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Background: Meningioma and dural arteriovenous fistula (dAVF) located at the same site are rare. The present case demonstrated the transformation of tumor feeding vessels into the pial feeder of the dAVF over time, which may help to elucidate the pathogenesis of tumor-associated dAVF. Case Description: A 71-year-old man presented with convulsion. Magnetic resonance (MR) imaging showed a right parasagittal sinus meningioma invading the superior sagittal sinus (SSS). Bilateral external carotid angiography showed dAVF at the SSS, near the site of tumor invasion. The right internal carotid angiography showed tumor staining from the anterior cerebral artery with intra-tumor arteriovenous shunting, with stagnation of tumor blood flow, suggesting impairment of perfusion to the SSS. Four years after the initial diagnosis, the patient was admitted to hospital with status epilepticus, and MR imaging showed an enlarged tumor. Carotid angiography revealed transformation of the tumor feeders to the pial feeder of the dAVF. The findings of shunting to the SSS had intensified, and stenosis had occurred in the posterior third of the SSS. The venous return showed retrograde flow anteriorly to the SSS. The patient underwent endovascular embolization and tumor resection. The shunt had disappeared. Conclusion: This report supports the proposal that impaired venous return is an important factor in the shunt occurrence of dAVF. Neurosurgeons should consider that cases of meningioma invading the venous sinuses may be complicated by dAVF and changes may occur over time.

Subcortical white matter infarction causes ischemic demyelination and loss of brain functions, as the result of disturbances of the blood flow. Although angiogenesis is one of the recovery processes after cerebral infarction, the dynamics of revascularization after white matter infarction still remains unclear. We induced white matter infarction in the internal capsule of Flk1-GFP::Flt1-tdsRed double transgenic mice by injection of endothelin-1 (ET-1), a vasoconstrictor peptide, together with N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and followed the changes in Flk1 and Flt1 expression in the vascular system in the infarct area. Reduction of Flt1-tdsRed-positive blood vessels 1 day after the injection and increase of Flk1-GFP-strongly-positive blood vessels 3 days after the injection were apparent. PDGFRβ-strongly-positive (PDGFRβ+) cells appeared in the infarct area 3 days after the injection and increased their number thereafter. Three days after the injection, most of these cells were in close contact with Flk1-GFP-positive endothelial cells, indicating these cells are bona fide pericytes. Seven days after the injection, the number of PDGFRβ+ cells increased dramatically, and the vast majority of these cells were not in close contact with Flk1-GFP-positive endothelial cells. Taken together, our results suggest revascularization begins early after the ischemic insult, and the emerging pericytes first ensheath blood vessels and then produce fibroblast-like cells not directly associated with blood vessels.

Objective Long-term effectiveness of selective ventralis intermedius nucleus (VIM)–ventralis oralis nucleus (VO) thalamotomy with depth microrecording for the treatment of focal dystonia was evaluated. The optimal thalamic areas for controlling focal dystonia were studied based on the electrophysiologic and anatomic data. Methods Stereotactic selective VIM-VO thalamotomy with depth microrecording was carried out in 8 patients with focal arm and hand dystonia and in 1 patient with cervical dystonia. Electrophysiologic data on the lateral part of thalamic VIM were studied in patients with focal dystonia. A very small and narrow therapeutic lesion was formed in the shape of a square on the sagittal plane and of an I, rotated V, Y, or inverse Y on the axial plane in the VIM-VO, which covered the kinesthetic response area topographically related to focal dystonia. Patients with arm and hand dystonia were followed up for 4.7 ± 3.0 years and 1 patient with cervical dystonia was followed up for 18.2 years. Results Marked improvement of focal dystonia was shown by functional assessment using the Unified Dystonia Rating Scale. Transient dysarthria was recognized in 1 patient. The sequence of body localization of kinesthetic response in the VIM was clearly shown in patients with focal dystonia. Decreases in the amplitude and amplitude ratio of electromyography on the forearm muscles were markedly significant after VIM thalamotomy, but insignificant after VO thalamotomy immediately after VIM thalamotomy. Conclusions Marked reduction of electromyographic tonic discharges of focal dystonia was shown after VIM lesioning. Selective VIM-VO thalamotomy showed good and long-term stable effects for focal dystonia.

A 40-year-old man was admitted to our hospital because of disorientation and mild left-sided weakness. Radiological examination revealed a solid and cystic tumor in the right temporal lobe, and total resection was performed. Histologically, the tumor was composed mainly of low-grade gangiloglioma and had some high-grade glial components with focal necrosis and microvascular proliferations. In the high-grade component, there were epithelioid cells with round cytoplasm and eccentric nuclei. The high-grade area with epithelioid cells was intermingled within the low-grade area, which suggests that epithelioid cells were an anaplastic transformation of ganglioglioma. The epithelioid cells were histologically similar to neoplastic cells of epithelioid glioblastoma (E-GBM), a rare aggressive variant of isocitric dehydrogenase wild-type glioblastoma. A BRAF V600E mutation, frequently observed in E-GBM, was detected in both the ganglioglioma and epithelioid cell components. The epithelioid cells were mitotically active, which suggests that if the surgery was delayed, the histological appearance might have eventually evolved into E-GBM. Indeed, a case of pleomorphic xanthoastrocytoma which transformed into E-GBM after a long latency was reported elsewhere. This is the first report to describe focal epithelioid cells in anaplastic ganglioglioma.

Objective The minimum and essential thalamic areas for reducing tremor were investigated in cases treated by superselective thalamotomy in the most lateral part of the ventralis intermedius nucleus (mlp-VIM). Methods Stereotactic superselective VIM thalamotomy with depth microrecording was performed in 21 patients with essential tremor (ET) and 15 patients with tremor-dominant Parkinson disease (PD). A very small and narrow (axial plane) therapeutic lesion was formed as a square on the sagittal plane and inverse V on the axial plane in the mlp-VIM, which covered the kinesthetic response area topographically related to tremor. Patients with ET were followed up for 4.7 ± 3.0 years and patients with PD for 7.9 ± 3.9 years. Results Almost complete tremor control was achieved in all patients immediately after surgery and continued for up to 8 years. A few adverse events were recognized but disappeared within 1 month without 1 patient with thalamic hemorrhage. The medial border of the therapeutic lesion was significantly more lateral in both patients with ET and patients with PD than the calculated standard target point and was in patients with PD than in patients with ET. The mean width was only about 2.4 mm. The individual differences of the adequate location of the therapeutic lesion were significantly greater in the ET than in the PD group. Conclusions The important area for reducing tremor was small and narrow and was located in the mlp-VIM, where the proprioceptive ascending signals from the tremor-dominant body part are conducted. Superselective thalamotomy in the mlp-VIM was safe and effective for the long-term in patients with ET and PD.

