Comparison of transposition and interposition methods in microvascular decompression for hemifacial spasm: an analysis of 109 cases performed by a single surgeon in a single-center retrospective study.

BACKGROUND: Microvascular decompression (MVD), the standard surgical approach for hemifacial spasm (HFS), can be divided into the interposition and transposition methods. Although the risk of HFS recurrence following interposition has been reported, there is limited data comparing long-term outcomes between both methods performed by a single surgeon. This study aimed to investigate the efficacy of MVD techniques on HFS by comparing surgical outcomes performed by a single surgeon in a single-center setting. METHODS: A total of 109 patients who underwent MVD were analyzed and divided into the transposition (86 patients) and interposition (23 patients) groups. Postoperative outcomes at 1 month and 1 year were assessed and compared, including rates of spasm relief, complications, and recurrence. RESULTS: Outcome assessment revealed higher rates of early spasm relief in the interposition group (66.3% vs. 100%, transposition vs. interposition, respectively, p = 0.0004), although spasm relief at 1-year postoperatively was comparable between the two groups (84.9% vs. 95.7%, transposition vs. interposition, respectively, p = 0.2929). No significant differences were observed in complication and recurrence rates. Kaplan-Meier analysis demonstrated no significant differences in the duration of spasm resolution by MVD method (p = 0.4347, log-rank test). CONCLUSION: This study shows that both the transposition (Surgicel® and fibrin glue) and interposition (sponge) methods were excellent surgical techniques. The interposition method may achieve earlier spasm resolution compared to the transposition method.

Clinical Significance of Early Venous Filling Detected via Preoperative Angiography in Glioblastoma.

Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between 1 April 2013 and 31 March 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of the 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angiography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, p = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.

Differentiation of astrocytoma between grades II and III using a combination of methionine positron emission tomography and magnetic resonance spectroscopy.

Objective: This study aimed to establish a method for differentiating between grades II and III astrocytomas using preoperative imaging. Methods: We retrospectively analyzed astrocytic tumors, including 18 grade II astrocytomas (isocitrate dehydrogenase (IDH)-mutant: IDH-wildtype = 8:10) and 56 grade III anaplastic astrocytomas (37:19). We recorded the maximum methionine (MET) uptake ratios (tumor-to-normal: T/N) on positron emission tomography (PET) and three MRS peak ratios: choline (Cho)/creatine (Cr), N-acetyl aspartate (NAA)/Cr, and Cho/NAA, between June 2015 and June 2020. We then evaluated the cut-off values to differentiate between grades II and III. We compared the grading results between contrast enhancement effects on MR and combinational diagnostic methods (CDM) on a scatter chart using the cutoff values of the T/N ratio and MRS parameters. Results: The IDH-mutant group showed significant differences in the Cho/NAA ratio between grades II and III using univariate analysis; however, multiple regression analysis results negated this. The IDH-wildtype group showed no significant differences between the groups. Contrast enhancement effects also showed no significant differences in IDH status. Accordingly, regardless of the IDH status, no statistically independent factors differentiated between grades II and III. However, CDMs showed higher sensitivity and negative predictive value in distinguishing them than MRI contrast examinations for both IDH statuses. We demonstrated a significantly higher diagnostic rate of grade III than of grade II with CDM, which was more striking in the IDH-mutant group than in the wild-type group. Conclusions: CDM could be valuable in differentiating between grade II and III astrocytic tumors.

Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

The Height and Mobility of Protruding Plaque After Carotid Artery Stenting Are Associated with Postoperative Ischemic Lesions.

BACKGROUND: Tissue protrusion (TP) is a possible cause of cerebral infarction after carotid artery stenting (CAS). Using optical frequency domain imaging (OFDI) and angioscopy, we investigated the relationship between the morphological features of TP and postoperative new ischemic lesions on magnetic resonance imaging (MRI)-diffusion weighted imaging (DWI) after CAS. METHODS: Fifty patients who underwent CAS and subsequent poststenting intravascular evaluation using both OFDI and angioscopy were included. CAS was performed for proximal protection via the femoral artery approach, and intravascular evaluation with OFDI and angioscopy were performed after stent placement. We compared the background and poststenting intravascular findings between patients with and without postoperative new ischemic lesions on MRI-DWI. RESULTS: TP was observed in 42 patients (84%), and postoperative new ischemic lesions on MRI-DWI were observed in 32 patients (64%). The frequency of TP did not differ between the 2 groups, but the height of TP was higher in the DWI-positive group (0.62 mm vs. 0.29 mm, P = 0.0028), and mobile TP was observed only in the DWI-positive group. The height of TP (P = 0.023) was an independent predictor of new periprocedural ischemic brain lesions after CAS, and its cut-off value for mobility was 0.55 mm on the receiver operating characteristic curve (area under the curve, 0.93). CONCLUSIONS: The height of TP on OFDI and mobile-TP on angioscopy after CAS were associated with postoperative new ischemic lesions on MRI-DWI. The intravascular evaluation using OFDI and angioscopy could be helpful for a detailed evaluation of TP.

