掲載種別：研究論文（学術雑誌）  

Background: Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS). Methods: Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated. Results: In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively. Conclusions: Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.

DOI： 10.1007/s00701-022-05363-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the treatment of primary central nervous system lymphoma (PCNSL), intraoperative rapid pathological diagnosis can dramatically change the surgical strategy, and more accurate diagnostic methods are required. In April 2020, we adopted intraoperative rapid immunohistochemistry (IHC) in addition to conventional rapid intraoperative diagnosis based on morphological assessment, mainly for patients with PCNSL. Here, we investigate the usefulness and significance of intraoperative rapid IHC based on our initial experience. We performed intraoperative rapid IHC using antibodies for cluster of differentiation (CD)20, CD3, leukocyte common antigen (LCA) and glial fibrillary acidic protein (GFAP) using enzyme-labeled antibody methods in 25 patients, including PCNSL patients, from April 2020 to July 2022. We examined the utility of this approach in determining treatment strategies for brain tumors. Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: diffuse large B-cell lymphoma, 16 cases; glioblastoma, six cases; pilocytic astrocytoma, one case; adenocarcinoma, one case; and inflammatory disorder, one case. The entire process took 32 min and staining for CD20, CD3, LCA, and GFAP was comparable to that using paraffin-embedded sections. In all cases, the results of intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In addition, in two cases, the results of conventional intraoperative rapid pathological diagnosis based on morphological assessments using frozen sections were drastically changed by adding intraoperative rapid IHC. Intraoperative rapid IHC contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. This may allow new therapeutic strategies not only for PCNSL but also for other brain tumors.

DOI： 10.1111/neup.12864

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Ischemic stroke is a leading cause of mortality and permanent disability. Chronic stroke lesions increase gradually due to the secondary neuroinflammation that occurs following acute ischemic neuronal degeneration. In this study, the ameliorating effect of a cytokine mixture consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 was evaluated on ischemic brain injury using a rat stroke model prepared by transient middle cerebral artery occlusion (tMCAO). The mixture reduced infarct volume and ameliorated ischemia-induced motor and cognitive dysfunctions. Sorted microglia cells from the ischemic hemisphere of rats administered the mixture showed reduced mRNA expression of tumor necrosis factor (TNF)-α and IL-1β at 3 days post-reperfusion. On flow cytometric analysis, the expression of CD86, a marker of pro-inflammatory type microglia, was suppressed, and the expression of CD163, a marker of tissue-repairing type microglia, was increased by the cytokine treatment. Immunoblotting and immunohistochemistry data showed that the cytokines increased the expression of the anti-apoptotic protein Bcl-xL in neurons in the ischemic lesion. Thus, the present study demonstrated that cytokine treatment markedly suppressed neurodegeneration during the chronic phase in the rat stroke model. The neuroprotective effects may be mediated by phenotypic changes of microglia that presumably lead to increased expression of Bcl-xL in ischemic lesions, while enhancing neuronal survival.

DOI： 10.3389/fnins.2022.941363

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The effectiveness of carmustine (BCNU) wafers on local recurrence of glioblastoma (GBM) remains contentious. We investigated the accumulating high-dose effects of BCNU released from the wafers on the survival of GBM patients by measuring BCNU concentration in the resection cavity of GBM over time. BCNU wafers (Gliadel®) were implanted with an Ommaya device in 15 patients, including 12 patients with GBM. BCNU concentrations in the tumor resection cavity were measured for 30 days postoperatively. The area under the curve (AUC)all was calculated from BCNU concentration curves, and the relationships between AUCall and survival, tumor phenotypes on MRI, and recurrence patterns were analyzed. The BCNU concentration was maximal 1 h postoperatively, rapidly decreased within 24 h, and remained relatively high for 7 days. GBM patients were classified into two groups: early recurrence (ER) and late or no recurrence (LN), using median progression-free survival as the cut-off. AUCall tended to be lower in the ER group than in the LN group, but the difference was not significant. MRI revealed that all patients in the ER group had highly invasive GBMs, whereas all patients in the LN group had less-invasive GBMs. A total of 9 patients experienced recurrence, with 6 local, 2 diffuse, and 1 disseminated patterns. No differences in AUCall were seen between local and non-local recurrence groups. Total BCNU concentrations did not correlate with tumor progression or survival. However, a high concentration of BCNU may have potential to provide some survival benefit for less-invasive type GBM.

DOI： 10.3390/brainsci12050567

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We previously reported that glioma stemlike cells (GSCs) exist in the area of the tumor periphery showing no gadolinium enhancement on magnetic resonance imaging. In the present work, we analyzed glucose metabolism to investigate whether lactate could be predictive of tumor invasiveness and of use in detection of the tumor invasion area in glioblastoma multiforme (GBM). METHODS: The expression of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase (PDH) was investigated in 20 patients. In GSC lines, LDH-A and PDH expression also was examined in parallel to assessments of mitochondrial respiration. We then investigated the relationship between lactate/creatine ratios in the tumor periphery measured by magnetic resonance spectroscopy, using learning-compression-model algorithms and phenotypes of GBMs. RESULTS: In 20 GBMs, high-invasive GBM expressed LDH-A at significantly higher expression than did low-invasive GBM, whereas low-invasive GBM showed significantly higher expression of PDH than did high-invasive GBM. The highly invasive GSC line showed higher expression of LDH-A and lower expression of PDH compared with low-invasive GSC lines. The highly invasive GSC line also showed the lowest consumption of oxygen and the lowest production of adenosine triphosphate. Lactate levels, as measured by magnetic resonance spectroscopy, showed a significant positive correlation with LDH-A transcript levels, permitting classification of the GBMs into high-invasive and low-invasive phenotypes based on a cutoff value of 0.66 in the lactate/creatine ratio. CONCLUSIONS: In the tumor periphery area of the highly invasive GBM, aerobic glycolysis was the predominant pathway for glucose metabolism, resulting in the accumulation of lactate. The level of lactate may facilitate prediction of the tumor-infiltrating area on GBM.

DOI： 10.1016/j.wneu.2021.06.044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Differentiating tumor from normal pituitary gland is very important for achieving complete resection without complications in endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenoma. To facilitate such surgery, we investigated the utility of indocyanine green (ICG) fluorescence endoscopy as a tool in ETSS. Twenty-four patients with pituitary adenoma were enrolled in the study and underwent ETSS using ICG endoscopy. After administering 12.5 mg of ICG twice an operation with an interval > 30 min, times from ICG administration to appearance of fluorescence on vital structures besides the tumor were measured. ICG endoscopy identified vital structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Elapsed times for internal carotid arteries did not differ according to tumor size. Conversely, as tumor size increased, elapsed times for normal pituitary gland were prolonged but those for the tumor were reduced. ICG endoscopy revealed a clear boundary between tumors and normal pituitary gland and enabled confirmation of no more tumor. ICG endoscopy could provide a useful tool for differentiating tumor from normal pituitary gland by evaluating elapsed times to fluorescence in each structure. This method enabled identification of the boundary between tumor and normal pituitary gland under conditions of a low-fluorescence background, resulting in complete tumor resection with ETSS. ICG endoscopy will contribute to improve the resection rate while preserving endocrinological functions in ETSS for pituitary adenoma.

DOI： 10.1007/s10143-020-01382-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The abilities to invade surrounding tissues and metastasize to distant organs are the most outstanding features that distinguish malignant from benign tumors. However, the mechanisms preventing the invasion and metastasis of benign tumor cells remain unclear. By using our own rat distant metastasis model, gene expression of cells in primary tumors was compared with that in metastasized tumors. Among many distinct gene expressions, we have focused on chloride intracellular channel protein 2 (CLIC2), an ion channel protein of as-yet unknown function, which was predominantly expressed in the primary tumors. We created CLIC2 overexpressing rat glioma cell line and utilized benign human meningioma cells with naturally high CLIC2 expression. CLIC2 was expressed at higher levels in benign human brain tumors than in their malignant counterparts. Moreover, its high expression was associated with prolonged survival in the rat metastasis and brain tumor models as well as with progression-free survival in patients with brain tumors. CLIC2 was also correlated with the decreased blood vessel permeability likely by increased contents of cell adhesion molecules. We found that CLIC2 was secreted extracellularly, and bound to matrix metalloproteinase (MMP) 14. Furthermore, CLIC2 prevented the localization of MMP14 in the plasma membrane, and inhibited its enzymatic activity. Indeed, overexpressing CLIC2 and recombinant CLIC2 protein effectively suppressed malignant cell invasion, whereas CLIC2 knockdown reversed these effects. Thus, CLIC2 suppress invasion and metastasis of benign tumors at least partly by inhibiting MMP14 activity.

DOI： 10.1016/j.neo.2021.06.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence, GSCs with highly invasive and highly migratory activities must assume a less-motile state and proliferate to regenerate tumor mass. Elucidating the molecular mechanism underlying this transition from a highly invasive phenotype to a less-invasive, proliferative tumor could facilitate the identification of effective molecular targets for treating GBM. Here, we demonstrate that severe hypoxia (1% O2) upregulates CD44 expression via activation of hypoxia-inducible factor (HIF-1α), inducing GSCs to assume a highly invasive tumor. In contrast, moderate hypoxia (5% O2) upregulates osteopontin expression via activation of HIF-2α. The upregulated osteopontin inhibits CD44-promoted GSC migration and invasion and stimulates GSC proliferation, inducing GSCs to assume a less-invasive, highly proliferative tumor. These data indicate that the GSC phenotype is determined by interaction between CD44 and osteopontin. The expression of both CD44 and osteopontin is regulated by differential hypoxia levels. We found that CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. Mouse brain tumors generated from CD44-knockdown GSCs exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene decreased GSC proliferation. These results suggest that interaction between CD44 and osteopontin plays a key role in tumor progression in GBM; inhibition of both CD44 and osteopontin may represent an effective therapeutic approach for suppressing tumor progression, thus resulting in a better prognosis for patients with GBM.

DOI： 10.1016/j.tranon.2021.101137

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Antiangiogenic therapy with bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is a common treatment for recurrent glioblastoma (GBM), but its survival benefit is limited. Resistance to Bev is thought to be a major cause of ineffectiveness on Bev therapy. To optimize Bev therapy, identification of a predictive biomarker for responsiveness to Bev is required. Based on our previous study, we focused on the expression and functions of CD44 and VEGF in the Bev therapy. Here, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti-VEGF therapy. CD44 and VEGF expression in the tumor core and periphery of 22 GBMs was examined, and the relationship between expression of these molecules and progression-free time on Bev therapy was analyzed. The degree of CD44 expression in the tumor periphery was evaluated by the ratio of the mRNA expression in the tumor periphery to that in the tumor core (P/C ratio). VEGF expression was evaluated by the amount of the mRNA expression in the tumor periphery. To elucidate the roles of CD44 in the Bev therapy, in vitro and in vivo studies were performed using glioma stem-like cells (GSCs) and a GSC-transplanted mouse xenograft model, respectively. GBMs expressing high P/C ratio of CD44 were much more refractory to Bev than those expressing low P/C ratio of CD44, and the survival time of the former was much shorter than that of the latter. In vitro inhibition of VEGF with siRNA or Bev-activated CD44 expression and increased invasion of GSCs. Bev showed no antitumor effects in mice transplanted with CD44-overexpressing GSCs. The P/C ratio of CD44 expression may become a useful biomarker predicting responsiveness to Bev in GBM. CD44 reduces the antitumor effect of Bev, resulting in much more highly invasive tumors.

