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Background and Purpose— A retrospective, multicenter, observational study was conducted to document clinical outcomes and to identify outcome predictors in patients treated with low-dose intravenous recombinant tissue plasminogen activator (0.6 mg/kg alteplase), which was approved in Japan in 2005, within 3 hours of stroke onset. Methods— Consecutive patients with stroke treated with recombinant tissue plasminogen activator in 10 Japanese stroke centers were included. Results— A total of 600 patients (377 men, 72±12 years old) were studied. Median National Institutes of Health Stroke Scale scores decreased from 13 before recombinant tissue plasminogen activator to 8 at 24 hours later. Symptomatic intracerebral hemorrhage within 36 hours with a ≥1-point increase from the baseline National Institutes of Health Stroke Scale score developed in 23 patients (3.8%; 95% CI, 2.6% to 5.7%). At 3 months, 43 patients had died (7.2%; 5.4% to 9.5%), and 199 patients (33.2%; 29.5% to 37.0%) had a modified Rankin Scale score ≤1. Analysis of 399 patients with a premorbid modified Rankin Scale score ≤1 who met the criteria of the European license (≤80 years old, an initial National Institutes of Health Stroke Scale score ≤24, etc) showed that 40.6% (35.9% to 45.5%) had a 3-month modified Rankin Scale score ≤1. After multivariate adjustment, younger age, lower initial National Institutes of Health Stroke Scale score, absence of internal carotid artery occlusion, higher Alberta Stroke Program Early CT Score on CT, and absence of intravenous antihypertensives just before recombinant tissue plasminogen activator were independently related to a 3-month modified Rankin Scale score ≤1. Congestive heart failure and hyperglycemia were independently related to mortality. Conclusions— Three-month outcomes of patients receiving low-dose intravenous recombinant tissue plasminogen activator therapy in the present study were similar to those from postmarketing surveys using 0.9 mg/kg alteplase.

Background: Temozolomide (TMZ) is active against newly diagnosed glioblastoma (GBM), and O 6 -methylguanine-DNA methyltransferase (MGMT) is implicated in resistance to TMZ and nitrosoureas. We evaluated the efficacy and safety of the standard 5-day TMZ regimen in patients with recurrent GBM after initial therapy including nitrosourea-based chemotherapy, in conjunction with an analysis of the prognostic value of MGMT protein expression regarding response to TMZ and survival. Methods: From September 2003 to January 2007, 30 patients having recurrent GBM received 150‐200 mg/m 2 /day of TMZ for five consecutive days every 28 days. Tumor tissue from 19 patients was analysed for MGMT protein expression using western blotting, and 17 of them were assessable for a response. Results: The overall response rate was 23.5% (one complete response and three partial responses). Six patients had stable disease (35.3%). Median progression-free survival (PFS) time was 2.2 months, and median overall survival (OS) time was 9.9 months from the initiation of TMZ therapy. Patients with low MGMT protein expression had a significantly improved PFS (P ¼ 0.016) and OS (P ¼ 0.019) compared to those with high expression. Both low MGMT expression (P ¼ 0.040) and re-resection at relapse (P ¼ 0.014) persisted as significant independent favorable prognostic factors for OS. The most common grade 3 and 4 hematological toxicity was lymphopenia (22.2%). Conclusions: The standard 5-day TMZ regimen resulted in moderate antitumor activity with an acceptable safety profile in patients with nitrosourea-pretreated recurrent GBM, and protein expression of MGMT is an important prognostic factor for patients treated with TMZ even after recurrence.

Object Malignant gliomas remain incurable despite modern multimodality treatments. Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL), also known as Apo2L, a member of the TNF family, preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, suggesting that it may serve as a potential therapeutic agent for intractable malignant gliomas. Here, the authors show that genotoxic ionizing radiation synergistically enhances TRAIL-induced cell death in human glioma cells expressing DR5. Methods Combination treatment with soluble human TRAIL plus radiation induced robust cell death, while each of them singly led to only limited cytotoxicity. The combination resulted in cleavage and activation of the apoptotic initiator caspase-8 and the effector caspase-3 as well as cleavage of Bid and another initiator caspase-9, a downstream component of the apoptosome. Accordingly, it augmented the release of cytochrome c from the mitochondria into the cytosol, as well as apoptosis-inducing factor. Synergistic cell death was suppressed by TRAIL-neutralizing DR5-Fc, caspase inhibitors, expression of dominant-negative Fasassociated protein with death domain and CrmA, which selectively blocks caspase-8, and overexpression of Bcl-XL. Finally, combination treatment had no influence on the viability of normal human astrocytes. Conclusions These results suggest that combination treatment with TRAIL and ionizing radiation kills human glioma cells through the activation of DR5-mediated death receptor pathways. This therapy involves direct activation of effector caspases as well as mitochondria-mediated pathways and provides a novel strategy in which TRAIL could be synergistically combined with DNA-damaging radiation.

