EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells. EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration. QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group. EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.

Background: Mechanical thrombectomy has improved the outcome of patients with acute ischemic stroke, but complications such as subarachnoid hemorrhage (SAH) can worsen the prognosis. This study investigates the frictional forces exerted by stent retrievers (SRs) on vessel walls, hypothesizing that these forces contribute to vascular stress and a risk of hemorrhage. We aimed to understand how vessel diameter, curvature, and stent deployment position influence these forces. Methods: Using a silicone vascular model simulating the middle cerebral artery, we created virtual vessels with diameters of 2.0 mm and 2.5 mm, each with branching angles of 60° and 120°. A Trevo NXT (4 × 28 mm) SR was deployed and retracted through these models, measuring the maximum static frictional force at the moment the SR began to move. The stent deployment position relative to the curvature (straight, distal 1/4, center, and proximal 1/4) was also varied to assess its impact on frictional forces. Each condition was tested 15 times, and the results were statistically analyzed. Results: The highest frictional force was observed in the 2.0 mm/120° model, followed by the 2.0 mm/60°, 2.5 mm/120°, and 2.5 mm/60° models. Narrower and more sharply curved vessels exhibited significantly higher frictional forces. Friction also increased with more distal stent deployment, particularly in the narrower vessels. Conclusion: Smaller vessel diameters, greater curvature, and more distal stent deployment positions increase frictional forces during thrombectomy, potentially leading to SAH. These findings highlight the importance of selecting appropriately sized SRs and considering stent deployment positions to minimize vascular stress.

The International Conference on Sports Concussion, held every four years since 2001, has been instrumental in forming the international consensus on sports-related concussions. However, due to the unprecedented global pandemic of COVID-19, not only the Tokyo Olympics 2020, but also the initially scheduled sixth conference was postponed multiple times. Finally, the 6th International Conference on Sports Concussion took place in Amsterdam at the end of October 2022. In July 2023, the Amsterdam Declaration, reflecting the outcomes of this sixth conference, was released. This paper provides an overview of the conference, in which significant updates were revealed and introduced, including revisions to the definition of sports-related concussions, as well as the latest version of the Sports Concussion Assessment Tool (SCAT), known as SCAT6, the Office Assessment Tool (SCOAT), and the updated staged return-to-play protocol.

Tumor-treating fields (TTFields) is an established treatment modality for glioblastoma. False progression to chemoradiation is a known problem in patients with glioblastoma multiforme (GBM), with most cases occurring within three months of radiation therapy. In this report, we present two cases of delayed pseudoprogression caused by TTFields. Two patients with GBM who received TTFields showed signs of radiographic progression six months after the completion of radiation therapy. Patient 1 was a 37-year-old female with a glioblastoma in the right temporal lobe. Patient 2 was a 70-year-old male with glioblastoma in the left temporal lobe. Both patients received radiation therapy, followed by temozolomide (TMZ) maintenance therapy and TTFields. Patient 1 underwent a second resection; however, the pathology revealed only a treatment effect, and the final diagnosis was a pseudoprogression. In Case 2, the disease resolved with steroid therapy alone. In both patients, the lesions appeared later than during the typical pseudoprogression period. A recent study reported that TTFields increase the permeability of the plasma cell membrane, which may result in further leakage of gadolinium into the extracellular lumen. Further studies are needed to better characterize delayed pseudoprogression and improve treatment outcomes.

Prolactin-secreting pituitary neuroendocrine tumors (PitNETs) are more common in women. Male patients may also have few symptoms and have macroadenomas extending outside the sella turcica. This study aimed to report the results of cabergoline treatment in male patients with prolactin-secreting PitNET. The study included nine male patients aged 26-65 years (median, 46 years) diagnosed with prolactin-secreting PitNETs. The age at onset, prolactin values, tumor size, symptoms, and treatment were assessed. The mean prolactin value at the initial presentation was 2734.6 ng/mL, and the mean maximum tumor diameter was 40.4 mm. Visual field disturbance was the most common symptom (44.4%), followed by headaches (33.3%), asymptomatic symptoms (11.1%), and galactorrhea (11.1%). Eight patients responded to cabergoline treatment with normalization of prolactin levels and tumor shrinkage. One patient did not respond to the cabergoline treatment and required surgical intervention. There were no cases of cerebrospinal fluid leakage. Cabergoline was found to be an effective treatment for male prolactin-secreting PitNETs.

