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The neuroprotective agents and induction of endogenous neurogenesis remain to be the urgent issues to be established for the care of cerebral stroke. Platelet-derived growth factor receptor beta (PDGFR-β) is mainly expressed in neural stem/progenitor cells (NSPCs), neurons and vascular pericytes of the brain; however, the role in pathological neurogenesis remains elusive. To this end, we examined the role of PDGFR-β in the migration and proliferation of NSPCs after stroke. A transient middle cerebral-arterial occlusion (MCAO) was introduced into the mice with conditional Pdgfrb-gene inactivation, including N-PRβ-KO mice where the Pdgfrb-gene was mostly inactivated in the brain except that in vascular pericytes, and E-PRβ-KO mice with tamoxifen-induced systemic Pdgfrb-gene inactivation. The migration of the DCX+ neuroblasts from the subventricular zone toward the ischemic core was highly increased in N-PRβ-KO, but not in E-PRβ-KO as compared to Pdgfrb-gene preserving control mice. We showed that CXCL12, a potent chemoattractant for CXCR4-expressing NSPCs, was upregulated in the ischemic lesion of N-PRβ-KO mice. Furthermore, integrin α3 intrinsically expressed in NSPCs that critically mediates extracellular matrix-dependent migration, was upregulated in N-PRβ-KO after MCAO. NSPCs isolated from N-PRβ-KO rapidly migrated on the surface coated with collagen type IV or fibronectin that are abundant in vascular niche and ischemic core. PDGFR-β was suggested to be critically involved in pathological neurogenesis through the regulation of lesion-derived chemoattractant as well as intrinsic signal of NSPCs, and we believe that a coordinated regulation of these molecular events may be able to improve neurogenesis in injured brain for further functional recovery.

We describe a higher magnifying power operating microscope system to improve one method of high-quality microsurgical clipping for cerebral aneurysm in some cases. This higher magnification is achieved by a new lens design in the optical system, which makes the image of the object very clear at high magnifications (distinctiveness of 7 μm). This higher-resolution operating microscope system provides the surgeon with higher-magnified images (at the maximum of more than 30× magnifications as each working distance) in the operating field. The magnifications can be changed from low power (2.9×) to high power (62.0×) depending on the circumstances in a given procedure. We have used this operating microscope system on 11 patients with microsurgical clipping for cerebral aneurysms. Microsurgical treatment could be performed safely and precisely. All aneurysms were treated without any technical complications. We think that the use of this microscope would have potential benefits for microsurgical treatment for cerebral aneurysms because of better visualization.

A 38-year-old man presented with a rare case of syringomyelia associated with Paget disease of the skull. Syringosubarachnoid (SS) shunting was performed. We speculate that deformation of the skull secondary to Paget disease caused narrowing of the foramen magnum with progressive impairment of the cerebrospinal fluid circulation, which led to syringomyelia and neurological symptoms. SS shunting is safe, effective, and technically simple, so may be a useful initial treatment for syringomyelia associated with Paget disease of the skull.

Objectives Cerebrospinal fluid (CSF) leakage is an undesirable complication of skull base surgery. We used dried human amniotic membrane (AM) as a patch graft for dural repair to determine its efficacy in preventing CSF leakage. Design Frontoparietal craniotomy and removal of dura were performed in 20 Wistar rats. A dried AM was placed to cover the dural defect without suturing in 16 animals. In four animals, an expanded polytetrafluoroethylene was implanted. At 2 weeks and 1, 3, and 6 months, histological examination was performed. Dried AM was also used as a substitute in 10 patients who underwent skull base surgery, after approval by the Ethics Committee of the University of Toyama. Results At 2 weeks after implantation, thick connective tissue completely enclosed the dried AM. At 1 month after implantation, the connective tissue became thin and the implanted AM shortened. At 3 and 6 months after implantation, histological examination revealed disappearance of the dried AM and formation of membranous tissue. In the clinical study, neither CSF leakage nor clinical adverse reactions directly related to the dried AM were observed. Conclusion Dried human AM appears to be an ideal substitute for dura, since it is replaced by natural tissue.

The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner. Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair. The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59). The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.

