Search

The Notch signal regulates both cell viability and apoptosis, and maintains stemness of various cancers including glioblastoma (GBM). Although Notch signal inhibition may be an effective strategy in treating GBM initiating cells (GICs), its applicability to the different subtypes of GBM remains unclear. Here, we analyzed the effectiveness of MRK003, a preclinical γ-secretase inhibitor, on GICs. Nine patient-derived GICs were treated by MRK003, and its efficacy on cell viability, apoptosis, sphere forming ability and Akt expression level which might be related to Notch downstream and be greatly important signals in GBM was evaluated. MRK003 suppressed viability and sphere-formation ability, and induced apoptosis in all GICs in varying doses of MRK003. Based on their sensitivities to MRK003, the nine GICs were divided into "relatively sensitive" and "relatively resistant" GICs. Sensitivity to MRK003 was associated with its inhibitory effect on Akt pathway. Transgenic expression of the myristoylated Akt vector in relatively sensitive GICs partially rescued the effect of MRK003, suggesting that the effect of MRK003 was, at least in part, mediated through inhibition of the Akt pathway. These GICs were differentiated by the expression of CD44 and CD133 with flow cytometric analysis. The relatively sensitive GICs are CD44-high and CD133-low. The IC50 of MRK003 in a set of GICs exhibited a negative correlation with CD44 and positive correlation with CD133. Collectively, MRK003 is partially mediated by the Akt pathway and has strong therapeutic potential for CD44-high and CD133-low GICs.

Hyperintense lesions around the resection cavity on magnetic resonance diffusion-weighted imaging (MR-DWI) frequently appear after brain tumor surgery due to the damage of surrounding brain. The putative connection between the lesion and the prognosis for patients with glioblastoma (GBM) was explored. This retrospective study reviewed consecutive sixty-one patients with newly diagnosed GBM. Postoperative MRI was performed within 2 weeks after the initial surgery. We classified the cases into two groups depending on whether DWI hyperintense lesions were observed or not [DWI(+) group and DWI(−) group]. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. Forty-two patients were identified. The various extents of hyperintense lesions around the resection cavity were observed in 28/42 (66.7 %) cases. In the DWI(+) and DWI(−) groups, median PFS was 10.0 [95 % confidence interval (CI) 8.4–11.5] and 6.7 (95 % CI 4.9–8.5) months, respectively (p = 0.042), and median OS was 18.0 (95 % CI 12.2–23.8) and 17.0 (95 % CI 15.7–18.3) months, respectively (p = 0.254). On multivariate analysis, the presence of DWI hyperintense lesion was more likely to be an independent predictor for 6-month PFS (p = 0.019; HR, 0.038; 95 % CI 0.002–0.582). Tumor recurrence appeared outside the former DWI hyperintense lesion. Hyperintense lesions surrounding the resected GBM on MR-DWI might be a favorable prognostic factor in patients with GBM.

Glioblastoma (GBM) is one of the most lethal malignancies in humans, and novel therapeutic strategies are urgently required for its treatment. Tyrosine kinases (TKs) play a pivotal role in intercellular signal transduction and regulate crucial processes of tumor cell biological activities in GBM. This information provides the basis for the molecular target therapies for GBMs. TK inhibitors (TKIs) are expected to be effective therapeutic strategies. However, one important limitation is that GBMs exhibit marked resistance to the TKIs currently available, yet the mechanisms underlying TKI resistance have not been fully characterized. In the current review, we will address the varieties of chemoresistance mechanisms against TKIs in GBM. The mechanisms responsible for TKI refractoriness in GBMs are divided into 2 aspects. The first includes tumor-related concerns, such as a lack of target expression, the multiplicity of targets, redundancy, the appearance of resistant cells, and tumor changes in characteristics. The second includes drug-related concerns, such as inefficient drug effects, delivery, pharmacokinetics, and intolerable side effects. A better understanding of these mechanisms is needed to develop accurate tests to predict the lack of response to TKIs and for developing novel approaches aimed at overcoming the resistance to TKIs.

Glioma, the most common primary brain tumor, is characterized by proliferative-invasive growth. However, the detailed biological characteristics of invading glioma cells remain to be elucidated. A monoclonal antibody (clone HMab-1) that specifically and sensitively recognizes the isocitrate dehydrogenase-1 (IDH1) protein carrying the R132H mutation can identify invading glioma cells by immunostaining. To investigate the degree of invasion in gliomas of distinct grades and the proliferative capacity of the invading cells, immunofluorescent staining was conducted using antibodies against IDH1-R132H and Ki-67 on 11 surgical and autopsy specimens of the tumor core and the invading area. Higher numbers of IDH1-R132H-positive cells in the invading area correlated with a higher tumor grade. Double staining for IDH1-R132H and Ki-67 demonstrated that most invading cells that expressed IDH1-R132H were not stained by the Ki-67 antibody, and the ratio of Ki-67-positive cells among IDH1-R132H-positive cells was significantly lower in the invasion area than in the tumor core in all grades of glioma. These data suggest that higher grade gliomas have a greater invasive potential and that invading cells possess low proliferative capacity.

We treated a case of recurrent glioblastoma (GBM) with bevacizumab and assessed its effect biologically. A 55-year-old man with a left frontal lobe GBM was experiencing recurrence 7 months postoperation. We administered bevacizumab concomitant with temozolomide (TMZ). Follow-up magnetic resonance imaging (MRI) showed dramatic but temporal tumor reduction; however, the patient died of re-recurrent disease 6 months after beginning bevacizumab. We obtained an autopsy and analyzed the detailed molecular change. In the autopsy specimen, the quantity of microvessels was significantly reduced. Vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 were downregulated, most likely due to a negative feedback mechanism by blocking of VEGF signaling. Matrix metalloproteinase (MMP)-2 and membrane-type 1 MMP were upregulated, resulting in the higher activation of MMP-2 in the autopsy specimen. MIB-1 staining index and phosphorylation levels of p44/42-mitogen-activated protein kinase did not change, whereas phosphorylated protein kinase B (Akt) was decreased in the autopsy specimen, suggesting compensation and/or amplification of other proliferative signaling pathways such as suppression of apoptosis signaling. Consequently, bevacizumab might inhibit the VEGF autocrine loop, which then causes a change in molecular expression related not only to enhancement of tumor invasion but also maintenance of tumor proliferation.

Arteriovenous shunting visualized by angiography is one of the major features of glioblastomas, and the visualization is dependent on the presence of extensive shunting. Extensive arteriovenous shunting is associated with the risk of poorly controlled intraoperative bleeding. When a tumor with extensive arteriovenous shunting is located in close proximity to the eloquent regions of the brain, a meticulous surgical procedure is necessary. In the present study, the site-oriented visualization of angiographical arteriovenous shunting was evaluated from the perspective of surgical treatment, with a particular focus on the perisylvian region that is in close proximity to motor and language regions (dominant hemisphere), as well as large arteries and veins. Twenty-six consecutive patients underwent a resection of glioblastoma between February 2007 and September 2012. All patients were presurgically examined using digital subtraction angiography. The patients were subdivided into the following two groups based on the location of the tumor: 1) perisylvian glioblastoma (18 patients) and 2) non-perisylvian glioblastoma (eight patients). Angiography to detect the arteriovenous shunting was performed. In addition, the number of intratumoral vessels, tumor proliferative activity (MIB-1 labeling index), and volume of intraoperative bleeding were evaluated and compared between the two groups. Angiographical arteriovenous shunting was definitively visualized in 13 of 18 (72 %) perisylvian glioblastomas, in contrast to only one of eight (13 %) non-perisylvian glioblastomas (p = 0.007). There were no significant differences between the two groups with respect to the number of intratumoral vessels, MIB-1 labeling index, and volume of intraoperative bleeding. However, massive intraoperative bleeding of > 2,000 mL occurred in one perisylvian glioblastoma patient. Glioblastomas in the perisylvian region tend to be associated with extensive arteriovenous shunting that can be definitively visualized by performing an angiography. Because arteriovenous shunting carries the risk of intraoperative bleeding, perisylvian glioblastomas—particularly in the dominant hemisphere—should be resected with a meticulous surgical procedure and strategy.

