected. Followed by Zidovudine-Lamivudine-Nevirapine regimen of whom 96% presented with at least one ADR where gastrointestinal (GI) side effects were maximum. Common CNS side-effects were dizziness followed by insomnia. Common GI side effects was anorexia followed by nausea and vomiting. Most of them were mild in severity assessment scale. Conclusions: The study shows the ART regimens used by HIV patients and assess the ADRs caused by them. It helped to obtain information regarding demographic factors and disease pattern in this region. Further and more elaborate studies are needed to have proper insight and practical gains in this regard.

PS-R06-4: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME TRIGGERED BY FLUID RETENTION AND HYPERTENSION AFTER STEROID INITIATION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Objectives: Central nervous system (CNS) involvement in antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis is common, with hypertrophic pachymeninges, cerebrovascular events, hypophysitis, or posterior reversible encephalopathy syndrome (PRES) being the most common CNS presentations. Design and Methods: Case report. Results: A 73-year-old Japanese woman presented with a fever and cough. The patient had no relevant medical history. Her c-reactive protein (CRP) level increased to 22.38 mg/dl, and meropenem was initiated; however, her fever and CRP levels did not improve. Furthermore, creatinine level increased from 0.83 to 3.44 mg/dl during hospitalization. She was transferred to our hospital for evaluation of renal function deterioration. Her consciousness level was alert, and her blood pressure was 140/80 mm Hg. A renal biopsy was performed, and histological examination of the kidneys revealed diffuse pauci-immune necrotizing and crescentic glomerulonephritis. Myeloperoxidase (MPO) -ANCA was 2.9 IU/mL and proteinase 3 (PR3) -ANCA was negative. On the basis of these findings, the patient was diagnosed with ANCA-associated vasculitis. On the fourth hospital day, she was treated with 500 mg intravenous methylprednisolone, once daily, for 3 days, followed by oral prednisolone (40 mg; 0.8 mg/kg). Although her fever and CRP levels improved after the initiation of immunosuppressive therapy, she required renal replacement therapy on the eighth hospital day. Rituximab (500 mg) was administered on the ninth hospital day. Her blood pressure subsequently increased, with the systolic blood pressure being 190 mmHg, and consciousness suddenly deteriorated on the 11th hospital day. Head fluid-attenuated inversion-recovery (FLAIR) MRI showed multiple lesions with high signal intensity, and she was diagnosed with PRES. After intravenous administration of nicardipine and fluid removal by hemodialysis, her blood pressure decreased and her consciousness dramatically improved. Conclusion: In addition to the vascular endothelial damage associated with vasculitis itself, steroid therapy, renal failure, elevated blood pressure, and administration of rituximab are related to an increased susceptibility of PRES. In particular, steroid administration increases blood pressure due to fluid retention and can be a risk factor for the development of PRES, suggesting the need for adequate fluid management during steroid administration.

Preoperative surgical risk assessment of meningiomas: a narrative review based on MRI radiomics.

Meningiomas are one of the most common intracranial primary central nervous system tumors. Regardless of the pathological grading and histological subtypes, maximum safe resection is the recommended treatment option for meningiomas. However, considering tumor heterogeneity, surgical treatment options and prognosis often vary greatly among meningiomas. Therefore, an accurate preoperative surgical risk assessment of meningiomas is of great clinical importance as it helps develop surgical treatment strategies and improve patient prognosis. In recent years, an increasing number of studies have proved that magnetic resonance imaging (MRI) radiomics has wide application values in the diagnostic, identification, and prognostic evaluations of brain tumors. The vital importance of MRI radiomics in the surgical risk assessment of meningiomas must be apprehended and emphasized in clinical practice. This narrative review summarizes the current research status of MRI radiomics in the preoperative surgical risk assessment of meningiomas, focusing on the applications of MRI radiomics in preoperative pathological grading, assessment of surrounding tissue invasion, and evaluation of tumor consistency. We further analyze the prospects of MRI radiomics in the preoperative assessment of meningiomas angiogenesis and adhesion with surrounding tissues, while pointing out the current challenges of MRI radiomics research.

Exploring the role of Tibetan medicinal formula Qishiwei Zhenzhu Pills (Ranasampel) against diabetes mellitus-linked cognitive impairment of db/db mice through serum pharmacochemistry and microarray data analysis.

