Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

Advanced T and Natural Killer Cell Therapy for Glioblastoma.

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the bloodbrain- barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versushost disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

Endoscopic Endonasal Optic Nerve Decompression in a Patient With Invasive Fungal Sinusitis Invasion Into the Orbital Apex: Intraoperative Video and Literature Review.

Invasive fungal sinusitis (IFS) is rare but potentially fatal in immunocompromised patients. Orbital extension of IFS can cause visual loss or ophthalmoplegia, and the rate of recovery of visual acuity can be low even after treatment with antifungal agents and sinus surgery. In this case, optic nerve decompression with the endoscopic endonasal approach was successful for the treatment of visual loss in a patient with IFS with orbital apex extension. The authors describe the recovery of visual acuity after optic nerve decompression in a patient with IFS who had exhibited visual loss caused by invasion into the orbital apex. The authors also provide an intraoperative video and literature review.

Utilizing a Novel Pituitary Retractor for Early Descent of the Diaphragma Sellae during Endoscopic Transsphenoidal Pituitary Surgery.

OBJECTIVE: Early descent of the diaphragm sellae (DS) during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary macroadenoma surgery is occasionally a troublesome event by blocking the surgical field. Here we introduce an alternative technique with the new pituitary retractor and present our clinical experiences. METHODS: We designed a simple and rigid pituitary retractor with the least space occupation in the nasal cavity to be compatible in EETS. The pituitary retractor was held by external holder system to support the herniated DS stably. We retrospectively reviewed a clinical 22 cases of pituitary macroadenomas underwent EETS using the pituitary retractor. RESULTS: The pituitary retractor stably pushed up the herniated DS in all cases, and the surgeon proceeded the procedure with bimanual maneuver. The pituitary retractor was helpful to remove tumors around the medial cavernous sinus and behind the DS in 16 and seven cases, respectively. In four cases, the meticulous hemostasis was completed with the direct visualization by the DS elevation with this retractor. Gross total tumor resection was performed in 20/22 patients (91%). The impaired visual function and hypopituitarism were improved in 18/20 (90%) and 7/14 (50%) patients after surgery, respectively. There was no complication related with the pituitary retractor. CONCLUSION: During EETS for pituitary macroadenomas, the novel pituitary retractor reported in this study is a very useful technique when the herniated DS block the surgical field and bimanual maneuver. This pituitary retractor can help to result in the excellent surgical outcomes with minimal morbidity.

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.

Evaluation of 3-Dimensional Exoscopes in Brain Tumor Surgery.

OBJECTIVE: Though the operating microscope (OM) has been the standard optical system in neurosurgery, a new technology called three-dimensional (3D) exoscope has emerged as an alternative. Herein, two types of 3D exoscopes for brain tumor surgery are presented. In addition, the advantages and limitations compared with the OM are discussed. METHODS: In the present study, 3D exoscope VOMS-100 or VITOM 3D was used in 11 patients with brain tumor who underwent surgical resection; the Kinevo 900 OM was used only in emergency. After completion of all surgeries, the participants were surveyed with a questionnaire regarding video image quality on the display monitor, handling of equipment, ergonomics, educational usefulness, 3D glasses, and expectation as a substitute for the OM. RESULTS: Among 11 patients, nine patients underwent neurosurgical resection with only 3D exoscope; however, two patients required additional aid with the OM due to difficulty in hemostasis. Regarding video image quality, VITOM 3D was mostly equivalent to the OM, but VOMS-100 was not. However, both 3D exoscopes showed advantages in accessibility of instruments in the surgical field and occupied less space in the operating theater. Differences in ergonomics and educational usefulness between the exoscopes were not reported. Respondents did not experience discomfort in wearing 3D glasses and thought the exoscopes could be currently, and in the future, used as a substitute for the OM. CONCLUSION: Although many neurosurgeons are not familiar with 3D exoscopes, they have advantages compared with the OM and similar image quality. Exoscopes could be a substitute for OM in the future if some limitations are overcome.

High-dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15-year multicenter experience.