Nonenhancing intrinsic brain tumors have been empirically treated with a strategy that has been adopted for World Health Organization (WHO) grade II gliomas (low-grade gliomas: LGGs), even though small parts of the tumors might have been diagnosed as WHO grade III gliomas after surgery. However, the best surgical strategy for nonenhancing gliomas, including LGGs, is still debatable. LGGs have the following features: slow growth, high possibility of histologically malignant transformation, and no clear border between the tumor and adjacent normal brain. We retrospectively examined 26 consecutive patients with nonenhancing gliomas who were surgically treated at Kanazawa University Hospital between January 2006 and May 2012, with special reference to functional reorganization, extent of resection (EOR), and functional mapping during awake surgery. These categories are closely related with the features of LGG, i.e. functional reorganization due to slow-growing nature, EOR with related malignant transformation, and functional mapping for delineating the unclear tumor border. Finally, we discuss surgical strategies for slow-growing gliomas that are represented by LGGs and nonenhancing gliomas. In conclusion, slow-growing gliomas tend to undergo functional reorganization, and the functional reorganization affects the presurgical evaluation for resectability based on tumor location related to eloquence. In the clinical setting, to definitely identify the reorganized functional regions, awake surgery is recommended. Therefore, awake surgery could increase the extent of the resection of the tumor without deficits, resulting in the delay of malignant transformation and increase in overall survival.

Introduction At present, the risk of future hemorrhage or ischemic insult from vertebral artery (VA) dissection cannot be estimated from available imaging data. We investigated the relationship between symptoms and the angiographic patterns of the dissecting site on balloon test occlusion (BTO) to develop guidelines for clinical decision-making. Methods We retrospectively reviewed 18 patients with unilateral VA dissection who presented with subarachnoid hemorrhage (SAH) or cerebral infarction. We analyzed the angiographic findings at the dissecting site on contralateral VA angiograms during BTO of the affected VA, classified the angiographic patterns into two types, and compared the symptoms they presented. Results Patients with dissection opacified from the distal to the proximal side are more likely to present with cerebral infarction than SAH. Conversely, patients with dissection opacified from the proximal to the distal side had a significantly higher incidence of SAH. Conclusions Angiographic findings at the dissecting site on contralateral VA angiograms during BTO of the affected VA are helpful for considering the treatment and prognosis of patients with VA dissecting aneurysms.

Accumulating evidence has revealed that the tyrosine kinases play a major role in glioma proliferation and invasion. The largest family of tyrosine kinases, the Eph family, and its ligands, the ephrins, are frequently overexpressed in glioma, suggesting important roles for their bidirectional signals in glioma pathobiology. Ephs bind to cell surface-associated ephrin ligands on neighboring cells and have many biological functions during embryonic development of the central nervous system, including axon mapping, cell migration, and angiogenesis. Recent findings suggest that Eph/ephrin signaling affects glioma cell growth, migration, and invasion in vitro and in vivo. However, their roles in glioma seem complex, because both tumor growth promoter and suppressor potentials have been ascribed to Ephs and ephrins. Here, we review recent advances in research on the role of Eph/ephrin signaling in glioma and suggest that the Eph/ephrin system could be a potential target of glioma therapy.

Background and importance We report the case of a patient with multiple neuroepithelial tumors of different histological cell types. In this patient, synchronous appearance of tumors of the central nervous system, ie, cervical ependymoma and a fourth ventricle choroid plexus papilloma, was noted. Clinical presentation A 36-year-old man presented with sensory disturbance of the bilateral upper extremities. Magnetic resonance imaging revealed a heterogeneously enhanced mass with syringomyelia in the upper cervical cord and a well-enhanced mass in the fourth ventricle. The patient underwent bilateral suboccipital craniotomy and laminectomy from the level of C1 to C3 for both lesions. The lesions were grossly resected. Histological and immunohistochemical examinations revealed that the cervical tumor was an ependymoma, and the fourth ventricle tumor was a choroid plexus papilloma. Conclusion The appearance of synchronous multiple neuroepithelial tumors of different histological cell types is extremely rare, and this is the first known case of ependymoma occurring synchronously with choroid plexus papilloma, both tumors having different histological cell types. Displacement and maldifferentiation of primitive, multipotent neuroepithelial cells may be a causative factor for this unique presentation.

Choroid plexus carcinoma (CPC) is a malignant tumor with a strong tendency to spread along the cerebrospinal fluid pathway. There is no standardized chemotherapy protocol for this rare tumor. We report a 38-year-old man with CPC in the lateral ventricle with obstructive hydrocephalus. Because of the poor demarcation between thalamus and fornix, subtotal tumor resection was performed. Postoperative spine magnetic resonance (MR) image revealed whole spinal axis dissemination. After diagnosis of CPC, the patient was treated with whole ventricular and spine radiation concomitant with temozolomide chemotherapy, although the O 6-methylguanine-DNA methyltransferase (MGMT) promoter was found to be unmethylated. Although MR images revealed transient stable disease during adjuvant therapy, tumor progression was depicted after four cycles of temozolomide therapy. We discuss the ineffectiveness of adjuvant temozolomide therapy for CPC in connection with O 6-methylguanine-DNA methyltransferase promoter methylation. © 2011 The Japan Society of Brain Tumor Pathology.

Glioblastoma (GBM) is the most aggressive and destructive form of brain cancer. Animal models that can unravel the mechanisms underlying its progression are needed to develop rational and effective molecular therapeutic approaches. In this study, we report the development of mouse models for spontaneous gliomas representing distinct progressive stages of disease that are governed by defined genetic alterations. Neural stem/progenitor cell (NPC)-specific constitutive Ras activation in vivo plus p53 deficiency led to development of primarily anaplastic astrocytoma (grade III), whereas combined loss of p53 plus p16Ink4a/p19Arf led to development of GBM (grade IV) at 100% penetrance within 6 weeks. These glioma models showed enhanced stem cell properties (stemness) accompanied by malignant progression. Notably, we determined that, in our models and in human specimens, downregulation of the homeodomain transcription factor NKX2.2, which is essential for oligodendroglial differentiation, was correlated with increased tumor malignancy. NKX2.2 overexpression by GBM-derived glioma-initiating cells (GIC) induced oligodendroglial differentiation and suppressed self-renewal capacity. By contrast, Nkx2.2 downregulation in mouse NPCs accelerated GBM formation. Importantly, the inhibitory effects of NXK2.2 on GIC self-renewal were conserved in human cells. Thus, our mouse models offer pathobiologically significant advantages to investigate the nature of brain tumors, with improved opportunities to develop novel mechanism-based therapeutic approaches. Cancer Res; 71(3); 1135–45. ©2010 AACR.