Object The authors report their investigation on the current status of neuroendoscopic biopsy for ventricular and paraventricular tumors as well as treatment for associated hydrocephalus in Japan. Methods Patients who had undergone therapeutic neuroendoscopy between 2005 and 2009 were included in this study. The main items examined were age; sex; localization of tumor; pathological diagnosis using biopsy; the presence, treatment, and efficacy of treatment of associated hydrocephalus; perioperative complications; activities of daily living (ADL) before and after therapeutic neuroendoscopy; and the presence of dissemination during the postoperative course. Results Seven hundred fourteen patients from 123 sites (462 male and 252 female patients, mean age 33.3 years) were enrolled. Localization of the tumor was mainly classified into the lateral ventricle in 91 patients, the third ventricle in 339, the fourth ventricle in 18, the suprasellar region in 75, and other paraventricular areas in 191 patients. The most commonly observed tumors were germ cell tumors in the third ventricle (177 cases [39%]), cystic lesions in the suprasellar region (56 cases [75%]), and astrocytic tumors in the thalamus-basal ganglia (71 cases [38%]). Although 641 (92.8%) of 691 patients could receive neuroendoscopic diagnosis using biopsy, the diagnosis obtained with endoscopic biopsy differed from the final diagnosis based on subsequent craniotomy in 18 patients and clinical course in 3 patients. Of these 21 patients, 7 had astrocytic tumors, 4 had pineal tumors, 6 had germ cell tumors, and 4 had other tumors. The final diagnostic accuracy rate was 89.7%. Associated hydrocephalus was observed in 517 patients (72.4%), of whom 316 and 39 underwent third ventriculostomy and fenestration of the septum, respectively. The response rates were 96.2% and 89.7%, respectively. Third ventriculostomy was required for recurrence of hydrocephalus in 41 patients (13.0%), and the long-term response rate was therefore 83.2% (263 of 316 patients). Perioperative complications other than fever, such as new onset of or progressive hydrocephalus, infection due to CSF leakage, and bleeding in the ventricle or tumor, were found in 81 patients (11.3%). The median Karnofsky Performance Scale score before endoscopic surgery was 80, but it increased to 90 after surgery. The score was thus significantly increased after surgery (p < 0.0001, Mann-Whitney U-test). Activities of daily living after surgery decreased due to perioperative complications in 15 patients (2.1%). The incidence of new dissemination after endoscopic biopsy was 6.8% and not high compared with routine surgical treatment. Conclusions The authors concluded that neuroendoscopic diagnosis using biopsy for ventricular and paraventricular tumors is adequately accurate and safe. It was demonstrated that endoscopic procedures play important roles not only in the treatment of hydrocephalus associated with intra- and paraventricular tumors but also in significantly improving ADL. Furthermore, the long-term outcome of endoscopic third ventriculostomy was clearly favorable.

Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding to WHO grade II. We present a case of CCM with histologically aggressive appearance and clinically aggressive behavior. The tumor demonstrated rapid regrowth and brain metastasis. The histological progression from the ordinal CCM to the atypical area and higher MIB-1 index was observed. We assume that the short time of recurrence and metastasis may result from atypical histological features in our case. If the CCM has a histologically aggressive appearance as in our case, we suggest that postoperative adjuvant radiotherapy should be performed despite total resection of the tumor.

A 62-year-old female complaining of sudden severe headache was referred to our stroke center in consultation. Computed tomography showed diffuse spread of thick subarachnoid hemorrhage to the basal cistern and both sylvian fissures, and digital subtraction angiography showed kissing aneurysms arising in the left lateral and occipital directions in the C1 portion of the internal carotid artery (ICA). The anterior choroidal artery was situated between the two aneurysms, and another small branch originating from the dome of the distal aneurysm was confirmed as a duplicated middle cerebral artery (MCA). Endovascular treatment was successfully performed to spare the two vessels involved. This case of kissing aneurysms and ICA-duplicated MCA is very rare, and presents difficulties for both surgical and endovascular treatments.

This study evaluated the usefulness of computed tomography (CT) angiography for the detection of high-risk aortas for carotid artery stenting (CAS). We investigated changes in the treatment method and modifications of endovascular techniques according to the information from CT angiography. CT angiography using three-dimensional and multi-planar reconstruction was performed in 43 consecutive patients with carotid artery stenoses intended to undergo CAS. Two neurosurgeons evaluated the images and estimated the risk and difficulties of CAS. CT angiography clearly depicted the entire aorta, the supra-aortic vessels, and the ilio-femoral arteries in all patients. Abnormal vascular findings were found in 17 patients. High-risk aortic lesions for CAS were detected in 5 patients, including thick aortic plaques with thrombi in 2. We changed the treatment strategy from CAS to carotid endarterectomy (CEA) in these 2 patients. CT angiograms proved very useful in evaluating the approach routes of CAS in 12 patients. One patient had dissecting aneurysm of the thoracic aorta and another had aberrant right vertebral artery. In these two, the treatment strategy was changed from CAS to CEA. The treatment method was changed in 4 patients in total. CT angiography is useful for the detection of high-risk aortas for CAS and for the evaluation of safe approaches to the carotid artery.

The horizontal head position was adopted in the unilateral anterior interhemispheric approach to treat an anterior communicating artery (ACoA) aneurysm. The patient was placed in the supine position. The patient's head was rotated to the right to orient the midline horizontally, and tilted 45 degrees superiorly. After bicoronal skin incision and bifrontal craniotomy, the dura on the right side (downside) was opened. Dissection of the right interhemispheric fissure allowed gravity to retract the right (downside) hemisphere, which fell away from the falx, while the falx supported the upside hemisphere. The present approach was used in three patients with ACoA aneurysm between January 2009 and April 2010. The aneurysms were adequately clipped with this approach. No complication related to the approach occurred. No patients exhibited anosmia after surgery. This approach is useful for ACoA aneurysms.