Brainstem volume, diffusion, and metabolism are associated with chronic consciousness disorders after traumatic brain injury.

BACKGROUND AND PURPOSE: We aimed to identify reliable neuroradiological features of the brainstem reflecting the neurological symptoms of patients with chronic disorders of consciousness (DOCs) due to severe traumatic brain injury (TBI). METHODS: We retrospectively examined 86 patients with chronic DOCs due to severe TBI caused by automobile accidents. We studied the relationships among (1) neurological symptoms, including consciousness level, (2) integrated cognitive/physical condition, and (3) neuroradiological features of the brainstem (brainstem volume on MRI, fractional anisotropy [FA] value in the brainstem, and standardized uptake value [SUV] of 18F-fluorodeoxyglucose [FDG] on positron emission tomography in the brainstem). RESULTS: Brainstem volume was significantly larger and FA values were significantly higher in patients with a better level of consciousness. However, brainstem volumes were significantly decreased and the maximum SUV (SUVmax ) of FDG significantly increased at 2 years following admission regardless of the level of consciousness at admission. The brainstem volume was significantly larger and the FA value and SUVmax of FDG were significantly higher in patients with better National Agency for Automotive Safety and Victims' Aid (NASVA) scores at admission. The decrease in the brainstem volume was significantly minimized and the SUVmax of FDG significantly increased in patients with more improvement in the NASVA score 2 years after admission. CONCLUSIONS: The volume, FA value, and SUVmax of FDG of the brainstem are important neuroradiological features associated with the neurological conditions of patients with chronic DOCs due to severe TBI.

Canagliflozin Inhibits Glioblastoma Growth and Proliferation by Activating AMPK.

Sodium-glucose transporter 2 (SGLT2) inhibitors are antidiabetic drugs affecting SGLT2. Recent studies have shown various cancers expressing SGLT2, and SGLT2 inhibitors attenuating tumor proliferation. We evaluated the antitumor activities of canagliflozin, a SGLT2 inhibitor, on glioblastoma (GBM). Three GBM cell lines, U251MG (human), U87MG (human), and GL261 (murine), were used. We assessed the expression of SGLT2 of GBM through immunoblotting, specimen-use, cell viability assays, and glucose uptake assay with canagliflozin. Then, we assessed phosphorylation of AMP-activated protein kinase (AMPK), p70 S6 kinase, and S6 ribosomal protein by immunoblotting. Concentrations of 5, 10, 20, and 40 µM canagliflozin were used in these tests. We also evaluated cell viability and immunoblotting using U251MG with siRNA knockdown of SGLT2. Furthermore, we divided the mice into vehicle group and canagliflozin group. The canagliflozin group was administrated with 100 mg/kg of canagliflozin orally for 10 days starting from the third days post-GBM transplant. The brains were removed and the tumor volume was evaluated using sections. SGLT2 was expressed in GBM cell and GBM allograft mouse. Canagliflozin administration at 40 µM significantly inhibited cell proliferation and glucose uptake into the cell. Additionally, canagliflozin at 40 µM significantly increased the phosphorylation of AMPK and suppressed that of p70 S6 kinase and S6 ribosomal protein. Similar results of cell viability assays and immunoblotting were obtained using siRNA SGLT2. Furthermore, although less effective than in vitro, the canagliflozin group significantly suppressed tumor growth in GBM-transplanted mice. This suggests that canagliflozin can be used as a potential treatment for GBM.

NMDA receptor signaling induces the chemoresistance of temozolomide via upregulation of MGMT expression in glioblastoma cells.