The postoperative metabolic states of subarachnoid hemorrhage (SAH) patients were investigated using indirect calorimetry (IDC) and various nutritional evaluations to establish any difference in perioperative metabolic and nutritional states between microsurgical and endovascular treatment. This study included 30 acute aneurysmal SAH patients with ruptured intracranial aneurysms treated by surgical clipping (n = 16) or coil embolization (n = 14) at a single institute. The resting energy expenditure (REE) and respiratory quotient were measured using IDC on days 1, 4, 7, 10, 14, and 17–21 after the operation. Various blood tests, including C-reactive protein (CRP) and prealbumin, were evaluated on the same days. The clipping group showed a significant increase in REE/basal energy expenditure (BEE) compared with the coiling group on days 1 and 4 (p = 0.04 and 0.03, respectively). No significant differences were found on days 7, 10, 14, and 17–21. The mean REE/BEE on days 1–14 and 1–21 showed no significant differences between the groups with repeated measures analysis of variance. The clipping group showed a significant decrease of prealbumin on day 4 and significant increase in CRP on days 1, 4, and 7. The clipping group was in the hypermetabolic state compared with the coiling group during the very early postoperative period. However, the difference associated with the treatment modality was relatively small compared to the effects of the SAH and of the sequelae.

In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron‐dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOX) to ferroptosis in oncogenic Ras‐expressing cancer cells. Several 12/15‐LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA‐mediated silencing of ALOX15 significantly decreased both erastin‐induced and RSL3‐induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds. Immunofluorescence analyses revealed that the ALOX15 protein consistently localizes to cell membrane during the course of ferroptosis. Importantly, treatments of cells with ALOX15‐activating compounds accelerated cell death at low, but not high doses of erastin and RSL3. These observations suggest that tumor ferroptosis is promoted by LOX‐catalyzed lipid hydroperoxide generation in cellular membranes.

Objective Various diseases can occur in the sellar and suprasellar regions. The potential of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) for the preoperative evaluation of sellar and parasellar lesions was investigated. Methods A total of 49 patients aged 8–82 years with sellar and parasellar macroscopic lesions (≥10 mm) underwent FDG PET. Twenty-two patients had pituitary adenomas, including 14 nonfunctioning and 8 growth hormone–secreting adenomas. Eleven patients had craniopharyngiomas, including 5 adamantinomatous and 6 squamous-papillary types. Eight patients had chordoma, 4 had meningioma, and 4 had a Rathke cleft cyst. The maximum standardized uptake value (SUVmax), and the ratio of the SUVmax in the tumor to the mean standardized uptake value in the normal cortex (T/N ratio) or in the normal white matter (T/W ratio) were calculated. The relationships between SUVmax, T/N ratio, and T/W ratio, and lesion disease were evaluated. Results Uptakes of FDG, including SUVmax, T/N ratio, and T/W ratio, were lower in chordoma and Rathke cleft cyst compared with pituitary adenoma. SUVmax, T/N ratio, and T/W ratio of nonfunctioning adenoma were significantly higher than those of growth hormone–secreting adenoma. SUVmax, T/N ratio, and T/W ratio of squamous-papillary type were significantly higher than those of the adamantinomatous type of craniopharyngioma. Conclusions FDG PET is useful for the preoperative diagnosis of sellar and parasellar macrolesions. High uptake in nonfunctioning pituitary adenoma, and low uptake in chordoma are significant. The difference in FDG uptake dependent on the histologic subtype may be related to the specific genetics of the craniopharyngioma subtype.

OBJECTIVEHead CT is sometimes performed immediately after minor head injury; however, which cases develop into chronic subdural hematoma (CSDH) remains unclear. Here, the authors retrospectively reviewed the rare cases of CSDH treated surgically in which early head CT had been performed after the initial head trauma.METHODSA total of 172 patients (133 male and 39 female, median age 76 years) underwent surgery for CSDH at Gunma University Hospital between April 2010 and December 2017. Among these patients were 23 who had visited Gunma University Hospital or a nearby hospital and had undergone head CT within 7 days after the initial head trauma. Characteristics of the initial head CT were examined to identify indicators of subsequent CSDH.RESULTSAmong the 23 CSDH cases (17 male and 6 female, median age 80 years), CT scans were obtained on the day of the initial injury (day 0) in 19 cases (25 sides) and 1–7 days after injury in 12 cases (19 sides); scans were obtained during both periods in 8 cases (12 sides), so that a total of 44 sides were examined. These CT scans were divided into two groups according to when they were obtained; cases in which scans were taken during both periods were included in both groups. Head CT performed on the day of injury showed normal findings in 5 (20%) of 25 sides, thin subdural effusion (SDE) ≤ 6 mm in 16 (64%) of 25 sides, thick SDE > 6 mm in 3 (12%) of 25 sides, and acute subdural hematoma (ASDH) in 1 (4%) of 25 sides. CT from 1–7 days after trauma showed thick SDE in 9 (47%) of 19 sides, thin SDE in 8 (42%) of 19 sides, and ASDH in 2 (11%) of 19 sides. A high-density line in the lateral direction (onion skin–like) was found between the skull and the brain in 9 (35%) of 26 sides with SDE on initial CT 0–7 days after the injury.CONCLUSIONSASDH was not a common cause of CSDH. Head CT at the time of trauma that precedes CSDH often showed SDE. Such SDE that precedes CSDH was often close to the detection limit of CT immediately after the injury but became more apparent from the day after the injury.

We report four cases of high-grade astrocytoma with a BRAF V600E mutation, ATRX inactivation, and CDKN2A/B homozygous deletion. Children to young adults aged 3–46 presented with a well demarcated contrast-enhancing mass in the supratentorial area. Pathological examination revealed packed growth of short spindle to round polygonal cells including some pleomorphic cells. The tumors had less ability to infiltrate into the adjacent brain parenchyma and presented a circumscribed growth pattern. Mitosis was readily found, accompanied by focal necrosis and/or microvascular proliferation. Tumors were histologically similar in part to pleomorphic xanthoastrocytoma (PXA) or anaplastic PXA, but did not fit criteria for either neoplasm. A BRAF V600E mutation and homozygous deletion of CDKN2A/B were observed, which is similar to the genetic features of PXA or epithelioid glioblastoma, but the additional loss of ATRX nuclear immunoreactivity and absence of TERT promoter mutation were unusual findings, indicating a novel genetic profile. Despite their malignant histological features, all patients had a favorable clinical course and remained alive for 6 months to 28 years under standard medical treatment for malignant glioma. In summary, high grade astrocytomas with BRAF V600E, ATRX, and CDKN2A/B alternations had unique clinicopathological features and may be a novel subset of high grade glioma.