Background: Recurrence of glioma frequently occurs within the marginal area of the surgical cavity due to invading residual cells. 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection has been used as effective therapeutic modalities to improve discrimination of brain tumour margins and patient prognosis. However, the marginal areas of glioma usually show vague fluorescence, which makes tumour identification difficult, and the applicability of 5-ALA-based photodynamic therapy (PDT) is hampered by insufficient therapeutic efficacy in glioma tissues. Methods: To overcome these issues, we assessed the expression of ferrochelatase (FECH) gene, which encodes a key enzyme that catalyses the conversion of protoporphyrin IX (PpIX) to heme, in glioma surgical specimens and manipulated FECH in human glioma cell lines. Results: Prominent downregulation of FECH mRNA expression was found in glioblastoma tissues compared with normal brain tissues, suggesting that FECH is responsible for PpIX accumulation in glioblastoma cells. Depletion of FECH by small interference RNA enhanced PpIX fluorescence after exposure to 5-ALA concomitant with increased intracellular PpIX accumulation in glioma cells. Silencing of FECH caused marked growth inhibition and apoptosis induction by PDT in glioma cells. Conclusion: These results suggest that knockdown of FECH is a potential approach to enhance PpIX fluorescent quality for optimising the subjective discrimination of vague fluorescence and improving the effect of 5-ALA-PDT.

In order to realize a less invasive robotic neurosurgery for the deeply seated tumor, a force detecting gripper with a flexible micro manipulator has been developed. Gripping force applied on the gripper is detected by strain gages fit on the gripper clip. Signal is conducted to the amplifier by the cables through the inner pipe of the manipulator. In order to approach to the deeply seated tumor through a narrow hole, a micro manipulator which can flex at the end part to face the gripper for the target and can rotate the closing direction of the gripper at the end of the manipulator has been developed. Some operation test showed that the developed manipulator can approach flexibly to the target, and the taking out force of a target on the soft material was detected clearly. © 2011 IEEE.

We experienced an unusual case of a 15-year-old girl who suffered acute bilateral blindness caused by a frontal lobe tumour. She underwent emergent operation, after which her vision recovered. This case emphasizes that a brain mass can cause sudden onset blindness and an emergency intervention might save the patient's sight.

金沢大学医薬保健研究域医学系, Background: The retrochiasmatic region is one of the most challenging areas to surgically expose. The authors evaluated the transcrusal approach, which involves removal of the superior and posterior semicircular canal from the ampulla to the common crus, to expose the retrochiasmatic region and compared it with the retrolabyrinthine approach, both of which are a variation of the posterior petrosal approach with hearing preservation, with a special emphasis on the influence of temporal lobe retraction. Methods: Six sides of silicone-injected cadaveric heads were dissected using two approaches: the transcrusal approach and the retrolabyrinthine approach. For each craniotomy, 3 exposure parameters in the retrochiasmatic region were measured: (1) horizontal distance, (2) vertical distance, and (3) triangular area of exposure, at three different levels of temporal lobe retractions: 0, 5, and 10 mm of retraction from the level of the tentorial incisura. Results: Without temporal lobe retraction, only the transcrusal and not the retrolabyrinthine approach provided a direct exposure of the retrochiasmatic region, especially in the horizontal distance (p < 0.001). At all levels of temporal lobe retraction, the transcrusal approach provided greater exposure in the horizontal and vertical distances and in the area of exposure. Nonetheless, in the horizontal distance, the difference between the transcrusal and retrolabyrinthine approaches decreased along with increased temporal lobe retraction, and almost no difference was obtained at 10 mm of retraction. Conclusions: Posterior petrosal approaches can provide an excellent exposure of the retrochiasmatic region. Of these two approaches, namely, transcrusal and retrolabyrinthine with hearing preservation, the transcrusal approach offers greater exposure than the retrolabyrinthine approach. The beneficial effect of partial labyrinthectomy of the transcrusal approach to the retrochiasmatic region is accentuated in the exposure of the horizontal distance with less temporal lobe retraction. © 2010 Springer-Verlag.

A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial subluxation (AAS). Here, we report a patient with ROP but without AAS. The patient was a 72-year-old man who did not have a history of rheumatoid arthritis or trauma to the head and neck. The patient was admitted to our hospital with gait disturbance, progressive motor weakness in both upper extremities and sensory disturbance in all four extremities. MRI showed a retro-odontoid mass with severe compression of the cervical spinal cord. A CT scan showed spondylotic changes in C5, C6, and C7 and bilateral facet fusion between C3 and C4. Dynamic radiography showed no evidence of AAS; there was loss of mobility at C2-C7 and excessive mobility at C1. Intraoperative pathological examination revealed that the lesion was a pseudotumor; therefore, posterior C1-C2 fixation was performed. MRI performed 6 months after the operation revealed that the pseudotumor was markedly reduced. To the best of our knowledge, patients with ROP without AAS are uncommon.

A 5-year-old male presented with scrotal migration of the catheter from a ventriculoperitoneal shunt manifesting as left scrotal swelling 4 months after implantation. Surgical obliteration of the patent peritoneal processus vaginalis that forms a corridor from the peritoneum to the scrotum was performed to avoid shunt malfunction. Review of the 26 reported cases including the present case revealed that most patients were up to 18 months old. Our patient was the oldest. Migration tended to occur within 6 months after implantation (mean 3.8 months, median 1.0 month). Involvement of the right side of the scrotum was prevalent (23 of 26 cases). Patent processus vaginalis and small peritoneal cavity probably contribute to scrotal catheter migration.

A 65-year-old man presented with a hyperplastic anomalous anterior choroidal artery (AChA) associated with a ruptured internal carotid artery aneurysm at the origin of a perforating artery manifesting as sudden onset of headache and vomiting. The aneurysm was too small for endovascular embolization, so we performed open surgery via the left pterional approach. Aneurysm clipping with preservation of the perforator was impossible, so we clipped the aneurysm neck and sacrificed the perforator. We also performed dome clipping because dome puncture resulted in continuous bleeding. Head computed tomography obtained 3 days after the operation showed cerebral infarction at the territory of the sacrificed perforator, but the patient suffered no neurological deficits. This case of internal carotid artery aneurysm with a perforating artery arising from the aneurysm dome shows that sacrifice of the perforator may be necessary to prevent rebleeding.

Dural arteriovenous fistulae (DAVF) occasionally lead to cognitive disorders whose reversibility after DAVF treatment remains unclear. We studied changes on pre- and post-treatment magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) scans in ten patients with cognitive disorder due to DAVF.We studied the symptoms, pre- and post-treatment MRI scans, SPECT findings, and mini-mental state examination (MMSE) and treatment results in ten patients with cognitive disorder due to DAVF. They were divided into two groups; the post-treatment MMSE score exceeded 25 points in group 1 (n = 6) and was lower than 24 points in group 2 (n = 4).In the six group 1 patients, pretreatment diffusion-weighted images (DWI) showed hyperintense areas, and SPECT scans demonstrated the preservation of vasoreactivity after acetazolamide challenge. In the four group 2 patients, pretreatment SPECT demonstrated hypoperfusion areas that coincided with the hyperintense areas seen on DWI; there were areas with marked disturbance in vasoreactivity. The post-treatment MMSE score in groups 1 and 2 improved by 13.7 +/- 2.4 and 3.8 +/- 1.0 points, respectively; the difference was significant at p0.01.In patients with cognitive disorder due to DAVF, the preservation of vasoreactivity on SPECT after acetazolamide challenge indicates that their cognitive disorder may be reversible by DAVF treatment.