PURPOSE: The alkylating agent temozolomide (TMZ) has a significant impact on the prognosis of glioblastoma (GBM) patients. Therefore, maximizing TMZ efficacy is important for GBM treatment. Many reports have shown that glutamate signaling promotes GBM progression via glutamate receptors, including N-methyl-D-aspartate receptors (NMDARs). Although NMDARs promote cell migration and invasion of GBM cells, their role in TMZ resistance remains unclear. Therefore, we focused on NMDAR signaling and investigated its effects on TMZ resistance. METHODS: We investigated the effect of NMDAR signaling on O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme that induces chemoresistance to TMZ, using quantitative real-time polymerase chain reaction and western blotting in human GBM T98G cells. In addition, we used memantine (MEM), an NMDAR antagonist, to investigate the cytotoxic effect of TMZ/MEM combination and its detailed mechanism. RESULTS: Activation of NMDAR by N-methyl-D-aspartate (NMDA) elevated MGMT expression and suppressed the effect of TMZ in T98G cells. In contrast, knockdown of NMDAR by NMDAR1 shRNA decreased MGMT expression and enhanced the effect of TMZ in T98G cells. The cytotoxic effect of TMZ was enhanced by MEM in T98G cells. Inhibition of NMDAR by MEM decreased MGMT expression and increased DNA alkylation by TMZ. CONCLUSION: NMDAR signaling induced chemoresistance of TMZ via the upregulation of MGMT expression in GBM cells. Furthermore, MEM inhibited TMZ-induced MGMT upregulation and increased the cytotoxic effect of TMZ on MGMT-positive cells. This study demonstrates that the combination of TMZ and MEM could be a new therapeutic strategy for MGMT-positive GBM. Overview of this study. NMDAR signaling controls the expression of MGMT and the cytotoxic effect of TMZ.

Radiological Prediction of Isocitrate Dehydrogenase (IDH) Mutational Status and Pathological Verification for Lower-Grade Astrocytomas.

Background and objective The isocitrate dehydrogenase (IDH) status of patients with World Health Organization (WHO) grade II or III astrocytoma is essential for understanding its biological features and determining therapeutic strategies. This study aimed to use radiological analysis to predict the IDH status of patients with lower-grade astrocytomas and to verify the pathological implications. Methods In this study, 47 patients with grade II (17 cases) or III astrocytomas (30 cases), based on 2016 WHO Classification, underwent methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) on the same day between January 2013 and June 2020. The patients were retrospectively assessed. Immunohistochemistry showed 23 cases of IDH-mutant and 24 of IDH-wildtype. Based on fluid-attenuated recovery inversion (FLAIR)/T2 imaging, three doctors blinded to clinical data independently allocated 18 patients to the clear boundary group between the tumor and the normal brain and 29 to the unclear boundary group. The peak ratios of N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and Cho/NAA and the tumor-to-normal region (T/N) ratio for maximum accumulation in MET-PET were calculated. For statistical analysis, Fisher's exact test was used to assess associations between two variables, and the Mann-Whitney U test to compare the values between the IDH-wildtype and IDH-mutant groups. The optimal cut-off values of MET T/N ratio and MRS parameters for discriminating IDH-wildtype from IDH-mutant were obtained using receiver operating characteristics curves. Results The unclear boundary group had significantly more IDH-wildtype cases than the clear boundary group (P<0.001). The IDH-wildtype group had significantly lower Cho/Cr (<1.84) and Cho/NAA (<1.62) ratios (P=0.02 and P=0.047, respectively) and a higher MET T/N ratio (>1.44, P=0.02) than the IDH-mutant group. The odds for the IDH-wildtype were 0.22 for patients who fulfilled none of the four criteria, including boundary status and three ratios, and 0.9 for all four criteria. Conclusions These results suggest that the combination of MRI, MRS, and MET-PET examination could be helpful for the prediction of IDH status in WHO grade II/III gliomas.

Perianeurysmal cyst formation in the brainstem after coil embolization: illustrative case.