Objectives In the endovascular treatment of acute cerebral large-vessel occlusion, cervical magnetic resonance angiography (MRA) is a useful modality for assessing the access route. However, we sometimes encounter cases in which not only the internal carotid artery (ICA), but also the common carotid artery (CCA) is poorly visualized, leading to hesitation over which devices and techniques to choose for revascularization. We retrospectively evaluated such cases, focusing on image findings and treatment results. Materials and Methods Data from 96 patients who underwent acute endovascular revascularization from January 2016 to December 2019 were analyzed. We extracted patients with poor CCA visualization on cervical MRA from 35 cases with ICA occlusion, and examined angiographic findings, treatment methods, and outcomes. Results Poor visualization of the CCA in cervical MRA was observed in 8 cases. All cases displayed atrial fibrillation or sick sinus syndrome. Angiographic findings showed true CCA occlusion in 2 patients and ICA occlusion in 6 patients. Reasons for the inability to visualize the CCA on cervical MRA were speculated to be stenosis of the external carotid artery (ECA), presence of embolism in the ECA, or severe heart failure. In cases of true CCA occlusion, thrombus was aspirated using the balloon guide catheter and good recanalization was obtained. Seven of 8 patients displayed favorable recanalization, with good prognosis after 90 days in 5 patients. Conclusions Poor CCA visualization on cervical MRA does not necessarily represent true CCA occlusion. Aspiration of thrombus from a balloon guide catheter is effective for true CCA occlusion.

Aiming to define the optimal treatment of large and giant aneurysms (LGAs) in the anterior circulation, we present our surgical protocol and patient outcome. A series of 42 patients with intracavernous LGAs (n = 16), paraclinoid (C2) LGAs (n = 17), and peripheral (middle cerebral artery—MCA or anterior cerebral artery—ACA) LGAs (n = 9) were treated after bypass under motor evoked potential (MEP) monitoring. Preoperatively, three categories of ischemic tolerance during internal carotid artery (ICA) occlusion were defined on conventional angiography: optimal, suboptimal, and insufficient collaterals. Accordingly, three types of bypass: low flow (LFB), middle flow (MFB) and high flow (HFB) were applied for the cases with optimal, suboptimal, and insufficient collaterals, respectively. Outcome was evaluated by the Glasgow Outcome Scale (GOS). All patients had excellent GOS score except one, who suffered a major ischemic stroke immediately after surgery for a paraclinoid lesion. Forty-one patients were followed up for 87.1 ± 40.1 months (range 13–144 months). Intracavernous LGAs were all treated by proximal occlusion with bypass surgery. Of paraclinoid LGA patients, 15 patients had direct clipping under suction decompression and other 2 patients with recurrent aneurysms had ICA (C2) proximal clipping with HFB. MEP monitoring guided for temporary clipping time and clip repositioning, observing significant MEP changes for up to 6 min duration. Of 9 peripheral LGAs patients 7 MCA LGAs had reconstructive clipping (n = 4) or trapping (n = 3) with bypass including LFB in 3 cases, MFB in 1 and HFB in 1. Two ACA LGAs had clipping (n = 1) or trapping (n = 1) with A3-A3 bypass. The applied protocol provided excellent results in intracavernous, paraclinoid, and peripheral thrombosed LGAs of the anterior circulation.

Pharmacological challenges to oncogenic Ras-expressing cancer cells have shown a novel type of cell death, ferroptosis, which requires intracellular iron. In the present study, we assessed ferroptosis following treatment of human fibrosarcoma HT1080 cells with several inhibitors of lysosomal activity and found that they prevented cell death induced by the ferroptosis-inducing compounds erastin and RSL3. Fluorescent analyses with a reactive oxygen species (ROS) sensor revealed constitutive generation of ROS in lysosomes, and treatment with lysosome inhibitors decreased both lysosomal ROS and a ferroptotic cell-death-associated ROS burst. These inhibitors partially prevented intracellular iron provision by attenuating intracellular transport of transferrin or autophagic degradation of ferritin. Furthermore, analyses with a fluorescent sensor that detects oxidative changes in cell membranes revealed that formation of lipid ROS in perinuclear compartments probably represented an early event in ferroptosis. These results suggest that lysosomal activity is involved in lipid ROS-mediated ferroptotic cell death through regulation of cellular iron equilibria and ROS generation.

We experienced a case of sphenoid sinus type meningoencephalocele manifesting as severe cerebrospinal fluid (CSF) rhinorrhea. A 35-year-old man became aware of serous nasal discharge 1 year previously, which had gradually worsened. The nasal discharge was diagnosed as CSF rhinorrhea. Head computed tomography (CT) showed several small depressions in the bone of the left middle cranial fossa, and the largest depression extended through the bone to the lateral sphenoid sinus. Head magnetic resonance imaging revealed that the meningoencephalocele projected to the lateral sphenoid sinus, through this small bone defect of the middle cranial fossa. We performed a combined craniotomy and epidural approach without intradural procedures using neuronavigation. Multiple meningoencephaloceles protruded into small depressions in the middle skull base. The small protrusions not passing through the sphenoid sinus were coagulated. The largest protrusion causing the CSF leakage was identified by neuronavigation. This meningoencephalocele was cut. Both the dural and bone sides were closed with double layers to prevent CSF leakage. The CSF rhinorrhea completely stopped after the surgery. In our case, identification of the leak site was easy with neuronavigation based on bone window CT. The epidural approach also has significant advantages with double layer closure, including both the dural and bone sides. If the site of CSF leakage is outside the foramen rotundum (as with the most common type of lateral sphenoid sinus meningoencephalocele), we recommend the epidural approach using neuronavigation for surgical treatment.

Background: The gold standard of the diagnosis of primary central nervous system lymphoma (PCNSL) is the histopathological diagnosis by biopsy surgery. However, we experience some cases with a high risk of biopsy surgery or difficulty in general anesthesia. We perform radiation and chemotherapy without histopathological confirmation for such patients based on imaging findings, ophthalmological evaluation, and cerebrospinal fluid examinations. In this study, we investigated clinical diagnosis and outcomes for patients suspected PCNSL. Method: From April 2016 to December 2019, all adult brain tumor patients that were diagnosed with PCNSL without histopathological confirmation and underwent radiation and/or chemotherapy were included. The following criteria were retrospectively analyzed. 1) Intraorbital lymphoma, 2) SUVmax>12 in 18F FDG-PET, 3) ADCmean1 in late phase of 123I IMP SPECT, 5) CSF β2 microglobulin >2.1 mg/l, 6) CSF sIL2R >77 U/ml, 7) Improvement of imaging findings or clinical symptoms by steroid. Result: 9 suspected PCNSL patients were included. 8 patients were positive for 3 or more above criteria. All these patients achieved CR by initial treatment with radiation or chemotherapy which indicated appropriate diagnosis for PCNSL. The remaining 1 patient was SD by radiotherapy, which was an atypical clinical course of PCNSL. The above criteria were positive in 2 and negative in 3. There were no examinations that could be performed in all cases before the treatment. Conclusion: Some useful markers for the diagnosis of PCNSL have been reported. However, all have limited sensitivity and specificity. Each examinations are also restricted by patient, institution and time. The combination of the useful examinations will improve the diagnostic accuracy of PCNSL.

