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We report a 5 year-old boy with primary anaplastic pleomorphic xanthoastrocytoma (PXA) with whole neuroaxis dissemination at diagnosis who experienced the sudden onset of generalized convulsion. Head- and spinal magnetic resonance imaging (MRI) showed widespread gadolinium (Gd)-enhanced lesions extending to the bilateral frontal- and medial temporal lobes and the spinal cord. Subsequent MRI study demonstrated that the lesion size increased without any neurological deterioration. Under a histopathologic diagnosis of anaplastic PXA he underwent adjuvant chemotherapy consisting of 12 cycles of carboplatin and vincristine. The patient is alive without any neurological deficits; follow-up MRI showed that the lesions remained stable during 18 months of chemotherapy. We report a very rare pediatric case of primary anaplastic PXA with dissemination involving the entire neuroaxis at the time of diagnosis.

非心原性脳梗塞症例に対して，チクロピジンからクロピドグレルに切り替えた47例に対して，安全性，発作予防効果，血小板凝集能の変化につき検討した．クロピドグレル切り替え後1例で軽度の肝機能障害，3例で皮疹が出現したが何れも軽症であった．1例で不安定狭心症が出現したが残りの46例では脳梗塞の再発および心血管イベントの出現はなかった．血小板凝集能を35例で切り替え前後に測定したところ，ADP凝集grading curveのgradeが変化しなかった症例は17例（48.6％），切り替え前より凝集能がより抑制された症例が9例（25.7％），凝集能が亢進した症例が9例（25.7％）見られた．しかしこのうちの7例はgrade −1あるいは0に復した症例で，2例のみがgradeが＋1以上になった．以上よりチクロピジンからクロピドグレルへの切り替え症例では安全性，血小板凝集能を含む効果の面でも良好な結果を得た．

A 69-year-old man presented with a rare case of retinal artery embolization, which occurred as a complication of carotid angioplasty and carotid artery stenting performed for recurrent cerebral infarction. Magnetic resonance imaging and angiography showed right internal carotid artery stenosis with ulceration. Carotid angioplasty and carotid artery stenting were performed using the distal protection system with the PercuSurge GuardWire. However, just after dilation, the patient complained of ocular pain and blurred vision on the right, which was subsequently diagnosed as retinal artery embolization. Heparin was given for 15 hours after stenting, and aspirin and ticlopidine medication were continued. The patient received hyperbaric oxygen therapy for 1 week. The patient's blurred vision gradually improved, but visual field defect remained. Debris was probably flushed into the external carotid artery, and passed through an anastomosis into the ophthalmic artery, resulting in retinal artery embolization.

We present the results and pitfalls of surgery for dural arteriovenous fistula (dAVF). Between 1976 and 2007, we treated 257 patients with dAVF. Among them, 19 (13 men, 6 women) underwent direct surgery including drainer ligation and sinus resection. Their ages ranged from 48 to 82 years (mean 62 years). Of 19 dAVFs, 10 were located in the anterior fossa (AF) dural arteriovenous fistula, 1 in the cavernous sinus (CS), 5 were tentorial (T) and 3 were transverse-sigmoid sinus (TS) dAVF. The 3 patients with TS dAVF underwent resection of an isolated sinus, and the other 16 were treated by ligation of the draining vein; in 9 of these, transarterial embolization was subsequently performed. In 18 patients (95%), there was postoperative confirmation of shunt obliteration. After direct surgery, 2 patients with T dAVF suffered cerebral hemorrhage. In 1, T dAVF retrograde flow to petrosal veins occurred after clipping of the draining vein. In 14 patients, the outcome was good, 2 each were moderately or severly disabled and 1 patient survived in a vegetative state. Although dAVF surgery is an effective treatment, attention must be paid to cerebral hemorrhage and the development of a new draining vein in patients with T dAVF.

Purpose: We evaluated the usefulness of rating diffusion-weighted images (DWI) using a semiquantitative score modified from the Alberta Stroke Programme Early CT Score (ASPECTS) to predict deterioration of neurological symptoms in patients with hyperacute ischemic stroke who had undergone thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). Materials and Methods: We examined 22 patients with acute stroke (14 men, 8 women, mean age 72.5 years) treated with intravenous rt-PA. All were assessed using the National Institutes of Health Stroke Scale (NIHSS) and underwent emergent magnetic resonance (MR) imaging within 3 hours and 24 hours of stroke onset. Patients were divided into a deteriorated group (16 patients), in which NIHSS scores were increased after thrombolysis, and a non-deteriorated group (6 patients). We compared the DWI score, ASPECTS, and volume of hyperintense ischemic lesion on DWI (DWI volume) of the 2 groups and examined correlations between these scores and initial NIHSS score or DWI volume. Results: The DWI score and ASPECTS tended to be lower in the deteriorated group than the non-deteriorated group. In addition, with a cutoff value≤7, the DWI score could discriminate the deteriorated group from the non-deteriorated group with a sensitivity of 50% and specificity of 87.5%, whereas for ASPECTS, sensitivity was 50% and specificity, 81.2%. The DWI score, ASPECTS, and DWI volume had no correlation with NIHSS score but weak negative correlations with the DWI volume (P

