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Epithelioid glioblastoma (E‐GBM) is a rare aggressive variant of IDH‐wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E‐GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E‐GBM are recognized as primary/de novo lesions; however, several E‐GBM with co‐ or pre‐existing lower‐grade lesions have been reported. To better understand associations between E‐GBM and the lower‐grade lesions, we undertook a histological and molecular analysis of 14 E‐GBM, 10 of which exhibited lower‐grade glioma‐like components (8 E‐GBM with co‐existing diffuse glioma‐like components, 1 E‐GBM with a co‐existing PXA‐like component and 1 E‐GBM with a pre‐existing PXA). Molecular results demonstrated that the prevalence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions in E‐GBM were 13/14 (93%), 10/14 (71%) and 11/14 (79%), respectively, and concurrent BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions were observed in 7/14 (50%) of E‐GBM. These alterations were also frequently seen in the lower‐grade lesions irrespective of the histology. Genetic analysis including array comparative genomic hybridization performed for 5 E‐GBM with co‐ and pre‐existing lower‐grade components revealed that all molecular changes found in the lower‐grade components were also observed in the E‐GBM components, and additional changes were detected in the E‐GBM components. In conclusion, E‐GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions and these alterations tend to coexist in E‐GBM. Taken together with the facts that only one PXA preceded E‐GBM among these lower‐grade lesions, and that co‐occurrence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions have been reported to be rare in conventional lower‐grade diffuse gliomas, the diffuse glioma‐like components may be distinct infiltrative components of E‐GBM, reflecting intratumoral heterogeneity.

Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor.Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing.The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age65 years alone significantly predicted overall survival relative to MyD88 wild type and age65. The MyD88 L265P mutation was predominantly present in patients aged65 years. Among age65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P0.04).The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailor-made treatment strategy might be needed for these patients.

Object Methylation of O6-methylguanine-DNA methyltransferase (MGMT) has been reported to be a good prognostic factor for patients with glioblastoma multiforme (GBM). To determine whether the absolute value of MGMT messenger RNA (mRNA) might be a prognostic factor and useful for predicting the therapeutic effectiveness of temozolomide, especially with regard to GBMs, the authors measured the absolute value of MGMT mRNA in gliomas by using real-time reverse-transcription polymerase chain reaction (RT-PCR). Methods MGMT mRNA was measured in 140 newly diagnosed gliomas by real-time RT-PCR using the Taq-Man probe. Among 73 GBMs, 45 had been initially treated with temozolomide and radiation. Results The mean MGMT mRNA value was significantly lower in oligodendroglial tumors than in other tumors. In the 73 GBMs, a significant prognostic factor for progression-free survival was fewer than 1000 copies/ μgRNA of MGMT mRNA (p = 0.0150). Of 45 patients with GBMs that had been treated with temozolomide and radiation, progression-free survival was significantly longer for those whose GMB had fewer than 1000 copies/μgRNA of MGMT mRNA than for those whose GBM had more than 1000 copies/μgRNA (p = 0.0090). In 32 patients with GBMs treated by temozolomide and radiation whose age was younger than 75 years and whose Karnofsky Performance Scale score was more than 70, progression-free and overall survival times were longer for those with GBMs of fewer than 5000 copies/μgRNA of MGMT mRNA than for those with GBMs of more than 5000 copies/μgRNA (p = 0.0365 and p = 0.0312). Conclusions MGMT mRNA might be useful as a prognostic factor and for predicting the results of therapy for GBMs treated by temozolomide. New individual adjuvant therapy based on the results of MGMT mRNA quantitation has been proposed.

While photodynamic therapy (PDT) is an effective treatment for glioma, induction of apoptotic cell death of glioma cells is important for ensuring efficacy and safety of PDT treatment in glioma patients, as necrotic cell death can induce late appearance of obstacles in treatment. Here, we investigated the relationship between type of cell death and PDT treatment conditions involved in laser and photosensitizer dosage in human glioblastoma T98G cells. Photosensitizer talaporfin sodium-mediated PDT (NPe6-PDT) treatment induced laser and NPe6 dose-dependent cell death in T98G cells, whereas almost all cells pretreated with NPe6 at ≥ 30 µg/mL were killed by laser irradiation, regardless of laser dose. Morphological analysis showed that combination of high doses of NPe6 and laser irradiation changes the dominant cell death process from apoptosis to necrosis. Biochemical analysis (detection of caspase-3 activity and staining of cell surface-exposed phosphatidylserine) also showed that increasing laser dose changes the type of cell death from apoptotic to necrotic cell death after high-dose treatment with NPe6. Lactate dehydrogenase leakage assay demonstrated that a laser dose of 5 J/cm(2) induced less leakage than 30 J/cm(2). Our results suggested that type of glioma cell death in NPe6-PDT changed with fluctuations in laser and NPe6 dose, and that combination of 30 µg/mL NPe6 with 5 J/cm(2) laser is the best treatment condition for inducing an increase in apoptotic cells while keeping rate of necrotic cell death low in this in vitro study.

BACKGROUND In WHO grade II diffuse gliomas (low-grade gliomas, hereafter called LGGs), chemotherapy and radiotherapy contribute to prolonged survival but could induce somatic mutations. The optimal timing of treatment in LGGs remain poorly understood. To delineate this, we designed a mathematical model for tumor growth and investigate the association among the treatment, malignant transformation (MT), and the accumulation of somatic mutations revealed by whole exome sequencing (WES) in LGGs. METHODS Totally, 290 patients with LGGs between 1990 and 2018 were analyzed. We assessed the statuses of IDH mutation and 1p19q co-deletion in all tumors. Among all, 114 patients (39%) underwent MT during follow-up periods (mean: 82.6 months). Tumor volume was evaluated with FLAIR and/or T2-weighted MRI. MT was evaluated with contrast-enhanced MRI and/or pathological diagnosis. To investigate the number of somatic mutations in a cohort of LGGs and their patient matched recurrence, WES was performed on 88 serial samples collected at least two time-points from 39 patients. RESULTS Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (OD) showed longer transformation-free survival compared to other subtypes. An exponential model was chosen to estimate growth rate in LGGs, since the exponential model provided a better fit to our data as compared to a linear model. The growth rate significantly decreased in the middle of chemotherapy and after radiotherapy. By contrast, these treatments increased the number of somatic mutations identified by WES and the rate of MT in each subtype. The increasing number of mutations in recurrent tumors showed strong correlation with the rise in MT rate. Based on the growth rate and the risk of MT, optimal timing of treatments could be calculated for each genetic subtype. CONCLUSIONS The mathematical model and WES analysis delineates the optimal timing of treatments in each subtype, which will help to decide the treatment for LGGs.