Between May 2000 and August 2009, we had 5 cases combined with cavernoma and developmental venous anomaly (DVA). In 3 of 5 cases, we removed the cavernoma. Because DVA plays a role in normal venous return, we must preserve the DVA during resection of the cavernoma. We report some surgical considerations to avoid injury of the DVA. In Case 1, a 40-year-old female presented with headache. Magnetic resonance imaging (MRI) showed a cavernoma in the parieto-occipital lobe. We selected a high parietal approach using a navigation system to confirm the location of the cavernoma and DVA. In Case 2, a 70-year-old female presented with cerebellar hemorrhage. MRI showed a cavernoma in the left cerebellopontine angle and DVA at the tentorial surface of the left cerebellar hemisphere. Using the lateral infratentorial supracerebellar approach, the DVA was confirmed and then the cavernoma was removed. In Case 3, a 31-year-old female presented with intracerebral hemorrhage. MRI showed 2 cavernomas in the left frontal lobe. We removed a hemorrhagic lesion by the interhemispheric approach with the horizontal head position. In all 3 cases, the cavernoma was totally removed and the DVA was preserved.

Background: Few multiple case studies of the effects of deep brain stimulation for camptocormia associated with Parkinson’s disease have been reported. Although deep brain stimulation was in some cases not effective against camptocormia, it is unclear in which types of patients it was effective in treating camptocormia. Objective: We treated 4 Parkinson’s disease patients with camptocormia and evaluated their paraspinal muscle status by computed tomography to specify the characteristics of cases of effective treatment. Methods: The 2 female and 2 male patients in this study were 60–69 years old, with a disease duration from onset to surgery of 7–13 years and a follow-up period of 18–40 months. The electrodes were implanted bilaterally in the subthalamic nuclei. Results: Camptocormia was improved in 3 cases, and was unchanged in the remaining case although other parkinsonian symptoms improved. The computed tomography number of paraspinal muscle in the unimproved patient was much smaller than that in the improved patients. Conclusions: A relationship may exist between improvement of camptocormia and severity of paraspinal muscle degeneration.

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5–15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity.

Object The intrinsic radioresistance of certain cancer cells may be closely associated with the constitutive activation of nuclear factor–kappa B (NF-κB) activity, which may lead to protection from apoptosis. Recently, nonapoptotic cell death, or autophagy, has been revealed as a novel response of cancer cells to ionizing radiation. In the present study, the authors analyzed the effect of pitavastatin as a potential inhibitor of NF-κB activation on the radiosensitivity of A172, U87, and U251 human glioma cell lines. Methods The pharmacological inhibition of NF-κB activation was achieved using pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Growth and radiosensitivity assays were performed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst 33258 staining, supravital acridine orange staining, and electron microscopy were performed utilizing 3 glioma cell lines with or without pitavastatin pretreatment to identify apoptosis or autophagy after irradiation. Results The growth of these 3 glioma cell lines was not significantly inhibited by pitavastatin at a concentration of up to 1 μM. Treatment with 0.1 μM of pitavastatin enhanced radiation-induced cell death in all glioma cell lines, with different sensitivity. Apoptosis did not occur in any pretreated or untreated (no pitavastatin) cell line following irradiation. Instead, autophagic cell changes were observed regardless of the radiosensitivity of the cell line. An inhibitor of autophagy, 3-methyladenine suppressed the cytotoxic effect of irradiation with pitavastatin, indicating that autophagy is a result of an antitumor mechanism. Using the most radiosensitive A172 cell line, the intracellular localization of p50, a representative subunit of NF-κB, was evaluated through immunoblotting and immunofluorescence studies. The NF-κB of A172 cells was immediately activated and translocated from the cytosol to the nucleus in response to irradiation. Pitavastatin inhibited this activation and translocation of NF-κB. Conclusions Autophagic cell death rather than apoptosis is a possible mechanism of radiation-induced and pitavastatin-enhanced cell damage, and radiosensitization by the pharmacological inhibition of NF-κB activation may be a novel therapeutic strategy for malignant gliomas.

【目的】脳卒中治療ガイドライン2004の発表前後で急性期脳梗塞診療の変化を検証する．【方法】2003年と2006年の各々2月1日～7月31日の6カ月間に富山県内の主要9病院へ入院した急性期脳梗塞患者を調査解析した．【結果】症例数は2003年293例/2006年237例．臨床病型は，ラクナ梗塞；39％/37％，アテローム血栓性脳梗塞；28％/30％，心原性脳塞栓症；21％/22％．心原性脳塞栓症では3時間以内の来院は34％ から57％ へ有意に増加した．しかし，2006年では発症3時間以内に来院した74例（31％）のうちrt-PA静注による血栓溶解療法は5例（2.1％）のみに施行された．治療開始前の病巣確認は43％ から52％ へ有意に増加し，MRI拡散強調画像の施行は54％ から92％ へ有意に増加した．【結論】ガイドライン発表後，臨床病型を考慮して治療が行われる傾向にあった．しかし，血栓溶解療法の実施率は未だ低かった．

OBJECTIVE: The neuroendoscope is playing an increasing role in the diagnosis and treatment of several types of lesions, in particular in the ventricular system. Hydrocephalus associated with intraventricular hemorrhage (IVH) is a good indication for neuroendoscopic surgery. We describe herein our experiences with 17 cases of IVH combined with hydrocephalus treated using a neuroendoscope. PATIENTS AND METHODS: The subjects comprised 17 patients with IVH combined with hydrocephalus treated in our department, including cases of thalamic hemorrhage (n=10), caudate hemorrhage (n=5), moya-moya disease (n=1), and dural arteriovenous fistula (n=1). We used a flexible fiberscope that was inserted into the anterior horn of the lateral ventricle. Hematoma was easily evacuated through the working channel of the neuroendoscope by manual maneuvers. Hematomas in the third ventricle, aqueduct and fourth ventricle could also be evacuated. With the addition of septostomy, hematomas in the contralateral lateral ventricle could also be evacuated. RESULTS: All patients underwent successful procedures with good outcomes. No permanent morbidity and mortality was associated with any neuroendoscopic procedures. Shunt insertion was required in 3 cases due to malabsorption of cerebrospinal fluid (CSF) in the chronic stage. CONCLUSIONS: Neuroendoscopic procedures with a flexible fiberscope for the removal of IVH allow resolution of the disturbed CSF circulation. This procedure improves the safety and accuracy of treatment for IVH combined with hydrocephalus.