INTRODUCTION: Temozolomide (TMZ), a standard drug for glioblastoma (GBM), induces inactivation of the DNA mismatch repair (MMR) system and hence causes hypermutator phenotype in the glioma especially with methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. MMR defects are also found in primary gliomas and are associated with resistance to TMZ and malignant progression to secondary GBM. However, the association between alteration of MMR system and clinical outcome of both primary and recurrent GBMs was yet to be elucidated. METHODS: We analyzed protein expression of MLH1, MSH2, MSH6, and PMS2 as well as MGMT methylation in a set of 117 primary GBMs and 34 paired sample of initial and recurrent gliomas. Protein expression was analyzed by Western blotting and/or immunohistochemistry. MGMT methylation was determined by methylation-specific PCR. Progression-free and overall survival times according to each molecular status were reviewed. RESULTS: Loss of MMR protein expression (MLH1, MSH2, MSH6, and PMS2) was observed in 12%, 10%, 50%, and 16% of the primary samples, respectively. Inactivation of MSH6 during the recurrence was associated with MGMT methylation at recurrence (p = 0.02), while MGMT methylation of the initial samples did not predict the changes of any MMR protein. Malignant progression from lower grade glioma was associated with inactivation of MSH6 (p = 0.035). Loss of MMR protein expression, as well as unmethylated MGMT promoter, was associated with shorter overall survival in patients with primary GBMs. In contrast, MMR inactivation was associated with longer survival in patients with recurrent GBMs, while MGMT methylation was not. CONCLUSION: Inactivation of MMR protein was associated with resistance to TMZ for primary GBMs, malignant progression of lower grade gliomas, and was predictive factor for survival of the patients with recurrent GBMs. Further investigation to define optimal treatment for glioma according to MGMT and MMR status is warranted.

We retrospectively analysed to demonstrate the selection of the treatment modality and its efficacy in our department. Subjects of the present study comprised patients in whom coil embolization was abandoned due to such reasons as broad neck, whom coil embolization was performed for residual aneurysm following incomplete clipping or recurrent cerebral aneurysm, whom coil embolization was performed after coil compaction, whom coil embolization and clipping were performed for the treatment of multiple cerebral aneurysms. In the treatment of cerebral aneurysm, selecting proper techniques by considering the characteristics of clipping and coil embolization is desirable. In other words, strategizing therapy by taking advantages of the merits of clipping and coil embolization is important.

Ruptured saccular aneurysms were severe condition for intracerebral Condition. And the cause for their rupture is not yet clear. In this study (I), since the configurations of aneurysms are considered to be a factor for the rupture of aneurysms, several shapes has been modeled using Aspect ratio AR and inclination angle of saccular aneurysms. In vitro the parametric study has been conducted on the range of Reynolds Number in human blood flow for aneurismal models of AR=2.1 and 1.3 and q =90° and 70°, As results, it was con firme d that there are characteristic flow patterns with Reynolds Number, And that the aneurismal configuration has effects on the shear stress and pressure losses. II) The object of this paper is to study the effects of STENTS. We made the model of aneurysm and performed in vitro study in range of Reynolds number of human blood flows using three kinds of STENTS. As results, it was confirmed that flow pattern and pressure loss changes with the kinds of STENTS. This study aims the accumulation of data to predict the hazard of aneurysmal rupture by their shapes and STENTS.

Pterional cnaniotomy is frequently used in neurosurgical practice, but still poses significant cosmetic and functional drawbacks. Here, we describe our modified technique to overcome such problems as the sterilization of the scalp without brush and razor, preemptive analgesia, preservation of the periostium for reconstruction, retrograde dissection of the temporal muscle, and complete sphenoidotomy using chisel or drills. The tips of our pterional craniotomy offer suitable size and depth of working field around the paraclinoidal regions, maintaining cosmetic satisfaction of the patients.