BACKGROUND: Perianeurysmal cysts in the brainstem after endovascular coil embolization are rare, and their underlying mechanism remains unclear. The authors reported a case of a postcoiling perianeurysmal cyst that developed 6 years after endovascular coil embolization for a ruptured aneurysm and reviewed the related literature. OBSERVATIONS: A 77-year-old woman had a history of subarachnoid hemorrhage 6 years earlier. The ruptured large left vertebral artery-posterior inferior cerebellar artery aneurysm was treated with endovascular coil embolization. Two years later, the aneurysm regrew and perianeurysmal brainstem edema was detected on magnetic resonance imaging (MRI); stent-assisted coil embolization combined with low-flow bypass was performed. Follow-up MRI showed that the perianeurysmal edema gradually transformed into a perianeurysmal cyst over the next 3 years. Finally, the perianeurysmal cyst caused gait disturbance with ataxia, and the patient received cyst puncture. After surgery, the symptom was immediately improved. LESSONS: The authors reported, for the first time, postcoiling of perianeurysmal cyst formation treated by cyst puncture. If perianeurysmal edema is detected after endovascular coil embolization, especially for large aneurysms, it is necessary to consider progression to cyst formation and follow up over time. In addition, cyst puncture is effective, depending on the symptoms and the lesion.

Nafamostat protects against early brain injury after subarachnoid hemorrhage in mice.

This study aimed to evaluate the effects of nafamostat, a serin protease inhibitor, in the management of subarachnoid hemorrhage (SAH). SAH was induced by endovascular perforation in male mice. Nafamostat was administered intraperitoneally four times immediately after SAH induction. Cerebral blood flow, neurological behavior tests, SAH grade and protein expression were evaluated at 24 h after SAH induction. In the in vitro model, human brain microvascular endothelial cells (HBMVECs), HBVECs were exposed to thrombin and hypoxia for 24 h; nafamostat was administered and the protein expression was evaluated. Eighty-eight mice were included in the in vivo study. Fifteen mice (17%) were excluded because of death or procedure failure. Nafamostat exerted no significant effect on the SAH grade or cerebral blood flow; however, it improved the neurological behavior and suppressed the thrombin and MMP-9 expression. In addition, nafamostat suppressed the ICAM-1 expression and p38 phosphorylation in the in vitro study. Nafamostat has a protective effect against HBMVEC after exposure to thrombin and hypoxia, suggesting its role in improving the neurological outcomes after SAH. These findings indicate that nafamostat has the potential to be a novel therapeutic drug in the management of SAH.

Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.

PURPOSE: Heparan sulfate (HS) is one of the factors that has been suggested to be associated with angiogenesis and invasion of glioblastoma (GBM), an aggressive and fast-growing brain tumor. However, it remains unclear how HS of endothelial cells is involved in angiogenesis in glioblastoma and its prognosis. Thus, we investigated the effect of endothelial cell HS on GBM development. METHODS: We generated endothelial cell-specific knockout of Ext1, a gene encoding a glycosyltransferase and essential for HS synthesis, and murine GL261 glioblastoma cells were orthotopically transplanted. Two weeks after transplantation, we examined the tumor progression and underlying mechanisms. RESULTS: The endothelial cell-specific Ext1 knockout (Ext1 CKO ) mice exhibited reduced HS expression specifically in the vascular endothelium of the brain capillaries compared with the control wild-type (WT) mice. GBM growth was significantly suppressed in Ext1 CKO mice compared with that in WT mice. After GBM transplantation, the survival rate was significantly higher in Ext1 CKO mice than in WT mice. We investigated how the effect of fibroblast growth factor 2 (FGF2), which is known as an angiogenesis-promoting factor, differs between Ext1 CKO and WT mice by using an in vivo Matrigel assay and demonstrated that endothelial cell-specific HS reduction attenuated the effect of FGF2 on angiogenesis. CONCLUSIONS: HS reduction in the vascular endothelium of the brain suppressed GBM growth and neovascularization in mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-021-00444-3.

Prediction of nuclide accumulation spread based on the volume of enhancing MRI lesion in glioblastoma patients.

BACKGROUND: 11C-methionine-PET (MET) and Thallium-201 chloride-SPECT (TL) are useful for predictive proliferation ability and tumor invasion range identification in glioma patients, however they are not always possible in any hospital or country. Our study aimed to assess whether the range of MET and Tl accumulation could be predicted from the contrast-enhanced lesions in Gadolinium (Gd)-T1 weighted MR image (Gd-MRI) in glioblastoma multiforme (GBM) patients. METHODS: In 25 cases, the MET-Area, TL-Area, O-Area where MET and TL overlap, and all accumulation area (AA-Area) were measured in the same axial cross section as the Gd enhanced maximum area (Gd-Area). This tracing operation was repeated with all axial fusion slices, and each volume was also measured (Gd-V, MET-V, TL-V, O-V, AA-V). RESULTS: The maximum accumulation distance of MET and TL beyond the Gd-Area was limited to within 30 mm, 35 mm, respectively. Significant positive correlations were showed in all combinations with Gd-Area: MET-Area (r=0.851, p<0.0001), TL-Area (r=0.955, p<0.0001), O-Area (r=0.935, p<0.0001) and AA-Area (r=0.893, p<0.0001), respectively. All combinations with Gd-V showed significant positive correlation: MET-V (r=0.867, p<0.0001), TL-V (r=0.952, p<0.0001), O-V (r=0.935, p<0.0001) and AA-V (r=0.897, p<0.0001), respectively. CONCLUSIONS: Approximate tumor volume Gd-V can be calculated using the formula A * B * C / 2, where A, B, and C represent the dimensions of Gd-enhanced lesion in 3 axes perpendicular to each other. The nuclide accumulation predictive table created using the obtained linear approximation functions can be used to predict the average tumor invasion range from the Gd-V without preoperative nuclear examinations.