DOI： 10.1002/cam4.3767

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

DOI： 10.1093/neuonc/noaa199

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To evaluate the effects on cognitive function of deep white matter hyperintensities (DWMHs) on magnetic resonance imaging (MRI) in patients treated surgically for unruptured intracranial aneurysms (UIAs). The subjects were 106 patients in whom a Wechsler adult intelligence scale-revised (WAIS-R) examination was performed 1 week before and 1 month after clipping surgery for asymptomatic UIAs. DWMH severity was evaluated on preoperative MR images by Fazekas scale, as follows: none (absence), mild (punctate foci), moderate (beginning confluence of foci), or severe (large confluent areas). A decrease of 7 or more points in intelligence quotient (IQ) postoperatively was considered deterioration. Fazekas score was none in 41 (none group), mild in 42 (mild group), moderate in 21, and severe in 2 patients (moderate/severe group). Patient characteristics, surgical factors, IQ change, and abnormal findings on postoperative MRI were compared among the groups. Although there was no statistically significant deterioration in IQ postoperatively in any group, the percentage of deteriorated patients was significantly higher in the moderate/severe group (34.8%) than in the other groups (4.9% in the none group, 7.1% in the mild group; p <0.01, p <0.05, respectively). Brain injury was observed more frequently on postoperative MR images in the moderate/severe group (17.4%) compared with the none group (2.4%; p = 0.052). The presence of moderate/severe DWMHs was an independent prognostic factor for postoperative cognitive dysfunction. In conclusion, the presence of moderate/severe DWMHs was a prognostic factor for postoperative cognitive dysfunction after surgery for UIAs.

DOI： 10.2176/nmc.oa.2020-0290

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma multiforme (GBM) is largely due to glioma stem cells (GSCs) that escape from total resection of gadolinium (Gd)-enhanced tumor on MRI. The aim of this study is to identify the imaging requirements for maximum resection of GBM with infiltrating GSCs. We investigated the relationship of tumor imaging volume between MRI and 11C-methionine (Met)-PET and also the relationship between Met uptake index and tumor activity. In ten patients, tumor-to-contralateral normal brain tissue ratio (TNR) was calculated to evaluate metabolic activity of Met uptake areas which were divided into five subareas by the degrees of TNR. In each GBM, tumor tissue was obtained from subareas showing the positive Met uptake. Immunohistochemistry was performed to examine the tumor proliferative activity and existence of GSCs. In all patients, the volume of Met uptake area at TNR ≦ 1.4 was larger than that of the Gd-enhanced area. The Met uptake area at TNR 1.4 beyond the Gd-enhanced tumor was much wider in high invasiveness-type GBMs than in those of low invasiveness type, and survival was much shorter in the former than the latter types. Immunohistochemistry revealed the existence of GSCs in the area showing Met uptake at TNR 1.4 and no Gd enhancement. Areas at TNR > 1.4 included active tumor cells with relatively high Ki-67 labeling index. In addition, it was demonstrated that GSCs could exist beyond the border of Gd-enhanced tumor. Therefore, to obtain maximum resection of GBMs, including infiltrating GSCs, aggressive surgical excision that includes the Met-positive area at TNR 1.4 should be considered.

DOI： 10.1007/s10143-020-01258-7

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion?


</sec>
<sec>
<title>Methods</title>
Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI).


</sec>
<sec>
<title>Results</title>
A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI.


</sec>
<sec>
<title>Conclusion</title>
CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.


</sec>

DOI： 10.1093/noajnl/vdab086

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その他リンク： http://academic.oup.com/noa/article-pdf/3/1/vdab086/39555495/vdab086.pdf

記述言語：英語  

Background: Onyx has already been reported as an effective and safe agent in transarterial embolization of cranial dural arteriovenous fistula (d-AVF). However, successful treatment is related to not only complete shunt obliteration but also preservation of a normal route of venous drainage. Here, we present a case of transverse sigmoid d-AVF in which successful treatment was achieved by transarterial Onyx embolization with targeted balloon protection of the venous drainage. Case Description: A 70-year-old man presented with a 3-month history of tinnitus in the left ear and mild headache. Magnetic resonance imaging (MRI) showed a cluster of abnormal blood vessels in the area of the left transverse sinus (TS)-sigmoid sinus (SS) junction. Cerebral angiography demonstrated a Cognard type IIa d-AVF at the left TS-SS junction, supplied mainly by vessels such as the left middle meningeal artery, left occipital artery, and left meningohypophyseal trunk. In the venous phase, the ipsilateral TS-SS was recognized as a functional sinus and the left vein of Labbe drained into the TS near the drainage channel. Based on these findings, we decided to perform endovascular treatment under a transarterial approach with Onyx using targeted balloon protection of the venous sinus to protect against Onyx migration and preserve antegrade sinus flow. The patient recovered well without sequelae, and follow-up MRI 12 months later showed complete disappearance of the d-AVF. Conclusion: This treatment strategy using targeted balloon protection may be very useful to preserve antegrade sinus flow in patients with Cognard type IIa d-AVF.

DOI： 10.25259/SNI_503_2021

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記述言語：英語  

Background: Sarcoidosis is a multisystem disorder characterized by noncaseating epithelioid granulomas. However, neurosarcoidosis occurring only in the medulla oblongata is very rare and lacks specific imaging and clinical features. We report a rare case of neurosarcoidosis arising from the medulla oblongata alone, suggesting the significance of pathological findings for accurate diagnosis. Case Description: A 78-year-old woman with a history of rheumatoid arthritis was admitted to our hospital with a 3-month history of progressive numbness in bilateral lower extremities and gait disturbance. Neurological examination on admission showed mild bilateral paired paralysis of the lower limbs (manual muscle test: right 2/V; left 4/V) and marked numbness in the right lower limb. Neuroimaging revealed a solid mass with clear boundaries in the dorsal medulla oblongata appearing hypointense on T1-weighted imaging (WI), hyperintense on T2-WI, and hypointense on diffusion WI (DWI), with strong enhancement on gadolinium-enhanced T1-WI. Cerebrospinal fluid analysis showed moderately elevated levels of protein and lymphocytic cells. Biopsy to determine the exact diagnosis revealed histological findings of noncaseating epithelioid granulomas and inflammatory infiltration, consistent with sarcoidosis. Postoperatively, corticosteroid therapy with prednisolone was initiated as soon as possible, resulting in marked reductions in lesion size. Follow-up neuroimaging after 12 months showed no signs of recurrence. Conclusion: Neurosarcoidosis is difficult to diagnose from routine neuroimaging and laboratory findings. Accurate diagnosis requires careful identification of clinical signs, hypointensity on DWI, and morphological findings from surgical biopsy.

DOI： 10.25259/SNI_195_2021

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記述言語：英語  

Background: In spinal instrumentation surgery, safe and accurate placement of implants such as lateral mass screws and pedicle screws should be a top priority. In particular, C2 stabilization can be challenging due to the complex anatomy of the upper cervical spine. Here, we present a case of Bow Hunter's syndrome (BHS) successfully treated by an O-arm-navigated atlantoaxial fusion. Case Description: A 53-year-old male presented with a 10-year history of repeated episodes of transient loss of consciousness following neck rotation to the right. Although the unenhanced magnetic resonance imaging showed no pathological findings, the MR angiogram with dynamic digital subtraction angiography revealed a dominant left vertebral artery (VA) and hypoplasia of the right VA. The latter study further demonstrated significant flow reduction in the left VA at the C1-C2 level when the head was rotated toward the right. With these findings of BHS, a C1-C2 decompression/posterior fusion using the Goel-Harms technique with O-arm navigation was performed. The postoperative cervical X-rays showed adequate decompression/fixation, and symptoms resolved without sequelae. Conclusion: C1-C2 posterior decompression/fusion effectively treats BHS, and is more safely/effectively performed utilizing O-arm navigation for C1-C2 screw placement.

DOI： 10.25259/SNI_786_2021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Recognizing the anatomical orientation surrounding the sellar floor is crucial in endoscopic endonasal transsphenoidal surgery (ETSS). Zero-echo-time (ZTE) sequences were recently suggested for a new bone identification technique on magnetic resonance imaging (MRI). This study aimed to evaluate the clinical usefulness of three-dimensional (3D)-ZTE-based MRI models in providing anatomical guidance for ETSS. PATIENTS AND METHODS: ZTE-based MRI and magnetic resonance angiography (MRA) data from 15 consecutive patients with pituitary tumor treated between September 2018 and May 2019 were used to create 3D-MRI models. From these, the architecture surrounding the sellar floor, particularly anatomical relationships between tumors and internal carotid arteries (ICAs), was visualized to preoperatively plan surgical procedures. In addition, 3D-ZTE-based MRI models were compared to actual surgical views during ETSS to evaluate model applicability. RESULTS: These 3D-ZTE-based MRI models clearly demonstrated the morphology of the sellar floor and matched well with intraoperative views, including pituitary tumor, by successively eliminating sphenoidal structures. The models also permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and tumors. With such 3D-MRI models, the surgeon could access the intracranial area through the sellar floor more safely, and resect the pituitary tumor maximally without complications. CONCLUSION: Our 3D-MRI models based on ZTE sequences allowed distinct visualization of vital structures and pituitary tumor around the sellar floor. This new method using 3D-ZTE-based MRI models showed low invasiveness for patients and was useful in preoperative planning for ETSS, facilitating maximum tumor resection without complications.

DOI： 10.1016/j.clineuro.2020.105743

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記述言語：英語  

Background: Epithelioid glioblastoma is a rare aggressive variant of glioblastoma multiforme (GBM), which was formally recognized by the World Health Organization classification of the central nervous system in 2016. Clinically, epithelioid GBMs are characterized by aggressive features, such as metastases and cerebrospinal fluid dissemination, and an extremely poor prognosis. A rare case of epithelioid GBM that was discovered as a multicentric glioma with different histopathology is reported. Case Description: A 78-year-old man was admitted to our hospital with mild motor weakness of the right leg. Neuroimaging showed small masses in the left frontal and parietal lobes on magnetic resonance imaging. The abnormal lesion had been increasing rapidly for 3 weeks, and a new lesion appeared in the frontal lobe. 11C-methionine positron emission tomography (PET) showed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the right frontal mass lesion was performed. Histological findings showed diffuse astrocytoma. Only radiotherapy was planned, but the left frontal and parietal tumors progressed further within a short period. Therefore, it was thought that these tumors were GBM, and a biopsy of the left parietal tumor was performed. The histological diagnosis was epithelioid GBM. Immunohistochemistry showed that most tumor cells were negatively stained for p53 and isocitrate dehydrogenase 1. BRAF V600E mutations were not identified, but TERT promoter mutations were identified. Immediately after surgery, the patient was given chemotherapy using temozolomide, extended local radiotherapy and then bevacizumab. After 6 months, he showed no signs of recurrence. Conclusion: Epithelioid GBM is one of the rarest morphologic subtypes of GBM and has a strongly infiltrative and aggressive nature. Therefore, careful identification of preoperative imaging studies and detailed evaluation of genetic studies are necessary to select the appropriate treatment for epithelioid GBM.

DOI： 10.25259/SNI_544_2019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup (P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro. However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM.

DOI： 10.1371/journal.pone.0243272

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記述言語：英語  

Background: The findings of a hyperintense sign on T2-weighted imaging (T2-WI) and gadolinium (Gd) contrast enhancement on magnetic resonance imaging (MRI) of the brain stem suggest malignant glioma. However, this pathological condition is probably uncommon, and it may be unknown that a dural arteriovenous fistula (DAVF) can imitate this radiological pattern. In addition, it is extremely rare to be caused by a spinal DAVF. Here, a rare case of spinal DAVF that mimicked malignant glioma of the medulla oblongata is presented. Case Description: A 56-year-old woman was admitted with a progressive gait disturbance, vertigo, and dysphasia. MRI showed a hyperintense signal in the medulla oblongata on fluid-attenuated inversion recovery (FLAIR) and moderate contrast enhancement on Gd-enhanced MRI. Interestingly, Gd-enhanced MRI demonstrated abnormal dilated veins around the brain stem and cervical spinal cord. Cerebral angiography showed spinal DAVF at the left C4/C5 vertebral foramen fed by the C5 radicular artery. The fistula drained into spinal perimedullary veins and flowed out retrograde at the cortical vein of the posterior cranial fossa. Therefore, surgical disconnection of the spinal DAVF was performed by a posterior approach. The patient's postoperative course was uneventful. Cerebral angiography showed complete disappearance of the DAVF, with marked reductions of the hyperintense sign of the medulla oblongata on FLAIR. Conclusion: This important case illustrates MRI findings mimicking brain stem glioma. In cases with the hyperintense sign-on T2-WI associated with contrast enhancement suspicious of brainstem glioma, careful checking for perimedullary abnormal vessels and additional cerebral angiography should be performed.