We investigated the mechanism of phorbol 12-myristate 13-acetate (PMA)-induced migration of glioblastoma cells focusing on the p38 mitogen-activated protein kinase (MAPK)/heat shock protein 27 (Hsp27) pathway. PMA-induced cell migration and activation of p38MAPK in A172 glioblastoma cells. PMA-induced formation of lamellipodia and focal complexes was blocked by inhibiting p38MAPK with SB203580 or small interfering RNA (siRNA). Furthermore, activation of p38MAPK resulted in phosphorylation of an F-actin polymerization regulator, Hsp27. Immunohistochemical analysis showed that upon PMA stimulation, both unphosphorylated and phosphorylated Hsp27 were translocated to the lamellipodia. SB203580 or p38MAPK siRNA blocked these phenomena, indicating that Hsp27 phosphorylation and translocation from cytosol to membrane were mediated by p38MAPK. To address the question of whether endogenous Hsp27 participates in PMA-induced migration, we inhibited the expression of Hsp27 using Hsp27 siRNA. Although knockdown of Hsp27 by siRNA had little effect on p38MAPK activation, lamellipodia and focal complex formation was markedly inhibited. Migration was also abolished in Hsp27 siRNA-transfected cells. In conclusion, p38MAPK activation followed by Hsp27 phosphorylation was required for PMA-induced migration. Furthermore, Hsp27 itself played critical roles in PMA-induced migration. Our data provide substantial evidence for a model elucidating the molecular mechanisms of regulation of actin dynamics and migration by PMA-activated protein kinase C in glioblastoma cells.

Background As direct surgery to treat giant aneurysms of the ICA is difficult, ICA occlusion is the conventional treatment in patients with BTO tolerance. To determine whether bypass surgery should be performed after carotid occlusion by trapping or proximal occlusion, we developed a treatment strategy that includes BTO and SPECT. Methods We report 19 patients with symptomatic giant aneurysms in the cavernous portion of ICA. The appropriate type of bypass surgery was determined by the results of BTO and SPECT. The type of ICA occlusion selected was based on the evaluation of retrograde filling of the aneurysm during BTO. Results In all 19 patients, the ICA was sacrificed; 10 patients also underwent bypass surgery (low-flow bypass with STA-MCA anastomosis, n = 7; medium-flow bypass with radial artery graft, n = 2; high-flow bypass with vein graft, n = 1). Coil trapping was performed in 11 patients; proximal occlusion in 8. In 18 patients, there were no ischemic complications after treatment; 1 patient who had been treated by proximal ICA occlusion developed transient ischemia due to an intra-aneurysmal thrombus. Cranial nerve palsies were improved in 16 patients. Conclusions Based on our experience, we recommend that patients with giant aneurysms in the cavernous portion of the ICA be evaluated by BTO and SPECT. In conjunction with bypass surgery, ICA trapping or proximal occlusion constitutes an effective treatment strategy.

OBJECTIVE: Because it is difficult to predict the compaction of Guglielmi detachable coils (GDCs) after endovascular surgery for aneurysms, we studied the relationship between the coil packing ratio and compaction. Here, we propose a simple method for the preoperative estimation of coil compaction. Using follow-up angiograms, we studied the timing and degree of coil compaction in small terminal and side-wall aneurysms with narrow necks. METHODS: We studied 62 patients with acute ruptured intracranial aneurysms that were small ( RESULTS: Of the 62 patients, 16 (25.8%) manifested angiographic coil compaction (10 minor and 6 major compactions); the mean coil packing ratio was 51.9 ± 13.4%. The mean coil packing ratio in the other 46 patients was 80.5 ± 20.2%, and the difference was statistically significant (P < 0.01). In all 6 patients with major compaction, the mean packing ratio was less than 50% and all underwent re-embolization after a mean of 24.9 ± 1.1 months. The 10 patients with minor compaction were conservatively treated, and the degree of compaction did not change during a mean period of 24 months. We detected 93.8% of the compactions within 12 months of coil placement. The aneurysm was of the terminal type in 5 of the 6 patients with major coil compaction. CONCLUSION: In patients who underwent embolization with GDC-10s of aneurysms that were small and had a small neck, the optimal coil packing ratio could be identified with the formula 0.3 × a × b × c. The probability of coil compaction was significantly higher when the coil packing ratio was less than 50%. To detect coil compaction after embolization, follow-up angiograms must be examined regularly for at least 12 months. To detect major coil compaction in patients with terminal type aneurysms, angiographic follow-up should not be shorter than 24 months.

Background Hydrocephalus associated with intracranial germ cell tumors or disseminated medulloblastoma has been treated with ventriculoperitoneal shunt. However, this procedure has a potential risk of intraperitoneal metastasis of these brain tumors. To prevent this potential risk and to minimize the risk of infection, we developed a percutaneous long-tunneled ventricular drainage (PLTVD). To confirm the effectiveness, we retrospectively analyzed the results of this procedure. Methods From 1979 to 2003, we have treated 96 patients with germ cell tumors and medulloblastoma in our hospital. Of 96 patients, 59 (germ cell tumor, 31; medulloblastoma, 28) had hydrocephalus and 13 needed long-term cerebrospinal fluid drainage to manage the obstructive hydrocephalus due to persistent tumor or communicating hydrocephalus due to dissemination. We performed PLTVD for these cases using a flow-controlled shunt device and percutaneous long-tunneled shunt tube (peritoneal catheter) exiting at the upper abdomen and connecting to a closed drainage system. The occurrence of extraneural metastasis and the incidence of infection were evaluated. Results The average duration of drainage was 74 days (range, 34-115 days). All 13 cases received full-dose chemotherapy and radiotherapy without infectious complications or extraneural metastasis. Conclusions Percutaneous long-tunneled ventricular drainage was an effective method to manage long-lasting obstructive or communicating hydrocephalus with germ cell tumors and medulloblastoma.

Late-onset idiopathic aqueductal stenosis (LIAS) has been recognized as one of the clinical entities of adulthood hydrocephalus for decades, although there have been no radiological reports that show normal ventricular systems before the development of LIAS. We present here an adolescent case of LIAS with a previously normal ventricular system on magnetic resonance imaging (MRI). A 17-year-old boy had been suffering from chronic headaches and mild intellectual disability (MID) since he became a teenager, and this had prevented him from leading an ordinary school life. MRIs on admission showed triventriculomegaly from the aqueductal stenosis that had not been detected on previous MRIs, at least until the age of 6. An endoscopic third ventriculostomy was successfully performed, which improved both the headache and the MID. The developmental mechanism of LIAS remains unclear, although the membranous ependymal-like tissue observed in the aqueduct suggested the preceding existence of an inflammatory process around this region. To the best of our knowledge, this case was noteworthy because the development of LIAS was clearly demonstrated on MRI for the first time.