The purpose of the study was to investigate the pathological and clinical significance of the expression of nestin, a type-VI intermediate filament transiently expressed during brain development, in glioma tissue. This study was conducted in 70 patients with newly diagnosed adult supratentorial gliomas who underwent multimodality treatment in our department, including surgery. The pathological diagnosis was grade II in 6 patients, grade III in 21 patients, and grade IV in 43 patients. Two specimen sections, one from the bulk of the removed tumor and one from the border between the tumor and normal brain tissue, were subjected to immunostaining with a mouse anti-human nestin monoclonal antibody. Analyses were performed to investigate possible correlation with pathological features, the relationship between nestin expression and the continuity of tumor with the subventricular zone (SVZ), correlation with the therapeutic prognosis, etc. Nestin was expressed specifically in astrocytoma lineage cells. In oligodendroglial tumors, nestin was expressed only in less-differentiated cells and cells suggestive of the presence of astrocytoma. In astrocytic tumors, the rate and level of nestin expression increased as the degree of malignancy increased. There was no significant correlation between the expression level of nestin and the continuity of tumor with the SVZ in the contrast-enhanced imaging before surgery. In addition, no correlation with the therapeutic prognosis was observed. Nestin, a neural stem cell marker, was specifically expressed in astrocytoma lineage cells in glioma tissue. A positive correlation was observed between the degree of malignancy and the level of nestin expression. However, the level of nestin expression was not related to the tumor localization in the SVZ and was not correlated with the therapeutic prognosis.

Object The objective of the present study was to perform a prospective evaluation of the potential efficacy and safety of intraoperative photodynamic therapy (PDT) using talaporfin sodium and irradiation using a 664-nm semiconductor laser in patients with primary malignant parenchymal brain tumors. Methods In 27 patients with suspected newly diagnosed or recurrent primary malignant parenchymal brain tumors, a single intravenous injection of talaporfin sodium (40 mg/m2) was administered 1 day before resection of the neoplasm. The next day after completion of the tumor removal, the residual lesion and/or resection cavity were irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm2 and a radiation energy density of 27 J/cm2. The procedure was performed 22–27 hours after drug administration. The study cohort included 22 patients with a histopathologically confirmed diagnosis of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%) were newly diagnosed glioblastomas multiforme (GBM). Results Among all 22 patients included in the study cohort, the 12-month overall survival (OS), 6-month progression-free survival (PFS), and 6-month local PFS rates after surgery and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which could be attributable to the administration of talaporfin sodium, were noted in 7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1 case). Skin photosensitivity test results were relatively mild and fully disappeared within 15 days after administration of photosensitizer in all patients. Conclusions Intraoperative PDT using talaporfin sodium and a semiconductor laser may be considered as a potentially effective and sufficiently safe option for adjuvant management of primary malignant parenchymal brain tumors. The inclusion of intraoperative PDT in a combined treatment strategy may have a positive impact on OS and local tumor control, particularly in patients with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026 (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862).

Surgery was performed in a 65-year-old male patient with malignant gliomas at two locations in the left and right cerebral hemispheres that showed no apparent continuity in imaging studies. Slight differences in histopathological appearance were seen between the tumors, and multicentric malignant glioma was diagnosed. Detailed genetic examination showed both the left- and right-side tumors to be of the IDH-1 wild type with a p53 mutation at the same locus. Whole genome analysis by comparative genomic hybridization revealed many of the same mutations to be present in both tumors. The O(6)-methylguanine-methyltransferase promoter in both cases was unmethylated, and the genetic profiles of both showed them to be homologous tumors. They were therefore inferred to be multiple gliomas from the same clone. There have been occasional reports of multicentric gliomas classified by diagnostic imaging. This report discusses the need to examine tumor origin by genomic profiling.

Summary Objective To investigate the kinetics of cell death in human glioma cell lines induced by photodynamic therapy (PDT) with the second-generation photosensitizer talaporfin sodium (TS) and a 664-nm diode laser. Materials and methods Three human glioma cell lines (T98G, A172, U251) were studied. After incubation of the cell lines with various concentrations of TS for 4 h, PDT using diode laser irradiation at 33 mW/cm 2 and 10 J/cm 2 was performed. Cell viability and changes in cell morphology were examined by the Cell Counting Kit-8 assay and phase-contrast microscopy, respectively. In addition, to evaluate the pathology of cell death, changes in cell viability after treatment with a caspase activation inhibitor and an autophagy inhibitor were also examined. Results In all 3 human glioma cell lines, TS induced dose-dependent cell death. However, the 50% lethal dose of TS varied among these cell lines. The main morphological feature of cell death was shrinkage of the cell body, and the number of cells with this morphological change increased in a time-dependent manner, resulting in cell death. In addition, a dose-dependent improvement in cell viability by the caspase inhibitor Z-VAD-fmk was observed. Conclusion PDT with TS induces dose-dependent apoptosis in human glioma cell lines. However, the sensitivity to PDT varied among the cell lines, indicating a possible difference in the intracellular content of TS, or a difference in the susceptibility to the intracellular oxidative stress caused by PDT.