DOI： 10.25259/SNI_437_2020

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記述言語：英語  

Background: Granular cell tumor (GCT) of the sellar region is a rare tumor of the sellar and suprasellar regions that originate from the neurohypophysis. This tumor is very difficult to differentiate from other pituitary neoplasms, such as pituitary adenoma, pituicytoma, and spindle cell oncocytoma. We report a rare case of GCT arising from the posterior pituitary of the sellar region and suggest a useful indicator for accurate diagnosis and pitfalls for surgical procedures. Case Description: A 42-year-old woman was admitted to our hospital with bitemporal hemianopsia. Neuroimaging showed a large pituitary tumor in the sellar and suprasellar regions with a hypointense part on T2-weighted magnetic resonance imaging, and the enhanced anterior pituitary gland was displaced anteriorly. Laboratory findings showed mild hyperprolactinemia. Subtotal resection of the tumor was achieved using an endoscopic endonasal transsphenoidal approach. Histological findings showed round or polygonal cells with abundant granular eosinophilic cytoplasm staining strongly for thyroid transcription factor 1. The tumor was, therefore, diagnosed as a GCT of the sellar region, belonging to tumors of the posterior pituitary. After surgery, visual impairment and anterior pituitary function were improved. Follow-up neuroimaging after 1 year showed no signs of recurrence. Conclusion: GCT of the sellar region is difficult to diagnose on routine neuroimaging. Therefore, accurate diagnosis requires careful identification of clinical signs, magnetic resonance imaging including hypointensity on T2-weighted imaging, and analysis of combined morphological and immunohistochemical studies.

DOI： 10.25259/SNI_111_2020

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Dermoid cysts are rare benign intracranial neoplasms derived from embryonal remnant tissues. Here, we describe a case of dermoid cyst located in the right frontal lobe, which showed repeated changes on CT. An 11-year-old girl was referred to our hospital to treat a brain neoplasm. Brain CT and MRI revealed a cystic tumor in the right frontal lobe. Incidentally, brain CT had been performed 6, 2, and 1 year before the presentation, which demonstrated repeated changes in the tumor over the clinical course. Gross total resection of the tumor was achieved through right frontal craniotomy. Histological findings revealed keratin flakes, mature bones, cholesterol crystals, and granulation with macrophages. The cyst wall was composed of squamous epithelium with adnexal structures, such as hair follicles and sebaceous glands. Therefore, we diagnosed the tumor as a dermoid cyst. The postoperative course was uneventful, and she was discharged on postoperative day 10 without neurological deficits. Dermoid cysts are difficult to be diagnosed on routine neuroimaging. An accurate diagnosis requires details of the clinical course and analysis of both imaging and pathological studies.

DOI： 10.11477/mf.1436204021

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

© 2018 We report a rare case of pituicytoma occurring in the sellar region resected by endoscopic transsphenoidal surgery (ETSS). We suggest useful indicators for the accurate diagnosis and pitfalls for the surgical procedure. A 38-year-old man was admitted to our hospital with polyuria, erectile dysfunction and bitemporal hemianopsia. Neuroimaging revealed pituitary tumor in the sellar region, and the enhanced anterior pituitary gland was displaced anteriorly. Gross total resection was achieved using ETSS. Histological findings revealed bipolar spindle cells staining strongly for thyroid transcription factor 1 (TTF-1). We diagnosed the tumor as pituicytoma originated from posterior pituitary. Pituicytoma is difficult to diagnose on routine neuroimaging and pathological analysis, so accurate diagnosis requires identification of the forward deviation of anterior pituitary gland and analysis of immunohistochemical studies using TTF-1.

DOI： 10.1016/j.inat.2018.12.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVEHigh invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT).METHODSIn vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated.RESULTSThe 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.CONCLUSIONSThe 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

DOI： 10.3171/2017.6.JNS162398

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Postoperative neurological deficits frequently occur in adult moyamoya disease. In this case report, we describe the time course and disease state of a patient with adult moyamoya disease, who experienced a postoperative neurological deficit due to transient hypoperfusion in the pretreated contralateral hemisphere. A 68-year-old female presented with a sudden onset of left hemianopia due to ischemic moyamoya disease. She had severely low cerebral blood flow(CBF)in the right hemisphere and deterioration of cerebrovascular reactivity in the left hemisphere. First, right combined bypass surgery was performed; subsequently, left combined bypass surgery was performed. Two days after left hemisphere surgery, left hemiparesis gradually appeared. Hypoperfusion of the right hemisphere and hyperperfusion of the left hemisphere were revealed by SPECT and CT perfusion imaging. Blood pressure was controlled to normal levels, and an antiepileptic drug, antiplatelet drug, and edaravone were administered. The patient gradually recovered 2 weeks later, and was able to resume her normal daily life. During the clinical course, laterality of CBF was improved following improvement of clinical symptoms. Abnormal postoperative disproportion of the CBF may occur after revascularization surgery for adult moyamoya disease. Prompt assessment of CBF and proper treatment are needed.

DOI： 10.11477/mf.1436203740

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Intracranial pure germinomas in children generally respond well to standard chemo-radiotherapy. However, some patients are refractory to standard therapy and require additional treatment. To investigate the characteristics of this subgroup, we retrospectively analyzed the clinical features and treatment outcomes of a cohort of 21 patients with intracranial pure germinomas who were diagnosed between April 2002 and December 2016 at Ehime University Hospital in Japan. Pure germinoma diagnosis was verified by histological examination of the tumor after surgery, and all patients received standard chemo-radiotherapy. A suite of clinical features, including neuroimaging, human chorionic gonadotropin-β subunit (HCG-β), and α-fetoprotein (AFP) in the cerebrospinal fluid (CSF), as well as immunohistochemical expression of HCG-β, AFP, and Ki-67 in the tumor tissue were analyzed. Nineteen of the 21 patients had a complete response to standard chemo-radiotherapy without early recurrence of the tumors. Of these 19 patients, 17 did not have elevated CSF HCG-β levels or express HCG-β in the tumor tissue. However, the two patients who were refractory to standard therapy had elevated CSF HCG-β levels and expressed HCG-β in the tumor cells. These data suggest that patients with pure germinoma presenting with both an elevation of HCG-β in the CSF and HCG-β expression in the tumor tissue may be refractory to frontline treatment. These markers may predict aggressive germinoma and may ultimately facilitate the development of more effective treatment options.

DOI： 10.1007/s10143-017-0891-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Small and broad-necked aneurysms are generally very difficult to treat using endovascular therapy. The arrival of the low-profile stent (e.g., Low-profile Visualized Intraluminal Support; LVIS) has enabled reconstructive treatment for these aneurysms. In addition, the bulging technique using LVIS is an effective and attractive technique for performing stent-assisted coiling to preserve parent arteries and achieve neck coverage. We report here a patient with a small and wide-necked ruptured basilar artery (BA) top aneurysm, in whom successful treatment was achieved by stent-assisted coiling with LVIS Jr. using the bulging technique. A 74-year-old woman with moderate hypertension consulted for treatment of subarachnoid hemorrhage with a ruptured BA top aneurysm measuring 2.7 mm in height with a 4.3 mm neck. We initially tried emergency balloon-assisted coiling, but coiling proved difficult. We therefore performed stent-assisted coiling with LVIS Jr. using the bulging technique. The postoperative course was uneventful, with no aggravation of neurological symptoms, and the patient was discharged 14 days postoperatively. This treatment strategy with LVIS Jr. using the bulging technique may be very useful for patients with a ruptured aneurysm with a small and broad neck that would otherwise require treatment with intravascular devices or open surgery.

DOI： 10.1177/1591019917743065

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記述言語：英語  

Medulloepithelioma is a rare and highly malignant primitive neuroectodermal tumor that usually occurs in childhood. The diagnosis of this entity required only morphological analysis until the World Health Organization classification of central nervous system (CNS) tumors was revised, and now genetic analysis is necessary. We report a case of medulloepithelioma in the posterior cranial fossa that was diagnosed by both morphological and genetic analyses based on this classification. A 10-month-old girl was admitted to our hospital with consciousness disturbance and vomiting. Neuroimaging revealed a partially calcified mass and cyst formation in the posterior cranial fossa. Partial resection of the tumor was performed and histological findings revealed multilayered rosettes with LIN28A staining, but genetic analysis showed no amplification of the C19MC microRNA cluster at 19q14.32. Therefore, we diagnosed the tumor as medulloepithelioma belonging to other CNS embryonal tumors. The patient was immediately treated with systemic high-dose chemotherapy. Follow-up neuroimaging 10 months later showed no signs of recurrence. Medulloepitheliomas are difficult to diagnose by routine HE staining and require combined morphological, immunohistochemical and genetic analyses to provide an accurate diagnosis.

DOI： 10.1111/neup.12431

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the study is to identify characteristic features of pineal germinoma that enhance preoperative accuracy in differentiating germinoma from other pineal region tumors. Twenty-one consecutive patients with pineal region tumors were enrolled. In all patients, tumor resection was performed to verify the histology. Clinical records including upward gaze palsy of Parinaud's syndrome and neuroimaging were analyzed. In addition, we evaluated the relationship between magnetic resonance imaging (MRI) findings and tumor progression patterns in pineal germinoma. Among 21 patients, 15 patients were diagnosed with germ cell tumor, 4 with pineal parenchymal cell tumor, and 2 with meningioma. Upward gaze palsy was seen in 11 patients; nine had pure germinomas and two had mixed germ cell tumors. These tumors occupied the pineal region with extension to the area of the mesodiencephalic junction (MDJ) and the bi-epithalamic area between the bilateral pulvinar and the third ventricle. Tumor involvement of the former area could cause upward gaze palsy by insulting the rostral interstitial nucleus of the medial longitudinal fasciculus located in the MDJ area. Tumor invasion into the latter area is commonly seen as a cardioid-shaped tumor as the tumor image on the axial MRI view. Upward gaze palsy and a cardioid-shaped tumor image on the axial MRI views were demonstrated to be specific features of pineal pure germinoma. It is suggested that combination of both features may become useful tools to preoperatively differentiate germinoma from other pineal tumors, resulting in achievement of the optimum treatment of pineal region tumors.

DOI： 10.1007/s10143-017-0835-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare and treatable variant of cerebral amyloid angiopathy, lacks specific imaging and clinical features, and requires invasive brain biopsy to confirm the diagnosis. We report the case of a patient with nonconvulsive status epilepticus (NCSE) caused by CAA-ri in the right occipital lobe. PRESENTATION OF CASE: A 78-year-old man with a history of hypertension and rheumatoid arthritis was admitted to our hospital following an episode of seizures. CT scan showed a low-attenuating subcortical lesion in the right occipital lobe. MRI revealed the lesion as hypointense on T1-weighted imaging (WI) and hyperintense on T2-WI, showing no enhancement on T1-WI contrast-enhanced with gadolinium. In addition, T2*-weighted gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI) revealed extensive cortical microbleeds. Biopsy to determine the exact diagnosis revealed histological findings of reactive changes and perivascular inflammatory infiltration associated with amyloid deposition in vessel walls. These findings were consistent with CAA-ri. Corticosteroid therapy with dexamethasone was initiated for a short period as a diagnostic and therapeutic maneuver, resulting in marked reductions in the lesion. DISCUSSION: CAA is generally associated with intracerebral hemorrhage, dementia, and small cerebral infarctions in the elderly population, but in a small proportion of cases is related to inflammatory responses to vascular deposits of Aβ, as so-called CAA-ri. CONCLUSION: CAA-ri should be considered among the differential diagnoses for causes of unprovoked seizure onset in elderly individuals, when associated with petechial hemorrhages on T2*-GRE and SWI sequences on MRI.