Background Postoperative infection remains a serious complication after radical resection of anterior skull base lesions because intracranial, nasal, and paranasal cavities are opened during surgery. To prevent complications from postoperative infection, we combined endonasal endoscopic sinus surgery (ESS) with the frontal transbasal approach in patients with skull base lesions. Methods Patients (n = 16) with anterior skull base lesions extending to the paranasal or nasal cavity underwent surgical resection via the frontal transbasal approach. After removal of the lesion via the transcranial approach, enlargement of the ostium or sinusotomy was performed bilaterally using our endonasal ESS procedure. The main purpose of ESS is the establishment of a wide drainage route to avoid dead space and postoperative infection. Furthermore, we confirmed the absence of residual lesion and leakage of cerebrospinal fluid (CSF), endoscopically. Results The frontal transbasal approach combined with endonasal ESS was performed in 16 patients with frontal skull base lesions. There were 8 malignant tumors, 6 benign tumors, and 2 mucoceles. Although 11 patients had preoperative active paranasal sinusitis, most frequently at the ethmoid sinus, none experienced postoperative infection. There was no complication related to ESS procedure. Furthermore, leakage of CSF and extracranial residual tumor were not found. Conclusion Endonasal ESS after frontal skull base surgery is a highly useful technique for preventing postoperative infection, especially for the cases with large skull base tumors extending into other regions involving the paranasal sinuses or nasal cavity and with active paranasal sinusitis.

OBJECTIVE:To investigate the characteristic clinical behavior and develop guidelines for the clinical management of posterior cerebral artery aneurysms, we reviewed 21 cases treated during a 15-year period.METHODS:Between 1988 and 2002, we treated 21 patients (10 male, 11 female; mean age, 49.8 yr) with posterior cerebral artery aneurysms at Kumamoto University Hospital and its affiliated hospitals. Data relating to the clinical, radiological, and surgical approaches were analyzed.RESULTS:There were 20 saccular aneurysms, 6 of which were giant or large aneurysms, and 1 dissecting aneurysm. Of the 21 patients, 15 presented with subarachnoid hemorrhage; in 3 patients, an unruptured saccular aneurysm was found incidentally during an evaluation for other cerebral pathological conditions. Two patients presented with progressive homonymous hemianopsia because of the mass effect of the aneurysm, and 1 patient experienced the sudden onset of homonymous hemianopsia because of thrombosis of the aneurysm and afferent artery. Open or endovascular surgery was performed in 19 patients: 14 made a good recovery, 2 had a moderate disability because of angiospasm or infarction after aneurysm trapping, 1 had a severe disability because of angiospasm and cerebral contusion, and 2 died because of severe angiospasm. Of 2 conservatively treated patients, 1 made a good recovery but the other died as a result of rebleeding.CONCLUSION:Posterior cerebral artery aneurysms have specific clinical characteristics compared with aneurysms located elsewhere. The aneurysmal site and size and the surgical technique did not significantly influence treatment outcomes.

In the endovascular treatment of cerebrovascular diseases, positioning the guiding catheter is of great importance. In cases where vessel tortuosity prohibits positioning the guiding catheter in the carotid artery via the femoral approach, we use a direct carotid approach via common carotid artery puncture. For direct puncture of the common carotid artery we devised a 6-Fr sheath with double insertion points. This new device facilitates the use of double microcatheters and provides safe and effective vascular access.

OBJECTIVE AND IMPORTANCE: Spinal arachnoid cysts are rare, and their cause and pathogenesis remain controversial. We experienced a rare case with a large congenital melanocytic nevus in which a spinal arachnoid cyst contained nevus cells, suggesting the congenital nature of a spinal arachnoid cyst. CLINICAL PRESENTATION: A 37-year-old Japanese man had been born with a large melanocytic nevus on his back. He experienced intermittent pain radiating to both thighs and to the lower back and waist. A magnetic resonance imaging study disclosed the presence of a posterior intradural extramedullary arachnoid cyst extending from T10 through T12. His spinal cord was displaced anteriorly and flattened. INTERVENTION: An osteoplastic laminoplasty was performed, and the arachnoid cyst was totally removed. The cyst membrane exhibited many foci of brown deposits, and histological examination disclosed the presence of melanin-containing cells in the cyst membrane. Morphologically and immunohistochemically, the melanin-containing cells in the cyst membrane were similar to nevus cells in the dermis. CONCLUSION: The histological findings of our case suggest that the patient's spinal arachnoid cyst was formed at the same stage of development as the melanocytic nevus.

Venous congestion of the brain stem due to dural arteriovenous fistulas (DAVFs) in the cavernous sinus is rare and presents therapeutic challenges. To assess the prognosis of patients with symptomatic DAVFs and brain stem dysfunction, we evaluated the degree of venous ischemia by examining pre- and post-treatment magnetic resonance images (MRI) in 2 patients presenting with venous congestion of the brain stem.A 56-year-old woman with left hemiparesis and a 70-year-old woman with gait disturbance attributable to right cavernous sinus DAVFs were referred to our hospital. In both cases, T2-weighted magnetic resonance imaging (MRI) disclosed a hyperintensity lesion in the brainstem due to venous congestion.Both patients underwent open surgery for direct embolization of the cavernous sinus because there were no approach routes for transvenous embolization. The patient whose pretreatment MRI demonstrated Gd enhancement continued to manifest neurological deficits and persistence of the abnormal hyperintensity on post-treatment T2-weighted MRI. In the other patient whose pretreatment MRI showed no Gd enhancement, treatment produced a complete response of her neurological deficit and disappearance of the abnormal hyperintensity area.We tentatively conclude that lesions corresponding to hyperintensity areas on non-Gd-enhanced, T2-weighted MRI may reflect a reversible condition whereas lesions identified as hyperintense areas on GD-enhanced T2-weighted MRI may be indicative of irreversibility.

Objective We analyzed the community incidence and early prognosis of first-ever aneurysmal subarachnoid hemorrhages (SAHs) to obtain the same prognostic information used by physicians and families in a defined geographic area in Japan. Methods During the 5-year period from January 1, 1996, to December 31, 2000, 2115 patients were registered in the Data Bank for Cerebral Aneurysms of Kumamoto Prefecture, a defined area in Japan with a population of 1.86 million. Registration was based on a comprehensive referral system for SAH patients; computed tomographic scans were available for all patients, including those who were moribund or dead on arrival. We compared the treatment outcomes at 3 months after the first-ever SAH in surgically and conservatively treated patients. Results The age-adjusted annual incidence of SAH for men, women, and both sexes was 15.9, 26.6, and 21.6 per 100,000 person-years, respectively. In men, the incidence reached a plateau after age 40 years. In women, conversely, it rose after age 40 and peaked in the 9th decade of life. Of the 1634 surgically treated patients, 1153 (70.6%) had a favorable outcome; this was true for only 27 of 477 (5.7%) conservatively treated patients. Four patients were lost to follow-up. The clinical outcome did not differ between patients treated by open surgery and those treated endovascularly. Approximately 30% of our patients were older than 70 years at the time they experienced their first SAH. Conclusion The incidence of SAH obtained in this study was similar to earlier Japanese reports and Finnish studies. The importance of managing elderly patients with cerebral aneurysms will continue to increase.