Abstract INTRODUCTION In meningioma surgery, the removal of the tumor and tumor-attached dura mater is essential. Due to its high affinity, absorbable artificial dura mater is used for the reconstruction of dural defects. In this study, we report a pathological examination of dural-like tissue in a case of meningioma that recurred at the same site after the use of absorbable artificial dura mater during initial surgery. METHOD We investigated two cases in which absorbable artificial dura mater was used for dural reconstruction during meningioma resection, and subsequently, a recurrent lesion was identified at the site of the dural reconstruction. We examined MRI images and surgical and pathological findings at the time of recurrence in these cases. RESULT All patients underwent total resection, and the pathological diagnosis was atypical meningioma. MRI images at the time of recurrence revealed multiple meningiomas along the artificial dura site. Gross findings during recurrent surgery indicated that the absorbable dura had been replaced by dura-like tissue, with the tumor also attached to the same site. Pathological findings showed bundles of fibrous tissue within the dura-like tissue, albeit with a sparser density compared to autologous dura mater. Meningioma cell invasion and angiogenesis were also observed in the dural-like tissue. DISCUSSION In all cases, multiple meningiomas were found along the dural-like tissue. This suggests that meningioma cells invading the dural-like tissue may have used it as a scaffold for meningioma recurrence. Future studies are necessary to determine the appropriateness of absorbable artificial dura mater for dural defect sites during malignant meningioma surgery.

Abstract INTRODUCTION DWIBS is an abbreviation for Diffusion Weighted Whole Imaging with Background body signal Suppression. It is an imaging method that uses MRI diffusion-weighted imaging (DWI) to image the entire body in multiple locations and then integrates them to form a wide-area image. In recent years, MRI has been used to search for heat sources of unidentified fever and distant metastasis of cancer. In this report, we describe two cases in which DWIBS was useful in the search for the primary tumor in patients with brain metastases. CASE PRESENTATION Case 1: Male in his 60s. The patient presented with headache and diplopia, and MRI showed a neoplastic lesion in the clivus bone. A transnasal endoscopic surgery was performed, and he was diagnosed with bone metastasis of squamous cell carcinoma. Contrast-enhanced whole body CT showed similar findings, and the patient was found to have brain metastasis of esophageal cancer. Case 2: Male, 50s. He presented with a complaint of left facial paralysis and left incomplete paralysis, and a head MRI showed a brain tumor in the right middle frontal gyrus. A craniotomy was performed, and the pathological diagnosis was adenocarcinoma. A systemic search did not reveal a primary tumor, and the patient was diagnosed with cancer of unknown primary, but later lung lesions became apparent. The DWIBS performed at that time also showed a high signal at the site where lung cancer was diagnosed. DISCUSSION In Japan, MRI is widely used, and DWIBS is gradually becoming popular as a whole-body search method because it can be performed with current MRI equipment. DWIBS may be an option for primary tumor detection in facilities or regions where 18F-FDG PET is not readily available. CONCLUSION DWIBS may be useful for close examination of primary metastatic brain tumors, and more cases should be accumulated in the future.

Objective To clarify the actual status of sleep disorders due to sports-related concussion (SRC) in Japan. Design Retrospective study. Setting SRC clinics in Japan. Participants The observation period was from September 2020 to March 2021, and 69 cases seen during this period were included. Selection criteria: 1) sports-related injury, 2) SRC cases, 3) cases evaluated by the same neurosurgeon, 4) cases that could be followed continuously for 28 days, and 5) Patients who were found to have insomnia-related items on the Sports Concussion Assessment tool (SCAT) and were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Criteria for control: Cases 1) to 4) are the same as above, but 5) no insomnia-related items were found in the SCAT at the time of examination. Statistical Methods A t-test was used. Main Results 25 of the 69 patients (36%) had sleep disturbances. The mean age of these 25 cases was 22 years, and 21 (84%) were male. The mean PSQI score was 5.2, the mean PHQ-9 score was 0.3, and the mean SDS score was 39.9. The mean SDS score in the 44 patients who did not show sleep disturbance was 34.3, and the difference between the mean SDS score in the two groups was clearly different (p < 0.05). Conclusions In Japanese SRC patients, sleep disturbances were observed to a certain extent, and the tendency toward depression was stronger than in patients without sleep disturbances. Further investigation of specific management interventions for each subgroup is needed.