DOI： 10.1016/j.ijscr.2018.05.016

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記述言語：英語  

Background: Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology within the third ventricular region, but with radiological and histopathological features mimicking benign lesions such as meningioma. We report a case of chordoid glioma of the third ventricle and suggest a useful indicator for accurate diagnosis. Case Description: A previously healthy 46-year-old woman was admitted to our hospital with mild headache. Neuroimaging revealed a large tumor measuring approximately 18 mm in the suprasellar region, and perifocal edema in the optic tract and internal capsule on magnetic resonance imaging. Laboratory findings revealed no pituitary dysfunction including diabetes insipidus. Gross total resection of the tumor was performed by the interhemispheric translamina terminalis approach. Histological findings revealed nests of regular epithelioid cells with large nuclei and abundant eosinophilic cytoplasm within myxoid stroma. Immunohistochemical studies demonstrated diffuse cytoplasmic expression of glial fibrillary acidic protein (GFAP) and CD34, and strong nuclear staining for thyroid transcription factor 1 (TTF-1). We, therefore, histologically classified the tumor as chordoid glioma of the third ventricle. Headache improved immediately postoperatively, and follow-up neuroimaging after 12 months showed no signs of recurrence. Conclusions: Chordoid glioma of the third ventricle is a very rare tumor that is difficult to diagnose on routine neuroimaging. Accurate diagnosis requires detailed analysis of neuroimaging and immunohistochemical studies using CD34 and TTF-1 staining.

DOI： 10.4103/sni.sni_306_18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and a subpopulation of glioma stem-like cells (GSCs) is likely responsible for the invariable recurrence following maximum resection and chemoradiotherapy. As most GSCs that are located in the perivascular and perinecrotic niches should be removed during tumor resection, it is very important to know where surviving GSCs are localized. Here, we investigated the existence and functions of GSCs in the tumor periphery, which is considered to constitute the invasion niche for GSCs in GBM, by analyzing expression of stem cell markers and stem cell-related molecules and measuring particular activities of cultured GSCs. In addition, the relationship between GSCs expressing particular stem cell markers and pathological features on MRI and prognosis in GBM patients was analyzed. We showed that GSCs that express high levels of CD44 are present in the tumor periphery. We also found that vascular endothelial growth factor (VEGF) is characteristically expressed at a high level in the tumor periphery. Cultured GSCs obtained from the tumor periphery were highly invasive and have enhanced migration phenotype, both of which were markedly inhibited by CD44 knockdown. Higher expression of CD44 in the tumor periphery than in the core was correlated with a highly invasive feature on MRI and was associated with early tumor progression and worse survival, whereas lower expression of CD44 in the tumor periphery corresponded to low invasion and was associated with longer survival. The low invasion type on MRI tended to show high levels of VEGF expression in the tumor periphery, thus presenting the tumor with high proliferative activity. These results imply the significance of GSCs with high levels of CD44 expression in the tumor periphery compared to the core, not only in tumor invasion but also rapid tumor progression and short survival in patients with GBM.

DOI： 10.1155/2018/5387041

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report the case of a patient who has progressed well over 5 years following single-stage aneurysm clipping and superficial temporal artery-middle cerebral artery(STA-MCA)double anastomoses in the acute phase, for a ruptured distal anterior choroidal artery(AChA)aneurysm accompanied by a twig-like MCA. The patient was a 49-year-old female who developed a sudden severe headache and disturbance of consciousness due to subarachnoid hemorrhage and intraventricular hemorrhage(IVH). Cerebral angiography showed a right twig-like MCA associated with an abnormal vascular network and a ruptured aneurysm in the distal AChA. A day after emergency ventricular drainage for acute hydrocephalus, right frontotemporal craniotomy enabled distal AChA aneurysm clipping, together with removal of the IVH via transchoroidal fissure approach, in addition to STA-MCA double anastomoses to prevent recurrence of hemorrhage. The IVH resolved after surgery and no new infarct area was observed. Cerebral angiography revealed the disappearance of the aneurysm, good patency of the double bypass, and reduction of the abnormal vascular network. The patient gradually recovered without any neurological deficits, except for mild memory disturbance. Five years after the surgery, the patient has experienced no recurrence. The single-stage operation of aneurysm clipping and STA-MCA double anastomoses was made possible by devising an approach for a ruptured cerebral aneurysm, even in the acute stage. The successful improvement of cerebral circulation and prevention of cerebral hemorrhage from an early stage could serve as a reference for the treatment of similar hemorrhagic cases.

DOI： 10.11477/mf.1436203576

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We investigated the efficacy of early superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses for patients with progressing stroke due to atherosclerotic occlusion. MATERIALS AND METHODS: Nine consecutive patients who underwent early STA-MCA double anastomoses were enrolled. All patients presented with progressing stroke despite maximal medical treatment. Cerebral blood flow in 7 patients was analyzed by single-photon emission tomography. Clinical outcomes were investigated postoperatively, and we evaluated the utility of early STA-MCA double anastomoses. RESULTS: Nine patients in the present study included those with middle cerebral artery occlusion (n = 6) and internal carotid artery occlusion (n = 3). The mean age was 58.4 years. Subjects comprised 1 female (11.1%) and 8 males (88.9%). The cause was low perfusion ischemia due to atherosclerotic occlusion with a small infarct. The mean regional cerebral blood flow (rCBF) ratio in the middle cerebral artery territory compared to the normal side was 69.6 ± 5.3%. The duration from onset to surgery was 1-8 days (median, 3.11 days). All patients underwent early STA-MCA double anastomoses, and no reperfusion-induced hemorrhage occurred. All of them slowly achieved obvious remission compared to symptoms on admission and achieved a good functional outcome. CONCLUSIONS: Early STA-MCA double anastomoses were safe and effective, and early revascularization resulted in rapid neurological improvement. We recommend this procedure for patients with progressive ischemia due to main trunk artery occlusion, when the rCBF flow ratio with the normal side was 70 ± 10%, even at the subacute stage.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.10.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Crowned dens syndrome is a rare disease entity which radiologically shows calcification of the cruciform ligament around the odontoid process. We report a patient with crowned dens syndrome who improved dramatically in 5days following treatment with oral nonsteroidal anti-inflammatory medication. PRESENTATION OF CASE: A 61-year-old man was admitted to our hospital with a severe occipital headache and sudden onset of neck stiffness. Neurological examination on admission revealed a high fever and cervical rigidity. Laboratory examination revealed a markedly elevated white blood cell count and C-reactive protein level, but cerebrospinal fluid studies revealed only a slight abnormality. A cervical computed tomography scan and its three-dimensional reconstruction detected a remarkable crown-like calcification surrounding the odontoid process. Cervical magnetic resonance imaging did not demonstrate strong direct compression of the cervical cord; however, the soft tissue surrounding the odontoid process was hyperintense on T2-weighted imaging with fat suppression. Based on the radiological findings, the patient was diagnosed with crowned dens syndrome and was immediately treated with non-steroidal anti-inflammatory drugs. The patient's condition drastically improved within 5days. DISCUSSION: It was very interesting that the soft tissue surrounding the odontoid process was hyperintense on magnetic resonance T2-weighted imaging with fat suppression, and the signal change disappeared 2 weeks after the administration of oral non-steroidal anti-inflammatory drugs. We think that magnetic resonance imaging is useful for proving inflammation in patients with crowned dens syndrome. CONCLUSION: This is the first report making reference to the magnetic resonance imaging findings of crowned dens syndrome.

DOI： 10.1016/j.ijscr.2016.11.045

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The long-term outcome of patients with adult moyamoya disease following revascularization surgery remains unclear. Here, we investigated these outcomes more than five years after revascularization surgery. PATIENTS AND METHODS: This study included 48 cerebral hemispheres from 26 patients who underwent revascularization surgery for adult moyamoya disease. The mean follow-up duration was 14.3(5.5-25.6)years. The risk factors of late-onset hemorrhage after revascularization surgery were compared between the bleeding and non-bleeding groups. We also estimated cumulative bleeding-free survival rates using Kaplan-Meier curves. RESULTS: Four patients experienced late-onset bleeding during the follow-up period. Bleeding occurred after an average of 11(8.5-16.4)years following revascularization surgery. The annual hemorrhagic rate was 1.14%. In the bleeding group, higher Suzuki stage(p=0.02), posterior cerebral artery(PCA)involvement(p<0.01), cerebral aneurysm(p=0.04), microbleeds(p=0.03), and post-operative periventricular anastomosis, especially in the thalamus and the choroidal artery(p<0.01 and p=0.01 respectively), were significantly different from those in the non-bleeding group. Kaplan-Meier analysis showed that the probability of late-onset bleeding was higher with postoperative periventricular anastomosis(p<0.01 for thalamic type, p=0.01 for choroidal type), higher Suzuki stage(p<0.01), PCA involvement(p<0.01), and cerebral aneurysm(p=0.02). CONCLUSIONS: In spite of good perfusion and reduction in moyamoya vessels after revascularization surgery, the risk of bleeding persisted. Periventricular anastomosis, especially in the thalamus and choroidal artery, after surgery, higher Suzuki stage, presence of obstructive lesions in the PCA, and cerebral aneurysm may be associated with late-onset bleeding after surgery. More studies are needed to identify the risk factors for late-onset bleeding after revascularization surgery for moyamoya disease.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Giant cell tumors (GCTs) are histologically benign bone neoplasms with a locally aggressive nature that primarily occur in the epiphyses of the long bones. A small proportion of these tumors, however, occur in the pelvis, spine, or skull bones. Among these, GCTs of the skull base cannot be completely resected and require adjuvant therapy. We report a juvenile case of clival GCT that was successfully treated by endoscopic endonasal transsphenoidal surgery and subsequent adjuvant therapy with denosumab, a monoclonal antibody to receptor activator of nuclear factor-κB ligand. CASE DESCRIPTION: A 16-year-old boy was admitted to our hospital with progressively intolerable headache and right oculomotor nerve palsy. Computed tomography and magnetic resonance imaging showed a large tumor mass in the sphenoid sinus with extensive erosion of the clivus and compression of the right cavernous sinus. The tumor was resected by endonasal transsphenoidal surgery and histologically diagnosed as GCT. The giant cells showed positive immunostaining for CD68 and Mib-1 labeling index was less than 1.0%. Postoperative course was uneventful and the oculomotor disturbance was markedly improved. However, magnetic resonance imaging 2 weeks after surgery revealed marked enlargement of the tumor. Adjuvant therapy with denosumab was therefore initiated, resulting in marked reductions in tumor size. CONCLUSIONS: This is the first report to describe beneficial effects of denosumab in the treatment of GCT of the skull base.