Proinflammatory and anti-inflammatory cytokines may play a pivotal role in cerebral inflammation, which is implicated in the development of brain injury. Systemic cytokine release is mediated by the sympathetic nervous system and catecholamines. The aim of this study was to investigate which parameters, among plasma levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha) and the levels of the catecholamines, epinephrine and norepinephrine, contribute to the clinical outcome in acute stroke patients.Thirty-seven acute stroke patients (ischemic, n = 19; hemorrhagic, n = 18) were enrolled. All of them were admitted to our hospital within 8 h after stroke onset. Neurological status was evaluated by a modified National Institute of Health Stroke Scale (mNIHSS) on admission and by a modified Rankin Scale (mRS) at 1 month. An mRS score of 3 or more at 1 month was considered to indicate poor outcome. Serum samples for the cytokine and catecholamine measurements were collected on admission. Plasma levels of IL-1beta, IL-6, IL-10, and TNF-alpha were determined by an enzyme-linked immunosorbent assay (ELISA) method and epinephrine and norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC).In the ischemic stroke patients, poor outcome was noted in 9 (47%). There were no significant differences in cytokine or catecholamine concentrations between patients with poor and good outcomes, and there was no association between clinical outcome and cytokine and catecholamine concentrations. In the hemorrhagic stroke patients, poor outcome was noted in 10 (56%). IL-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54).In ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.

Background Angiotensin II type 1 (AT1) receptor blockers decrease ischemia by mechanisms dependent on and independent of arterial blood pressure in hypertensive rats and AT1-R knockout mice, respectively. However, the detailed mechanisms underlying the effects of AT1 receptor blockers remain unclear. Aims To elucidate the systemic and focal effects of AT1 receptor blockers against cerebral ischemia in in-vivo and in-vitro studies. Methods Normotensive Wistar rats were treated for 2 weeks with 0.5 or 1 mg/kg candesartan cilexetil and then subjected to 2-h middle cerebral artery occlusion-reperfusion. Human umbilical endothelial cells were stimulated with the active form of candesartan and angiotensin II in the absence and presence of an angiotensin II type 2 (AT2) receptor antagonist. Results In candesartan-pretreated hypotensive and nonhypotensive rats, blood pressure was moderately increased during middle cerebral artery occlusion and fell gradually to the baseline after the reperfusion; it remained elevated in the control even after the reperfusion occlusion. Candesartan treatment resulted in a decrease in the cortical infarct volume and oxidative damage, the hypoxic status was improved, and the expression of repair-associated and growth-associated proteins in the cortical penumbra was augmented. Candesartan also increased the eNOS mRNA level and the lumen size of the middle cerebral artery. In human umbilical endothelial cells, candesartan increased the eNOS protein level AT2-R dependently, inhibited the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and angiotensin II-induced intracellular reactive oxygen species and nitric oxide, and promoted the extracellular release of nitric oxide, suggesting that it augmented the bioavailability of nitric oxide. Conclusion Among the mechanisms candesartan exerts in its protection against cerebral ischemia, restoration of endothelial function may represent an attractive therapeutic goal to address cerebral ischemia.

We report the characteristics, diagnosis and treatment of dural arteriovenous fistula (DAVF) of the hypoglossal canal in nine patients with this relatively rare vascular disorder. Of 248 patients with intracranial DAVFs managed at our institution, nine patients (3.6%; four men, five women; mean age 62 years) were diagnosed with hypoglossal canal DAVF. We investigated patient characteristics with respect to clinical symptoms, neuroradiological findings, efficacy and complications related to endovascular treatment. Seven patients had experienced head injury. All patients presented with pulsatile tinnitus. One patient displayed ipsilateral hypoglossal nerve palsy before treatment. MR angiography showed a “magic wand” appearance between the affected hypoglossal canal and the internal jugular vein in four patients. Angiography demonstrated an AV fistula on the medial aspect of the superior jugular bulb, mostly arising from the bilateral occipital, ascending pharyngeal and vertebral arteries with drainage to the internal jugular vein via the anterior condylar vein. Contralateral carotid injection accurately clarified the shunting point. Five patients underwent endovascular treatment: transarterial embolization (TAE; n = 2), transvenous embolization (TVE; n = 2), and TAE/TVE (n = 1). Complete shunt obliteration was achieved in four patients and shunt reduction in one. The remaining four patients were treated conservatively and the shunt had disappeared at follow-up. Postoperative hypoglossal nerve palsy occurred in one patient after TVE, possibly due to coil overpacking. The incidence of hypoglossal canal DAVF was not very low in our series. Contralateral carotid injection is an essential examination to provide an accurate diagnosis. TVE should be considered when access is available, although TAE is also appropriate for shunt reduction.