Over the decades, the problem of postoperative recurrence of chronic subdural hematoma (CSDH) has not been resolved. The objective of our study was to investigate whether the recurrence rate of CSDH is decreased when artificial cerebrospinal fluid (ACF) is used as irrigation solution for CSDH surgery. The present study was a multi-center, prospective, randomized, open parallel group comparison test of patients enrolled from 10 hospitals in Japan. Eligible patients with CSDH were randomly assigned to undergo burr hole drainage with either normal saline (NS) or ACF irrigation. The primary end-point was postoperative recurrence of ipsilateral CSDH. A total of 402 patients with newly diagnosed CSDH were enrolled during the study period. After applying inclusion and exclusion criteria, and taking into consideration cases lost to follow-up, our final study cohorts consisted of 177 ACF patients and 165 NS patients, representing 85.7% of the initial cohort. The overall recurrence rate was 11.4%, occurring in 39 of the 342 analyzed patients during 90 days of follow-up. Recurrence rates in the ACF and NS groups were 11.9% (21 of 177) and 10.9% (18 of 165), respectively. No significant difference was evident between groups (p = 0.87). In addition, no significant difference in time to recurrence was seen between groups (p = 0.74). No serious adverse effects related to irrigation fluid were seen in either group. Regarding the irrigation fluid for CSDH surgery, no differences in recurrence rate or time to recurrence were seen between the ACF and NS groups. However, ACF offers sufficient safety as irrigation fluid for CSDH.

Background Microvascular decompression for hemifacial spasm is performed at the root exit zone. More proximal segments of the facial nerve, defined as the root emerging zone (REmZ), may also be susceptible to neurovascular compression. Consequently, detailed knowledge of the microanatomy around facial nerve fibers at the pontomedullary junction is essential for consistent success of microvascular decompression. Methods Five human brainstems obtained from cadavers were investigated using correlative light microscopy and block-face imaging, which obtains arbitrary two-dimensional light microscopic and three-dimensional volume data from a single specimen. The entire facial nerve pathway, including the myelin transition, was evaluated inside and outside the brainstem. Results Correlative light microscopy and block-face imaging showed the intra-brainstem facial nerve fibers emerging at the brainstem surface deep at the pontomedullary sulcus (REmZ) and coursing along the pontine surface before detaching from the pons (root exit zone). An acute emerging angle significantly increased the surface area with central myelin. The facial nerve bundle formed 1 fasciculus in the portion covered by central myelin but divided into 2 fasciculi in the myelin transitional portion and then into multiple fasciculi more distally. Arteries around the REmZ were often anchored by perforating branches entangled with lower cranial nerves. Conclusions Facial nerve fibers are susceptible to vascular compression on emerging onto the deep brainstem surface at the pontomedullary sulcus. The key procedure in microvascular decompression is full dissection of the lower cranial nerves down to the brainstem origin to explore both the root exit zone and the REmZ.

Objective The supplementary motor area (SMA) is important for the prediction of post-operative symptoms after surgical resection of gliomas. We investigated the relationships between clinical factors and the resection range of SMA gliomas, and the post-operative neurological symptoms. Methods We retrospectively studied 18 consecutive surgeries for gliomas involving the SMA proper performed in 13 patients. Seven cases were recurrence of the tumour. Clinical factors and details of specific resection of the SMA proper (resection of posterior part, medial wall) and cingulate motor area (CMA) were examined. Results Eight cases suffered new post-operative neurological deficits. Six of these eight cases had transient deficits. Permanent deficits persisted in two cases with partial weakness or paresis, after rapid improvement of post-operative global weakness or hemiplegia, respectively. The risk of post-operative neurological deficits was not associated with the resection of the posterior part of the SMA proper or the CMA, but was associated with resection of the medial wall of the SMA proper. Surgery for recurrent tumour was associated with post-operative neurological deficits. The medial wall was frequently resected in recurrent cases. Discussion The frequency of post-operative neurological symptoms, including SMA syndrome, may be higher after resection of the medial wall of the SMA proper compared with the resection of only the lateral surface of the SMA proper.

Moyamoya disease usually manifests as ischemic events in childhood, and as more severe hemorrhagic events, including intraventricular hemorrhage, in adults. Recently, the indication for neuroendoscopic surgery has been extended to cast-formation intraventricular hematomas. However, detailed information about the use of neuroendoscopic surgery for the treatment of intraventricular hemorrhage associated with moyamoya disease has not been reported. We describe two cases of intraventricular hemorrhage with moyamoya disease; one in a 62-year-old and another in a 33-year-old women who both presented with severe neurological symptoms. Cerebral angiography revealed unilateral moyamoya disease. Neuroendoscopic surgery to remove the intraventricular hematoma was performed via bilateral frontal burr holes in both cases. Abnormal findings in the ventricle were observed only in the affected side and the intact side was normal. Specific findings of neuroendoscopic observation were dilated and tortuous vessels, intersection vessels, black-brown macules in the subependyma, and rattan blind-like (Japanese sudare) bleeding vessels. These characteristic neuroendoscopic findings may be useful for the exact diagnosis and treatment of intraventricular hemorrhage associated with moyamoya disease. Endoscopic evacuation of the ventricular hematoma may be important for intracranial pressure control in patients with intraventricular hemorrhage in adult moyamoya disease.

Intraoperative computed tomography (iCT) is a reliable method for the detection of residual tumour, but previous single-slice low-resolution computed tomography (CT) without coronal or sagittal reconstructions was not of adequate quality for clinical use. The present study evaluated the results of multi-slice iCT-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma.This retrospective study included 30 consecutive patients with newly diagnosed or recurrent pituitary macroadenoma with supradiaphragmatic extension who underwent endoscopic transsphenoidal surgery using iCT (eTSS+iCT group), and control 30 consecutive patients who underwent conventional endoscope-assisted transsphenoidal surgery (cTSS group). The tumour volume was calculated by multiplying the tumour area by the slice thickness. Visual acuity and visual field were estimated by the visual impairment score (VIS).The resection extent, (preoperative tumour volume - postoperative residual tumour volume)/preoperative tumour volume, was 98.9% (median) in the eTSS+iCT group and 91.7% in the cTSS group, and had significant difference between the groups (P = 0.04). Greater than 95 and90% removal rates were significantly higher in the eTSS+iCT group than in the cTSS group (P = 0.02 and P = 0.001, respectively). However, improvement in VIS showed no significant difference between the groups. The rate of complications also showed no significant difference.Multi-slice iCT-assisted endoscopic transsphenoidal surgery may improve the resection extent of pituitary macroadenoma. Multi-slice iCT may have advantages over intraoperative magnetic resonance imaging in less expensive, short acquisition time, and that special protection against magnetic fields is not needed.