DOI： 10.1016/j.wneu.2016.04.054

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Herein, we describe the case of a superficial temporal artery(STA)- and occipital artery (OA)-middle cerebral artery (MCA) double anastomoses that we performed to treat a hemorrhagic twig-like MCA. A 55-year-old man presented to our hospital for investigation of an incidentally identified left MCA occlusion. Left cerebral angiography revealed a twig-like MCA. The (123)I-IMP-single photon emission computed tomography( SPECT) demonstrated no reduction in the cerebral blood flow (CBF), so the patient was initially observed with no treatment. Three months later, he was readmitted with a disturbance of consciousness. The cranial computed tomography revealed a subcortical hemorrhage in the left frontotemporal region and a subdural hematoma. The hematoma was removed via emergency craniotomy. The abnormal vessels were identified and resected, but the parietal branch of the STA was damaged during the skin incision. The histological examination did not reveal the marked fibrous thickening of the intima or wavy internal elastic lamina typically seen with Moyamoya disease. Six months after the initial surgery, a STA-MCA bypass surgery was planned to prevent a future hemorrhage by reducing the hemodynamic overload of the twig-like MCA and improving the cerebral ischemia in the MCA territory that was detected on the preoperative SPECT. However, the parietal branch of the left STA had been injured during the first operation, so we performed a double anastomoses to the MCA using the frontal branch of the STA and the OA. The patient's postoperative course was uneventful and he was discharged 2 weeks after surgery. The follow-up study performed 1 year postoperatively demonstrated no evidence of cerebral infarction and revealed an improvement in the resting CBF and vascular reactivity in the left cerebral hemisphere. No subsequent cerebrovascular events have occurred in this patient during the 7 years since the double anastomoses surgery. Direct bypass for flow conversion from the internal carotid artery to the external carotid artery can be an indispensable treatment for patients with a hemorrhagic twig-like MCA.

DOI： 10.11477/mf.1436203312

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Multicentric gliomas are well-separated tumors in different locations of the brain, without anatomical continuity between lesions. We report a rare case of multicentric gliomas that occurred in both supra- and infratentorial regions with different histopathology. CASE PRESENTATION: A 27-year-old man was admitted to our hospital with mild motor weakness of the right leg. Magnetic resonance imaging (MRI) showed a large tumor occupying the left insula, extending to the left basal ganglia, so tumor resection was performed. Histological diagnosis was diffuse astrocytoma. Tumor cells showed sporadic immunoreactivity for p53 and negative immunostaining for epidermal growth factor receptor (EGFR). Postoperative course was uneventful, and adjuvant therapy was not performed. At 7 months after surgery, MRI disclosed a left cerebellar tumor displaying an irregular ring formation on enhancement with gadolinium (Gd) and marked peritumoral edema. MRI studies including T2-weighted imaging demonstrated that this paravermian tumor had no contact with the initial left insular tumor. In addition, MRI studies of the whole neuraxis, cytological examination of the cerebrospinal fluid, and neurological findings demonstrated that no dissemination had occurred through the subarachnoid space or as intracerebral metastases. Therefore, the second surgery was performed. Histological diagnosis was glioblastoma. Immunohistochemistry revealed that most tumor cells were positively stained for both p53 and EGFR but negatively stained for isocitrate dehydrogenase 1 (IDH1). CONCLUSIONS: We reported a case of multicentric gliomas occurring in both supra- and infratentorial regions with different histopathology. Immunohistochemical examinations suggest that different genetic pathways may participate in the occurrence of these tumors.

DOI： 10.1186/s12957-016-0907-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Blood vessels in brain tumors, particularly glioblastomas, have been shown to express CD90. CD90(+) cells in and around blood vessels in cancers including brain tumors have been identified as endothelial cells, cancer stem cells, fibroblasts or pericytes. In this study, we aimed to determine the nature or type(s) of cells that express CD90 in human brain tumors as well as an experimental rat glioma model by double immunofluorescence staining. The majority of CD90(+) cells in human glioblastoma tissue expressed CD31, CD34 and von Willebrand factor, suggesting that they were endothelial cells. Vasculatures in a metastatic brain tumor and meningioma also expressed CD90. CD90(+) cells often formed glomeruloid structures, typical of angiogenesis in malignant tumors, not only in glioblastoma but also in metastatic tumors. Some cells in the middle and outer layers of the vasculatures expressed CD90. Similar results were obtained in the rat glioma model. There were cells expressing both α-smooth muscle actin and CD90 in the middle layer of blood vessels, indicating that smooth muscle cells and/or pericytes may express CD90. CD90(+) vasculatures were surrounded by tumor-associated macrophages (TAMs). Thus, in addition to endothelial cells, some other types of cells, such as smooth muscle cells, pericytes and fibroblasts constituting the vasculature walls in brain tumors expressed CD90. Because CD90 has been shown to interact with integrins expressed by circulating monocytes, CD90 might be involved in angiogenesis through recruitment and functional regulation of TAMs in tumors. CD90(+) vasculatures may also interact with tumor cells through interactions with integrins. Because CD90 was not expressed by vasculatures in normal brain tissue, it might be a possible therapeutic target to suppress angiogenesis and tumor growth.

DOI： 10.1111/neup.12244

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Adult unilateral moyamoya disease with intracranial aneurysm is frequently reported in the literature, but there is much variation in its treatment. In this case report, we describe the time course and treatment regimen of a patient with moyamoya disease and review the literature regarding moyamoya disease with intracranial aneurysm. A 64-year-old man had untreated intracranial aneurysm and unilateral moyamoya disease for 10 years. He presented with sudden-onset right hemiparesis and aphasia due to a subcortical hemorrhage. He was admitted to the local neurosurgical unit, and upon resolution of symptoms, he was admitted to our hospital. A cerebral angiogram revealed the champagne bottleneck sign of the left carotid artery and obliteration of the top of the left intracranial carotid artery with a moyamoya phenomenon. Two unruptured intracranial aneurysms were identified in the anterior communicating artery(Acom A) and the right intracranial carotid artery(C3). We performed superficial temporal artery-middle cerebral artery anastomosis followed by aneurysmal neck clipping of the Acom A aneurysm. Postoperative imaging showed no new ischemic damage and improved cerebral blood flow. Although the patient experienced temporal worsening of aphasia, his function recovered a few months later and he was able to resume his normal daily life activities. The combination of direct bypass surgery and aneurysmal neck clipping might be a therapeutic option for hemorrhagic unilateral moyamoya disease with unruptured intracranial aneurysm.

DOI： 10.11477/mf.1436203242

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Carmustine wafers are approved for localized treatment of malignant glioma. In this study, overall changes in computed tomography (CT) and magnetic resonance (MR) images of malignant glioma patients treated with carmustine wafer implantation were evaluated. The subjects were 25 patients undergoing craniotomy for malignant glioma resection and carmustine wafer implantation. Changes in the appearance of wafers, the resection cavity, and the adjacent parenchyma on CT and MR imaging were evaluated retrospectively. On CT, the wafers changed from an initially high-dense to an iso-dense appearance. All MR studies showed a low-intense wafer within 2 days. The wafers changed to a high- or iso-intense appearance on fluid attenuated inversion recovery and T1-weighted imaging, whereas they changed to an iso- to low-intense appearance on T2-weighted imaging. Gas in the cavity increased gradually after surgery, achieved a peak at 1 week postoperatively, and then disappeared in 1-3 months. Increased volume of the resection cavity was observed in 48% of patients. Regarding changes in the adjacent parenchyma, obvious contrast enhancement at the wall of the resection cavity was seen in 91% of cases at 1 month, but this disappeared gradually. Edema around the resection cavity was increased in 7 patients (28%), of whom only two experienced symptoms due to edema. We conclude that these radiological changes after carmustine wafer implantation should be carefully followed up, because these changes can easily be mistaken for infectious disease or recurrent tumors.

DOI： 10.1007/s11060-015-1941-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: We report a patient treated successfully via endovascular surgery within 24h after intravenous thrombolysis using recombinant tissue plasminogen activator for acute cervical internal carotid artery occlusion. PRESENTATION OF CASE: A 68-year-old man was admitted to our hospital. Neurological examination revealed severe left-sided motor weakness. Magnetic resonance imaging showed no cerebral infarction, but magnetic resonance angiography revealed complete occlusion of the right internal carotid artery. Systemic intravenous injection of recombinant tissue plasminogen activator was performed within 4h after the onset. But, magnetic resonance angiography still revealed complete occlusion. Revascularization of the right cervical internal carotid artery was performed via endovascular surgery. The occluded artery was successfully recanalized using the Penumbra System(®) and stent placement at the origin of the internal carotid artery. Immediately after surgery, dual antiplatelet therapy (aspirin and clopidogrel) was initiated, and then cilostazol was added on the following day. Carotid ultrasonography and three-dimensional computed tomographic angiography at 14days revealed no further obstruction to flow. DISCUSSION: When trying to perform emergency carotid artery stenting within 24h after intravenous recombinant tissue plasminogen activator administration, several issues require attention, such as the decisions regarding the type of stent and embolic protection device, the selection of antiplatelet therapy and the methods of preventing hyperperfusion syndrome. CONCLUSION: Emergency carotid artery stenting for the acute internal carotid artery occlusion may be considered a safe procedure in preventing early stroke recurrence in selected patients.

DOI： 10.1016/j.ijscr.2016.07.027

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We describe a case of a peripheral ruptured middle cerebral artery(MCA)aneurysm showing repeated morphological changes within a short period of 3 months. A 69-year-old woman was admitted to her primary care hospital with headache. Cranial computed tomography (CT) showed subarachnoid hemorrhage (SAH), but ruptured aneurysm was not confirmed on 4-vessel cerebral angiography. Conservative treatment was provided in the form of pain relief and blood pressure control. However, left internal carotid artery angiography (ICAG) conducted 12 days post-onset showed a peripheral MCA aneurysm, which was enlarged 1 week later. The patient did not tolerate balloon test occlusion, showing neurological deficit. Direct surgery was planned, but angiography on day 30 revealed a reduction in aneurysm size. Medical therapy was therefore continued for 1 month; however, the aneurysm showed repeated enlargements over 3 months. The patient therefore consulted our hospital for surgery, which was performed using a transsylvian approach. As we were unable to rule out pseudoaneurysm, we performed superficial temporal artery-MCA anastomosis as a form of trapping surgery. However, the lesion appeared to likely represent a congenital aneurysm when viewed macroscopically, so we performed neck clipping as a definitive treatment. Navigation and motor-evoked potential monitoring were useful to approach the aneurysm and predict the preservation of motor function. Histological examination revealed a congenital aneurysm with organized thrombus. The postoperative course was uneventful and the patient was discharged 2 weeks after surgery without any neurological deficit.

DOI： 10.11477/mf.1436203108

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We present two rare cases of pineal-region meningiomas. These tumors are the first reported cases of dura-unrelated meningiomas originating from the arachnoid membrane over the vein of Galen (AMG). CASE DESCRIPTION: In Case 1, a 37-year-old woman presented with a progressing headache. Magnetic resonance imaging (MRI) showed a large tumor in the pineal region, displacing the vein of Galen upward. Angiography disclosed occlusion of the vein of Galen, with deep venous flow draining through the veins on the right medial surface of the occipital lobe to the superior sagittal sinus. In Case 2, a 67-year-old man presented with dizziness. MRI demonstrated a large mass in the pineal region, displacing the vein of Galen inferiorly. Angiography disclosed occlusion of the vein of Galen, with deep venous flow draining through the collateral venous channel into the transverse sinus. Both tumors were totally excised (Simpson Grade III for Case 1, Grade I for Case 2) via a left occipital transtentorial approach. No dural attachment was recognized in either case, but the tumor in Case 1 was firmly adherent to the inferior portion of the AMG, while that in Case 2 was attached to the superior portion of the AMG, but remained dissectible. CONCLUSIONS: We reported two cases of pineal-region meningiomas originating from the arachnoid membrane over the vein of Galen, resulting in meningioma without dural attachment. These tumors can be totally resected by careful dissection of the tumor from the arachnoid membrane surrounding the vein of Galen.