AIM: Primary central nervous system lymphoma (PCNSL) is rare disease and shows poor prognosis although methotrexate-based chemotherapy is used. Here, we present our experiences with high-dose methotrexate (HD-MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival. METHODS: PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD-MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8 g/m2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy. RESULTS: A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty-six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty-one patients with recurrence or progression following HD-MTX underwent second-line treatment. Progression-free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression-free survival and overall survival (P < 0.05). CONCLUSION: MTX-monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non-CR responders to induction chemotherapy.

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas.

BACKGROUND/AIM: Glioblastoma is the most malignant form of astrocytoma. The purpose of this study was to analyze the genetic characteristics of primary and recurrent glioblastomas using targeted sequencing and investigate the differences in mutational profiles between the locations of tumor recurrence. MATERIALS AND METHODS: Fourteen glioblastoma patients who developed local (n=10) or distal (n=4) recurrence were included in the study. Targeted sequencing analysis was performed using the primary (n=14) and corresponding recurrent (n=14) tumor tissue samples. RESULTS: The local and distal recurrence groups showed different genetic evolutionary patterns. Most of the locally recurrent glioblastomas demonstrated concordant mutational profiles between the primary and recurrent tumors, suggesting a linear evolution. In contrast, all cases of distally recurrent glioblastomas showed changes in mutational profiles with newly acquired mutations when compared to the corresponding primary tumors, suggesting a branching evolution. CONCLUSION: Locally and distally recurrent glioblastomas exhibit different evolutionary patterns.

A National Consensus Survey for Current Practice in Brain Tumor Management I: Antiepileptic Drug and Steroid Usage.

BACKGROUND: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors. As part I of the survey, the aim of this study is to evaluate national patterns of clinical practice about antiepileptic drug (AED) and steroid usage for management of brain tumors. METHODS: A web-based survey was sent to all members of the KSNO by email. The survey included 9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questions were developed by consensus of the Guideline Working Group. RESULTS: The overall response rate was 12.8% (54/423). Regarding AED usage, the majority of respondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperative period. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naïve patients, and others prescribed AED as the case may be. The duration of AED prophylaxis showed wide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) was the most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents use steroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoral edema (90.9%) was considered as the most important factor determining steroid usage followed by degree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue the steroids within a week after surgery if there are no specific medical conditions, while 7.3% preferred slow tapering up to a month after surgery. CONCLUSION: The survey demonstrated the prevailing practice patterns on AED and steroid usage in neuro-oncologic field among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain tumor patients.

A National Consensus Survey for Current Practice in Brain Tumor Management II: Diffuse Midline Glioma and Meningioma.

BACKGROUND: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors. As part II of the survey, the aim of this study is to evaluate the national patterns of clinical practice for patients with diffuse midline glioma and meningioma. METHODS: A web-based survey was sent to all members of the KSNO by email. The survey included 4 questions of diffuse midline glioma and 6 questions of meningioma (including 2 case scenarios). All questions were developed by consensus of the Guideline Working Group. RESULTS: In the survey about diffuse midline glioma, 76% respondents performed histologic confirmation to identify H3K27M mutation on immunohistochemical staining or sequencing methods. For treatment of diffuse midline glioma, respondents preferred concurrent chemoradiotherapy with temozolomide (TMZ) and adjuvant TMZ (63.8%) than radiotherapy alone (34.0%). In the survey about meningioma, respondents prefer wait-and-see policy for the asymptomatic small meningioma without peritumoral edema. However, a greater number of respondents had chosen surgical resection as the first choice for all large size meningiomas without exception, and small size meningiomas with either peritumoral edema or eloquent location. There was no single opinion with major consensus on long-term follow-up plans for asymptomatic meningioma with observation policy. As many as 68.1% of respondents answered that they would not add any adjuvant therapies for World Health Organization grade II meningiomas if the tumor was totally resected including dura. CONCLUSION: The survey demonstrates the prevailing clinical practice patterns for patients with diffuse midline glioma and meningioma among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of diffuse midline glioma and meningioma.

A National Consensus Survey for Current Practice in Brain Tumor Management III: Brain Metastasis and Primary Central Nervous System Lymphoma.