Objectives: The present study characterized glial cell injury provoked in adult rat chiasm within 24 hours after a single, high-dose irradiation of 20 Gy. Methods: All chiasmal glial cells in a section were counted, and the percentage of TUNEL-positive glial cells exhibiting apoptotic morphology was defined as the apoptotic rate. Results: Numbers of apoptotic cells increased significantly (p

✓ The anterior clinoid process (ACP), located on the skull base, is a relatively small structure, although its removal provides enormous gain in facilitating the management of lesions—either tumors or aneurysms—in the paraclinoid region and upper basilar artery. The extensive surgical field gained contributes to safer exposure of the neurovascular elements in the vicinity while avoiding excessive and hazardous retraction of the brain. In this report the authors present a technically simpler avenue for performing an extradural anterior clinoidectomy after reviewing the anatomy of the ACP and its anatomical variations. Additionally, the original Dolenc procedure and its subsequent derivatives are compared and contrasted to the authors' simpler and less laborious technique. Different clinical situations in which to use the procedure are described based on the authors' experience from 60 cases (40 aneurysm cases and 20 tumor cases) during a 4-year period.

The etiology and proper treatment of symptomatic subacute subdural hematomas remains to be elucidated. We describe two cases of this entity successfully treated with small craniotomy and evacuation. Both patients initially treated conservatively for traumatic thin subdural hematomas because of poor medical condition and mild neurological symptoms, but suffered abrupt neurological deterioration between 2 and 3 weeks after the admission. CT scan showed decreased density of hematomas with minimal increase in volume, and significant swelling of ipsilateral cerebral hemisphere. Urgent two-burr-hole small craniotomy was effective for evacuation of partially organized hematoma. During surgery, definite hematoma membrane was not confirmed. Postoperatively, brain swelling rapidly disappeared and both patients discharged ambulatory without neurological deficit. The present cases are a reminder of this peculiar type of hematoma in patients with delayed neurological deterioration after nonsurgical management of acute subdural hematoma. The rationale for use of small craniotomy is discussed in terms of current understanding of pathogenetic mechanism for this unusual condition.

The purpose of this study is to investigate the mechanism of increased atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with subarachnoid hemorrhage due to ruptured aneurysms. ANP and BNP plasma concentrations were measured by immunoradiometoric assay in 53 patients at the day of onset of ruptured aneurysm, the correlation between values of increased ANP or BNP, and sex, age, location of ruptured aneurysm, degree of SAH, and severity of WFNS were statistically studied. The concentration of BNP in ruptured anterior communicating artery aneurysm (A-com) shows a significant elevation compared with other site aneurysms (p = 0.0007). The patients classified as WFNS Grade V, show a significantly higher concentration of BNP, compared with the patients classified as Grade I-IV (p =0.01). It is concluded that the hypersecretion of BNP, but not ANP, is caused by direct mechanical damage at the anterior hypothalamus by ruptured A-com aneurysm and a higher increase of BNP is also observed in cases suffering from severe neurological deficit.

A 68-year-old man presented with progressive headaches. Physical and neurological examinations revealed no abnormalities. CT demonstrated a heterogeneously enhanced mass occupying the lateral aspect of the left sphenoid sinus (Fig. 1A; arrowheads), eroding both the sinus wall and the floor of the middle cranial fossa (Fig. 1B; arrow). MRI delineated no obvious tumor involvement of the middle cranial fossa (Fig. 1C). The lesion was avascular on cerebral angiography. A left zygomatic extradural subtemporal approach through a straight pre-auricular skin incision allowed total resection of an elastic hard tumor containing xanthochromic fluid. The tumor originated from the maxillary division of the trigeminal nerve at the eroded foramen rotundum, but the major part of the tumor involved the sphenoid sinus, destroying the lateral wall. Dural invasion was not seen. Postoperatively, he recovered well with mild paresthesia in the maxillary nerve. Histopathological examination confirmed the diagnosis of schwannoma (Fig. 1D). Trigeminal neurinoma is known to extend extracranially along the three divisions of the nerve, occasionally manifesting as orbital, nasomaxillary, or infratemporal masses [4, 5]. Very rarely, however, main involvement of the sphenoid sinus occurs [1–3], where mucocele or bone tumor has a predilection for chronic expansion. The present case offers a reminder of the considerable variability displayed by trigeminal neurinoma.