Real-world treatment results for ruptured blood-blister aneurysm of the internal carotid artery: analysis of a Japanese nationwide multicenter study.

Ruptured blood-blister aneurysm (BBA) of the internal carotid artery (ICA) remains a challenging lesion, even in the age of modern neurosurgery and endovascular treatment. This retrospective multicenter study aimed to investigate the real-world treatment choice and treatment results. We included 182 ruptured BBAs of the ICA treated at 51 neurosurgical centers in Japan between 2013 and 2017. The baseline patient characteristics, radiological features of the aneurysm, treatment modality, details of treatment, complications of treatment, and treatment results were retrospectively collected. The treatment strategy was divided into deconstructive and reconstructive procedures. Primary clinical outcomes were evaluated using the modified Rankin scale (mRS) at final follow-up. Direct surgery was performed in 144 (79%) cases, and the remaining 38 (21%) cases received endovascular treatment. The majority of treatment selections were deconstructive and reconstructive procedures in the direct surgery group and endovascular treatment group, respectively. Overall, favorable clinical outcomes (mRS 0 to 2) were achieved in 66% of cases, and the mortality rate was 15% at the final follow-up (mean 23 months). There was no significant difference in clinical outcome between direct and endovascular treatment groups. Our large nationwide study compared the real-world treatment options for ruptured BBAs and their results. Our findings may offer beneficial information for treatment decision and for future studies investigating ruptured BBAs.

Glucose transporter Glut1 controls diffuse invasion phenotype with perineuronal satellitosis in diffuse glioma microenvironment.

BACKGROUND: Gliomas typically escape surgical resection and recur due to their "diffuse invasion" phenotype, enabling them to infiltrate diffusely into the normal brain parenchyma. Over the past 80 years, studies have revealed 2 key features of the "diffuse invasion" phenotype, designated the Scherer's secondary structure, and include perineuronal satellitosis (PS) and perivascular satellitosis (PVS). However, the mechanisms are still unknown. METHODS: We established a mouse glioma cell line (IG27) by manipulating the histone H3K27M mutation, frequently harboring in diffuse intrinsic pontine gliomas, that reproduced the diffuse invasion phenotype, PS and PVS, following intracranial transplantation in the mouse brain. Further, to broadly apply the results in this mouse model to human gliomas, we analyzed data from 66 glioma patients. RESULTS: Increased H3K27 acetylation in IG27 cells activated glucose transporter 1 (Glut1) expression and induced aerobic glycolysis and TCA cycle activation, leading to lactate, acetyl-CoA, and oncometabolite production irrespective of oxygen and glucose levels. Gain- and loss-of-function in vivo experiments demonstrated that Glut1 controls the PS of glioma cells, that is, attachment to and contact with neurons. GLUT1 is also associated with early progression in glioma patients. CONCLUSIONS: Targeting the transporter Glut1 suppresses the unique phenotype, "diffuse invasion" in the diffuse glioma mouse model. This work leads to promising therapeutic and potential useful imaging targets for anti-invasion in human gliomas widely.

Pediatric Giant Cell Glioblastoma Presenting with Intracranial Dissemination at Diagnosis: A Case Report.