BACKGROUND: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted the nationwide questionnaire survey for diverse queries facing to treat patients with brain tumor. As part III of the survey, the aim of this study is to evaluate the national patterns of clinical practice for patients with brain metastasis and primary central nervous system lymphoma (PCNSL). METHODS: A web-based survey was sent to all members of the KSNO by email. The survey included 7 questions of brain metastasis and 5 questions of PCNSL, focused on the management strategies in specific situations. All questions were developed by consensus of the Guideline Working Group. RESULTS: In the survey about brain metastasis, respondents preferred surgical resection with adjuvant treatment for patients with a surgically accessible single brain metastatic lesion less than 3 cm in size without extracranial systemic lesions. However, most respondents considered radiosurgery for surgically inaccessible lesions. As the preferred treatment of multiple brain metastases according to the number of brain lesions, respondents tended to choose radiotherapy with increasing number of lesions. Radiosurgery was mostly chosen for the brain metastases of less than or equal to 4. In the survey about PCNSL, a half of respondents choose high-dose methotrexate-based polychemotherapy as the first-line induction therapy for PCNSL. The consolidation and salvage therapy showed a little variation among respondents. For PCNSL patients with cerebrospinal fluid dissemination, intrathecal chemotherapy was most preferred. CONCLUSION: The survey demonstrates the prevailing clinical practice patterns for patients with brain metastasis and PCNSL among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain metastasis and PCNSL.

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade III Cerebral Gliomas in Adults: Version 2019.01.

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.

The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01.

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.

Endoscopic Endonasal Transpterygoid Approach Using Pedicled Nasoseptal Flap for Petrous Apex Cholesterol Granuloma With Intraoperative Video.

With the development of minimally invasive endoscopic surgery and image-guided navigation systems, the endoscopic endonasal approach to petrous apex lesions has become more favorable. In this case, a petrous apex cholesterol granuloma was successfully treated with an endoscopic endonasal transpterygoid approach. A navigation system was used, and a contralateral nasoseptal flap and silicone tube stent were applied to maintain the cholesterol granuloma drainage pathway. The authors describe the endoscopic endonasal transpterygoid approach using a pedicled nasoseptal flap for petrous apex cholesterol granuloma and provide an intraoperative video and a literature review.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01.

BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 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. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.

Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells.

OBJECTIVE: Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines. METHODS: Glioma cell lines (T-98 G and U-251 MG) were used for this study. RESULTS: The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells. CONCLUSION: Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.

Pulmonary metastases from benign calvarial meningioma: a case report.

The most common intracranial tumour is meningioma, which rarely presents with extracranial metastasis, especially in benign cases. We report a case of meningioma recurrence with multiple pulmonary metastases in a patient who had a benign meningioma removed 12 years prior.

Preoperative predictive factors for surgical and functional outcomes in chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is a frequently encountered neurosurgical condition, especially in the elderly. We investigated predictive factors for surgical and functional outcomes after burr-hole drainage (BHD) surgery. METHODS: All patients with CSDH treated by BHD between January 2012 and December 2014 were included in this study. All patients were classified by symptom, clinical grade, time, location, hematoma density, midline shift, and other characteristics. Pre- and postoperative CT evaluation was performed at 0, 3, and 6 months. Clinical grades were classified as described in Markwalder et al. Surgical and clinical outcomes were evaluated with the brain expansion rate and modified Rankin Scale (mRS). Brain expansion rate was calculated as the ratio between post- and pre-operative hematoma thickness. Recurrence was defined as the occurrence of symptoms and hematoma on CT within 6 months. RESULTS: This study included 130 patients over 2 years. Among the variable parameters, young age (<75), iso-density of hematoma on CT, and short duration from symptom to surgery were correlated with good brain expansion. Patients with good brain expansion had fewer recurrences. In terms of mRS, young age, iso-density, and good clinical grade were correlated with good functional outcomes. CONCLUSIONS: Clinicians should be more aware of general conditions and medical problems, especially in elderly patients. Membranectomy should be considered in patients with a long duration of symptoms or hypo-dense hematomas to promote good brain expansion and good mRS scores.

Unusual Radiologic Finding of Intracranial Inflammatory Myofibroblastic Tumor Presenting a Cyst with Mural Nodule.

An intracranial cyst tumor with a mural nodule can be representative of some types of brain tumors, but is a rare presentation of intracranial inflammatory myofibroblastic tumor (IMT). Herein, we report the case of an intracranial IMT in a 48-year-old woman presenting with the extremely unusual radiologic findings of a cyst with a mural nodule.