Background and Purpose— To clarify hemodynamic risk factors for hemorrhage in arteriovenous malformations (AVMs), the mean transit time (MTT) of feeding arteries and draining veins in AVMs with and without hemorrhage was measured and analyzed. Methods— Morphological features such as the number and diameter of draining and feeding vessels and the AVM nidus volume were evaluated in 30 patients with supratentorial AVMs. The MTT of feeding arteries and draining veins was measured with the use of time-density curves obtained by digital subtraction angiography. The correlation between hemorrhage and morphology and hemorrhage and MTT was analyzed statistically. Results— The nidus volume was not significantly different between hemorrhagic and nonhemorrhagic AVMs. However, between ruptured and unruptured AVMs there was a significant difference in the mean number of draining veins (1.5±0.69 versus 2.3±0.50; P =0.006), the MTT of the feeding artery (1.10±0.24 versus 1.62±0.55; P =0.03), and the ratio of the MTT of the draining to the feeding vessels (1.71±0.43 versus 1.05±0.07; P Conclusions— A high ratio of the MTT of draining veins to feeding arteries suggests disequilibrium between nidal inflow and outflow. The consequent increased pressure in the draining vein may contribute to the development of AVM hemorrhage.

OBJECTIVE AND IMPORTANCE Hyperperfusion has been reported after carotid endarterectomy or stenting for stenosis of the internal carotid artery. Because few reports have examined postoperative hyperperfusion after treatment for dural arteriovenous fistulae (DAVFs), we present a case describing a patient who manifested this clinical entity. CLINICAL PRESENTATION The patient was a 63-year-old man with a DAVF in the left transverse sigmoid sinus with retrograde leptomeningeal venous drainage. He experienced slowly progressive disorientation lasting for several months. Preoperative single-photon emission computed tomography with 123I-labeled N-isopropyl-p-iodoamphetamine revealed an area of hyperintensity on T2-weighted magnetic resonance imaging (MRI) scans that coincided with the hypoperfusion area; it was not increased after acetazolamide challenge. Complete DAVF obliteration was achieved by embolization, then sinus isolation. After treatment, he experienced frequent generalized convulsions that were terminated by 2-day barbiturate therapy. INTERVENTION On T2-weighted MRI scans obtained 3 days after surgery, the hyperintense area not only persisted but had expanded to the left parietal lobe. Moreover, a subcortical hyperintense lesion was recognized on T1-weighted MRI scans; this was considered to reflect cortical laminar necrosis. Single-photon emission computed tomography revealed hyperperfusion in the left parietal lobe; it changed to hypoperfusion a month after treatment. CONCLUSION In patients with DAVFs with preoperative findings of marked low perfusion and a poor perfusion reserve, postoperative study may reveal hyperperfusion on single-photon emission computed tomography or cortical laminar necrosis on MRI. This may be evidence of severe perfusion disturbance as a result of venous infarction. In these patients, careful blood pressure control and early treatment of seizures are important after DAVF treatment.

¶Background. In the treatment of vertebral artery (VA) dissecting aneurysms, only proximal occlusion of the VA does not necessarily prevent rerupture. We evaluated the efficacy of coil trapping for the ruptured VA dissecting aneurysms using the double microcatheters technique. Methods. We treated 11 patients who presented with subarachnoid haemorrhage (SAH) due to rupture of a VA dissecting aneurysm which did not involve the posterior inferior cerebellar artery at the site of dissection. All patients tolerated the balloon occlusion test. Within 3 days of the SAH, the dissection site was trapped with a Guglielmi detachable coil (GDC) using the double microcatheters technique. The proximal and distal sites of the dissecting aneurysm were embolized simultaneously. Findings. GDC trapping at the affected site was successful in all 11 patients. Radiographic findings showed complete occlusion of the dissection site and patency of the unaffected artery. Although one patient experienced transient dysphagia, there were no major complications. Interpretation. The double microcatheters technique is effective for coil trapping of ruptured VA dissecting aneurysms in selected patients. The risks posed by this simple technique are minimal, even in the acute stage.

The prevention of rebleeding is one of the most important issues in the successful treatment of moyamoya disease with hemorrhagic onset. However, the natural course of hemorrhagic moyamoya disease and the characteristics of rebleeding remain unclear.To study the natural course of the disease in conservatively treated patients, we analyzed long-term follow-up reports on 36 patients (12 male and 24 female) treated without bypass surgery at our hospitals before 1994 (mean follow-up, 12.7 +/- 7.1 yr; range, 2.9-27.0 yr).Of our 36 patients, 22 (61.1%) experienced rebleeding; there were 29 rebleeding episodes. The outcomes in patients with rebleeding were worse than in patients who did not rebleed (P0.05); in most cases, unsatisfactory results were attributable to rebleeding. Kaplan-Meier and multivariate analysis of rebleeding-free survival showed that age at onset (36 yr) was a statistically significant risk factor; sex, hypertension, type of intracranial bleeding, and outcome after the first bleeding episode were not. Although the intervals between the first and subsequent episodes varied, both the rebleeding rate and the number of rebleeding episodes were highest in patients 46 to 55 years old.Rebleeding is the most important factor in unsatisfactory outcomes of patients with hemorrhagic moyamoya disease. Rebleeding seems to be age-related; rebleeding occurs at an increased rate when patients reach the age range of 46 to 55 years. Patients with hemorrhagic moyamoya must be followed up throughout their lives, even if their neurological status is excellent.

A 60-year-old man was admitted to our hospital with sudden onset of motor aphasia, Gerstmann syndrome, and incomplete right hemiparesis one week after administration of chemotherapy for mucosa-associated lymphoid tissue (MALT) lymphoma. Computed tomography showed an intracerebral hematoma in the left subcortical area. Cerebral angiography revealed 2 aneurysms on the distal middle cerebral artery (MCA) that increased in size in the course of 2 weeks. The aneurysms were excised and a bypass placed using a superficial temporal artery (STA) graft. Histological study showed no bacteria, infiltration of inflammatory cells, or lymphoma cells in the aneurysm wall. The chemotherapy against MALT lymphoma was highly effective, so we presumed that the lymphoma cells had disappeared. The source of the distal MCA aneurysms was thought to be oncotic. Distal MCA aneurysms caused by MALT lymphoma are extremely rare. Surgical reconstruction using the STA may be effective in patients with ruptured distal MCA aneurysms if the wall is intact.

WARRIORS THROUGHOUT THE AGES have considered the unprotected head to be particularly vulnerable. The traditional Japanese helmet, the Kabuto, was the part of a protective suit of armor that reflected the wearer's character and personality. Over time, it changed from a primarily protective device to a vehicle for the expression of a distinctly Japanese sense of magnificent artistry. Each Kabuto was custom-made, and these helmets remain without peer in the world. They were designed and crafted to answer the demands of their era, and thus they provide historical evidence not only of the state of Japanese warfare, but also of social organization, metallurgical knowledge, artisanship, and aesthetic sensibility. Even now, during the national Golden Week Festival in early May, Kabuto are displayed in the alcoves of Japanese homes as a petition that the boys in the house be granted courage and good health. Thus, even in modern Japan, the Kabuto represents a talisman. We present an overview of the evolution of the Kabuto, with special reference to the Japanese sword and the warrior tradition.