Photodynamic therapy (PDT) induces selective cell death of neoplastic tissue and connecting vasculature by combining photosensitizers with light. Here we clarified the types of cell death induced by PDT in combination with the photosensitizer talaporfin sodium (mono-L-aspartyl chlorine e6, NPe6) in order to evaluate the potential of this therapy as a treatment for glioma. PDT with NPe6 (NPe6-PDT) induces dose-dependent cell death in human glioblastoma T98G cells. Specifically, cell death modalities were observed in NPe6-PDT treated T98G cells, including signs of apoptosis (activation of caspase-3, expression of phosphatidylserine, and DNA fragmentation) and necrosis (stainability of propidium iodide). In addition, high doses of NPe6-PDT decreased the proportion of apoptotic cell death, while increasing necrosis. Closer examination of apoptotic characteristics revealed release of cytochrome-c from mitochondria as well as activation of both caspse-9 and caspase-3 in cells treated with low doses of NPe6-PDT. Benziloxycarbonyl-Leu-Gln(OMe)-His-Asp(OMe)-fluoromethyl-ketone (Z-LEHD-fmk), a caspase-9 specific inhibitor, and benziloxycarbonyl-Asp(OMe)-Gln-Met-Asp(OMe)-fluoromethyl-ketone (Z-DQMD-fmk), a caspase-3 specific inhibitor, showed dose-dependent prevention of cell death in NPe6-PDT treated cells, indicating that mitochondrial apoptotic pathway was a factor in the observed cell death. Further, the cell morphology was observed after PDT. Time- and NPe6-dose dependent necrotic features were increased in NPe6-PDT treated cells. These results suggest that NPe6-PDT could be an effective treatment for glioma if used in mild doses to avoid the increased necrosis that may induce undesirable obstacles.

Aim Assessment of plaque characteristics is important for the optimal treatment of carotid stenosis, particularly in elderly patients. Macrophage infiltration is reported to be involved in carotid plaque instability. However, immunohistochemical assessment of the detailed localization of macrophage infiltration in carotid plaques remains limited. We attempted to elucidate this using 3-D ultrasonography (3D-US). We compared findings of the detailed localization of macrophage infiltration with findings from the newly developed tomographic ultrasound imaging (TUI). Methods We obtained specimens of carotid arteries from 18 patients undergoing carotid endarterectomy (CEA), and investigated the localization of macrophages and vascular smooth muscle cells. Their localization obtained from 11 patients was compared with their preoperative TUI findings. Results We classified the localization of macrophage infiltration into four types: (i) focal infiltration in the thick fibrous cap (12 cases); (ii) subendothelial zonal infiltration (2 cases); (iii) peripheral infiltration around the lipid core (8 cases); and (iv) local infiltration near the shoulder of the fibrous cap (2 cases). Among them, preoperative TUI was available in 11 CEA cases for histological comparison. We identified two sites of focal macrophage infiltration that corresponded to local echogenic lesions without an acoustic shadow on TUI. The proliferation of smooth muscle cells failed to show an apparent echogenicity. Conclusions TUI could not only evaluate the morphological features, but also showed the two types of focal macrophage infiltration relevant to plaque instability as an echogenic focus. TUI carried out by 3D-US is an easily applicable and non-invasive method that is considered useful for evaluating carotid plaques in elderly patients. Geriatr Gerontol Int 2013; 13: 834–841.

Sarcoidosis is a systemic granulomatous disease with unknown cause, which very rarely occurs exclusively in the central nervous system. The authors performed biopsy sampling of a mass that developed in the left tentorium cerebelli that appeared to be a malignant tumor. The mass was diagnosed as a sarcoid granuloma, which was confirmed with the onset of antibody reaction product against Propionibacterium acnes. Findings suggesting sarcoidosis to be an immune response to P. acnes infection have recently been reported, and they give insight for diagnosis and treatment of this disease. The authors report the possible first case that was confirmed with P. acnes infection in a meningeal lesion in solitary neurosarcoidosis.

Background A neuroendocrine tumor (NET) can develop anywhere in the body, but is mainly found in the pancreas, gastrointestinal tract, and lungs. This report is a retrospective study of the clinicopathological features of NET patients with brain metastasis whose tissue diagnosis was made at our hospital. Methods Patients with brain metastasis evidenced by clinical records and images were accumulated among 302 patients in whom tissue diagnosis of NETs was made at our hospital between 2008 and 2013. In the patients, the primary lesion, pathological classification, pattern of metastasis, details of treatment, and outcomes were analyzed. Results Brain metastasis was observed in 31 patients (10.3 %). The primary lesion was in the lungs in 26 patients (83.9 %), and the mammary glands, esophagus, and uterus in 1 patient each. Primary lesions were unknown in 2 patients, including 1 patient in whom NETs were detected in the lymph nodes alone. Pathological classification of the primary lesion was NET Grade 2 (Ki-67: 3 to 20 %) in 3 patients and neuroendocrine carcinoma (NEC, Ki-67: ≥21 %) in 26 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months, and the brain lesion preceded brain metastasis in 6 patients. Ten patients had a single metastasis whereas 21 patients had multiple metastases, but no characteristics were observed in their images. Brain metastasis was extirpated in 10 patients. Stereotactic radiotherapy alone was administered in 6 patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months, and the major cause of death was aggravation of the primary lesion or metastatic lesions in other organs. Conclusion Most of NET patients with brain metastasis showed the primary lesion of NEC in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of NETs should be immediately established based on further analyses of NET patients with brain metastasis.