もやもや病の中で片側もやもや病（疑診例）は異なる病態として区別され，家族内発生の報告はほとんどない．我々は疑診例の母親を有する両側もやもや病（確診例）姉妹の家系を経験した．母親は31歳時に脳室内出血にて発症した右側の疑診例である．左内頸動脈終末部に狭窄は認められず16年間経過後進行は認められていない．19歳の長女と12歳の次女は，両側の内頸動脈終末部に狭窄を認め，確診例と診断された．姉妹共にそれぞれ両側の直接または，間接吻合術を施行した．今回我々の経験した家系は疑診例と確診例の病態を考察する上で，示唆に富む症例であると考えられたので報告する．

Object Intracranial aneurysms are the leading cause of subarachnoid hemorrhage, which is associated with high morbidity and mortality rates. Despite advances in the microsurgical and endovascular treatment of intracranial aneurysms, little is known about the mechanisms by which they originate, grow, and rupture. To clarify the series of early events leading to formation of intracranial aneurysms, the authors compared aneurysmal morphological changes on vascular corrosion casts with parallel pathological changes in the cerebral arteries of rats. Methods The authors induced cerebral aneurysms by renal hypertension and right common carotid artery ligation in 40 male Sprague–Dawley rats; 10 intact rats served as the controls. The anterior cerebral artery–olfactory artery bifurcation was assessed morphologically by using vascular corrosion casts of Batson plastic reagent and immunohis-tochemically by using antibodies against endothelial nitric oxide synthase, α–smooth muscle actin, macrophages, and matrix metalloproteinase–9. Results Surgically treated rats manifested different degrees of aneurysmal changes. Based on these staged changes, the authors propose that the formation of intracranial aneurysms starts with endothelial injury at the apical intimal pad (Stage I); this leads to the formation of an inflammatory zone (Stage II), followed by a partial tear or defect in the inflammatory zone. Expansion of this defect forms the nidus of the intracranial aneurysm (Stage III). Conclusions This is the first study to demonstrate the in vivo mechanisms of intracranial aneurysm formation. The inflammatory response that follows endothelial injury is the basic step in the pathogenesis of these lesions. In this study the investigators have expanded the understanding of the origin of intracranial aneurysms and have contributed to the further development of measures to prevent and treat aneurysms.

We report a 17-year-old male with disseminated intracranial choriocarcinoma at the basal ganglia whose consciousness level was very low at diagnosis. He received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy prior to radical excision of the tumor. Postoperatively he was treated with three courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and etoposide (VP-16)) and peripheral blood stem-cell transplantation. This combination of therapies resulted in tumor regression on MRI and remarkable improvement in his neurological condition. Ours is the first report of the effectiveness of NAT followed by radical surgery in a patient with disseminated primary intracranial choriocarcinoma.

Craniopharyngiomas are 5–10 % of all pediatric tumors, but are seldomly encountered in the perinatal period. Only seven instances of a truly antenatal diagnosis of a congenital craniopharyngioma that subsequently underwent radical surgery have been reported. We present the case of a patient who received the diagnosis of a suprasellar tumor during the prenatal period and received radical surgery. We report a case of a neonatal craniopharyngioma treated surgically. The pregnancy progressed uneventfully until a routine ultrasound at 37 weeks of gestation showed a 15 × 15 mm high echoic mass in the center of the fetal head. Neonatal Gd-enhanced T1-weighted MRI at 5 days of life showed a homogenously enhanced mass (16×22×15 mm) in the sellar and suprasellar lesion. As the tumor showed rapid growth at the 3rd month of life, the patient underwent a surgical treatment and the mass was totally removed. Three years later, the physical and mental development of the patient was normal, and Gd-MRI studies showed no tumor recurrence. The present case is the eighth case of a truly antenatal diagnosis of a craniopharyngioma that underwent successful radical surgery. Craniopharyngioma is a benign tumor and thought to be a slow growing tumor in childhood. The results of radical surgery were very poor, and the mortality and morbidity rates were high in the previous reports due to the huge size of tumor at operation. The present case demonstrated the rapid growth in short interval of Gd-MRI. This is the first report of tumor kinetics of congenital craniopharyngioma with previous reports. The calculated tumor doubling time in our case was 37 days.

Purpose In the imaging of intra-axial brain tumors, we sometimes found areas of high signal intensity around the enhanced tumor lesions on arterial spin labeling (ASL) magnetic resonance (MR) imaging. We undertook this study to investigate the relationship between high signal intensity on ASL imaging outside the area of contrast enhancement (CE) and histological diagnosis of intra-axial brain tumors. Methods We examined images from 28 consecutive patients with intra-axial brain tumors who underwent ASL and CE MR imaging-three with low grade glioma (LGG), 13 with high grade glioma (HGG), six with metastasis, and six with primary central nervous system lymphoma (PCNSL)-and divided imaging findings into an "ASL dominant" group when hyperintensity on ASL was found outside the CE area and a "CE dominant" group when hyperintensity on ASL was not found outside the area of enhancement. We then analyzed the relationship between imaging findings and the histological diagnosis of the tumors. Results Four cases were excluded because of poor quality of ASL images, 7 cases were classified as ASL dominant, and 17 cases were classified as CE dominant. The histological diagnoses of ASL dominant cases were LGG in 3 cases, HGG in 3 cases, and PCNSL in one case. Those of CE dominant cases were HGG in 10 cases, metastasis in 5 cases, and PCNSL in 2 cases. All cases with brain metastasis were classified as CE dominant. Conclusion The high signal intensity outside the area of contrast enhancement is probably caused by increased perfusion or vascular proliferation, which indicates the presence of glioma or PCNSL and not metastasis. This finding indicates a new utility for ASL images in the diagnosis of brain tumors as a supplement to the conventional measurement of perfusion obtained from ASL images.

