GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects.

GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aß) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear. This study aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer's disease (3xTg-AD) mice. GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta1-42 (Aß1-42), phosphorylated tau, volume of dentate gyrus, ß-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins. GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aß1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated ß-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins. We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.

GV1001 modulates neuroinflammation and improves memory and behavior through the activation of gonadotropin-releasing hormone receptors in a triple transgenic Alzheimer's disease mouse model.

GV1001 protects neural cells from amyloid-ß (Aß) toxicity and other stressors in in vitro studies and demonstrates clinically beneficial effects in patients with moderate to severe Alzheimer's disease (AD). Here, we investigated the protective effects and mechanism of action of GV1001 in triple transgenic AD (3xTg-AD) mice. We found that GV1001 improved memory and cognition in middle- and old-aged 3xTg-AD mice. Additionally, it reduced Aß oligomer and phospho-tau (Ser202 and Thr205) levels in the brain, and mitigated neuroinflammation by promoting a neuroprotective microglial and astrocyte phenotype while diminishing the neurotoxic ones. In vitro, GV1001 bound to gonadotropin releasing hormone receptors (GnRHRs) with high affinity. Levels of cyclic adenosine monophosphate, a direct downstream effector of activated GnRHRs, increased after GV1001 treatment. Furthermore, inhibition of GnRHRs blocked GV1001-induced effects. Thus, GV1001 might improve cognitive and memory functions of 3xTg-AD mice by suppressing neuroinflammation and reducing Aß oligomers levels and phospho-tau by activating GnRHRs and their downstream signaling pathways.

The genes significantly associated with an improved prognosis and long-term survival of glioblastoma.

BACKGROUND AND PURPOSE: Glioblastoma multiforme (GBM) is the most devastating brain tumor with less than 5% of patients surviving 5 years following diagnosis. Many studies have focused on the genetics of GBM with the aim of improving the prognosis of GBM patients. We investigated specific genes whose expressions are significantly related to both the length of the overall survival and the progression-free survival in patients with GBM. METHODS: We obtained data for 12,042 gene mRNA expressions in 525 GBM tissues from the Cancer Genome Atlas (TCGA) database. Among those genes, we identified independent genes significantly associated with the prognosis of GBM. Receiver operating characteristic (ROC) curve analysis was performed to determine the genes significant for predicting the long-term survival of patients with GBM. Bioinformatics analysis was also performed for the significant genes. RESULTS: We identified 33 independent genes whose expressions were significantly associated with the prognosis of 525 patients with GBM. Among them, the expressions of five genes were independently associated with an improved prognosis of GBM, and the expressions of 28 genes were independently related to a poorer prognosis of GBM. The expressions of the ADAM22, ATP5C1, RAC3, SHANK1, AEBP1, C1RL, CHL1, CHST2, EFEMP2, and PGCP genes were either positively or negatively related to the long-term survival of GBM patients. CONCLUSIONS: Using a large-scale and open database, we found genes significantly associated with both the prognosis and long-term survival of patients with GBM. We believe that our findings may contribute to improving the understanding of the mechanisms underlying GBM.

Changes in Disc Height as a Prognostic Factor in Patients Undergoing Microscopic Discectomy.

Objective: Some patients with disc herniation who underwent discectomy complain of back pain after surgery and are unsatisfied with the surgical results. This study aimed to evaluate the relationship between preoperative disc height (DH), postoperative DH, and pain score 12 months after surgery in patients who underwent microdiscectomy for herniated lumbar disc (HLD). Methods: This study enrolled patients who underwent microdiscectomy at a medical center between January 2012 and December 2020. Patients with X-ray or computed tomography and pain score assessment (visual analog scale score) prior to surgery, immediately post-op, and at 1, 6, and 12 months after surgery were included. The DH index (DHI) was defined as DH/overlying vertebral width. The DH ratio was defined as the postoperative DH/preoperative DH. Simple linear regression and multivariate linear regression analyses were applied to assess the correlation between DHs and leg pain scores 12 months after surgery. Results: A total of 118 patients who underwent microdiscectomy were included. DH decreased up to 12 months after surgery The DH ratio at 1, 6, and 12 months after discectomy showed a significant positive correlation with the pain scores at 12 months after discectomy (1 month: p=0.045, B=0.52; 6 months: p=0.008, B=0.78; 12 months: p=0.005, B=0.69). Multivariate linear regression analysis revealed that the level of surgery, sex, age, and BMI had no significant relationship with back pain scores after 12 months. Conclusion: In patients who underwent microdiscectomy, the DH ratios at 1, 6, and 12 months after surgery were prognostic factors for back pain scores at 12 months after surgery. Aggressive discectomy is recommended for lower postoperative DH ratios and VAS scores, leading to improved patient satisfaction.