DOI： 10.1186/s12957-015-0645-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endoscopic endonasal transsphenoidal surgery (ETSS) has been widely applied to pituitary adenomas. However, anatomical orientation is difficult when structures of the sphenoidal sinus are complicated. This study investigated the usefulness of three-dimensional computed tomography (3D-CT) modeling in planning surgical procedures for ETSS and providing anatomical guidance during surgery. CT data from 99 consecutive patients with pituitary adenoma treated between January 2008 and March 2014 were used to reconstruct 3D-CT models. Based on these images, the architecture of sphenoidal sinus, particularly structures surrounding the sellar floor, was visualized for preoperative simulation of surgical procedures. These 3D-CT images were also compared to surgical views during ETSS to evaluate applicability of the images. These models clearly demonstrated the morphology of the nasal cavity and structures of the sphenoidal sinus, including bony prominences of the internal carotid arteries (ICAs) and optic canals by successively eliminating sphenoidal structures. The 3D-CT images permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and optic canals. With this 3D-CT model, the surgeon could access the sella more easily, open the floor widely enough for each individual patient, and resect the tumor maximally without complications. Preoperative 3D-CT models distinctly visualized the optic canals, bilateral ICAs, and complicated structures of sphenoidal septa. The 3D-CT images were useful for preoperative planning and as a road map during endoscopic surgery for pituitary adenoma, facilitating maximum tumor resection without complications.

DOI： 10.1007/s10143-015-0625-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Drug resistance is a major obstacle for the efficacy of chemotherapeutic treatment of tumors. Oct-3/4, a self-renewal regulator in stem cells, is expressed in various kinds of solid tumors including glioblastoma. Although Oct-3/4 expression has been implicated in the malignancy and prognosis of glioblastomas, little is known of its involvement in drug resistances of glioblastoma. METHODS: The involvement of Oct-3/4 in drug resistance of glioblastoma cells was assessed by lactate dehydrogenase assay, efflux assay of an anticancer drug, poly ADP-ribose polymerase cleavage, and in vivo xenograft experiments. Involvement of a drug efflux pump ATP binding cassette transporter G2 in Oct-3/4-induced drug resistance was evaluated by quantitative PCR analysis and knockdown by shRNA. RESULTS: Oct-3/4 decreased the susceptibility to chemotherapeutic drugs by enhancing excretion of drugs through a drug efflux pump gene, ATP binding cassette transporter G2. Moreover, the expression of Oct-3/4 was well correlated to ATP binding cassette transporter G2 expression in clinical GB tissues. CONCLUSION: Oct-3/4 elevated the ATP binding cassette transporter G2 expression, leading to acquisition of a drug-resistant phenotype by glioblastoma cells. GENERAL SIGNIFICANCE: If the drug-resistance of glioblastoma cells could be suppressed, it should be a highly ameliorative treatment for glioblastoma patients. Therefore, signaling pathways from Oct-3/4 to ATP binding cassette transporter G2 should be intensively elucidated to develop new therapeutic interventions for better efficacy of anti-cancer drugs.

DOI： 10.1016/j.bbagen.2015.01.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Two types of macrophages in lesion core of rat stroke model were identified according to NG2 chondroitin sulfate proteoglycan (NG2) and CD200 expression. NG2(+) macrophages were CD200(-), and vice versa. NG2(-) macrophages expressed two splice variants of CD200 that are CD200L and CD200S. CD200(+) macrophages expressed CD8, CD68, CD163, CCL2, inducible nitric oxide synthase, interleukin-1β, Toll-like receptor 4 and transforming growth factor β, whilst NG2(+) cells expressed a costimulatory factor CD86. Both cell types expressed insulin-like growth factor 1 and CD200R. These results demonstrate that the two macrophage types cannot be classified as either M1 or M2.

DOI： 10.1016/j.jneuroim.2015.03.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The current optimal surgery for glioblastomas (GBMs) near the pyramidal tract (PT) is to remove as much tumor as possible and to preserve motor function. The purpose of this study is to investigate the usefulness of tractography-integrated navigation-guided fence-post catheter techniques and motor-evoked potentials (MEPs) for preserving postoperative motor function after GBM surgery. We retrospectively examined 49 patients who underwent resection for GBM near the PT. Diffusion tensor (DT) imaging-based tractography of the PT was performed preoperatively and integrated into the navigation system. When possible, silicon catheters were used as "fence-posts" and were inserted along the tumor boundaries, avoiding the PT, before tumor removal using the navigation system (fence-post catheter techniques). Cortical and subcortical MEPs were also monitored during resection of the tumor. Fence-post catheter techniques using a tractography-integrated navigation system were used in 45 of 49 patients. This technique enabled placement of the catheters, avoided the motor pathways, and allowed easier resection of the tumors. Tumors near the PT were resected using subcortical and cortical MEPs. The amplitudes of cortical MEPs after tumor removal were maintained at over 33 % of those obtained before resection. Thirty-six patients showed obvious responses of subcortical MEPs at ≤20 mA. The degree of resection was gross total in 21 patients, subtotal in 21, and partial in seven. One month after surgery, only one patient showed worsened motor function. Therefore, fence-post catheter techniques using a tractography-integrated navigation system and MEPs may contribute to preserving motor function after surgery for GBMs that are near the PT.

DOI： 10.1007/s10143-014-0593-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ethmoidal dural arteriovenous fistulas (AVFs) are rare intracranial lesions associated with a high risk of intracranial hemorrhage. In particular, this entity with reflux drainage directly into the ophthalmic vein is extremely rare. We report a case of ethmoidal dural AVF with direct drainage of the superior ophthalmic vein (SOV) and inferior ophthalmic vein (IOV), successfully treated by endovascular surgery. A 58-year-old man presented with progressive diplopia. Angiography and contrast-enhanced CT showed an ethmoidal dural AVF supplied via the bilateral anterior ethmoidal arteries and venous drainage through the left SOV and IOV. A transarterial approach through the bilateral anterior ethmoidal arteries was used to place the microcatheter close to the fistula site. After intra-arterial embolization with 20% N-butyl cyanoacrylate, the dural AVF was completely occluded. In patients with good vascular access, endovascular transarterial embolization may be an effective and less invasive treatment strategy for ethmoidal dural AVF.

DOI： 10.1136/neurintsurg-2013-011098.rep

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with severe internal carotid artery (ICA) stenosis with multiple medical problems generally undergo carotid artery stenting (CAS). However, it is difficult to perform CAS in some patients because iodinated contrast medium is hard to use. We report a patient with asymptomatic ICA stenosis and chronic renal failure, in whom successful treatment was achieved using CAS with minimal use of iodinated contrast medium. A 68-year-old man with severely chronic renal failure was consulted for treatment of left ICA stenosis. Magnetic resonance angiography (MRA) and carotid echography revealed left ICA severe stenosis, and systemic non-contrast MRA showed left femoral artery constriction, but right femoral artery to be intact. CAS was therefore performed through the right femoral artery, using non-contrast three-dimensional computed tomography (3D-CT) with MRA fusion imaging, intravascular ultrasonography, and a small amount of iodinated low-osmolar contrast medium. Postoperative course was uneventful with no aggravation of renal dysfunction, and he was discharged 7 days postoperatively. These techniques are very useful for patients with chronic renal failure, and this present case represents the first report of CAS treated by using non-contrast 3D-CT with MRA fusion image technique.

DOI： 10.1177/1591019915581941

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Accumulating evidence shows that the expression level of Oct-3/4, a self-renewal regulator in stem cells, is positively correlated with the progression of various solid tumors. However, little is known regarding the influence of Oct-3/4 in the tumor angiogenesis of glioblastomas. In the present study, we subcutaneously transplanted Oct-3/4-overexpressing human glioblastoma U251 (U251/EGFP-Oct-3/4) cells into the right thighs of nude mice to evaluate the roles of Oct-3/4 in the tumor angiogenesis. Both tumor size and the number of large vessels growing in the tumor were markedly increased. In an in vitro model of angiogenesis, the conditioned media from U251/EGFP-Oct-3/4 cells significantly accelerated capillary-like tube formation compared with that of U251/EGFP cells. In comparison with U251/EGFP cells, U251/EGFP-Oct-3/4 cells had markedly elevated the expression of vascular endothelial growth factor mRNA under the control of hypoxia-inducible factor (HIF) 1α. In U251/EGFP-Oct-3/4 cells, enhanced protein expression and nuclear translocation of HIF1α were observed. Furthermore, we demonstrated that the involvement of AKT, an oncogenic signaling molecule, in the Oct-3/4 induced upregulation of HIF1α protein. Our findings suggest that Oct-3/4-expressing glioblastoma cells have the ability to adapt to low-oxygen environments within tumor masses by promoting tumor angiogenesis through AKT-HIF1 pathway.

DOI： 10.1007/s10014-014-0203-3

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report herein a case of cerebellar hemangioblastoma complicated by pregnancy and concerns about the period in which surgery could be performed successfully. A 19-year-old woman, who was also 35 weeks pregnant, was admitted to our hospital with headache, nausea, and general fatigue. Neurological examination on admission revealed disturbed consciousness, and the patient's general condition was poor. Computed tomography and magnetic resonance imaging showed a large tumor in the cerebellar vermis along with an obstructive hydrocephalus. Computed tomographic angiography with three-dimensional reconstruction revealed feeding arteries and a draining vein in this tumor. Based on the clinical features, hemangioblastoma was suspected, and surgical excision and extraction of the fetus were scheduled. However, because of rapid neurological deterioration due to tumor progression, an emergency cesarean section was performed under general anesthesia. After extracting the fetus, the level of consciousness improved, so a tumor resection was planned after the patient's general condition improved. However, the neurological state deteriorated again due to the worsening hydrocephalus, which was suspected to be caused by the increased cerebral blood flow following uterine contraction. Emergency surgery for the brain tumor was performed two days after delivery. The tumor was resected completely and histopathological examination confirmed a diagnosis of hemangioblastoma. The postoperative course was uneventful, and the patient and newborn were discharged with no neurological deficits three weeks after the operation. This case suggested that if we encounter patients with brain tumors complicated by pregnancy, not only is earlier diagnosis from clinical features important, but also persistent additional treatment should be carried out without delay to effectively control intracranial pressure.

DOI： 10.11477/mf.1436202946

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose. We investigate the usefulness of multimodal assistant systems using a fusion model of preoperative three-dimensional (3D) computed tomography (CT) and magnetic resonance imaging (MRI) along with endoscopy with indocyanine green (ICG) fluorescence in establishing endoscopic endonasal transsphenoidal surgery (ETSS) as a more effective treatment procedure. Methods. Thirty-five consecutive patients undergoing ETSS in our hospital between April 2014 and March 2015 were enrolled in the study. In all patients, fusion models of 3D-CT and MRI were created by reconstructing preoperative images. In addition, in 10 patients, 12.5 mg of ICG was intravenously administered, allowing visualization of surrounding structures. We evaluated the accuracy and utility of these combined modalities in ETSS. Results. The fusion model of 3D-CT and MRI clearly demonstrated the complicated structures in the sphenoidal sinus and the position of the internal carotid arteries (ICAs), even with extensive tumor infiltration. ICG endoscopy enabled us to visualize the surrounding structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Conclusions. Preoperative 3D-CT and MRI fusion models with intraoperative ICG endoscopy allowed distinct visualization of vital structures in cases where tumors had extensively infiltrated the sphenoidal sinus. Additionally, the ICG endoscope was a useful real-time monitoring tool for ETSS.

DOI： 10.1155/2015/694273

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: In-stent thrombosis (IST) after carotid artery stenting (CAS) is a rare complication that can lead to severe thromboembolic events. The purpose of this study was to investigate the pathogenesis of IST after CAS. PATIENTS AND METHODS: A total of 101 patients underwent CAS from January 2006 to September 2013 at our hospital. Five of these patients experienced IST. We reviewed their clinical course and treatment. In addition, we compared various parameters, including basal disease, preceding anti-platelet therapy, rate of stenosis, length of stenosis, preoperative examination, type of stent, length of stent, post dilatation, and postoperative examination, between the IST and the non-IST groups. OUTCOME: All cases in the IST group had low echoic plaque and open cell stent, and all thrombi were located at the dorsal side of the internal carotid artery and the distal side of the stent flexion. Four cases without neurological symptoms were found to have resolution of IST at 3-6 weeks after CAS with anticoagulant therapy. One case had symptomatic thromboembolism at 1 month after CAS, and the thrombus was removed along with the stent due to growth of the thrombus despite anticoagulant therapy. No significant differences were observed between the IST and non-IST groups with regard to the factors described in the methods section. CONCLUSIONS: This study did not identify factors related to IST. We hypothesize that soft plaque can easily protuberate in the context of a stent with a large cell and that protrusion plaque may increase the risk of thrombus formation in combination with turbulent flow at the site of stent flexion. Further investigation in a larger number of patients is needed to clarify the risk factors related to IST.