T1-Cube (GE HealthCare) is a relatively new 3-dimensional (3D) fast spin-echo (FSE)-based magnetic resonance (MR) imaging sequence that uses a variable flip angle to acquire gap-free volume scans. We compared the gadolinium enhancement characteristics of a heterogeneous population of brain tumors imaged by T1-Cube and then 3D fast spoiled gradient recall acquisition in steady state (3D FSPGR) 3-tesla MR imaging to identify the superior modality for specific diagnostic purposes.We examined 61 lesions from 32 patients using the 2 sequences after administration of gadopentetic acid (Gd-DTPA; 0.1 mmol/kg). Two neuroradiologists independently measured each lesion twice using a region-of-interest (ROI) method. We measured the contrast-to-noise ratio (CNR), the difference in signal intensity (SI) between the tumor and normal white matter relative to the standard deviation (SD) of the SI within the lesion, for both post-contrast 3D FSPGR and post-contrast T1-Cube images of the same tumor and compared modality-specific CNRs for all tumors and in subgroups defined by tumor size, enhancement ratio, and histopathology.The mean CNR was significantly higher on T1-Cube images than 3D FSPGR images for the total tumor population (1.85 ± 0.97 versus 1.12 ± 1.05, P0.01) and the histologic types, i.e., metastasis (P0.01) and lymphoma (P0.05). The difference in CNR was even larger for smaller tumors in the metastatic group (4.95 to 23.5 mm(2)) (P0.01). In contrast, mean CNRs did not differ between modalities for high grade glioma and meningioma.Gadolinium enhancement of brain tumors was generally higher when imaged by T1-Cube than 3D FSPGR, and T1-Cube with Gd enhancement may be superior to 3D FSPGR for detecting smaller metastatic tumors.

Some patients develop chronic subdural hematomas (CSDHs) after the clipping/coating of unruptured aneurysms. The risk factors are not well understood and while no preventive methods are currently available, arachnoid plasty (ARP) may intercept the development of postoperative CSDH. We investigated the risk factors for CSDH and the usefulness of ARP to prevent postoperative CSDH. Between January 2009 and June 2013, 393 patients underwent 416 aneurysm surgeries via the pterional approach at Kushiro Kojinkai Memorial Hospital. Of these, 394 aneurysms (371 patients) were included in this study. Using multivariate analysis we evaluated the relationship between the patient demographics and clinical characteristics, and the development of postoperative symptomatic CSDH. We also studied the effect of ARP performed during aneurysm surgery. We found that symptomatic CSDH developed after 20 (5.1%) of the 394 operations; it was addressed by burr hole surgery and evacuation/irrigation. Male gender, advanced age, and oral anticoagulant therapy were significant risk factors for CSDH. Additive ARP, performed in the course of 132 surgeries (33.5%) was found to be a significant negative risk factor. The incidence of CSDH was significantly lower in patients who had undergone ARP than in patients who had not undergone it (0.8% vs. 7.3%, p < 0.01). We first report that ARP is useful for the prevention of CSDH in patients treated by aneurysm surgery.

Background and Purpose— This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke. Methods— Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 μg/kg and then 90 μg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography. The incidence of symptomatic intracranial hemorrhage (≤72 hours) was defined as the primary end point. The occurrence of asymptomatic ICH, symptomatic cerebral edemas, and adverse events were other safety outcomes of special interest. Results— Symptomatic intracranial hemorrhage was observed within 72 hours in 2 patients treated with placebo and in 1 patient treated with 70 μg/kg desmoteplase. Any ICH (symptomatic or asymptomatic ICH) within 72 hours were observed in 7 (43.8%) patients treated with placebo, in 8 (50%) patients treated with 70 μg/kg desmoteplase, and in 9 (56.3%) patients treated with 90 μg/kg desmoteplase. Desmoteplase treatment with 70 or 90 μg/kg was not associated with an increased risk of symptomatic cerebral edema compared with placebo. There were no other serious safety concerns associated with desmoteplase. Conclusions— Desmoteplase in both 70 and 90 μg/kg doses had a favorable safety profile and was well tolerated in Japanese patients with acute ischemic stroke when administered 3 to 9 hours after stroke symptoms onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01104467.

OBJECT The severity of clinical signs and symptoms of cranial dural arteriovenous fistulas (DAVFs) are well correlated with their pattern of venous drainage. Although the presence of cortical venous drainage can be considered a potential predictor of aggressive DAVF behaviors, such as intracranial hemorrhage or progressive neurological deficits due to venous congestion, accurate statistical analyses are currently not available. Using a decision tree data mining method, the authors aimed at clarifying the predictability of the future development of aggressive behaviors of DAVF and at identifying the main causative factors. METHODS Of 266 DAVF patients, 89 were eligible for analysis. Under observational management, 51 patients presented with intracranial hemorrhage/infarction during the follow-up period. RESULTS The authors created a decision tree able to assess the risk for the development of aggressive DAVF behavior. Evaluated by 10-fold cross-validation, the decision tree's accuracy, sensitivity, and specificity were 85.28%, 88.33%, and 80.83%, respectively. The tree shows that the main factor in symptomatic patients was the presence of cortical venous drainage. In its absence, the lesion location determined the risk of a DAVF developing aggressive behavior. CONCLUSIONS Decision tree analysis accurately predicts the future development of aggressive DAVF behavior.