A brainstem glioma is often the initially suspected diagnosis hen a diffuse abnormal signal is found localized in the brainstem n magnetic resonance imaging (MRI). An appropriate differential iagnosis is needed based on clinical presentation, neuroimagng results and pathological finding by surgical biopsy, in order o make a rapid and accurate diagnosis of this pathological conition, which can have a fatal clinical course. Two patients were nitially given a diagnosis of brainstem glioma, but subsequently iven a diagnosis of posterior reversible encephalopathy synrome (PRES) due to their distinctive clinical presentation and euroimaging results and could be avoided dangerous surgical iopsy. Case 1. The patient was a 54-year-old woman with no hisory of hypertension. She began to experience insomnia a month efore admission due to work stress. She went to a local clinic or a physical examination and a head MRI scan due to the suden onset of dysarthria and right mild hemiparesis. In addition to acunar infarction of the left corona radiata, she was highly susected a diagnosis of brainstem glioma, because the differential iagnosis of the physician was limited. Her blood pressure was

14-3-3 proteins are now recognized to have a wide range of potential functions and pathological relevance, such as regulating the intercellular signal processes of differentiation, the development and growth of cells, or preventing or mediating cell apoptosis and survival by controlling the localization of potential signaling molecules. We investigated the immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human cerebral and carotid arteries using 14-3-3 isoform-specific antibodies to distinguish 7 isoforms, and confirmed the cell type localization using double immunofluorolabeling. 14-3-3 common (COM)-like immunoreactivity (IR) was intense, mainly in the foam cells and multinucleated giant cells of the carotid artery. The beta, gamma, epsilon, tau, eta, and zeta (6/7) isoform-specific antibodies showed similar results to those with anti-14-3-3 COM antibody. However, among these isoform-specific antibodies, the anti-eta isoform antibody most intensely immunolabeled multinucleated giant cells and foam cells, and the anti-zeta isoform antibody most intensely immunolabeled infiltrating vascular smooth muscle cells (VSMCs), in carotid plaques. Zeta IR was also observed in one part of the mural thrombus and in the nuclei of foam cells. Gamma isoform-like IR was relatively limited in cell components, but extracellular lesions were partly positive for this isoform. In the main cerebral arteries, the anti-epsilon isoform antibody most intensely immunolabeled infiltrating VSMCs in the intima of thickened fibrous cap plaques. Endothelial cells were also positive for the epsilon isoform. These findings may provide a basis for understanding the isoform-specific role associated with atherosclerotic lesions of the cerebral and carotid arteries.

Background: Oculomotor ophthalmoplegic migraine (O-OPM) occurs in many children, and in some cases MRI shows a small mass in the root exit zone (REZ) of the oculomotor nerve. This mass is considered to result from nerve hypertrophy caused by repeated demyelination. Case results: A 51-year-old man has been on oral medication for O-OPM, which he had from 6 years of age. However, the frequency and intensity of his migraine attacks have gradually increased. Brain magnetic resonance imaging (MRI) revealed a small nodular mass in the REZ of the oculomotor nerve. The mass was initially diagnosed as oculomotor schwannoma and tumor resection was attempted. However, as the mass was tightly adhered to the oculomotor nerve and hemorrhagic, biopsy was performed. The pathological diagnosis was neuromuscular hamartoma. Conclusion: The small nodular mass in the REZ of the oculomotor nerve may be a hamartoma associated with congenital factors and may possibly be the primary pathology of O-OPM in this case.

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.

Summary Object The usefulness of photodynamic therapy (PDT) as a local therapy for malignant glioma was evaluated by investigating histological changes in a rat C6 glioma model treated with a combination of talaporfin sodium, a water-soluble photosensitizer derived from chlorophyll and exposure to a diode laser. Methods Glioma cells (C6) at the confluence stage were transplanted stereotactically into the right frontal lobe of SD rats. Five days later, the rats underwent right frontal craniotomy and intravenous administration of talaporfin sodium. One hour after talaporfin sodium administration, each rat was irradiated by a 664 nm diode laser beam. The brain was removed 1, 3 or 6 h after laser irradiation for histological examination of tumor-affected brain tissue and surrounding normal brain tissue. Results In addition to the tumor mass, tumor cells invading surrounding edematous brain tissue were seen in untreated rats, ranging from the brain surface to a depth of 2 mm. One hour after PDT, coagulation necrosis as well as disappearance of indication of cell viability such as disappearance of tumor cell processes and foamy changes of cytoplasm were noted in the tumor tissue at a depth of 0.5 mm, accompanied by reduction of cytoplasmic glial fibrillary acidic protein (GFAP) expression and appearance of granular M30 cytodeath positivity. Three hours later, the cytoplasm of the residual tumor cells showed disappearance of GFAP expression and increased expression of M30 cytodeath. Six hours later, the foamy cytoplasm of swollen tumor cells demonstrated strong positivity for M30 cytodeath. Conclusion PDT using talaporfin sodium induced coagulation necrosis and apoptosis in rats with C6 glioma.

A 48-year-old woman with a history of viral influenza infection was admitted with rapidly progressive numbness and weakness of the right extremities. On admission, general physical examination revealed no abnormality. Cerebrospinal fluid analysis showed no abnormal findings. Brain computed tomography and magnetic resonance imaging showed an open ring-like enhanced lesion in the white matter of the right parietal lobe with massive perifocal edema. Cerebral angiography showed no tumor staining and thallium-201 single photon emission computed tomography showed no abnormal uptake. The preoperative diagnosis was malignant glioma and partial resection was performed. Histological examination showed perivascular accumulation of small lymphocytes and a large number of macrophages with reactive astrocytes. Phagocytosis of myelin was observed in the macrophages and nuclear fragmentation in the reactive astrocytes. The histological diagnosis was acute inflammatory demyelinating disease. After therapy with methylprednisolone, her neurological symptoms improved gradually and no relapse occurred during 18 months of follow up. Tumor-like masses of demyelination may occupy an intermediate position between acute multiple sclerosis and postinfectious encephalitis. Open ring sign may be a pathognomonic feature of these lesions.