Background It is said atheromatous plaque is located very focally, but there have been few reports regarding this matter. Various aspects of the pathogenesis of the development of atheromatous plaque at the carotid bifurcation have previously been discussed. We have noted the correlation of plaque localization with characteristics of the cervical carotid artery wall. Methods Morphological and histopathologic changes in the carotid bifurcation were examined in 72 cadaver cases with or without atheromatous plaque. We determined the level at which the wall structure changed to muscular artery from elastic artery and analyzed its influence on the development of atheromatous plaque. Result Atheromatous plaques at the distal site of the ICA extended within 0 to 37 mm from the carotid bifurcation. The proximal side of the CCA more than 5 mm away from the bifurcation was elastic artery, whereas the distal side of the ICA more than 15 mm from the bifurcation was muscular artery. The area of the carotid bifurcation between elastic artery and muscular artery was a transitional zone. Approximately 80% of them were located within 15 mm, and these areas were coincident with the transitional zone. Conclusion Most atheromatous plaque was located in the transitional zone. The arterial wall structure is related to the development of atheromatous plaque at the cervical carotid bifurcation.

A 34-year-old woman presented with segmental neurofibromatosis manifesting as a soft lump with a large cafe-au-lait macule on her occipital region and neck. Magnetic resonance imaging showed a thick skin tumor in the occipital region and posterior neck, and a suboccipital meningocele which seemed to have no association with her symptoms. Biopsy lead to a histological diagnosis of giant plexiform neurofibroma. During biopsy, massive local bleeding occurred and hemostasis was achieved by electrocautery and meticulous suture ligation. The postoperative course was uneventful and observation was continued for both the giant plexiform neurofibroma and the meningocele.

We report a case of oligoastrocytoma resembling dysembryoplastic neuroepithelial tumor (DNT) with malignant transformation. A 35-year-old woman presented with headache and generalized convulsion in May 2003. Magnetic resonance imaging (MRI) revealed an extensive left temporal lobe tumor. She underwent partial resection of the tumor under awake surgery, while preserving her language function. The surgical specimen showed that the majority of the tumor was composed of a glioneuronal element. However, there was also an abundant oligoastrocytoma component. Therefore, our first pathological diagnosis was oligoastrocytoma and DNT. She then underwent radiation therapy. The tumor recurred at the left temporal lobe in June 2005. She then underwent open biopsy. The pathological diagnosis was anaplastic oligoastrocytoma with a MIB-1 staining index of 79%. She received PAV (procarvazine, ACNU, and vincristine) chemotherapy, and the tumor subsided transiently. However, she died 3 years after the first operation. Although the histological findings of the first surgical specimen closely resembled those of DNT, radiologic findings and clinical course were different from those of DNT. The authors concluded that this tumor could be a malignant transformation of oligoastrocytoma mimicking DNT, and we wish to give warning that the presence of a glioneuronal component is not an absolute benign hallmark.

BACKGROUND AND PURPOSE: Selective venous sampling from the posterior portion of the cavernous sinus (CS) is recommended for the diagnosis of Cushing disease, because samples from the posterior portion yield higher adrenocorticotropic hormone (ACTH) levels than those from the anterior and middle portions. We prospectively assessed this intracavernous gradient of ACTH level to determine which site in the CS yields adequate sampling. MATERIALS AND METHODS: In 5 patients with Cushing syndrome, cavernous sinography was performed to assess drainage pattern of the CS. Sampling was performed from the anterior, middle, and posterior parts of the CS, inferior petrosal sinus (IPS), and the peripheral vein. The ratio of the concentration in CS and IPS to that in peripheral blood plasma (C/P ratio) was calculated. RESULTS: Cavernous sinography showed that the main drainage route was the IPS in 6 sides and that the pterygoid plexus (PP) was developed to the same extent as the IPS in 3 sides. In 1 patient, the CS drained mainly to the PP. In 1 patient with an ectopic lesion, no increase in ACTH level was detected. In 3 of 4 patients with Cushing disease, the highest C/P ratio was obtained from the posterior portion. In 1 patient whose main drainage route was the PP, the highest C/P ratio was obtained from the anterior portion. In this case, sampling data from the posterior portion and the IPS yielded false-negative results. CONCLUSION: Understanding the drainage patterns of the CS is essential for interpretation of sampling data from the CS and avoiding false-negative results.