This study sought to determine the diagnostic utility of perfusion parameters derived from dynamic contrast-enhanced (DCE) perfusion MRI with a short acquisition time (approximately 3.5 min) in patients with glioma, brain metastasis, and primary CNS lymphoma (PCNSL). Twenty-six patients with 29 lesions (4 low-grade glioma, 13 high-grade glioma, 7 metastasis, and 5 PCNSL) underwent DCE-MRI in a 3 T scanner. A ROI was placed on the hotspot of each tumor in maps for volume transfer contrast K trans , extravascular extracellular volume V e , and fractional plasma volume V p . We analyzed differences in parameters between tumors using the Mann–Whitney U test. We calculated sensitivity and specificity using receiver operating characteristics analysis. Mean K trans values of LGG, HGG, metastasis and PCNSL were 0.034, 0.31, 0.38, 0.44, respectively. Mean Ve values of each tumors was 0.036, 0.57, 0.47, 0.96, and mean Vp value of each tumors was 0.070, 0.086, 0.26, 0.17, respectively. Compared with other tumor types, low-grade glioma showed lower K trans (P

Introduction: T2*-weighted imaging (T2*WI) can detect acute endovascular clots by the susceptibility vessel sign (SVS). Stagnant flow in front of middle cerebral artery (MCA) occlusion sites may contribute to intra-arterial high-intensity signal on arterial spin labeling (ASL) magnetic resonance imaging (MRI), making it another potential marker of MCA occlusion. We compared intra-arterial high-intensity signal and SVS in patients with symptomatic and asymptomatic MCA occlusion and patients without major vessel occlusion. Methods: We identified transient ischemic attack or ischemic stroke patients by (a) 3-T MRI, diffusion-weighted imaging, ASL, T2*WI, and magnetic resonance angiography (MRA) performed within 24 h after stroke onset and (b) the presence of MCA occlusion (n=34 patients) or the absence of major vessel occlusion (n=24 patients). We included asymptomatic patients with MCA occlusion (n=6). The presence or absence of intra-arterial high-intensity signal and SVS was recorded as was its coincidence with the presence of MCA occlusion on MRA. Results: In patients with acute ischemic stroke the sensitivity of intra-arterial high-intensity signal was significantly higher than of the SVS (88% vs 50%; p Conclusions: The intra-arterial high-intensity signal on ASL could identify stagnant flow in front of occlusion sites due to acute arterial occlusion.

Background and Purpose: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in regulating not only lipid and glucose metabolism but also atherosclerosis and inflammation which are associated with intracranial aneurysmal rupture. It has been suggested that PPARγ is present in various kinds of cell types including macrophages which we reported to contribute to intracranial aneurysm formation. In addition, macrophage PPARγ regulates inflammatory cytokines negatively. Therefore we hypothesized that macrophage PPARγ is protective against intracranial aneurysmal rupture. We tested this hypothesis by using our own established mouse model of intracranial aneurysm. Methods: Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle or PPARγ agonist (pioglitazone:PGZ) or clodronate liposome. PPARγ antagonist (GW9662) was added to PGZ treatment. We induced aneurysms to macrophage-specific PPARγ knockout mice and treated them with vehicle or PGZ with the same protocol mentioned above. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Results: Both PGZ and depletion of macrophage by clodronate liposome reduced the incidence of ruptured aneurysms and rupture rate. PGZ treatment decreased the inflammatory cytokines that were increased in cerebral arteries of mice with aneurysm induction compared to mice without aneurysm induction. To examine whether the macrophage PPARγ is associated with intracranial aneurysmal rupture, we administered PGZ to macrophage-specific PPARγ knock out mice. PGZ did not have protective effect against aneurysmal rupture in macrophage-specific PPARγ knock out mice although it exerted protective effects in wild type mice. Conclusion: PPARγ activation is protective against intracranial aneurysmal rupture by suppressing inflammatory cytokines and macrophage PPARγ is associated with this protective effects.