Risk Factors for Prevertebral Soft Tissue Swelling Following Single-Level Anterior Cervical Spine Surgery.

OBJECTIVE: Anterior cervical spine surgery (ACSS) is a common surgical procedure used to treat cervical spinal degenerative diseases. One of the complications associated with ACSS is prevertebral soft tissue swelling (PSTS), which can result in airway obstruction, dysphagia, and other adverse outcomes. This study aims to investigate the correlation between various cervical sagittal parameters and PSTS following single-level ACSS, as well as to identify independent risk factors for PSTS. METHODS: A retrospective study conducted at a single institution. The study population included all patients who underwent single-level ACSS between January 2014 and December 2022. Patients with a history of cervical spine surgery or trauma were excluded from the study. The presence and severity of PSTS was assessed by reviewing pre- and postoperative imaging studies. The potential risk factors for PSTS that were examined include patient age, sex, body mass index, tobacco use, comorbidities, serum albumin levels, operative time, implant type, implanted level, and various cervical spine sagittal parameters. Multivariate linear regression analysis was performed to identify the independent risk factors for PSTS. RESULTS: A total of 62 consecutive patients who underwent single-level ACSS over a 8-year period at a single institution were enrolled in this study. Only preoperative segmental angle showed positive correlation with PSTS among various cervical spine sagittal parameters (r=0.36, p=0.005). Artificial disc replacement showed a negative correlation with PSTS (ß=-0.38, p=0.002), whereas the use of demineralized bone matrix (DBM) had a positive impact on PSTS (ß=0.33, p=0.009). We found that male sex, lower preoperative serum albumin, and implantation of upper cervical level (above C5) were independent predictors for PSTS after single-level ACSS (ß=1.21; 95% confidence interval [CI], 0.27 to 2.15; p=0.012; ß=-1.63; 95% CI, -2.91 to -0.34; p=0.014; ß=1.44; 95% CI, 0.38 to 2.49; p=0.008, respectively). CONCLUSION: Our study identified male sex, lower preoperative serum albumin levels, and upper cervical level involvement as independent risk factors for PSTS after single-level ACSS. These findings can help clinicians monitor high-risk patients and take preventive measures to reduce complications. Further research with larger sample sizes and prospective designs is needed to validate these findings.

DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas.

PURPOSE: We previously reported that expression of dickkopf-3 (DKK3), which is involved in the Wnt/ß-catenin pathway, is significantly associated with prognosis in patients with glioblastoma multiforme (GBM). The aim of this study was to compare the association of DKK3 with other Wnt/ß-catenin pathway-related genes and immune responses between lower grade glioma (LGG) and GBM. METHODS: We obtained the clinicopathological data of 515 patients with LGG (World Health Organization [WHO] grade II and III glioma) and 525 patients with GBM from the Cancer Genome Atlas (TCGA) database. We performed Pearson's correlation analysis to investigate the relationships between Wnt/ß-catenin-related gene expression in LGG and GBM. Linear regression analysis was performed to identify the association between DKK3 expression and immune cell fractions in all grade II to IV gliomas. RESULTS: A total of 1,040 patients with WHO grade II to IV gliomas were included in the study. As the grade of glioma increased, DKK3 showed a tendency to be more strongly positively correlated with the expression of other Wnt/ß-catenin pathway-related genes. DKK3 was not associated with immunosuppression in LGG but was associated with downregulation of immune responses in GBM. We hypothesized that the role of DKK3 in the Wnt/ß-catenin pathway might be different between LGG and GBM. CONCLUSION: According to our findings, DKK3 expression had a weak effect on LGG but a significant effect on immunosuppression and poor prognosis in GBM. Therefore, DKK3 expression seems to play different roles, through the Wnt/ß-catenin pathway, between LGG and GBM.

Predicting cognitive stage transition using p-tau181, Centiloid, and other measures.