We investigated histological changes in aneurysmal orifices after embolization with Guglielmi detachable coils (GDCs) and determined the effects of the wound-healing factor, factor XIII, on promoting intimal proliferation by scanning electron microscopy (SEM). GDC embolization was performed in an experimental model of aneurysm in swine. In the control group (17 aneurysms), the aneurysms were resected immediately after surgery, at 1 and 3 weeks after the procedure. In the factor XIII-administered group (13 aneurysms), the swine received factor XIII postoperatively, and the aneurysms were excised at 1 and 3 weeks. The endothelial cell proliferation changes in the aneurysm orifices in both groups were evaluated by SEM. The histological changes at the orifices began immediately after the procedure, and endothelialization was observed at 1 week. One week after the procedure, the rate of endothelial cell proliferation was significantly higher in the factor XIII group (P

To date, various particulate embolic materials have been developed and investigated experimentally, but none have reached a stage where they are permanently suitable for routine clinical application. The particles should have a non-absorbable character and good biocompatibility. ES particles (ES; BioSphere Medical, MA) fulfill these general requirements. The particles should be spherical so that they can be sorted into various sizes by sieving, providing uniformly graded and calibrated material. Spherical particles provide geometrically optimal occlusion of the vascular lumen. They are hydrophilic, non-absorbable, collagen-coated, acrylic microspheres. Distal portions of the microvasculature can be reached by the microspheres. PVA particles have been the most commonly used for embolization 5. Embolization experiments were independently conducted in an animal model using a combination of ES. However, this embolic material is not radiopaque. We thought that combining it with titanium could solve this problem. Pure titanium is radiolucency material. Before clinical use, we investigated ES experimental study using combination with titanium. In this paper, we report the clinical application of ES compared with PVA in the embolization of meningiomas.

Hyponatremia and hypovolemia following aneurysmal subarachnoid hemorrhage (SAH) might be speculated by exaggerated secretion of natriuretic peptides and resulted ischemic sequela caused by cerebral vasospasm. We measured serum concentration of natriuretic peptides and investigated their influence on post-SAH hyponatremia. Among 49 patients of SAH, their plasma concentration of the natriuretic peptides (atrial natriuretic peptide: ANP and brain natriuretic peptide: BNP) were measured at the day of ictus and 7th day of SAH. The correlation between concentration of natriuretic peptides and location of aneurysm, severity of SAH, incidence of hyponatremia and symptomatic vasospasm were elucidated. The plasma concentration of ANP did not alter on admission and 7th day post SAH, whereas that of BNP increased in the patients with moribund SAH and those with ruptured A-com aneurysm. The initial increase of BNP following SAH could be attributed to direct damage of SAH on the hypothalamus. Hyponatremia and symptomatic vasospasm tended to occur in the patients who had persistent increase of plasma BNP concentration during one week post SAH. Therapeutic intervention to maintain normonatremia by fluid-management decreased occurrence of symptomatic vasospasm, even though patients with increased plasma BNP concentration. It might be concluded that increased secretion of BNP following SAH is caused by direct effect to the hypothalamus and prolonged hyper secretion of BNP resulted hyponatremia, hypovolemia and exaggerated symptomatic vasospasm.

Purpose: To determine whether application of a volume-rendered display of 3D time-of-flight (TOF) MR angiography could assist the diagnosis of cerebral arteriovenous malformations (AVMs). Material and Methods: Volume-rendered 3D images of postcontrast 3D time-of-flight MR angiography were compared with conventional angiograms in 12 patients. The correlation between the 3D images and the operative findings was also analyzed in 5 patients. Results: The 3D-displayed images showed all of the feeders and drainers in 10 and 9 patients, respectively. In all patients, the nidus was three-dimensionally visualized. In 3 patients with hematomas, the relationship between the hematoma and the AVM was well demonstrated. The 3D images corresponded well with the operative findings in the 5 patients. Conclusion: This method is of help in assessing the relationship between the components of an AVM as well as that between an AVM and an associated hematoma.