Distinction of gliomatosis cerebri (GC), a rare entity characterized by a widespread infiltration of the brain by tumor, from diffuse glioma is a difficult clinical problem. Most previously reported cases of GC have been autopsy cases because of the lack of objective and quantitative clinical diagnostic criteria. In order to better define this entity, we report the neuroradiological and pathological findings of three cases of GC. Three patients (one man and two women, aged 46–71 years) presented with symptoms of mild increased intracranial pressure, cognitive impairment, or seizure. Magnetic resonance imaging (MRI) was done with T1-weighted images after gadolinium injection, and with T2 -weighted images and fluid attenuated inversion recovery (FLAIR) in all cases. Histological confirmation of glial proliferation was obtained in all cases by craniotomy. The topography of the tumoral infiltration was characteristic, involving mainly the white matter, basal ganglia, thalamus, and commissural fibers. More than two cerebral lobes were affected. Contrast enhancement was absent, and mass effects were minimal compared with the extent of tumoral infiltration, but one patient presented with a small frontal enhanced mass during the clinical course. The pathological analyses demonstrated infiltration of the brains by variably differentiated neoplastic glial cells with destruction of the myelin sheath, but the involved axis cylinder and neuronal cells were preserved. Diagnosis of GC should be faithful to the pathological diagnosis criteria of Scheinker and Evans, and therefore the precise assessment of MRI findings according to these criteria is required for clinical, antemortem diagnosis of GC.

We investigated long-term outcome of 6 patients with a large or giant aneurysm of the vertebral artery. Patients were 4 men and 2 women, aged from 26 to 74 (mean 56) years old. Only 1 patient presented with subarachnoid hemorrhage, whereas 3 patients presented with signs of brain stem compression and 2 patients with headache. Aneurysms were 18 to 40 (mean 26) mm in maximum diameter and 5 of them were thrombosed in various degrees. Three patients underwent direct surgery (neck clipping+aneurysmectomy, trapping, coating) and 3 patients were treated conservatively at initial presentation. The latter 3 patients developed deterioration of neurological symptoms and enlargement of the aneurysm within the following 4 to 6 years, and thus 2 patients underwent surgery (neck clipping+aneurysmectomy, endovascular parent artery occlusion). One month after endovascular surgery, however, 1 of the patients died of rupture of aneurysm. Long-term outcome in GOS was as follows: GR (2), SD (1), and D (3). Two patients with GR underwent direct surgery via transcodylar approach at initial presentation for aneurysms less than 30 mm in size. Although difficult in many cases, neck clipping or trapping with aneurysmectomy via the cranial base approach, before enlarging to “untreatable” size, is the best therapeutic strategy for these aneurysms. On the contrary, long-term outcome of patients with conservative treatment was poor.

Background: Olfactory hallucination, a symptom of medial temporal lobe epilepsy, is rarely associated with unruptured intracranial aneurysms. Case Description: We encountered this situation in a 70-year-old woman with an unruptured aneurysm at the bifurcation of the internal carotid and posterior communicating artery. We were able to achieve epileptic control by craniotomy clipping and medial temporal lesionectomy. Conclusion: According to our knowledge, previous reports are limited to cases of large middle cerebral artery aneurysms compressing the lateral orbitofrontal cortex, and this is apparently the first report of a case where olfactory hallucinations occurred from direct stimulation of the entorhinal cortex by an internal carotid and posterior communicating artery bifurcation aneurysm. We examined the pathophysiology underlying the development of olfactory hallucinations. We found craniotomy clipping and focal resection to be useful from the standpoint of seizure control. Whether seizure control can also be obtained with intracranial aneurysm coiling should be investigated in the future.

Motor-evoked potential (MEP) monitoring was performed during 196 consecutive spinal (79 cervical and 117 lumbar) surgeries for the decompression of compressive spinal and spinal nerve diseases. MEP monitoring in spinal surgery has been considered sensitive to predict postoperative neurological recovery. In this series, transcranial stimulation consisted of trains of five pulses at a constant voltage (200-600 V). For the normalization of MEP, we recorded compound muscle action potentials (CMAP) after peripheral nerve stimulation, usually on the median nerve at the wrist 2 seconds before or after each transcranial stimulation of the motor area, for all operations. The sensitivity and specificity of MEP monitoring was 100% and 97.4%, respectively, or 96.9% with or without CMAP compensation (if the threshold of postoperative motor palsy was defined as 20% relative amplitude rate [RAR]). The mean RAR after CMAP normalization, of the most affected muscle in the patient group with excellent postoperative results (recovery rate of a Japan Orthopedic Association score of more than 50%) was significantly higher than that in the other groups (p=0.0224). All patients with an amplitude increase rate (AIR) with CMAP normalization of more than 20% achieved neurological recovery postoperatively. Our results suggest that if the RAR is more than 20%, postoperative motor palsy can be avoided in spinal surgery. If the AIR with normalization by CMAP after peripheral nerve stimulation is more than 20%, neurological recovery can be expected in spinal surgery.

Summary Background Photodynamic therapy (PDT) induces selective cell death of neoplastic tissue and connecting vasculature by combining photosensitizers with light. We have previously reported that PDT induces apoptotic cell death in glioma cells when the photosensitizer talaporfin sodium (NPe6) is used. Here, we investigated the combined effect of NPe6-PDT with temozolomide, a DNA-alkylating drug used in glioma therapy. Methods Human glioblastoma T98G cells and human glioma U251 cells were used as glioma cells. Cell viability was evaluated by WST-8 assay. Apoptosis was evaluated by measurement of caspase-3 activity and DNA-fragmentation. Intracellular reactive oxygen species were evaluated by dihydrorhodamine assay. Results While the degree of NPe6-PDT induced cell death unchanged in T98G and U251 cells when temozolomide treatment was adjuvant, it was dose-dependently increased by concomitant treatment with temozolomide. Further, concomitantly administered temozolomide dose-dependently increased caspase-3 activity and DNA-fragmentation, while adjuvant-temozolomide did not. These results are suggesting that concomitantly administered temozolomide potentiates the effect of NPe6-PDT to facilitate apoptotic cell death. Additionally, concomitantly administered temozolomide increased intracellular NPe6-fluorescence and reactive oxygen species, suggesting that the augmentation effect of combined treatment may be due to increased intracellular accumulation of NPe6. Conclusion These results suggest that concomitant treatment with NPe6-PDT and temozolomide is a potentially useful therapy for glioma.