BACKGROUND: A combination of plasma phospho-tau (p-tau), amyloid beta (Aß)-positron emission tomography (PET), brain magnetic resonance imaging, cognitive function tests, and other biomarkers might predict future cognitive decline. This study aimed to investigate the efficacy of combining these biomarkers in predicting future cognitive stage transitions within 3 years. METHODS: Among the participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE-V) study, 49 mild cognitive impairment (MCI) and 113 cognitively unimpaired (CU) participants with Aß-PET and brain imaging data were analyzed. RESULTS: Older age, increased plasma p-tau181, Aß-PET positivity, and decreased semantic fluency were independently associated with cognitive stage transitions. Combining age, p-tau181, the Centiloid scale, semantic fluency, and hippocampal volume produced high predictive value in predicting future cognitive stage transition (area under the curve = 0.879). CONCLUSIONS: Plasma p-tau181 and Centiloid scale alone or in combination with other biomarkers, might predict future cognitive stage transition in non-dementia patients. HIGHLIGHTS: -Plasma p-tau181 and Centiloid scale might predict future cognitive stage transition. -Combining them or adding other biomarkers increased the predictive value. -Factors that independently associated with cognitive stage transition were demonstrated.

Relationship between telomere shortening and early subjective depressive symptoms and cognitive complaints in older adults.

Telomere length (TL) has been reported to be associated with depression and cognitive impairment in elderly. Early detection of depression and cognitive impairment is important to delay disease progression. Therefore, we aimed to identify whether TL is associated with early subjective depressive symptoms and cognitive complaints among healthy elderly subjects. This study was a multicenter, outcome assessor-blinded, 24-week, randomized controlled trial (RCT). Measurement of questionnaire and physical activity scores and blood sample analyses were performed at baseline and after six months of follow-up in all study participants. Linear regression analyses were performed to identify whether early subjective depressive symptoms, cognitive complaints, and several blood biomarkers are associated with TL. Altogether, 137 relatively healthy elderly individuals (60-79 years old) were enrolled in this prospective RCT. We observed an approximate decrease of 0.06 and 0.11-0.14 kbps of TL per one point increase in the geriatric depression scale and cognitive complaint interview scores, respectively, at baseline and after six months of follow-up. We also found an approximate decrease of 0.08-0.09 kbps of TL per one point increase in interleukin (IL)-6 levels at baseline and after six months of follow-up. Our study showed that both early subjective depressive symptoms and cognitive complaints were associated with a relatively shorter TL in relatively healthy elderly individuals. In addition, based on our findings, we believe that IL-6 plays an important role in the relationship between shortening TL and early subjective depressive symptoms and cognitive complaints.

Identification of genes from ten oncogenic pathways associated with mortality and disease progression in glioblastoma.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with an extremely poor prognosis. The Cancer Genome Atlas (TCGA) database has been used to confirm the roles played by 10 canonical oncogenic signaling pathways in various cancers. The purpose of this study was to evaluate the expression of genes in these 10 canonical oncogenic signaling pathways, which are significantly related to mortality and disease progression in GBM patients. Clinicopathological information and mRNA expression data of 525 patients with GBM were obtained from TCGA database. Gene sets related to the 10 oncogenic signaling pathways were investigated via Gene Set Enrichment Analysis. Multivariate Cox regression analysis was performed for all the genes significantly associated with mortality and disease progression for each oncogenic signaling pathway in GBM patients. We found 12 independent genes from the 10 oncogenic signaling pathways that were significantly related to mortality and disease progression in GBM patients. Considering the roles of these 12 significant genes in cancer, we suggest possible mechanisms affecting the prognosis of GBM. We also observed that the expression of 6 of the genes significantly associated with a poor prognosis of GBM, showed negative correlations with CD8+ T-cells in GBM tissue. Using a large-scale open database, we identified 12 genes belonging to 10 well-known oncogenic canonical pathways, which were significantly associated with mortality and disease progression in patients with GBM. We believe that our findings will contribute to a better understanding of the mechanisms underlying the pathophysiology of GBM in the future.