DOI： 10.11477/mf.1436200024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.clineuro.2014.06.038

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

This report describes a case of successful recanalization of intracranial internal carotid artery occlusion by rapidly changing from the Penumbra System® to the Merci® Retrieval System for the retrieval of a predicted white thrombus. A 72-year-old man was consulted to our department with a consciousness disturbance. The patient had undergone graft placement for the management of a thoracic aortic aneurysm 14 days prior. Neurological examination revealed left-sided severe motor weakness and dysarthria. Magnetic resonance(MR)imaging showed a cerebral infarction in the territory of the right internal carotid artery(ICA), while MR angiography revealed occlusion of the right ICA. The systemic intravenous injection of recombinant tissue plasminogen activator was contraindicated, so a mechanical thrombectomy was performed. The use of the Penumbra System® failed to achieve recanalization of the right ICA;therefore, revascularization using the Merci® Retrieval System was performed. As a result, complete recanalization was achieved approximately 2 hours and 45 minutes after symptom onset. The retrieved specimen was elastic and hard, and histological examination revealed a white thrombus without endovascular organization. Postoperatively, the patient was restless for 1 day but did not show any neurological abnormalities. His postoperative course was uneventful, and he was discharged 7 days later without any neurological deficits.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ethmoidal dural arteriovenous fistulas (AVFs) are rare intracranial lesions associated with a high risk of intracranial hemorrhage. In particular, this entity with reflux drainage directly into the ophthalmic vein is extremely rare. We report a case of ethmoidal dural AVF with direct drainage of the superior ophthalmic vein (SOV) and inferior ophthalmic vein (IOV), successfully treated by endovascular surgery. A 58-year-old man presented with progressive diplopia. Angiography and contrast-enhanced CT showed an ethmoidal dural AVF supplied via the bilateral anterior ethmoidal arteries and venous drainage through the left SOV and IOV. A transarterial approach through the bilateral anterior ethmoidal arteries was used to place the microcatheter close to the fistula site. After intra-arterial embolization with 20% N-butyl cyanoacrylate, the dural AVF was completely occluded. In patients with good vascular access, endovascular transarterial embolization may be an effective and less invasive treatment strategy for ethmoidal dural AVF.

DOI： 10.1136/bcr-2013-011098

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Here, we report a case of primary intracranial tumor in a chronic hemodialysis patient in which neurosurgery was successful. A 50-year-old man who had been on hemodialysis for 4 years was admitted to our hospital with general fatigue. Neurological examination on admission revealed mild restless. Computed tomography and magnetic resonance imaging performed on admission revealed a large (55 mm×40 mm) tumor mass in contact with the falx. The size of this tumor rapidly increased over the next month. 201Thallium-chloride single photon emission computed tomography revealed abnormal uptake in the same location as the lesion. This suggested a malignant brain tumor and surgical excision was scheduled. Two weeks prior to surgery, frequent hemodialysis was performed using nafamostat mesilate instead of heparin to prevent bleeding and to maintain electrolyte balance, and red cell concentrates and erythropoietin were administered for the improvement of anemia. A triple lumen catheter was inserted in the right internal jugular vein in preparation for emergency continuous hemodiafiltration to maintain homeostasis of circulatory dynamics. Surgery was completed without incident and the tumor was resected totally. During surgery, cerebral edema was well controlled by hyperventilation and a slightly upturned head position. Histopathological examination of the specimen confirmed atypical meningioma. Continuous hemodiafiltration was performed for 24 hours after surgery, and hemodialysis was initiated on the third day after surgery. The postoperative course was uneventful. Three weeks after surgery, the patient was discharged with no neurological deficit and resumed his daily life on maintenance hemodialysis.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case treated successfully by emergency carotid artery stenting(CAS)within 24 h after intravenous thrombolysis for acute ischemic stroke. An 80-year-old man was admitted to our hospital with disturbance of consciousness. Neurological examination on admission revealed severe right-sided motor weakness and motor aphasia. Magnetic resonance(MR)imaging showed cerebral infarction in the territory of the perforating artery and cortical branch of the left middle cerebral artery(MCA). MR angiography(MRA)revealed occlusion of the bilateral cervical internal carotid arteries(ICAs). Systemic intravenous injection of recombinant tissue plasminogen activator(iv rt-PA)was therefore performed 2.5h after onset. Following iv rt-PA therapy, neurological symptoms improved for 1h, but MRA and cerebral angiography revealed severe stenosis of the left cervical ICA, complete occlusion of the right cervical ICA and left MCA occlusion. Revascularization of the left cervical ICA was then performed using endovascular surgery(percutaneous transluminal angioplasty and CAS)3.5h after iv rt-PA therapy. Postoperative course was uneventful except for mild restlessness, and hyperperfusion syndrome(HPS)did not develop. Strict control of blood pressure under dexmedetomidine anesthesia allowed effective prevention of HPS. After 1 week, recanalization of the left MCA was recognized on MRA and ¹²³I-IMP-single photon emission computed tomography. The patient was discharged with no neurological deficit after 2 weeks.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Vertebral artery (VA) dissecting aneurysm (VADA), which presents with headache and neck pain as the only manifestations, is an uncommon pathology, but is increasingly recognized as a cause of posterior circulation stroke in young adults. We report a case of VADA with isolated occipital headache at the time of onset and treatment using an endovascular approach. A 58-year-old man was admitted to our hospital with left occipital headache. Cranial magnetic resonance imaging (MRI) showed neither subarachnoid hemorrhage(SAH)nor cerebral infarction, but magnetic resonance angiography (MRA)revealed left VADA. Conservative treatment including pain relief and blood pressure control was provided. After 2 weeks, the dissecting lesion showed spontaneous improvement and occipital headache was gradually improving. However, 4 months after onset, the VADA showed growing aneurysmal dilatation. We therefore performed endovascular surgery (coil embolization with parent artery occlusion). Symptoms improved, and the postoperative course was uneventful. Although the natural history of VADA with isolated headache remains unclear, endovascular treatment should be considered for patients with growing aneurysmal dilatation, since the prognosis for patients with subsequent SAH is very poor.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Cryptococcal infections of the central nervous system (CNS) are infrequent in immunocompetent hosts and usually present as meningitis. However, fungal masses called cryptococcoma can sometimes be formed. We report a case in which intraventricular cryptococcoma in an immunocompetent patient was completely cured using liposomal amphotericin B (L-AMB) and voriconazole (VRCZ). A 56-year-old previously healthy man was admitted to our hospital with fever, headache and bilateral hand tremor lasting over three weeks. Cerebrospinal fluid (CSF) studies on admission showed meningitis with a white blood cell count of 228 cells/μL: mononuclear leukocytes, 96%; polymorphonuclear leukocytes, 4%; proteins, 157 mg/dL; and glucose, 50 mg/dL. Magnetic resonance imaging (MRI) showed a small, homogeneously enhanced lesion in the right lateral ventricle, and 18F-fluoro-2-deoxy-D-glucose and 11C-methionine positron emission tomography revealed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the lesion was performed. Histopathological examination of the specimen showed moderate lymphocyte infiltration and numerous fungal spores, and periodic acid-Schiff and Grocott staining revealed the presence of Cryptococcus neoformans (C.neoformans) within the granuloma, leading to a diagnosis of CNS cryptococcoma. The patient underwent treatment with intravenous L-AMB for 2 weeks and oral VRCZ for 10 months. CSF cultures were negative for C.neoformans and no recurrences were identified on MRI. CNS cryptococcoma is a rare infection that may occur in patients with no known history of immunosuppression. This pathology can be difficult to distinguish from brain tumor, so early pathological diagnosis from an excised specimen is very important. Furthermore, administration of L-AMB and VRCZ may be effective in treating cases of CNS cryptococcoma.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

As a result of increased glioblastoma migration and invasion into normal brain parenchyma, treatment of local tumor recurrence following initial treatment in glioblastoma patients remains challenging. Recent studies have demonstrated increased Oct-3/4 expression, a self-renewal regulator in stem cells, in glioblastomas. However, little is known regarding the influence of Oct-3/4 in glioblastoma cell invasiveness. The present study established Oct-3/4-overexpressing glioblastoma cells, which were prepared from human glioblastoma patients, to assess migration, invasion, and mRNA expression profiles of integrins and matrix metalloproteinases (MMPs). Compared with control cells, Oct-3/4 expressing-glioblastoma cells exhibited increased migration and invasion in wound healing and Matrigel invasion assays. Oct-3/4 overexpression resulted in upregulated FAK and c-Src expression, which mediate integrin signals. Vinculin accumulated along the leading edges of Oct-3/4 expressing-glioblastoma cells and associated with membrane ruffles during cell migration. Oct-3/4 expressing-cells exhibited increased MMP-13 mRNA expression and MMP-13 knockdown by shRNA suppressed cell invasion into Matrigel and organotypic brain slices. These results suggested that Oct-3/4 enhanced degradation of surrounding extracellular matrix by increasing MMP-13 expression and altering integrin signaling. Therefore, Oct-3/4 might contribute to tumor promoting activity in glioblastomas.

DOI： 10.1002/jcb.23374

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Diffusion tensor (DT) imaging-based fiber tracking is a noninvasive magnetic resonance technique that can delineate the course of white matter fibers. OBJECTIVE: To evaluate the accuracy and usefulness of this DT imaging-based fiber tracking for surgery in patients with gliomas near the pyramidal tract (PT). METHODS: Subjects comprised 32 patients with gliomas near the PT. DT imaging-based fiber tracks of the PT were generated before and within 3 days after surgery in all patients. A tractography-integrated navigation system was used during the operation. Cortical and subcortical motor-evoked potentials (MEPs) were also monitored during resection to maximize the preservation of motor function. The threshold intensity for subcortical MEPs was examined by searching the stimulus points and changing the stimulus intensity. Minimum distance between the resection border and the illustrated PT was measured on postoperative tractography. RESULTS: In all subjects, DT imaging-based tractography of the PT was successfully performed, preoperatively demonstrating the relationship between tumors and the PT. With the use of the tractography-integrated navigation system and intraoperative MEPs, motor function was preserved postoperatively in all patients. A significant correlation was seen between threshold intensity for subcortical MEPs and the distance between the resection border and PT on postoperative DT imaging. CONCLUSION: DT imaging-based fiber tracking is a reliable and accurate method for mapping the course of subcortical PTs. Fiber tracking and intraoperative MEPs were useful for preserving motor function in patients with gliomas near the PT.

DOI： 10.1227/NEU.0b013e31823020e6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The usefulness of endoscope-assisted microsurgical removal of vestibular schwannomas in the internal auditory canal (IAC) was evaluated. Microsurgical removal using the endoscope was done in 28 procedures and microsurgical removal without an endoscope was done in 43 procedures. A retrosigmoid approach was used. The tumor location in the IAC was classified as grade 1 (located up to the mid-portion), 2, 3, or 4 (located up to the fundus with bony destruction) according to the tumor extent, and residual tumor in the IAC was evaluated as grade A (remnant tumor was not observed), B, C, or D (remnant tumor was observed over the mid-portion) according to the extent of remnant tumor. The residual tumor in the IAC was less in the endoscope-assisted group than in the microsurgery group. There was a significant difference only in grade 2, that is, tumor located beyond the mid-portion of the IAC. There was no significant difference in the results of preservation of useful hearing, facial nerve function, and tumor recurrence between the two groups. The benefit of endoscope-assistance microsurgery was shown for those patients whose tumors extended beyond the mid-portion of the IAC but did not reach the fundus.