Purpose The advent of multidetector-row computed tomography (MDCT) has enabled images with good spatial resolution to be obtained over a wide range in a short scanning time. Our purpose was to determine whether CT angiography using the MDCT system could effectively depict extracranial-intracranial (EC-IC) bypass routes. Method Helical CT angiography was performed using an MDCT scanner in 12 patients who had undergone EC-IC bypass surgery: 10 patients had undergone superficial temporal artery-middle cerebral artery (MCA) anastomosis, 1 patient had undergone an encephaloduroarteriosynangiosis procedure for the treatment of moyamoya disease, and 1 patient had undergone an external carotid artery-MCA anastomosis using a graft. The resulting CT angiograms were visually evaluated for their depiction of the EC-IC bypass route. Conventional angiograms were available for comparison in all 12 patients. Results The EC-IC bypass was visualized to be patent at the site of anastomosis in all 12 patients. Branches of the MCA secondary or more to those connected to a donor artery were demonstrated in 9 patients, whereas MCA branches immediately distal to the anastomosis were demonstrated in 3 patients. The CT angiography findings corresponded well with the conventional angiography findings in all patients. Conclusion Helical CT angiography using the MDCT technique is an effective method for visualizing EC-IC bypass routes.

We report one patient with agenesis and two with hypoplasia of the internal carotid artery (ICA) from an angiographic series of 1275 consecutive patients. In all three patients, MRI and MR angiography were used to establish the anatomical situation; however, they may not clearly distinguish between hypoplasia and agenesis or acquired stenosis or occlusion of the ICA. In such cases, CT of the skull base may be obtained to clarify matters. In all patients, retrograde flow via a large posterior communicating artery was demonstrated. Single-photon emission computed tomography confirmed both the adequacy of cerebral perfusion and the preservation of vasomotor reactivity.

The current technique for cranioplasty using artificial bone requires further improvement with regard to infection, strength and comfort through good fitting. We have carried out cranioplasty using the patient's autogenous bone flap obtained during first surgery. It was immersed in 200 mg of Amikacin Sulphate, and frozen at -16 degrees C until its use in cranioplasty. From 1980 to 1998, cranioplasty has been carried out on 206 patients. They consisted of 118 males and 88 females, and their age ranged in our institute from 1 to 81; average age 51.1. Ruptured aneurysm (48%), head injury (14%), intracranial hemorrhage (23%) and cerebral infarction (12%) were the major causes requiring decompression surgery. We analyse the bone preservation period and the time between cranioplasty and the onset of infection. The infection rates per bone preservation periods, the causes of decompression and age groups are studied. Of the 208 case studies, infection necessitating bone removal or debridement was noted in 8 cases (3.88%). Average bone preservation period in the infected group was 31.1 days as compared with 54.9 days for the non-infected group (p0.05). Not patient age but the type of head injury is also a significant factor in post cranioplasty infection.

BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM including longitudinal and combined chemotherapy will be also discussed.

Background: The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke. Methods and Results: Of the 1,369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Among the institutions that responded, data on patients hospitalized for stroke between April 1, 2010 and March 31, 2011 were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, comorbidities, and the number of fulfilled CSC items in each component and in total. Data from 265 institutions and 53,170 emergency-hospitalized patients were analyzed. Mortality rates were 7.8% for patients with ischemic stroke, 16.8% for patients with intracerebral hemorrhage (ICH), and 28.1% for patients with subarachnoid hemorrhage (SAH). Mortality adjusted for age, sex, and level of consciousness was significantly correlated with personnel, infrastructural, educational, and total CSC scores in patients with ischemic stroke. Mortality was significantly correlated with diagnostic, educational, and total CSC scores in patients with ICH and with specific expertise, infrastructural, educational, and total CSC scores in patients with SAH. Conclusions: CSC capabilities were associated with reduced in-hospital mortality rates, and relevant aspects of care were found to be dependent on stroke type., PLoS ONE, 9(5), e96819; 2014

A 38-year-old otherwise healthy man presented with hiccups that had persisted for 8 weeks. The bouts were nearly continuous and severely distressing, depriving the patient of nutrition and sleep. On admission, he was afebrile with a blood pressure of 116/76 mm Hg and had no neurologic deficits. He had no headache, vertigo, or vomiting. Physical and ocular examination revealed no abnormalities, and the results of routine laboratory tests were normal. He had no history of familial disorders. Several physical maneuvers including breath holding, sneezing, and palatal stimulation did not relieve the symptom. Pharmacologic treatment with metoclopramide and diazepam was also ineffective. …