Background and Purpose: Peripheral macrophages include M1- and M2 macrophages; they produce pro-inflammatory and anti-inflammatory cytokines, respectively. Inflammation produces group-specific component protein-derived macrophage activating factor (GcMAF). The role of M1- and M2 macrophages activated by GcMAF in the post-ischemic brain remains unclear. We hypothesized that the role of GcMAF after ischemia is time-dependently different and that the dominant activation of M2 macrophages facilitates brain repair. Methods: After subjecting 7-week-old male Wistar rats to 2-hr middle cerebral artery occlusion they were divided into a group injected for 7 days with GcMAF and a group serving as the vehicle control in the early- and late phase after ischemia induction. Results: Within 3 days of post-ischemia, the predominant increase in M1 macrophages was associated with expanded ischemic brain damage that was exacerbated by GcMAF. At the 7th post-ischemic day the infarct size was stabilized and M1 macrophages were decreased, although the higher expression in M1- than M2 macrophages persisted. Interestingly, GcMAF treatment from this point cleaned the infarct area, which was associated with phagocytosis via a predominant increase in microglia and M2 macrophages. The effect of GcMAF was abrogated by macrophage-depleting clodronate liposomes. Furthermore, the increase in M2 macrophages was associated with increased BrdU incorporation and the appearance of survival-related molecules and neurovascular unit, suggesting the promotion of neurogenesis. Conclusion: The activation of M2 macrophages by GcMAF in the late phase of cerebral ischemia may be associated with brain repair.

Introduction: To prevent subarachnoid hemorrhage (SAH), its pathogenesis must be understood. SAH and cerebral aneurysms are located at vascular walls exposed to hemodynamic stress and turbulence. In our experimental aneurysm model, rats were subjected to oophorectomy, right common carotid artery ligation (CCA), and bilateral posterior renal ligation; they received a high-salt diet. Although we noted a high incidence of aneurysms at the anterior cerebral artery-olfactory artery (ACA-OA) bifurcation, no SAH occurred at this site. As hemodynamic changes are thought to stimulate the vascular wall locally, we hypothesized that additive hemodynamic changes lead to the development and rupture of cerebral aneurysms. Methods: We divided 42 rats into 3 groups, group A (n=26) underwent ligation of the right CCA, in group B (n=10) we ligated the right pterygopalatine artery, the right external carotid artery, and the left CCA, and in group C (n=6) we additionally ligated the bilateral vertebral arteries. Results: In the 12 weeks after aneurysm induction, 5 group A (19%)-, 3 group B (30%)-, and 3 group C (50%) rats suffered aneurysmal rupture. As in humans, the ruptured aneurysms were primarily located at the anterior communicating artery, the posterior communicating artery, and the internal carotid-posterior communicating artery. There were no ruptured aneurysms at the ACA-OA bifurcation. Conclusion: Our findings suggest that hemodynamic changes are at least partly associated with the vulnerability of the vascular wall at the circle of Willis. Studies are underway to identify the mechanisms underlying the pathologic vascular changes.

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* 5 0 indicating excellent agreement and vr* 5 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1–4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1–4.4) for panel members and 4.5 (95% CI 4.3–4.6) for external reviewers (p 5 0.017). Mean Likert scores were 4.2 (95% CI 4.1–4.3) for interventional reviewers (n 5 56) and 4.1 (95% CI 3.9–4.4) for noninterventional reviewers (n 5 12) (p 5 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019–0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA. Neurology® 2015;85:881–889

Camptocormia, known also as "bent spine syndrome", is characterized by involuntary truncal flexion of the thoraco-lumbar spine that appears in the sitting or standing position. Although Parkinson's disease (PD) is the most frequent etiologic factor, this postural disorder responds poorly to levodopa or other medications. We report a PD patient in whom chronic bilateral subthalamic nucleus stimulation produced a striking alleviation of camptocormia.

Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty-five patients underwent bilateral STN stimulation. Pre- and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab-England (S-E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug-induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients’ psychiatric symptoms. Postoperative S-E score showed a significant improvement compared to the pretreatment baseline in both of “on” and “off” medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S-E score in “on” state (p

CT is a widely used imaging modality for diagnosis of cerebral vascular disease. However, the sensitivity of detection at early stage of cerebral infarction is not adequate depending on the ability of observers and instruments. The high sensitivity of diffusion-weighted imaging on MRI for the diagnosis of acute cerebral infarction has bee reported. Furthermore, MRI can demonstrate perfusion and vascular information without usage of contrast medium. In addition, the recent work showed that susceptibility imaging on MRI has the same quality to detect acute cerebral hemorrahge as CT. We consider that MRI has a possibility to become the first selected modality for the acute cerebral infarction.

The treatment of unruptured cerebral arteriovenous malformation (AVM) is still controversial. We have been treating these patients according to the Spetzler & Martin (S&M) grading system. We retrospectively evaluated the outcomes of 46 unruptured AVM patients and also evaluated the bleeding rate during follow-up period. Recently we also started performing functional MRI, tractography, and 3-dimensional (3D) angiography for these patients before treatment. In 18 of 22 patients in S&M Grade I and II, AVMs were surgically removed and the outcome was good. Six of 9 patients in S&M Grade IV and V, were conservatively treated. In patients in S&M Grade III, various treatments were performed according to the location of the AVM, but all their outcomes were favorable. The rate of permanent surgical complications was 15.3% in 26 unruptured AVM patients. Based on our treatment results, aggressive treatment should be performed in patients with S&M Grade I and II. However, treatment decisions must be carefully considered based on functional MRI, tractography of AVM, and 3D angiography.