A 22-year-old woman presented with a basal encephalocele associated with hypoplasia of the internal carotid artery (ICA) manifesting as a 6-year history of decreased vision in the right eye. She underwent encephalo-arterio-synangiosis under a diagnosis of hypoplasia of the ICA at age 6 years. Magnetic resonance imaging showed the encephalocele medial to the right temporal lobe. Frontotemporal craniotomy was performed for resection of the encephalocele and repair of the defect of the skull base. The pathogeneses of these developmental anomalies were probably related to developmental failure of the embryonic primordium during the 4th and 10th weeks.

A 54-year-old woman presented a midline clival tumor manifesting as right abducens palsy in May 1997. Magnetic resonance (MR) imaging revealed a midline clival tumor. She underwent surgery twice with the transsphenoidal approach and gamma knife surgery for residual tumor. The histological diagnosis was chordoma. MR imaging revealed that the tumor had extended to the right cerebellopontine angle, with spinal seeding in February 2002. She underwent partial removal of the right cerebellopontine angle tumor. The histological diagnosis was chordoma with slight nuclear atypism. She died 5 years and 5 months after the first gamma knife surgery. Autopsy revealed multiple areas of spinal seeding. Histological examination confirmed malignant transformation with unique epithelial characteristics, possibly caused by gamma knife surgery.

The prognostic factors were retrospectively analyzed in 30 patients aged 70 years or over with supratentorial malignant gliomas treated by surgery in our hospital. The histological diagnosis was confirmed as grade 3 in 13 patients and grade 4 in 17. Seventeen patients received adjuvant radiation therapy. Only 10 patients underwent chemotherapy. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. Univariate analysis showed preoperative Karnofsky performance status (KPS) score of 70 or greater and radiation therapy were significantly associated with longer survival. However, multivariate analysis revealed that preoperative KPS score of 70 or greater was the only independent prognostic factor and radiation therapy lost its significance due to selection bias. Neurological deterioration and medical complications occurred in six and seven patients, respectively. Performance status rather than histological grade is the key prognostic factor in elderly patients with supratentorial malignant gliomas. Patients with good preoperative KPS score should be aggressively treated with extensive resection and radiotherapy.

症例1 : 63歳, 男性. 右完全片麻痺, 全失語にて発症. CTにて明らかな異常を認めず, 脳血管撮影にて巨大塞栓子による左頚部内頚動脈閉塞を認めた. 血栓の脇にカテーテルを進め末梢側で造影したところ, 内頚動脈分岐部で閉塞を認めた. 末梢部の血栓溶解を施行し側副血行路を開通させ, 症状の回復が見られたが, 2日後に頚部血栓が末梢へ移動し, 高度の後遺症が残存した. 症例2 : 79歳, 男性. 右不全片麻痺, 失語にて発症. 脳血管撮影では, 巨大塞栓子による左頚部内頚動脈閉塞を認め, 側副血行により左中大脳動脈が描出された. 左内頚動脈が逆行性に錐体部まで描出されていたため, 緊急で頚動脈血栓摘出術を施行し, 術後, 症状の改善が見られた. 巨大塞栓子による急性期頚部内頚動脈閉塞症は稀な疾患であり, 血栓溶解療法による再開通が困難で, 開通した場合でも末梢塞栓を起こしやすい. われわれが経験した2症例を踏まえ, 治療フローチャートを提唱する.

The intracranial internal carotid artery (ICA) is well known to be a muscular artery that lacks an external elastic lamina. Elastic fibers are concentrated inside the internal elastic lamina of the wall of the intracranial ICA. We examined a portion where the external elastic lamina disappeared in the course of the ICA. We extirpated 32 intracranial ICA specimens from 50 cadavers. We made running specimens of the ICA every 3 mm and stained them using the Elastica van Gieson method and then investigated a portion where the external elastic lamina disappeared in the wall of the ICA. We also examined the intimal thickness of various portions of the ICA. We identified both the internal elastic lamina and the external elastic lamina in the petrous portion of the ICA in all cases. In the intradural portion of the ICA, the external elastic lamina was not recognized and only the internal elastic lamina was seen in all cases. In 31 of the 32 specimens (98%), the external elastic lamina disappeared in the horizontal portion of the cavernous portion of the ICA. The intimal thickness of the ICA was recognized in 23/32 specimens. The starting point of the intimal thickness approximated the portion where the external elastic lamina disappeared. The external elastic lamina of the ICA disappeared at the horizontal portion of the cavernous sinus, which was a site where intimal thickness was frequently observed. Changes in the elasticity of the wall of the intracranial ICA may therefore cause atherosclerotic changes in the ICA.

The rate of head injury is 1.86-6 times higher for snowboarding than for skiing. Detailed data about the usefulness of a helmet or knit cap for protecting against serious head injuries have not been reported. The present study evaluated the use of a helmet or knit cap for preventing head injuries. Questionnaire data were collected from 1,190 consecutive patients in a hospital during the 1999/2000-2002/2003 winter seasons at Uonuma ski resort, Niigata, Japan. Patients were divided into the helmet, knit cap, and no cap groups. Upper technical level was highest and jumping as the cause of injury was most frequent in the helmet group. After adjustment for other confounders, there was a significant negative association between the occurrence of serious head injury during snowboarding and female sex (adjusted odds ratio 0.55, 95% confidence interval 0.421-0.718, p < 0.0001) and a significant positive association between serious head injury and jumping (adjusted odds ratio 2.25, 95% confidence interval 1.48-3.43, p = 0.0001). Among snowboarding maneuvers, only jumping showed a significant negative association between wearing of a helmet or knit cap and the occurrence of serious head injury (p = 0.036). Snowboarders who wear helmets might attempt dangerous maneuvers causing injuries. Wearing of a helmet or knit cap protected against serious head injuries on jumping. Every snowboarder should wear a helmet or knit cap on jumping to prevent head injury.