Abstract INTRODUCTION Aroma essential oils apply to cancer therapy because of their immune-enhancing and sedative effects, and their ability to reduce the side effects of chemotherapy. Recently, aroma essential oils have also been reported to have anti-tumor effects. We investigate the anti-tumor effects of aromatic compounds contained in essential oils as a novel treatment for glioblastoma. In this study, we analyzed the antitumor effect of lemongrass essential oil and investigated its antitumor aroma therapy for glioblastoma. methods and RESULTS Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used in the study. Tumor cells were cultured in the presence of lemongrass essential oil for 72 hours, and the growth inhibitory effect was observed, suggesting that the evaporated lemongrass essential oil components acted on tumor cells in the vicinity. In addition, a similar effect was observed with citral alone, which is the main component of lemongrass. Analysis of the effects of citral revealed that citral strongly binds to MARK4 and inhibits its enzyme activity, and that citral decreases the phosphorylation of tau protein. Next, a mouse brain tumor model with RSV-M was established, and the anti-tumor effect of lemongrass essential oil was studied. The results showed that the mice that inhaled lemongrass essential oil for 12 h/day had a significantly prolonged survival period compared to the control group. DISCUSSION Citral is the main component of lemongrass essential oil, which contains 70-80% of lemongrass essential oil. This study suggests a mechanism of inhibition of tumor cell proliferation by citral in malignant gliomas. Citral is a volatile monoterpene, and its anti-tumor effect was demonstrated by diffusion through evaporation. CONCLUSION Citral in lemongrass essential oil shows anti-tumor effects and is expected to be applied to a new glioblastoma therapy using “aroma”

Abstract BACKGROUND In glioblastoma, the only chemotherapy with a clear prognostic effect is temozolomide. Research and development of novel therapies to overcome glioblastoma resistance to treatment is ongoing. We have been studying antitumor aromatherapy using aromatic compounds in aromatic essential oils as a new treatment for glioblastoma. In this study, we focus on citral, the main component of lemongrass essential oil, and report that lemongrass essential oil shows anti-tumor effects in glioma cells and mouse brain tumor models. METHODS We used human glioma cells (U251, T98G) and mouse brain tumor cells (RSV-M). We examined the proliferation ability of lemongrass in glioma cells by transpiration and direct administration. The antitumor aroma effect of lemongrass essential oil inhalation in a mouse glioma brain tumor model was evaluated by survival time analysis using the Kaplan-Meier method. RESULTS After 72 hours of incubation of tumor cells in the presence of lemongrass essential oil, U251, T98G, and RSV-M all showed anti-proliferative effects, suggesting that the transpired lemongrass essential oil components acted on tumor cells in the vicinity. Direct administration of lemongrass essential oil also inhibited cell proliferation in all glioma cells in a dose- and time-dependent manner. Then, we examined the antitumor effect of lemongrass essential oil in a mouse brain tumor model using RSV-M. The results showed that the survival period was significantly prolonged in the lemongrass essential oil-inhaled group (n=6) compared to the control group (n=6) (p=0.0102), and the cumulative survival rate was not less than 50% at the end of the study. CONCLUSION Citral is the main component of lemongrass essential oil, containing about 80%. Citral may have an antitumor effect on glioblastoma, as evidenced by its transpiration effect. In addition, its antitumor effect was also observed in animal experiments, suggesting that it could be a new treatment for glioblastoma.

Objective:Since the efficacy of mechanical thrombectomy (MT) for acute cerebral infarction due to large vessel occlusion has been proven, the time available for treatment has gradually increased. Currently, under certain conditions, treatment is indicated up to 24 h from onset. Based on neurological signs and imaging diagnosis, Stroke Treatment Guideline 2021 recommends initiation of MT within 6-24 h from onset. Herein, we retrospectively investigated the relationship between cerebral perfusion imaging evaluation and prognosis in patients with acute cerebral infarction due to large or median vessel occlusion. Methods:Fifty-one patients diagnosed with acute cerebral infarction due to large or median vessel occlusions in anterior circulation between November 2019 and December 2021 were divided into medical care and reconstructive therapy (including tissue plasminogen activator [t-PA] therapy and MT) groups. The primary outcome was changes in the National Institutes of Health Stroke Scale (NIHSS) at admission and 1 week after onset. Patients in the medical care group were divided into those whose NIHSS did not worsen and those whose NIHSS worsened. Those in the reconstructive therapy group were divided into those whose NIHSS improved and those whose NIHSS did not improve. We evaluated the relationship between improvement factors in acute neurological symptoms and penumbral and core volumes from computed tomography perfusion performed at admission. Results:Of 45 eligible patients, 10 received medical care without t-PA or MT and 35 underwent reconstructive therapy, including t-PA and MT. Among the 10 patients in the medical care group, 3 had worsening symptoms and 7 did not. The mean and median (interquartile range [IQR]) penumbra volumes were significantly higher in patients with worsening symptoms than in those without. The receiver operating characteristic (ROC) curve showed a threshold value of 28.6 mL with an area under the curve (AUC) of 0.952. Among the 35 patients in the reconstructive therapy group, symptoms improved for 29 but did not improve for 6. The mean and median (IQR) core volumes were significantly higher in patients whose symptoms did not improve than in those whose symptoms improved. The ROC curve showed a threshold value of 25 mL and an AUC of 0.632. Conclusion:Evaluation of penumbra volumes could detect cases with worsening symptoms in cases where medical care was performed, and evaluation of core volumes may detect cases with non-improved symptoms in cases that received reconstructive therapy.