Background and Purpose —Intracranial fusiform aneurysms can be divided into 2 clinically different subtypes: acute dissecting aneurysms and chronic fusiform or dolichoectatic aneurysms. Of these 2, the natural history and growth mechanism of chronic fusiform aneurysms remains unknown. Methods —A consecutive series of 16 patients with chronic fusiform aneurysms was studied retrospectively to clarify patient clinical and neuroradiological features. Aneurysm tissues were obtained from 8 cases and were examined to identify histological features that could correspond to the radiological findings. Results —Four histological features were found: (1) fragmentation of internal elastic lamina (IEL), (2) neoangiogenesis within the thickened intima, (3) intramural hemorrhage (IMH) and thrombus formation, and (4) repetitive intramural hemorrhages from the newly formed vessels within thrombus. IEL fragmentation was found in all cases, which suggests that this change may be one of the earliest processes of aneurysm formation. MRI or CT detected IMH, and marked contrast enhancement of the inside of the aneurysm wall (CEI) on MRI corresponded well with intimal thickening. Eight of 9 symptomatic cases but none of 7 asymptomatic cases presented with both radiological features. Conclusions —Data suggest that chronic fusiform aneurysms are progressive lesions that start with IEL fragmentation. Formation of IMH seems to be a critical event necessary for lesions to become symptomatic and progress, and this can be monitored on MRI. Knowledge of this possible mechanism of progression and corresponding MRI characteristics could help determine timing of surgical intervention.

We isolated a cDNA for the human homologue of system asc transporter Asc-1 from human brain. The encoded protein designated as hAsc-1 (human Asc-1) exhibited 91 % sequence identity to mouse Asc-1. Consistent with mouse Asc-1, hAsc-1 required 4F2 heavy chain for its functional expression in Xenopus oocytes. hAsc-1 exhibited the properties of amino acid transport system asc which transports small neutral amino acids in a Na(+)-independent manner. hAsc-1 transported D-serine at high affinity with a K(m) value of 22.8 microM. In brain, 2.0 kb mRNA was highly expressed. hAsc-1 gene was mapped to human chromosome 19, region q12-q13.1. Because of the high-affinity transport with the K(m) value close to the physiological concentration of D-serine, together with the high levels of expression in brain, hAsc-1 is proposed to play significant roles in the D-serine mobilization in brain.

The authors report a case of postoperative middle meningeal arteriovenous fistula found after craniotomy for aneurysmal surgery using the pterional approach. It was no longer demonstrable at the follow-up examination 3 months later.

BACKGROUND Whereas multiple aneurysms may be found in 20% of patients in whom one aneurysm is discovered, the identification of five vertebrobasilar aneurysms is distinctly rare. We described such a case treated by surgical and endovascular method. CASE DESCRIPTION A case of multiple aneurysms treated with combined surgical clipping and intravascular surgery is described. Five separate posterior circulation aneurysms and bilateral internal carotid artery occlusion were identified in one patient. Three of the aneurysms were treated surgically. Access to the fourth aneurysm was deemed difficult because of its location and because of the previously placed surgical clips; this aneurysm was treated by endovascular approaches that provided optimum therapy in this unusual multiple aneurysms case. CONCLUSIONS We have described an unusual case of multiple posterior circulation aneurysms in the setting of bilateral internal carotid occlusions, treated by a combination of surgical and endovascular therapies. We will be able to provide safer treatment for such difficult cases in the future.

Cisternal injections of blood in the rat and squirrel monkey produce an angiographically demonstrable biphasic vasospasm with a maximal late spasm at two days in the rat and six days post-subarachnoid hemorrhage (SAH) in the monkey. The SAH induces a decrease in cerebral blood flow of about 25% and a corresponding increase in glucose uptake of between 30% and 50%. In about half of the animals low-flow areas were noted in the cortex and the basal ganglia with a corresponding marked increase in glucose uptake. Lesioning of the A2-nucleus, its ascending pathway or the median eminence prevents the occurrence of spasm. Similarly, treatment with a substance P antagonist or gammaglobulin against substance P prevents or significantly reduces the degree of spasm. A unilateral post-ganglionic trigeminal lesion causes an ipsilateral constriction of the cerebral arteries of 27%, while a preganglionic lesion does not affect the baseline diameter. A pre- or post-ganglionic trigeminal lesion induces an increase in glucose uptake globally of about 50% without influencing cerebral blood flow. Following SAH the decrease in blood flow in both groups of lesioned animals is similar to that seen in controls. After SAH there is no further change in glucose uptake in the animals with a preganglionic lesion, while in the post-ganglionically lesioned animals there is an additional increase in glucose uptake of about 50% as compared to controls or the animals with a preganglionic lesion.