High DKK3 expression related to immunosuppression was associated with poor prognosis in glioblastoma: machine learning approach.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive malignant primary brain tumor. Wnt/ß-catenin is known to be related to GBM stemness. Cancer stem cells induce immunosuppressive and treatment resistance in GBM. We hypothesized that Wnt/ß-catenin-related genes with immunosuppression could be related to the prognosis in patients with GBM. METHODS: We obtained the clinicopathological data of 525 patients with GBM from the brain cancer gene database. The fraction of tumor-infiltrating immune cells was evaluated using in silico flow cytometry. Among gene sets of Wnt/ß-catenin pathway, Dickkopf-3 (DKK3) gene related to the immunosuppressive response was found using machine learning. We performed gene set enrichment analysis (GSEA), network-based analysis, survival analysis and in vitro drug screening assays based on Dickkopf-3 (DKK3) expression. RESULTS: In analyses of 31 genes related to Wnt/ß-catenin signaling, high DKK3 expression was negatively correlated with increased antitumoral immunity, especially CD8 + and CD4 + T cells, in patients with GBM. High DKK3 expression was correlated with poor survival and disease progression in patients with GBM. In pathway-based network analysis, DKK3 was directly linked to the THY1 gene, a tumor suppressor gene. Through in vitro drug screening, we identified navitoclax as an agent with potent activity against GBM cell lines with high DKK3 expression. CONCLUSIONS: These results suggest that high DKK3 expression could be a therapeutic target in GBM. The results of the present study could contribute to the design of future experimental research and drug development programs for GBM.

Efficacy of Cytokine-Induced Killer Cell Immunotherapy for Patients With Pathologically Pure Glioblastoma.

The most common malignant central nervous system tumor is glioblastoma multiforme (GBM). Cytokine-induced killer (CIK) cell therapy is a promising type of adoptive cell immunotherapy for various cancers. We previously conducted a randomized clinical trial on CIK cell therapy in patients with GBM. The aim of this study was to evaluate the efficacy of CIK immunotherapy for patients with pathologically pure GBM, using data from our previous randomized clinical trial. The difference between overall survival (OS) and progression-free survival (PFS) according to CIK immunotherapy was analyzed using the Kaplan-Meier method. Hazard ratios were calculated using univariate and multivariate Cox regression analyses to determine whether CIK cell immunotherapy was independently associated with higher OS and PFS in patients with pure GBM. A total of 156 eligible patients were included in the modified intention-to-treat (mITT) population. We confirmed that 125 (80.1%) GBM samples were pure GBM tumors without the presence of other types of tumors. For patients with pure GBM, Kaplan-Meier analysis showed no significant difference in OS between the CIK cell treatment and control groups. However, multivariate Cox regression demonstrated CIK cell immunotherapy as an independent predictor of greater OS (hazard ratio, 0.59; 95% CI, 0.36-0.97; p = 0.038) and PFS (hazard ratio, 0.55; 95% CI, 0.36-0.84; p = 0.001) in patients with pathologically pure GBM in the mITT population. This study showed that CIK cell immunotherapy combined with conventional temozolomide chemoradiotherapy could prolong OS and PFS in patients with newly diagnosed pathologically pure GBM, with no significant adverse events related to treatment. However, unlike the results of multivariate Cox analysis, no statistical significance of CIK cell immunotherapy in OS in Kaplan-Meier analysis raises a question. Further studies are required to validate these results.

Association between sleep parameters and longitudinal shortening of telomere length.

BACKGROUND: The relationship between sleep parameters and longitudinal shortening of telomere length is unclear. This study aimed to investigate the relationship between sleep parameters and the shortening of leukocyte telomere length (LTL) over a year. METHODS: Among the participants in the validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, participants who measured both baseline and follow-up (two years later) of LTL were analyzed. They were dichotomized according to the degree of LTL attrition over two years. Clinical characteristics were compared between the faster and slower LTL shortening groups (cut-off points: -0.710 kbp, n = 119 each). Multivariable logistic regression analyses were performed to determine independent relationships between faster shortening of LTL length and sleep parameters. RESULTS: A total of 238 participants, aged 55-88 years, were included. Participants with faster LTL shortening had a shorter duration of sleep (P = 0.013) and longer sleep latency (P = 0.007). Among the components of the PSQI, subjective measures of sleep quality, sleep latency, sleep duration, and sleep efficiency were significantly worse in participants with faster LTL shortening. Multivariate logistic regression analysis showed that sleep duration (per hour, OR = 0.831, 95% CI = 0.698-0.989), sleep latency (per minute, OR = 1.013, 95% CI = 1.002-1.024), global PSQI score (OR = 1.134, 95% CI = 1.040-1.236), shortest sleep duration (OR = 5.173, 95% CI = 1.563-17.126), and lowest sleep efficiency (OR = 7.351, 95% CI = 1.943-27.946) were independently associated with faster LTL shortening. CONCLUSIONS: Poor sleep quality, specifically short sleep duration, long sleep latency, and low sleep efficiency were associated with faster longitudinal shortening of LTL.