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.

Abstract INTRODUCTION Diffusion Weighted Whole Body Imaging with background body signal Suppression (DWIBS) is an imaging technique that encompasses comprehensive imaging of the entire body through diffusion-weighted imaging (DWI). In recent years, it has been increasingly utilized for investigating the etiology of fever or primary cancer. Here we present two cases of DWIBS for searching for primary cancer in patient with intracranial metastasis. CASE PRESENTATION Case1: A 60-year-old man presented with headache and diplopia and was admitted to our hospital. MRI revealed a tumor in the clivus exhibiting contrast enhancement. Endoscopic transsphenoidal surgery confirmed the diagnosis of squamous cell carcinoma. DWIBS demonstrated high intensity in a region similar to the esophagus seen on contrast-enhanced CT, leading to the diagnosis of brain metastasis from esophageal cancer. Case 2: A 50-year-old man presented with left facial paralysis and left hemiplegia and was admitted to our hospital. MRI revealed a tumor in the right middle frontal gyrus. Craniotomy confirmed the diagnosis of adenocarcinoma. Although the primary cancer remained unidentified upon initial examination, subsequent investigations revealed it originated from the lung. DWIBS showed high intensity in a region similar to the lung. DISCUSSION While FDG-PET is commonly utilized for cancer detection, its invasiveness and limitations prompt consideration of alternative modalities such as DWIBS. Recently there are some studies that have shown DWIBS to be superior to FDG PET in detecting esophageal and lung cancers. Thus, DWIBS may serve as a viable option for primary cancer screening in hospitals or communities where access to FDG PET is limited. CONCLUSION Its non-invasive nature makes DWIBS an appealing option for primary cancer detection, and further advancements are anticipated.

Abstract INTRODUCTION Aromatic essential oils have antibacterial, antifungal, antiviral, anti-inflammatory, and antitumor effects. We previously investigated the antitumor effects of aromatic essential oils administered by inhalation as a novel treatment for glioblastoma. The aromatic monoterpene α-pinene, a component of many essential oils, is known to inhibit tumor growth. This study analyzed the antitumor effects of frankincense essential oil, mainly composed of α-pinene, and explored its potential for antitumor aroma therapy in glioblastoma. METHODS AND RESULTS Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Tumor cells cultured in the presence of frankincense essential oil for 72 hours showed growth inhibition, suggesting that the evaporated components acted on nearby tumor cells. α-Pinene and limonene, the main components of frankincense, also showed similar effects alone. Inhalation studies in mice demonstrated that 30 minutes of α-pinene inhalation had the same brain transfer effect as 90 minutes. Intraperitoneal administration of α-pinene showed minimal brain transfer. For limonene, brain transfer increased with 90 minutes of inhalation compared to 30 minutes. Inhalation resulted in higher brain transfer than intraperitoneal administration. Additionally, α-pinene’s antitumor effects suggested induction of apoptosis and cell cycle arrest. DISCUSSION α-Pinene, comprising about 40% of frankincense essential oil, was found to inhibit tumor cell growth in malignant gliomas. This study suggests that α-pinene exerts antitumor effects when administered by inhalation. CONCLUSION α-Pinene in frankincense essential oil has antitumor effects and may be a novel “aroma” therapy for treating glioblastoma.