BACKGROUND Carotid stenosis is known to have negative impacts on cognitive function. However, it is still unclear through which mechanisms cognitive function is impaired in patients with carotid stenosis. This study was aimed to clarify the impact of cerebral hemodynamics on cognitive function in carotid stenosis. METHODS This prospective study included totally 109 patients with carotid stenosis who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS). Using N-isopropyl-p-[123I]-iodoamphetamine SPECT, cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were quantitatively measured in all patients before and after CEA/CAS. Based on preoperative data, the patients were categorized into three groups: Type 1 (CBF ≥32 mL/min/100 g, CVR ≥10%), Type 2 (CBF ≥32 mL/min/100 g and CVR

Background Accumulating evidence indicates that cancer stem cells (CSCs) drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS) forming model, to generate a population in which glioma stem cells (GSCs) become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability. Methodology/Principal Findings To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres). Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone). Log-log plots of distributions of clone sizes yielded a good fit (r>0.90) to a straight line (log(% total clones) = k*log(#cells/clone)) indicating that the system follows a power-law (y = xk) with a specific degree exponent (k = −1.42). Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = −1.01 to −1.17). Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law-dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM), suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population. Conclusions/Significance Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous glioma stem cell populations. That the data always fit a power-law suggests that: (i) clone sizes follow continuous, non-random, and scale-free hierarchy; (ii) precise biologic rules that reflect self-organizing emergent behaviors govern the generation of neurospheres. That the power-law behavior and the original GS heterogeneity are maintained over multiple passages indicates that these rules are invariant. These self-organizing mechanisms very likely underlie tumor heterogeneity during tumor growth. Discovery of this power-law behavior provides a mechanism that could be targeted in the development of new, more effective, anti-cancer agents.

Object. Endoscopic third ventriculostomy (ETV) has been widely performed for the treatment of noncommunicating hydrocephalus. In cases of hydrocephalus in conjunction with deformed and complex ventricular anatomy, it is preferable to use a rigid-rod endoscope for ETV, because the excellent visibility provided by this instrument yields a smooth and correct orientation in the ventricle. The authors report on ETV procedures in which they used a transparent endoscopic sheath that has a common channel in which a rigid-rod endoscope and an instrument can be inserted. Methods. In 15 cases of noncommunicating hydrocephalus, a transparent endoscopic sheath and a rigid endoscope were used for ETV. In 11 of the 15 patients, the diameter of the foramen of Monro and the width of the third ventricle were greater than 5 mm, and thus a transparent endoscopic sheath and a rigid endoscope could be smoothly introduced through the foramen of Monro and an ETV successfully performed. Four patients had congenital or acquired narrowing of the foramen of Monro and an anatomically deformed ventricular system. In three of the patients, opening of the narrowed foramen and an ETV were successfully performed using the transparent endoscopic sheath under direct visualization through the rigid-rod endoscope. Conclusions. A transparent endoscopic sheath increases safety by offering a corridor to the third ventricle. It also provides excellent visibility without troublesome bleeding from tissues surrounding the foramen of Monro during endoscopic procedures in which a rigid endoscope is used.

A cDNA clone similar to human serine dehydratase (SDH) is deposited in the GenBank/EMBL databases, but its structural and functional bases remain unknown. Despite the occurrence of mRNA, the expected protein level was found to be low in cultured cells. To learn about physicochemical properties of the protein, we expressed the cDNA in Escherichia coli, and compared the expressed protein with that of a hepatic SDH. The purified protein showed l -serine and l -threonine dehydratase activity, demonstrating to be an isoform of SDH. However, their Km and Vmax constants were different in a range of two-order. Removal of Pro128 from the hepatic SDH consisting of 328 residues, which is missing in the corresponding position of the isoform consisting of 329 residues, significantly changed the Michaelis constants and Kd value for pyridoxal 5′-phosphate, whereas addition of a proline residue to the isoform was without effect. These findings suggest the difference in the structures of the active sites of the two enzymes. Another striking feature was that the expressed level of the isoform in E. coli was 7-fold lower than that of the hepatic SDH. Substitution of Val for Leu287 in the isoform dramatically increased the protein level. The high yield of the mutated isoform was also confirmed by the in vitro transcription and translation experiment. The poor expression of the isoform could be explained by the more stable secondary structure of the mRNA than that of the hepatic SDH mRNA. The present findings may provide a clue as to why the protein level in cultured cells is low.