Current Immunotherapeutic Approaches for Malignant Gliomas.

Glioblastoma is the most common malignant central nervous system (CNS) tumor (48.3%), with a median survival of only about 14.6 months. Although the CNS is an immune-privileged site, activated T cells can cross the blood-brain barrier. The recent successes of several immunotherapies for various cancers have drawn interest in immunotherapy for treatment of malignant glioma. There have been extensive attempts to evaluate the efficiency of immunotherapy against malignant glioma. Passive immunotherapy for malignant glioma includes monoclonal antibody-mediated immunotherapy, cytokine-mediated therapy, and adoptive cell transfer, also known as chimeric antigen receptor T cell treatment. On the other hand, active immunotherapy, which stimulates the patient's adaptive immune system against specific tumor-associated antigens, includes cancer vaccines that are divided into peptide vaccines and cell-based vaccines. In addition, there is immune checkpoint blockade therapy, which increases the efficiency of immunotherapy by reducing the resistance of malignant glioma to immunotherapy. Despite centuries of efforts, immunotherapeutic successes for malignant glioma remain limited. However, many clinical trials of adoptive cell transfer immunotherapy on malignant glioma are ongoing, and the outcomes are eagerly awaited. In addition, although there are still several obstacles, current clinical trials using personalized neoantigen-based dendritic cell vaccines offer new hope to glioblastoma patients. Furthermore, immune checkpoint targeted therapy is expected to decipher the mechanism of immunotherapy resistance in malignant glioma in the near future. More studies are needed to increase the efficacy of immunotherapy in malignant glioma. We hope that immunotherapy will become a new treatment of malignant glioma.

The Osteoporotic Condition as a Predictive Factor for Hemorrhagic Transformation in Acute Cardioembolic Stroke.

OBJECTIVE: Hemorrhagic transformation (HT) can be occurred after acute cerebral infarction. HT can worse symptoms in severe cases and adversely affect long-term prognosis. As bone and vascular smooth muscle are composed of type 1 collagen, we aimed to identify a potential relationship between bone mineral density (BMD) and HT after acute cardioembolic stroke. METHODS: As an indicator of BMD, we used mean frontal skull Hounsfield unit (HU) values on brain computed tomography (CT). Multivariative hazard ratios were calculated using Cox regression analysis to identify whether the osteoporotic condition was an independent predictor of HT after acute cardioembolic stroke. RESULTS: This 11-year analysis enrolled 506 patients who diagnosed as acute cardioembolic infarction. The first tertile of skull HU value was an independent predictor of HT development compared to the third tertile (hazard ratio, 2.12; 95% confidence interval, 1.13-3.98; p=0.020). We observed no interactions between age and skull HU with respect to HT statistically. CONCLUSION: The results of this study revealed an association between osteoporotic conditions and HT development after acute cardioembolic stroke. A convenient method to measure the cancellous bone HU value of the frontal skull using brain CT images may be useful for predicting HT in patients with acute cerebral infarction.

Effect of osteoporotic conditions on the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma.

PURPOSE: Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma. METHODS: A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation. RESULTS: A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11-24.46; p = 0.037). CONCLUSIONS: Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study's small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made.

Effect of Possible Osteoporosis on Parenchymal-Type Hemorrhagic Transformation in Patients with Cardioembolic Stroke.