DOI： 10.1055/s-0032-1304555

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioblastoma is the most malignant type of primary brain tumor that has been shown to contain a small population of cancer stem cells. Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. In this study, we isolated tumor sphere-forming cells bearing cancer stem-like characteristics such as self-renewal, multipotency, drug-resistibility, and in vivo tumorigenicity, from the human glioblastoma cell line U251, under serum-free neural stem cell culture condition, and assessed their migratory and invasive ability. These cells showed enhanced migratory and invasive ability on both Matrigel and organotypic brain slices compared to parental U251 cells. The expression of matrix metalloproteinase (MMP)-13 was specifically expressed in tumor sphere-forming cells derived from U251 and primary human glioma cells. Knockdown of MMP-13 expression by shRNA suppressed the migration and invasion of these cells. The results suggest that the highly invasive potential of cancer stem cells depends on MMP-13 enzymatic activity, thus MMP-13 might be a potential therapeutic target for glioblastomas.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Dexmedetomidine is a central alpha2 adrenoceptor agonist recently shown to be a safe and acceptable sedative agent for patients requiring sedation after brain surgery. We report two patients successfully treated by carotid endarterectomy (CEA) with postoperative management under dexmedetomidine anesthesia for transient ischemic attack (TIA) resulting from severe stenosis of the internal carotid artery (ICA). Case 1: A 75-year-old man was admitted to our hospital with aphasia and weakness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on magnetic resonance imaging (MRI)/diffusion-weighted image (DWI), MR angiography (MRA) revealed severe stenosis of the left cervical ICA. (123)I-IMP-single photon emission tomography (SPECT) and transcranial Doppler (TCD) revealed marked reduction of cerebral blood flow in the left cerebral hemisphere. Although CEA induced hyperperfusion, aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged without neurological deficits. Case 2: A 68-year-old man was admitted to our hospital with amaurosis fugax and numbness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on MRI/DWI, MRA disclosed severe stenosis of the left cervical ICA. (123)I-IMP-SPECT revealed extremely low perfusion and disturbance of vascular reactivity in the territory of the left ICA. Although conservative therapy was performed, crescendo TIA was noted. Revascularization using CEA was therefore performed. After surgery, hyperperfusion was observed in the same fashion as in case 1, and again aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged 1 month postoperatively without neurological deficits. Dexmedetomidine is a safe and acceptable sedative drugs preventing hyperperfusion syndrome after CEA.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1(+)/NG2(+) Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors.

DOI： 10.1038/jcbfm.2009.233

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The secreted protein acidic and rich in cysteine (SPARC) is a secreted glycoprotein that plays an essential role in promoting the motility of invasive tumor cells. In the present study, we investigated the role of SPARC in the motile and invasive activities of human glioma cells by silencing the SPARC gene. Introduction of SPARC-targeted small interfering RNA (siRNA) into glioma cell lines resulted in downregulation of SPARC expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with SPARC siRNA compared with those transfected with control siRNA. In an organotypic brain slice model, co-culture of glioma spheroids and rat brain slices showed that SPARC siRNA-transfected glioma cells failed to invade the surrounding normal brain tissue. In addition, intracerebral injection of glioma cells transfected with SPARC siRNA in nude mice resulted in the formation of a non-invasive tumor, whereas injection of cells transfected with control siRNA resulted in diffuse invasive tumors. Since SPARC was exclusively expressed in the invasive zone of the tumor margin and the area surrounding tumor necrosis, we investigated the relationship between SPARC expression and hypoxic stress. SPARC expression was upregulated under hypoxic stress of 1% oxygen concentration in glioma cells. Silencing hypoxia-inducible factor-1alpha with siRNA reduced the overexpression of SPARC induced under hypoxic conditions. These results suggest that SPARC plays an essential role in the invasive activity of human glioma cells, under hypoxic conditions. Downregulation of SPARC may be a novel anti-invasion therapeutic strategy for malignant gliomas.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Vertebral artery dissecting aneurysm is now increasingly recognized as a cause of posterior circulation stroke in young adults. Here, we report a case of bilateral VADA with SAH, treated by bilateral coil occlusion using GDCs. CASE DESCRIPTION: A 64-year-old woman was admitted to our hospital with consciousness disturbance (Hunt and Kosnik: grade 4). Computed tomography showed diffuse SAH with a thick hematoma in the left C-P angle. Magnetic resonance angiography, 3D-CTA, and cerebral angiography revealed bilateral VADAs. First, the ruptured left VADA involving the PICA and a perforating branch was treated by occluding the lower half of the VADA and the proximal VA with GDCs in the acute stage. Thereafter, the residual VADA and contralateral VADA exhibited enlargement on cerebral angiography and MRA for 2 months after the initial surgery; thus, the right VADA was occluded by GDCs just proximal to the right PICA after confirming BTO tolerance. CONCLUSION: Staged bilateral VA coil occlusions combined with BTO may be one of the treatment strategies for bilateral VADA with SAH in cases presenting surgical difficulty due to anatomical factors or severe grade of SAH.

DOI： 10.1016/j.surneu.2007.04.019

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report 2 cases of multiple aneurysms (AN) associated with main trunk artery occlusion. CASE 1: A 52-year-old male was admitted to our hospital with dysarthria and weakness of the right side of the body. Computed tomography (CT) showed cerebral infarction in the left corona radiata. MR angiography and conventional angiography showed occlusion of the left middle cerebral artery (MCA) and saccular aneurysms (ANs) at the origin of the anterior communicating artery (A-com) and bifurcation of the right MCA. Subsequent 123I-IMP-single photon emission tomography (SPECT) revealed marked reduction of cerebral blood flow and disturbed reactivity to acetazolamide in the left cerebral hemisphere. Superficial temporal artery (STA)-MCA anastomosis was performed to improve cerebral blood flow and reduce hemodynamic stress for AN of the A-com and right MCA. At 5 months after the first operation, neck clipping was performed successfully for the non-ruptured A-com AN and right MCA AN. CASE 2: A 65-year-old male was admitted to our hospital. CT revealed subarachnoid hemorrhage (SAH), and 3D-computed tomographic angiography (CTA) and cerebral angiography showed basilar top AN, A-com AN and right MCA AN associated with right internal carotid artery occlusion. Right ACA and MCA territories were visualized from the A-com artery and posterior cerebral artery. STA-MCA anastomosis was performed to improve cerebral blood flow and reduce hemodynamic stress for ANs. In the same operation, successful neck clipping was performed for BA top AN and right MCA AN. In such cases as these, particularly in ischemic cases associated with main trunk artery occlusion, it was important to consider surgery for AN after STA-MCA anastomosis in anticipation of improved cerebral blood flow and reduce hemodynamic stress for AN.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Idiopathic spinal cord herniation was assumed to be a rare disease. However, the incidence of discovering this condition appears to have been increasing recently with advances in neuroradiological diagnosis using magnetic resonance imaging (MRI) and computed tomographic myelogram (CTM). We present herein an operated case of high-aged idiopathic spinal cord herniation. A 71-year-old female presented with spastic paresis of the right lower limb and sensory disturbance of pain and temperature below the level of the left Th4 dermatome, consistent with Brown-Séquard syndrome. MRI and CTM revealed right ventral displacement of the spinal cord and dilatation of the dorsal subarachnoid space at Th2/3. Laminectomy of Th1-3 was performed, herniated spinal cord was untethered and repositioned, and the dural defect was sealed with GORE-TEX dura substitute. Postoperative MRI revealed normal location of the spinal cord and neurological state improved slightly. The patient was discharged 1 month after the operation. Among many cases of spinal cord herniations, this is considered to be a rare case of idiopathic spinal cord herniation in an elderly patient.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 59-year-old female was found to be drawn in a swimming pool and transferred to our hospital. The patient was comatose on admission (Hunt & Kosnk: Grade IV). Computed tomography (CT) showed diffuse subarachnoid hemorrhage (SAH) with thick hematoma in the left ambient cistern. Conventional cerebral angiography and 3D-digital subtraction angiography revealed aneurysms (ANs) of the left posterior cerebral artery (P2), and bifurcation of the left internal carotid and posterior communicating arteries (IC-PC). Successful neck clipping was performed the same day through the temporal horn via the insula for ruptured P2 AN, and the non-ruptured IC-PC AN was also obliterated using a pterional approach. Postoperative course was uneventful except for initial disturbance of consciousness and aphasia. The patient was discharged with no neurological deficit 1 month after surgery. This approach may be preferable in cases involving high positioned PCA AN in the ambient cistern, particularly in the acute phase of severe SAH, as the brain is protected from the detrimental effects of strong temporal retraction and a wider working space is provided.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case treated successfully by emergency carotid endarterectomy (CEA) for progressing stroke resulting from pseudo-occlusion of the internal carotid artery (ICA). A 67-year-old male was admitted to our hospital with dysarthria. Neurological examination on admission revealed mild left-sided motor weakness and dysarthria. Computed tomography (CT) showed cerebral infarction in the territory of the perforating artery of right middle cerebral artery (MCA). Magnetic resonance (MR) imaging indicated similar findings and cervical MR angiography revealed occlusion of right cervical ICA. Cerebral conventional angiography and CT angiography revealed pseudo-occlusion of the right ICA. ECD-single photon emission tomography (SPECT) indicated low perfusion in the territory of the right ICA. Conservative therapy was performed using free radical scavengers and antiplatelet drugs, but neurological signs deteriorated. Revascularization using CEA was therefore performed. After surgery, the patient was restless with neurological abnormalities, and trans-cranial Doppler (TCD), INVOS-3100 and MRA revealed hyperperfusion. Strict control of blood pressure under propofol anesthesia allowed effective management of hyperperfusion syndrome. After a 1-month follow-up period, the patient was discharged with only mild left hemiparesis.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case in which C2 neurinoma was completely removed with preservation of the surrounding supportive tissue. A 47-year-old female was admitted to our hospital with gait disturbance and spinal tumor identified in other hospital. Neurological examination on admission revealed hyperreflexia in bilateral limbs and pathological reflexes. Cervical plain X-radiography showed erosion of the left C2 lamina. Axial Gd-enhanced T1 weighted magnetic resonance (MR) images showed partial enhancement of a dumbbell shaped tumor at the C1-2 level, revealing compression of the spinal cord to the right and extending to postero-laterally, and coronal MR images demonstrated that the tumor was clearly surrounded by the semispinalis capitis, semispinalis cervicis and inferior oblique muscles. The tumor was resected through a posterior approach without injuring the surrounding supportive tissue. Post operatively, she did not complain of nuchal pain during neck movement. After a 6-month follow-up period, cervical plain X-radiography showed preservation of cervical alignment, and coronal Gd-enhanced T1-weighted MR images demonstrated preservation of the posterior group of cervical muscles. It is desirable to preserve the surrounding supportive tissue as far as possible in order to minimize the postoperative neck pain and instability of cervical spine, like this case.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case of left common carotid artery dissection showing complete remission in the short term. A 48-year-old man presented a 1-week history of weakness in the right arm. Neurological findings revealed mild motor weakness of the right upper extremity. Magnetic resonance imaging (MRI) showed sporadic cerebral infarction and hemorrhagic infarction in the area of the left middle cerebral artery (MCA) and the posterior border zone. Computed tomographic angiography (CTA) revealed irregular stenosis with a smooth surface in the left common carotid artery and ultrasonography indicated an iso-echoic lesion in the same area. ECD-single-photon emission tomography (SPECT) showed low perfusion only in the infarcted territory. Conservative therapy using a free radical scavenger and aspirin was carried out and the patient displayed full neurological recovery. After a 3-week follow-up period, carotid angiography and CTA showed almost complete disappearance of the stenotic lesion.

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