To evaluate complications and their prevention in endovascular treatment of dural arteriovenous fistulas (AVFs), we analyze the medical records of 105 patients (47 men 58 women, mean age of 64.2 years) treated with endovascular procedures from 1990 to 2003 in our clinic. Dural AVF was located at the cavernous sinus in 43 patients, transverse-sigmoid sinus in 43, and other regions in 19. There were 201 procedures, including 97 transarterial embolizations (TAE), 84 transvenous embolizations (TVE), 17 surgical TVEs, and 3 sinoplasties. Twelve complications were recorded in 10 patients (3 cavernous sinus, 5 transverse-sigmoid sinus, and 2 craniocervical junction lesions). The complications were divided into 4 categories: wrong strategy (1 case), venous thrombosis (2 cases), procedural error (7 cases), and general condition (1 case; pulmonary embolism). One of the superficial middle cerebral veins was obliterated after coiling of the cavernous sinus in 1 patient, resulting in a mild transient hemiparesis (wrong strategy). The syndrome of paradoxical worsening occurred in 1 patient with cavernous sinus dural AVF after TAE (venous thrombosis of the central retinal vein). One patient with sigmoid sinus dural AVF suffered long-lasting dizziness after TVE. Ipsilateral endolymphatic hydrops were observed and speculated to be a causative factor of the patient's dizziness (venous thrombosis of the inner ear). The procedural error included trigeminal nerve palsy due to excess coil packing (1 case in TVE), ischemic cranial neuropathy (3 cases in TAE), and migration of the embolic materials via the feeding arterial collateral network (3 cases in TAE). Morbidity and mortality were 4.8% and 1.0%, respectively. We discuss causes and preventive measures.

Duplication of the middle cerebral artery is an anomalous vessel arising from the internal carotid artery. There have only been 14 reports of aneurysms arising from the origin of a duplication of the middle cerebral artery and 5 of these patients had multiple aneurysms. Aneurysms at this site have a high rupture rate compared to aneurysms in other locations and aggressive management is indicated.

A novel acidic polysaccharide, nostoflan, was isolated from a terrestrial cyanobacterium, Nostoc flagelliforme. Nostoflan exhibited a potent anti-herpes simplex virus type 1 (HSV-1) activity with a selectivity index (50% cytotoxic concentration/50% inhibitory concentration against viral replication) of 13,000. Sugar composition and methylation analyses revealed that it was mainly composed of -->4)-D-Glcp-(1-->, -->6,4)-D-Glcp-(1-->, -->4)-D-Galp-(1-->, -->4)-D-Xylp-(1-->, D-GlcAp-(1-->, D-Manp-(1--> with a ratio of ca. 1:1:1:1:0.8:0.2. Two pyridylaminated oligosaccharides were prepared by partial acid hydrolysis and pyridylamination. On the basis of MALDI-TOF-MS and NMR analyses, they were found to be beta-D-Glcp-(1-->4)-D-Xyl-PA and beta-D-GlcAp-(1-->6)-beta-D-Glcp-(1-->4)-D-Gal-PA. From these results, nostoflan might be mainly composed of the following two types of sugar sequence: -->4)-beta-D-Glcp-(1-->4)-D-Xylp-(1--> and -->4)-[beta-D-GlcAp-(1-->6)-]-beta-D-Glcp-(1-->4)-D-Galp-(1-->. Besides anti-HSV-1 activity, nostoflan showed potent antiviral activities against HSV-2, human cytomegalovirus, and influenza A virus, but no activity against adenovirus and coxsackie virus was observed. Therefore, nostoflan has a broad antiviral spectrum against enveloped viruses whose cellular receptors are carbohydrates. Furthermore, nostoflan showed no antithrombin activity, unlike sulfated polysaccharides.

Object. Increased platelet consumption is expected in patients with cerebral vasospasm, according to data from clinical and experimental studies. The authors investigated sequential changes in platelet counts in patients with subarachnoid hemorrhage (SAH) and the difference in platelet consumption between patients with and those without symptomatic vasospasm (SV). Variables related to platelet count as well as other clinical and radiological variables were analyzed as independent predictors of SV. Methods. One hundred consecutive patients who had undergone surgery within 48 hours after SAH onset were entered in the study. Clinical and radiological variables and blood cell counts, including red blood cells, white blood cells, and platelets, after SAH were retrospectively examined. Twenty of these variables were entered into univariate and multivariate analyses to determine predictors for SV. After SAH, the platelet count decreased to a minimum and then increased rapidly to levels greater than those recorded on admission. This change was specific to SAH, and platelet consumption was more severe in patients with SV than in those without. There were three independent predictors of SV: a ratio of the lowest platelet count and the admission count greater than 0.7 (odds ratio [OR] 0.322, 95% confidence interval [CI] 0.124–0.834, p = 0.0196) and a history of hypertension (OR 0.338, 95% CI 0.126–0.906, p = 0.0311) were negatively significant (that is, decreases the occurrence of SV), and a Fisher Grade 3 (OR 4.42, 95% CI 1.48–13.2, p = 0.0077) was positively significant (that is, increases the occurrence of SV). Conclusions. The association between a decrease in platelet count and the occurrence of SV indicates the important role of platelets in the pathophysiology of vasospasm following SAH.