Giant cell glioblastoma (GCG) is a rare subtype of glioblastoma multiforme (GBM), and it often occurs in younger patients; however, its onset in children is extremely noticeable. A 7-year-old girl presented with a headache and restlessness. A giant tumor that was 7 cm in diameter was found by magnetic resonance imaging (MRI) in the left frontal lobe with intracranial dissemination. Because the tumor had extended to the lateral ventricles and occluded the foramen of Monro causing hydrocephalus, she underwent ventricular drainage and neuro-endoscopic biopsy from the left posterior horn of the lateral ventricle. The initial pathological diagnosis was an atypical teratoid/rhabdoid tumor (AT/RT). When the dissemination subsided after the first chemotherapy with vincristine, doxorubicin, and cyclophosphamide, she underwent the first tumor resection via a left frontal transcortical approach. After surgery, the second chemotherapy with ifosfamide, cisplatin, and etoposide was not effective for the residual tumor and intracranial dissemination. The second surgery via a transcallosal approach achieved nearly total resection leading to an improvement of the hydrocephalus. The definitive pathological diagnosis was GCG. Despite chemo-radiation therapy, the dissemination in the basal cistern reappeared and the hydrocephalus worsened. She was obliged to receive a ventriculo-peritoneal (VP) shunt and palliative care at home; however, her poor condition prevented her discharge. Ten months after admission, she died of tumor progression. The peritoneal dissemination was demonstrated by cytology of ascites. In conclusion, although unusual, pediatric GCG may be disseminated at diagnosis, in which case both tumor and hydrocephalus control need to be considered.

Diffuse midline glioma in the spinal cord with rapid respiratory deterioration.

BACKGROUND: Neurogenic acute respiratory failure is usually caused by either infection or vascular insufficiency. We report the case of a patient who developed acute respiratory failure secondary to a spinal tumor. CASE PRESENTATION: A 32-year-old man, presenting with numbness and muscle weakness in his legs for 2 weeks, was transferred to our hospital with worsening quadriplegia and development of respiratory symptoms. We carried out emergent spinal decompression and initiated steroid pulse therapy, with no resolution of symptoms; a tumor incision biopsy after contrast cervical magnetic resonance imaging revealed an intraspinal tumor with a pathological diagnosis of World Health Organization grade IV glioma. The patient developed bradycardia, severe sepsis, status epilepticus, and cardiopulmonary arrest due to hypoxemia and was treated with chemoradiotherapy under mechanical ventilation. He was later transferred to another hospital for subacute care. CONCLUSION: Acute respiratory failure caused by spinal tumors is uncommon. However, acute care practitioners should be mindful of neoplastic lesions as a potential cause.

Riluzole enhances the antitumor effects of temozolomide via suppression of MGMT expression in glioblastoma.

OBJECTIVE: Glutamatergic signaling significantly promotes proliferation, migration, and invasion in glioblastoma (GBM). Riluzole, a metabotropic glutamate receptor 1 inhibitor, reportedly suppresses GBM growth. However, the effects of combining riluzole with the primary GBM chemotherapeutic agent, temozolomide (TMZ), are unknown. This study aimed to investigate the efficacy of combinatorial therapy with TMZ/riluzole for GBM in vitro and in vivo. METHODS: Three GBM cell lines, T98G (human; O6-methylguanine DNA methyltransferase [MGMT] positive), U87MG (human; MGMT negative), and GL261 (murine; MGMT positive), were treated with TMZ, riluzole, or a combination of both. The authors performed cell viability assays, followed by isobologram analysis, to evaluate the effects of combinatorial treatment for each GBM cell line. They tested the effect of riluzole on MGMT, a DNA repair enzyme causing chemoresistance to TMZ, through quantitative real-time reverse transcription polymerase chain reaction in T98G cells. Furthermore, they evaluated the efficacy of combinatorial TMZ/riluzole treatment in an orthotopic mouse allograft model of MGMT-positive GBM using C57BL/6 J mice and GL261 cells. RESULTS: Riluzole displayed significant time- and dose-dependent growth-inhibitory effects on all GBM cell lines assessed independently. Riluzole enhanced the antitumor effect of TMZ synergistically in MGMT-positive but not in MGMT-negative GBM cell lines. Riluzole singularly suppressed MGMT expression, and it significantly suppressed TMZ-induced MGMT upregulation (p < 0.01). Furthermore, combinatorial TMZ/riluzole treatment significantly suppressed tumor growth in the intracranial MGMT-positive GBM model (p < 0.05). CONCLUSIONS: Riluzole attenuates TMZ-induced MGMT upregulation and enhances the antitumor effect of TMZ in MGMT-positive GBMs. Therefore, combinatorial TMZ/riluzole treatment is a potentially promising novel therapeutic regimen for MGMT-positive GBMs.