Preoperative embolization for intracranial meningioma has been controversial for several decades. This study retrospectively reviewed our experience using n-butyl cyanoacrylate (n-BCA) to identify the factors for effective devascularization and procedure-related complications.Fifty-seven patients who underwent preoperative embolization with n-BCA were analyzed to collect the following data: age, sex, tumor size, location, pathology, and presence or absence of pial arterial supply. The predictive factors for total devascularization and complications were examined using univariate and multivariate analyses.Injected n-BCA penetrated into the tumor vessels in 51 cases (89%) but resulted in feeder occlusion in 6 (11%). Angiographic total devascularization was achieved in 29 cases (51%) and partial devascularization in 28 (49%). Small size, superficial location, and absence of pial supply were independent factors for total devascularization. No major complication was encountered, but asymptomatic or transient adverse events occurred in nine patients and were significantly associated with elderly patients and large tumors.Preoperative embolization for intracranial meningiomas using n-BCA can attain effective devascularization without major complications. The effect of preoperative embolization on surgical resection or patient outcome is still unknown.

Superficial siderosis is a rare condition caused by hemosiderin deposits in the central nervous system (CNS) due to prolonged or recurrent low-grade bleeding into the cerebrospinal fluid (CSF). CNS tumor could be one of the sources of bleeding, both pre- and postoperatively. We report an extremely rare case of superficial siderosis associated with purely third ventricle craniopharyngioma, and review previously reported cases of superficial siderosis associated with CNS tumor. A 69-year-old man presented with headache, unsteady gait, blurred vision, and progressive hearing loss. Brain magnetic resonance (MR) imaging with gadolinium revealed a well enhanced, intraventricular mass in the anterior part of the third ventricle. T2*-weighted gradient echo (GE) MR imaging revealed a hypointense rim around the brain particularly marked within the depth of the sulci. Superficial siderosis was diagnosed based on these findings. The tumor was diffusely hypointense on T2*-weighted GE imaging, indicating intratumoral hemorrhage. The lateral ventricles were dilated, suggesting hydrocephalus. [(18)F]fluorodeoxyglucose positron emission tomography revealed increased uptake in the tumor. The whole brain surface appeared dark ocher at surgery. Histological examination showed the hemorrhagic tumor was papillary craniopharyngioma. His hearing loss progressed after removal of the tumor. T2*-weighted GE MR imaging demonstrated not only superficial siderosis but also diffuse intratumoral hemorrhage in the tumor. Superficial siderosis and its related symptoms, including hearing loss, should be considered in patients with hemorrhagic tumor related to the CSF space. Purely third ventricle craniopharyngioma rarely has hemorrhagic character, which could cause superficial siderosis and progressive hearing loss.

The efficacy and limitations of transarterial acrylic glue embolization for the treatment of intracranial dural arteriovenous fistulas (DAVFs) were investigated. Thirty-four DAVFs treated by transarterial embolization using n-butyl cyanoacrylate were retrospectively reviewed. The locations of DAVFs were the transverse-sigmoid sinus in 11, tentorium in 10, cranial vault in 9, and superior sagittal sinus, jugular bulb, foramen magnum, and middle cranial fossa in 1 each. Borden classification was type I in 7, type II in 3, and type III in 24. Eight patients had undergone prior transvenous coil embolization. Complete obliteration rate was 56% immediately after embolization, 71% at follow-up angiography, and 85% after additional treatments (1 transvenous embolization and 4 direct surgery). Complications occurred in three patients, consisting of asymptomatic vessel perforations during cannulation in two patients and leakage of contrast medium resulting in medullary infarction in one patient. Transarterial glue embolization is highly effective for Borden type III DAVF with direct cortical venous drainage, but has limitations for Borden type I and II DAVFs in which the affected sinus is part of the normal venous circulation. Onyx is a new liquid embolic material and is becoming the treatment of choice for DAVF. The benefits of glue embolization compared to Onyx embolization are high thrombogenicity, and relatively low risks of cranial nerve palsies and of excessive migration into the draining veins of high flow fistula. Transarterial glue embolization continues to be useful for selected patients, and complete cure can be expected in most patients with fewer complications if combined with transvenous embolization or direct surgery.

Atypical teratoid/rhabdoid tumors (AT/RT) are rare malignant neoplasms that mainly affect infants and young children, and are typically located in the cerebellar hemispheres. These tumors are histologically characterized by varying proportions of rhabdoid cells, and nuclear INI1 immunonegativity. Here, we report a case of a 15-year-old male with primary diffuse leptomeningeal AT/RT. The patient had symptoms similar to those of meningitis. Magnetic resonance imaging revealed leptomeningeal thickening. Cytological examination using cerebrospinal fluid was repeatedly performed and revealed rhabdoid cells with loss of INI1 reactivity, and shortly after, the diagnosis of AT/RT was confirmed by tissue biopsy. Multiplex ligation-dependent probe amplification analysis revealed compound heterozygous microdeletion of the SMARCB1/INI1 locus. Leptomeningeal AT/RT without primary mass is extremely rare - only four cases have been previously reported to date. To the best of our knowledge, this is the first case report of primary leptomeningeal AT/RT with detailed genetic information.