BACKGROUND: hemorrhagic transformation (HT) is a frequent complication of ischemic stroke, and parenchymal hematoma (PH)-type HT has been shown to correlate with symptomatic deterioration. Because both bone and vascular smooth muscle cells are composed of type 1 collagen, we hypothesized that the integrity of blood vessels around the infarction area might be more damaged in osteoporotic conditions after a cardioembolic stroke. METHODS: we measured frontal skull Hounsfield unit (HU) values on brain CT images from cardioembolic stroke patients. We conducted a receiver operating characteristic curve analysis in a large sample registry to identify the optimal HU threshold for predicting osteopenia and osteoporosis. Hazard ratios were estimated using a Cox regression analysis to identify whether osteoporotic conditions were an independent predictor of PH-type HT in patients with cardioembolic stroke. RESULTS: altogether, 600 consecutive patients (>18 years old) with cardioembolic stroke were enrolled over a 12-year period at our hospital. The infarction volume and hypothetical osteoporosis were independent predictive factors for PH-type HT development in patients with cardioembolic stroke. In the male group, hypothetical osteoporosis was an independent predictor for PH-type HT development after cardioembolic stroke (hazard ratio, 4.12; 95% confidence interval, 1.40-12.10; p = 0.010). CONCLUSIONS: our study suggests an association between possible osteoporosis and the development of PH-type HT in patients with cardioembolic stroke. Our findings could help to predict PH-type HT by providing a convenient method for measuring the HU value using brain CT images.

Association between tumor size and peritumoral brain edema in patients with convexity and parasagittal meningiomas.

BACKGROUND AND PURPOSE: Peritumoral brain edema (PTBE) is a common complication in meningioma and disruption of the tumor-brain barrier in meningioma is crucial for PTBE formation. To evaluate the association between meningioma size and PTBE, we measured meningioma volumes using the 3D slicer in patients with convexity and parasagittal meningiomas. METHODS: Receiver operating characteristic curve analysis was used to determine the optimal cut-off meningioma volume values for predicting PTBE occurrence. Logistic regressions were used to estimate the odds ratios for PTBE occurrence in patients with convexity and parasagittal meningiomas according to several predictive factors. RESULTS: A total of 205 convexity or parasagittal meningioma patients with no other brain disease who underwent one or more contrast-enhanced brain MRIs were enrolled in this 10-year analysis in two hospitals. The optimal cut-off meningioma volume value for prediction of PTBE in all study patients was 13.953 cc (sensitivity = 76.1%; specificity = 92.5%). If a meningioma is assumed to be a complete sphere, 13.953 cc is about 2.987 cm in diameter. CONCLUSIONS: Our study suggests a cut-off value of 3 cm meningioma diameter for prediction of PTBE in patients with convexity and parasagittal meningiomas. We believe that we have revealed why the meningioma diameter of 3 cm is clinically meaningful.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1.

BACKGROUND: There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As 'diffuse midline glioma' was recently defined, and there was no international guideline, trials and guidelines of 'diffuse intrinsic pontine glioma' or 'brain stem glioma' were thoroughly reviewed first. RESULTS: The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma's protocol is recommended. CONCLUSION: The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1.

BACKGROUND: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. METHODS: The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. RESULTS: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. CONCLUSION: The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

Effect of Osteoporotic Condition on Ventriculomegaly and Shunt-Dependent Hydrocephalus After Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Hydrocephalus is a common complication in aneurysmal rupture subarachnoid hemorrhage (SAH). As both the bone and arachnoid trabeculae are composed of type 1 collagen, we identified the possible relationship between bone mineral density and ventriculomegaly and shunt-dependent hydrocephalus (SDHC) development after aneurysmal rupture SAH in younger patients. METHODS: We measured frontal skull Hounsfield unit (HU) values on brain computed tomography upon admission, and mean frontal skull HU values were used instead of T-score value. Hazard ratios were calculated using Cox regression analysis to identify whether osteoporotic condition is an independent predictor for ventriculomegaly and SDHC after surgical clipping for SAH in younger patients. RESULTS: Altogether, 412 patients (≤65 years) who underwent surgical clipping for primary spontaneous SAH from a ruptured aneurysm were enrolled in this 11-year analysis in 2 hospitals. We observed that the first tertile group of skull HU was an independent predictor of SDHC after SAH compared with the third tertile of skull HU values (hazard ratio, 2.55 [95% CI, 1.25-5.20]; P=0.010). There were no significant interactions between age and skull HU with respect to ventriculomegaly and SDHC in younger patients. CONCLUSIONS: Our study suggests a relationship between possible osteoporotic conditions and ventriculomegaly and SDHC development after SAH in younger patients. Our findings may be useful in predicting hydrocephalus in young SAH patients using a convenient method of measuring skull HU value on brain computed tomography upon admission.