Diabetes cognitive impairment (DCI) is a common diabetic central nervous system disorder that severely affects the quality of life of patients. Qishiwei Zhenzhu Pills (Ranasampel) is a valuable Tibetan medicine formula with the ability to improve cerebral blood vessels, protect nerves and improve learning and memory, which has also been widely verified in clinical and basic research. Currently, the prevention and treatment of DCI are still in the exploratory research stage, and the use of Ranasampel will provide new ideas and insights for its treatment. This study is to explore the absorbed components in serum derived from Ranasampel using serum pharmacochemistry, then identify the potential mechanism of Ranasampel for the treatment of DCI through bioinformatics and microarray data validation. The UPLC-Q-Exactive MS/MS-based serum pharmacochemistry method was conducted to identify the main active components in serum containing Ranasampel. Then, these components were used to predict the possible biological targets of Ranasampel and explore the potential targets in treating DCI by overlapping with differentially expressed genes (DEGs) screened from Gene Expression Omnibus datasets. Afterward, the protein-protein interaction network, enrichment analyses, hub gene identification, and co-expression analysis were used to study the potential mechanism of Ranasampel. Particularly, the hub genes and co-expression transcription factors were further validated using hippocampal expression profiles of db/db mice treated with Ranasampel, while the Morris water-maze test and H&E staining were used to assess the spatial learning and memory behaviors and histopathological changes. Totally, 40 compounds derived from Ranasampel had been identified by serum sample analysis, and 477 genes related to these identified compounds in Ranasampel, 110 overlapping genes were collected by the intersection of Ranasampel target genes and DEGs. Further comprehensive analysis and verification emphasized that the mechanism of Ranasampel treatment of DCI may be related to the improvement of learning and memory function as well as insulin resistance, hyperglycemia-induced neuronal damage, and neuroinflammation. This study provided useful strategies to explore the potential material basis for compound prescriptions such as Ranasampel. These hub genes and common pathways also provided new ideas for further study of therapeutic targets of DCI and the pharmacological mechanism of Ranasampel.

Integrated response analysis of pediatric low-grade gliomas during and after targeted therapy treatment.

Pediatric low-grade gliomas (pLGGs) are the most common central nervous system tumor in children, characterized by RAS/MAPK pathway driver alterations. Genomic advances have facilitated the use of molecular targeted therapies, however, their long-term impact on tumor behavior remains critically unanswered. We performed an IRB-approved, retrospective chart and imaging review of pLGGs treated with off-label targeted therapy at Dana-Farber/Boston Children's from 2010 to 2020. Response analysis was performed for BRAFV600E and BRAF fusion/duplication-driven pLGG subsets. Fifty-five patients were identified (dabrafenib n = 15, everolimus n = 26, trametinib n = 11, and vemurafenib n = 3). Median duration of targeted therapy was 9.48 months (0.12-58.44). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation were 62.1%, 38.2%, and 31.8%, respectively. Mean volumetric change for BRAFV600E mutated pLGG on BRAF inhibitors was -54.11%; median time to best volumetric response was 8.28 months with 9 of 12 (75%) objective RAPNO responses. Median time to largest volume post-treatment was 2.86 months (+13.49%); mean volume by the last follow-up was -14.02%. Mean volumetric change for BRAF fusion/duplication pLGG on trametinib was +7.34%; median time to best volumetric response was 6.71 months with 3 of 7 (43%) objective RAPNO responses. Median time to largest volume post-treatment was 2.38 months (+71.86%); mean volume by the last follow-up was +39.41%. Our integrated analysis suggests variability in response by pLGG molecular subgroup and targeted therapy, as well as the transience of some tumor growth following targeted therapy cessation.

High expression of GSKIP is associated with poor prognosis in meningioma

Meningiomas are the most common extra-axial primary central nervous system tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. glycogen synthesis kinase 3β interaction protein (GSKIP) is an A-kinase anchor protein that has cytosolic scaffolding function and binds to a protein kinase A and glycogen synthesis kinase 3β to modulate different biological processes and malignant tumorigenesis through the Wnt pathway. The purpose of this study was to investigate the relationship between GSKIP expression and the clinico-pathological parameters in meningioma using immunohistochemical staining. We collected samples from 74 patients, from 2008 to 2012, in the Kaohsiung Medical University Hospital that had data on the staging and prognosis of the meningioma pathological section. Chi-square, Kaplan-Meier method, and cox regression were used to analyze the correlation between clinical parameters and immunohistochemistry staining for GSKIP. Following our immunohistochemical score, we found that higher expression of GSKIP was associated with high World Health Organization grading, recurrence, malignant transformation, and reduced overall survival time and recurrence-free survival time in meningioma. GSKIP may be a biomarker of poor prognosis and a target protein for therapy in meningioma.

Current studies and future directions for medulloblastoma: A review from the pacific pediatric neuro-oncology consortium (PNOC) disease working group

Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood, comprising a heterogenous group of tumors each with distinct biology, clinical behavior, and prognosis. Long-term survival remains unacceptable, and those who do survive face high late mortality risk, new chronic treatment-related medical conditions, neurocognitive impairments, and poor health-related quality of life. Up-front treatment strategies now integrate molecular subgrouping with standard clinico-radiological factors to more actually risk stratify newly-diagnosed patients. To what extent this new stratification will lead to improvements in treatment outcome will be determined in the coming years. In parallel, discovery and appreciation for medulloblastoma's inter- and intra-tumoral heterogeneity continues growing. Clinical trials treating relapsed disease now encompass precision medicine, epigenetic modification, and immune therapy approaches. The Pacific Pediatric Neuro-Oncology (PNOC) Medulloblastoma Working Group is committed to developing clinical trials based on these evolving therapeutic strategies and supports translational efforts by PNOC researchers and the multi-stakeholder medulloblastoma community at large.