High mobility group box 1 (HMGB1) elevation after cerebral ischemia activates inflammatory pathways via receptors such as the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) and leads to brain damage. Eicosapentaenoic acid (EPA), a peroxisome proliferator–activated receptor gamma (PPARγ) agonist, attenuates postischemic inflammation and brain damage in male animals. However, postischemic HMGB1 signaling and the effects of EPA on ovariectomized (OVX + ) rats remain unclear. We hypothesized that EPA attenuates brain damage in OVX + rats via the inhibition of HMGB1 signaling in a PPARγ-dependent manner. Seven-week-old female Sprague-Dawley rats were divided into 3 groups; nonovariectomized (OVX − ) rats and EPA-treated and EPA-untreated OVX + rats before cerebral ischemia induction. Another set of EPA-treated OVX + rats was injected with the PPARγ inhibitor GW9662. OVX + decreased the messenger RNA level of PPARγ and increased that of HMGB1, RAGE, TLR9, and tumor necrosis factor alpha (TNFα) in parallel with ischemic brain damage. EPA restored the PPARγ expression, downregulated the HMGB1 signal–related molecules, and attenuated the ischemic brain damage. Neither OVX + nor EPA affected the expression of TLR2 or TLR4. Interestingly, GW9662 partially abrogated the EPA-induced neuroprotection and the downregulation of RAGE and TLR9. In contrast, GW9662 did not affect HMGB1 or TNFα. These results suggest that EPA exerts PPARγ-dependent and PPARγ-independent effects on postischemic HMGB1/TLR9 pathway. The cortical infarct volume exacerbated by OVX + is associated with the upregulation of the HMGB1/TLR9 pathway. Suppression of this pathway may help to limit ischemic brain damage in postmenopausal women.

Background Although accurate diagnosis of the ischemic stroke subtype is one of the most important factors for selection of therapeutic approach, it is sometimes difficult at the time of admission. We previously reported that susceptibility vessel sign (SVS) with two layers (termed two-layered SVS) on 3-tesla-T2*-weighted image (T2*-WI) might be useful to predict cardioembolic stroke in patients with cerebral major vessel occlusion. We studied about biomarkers on magnetic resonance imaging (MRI), including two-layered SVS for diagnosing cardioembolic stroke. Methods We included 132 ischemic stroke patients within 24h from onset who suffered internal carotid artery or middle cerebral artery occlusion due to cardioembolic stroke (group CE) or large artery atherosclerosis (group LAA). We studied about biomarkers on MRI such as two-layered SVS and abnormal finding patterns of diffusion-weighted image (DWI) for diagnosis of cardioembolic stroke in addition to laboratory data, physiological examination, and clinical findings. Results In this study, 132 patients (72 men and 60 women, age 74.5±12.1years) were included. Of these, 63 (47.7%) were cardioembolic stroke. In univariate analysis, frequency of comorbid atrial fibrillation, presence of two-layered SVS on T2*-WI and that of single corticosubcortical infarct on DWI, intima-media thickness were significantly higher in group CE. In multivariate analysis, the presence of two-layered SVS and single corticosubcortical infarct were associated with cardioembolic stroke (odds ratio, two-layered SVS, 30.08, p p Conclusion Biomarkers associated with cardioembolic stroke may be two-layered SVS on T2*-WI and single corticosubcortical infarct on DWI.

Ultrasound imaging of carotid artery plaques not only identifies the existence and size of the plaques but also provides information on the histological features of the plaques such as lipid pools and fibrous or calcified tissue. We attempted to develop a novel system to obtain the characteristics

Background and Purpose— A susceptibility vessel sign (SVS) on 1.5-tesla (T)-T2*-weighted images may predict cardioembolism. It has also been detected in patients with large artery atherosclerosis. In patients with major vessel occlusion, the SVS was comprised 2 layers on 3T-T2*-weighted images. We assessed the efficacy of 2-layered SVS on 3T-T2*-weighted imaging scans for predicting cardioembolism. Methods— Our study included 132 patients who had ischemic stroke within the preceding 24 hours and presented with internal carotid artery or middle cerebral artery occlusion because of cardioembolism or large artery atherosclerosis. We compared 2-layered SVS and SVS on 3T-T2*-weighted imaging scans for their sensitivity, specificity, and diagnostic odds ratio for predicting cardioembolism. Results— We enrolled 132 patients (72 men; mean age, 74.5 years); of these, 63 (47.7%) were presented with cardioembolism. Although the sensitivity of SVS and 2-layered SVS for cardioembolism and large artery atherosclerosis was not statistically different (74.6% and 58.0%, respectively), the sensitivity of 2-layered SVS was significantly higher in patients with cardioembolism (42.9%) than those with large artery atherosclerosis (2.9%; P Conclusion— The specificity of 2-layered SVS for cardioembolism was high. It may be useful for predicting cardioembolism and for the management of patients with acute ischemic stroke.