OBJECTIVE AND IMPORTANCE We present two interesting cases involving carotid-cavernous dural fistulae draining only or predominantly into the petrosal vein after previous incomplete, complicated, endovascular treatments. Transvenous embolization with Guglielmi detachable coils, via the petrosal vein, during surgical exposure completely obliterated the fistulae. CLINICAL PRESENTATION A 64-year-old man manifesting left ocular symptoms after incomplete embolization of a left carotid-cavernous dural fistula and a 56-year-old woman manifesting left hemiparesis after complicated embolization of a right carotid-cavernous dural fistula were referred to our hospital. A percutaneous transvenous approach was attempted in both cases, but the catheter could not reach the fistula site. A combined open surgical and endovascular approach was then used. INTERVENTION The hemispheric branch of the petrosal vein was exposed via a retromastoid craniectomy. The catheter was then directly introduced into the hemispheric branch, followed by navigation into the fistula site. The fistula was completely embolized with Guglielmi detachable coils. CONCLUSION The technique of surgical transvenous embolization via a petrosal vein is a valuable alternative for the treatment of carotid-cavernous dural fistulae that drain only or predominantly into the petrosal vein, when the percutaneous transvenous route is not accessible.

Object. In patients with aneurysms that require occlusion of the posterior inferior cerebellar artery (PICA), revascularization of this artery should be performed. A novel surgical method for revascularization of the PICA is presented. Methods. After a segment of the superficial temporal artery (STA) was harvested, the aneurysm was treated by trapping, followed by placement of a vertebral artery (VA)—PICA bypass in which the STA segment was used as a graft. When the length of the proximal PICA was inadequate, the distal end of the STA was anastomosed to the proximal PICA in an end-to-side fashion. When the length of the proximal PICA was adequate, the STA was anastomosed to the proximal PICA in an end-to-end fashion. In either case, the proximal end of the STA was anastomosed to the VA in an end-to-side fashion. This procedure was used in nine patients whose aneurysms involved the PICA. Although partial lateral medullary syndrome developed in one of them, follow-up evaluation revealed graft patency in all patients. There were no instances of recurrent hemorrhage or ischemia. Conclusions. Although this procedure requires harvesting of an STA graft and two anastomoses, it facilitates anterograde flow to the PICA territory. It also involves minimal mobilization of brainstem perforating vessels and the proximal PICA.

A 55-year-old male presented with a ruptured distal posterior inferior cerebellar artery (PICA) aneurysm manifesting as subarachnoid hemorrhage. Angiography demonstrated a saccular aneurysm arising from the lateral medullary segment of the left PICA and located on the medial side of the left vertebral artery (VA) and the anterior surface of the medulla oblongata. A transcondylar fossa approach was used to ensure a sufficient operating field and to obtain adequate visualization of the aneurysm, the parent artery, and the perforating arteries to the medulla oblongata. The aneurysm dome protruded medially at the hairpin curve, and was located on the medial side of the left VA and on the anterior surface of the medulla oblongata. There was no vessel branches in the vicinity of the aneurysm. The aneurysm was successfully clipped with minimum retraction of the cerebellar hemisphere and medulla oblongata. Distal PICA aneurysms can be located at various sites in the posterior fossa. The exact location of the aneurysm must be established to select the best surgical approach.

A 42-year-old woman presented with right oculomotor, abducens, and trigeminal palsy. Neuroimaging revealed a small lesion in the right cavernous sinus mimicking meningioma. Because the symptoms gradually worsened, the patient underwent an endoscopic endonasal transsphenoidal surgery for tumor biopsy. Histological examination of the surgical specimen revealed adenoid cystic carcinoma (ACC). Before and after the operation, no evidence of other primary lesions could be detected. The patient was treated with stereotactic radiosurgery (SRS). ACC in the cavernous sinus can be difficult to diagnosis before histological confirmation, because it is extremely rare as a primary lesion and resembles a cavernous sinus meningioma on neuroimaging studies. Two years after the first SRS, the tumor recurred along the trigeminal nerve and SRS was performed again. Our study illustrates that in case in which a lesion in the cavernous sinus progresses on neurological and neuroimaging studies, a biopsy should be taken to provide most accurate diagnosis and treatment.

BACKGROUND AND PURPOSE: The hemodynamics of the inflow zone of cerebral aneurysms may be a key factor in coil compaction and recanalization after endovascular coil embolization. We performed 4D flow MR imaging in conjunction with 3D TOF MRA and compared their ability to identify the inflow zone of unruptured cerebral aneurysms. MATERIALS AND METHODS: This series comprised 50 unruptured saccular cerebral aneurysms in 44 patients. Transluminal color-coded 3D MRA images were created by selecting the signal-intensity ranges on 3D TOF MRA images that corresponded with both the luminal margin and the putative inflow. RESULTS: 4D flow MR imaging demonstrated the inflow zone and yielded inflow velocity profiles for all 50 aneurysms. In 18 of 24 lateral-projection aneurysms (75%), the inflow zone was located distally on the aneurysmal neck. The maximum inflow velocity ranged from 285 to 922 mm/s. On 4D flow MR imaging and transluminal color-coded 3D MRA studies, the inflow zone of 32 aneurysms (64%) was at a similar location. In 91% of aneurysms whose neck section plane angle was

Background and Purpose —The feasibility of preventing vasospasm by intrathecal anterograde infusion of urokinase (UK) into the cisterna magna was studied in patients with recently ruptured aneurysms who had just undergone the placement of a Guglielmi detachable coil (GDC). Methods —Immediately after complete embolization with the use of GDC-10 coils, 15 patients with Hunt and Hess neurological grades III and IV received 60 000 IU of UK in normal saline through a microcatheter advanced into the cisterna magna. UK infusion was repeated once or twice over a period of 2 to 3 days according to a decision based on CT evidence of a subarachnoid clot remaining in the cisterns. Before administering the last UK infusion, we obtained CT confirmation of almost complete clearance of clots in the basal cisterns. Results —In all 15 patients, the microcatheter was advanced easily into the cisterna magna by use of the over-the-wire microcatheter technique. In 8 patients who received thrombolytic therapy within 24 hours of the ictus, there was almost complete clearance of the clot in the basal cisterns within 2 days of suffering the insult. When UK was injected at 24 to 48 hours after the insult, 7 patients manifested CT evidence of clearance at the latest 4 days after suffering the insult. In all 15 patients, CT scans obtained within 24 hours of the final UK administration showed complete resolution of clots in the basal cistern and almost complete resolution of clots in the basal interhemispheric fissure and bilateral proximal sylvian fissures. Although one patient developed a transient neurological deficit, no patients manifested permanent delayed neurological deficits as a result of vasospasm. Outcome assessment according to the Glasgow Outcome Scale, no less than 3 months after GDC placement, revealed good recovery in all patients, and none developed hydrocephalus requiring a shunt procedure. Conclusions —In patients with recently ruptured aneurysms, GDC placement followed by immediate intrathecal administration of UK from the cisterna magna may be a safe and reasonable means of preventing vasospasms and may result in improved treatment outcomes.