OBJECTIVEThe first choice of treatment in cases of vertebral artery dissecting aneurysms (VADAs) is endovascular internal trapping (EIT) of the dissecting segment using coils. However, this procedure carries the risk of medullary infarction, and the risk factors for this complication are not well understood. This study investigated the risk factors causing medullary infarction.METHODSOne hundred patients who underwent EIT for VADAs were included in this study. Ninety-three patients presented with subarachnoid hemorrhage. In cases involving the posterior inferior cerebellar artery (PICA), partial internal trapping targeting the ruptured site was performed to preserve the PICA. The VADAs were classified into the distal VA stump group, proximal VA stump group, and entire VA stump group, according to the location of VA segments without adequate flow-out vessels (such as the PICA [VA stump]) at risk of delayed thrombosis. The occurrence of medullary infarction was examined in each group using diffusion-weighted MRI and/or clinical symptoms. Various measurements were performed on digital subtraction angiography, and the risk factors for medullary infarction were analyzed.RESULTSMedullary infarction occurred in 30 patients, affecting the posterolateral medulla in 27 patients and the anteromedial medulla in 3 patients. Medullary infarction occurred in 3 of 47 patients (6%) in the distal VA stump group, 10 of 19 patients (53%) in the proximal VA stump group, and 17 of 34 patients (50%) in the entire VA stump group. The length of trapping was significantly longer in the infarction group than in the noninfarction group but did not differ among the 3 groups. Total length (length of trapping plus VA stump) was a risk factor for medullary infarction in the proximal VA stumps.CONCLUSIONSThe primary risk factor for medullary infarction after EIT is not the length of trapping; rather, it is the anatomical location of the VADAs. The risk of medullary infarction is low in cases with distal VA stumps, but the symptoms are severe. Preservation of the origin of the anterior spinal artery can reduce the risk of medullary infarction. The risk of medullary infarction is high in cases with proximal VA stumps, but the symptoms are mild. A shorter length of trapping, although less likely to lead to complications, cannot prevent medullary infarction because the total length depends on the anatomical location of the PICA and not on the surgical technique. Reconstructive therapy should be indicated for patients with ruptured VADAs at high risk of severe ischemic complications (e.g., patients with hypoplasia of the contralateral VA or cases involving the PICA or anterior spinal artery, which are inappropriate for partial internal trapping) or for patients with unruptured VADAs.

Adult cerebellar high-grade gliomas (HGG) are rare and their molecular basis has not been fully elucidated. Although a diffuse midline glioma H3 K27M-mutant, a recently characterized variant of HGG, was reported to occasionally occur in the cerebellum, adult cases were rarely tested for this mutation; only five mutant cases have been reported to date. It currently remains unknown whether H3 K27M-mutant cerebellar gliomas share common histological features or have a uniformly dismal prognosis. In the present study, we assessed the prevalence of histone H3 K27M mutations in ten adult cerebellar HGG, identifying two H3F3A-mutant cases. One case was a 70-year-old female with a cystic lesion. Histologically, the tumor was considered to be glioblastoma; however, a part of the tumor exhibiting low proliferative activity appeared to be consistent with long-standing H3 K27M-mutant tumors in the literature. Another case was a 69-year-old male. The tumor showed a distinct circumscribed histology with minimal astrocytic differentiation, suggesting a nosological issue in the diagnosis of diffuse midline glioma. More cerebellar tumors need to be tested for H3 K27M mutations to clarify the clinical and histopathological spectra of this tumor.

We previously reported transplantation of brain microvascular endothelial cells (MVECs) into cerebral white matter infarction model improved the animal's behavioral outcome by increasing the number of oligodendrocyte precursor cells (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted survival and proliferation of OPCs in vitro. In this study, we investigated the mechanism how EVs derived from MVECs contribute to OPC survival and proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay revealed fibronectin was abundant on the surface of EVs from MVECs. As fibronectin has been reported to promote OPC survival and proliferation via integrin signaling pathway, we blocked the binding between fibronectin and integrins using RGD sequence mimics. Blocking the binding, however, did not attenuate the survival and proliferation promoting effect of EVs on OPCs. Flow cytometric and imaging analyses revealed fibronectin on EVs mediates their internalization into OPCs by its binding to heparan sulfate proteoglycan on OPCs. OPC survival and proliferation promoted by EVs were attenuated by blocking the internalization of EVs into OPCs. These lines of evidence suggest that fibronectin on EVs mediates their internalization into OPCs, and the cargo of EVs promotes survival and proliferation of OPCs, independent of integrin signaling pathway.

The optimal treatment for large or giant paraclinoid aneurysms is still controversial. The present study evaluated the results of endovascular coiling and microsurgical clipping with special reference to visual outcomes. The clinical data and treatment outcomes of 39 cases of large (>15 mm) paraclinoid aneurysms were retrospectively reviewed. Presenting symptoms were subarachnoid hemorrhage in 16 aneurysms and visual impairment in 18. Twenty-one aneurysms were treated by endovascular therapy and 18 were treated by direct surgery. Maximal aneurysm diameter ≥25 mm and preoperative visual acuity

A woman in her 40s. A biopsy of multiple intracranial lesions was performed, and the patient was diagnosed with DLBCL. As an initial treatment, 6 courses of high dose MTX therapy were performed and CR was achieved. Radiation therapy was not desired by the patient. On the 19th month after initial treatment, tumor recurrence was confirmed by MRI and added 2 courses of HD-MTX. On the 23rd month, second recurrence around the left basal ganglia were observed. One additional course of HD-MTX was performed, but due to the appearance of renal damage that was thought to be acute tubular necrosis, additional HD-MTX was not performed and whole brain irradiation was performed. She began complaining of pain in the trunk and extremities during radiation. When MRI and FDG-PET were performed in the 25th month, multiple lesions were found in the ganglia, plexus, and peripheral nerves from the cervical spinal cord to the sacral spinal cord. Cerebrospinal fluid cytology revealed atypical lymphocytes and lymphoma dissemination in the spinal cord. When intrathecal administration of the anticancer agent was performed nine times weekly, the CSF cytology was negative. Imaging findings showed that the lesions relapsed, although the lesions were temporarily reduced. After confirming that the renal function had recovered, two additional courses of HD-MTX were performed. Accumulation of FDG-PET in the lesion disappeared in the 29th month. However, peripheral neuropathic pain and paraplegia remained. Discussion: Neurolymphomatosis is considered to be a clinically rare disease that presents invasion of lymphoma into peripheral nerves including the cranial nerves, nerve roots or plexus. Diagnosis of NL has been required to be proved by nerve biopsy or autopsy, but noninvasive FDG-PET has been reported to be effective. In this case, CR was not obtained with anticancer drug intrathecal injection, and HD-MTX therapy was successful.

A 37-year-old woman presented with an extremely rare large oculomotor schwannoma associated with acute hydrocephalus manifesting as semicoma and anisocoria. Brain computed tomography and magnetic resonance imaging revealed a tumor in the oculomotor cistern. Cerebral angiography revealed separation of the posterior cerebral artery (PCA) and superior cerebellar artery (SCA). The tumor was removed subtotally by two stage surgery. Histological examination revealed ordinary schwannoma. The diagnosis of oculomotor nerve schwannoma was based on the intraoperative finding of the tumor origin in the oculomotor nerve. Oculomotor nerve schwannoma can cause acute hydrocephalus and manifest as impaired consciousness. The angiographical separation of the PCA and SCA was very useful for the preoperative diagnosis of oculomotor nerve schwannoma.