BACKGROUND Sphenoid sinus aspergillosis is a rare disease known to show an aggressive course with high mortality. Early diagnosis, though difficult, is required to prevent lethal fungal meningoencephalitis. CASE REPORT We describe two cases of parasellar Aspergillus granuloma extending from the sphenoid sinus clinically indistinguishable from intracranial neoplasms. In the first patient, the fungus colony was visualized by computed tomography (CT) and magnetic resonance imaging (MRI) as a calcified concretion and total removal was curative. In the second patient, partial removal and subsequent antifungal therapy had minimal effect. CONCLUSIONS The prognosis of the patients with this disease depends on prompt surgical treatment before intradural invasion occurs, and CT and MRI are useful diagnostic maneuvers for detecting calcified Aspergillus colonies.

We report a 56-year-old woman whose father and 2 of 3 sisters had cerebral aneurysms, and who developed de novo aneurysm 5 years after a screening.

Cerebral vasospasm following subarachnoid hemorrhage was induced in the squirrel monkey in order to evaluate the involvement of cerebrovascular sensory nerves in the development of the vasospasm. A unilateral surgical section of the trigeminal nerve at post- but not at pre-Gasserian level caused constriction of the major ipsilateral cerebral arteries. A pre- or postganglionic trigeminal lesion induced an increased glucose uptake globally without influencing the cerebral blood flow. Following a subarachnoid hemorrhage, the decrease in cerebral blood flow was similar of that seen in control animals, while post-ganglionically lesioned animals had an additional increase in glucose uptake. Intrathecal injection of gamma-globulin against substance P prevented the occurrence of vasospasm and the decrease in cerebral blood flow, while calcitonin gene-related peptide (CGRP) anti-gamma-globulin injection significantly reduced the resting vessel diameter and did not influence spasm development. It is concluded that a nervous reflex mechanism could underlie cerebral vasospasm. The cerebrovascular sensory nerves have both a peripheral and a central function. A peripheral or axon reflex mechanism exerts a tonic effect on the cerebral arteries. Central neurotransmission seems to be involved in the regulation of cerebral metabolism and possibly in the coordination of cerebral blood flow and glucose metabolism. CGRP could be the transmitter involved in a peripheral axon reflex and substance P might be the neurotransmitter conveying information to the brainstem vascular centers.

Since the publication of the temporo-polar approach to basilar artery aneurysms by Sano (1980 and 1987), various modifications of the approach were reported. The approach provides a better view and a wider operating field than the subtemporal or pterional ones. Usually the approach does not need temporary remove of the zygomatic arch. If however, a basilar tip aneurysm is located very high above the posterior clinoid, temporary removal of the zygomatic arch is necessary which is sutured back to its original position at the end of the operation.

Background: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. In elderly population, the incidence of cerebral embolism (CE) caused by AF tends to be increasing. In this study, we assessed the distribution and the most frequent factor in elderly patients with an embolic event due to nonvalvular AF (NVAF). Methods: Among 435 consecutive patients with cardiogenic embolus who were referred to Stroke Care Unit at our institute, 301 patients were diagnosed as CE caused by NVAF. Of the patients, 188 patients were 75 years old or more. Patients were excluded when AF episodes were not documented on electrocardiographic monitoring. The CHADS2 score was evaluated for each of the 188 patients. Results: In 75 years old or more, the CHADS2 score was 1 in 29 (15%), 2 in 62 (33%). Among patients with a CHADS2 score of 2, a combination of hypertension and age >75 years was the most frequent pattern (85%). Conclusions: The most frequent factor was hypertension in patients 75 years old or more with CE due to NVAF. The management of blood pressure is very important for preventing cerebral embolic events in elderly population with NVAF.