A 72-year-old female presented with an intra-fourth ventricular meningioma manifesting as truncal ataxia. Computed tomography (CT) showed a slightly high-density, well-demarcated, and homogeneously enhanced mass located in the fourth ventricle and extending to the right lateral recess. T2-weighted magnetic resonance (MR) imaging revealed a peritumoral high-intensity band without dural tail sign. Bilateral vertebral angiography revealed faint tumor staining supplied from the choroidal branches of the posterior inferior cerebellar arteries. The mass was totally resected via a suboccipital approach. CT, T2-weighted MR imaging, and vertebral angiography are informative for the preoperative diagnosis of fourth ventricular meningioma.

The objective of the present study was to perform a prospective evaluation of the potential efficacy and safety of intraoperative photodynamic therapy (PDT) using talaporfin sodium and irradiation using a 664-nm semiconductor laser in patients with primary malignant parenchymal brain tumors.In 27 patients with suspected newly diagnosed or recurrent primary malignant parenchymal brain tumors, a single intravenous injection of talaporfin sodium (40 mg/m(2)) was administered 1 day before resection of the neoplasm. The next day after completion of the tumor removal, the residual lesion and/or resection cavity were irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm(2) and a radiation energy density of 27 J/cm(2). The procedure was performed 22-27 hours after drug administration. The study cohort included 22 patients with a histopathologically confirmed diagnosis of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%) were newly diagnosed glioblastomas multiforme (GBM).Among all 22 patients included in the study cohort, the 12-month overall survival (OS), 6-month progression-free survival (PFS), and 6-month local PFS rates after surgery and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which could be attributable to the administration of talaporfin sodium, were noted in 7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1 case). Skin photosensitivity test results were relatively mild and fully disappeared within 15 days after administration of photosensitizer in all patients.Intraoperative PDT using talaporfin sodium and a semiconductor laser may be considered as a potentially effective and sufficiently safe option for adjuvant management of primary malignant parenchymal brain tumors. The inclusion of intraoperative PDT in a combined treatment strategy may have a positive impact on OS and local tumor control, particularly in patients with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026 (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862).

Assessment of plaque characteristics is important for the optimal treatment of carotid stenosis, particularly in elderly patients. Macrophage infiltration is reported to be involved in carotid plaque instability. However, immunohistochemical assessment of the detailed localization of macrophage infiltration in carotid plaques remains limited. We attempted to elucidate this using 3-D ultrasonography (3D-US). We compared findings of the detailed localization of macrophage infiltration with findings from the newly developed tomographic ultrasound imaging (TUI).We obtained specimens of carotid arteries from 18 patients undergoing carotid endarterectomy (CEA), and investigated the localization of macrophages and vascular smooth muscle cells. Their localization obtained from 11 patients was compared with their preoperative TUI findings.We classified the localization of macrophage infiltration into four types: (i) focal infiltration in the thick fibrous cap (12 cases); (ii) subendothelial zonal infiltration (2 cases); (iii) peripheral infiltration around the lipid core (8 cases); and (iv) local infiltration near the shoulder of the fibrous cap (2 cases). Among them, preoperative TUI was available in 11 CEA cases for histological comparison. We identified two sites of focal macrophage infiltration that corresponded to local echogenic lesions without an acoustic shadow on TUI. The proliferation of smooth muscle cells failed to show an apparent echogenicity.TUI could not only evaluate the morphological features, but also showed the two types of focal macrophage infiltration relevant to plaque instability as an echogenic focus. TUI carried out by 3D-US is an easily applicable and non-invasive method that is considered useful for evaluating carotid plaques in elderly patients.

A 32-year-old man presented with a rapidly progressive decrease in visual acuity and diplopia. Magnetic resonance imaging (MRI) revealed a suprasellar cystic mass extending to the upper part of the clivus. The content of this cyst showed a slightly higher signal intensity than that of his cerebrospinal fluid (CSF) on T1-weighted images. The cyst stretched the pituitary stalk, but a normal pituitary signal was observed. The cyst wall was maximally resected under neuroendoscopy, which yielded fluid contents that were white and mucous like, with a carcinoembryonic antigen (CEA) level 1,400 ng/ml or higher. On light microscopy, one to two layers of epithelial cells with cylindrical nuclei on loose connective tissue lined the cyst cavity. These cells were positive for periodic acid-Schiff, CEA, and cytokeratin 7 and negative for cytokeratin 20. On electron microscopy, epithelial cells showed many short microvilli with coating material. The cytoplasm was rich in electron-dense material, and dense intercellular adhesion was observed, but neither goblet cells nor cilia were present. On the basis of MRI features, cytokeratin expression patterns and electron microscopic findings, the patient was considered to have a suprasellar endodermal cyst derived from Seessel’s pouch.