Recent prospective studies have shown that the rupture rate of small unruptured intracranial aneurysms is very low. However, awareness of harboring an aneurysm often provokes anxiety and depression, which may reduce the quality of life (QOL). This cross-sectional study enrolled 52 patients who had previously been notified of the presence of untreated unruptured aneurysms. A Markov model was constructed to simulate the natural history over time, and the age- and size-specific loss of quality-adjusted life year (QALY) caused by the aneurysms was calculated. Preference-based subjective QALY losses (PSG and PTTO) were assessed using the standard gamble (SG) and time trade-off (TTO) according to patient’s own perceptions. Calculated theoretical QALY losses were relatively small with median values of 0.4 years (interquartile range [IQR] 0.1–1.0 years) and 1.9 % (IQR 1.1–3.7 %) of expected lifetime. The median values of PSG and PTTO were 10.0 % (IQR 5.0–14.3 %) and 19.5 % (IQR 9.0–25.0 %), respectively. Although theoretical QALY losses were smaller in the patients with small aneurysms (

We have developed an imaging method designated as correlative light microscopy and block-face imaging (CoMBI), which contributes to improve the reliability of morphological analyses. This method can collect both the frozen sections and serial block-face images in a single specimen. The frozen section can be used for conventional light microscopic analysis to obtain 2-dimensional (2D) anatomical and molecular information, while serial block-face images can be used as 3-dimensional (3D) volume data for anatomical analysis. Thus, the sections maintain positional information in the specimen, and allows the correlation of 2D microscopic data and 3D volume data in a single specimen. The subjects can vary in size and type, and can cover most specimens encountered in biology. In addition, the required system for our method is characterized by cost-effectiveness. Here, we demonstrated the utility of CoMBI using specimens ranging in size from several millimeters to several centimeters, i.e., mouse embryos, human brainstem samples, and stag beetle larvae, and present successful correlation between the 2D light microscopic images and 3D volume data in a single specimen.

Background and Purpose— The frequency and pattern of symptomatic recurrence of spontaneous intracranial arterial dissection (IAD) are unknown. Methods— A follow-up study of 143 patients (85 men, 58 women; mean age, 50.7 [7–83] years) with spontaneous IADs at The University of Tokyo and affiliated hospitals from 1980 to 2000 was conducted. Tissue samples of IAD vessels obtained from 13 patients at various intervals from onset were also examined histologically. Results— With a mean follow-up of 8.2 years, symptomatic recurrence occurred in 47 patients (33%). Of 37 cases initially presenting with hemorrhage, 35 developed hemorrhagic recurrence with a mean interval of 4.8 days, and 2 developed nonhemorrhagic recurrences after 21 and 85 months, respectively. Of 10 patients initially presenting with nonhemorrhagic symptoms, 1 developed hemorrhagic recurrence 4 days later, and 9 developed nonhemorrhagic recurrences with a mean interval of 8.6 months. Histopathologically, the affected vessels in the acute stage of hemorrhage (days 0–6) demonstrated insufficient granulation formation within the pseudolumen, followed by marked intimal thickening around the pseudolumen and recanalizing vessel formation in the late stage (>day 30). In the late stage of brain ischemia, subintimal and subadventitial hemorrhage accompanied with intimal thickening was observed. Conclusions— These data indicate that IAD is a disease carrying a relatively high risk of symptomatic recurrence, apparently occurring in 3 phases and patterns: early hemorrhagic recurrence, late nonhemorrhagic recurrence, and chronic fusiform aneurysm transformation. Knowledge of this triphasic recurrence and corresponding histopathological characteristics help determine the treatment and follow-up strategy for IAD patients.

Chronic subdural hematoma (CSDH) is generally treated by twist drill, and one and two burr-hole craniostomy. We proposed new classification of the intraoperative condition of CSDH, and present a safer technique for aspiration of CSDH in one burr-hole surgery. The intraoperative condition of CSDH was classified according to the connections between the hematoma cavity and the extracranial space as follows. The "closed condition" represents only a single route consisting of a tube inserted intraoperatively connecting the extracranial space to the hematoma cavity. The "open condition" includes another route or space, which can freely pass air, saline, or old hematoma fluid, in addition to the tube inserted intraoperatively. Twist drill craniostomy and two burr-hole craniostomy clearly involve the intraoperative closed and open conditions, respectively. One burr-hole craniostomy may involve either condition due to the operative procedure. Aspiration and irrigation of the hematoma is basically free and safe in the open condition, but risky in the closed condition. All of the hematoma can be aspirated through one burr hole under certain open conditions with temporary replacement of the hematoma cavity with air followed by replacement of air with saline. Twenty-seven patients with symptomatic CSDH underwent one burr-hole craniostomy by the above mentioned aspiration technique. There were no special complications. The recurrence rate was average. The substitution of saline after complete aspiration of hematoma carries little risk only under the "open condition," shortens the operation time, and achieves good irrigation of the hematoma.

We have successfully developed a robust ReRAM true random number generator, using current difference, that does not require extra chip area. True random numbers are guaranteed by the current difference in the 1/fβ noise generated by Brownian motion, as tested using a fractional SDE model and verified using 1/fβ noise distribution. A highly reliable 40-nm ReRAM true random number generator circuit was designed and passed NIST SP800-22 randomness tests across all combinations of voltage (VDD ± 0.1 V) and temperature (−40 to 125 °C). The random number throughput achieves 32 Mbps with a low power consumption of 0.04 nJ/bit.

This paper presents a secure application—a physically unclonable function (PUF)—that uses the physical property of resistive random access memory (ReRAM). The proposed PUF-generating method and reproducing algorithm achieves highly reliable with bit error rate (BER) < 0.5% and reproduction exceeding 1010 times at −40 to 125°C after 10 years at 125°C and high uniqueness as evidenced by passing NIST tests. Evaluations on 40nm ReRAM test chips have demonstrated the feasibility of a scaled-down ReRAM cell enhanced with PUF.

Recent prospective multicenter studies have shown that the probability of rupture of unruptured aneurysms with maximal diameter7 mm is rather low. However, the overall risks and long-term impact of unruptured aneurysms on lifetime quality of life are still unknown.A mathematical model of the natural history of intracranial aneurysms was constructed, in which the hypothetical individuals with or without unruptured aneurysm transit between discrete health states. The annual rupture rate of small aneurysms was assumed to be 0.5% in the baseline analysis, followed by the subsequent sensitivity analysis. The analyses were continued until cumulative death rate from subarachnoid hemorrhage or other causes reached 1.0.Age-specific ratios of death of subarachnoid hemorrhage in the individuals harboring unruptured aneurysm, if dying at 60 years old, were 25% in men and 43% in women. These ratios decreased rapidly with higher age. Most (more than 90%) patients with small aneurysms were expected to die of diseases other than subarachnoid hemorrhage. In the baseline analysis (60-year-old individuals), lifetime lost to small aneurysms could be estimated as 3.8% for men and 4.2% for women, but a somewhat larger impact could be identified in the young and/or female individuals compared with in the elderly and/or male individuals.Lifetime effects of small unruptured aneurysms without risk factors increasing the probability of rupture are relatively small, and most patients were expected to die of diseases other than subarachnoid hemorrhage.