Objective: Craniocervical junction arteriovenous fistula (CCJ-AVF) is a rare disease, and preoperative imaging evaluation is important in developing treatment strategies due to the complexity of the vascular architecture, such as the feeding vessels, shunt points, and draining veins. In the present study, we report a case of hemorrhagic perimedullary CCJ-AVF with multiple feeding vessels in which the common single draining vein was dissected by craniotomy and completely treated. Case presentation: A 71-year-old woman presented with subarachnoid hemorrhage (Hunt & Kosnik, grade II). Cerebrovascular CTA showed no intracranial cerebral aneurysm and findings suggestive of shunt disease at the CCJ. Based on cerebral angiography, the patient was diagnosed with perimedullary CCJ AVF, with the right radicular and the left anterior spinal arteries as feeders which drain into a common dilated coronary vein through a shunt located on the ventral side of the spinal cord and then drain into the ascending and descending anterior spinal veins. Ventricular drainage was performed for acute hydrocephalus, and arteriovenous fistula was dissected electively by craniotomy on day 17 after onset. A clip was applied to the single draining vein, which had been evaluated using preoperative imaging diagnosis. Intraoperative digital subtraction angiography (DSA) confirmed the disappearance of shunt blood flow, and the surgery was completed. The follow-up DSA did not show shunt blood flow, and the patient was transferred to a rehabilitation hospital with a modified Rankin scale score of 2. Conclusion: CCJ-AVF cases often have a complex vascular architecture, and it is important to use various modalities to understand the vascular anatomy in detail and develop an appropriate treatment strategy.

Abstract Metastatic brain tumors were previously reported with prognoses of approximately 6 months. The accuracy of diagnostic imaging and advances in drug therapy have improved the treatment outcomes of various types of cancer. On the other hand, patients with advanced cancer who are detected with neurological symptoms caused by metastatic brain tumors usually face difficulty in deciding on a treatment strategy. In this study, we reported the results of cancer patients who were first detected with central nervous system symptoms in the last 10 years and treated at our hospital.There were 14 patients treated at our hospital from 2013 to 2022 with CNS symptoms as the initial symptom. The mean age was 65.5 years, and the most common primary cancer was lung cancer in 11 cases (9 NSCLC and 2 SCLC). The OS examined in the 11 lung cancer cases was 14 months. Among NSCLC, only 2 cases had EGFR mutation and no cases had ALK fusion gene. The mean Lung-molGPA was 0.89 in 9 patients with NSCLC and 0.75 in 2 patients with SCLC, and the expected survival time was 6.9 months and 2.8 months.With advances in drug therapy, median survival for patients with NSCLC brain metastases has been reported to range from 7 months to 2 years for patients with EGFR mutations and 4 years for patients with ALK fusion gene. Thus, it is necessary to consider treatment strategies according to primary tumor, histology, and genetic information, rather than considering metastatic brain tumors as a single entity.The results of this study suggest that aggressive therapeutic intervention may prolong the survival period expected at the time of initial diagnosis, even in cancer patients who are found to have metastatic brain tumors.

Abstract Aromatic essential oils have been used in cancer treatment to enhance immunity, induce sedation, and reduce the side effects of chemotherapy. Recently, essential oils have been reported to have anti-tumor effects. We have been investigating anti-tumor aroma of essential oils as a novel treatment for glioblastoma and have found that hiba essential oil has a proliferation inhibitory effect. In this study, we investigated the antitumor effect of lemongrass essential oil for glioblastoma and its antitumor aromatherapy. Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Lemongrass essential oil was added to each tumor cell line, and growth inhibition was observed in all cell lines. In addition, lemon grass essential oil showed growth inhibition effect when the tumor cells were separated from the oil, as was the case with direct administration, suggesting that the lemongrass essential oil components that evaporated acted on tumor cells in the surrounding area. The antitumor component of lemongrass essential oil was isolated and identified as citral, an antitumor factor, by gas chromatography. Analysis of the effects of citral showed that it strongly inhibited MARK4 activity and growth in three cell lines. The mechanism revealed that citral decreased the phosphorylation of Tau protein. MARK4 is highly expressed in glioblastoma and has been reported to be involved in cell proliferation. This study suggests a potential mechanism for citral to inhibit tumor cell proliferation via MARK4 in malignant gliomas. Citral is a volatile monoterpene and may exert its antitumor effect by evaporation diffusion. Lemongrass essential oil contains citral, which shows antitumor effects, and is expected to be applied to a new glioblastoma therapy using "aroma".