Summary Objectives To investigate the safety and efficacy of photodynamic therapy (PDT) using talaporfin sodium in patients with surgically, completely unresectable malignant gliomas with invasion into the eloquent areas of the brain associated with language and motor functions. Materials and methods Subjects consisted of consecutive 14 adult patients with malignant gliomas that were shown on preoperative diagnostic imaging to have invaded the eloquent areas of the brain. Of these, 6 patients had newly diagnosed tumors and 8 patients had recurrent tumors. In 15 craniotomy and tumor resection procedures, PDT was used as additional intraoperative treatment 24 h after 40 mg/m 2 of talaporfin sodium had been injected intravenously. After the tumor bulk had been resected as extensively as possible either 1 or 2 sites of probable tumor invasion in the bottom of resection cavity were irradiated superficially with a 664-nm diode laser for 180 s (27 J/cm 2 ) at a power density of 150 mW/cm 2 . Results PDT achieved a response rate of 80% at the treated sites in the 6 patients with newly diagnosed malignant gliomas. In these patients, the median progression-free survival time was 23 months. The median survival time in 3 patients who died was 26 months, and the remaining 3 patients survived for more than 3 years with a good Karnofsky Performance Scale (KPS). In the 8 patients with recurrent tumors who received PDT, their response rate was low (25.0%), their gliomas recurred 3 months after PDT, and their survival time was only 9 months following PDT. No adverse events directly attributable to PDT occurred in any patients. Protection against light was only required for approximately 3 days after PDT. Conclusion We examined the safety and efficacy of PDT using talaporfin sodium as an additional intraoperative treatment for malignant glioma. PDT in addition to surgical resection achieved better therapeutic results than conventional protocols, especially in patients with newly diagnosed malignant gliomas. However, the current methodology has some limitations with respect to patients with recurrent tumors. Larger-scale studies are required to confirm the clinical feasibility of PDT plus surgery.

Regarding the definition of gliomatosis cerebri (hereinafter referred to as "GC"), the 3rd edition of the WHO Classification of Central Nervous System Tumors (hereinafter referred to as "3rd ed.") provides only a five-line description that GC is a diffuse, frequently bilateral, glioma that infiltrates the brain, involving more than two lobes. It often extends to the infratentorial structures and even to the spinal cord. Compared with this, the definition in its 4th edition (hereinafter referred to as "4th ed.") is described in 13 lines, stating that GC involves at least 3 lobes and is usually bilateral, extending from the cerebral white matter, including the deep and subcortical portions, and often infiltrating the brain stem and the spinal cord. In the 4th ed., GC is characterized by a widespread infiltration of the brain by tumor, occurring as bilateral lesions involving commissural fibers, and frequently infiltrating from the brain stem to the spinal cord. Moreover, the 4th ed. states that GC is mainly astrocytic tumor but, in some cases, mainly consists of oligodendroglial tumor cells (Akimoto, 2004; Balko, 1996; Levin, 2004; Sanson, 2004, Taillibert, 2006). Unlike the 3rd ed., which specifies the histological malignancy as Grade III, the 4th ed. rates it basically as Grade III, without specifying it, although recognizing the importance of the evaluation of histological malignancy, in consideration of the possibility that the grade may be underestimated in some cases due to tissue sampling problems (Akimoto, 2004; Nishioka, 1996). These changes in the description of the definition in the WHO Classification have reflected the findings of many clinicopathological researches on GC. This situation requires us neuro-oncologists to diagnose GC before operation and to provide appropriate treatment. In that sense, it is important to evaluate the extent of tumor progression by imaging diagnosis, mainly using MRI, and to perform adequate tissue sampling to enable accurate histopathological diagnosis, in accordance with the 4th ed. (Akimoto et al., 2004). In addition, it is important to establish a treatment protocol mainly consisting of adjunctive therapy.

Objective Lipoprotein(a) [Lp(a)] is a risk factor for stroke, as has recently been further confirmed by meta analysis, and consists of low-density lipoprotein and apolipoprotein(a), which shares a significant amino acid homology with plasminogen. Oxidized Lp(a) [Ox-Lp(a)] is a more pathogenic species of Lp(a). A monoclonal antibody, specific to Ox-Lp(a), distinguishes immunolocalization of Ox-Lp(a) from that of Lp(a) and that of plasminogen which carries highly homologous domains. It is worth examining their possibly differential immunolocalizations around atherosclerotic lesions in human carotid and cerebral arteries. Methods and results Stage-related differences in immunolocalization of Ox-Lp(a), native Lp(a), and plasminogen were investigated in various atherosclerotic lesions of the human carotid (obtained from 13 patients undergoing carotid endarterectomy) and cerebral arteries (from 11 cadavers). Native Lp(a) was seen in the fibrous cap, extracellular matrix, endothelial cells, and subendothelial layer. Unorganized mural thrombi were positive for plasminogen, but not Lp(a). In contrast, fibrin deposits in thickened intima were positive for Lp(a), but not plasminogen. Ox-Lp(a)-like immunoreactivity was seen in endothelial cells in the early stage of atherosclerosis. Ox-Lp(a) deposition was more abundant in synthetic phase vascular smooth muscle cells (VSMC) than in contractile phase VSMC. Conclusion We demonstrated differential immunoexpression patterns between native Lp(a) and plasminogen, and suggested that Lp(a)-plasminogen interaction may play a part in differential mechanisms in all atherosclerotic lesions of human carotid and cerebral arteries. The preferential presence of Ox-Lp(a) seen in endothelial cells suggests initial dysfunction of endothelial cells in atherosclerosis. The relative abundance of Ox-Lp(a) in synthetic phase VSMC is associated with their phenotypic changes during the progression of atherosclerosis.

A new adjuvant therapy, individual adjuvant therapy (IAT), which is individualized according to the results of real-time reverse-transcription polymerase chain-reaction (RT-PCR) for O6-methylguanine-DNA methyltransferase (MGMT), was used to treat malignant gliomas. Immediately after the operation, mRNA expression for drug-resistance genes was investigated in frozen samples of malignant gliomas from 55 patients (30 glioblastoma multiformes, 20 anaplastic astrocytomas and 5 anaplastic oligodendroglial tumors) by real-time quantitative RT-PCR with specific primers for MGMT. Forty-two patients were treated with 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapies since the relative quantitation value (RQV) of MGMT in real-time RT-PCR with SYBR-Green I was1.0 or the absolute value of MGMT mRNA as measured by Taq Man probe methods normalized to the level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was6.0x10(3) copies/microg RNA. Thirteen patients, whose tumors had an RQV of1.0 or who had an absolute value of MGMT of6.0x10(3) copies/microg RNA, were treated by platinum-based chemotherapy using cisplatin or carboplatin. The response rate was 40.9% for glioblastoma multiformes, 60.0% for anaplastic astrocytomas and 80.0% for anaplastic oligodendroglial tumors. The median survival period of 30 patients with glioblastoma treated by IAT was 21.7 months. The 2-year survival rate of glioblastoma patients treated by IAT was 70.9%. Our IAT, based on the results of real-time RT-PCR, may lead to a beneficial glioma therapy.