Object. Of all intracranial dural arteriovenous fistulas (DAVFs), those with cortical venous drainage associated with cortical venous ectasia or varices are predisposed to an aggressive course and produce progressive neurological symptoms or hemorrhages. The authors undertook a histological examination of venous aneurysms and arterialized veins in the proximity of these aneurysms that had been surgically removed in patients with DAVFs.Methods. Surgical specimens were obtained in eight patients. The excised venous aneurysms and the arterialized veins in their proximity were stained using hematoxylin and eosin, van Gieson's elastic, and Masson's trichrome stain. Immunostaining was also performed for alpha smooth-muscle actin, desmin, and factor VIII antigen. Five of the patients had presented with venous hypertension, and three had intracranial hemorrhages. The arterialized vein obtained in the proximity of the venous aneurysm exhibited local irregular intimal thickening; the internal elastic lamina (IEL) was grossly preserved. All venous aneurysms in patients with venous hypertension manifested medial thickening and local intimal thickening with loss of IEL; the thickness of the wall was relatively uniform. In contrast, the wall thickness of venous aneurysms in patients with hemorrhage was extremely irregular and there was no clear delineation between the media and the intima. In media with complete disappearance of IEL, there was scant muscle tissue.Conclusions. Degenerative changes in venous aneurysms in patients with hemorrhage were much greater than in patients with venous hypertension, possibly because hemorrhages result from a more complicated interplay of anatomical, hemodynamic, and degenerative factors.

A 51-year-old woman with bone wax-induced osteohypertrophy presented with exophthalmos 9 years after a craniotomy for a right internal carotid bifurcation aneurysm. CT scans revealed thickening of the frontotemporal bone flap and surrounding bone, thickening of the upper and lateral orbital walls, and a limited intraorbital cavity. Intraoperative findings revealed residual bone wax under the bone flap, grayish-white discoloration of the flap, and degeneration of the temporal muscle. Pathological examination revealed granulation and osteogenesis due to a foreign body. To our knowledge, this is the first report of bone wax-induced hyperostosis leading to exophthalmos.

金沢大学附属病院脳神経外科, A 30-year-old man presented with a history of several convulsive episodes. A CT scan showed a calcified focus in the right temporal lobe. Cerebral angiography yielded no abnormal findings. At craniotomy, the M3 portion of the middle cerebral artery was found to terminate with a blind end at the junction with the calcified mass. A pathological diagnosis of an ossified cerebral aneurysm was made. Calcified cerebral aneurysms are not rare; they are thought to be the result of intra-aneurysmal thrombosis or degenerative changes in the aneurysmal wall. However, complete mural ossification of a cerebral aneurysm is seldom seen, and ossified peripheral middle cerebral artery aneurysms are extremely rare in young individuals. The ossified aneurysm that we report developed over a prolonged period and may have arisen during childhood. © 2008 Elsevier Ltd. All rights reserved..

Calcineurin belongs to the family of Ca2+/calmodulin-dependent protein phosphatase, protein phosphatase 2B. Calcineurin is the only protein phosphatase which is regulated by a second messenger, Ca2+. Furthermore, calcineurin is highly localized in the central nervous system, especially in those neurons vulnerable to ischemic and traumatic insults. For these reasons, calcineurin is considered to play important roles in neuron-specific functions. Recently, on the basis of the finding that FK506 and cyclosporin A serve as calcineurin-specific inhibitors, this enzyme has become the subject of much study. It is clear that calcineurin is involved in many neuronal (or non-neuronal) functions such as neurotransmitter release, regulation of receptor functions, signal transduction systems, neurite outgrowth, gene expression and neuronal cell death. In this review, we describe the calcineurin functions, functions of the substrates, and the pathogenesis of traumatic and ischemic insults, and we discuss the potential role of calcineurin. There are many similarities in traumatic and ischemic pathogenesis of the brain in which the release of excessive glutamate is followed by an intracellular Ca2+ increase. However, the intracellular cascade which leads to neuronal cell death after the release of excess Ca2+ is unclear. Although calcineurin is thought to be a key toxic enzyme on the basis of studies using immunosuppressants (FK506 or cyclosporin A), many of the functions of the substrates for calcineurin protect against neuronal cell death. We concluded that calcineurin is a bi-directional enzyme for neuronal cell death, having protective and toxic actions, and the balance of the bi-directional effects may be important in ischemic and traumatic pathogenesis.

Background Aneurysms of the spinal artery are exceedingly rare. We report on the first case of a pathologically proven aneurysm arising from the feeding pedicle of a perimedullary arteriovenous fistula (AVF). Case Description A 42-year-old man presented with subarachnoid hemorrhage (SAH) and spinal angiography demonstrated a thoracic perimedullary AVF fed by the left T8 intercostal artery that also harbored a spinal aneurysm. He underwent laminectomy 18 days postonset. The aneurysm was resected and the fistula was interrupted. Conclusion For appropriate treatment planning, it is necessary to rule out the presence of aneurysms on the feeding vessel in patients with spinal perimedullary AVF who present with SAH.

Objective The arcuate fasciculus has been recognized as an important pathway for language processing. Brain tumors located in proximity to the fasciculus frequently cause preoperative language impairment, and in some cases, no language recovery occurs after tumor resection. No predictive value has been presented for possible postoperative language recovery after tumor resection. The aim of this study is to analyze the preoperative state of the arcuate fasciculus in the patients with brain tumor from the perspective of its usefulness as a predictive factor for postoperative recovery of language functions. Methods For 12 right-handed patients with brain tumors in the left hemisphere, preoperative arcuate fasciculi were analyzed with fractional anisotropy (FA) of the diffusion tensor imaging (DTI) tractography. Language functions were evaluated pre- and postoperatively by using the Western Aphasia Battery (WAB). The preoperative value of the FA of the arcuate fasciculus on the lesion side was examined in relation with the language recovery. Results There was a positive relationship between preoperative increasing values of the FA of the left arcuate fasciculus and improvement of the postoperative total WAB score ( p =0.0056), and the scores of the naming ( p =0.018), reading ( p =0.029), and writing subcategories ( p =0.012) Conclusion The preoperative increasing value of the FA of the arcuate fasciculus in the dominant hemisphere could be a predictor for postoperative language recovery following tumor resection. Meticulous procedure should be performed especially in the cases with higher FA of the arcuate fasciculus harboring high possibility of language recovery.

Background. Extensive evidence implicates the Eph receptor family of tyrosine kinases and its ligand, ephrin, in glioma invasion, but it remains incompletely understood how these receptors affect chemotactic behavior of glioma. We sought to identify the Eph family members that correlate with patients’ survival and to reveal the function of Eph in glioma invasion. Methods. Clinical relevance of EphB genes was confirmed in a clinically annotated expression data set of 195 brain biopsy specimens. The function of EphB was analyzed in vitro and in vivo. Results. Levels of mRNA of certain EphB members were significantly different in histological grades of glioma. According to Kaplan–Meier analysis, only the EphB1 level among 5 members of EphB emerged to be a powerful predictor of favorable survival in malignant glioma (n ¼ 97, P ¼ .0048), although the levels of EphB1 expression did not vary across the tumor grades. Immunoprecipitation showed that tyrosine phosphorylated EphB1 was not detected in all glioma cells tested. Forced overexpression and autophosphorylation of EphB1 in low expressor cell lines (U251, U87) did not affect cell migration or invasion in vitro, whereas EphB1 phosphorylation induced by ephrin-B2/Fc significantly decreased migration and invasion. Cells expressing ephrin-B2 showed noteworthy morphological changes consistent with migration induction; this alteration was negated by EphB1 overexpression. Concomitantly, overexpression of EphB1 abrogated the increased migration and invasion induced by ephrin-B2 in vitro and in vivo. Conclusions. These data suggest that ligand-dependent EphB1 signaling negatively regulates glioma cell invasion, identifying EphB1 as a favorable prognostic factor in malignant glioma.