Background Optic neuritis (ON) is unilateral painful optic nerve inflammation in a young healthy female diagnosed by excluding glaucoma. ON onset during pregnancy is rare, with only 2 cases reported to date. Case Description A 35-year-old previously healthy parous woman who was pregnant with her second child suffered rapidly progressive visual acuity loss. Magnetic resonance imaging (MRI) revealed a pituitary tumor. Emergency surgery was performed for optic nerve compression; however, her visual impairment worsened. Postoperative diffusion-weighted MRI showed high intensity in the bilateral optic nerves, and ON was diagnosed. Administration of methylprednisolone was effective, and her visual acuity recovered over 6 months. Conclusions Associated pituitary macroadenoma complicated the true diagnosis of ON, because contrast medium cannot be used in pregnant women. The diffusion-weighted MRI findings were useful for diagnosing this complex clinical condition.

Venous thromboembolism (VTE) is a life-threatening complication in neurosurgical patients. This study retrospectively analyzed the effectiveness and safety of a screening strategy for the detection and prevention of VTE in patients undergoing elective brain tumor surgery.A total of 419 consecutive patients who underwent brain tumor surgery during 5 years were enrolled. At the midpoint of the study period, screening for VTE was introduced based on measurement of serum D-dimer level on the day after surgery and then once or twice every week. Anticoagulant therapy was started after the diagnosis of VTE. The two groups with (228 patients) and without (191 patients) screening were compared.Most of the demographic and clinical characteristics were relatively well balanced in the groups. VTE was diagnosed in 23 (5.5%) patients overall; the rate was higher in the screening group (7.0%) than in the non-screening group (3.7%). Although the rate of VTE-related adverse events was lower in the screening group (1.3% vs. 2.6%), the rate of hemorrhagic complications was higher (2.2% vs. 0.5%). Multivariate analysis indicated that malignant histology and preoperative paresis were independent risk factors for the diagnosis of VTE.Many VTE patients may not exhibit signs or symptoms, so screening using surrogate markers for VTE (D-dimer) may be useful in the early detection of asymptomatic VTE. However, most distal, deep venous thrombosis in isolation is not life-threatening, so the added efficacy of anticoagulant agents at this stage has to be weighed against the risks of hemorrhagic complications, especially in the early postoperative period.

Various degrees of peritumoral brain edema (PTBE) are observed in patients with intracranial meningiomas. Factors affecting the occurrence of PTBE in intracranial meningioma were investigated. PTBE was investigated retrospectively for 110 patients with primary intracranial meningiomas. Predictive factors related to PTBE were analyzed, for example patient age, sex, magnetic resonance imaging features (contrast enhancement, tumor shape, tumor location, tumor volume), angiographical features (tumor stain, pial-cortical arterial supply, venous obstruction), and histopathological features (histological subtypes, mindbomb homolog 1 labeling index (MIB1-LI)). Histological subtypes were classified into World Health Organization (WHO) grade I common type (meningothelial, transitional, fibrous), grade I uncommon type, and grade II and III types. The extent of PTBE was assessed by calculation of the edema index (EI). PTBE was present in 53 cases (48 %). Male sex, heterogeneous enhancement, superficial location, tumor volume (≥10 cm(3)), remarkable tumor stain, pial supply, venous obstruction, malignant pathology, and MIB1-LI ≥4 % were correlated with PTBE in univariate analysis. Pial supply and remarkable tumor stain were correlated with PTBE in multivariate analysis. WHO grade I uncommon type had obviously higher EI than WHO grade I common type, and WHO grade II and III types (P 0.001). Seven cases with prominently high EI (EI ≥10) were all WHO grade I uncommon type, including angiomatous, microcystic, secretory, and lymphoplasmacyte-rich meningioma. Prominently extensive PTBE might indicate the presence of WHO grade I uncommon type meningioma.

Background and Purpose— Management of asymptomatic unruptured intracranial aneurysms remains controversial, and recent prospective follow-up studies showed that the rupture rate of small aneurysms is very low. These results are inconsistent with the finding that the majority of ruptured aneurysms in patients with subarachnoid hemorrhage are small. Methods— A Markov model was constructed to simulate the natural history of intracranial aneurysms. All epidemiological and statistical data obtained from the Portal Site of Official Statistics of Japan (e-Stat) were adjusted to the standardized age distribution. From the selected data of aneurysm formation, the prevalence of unruptured aneurysms was estimated as 1.45% and the incidence of subarachnoid hemorrhage calculated to be 19.7/100 000/year in the whole standardized population. Results— The function for rupture rate constant with time was first analyzed. Selected values for annual rupture rates of 0.3%, 0.5%, 0.7%, and 1.0% showed inconsistencies in the relationship between the prevalence of unruptured aneurysm and the incidence of subarachnoid hemorrhage. Next, the function for a short period of high risk followed by a long period of low risk was considered. Annual rupture rates of 0.5%, 0.7%, and 1.0% indicated epidemiological compatibility with additional early rupture rates of 20%, 15%, and 10%, respectively. Conclusions— This study suggests that some aneurysms bleed shortly after formation and thus are rarely detected as unruptured aneurysms. Most aneurysms without early rupture remain stable for the remainder of life through some healing process, and prophylactic treatment for incidentally identified small unruptured aneurysms has no rationale.

Pilomyxoid astrocytoma (PMA) is a newly identified variant of pilocytic astrocytoma (PA). We report three cases of PMA with comparison to seven cases of PA in terms of their clinicopathological features. The three cases occurred at the ages of 2, 36 and 6 years, and their tumors were located in the left basal ganglia, the pineal gland, and the cerebellum, respectively. They were diagnosed PMA by surgical specimens that showed a characteristic monomorphous architecture with an angiocentric growth pattern and myxoid background. One patient developed localized relapse at 6 months after the surgery, but the other patients remained alive without tumor progression more than 5 years after treatment. In analysis of the immunohistochemical association in PMA and PA, no specific staining was found to be useful for differential diagnosis of PMA from PA. The expression of biomarkers including O-6-methylguanine-DNA methyltransferase, p53, MIB-1, and EGF receptor neither distinguished PMA from PA nor correlated with outcome. But almost all PMA and PA that demonstrated prominent positivity for nestin showed a high MIB-1 labelling index (LI), and four of these five patients suffered a relapse in the early phase. These results suggest that immunohistochemical expression of nestin and MIB-1 LI may correlate with the aggressiveness of the tumor in PA and PMA.