We encountered 2 patients with germinoma arising from the medulla oblongata in whom preoperative radiological diagnosis was difficult. A 30-year-old woman presented due to aspiration pneumonia caused by bilateral lower cranial nerve palsies, and a 24-year-old man presented with headache caused by obstructive hydrocephalus. In both patients, there was a midline tumor that extended from the lower part of the fourth ventricle to the C1 lamina level. It was well-demarcated and homogeneously enhanced tumor with a slightly high density on plain CT scan. The preoperative diagnosis for both patients was ependymoma. The former patient had persistent lower cranial nerve palsies due to brain stem injury after tumor resection. Both patients achieved complete remission with adjuvant therapy. Fewer than 10 cases of germinoma affecting the medulla oblongata have been reported. Radiological findings resembling those of the pineal region germinoma were observed in the two patients reported here. We would like to stress the importance of remembering germinoma when making a preoperative differential diagnosis of fourth ventricular tumors in young adults.

A 48-year-old woman with a history of viral influenza infection was admitted with rapidly progressive numbness and weakness of the right extremities. On admission, general physical examination revealed no abnormality. Cerebrospinal fluid analysis showed no abnormal findings. Brain computed tomography and magnetic resonance imaging showed an open ring-like enhanced lesion in the white matter of the right parietal lobe with massive perifocal edema. Cerebral angiography showed no tumor staining and thallium-201 single photon emission computed tomography showed no abnormal uptake. The preoperative diagnosis was malignant glioma and partial resection was performed. Histological examination showed perivascular accumulation of small lymphocytes and a large number of macrophages with reactive astrocytes. Phagocytosis of myelin was observed in the macrophages and nuclear fragmentation in the reactive astrocytes. The histological diagnosis was acute inflammatory demyelinating disease. After therapy with methylprednisolone, her neurological symptoms improved gradually and no relapse occurred during 18 months of follow up. Tumor-like masses of demyelination may occupy an intermediate position between acute multiple sclerosis and postinfectious encephalitis. Open ring sign may be a pathognomonic feature of these lesions.

A 43-year-old woman who had undergone breast cancer surgery 1 year previously complained of headache and nausea. Her brain computed tomography (CT) scan and magnetic resonance imaging (MRI) showed a well-circumscribed, heterogeneously enhanced tumor in the right thalamus. She underwent gross total resection of the tumor followed by radiochemotherapy, and her clinical course was uneventful after surgery. Histological examination revealed a moderate number of tumor cells with fine bipolar processes in a mucoid matrix, which suggested pilocytic astrocytoma. The tumor was associated with microvascular proliferation but did not show significant mitosis or necrosis. In some areas, it had an epithelioid appearance, with ribbon-like, cribriform, and pseudoglandular patterns involving cuboid-shaped cells showing nuclear atypia and mitotic figures. Immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein (GFAP) and vimentin in the area resembling pilocytic astrocytoma, but in the epithelioid area they were negative for GFAP and vimentin as well as for breast cancer markers, including AE1/AE3. The proliferating potential, represented by the MIB-1 labeling index, was high (82.5%) in the area of epithelioid appearance, compared to only 3% in the area of pilocytic astrocytoma-like appearance. As a rare histoarchitectural variant of glioblastoma, the epithelioid pattern may represent a very primitive tumor cell phenotype. Typically, this pattern is characterized by well-circumscribed masses, although its clinical significance is unknown.

Since there is no current consensus on the diagnostic standards or surgical indications for symptomatic cysts of the septum pellucidum (CSP), we presented our experience treating such cases with neuroendoscopic surgery in order to possibly make a contribution to the attainment of such a consensus. In the last 5 years, we effectively treated 5 patients (4 males and 1 female) with CSP by neuroendoscopic surgery. The 3 congenital cases were young: 9, 14, and 29 years old. The 2 secondary cases were adults aged 51 and 65 years old. We were able to fenestrate, and biopsy for pathological analysis, the cyst walls of symptomatic CSP using a minimally invasive neuroendoscopic technique, with postoperative improvement in compression of adjacent structures, as well as clinical signs. It is necessary to consider the overall picture including clinical signs, progress of the condition, intracranial pressure, and cerebral circulation, in deciding whether surgery is indicated. Neuroendoscopic surgery is an effective, optimal, and convenient therapeutic modality for symptomatic CSP.

In contrast to aneurysms of the middle cerebral artery at the bifurcation, aneurysms at the origin of the lenticulostriate arteries (LSA) are uncommon. Six surgically treated patients (34 to 70 year-old; 3 men, 3 women) were reviewed. 5 patients presented with subarachnoid hemorrhage (HH grade 2:3, 3:1, 4:1; Fisher type 2:1, 3:3, 4:1) and 2 patients had multiple aneurysms. All aneurysms arose from the postero-superior surface of the M1. Although neck clipping was achieved in every patient, re-application of the clip was necessary during surgery in 3 patients because the tip of the blade extended to the other perforators that ran parallel to the M1. Results were as follows: GR 3, MD1, SD 1, D1. Apart from a 70 year-old patient who died of vasospasm (HH 4), fair results in two patients were accompanied by ischemic complications of the LSA. All 3 patients who required re-application of the clip during surgery showed a lacunar infarct of perforating arteries on post-operative CT. Special care of perforating arteries not only around the neck (the LSA) but also behind the aneurysm is essential for successful neck-clipping of aneurysms at this location.