Inflammatory reaction is very important for formation of the neomembrane of chronic subdural hematoma (CSDH). The present study evaluated medical treatment with the platelet-activating factor receptor antagonist, etizolam, for the resolution of CSDH, and the factors indicating surgery or conservative therapy. Alternate patients were assigned to the etizolam group or control group without medical treatment. Patients in the etizolam group received 3.0 mg etizolam per day for 14 days. A total of 53 patients were followed up for at least 6 months. Univariate analysis of differences in demographic characteristics, clinical findings, and initial computed tomography (CT) findings, and multiple logistic regression analysis of the relationship between etizolam treatment and requirement for surgery using age, sex, low density of hematoma on CT, and paresis as confounders were performed. Etizolam treatment (adjusted odds ratio [OR] 0.156, 95% confidence interval [CI] 0.024-0.999, p = 0.049) was negatively correlated with requirement for surgery. Low density of hematoma (adjusted OR 0.125, 95% CI 0.019-0.846, p = 0.033) was found to be an independent negative predictor, and paresis as an initial symptom (adjusted OR 6.35, 95% CI 1.04-38.7, p = 0.045) was an independent positive predictor of requirement for surgery. Etizolam administration can promote the resolution of CSDH, especially at the stage of hygroma appearing as low density on CT. Surgery is recommended if the patient presents with paresis.

Pseudo-occlusion of the internal carotid artery has been subdivided from carotid near occlusion, and defined as a more severely stenosed group. Angiographic characteristics of pseudo-occlusion include “string like” residual filling of the internal carotid artery (ICA) beyond the carotid bifurcation, and retrograde filling of the ICA via the ophthalmic artery reaching the skull base. Eight patients with pseudo-occlusion were treated with carotid endarterectomy. Clinical features, radiological findings, and operative records were retrospectively examined. Four patients presenting progressing strokes and 1 presenting minor stroke were treated in an acute period, and 2 patients presenting minor strokes and 1 presenting transient ischemic attack (TIA) in a chronic period after their last ischemic attack. All patients had suffered from recent TIA confined to the ipsilateral carotid artery territory. The pattern of ischemic brain lesions evaluated by means of computed tomography and magnetic resonance imaging revealed that most of the subjects had a hemodynamic pathogenesis. Ischemic brain lesions suggesting embolism were also found in 2 cases in an acute period. CEA was successfully performed in all patients. Intraoperatively, a patent but collapsed ICA distal to a localized atheromatous plaque was recognized in all cases. CEA is benefit for patients with pseudo-occlusion of the internal carotid artery.

Heparin cofactor II functions as a physiological inhibitor of thrombin activity. The rate of inactivation of thrombin by heparin cofactor II is increased in the presence of dermatan sulfate, which is produced by fibroblasts or smooth muscle cells. To elucidate the role of heparin cofactor II in the extravascular cells, we induced expression of heparin cofactor II in cultured human fibroblasts or vascular smooth muscle cells using adenovirus-mediated gene transfer. After infection of adenovirus vector, these cells secreted heparin cofactor II protein into culture medium. The expressed heparin cofactor II formed the complex with exogenous thrombin and inhibited the proteolytic activity of thrombin. Expression of heparin cofactor II by infection of adenovirus vector inhibited thrombin-induced tissue-type plasminogen activator and interleukin-6 releases from fibroblasts and thrombin-induced interleukin-6 release from vascular smooth muscle cells. These findings show that fibroblasts and vascular smooth muscle cells expressing heparin cofactor II are resistant to thrombin-induced cellular responses.

It has been proved that development of the atheromatous plaque at the carotid bifurcation is related with its variability. We examined a correlation of plaque localization with characteristics of the cervical carotid artery wall. We studied the thickness and length of the atheromatous plaque of the carotid bifurcation and wall characteristics of the carotid artery. Our results suggest the atheromatous plaque localized at the carotid bifurcation, restricted elastic artery and transitional zone that changed to muscular artery.

Place cells in the rodent hippocampal formation (HF) are suggested to be the neural substrate for a spatial cognitive map. This specific spatial property of the place cells are regulated by both allothetic cues (i.e., intramaze local and distal cues) as well as idiothetic sensory inputs; the context signaled by the distal cues allows local and idiothetic cues to be employed for spatial tuning within the maze. To investigate the effects of distal cues on place-related activity of primate HF neurons, 228 neurons were recorded from the monkey HF during virtual navigation in a similar situation to a rodent water maze, in which distal cues were important to locate the animal's position. A subset of 72 neurons displayed place-related activity in one or more virtual spaces. Most place-related responses disappeared or changed their spatial tuning (i.e., remapping) when the arrangements of the distal cues were altered/moved in the virtual spaces. These specific features of the monkey HF might underlie neurophysiological bases of human episodic memory. © 2005 Wiley-Liss, Inc.

A 22-year-old woman presented with a rare case of multiple epidermoid cysts located in the pineal and extracranial regions. Magnetic resonance (MR) imaging showed a lesion in the pineal region as hypointense on the T(1)-weighted image and hyperintense on the T(2)-weighted image, without enhancement. Neuroendoscopic treatment was performed under a diagnosis of pineal cyst. However, the cyst wall was too thick to perforate, although third ventriculostomy was performed. Diffusion-weighted MR imaging demonstrated the lesions in the pineal and extracranial regions as marked hyperintensity. The diagnosis was epidermoid cyst. Subsequently, neuroendoscopic treatment of the pineal epidermoid cyst was performed. Careful preoperative diagnosis of epidermoid cysts based on diffusion-weighted MR imaging is required.