Object. The increased incidence of cerebral aneurysms in postmenopausal women appears to be related to low levels of circulating estrogen. Using a rat model of aneurysm induction, the authors found that oophorectomy increased the incidence of experimental cerebral aneurysms (Part I in this issue). In the current study they examined the effects of hormone replacement therapy (HRT) on the formation of cerebral aneurysms in rats. Methods. Forty-five female Sprague—Dawley rats were divided into three equal groups. The animals in Groups A and B were subjected to a cerebral aneurysm induction procedure (renal hypertension and right common carotid artery ligation) followed 1 month later by bilateral oophorectomy. After an additional week the rats in Group A received 17β estradiol continuous-release pellets. The rats in Group C served as controls. Three months after the aneurysm induction procedure, all the rats were killed and vascular corrosion casts of their cerebral arteries were prepared and checked for aneurysmal changes. Using a scanning electron microscope, the authors recorded aneurysmal changes as endothelial changes alone (Stage I), endothelial changes with intimal pad elevation (Stage II), and saccular aneurysm formation (Stage III). Aneurysmal changes (Stages I, II, and III) occurred in one third of rats that had undergone oophorectomy and were receiving HRT (Group A), compared with 87% of the rats that had undergone oophorectomy but did not receive HRT (Group B). Although most of the aneurysmal changes identified in Group A rats were limited to Stage I or II, most changes in Group B animals were identified as saccular dilation (Stage III). Conclusions. The findings demonstrated the significant protective role of estrogen against the formation and progression of cerebral aneurysms. It appears to be related to the beneficial effects of estrogen on the function and growth of endothelial cells, which play a major role in preserving the integrity of the vascular wall.

Object. Estrogen has been shown to play a central role in vascular biology. Although it may exert beneficial vascular effects, its role in the pathogenesis of cerebral aneurysms remains to be determined. To elucidate the role of hormones further, the authors examined the effects of bilateral oophorectomy on the formation and progression of cerebral aneurysms in rats. Methods. Forty-five female, 7-week-old Sprague—Dawley rats were divided into three equal groups. Group I consisted of intact rats (controls). To induce cerebral aneurysms, the animals in Groups II and III were subjected to ligation of the right common carotid and bilateral posterior renal arteries. One month later, the rats in Group II underwent bilateral oophorectomy. Three months after the experiment began all animals were killed and cerebral vascular corrosion casts were prepared and screened for cerebral aneurysms by using a scanning electron microscope. Plasma was used to determine the level of estradiol and the gelatinase activity. Hypertension developed in all rats except those in the control group. The estradiol level was significantly lower in Group II than in the other groups (p < 0.01). The incidence of cerebral aneurysm formation in Group II (60%) was three times higher than that in Group III (20%), and the mean size of aneurysms in Group II (76 ± 27 µm, mean ± standard deviation) was larger than that in Group III (28 ± 4.6 µm) (p < 0.05). No aneurysm developed in control animals (Group I), and there was no significant difference in plasma gelatinase activity among the three groups. Conclusions. The cerebral aneurysm model was highly reproducible in rats. Bilateral oophorectomy increased the susceptibility of rats to aneurysm formation, indicating that hormones play a role in the pathogenesis of cerebral aneurysms.

Reactive species of oxygen and nitrogen mediate the oxidative modification of low-density lipoprotein (LDL). Oxidation of LDL is inhibited by endogenous radical scavenging enzymes such as manganese superoxide dismutase (SOD) and Cu-ZnSOD that catalyze dismutation of oxygen to H2O2. Low-molecular antioxidants such as uric acid regulate the inactivation that appears to be linked to an increase in peroxynitrite resulting in oxidized LDL (OxLDL) elevation. The authors evaluated whether a focal imbalance between pro- and antioxidant systems induces plaque vulnerability in patients with carotid artery (CA) stenosis.Carotid artery plaques obtained in 35 patients who had undergone carotid endarterectomy were classified as vulnerable or stable based on histopathological findings. In vulnerable plaques, OxLDL, measured using enzyme-linked immunosorbent assay, was significantly higher (p0.01) and SOD activity significantly lower than in stable plaques (p0.05). The plaque and plasma OxLDL levels were inversely correlated with plaque SOD activity (p0.01). The physiological uric acid level in all plaques was one fourth to one eighth of that in plasma and appeared to be unable to protect Cu-ZnSOD from degradation by H2O2. Immunohistochemical analysis showed increased peroxynitrite and OxLDL in vulnerable plaques. There was a significant correlation between plaque and plasma OxLDL levels (p0.01).Analysis of the results suggests that a focal imbalance between pro- and antioxidant defense systems in patients with CA plaques induces an increase in plaque OxLDL levels and consequent plaque instability, contributing to high levels of plasma OxLDL.

Objective We assessed whether angiographic changes in venous drainage patterns occur over time in cavernous sinus dural arteriovenous fistulae (dAVFs) without a complete cure. Methods We classified 65 cavernous sinus dAVFs into three types on the basis of initial angiographic findings. In Type 1, both anterior and posterior drainage routes were open; in Type 2, the posterior drainage route was closed, whereas the anterior drainage route was open; and in Type 3, both the posterior and anterior drainage routes were closed. Results Of the 65 dAVFs, 40 were of Type 1, 21 of Type 2, and 4 of Type 3. During the follow-up period, 17 of the dAVFs that were treated palliatively with transarterial embolization (n = 11) or monitored without therapy (n = 6) demonstrated angiographic changes. In these 11 patients, there was a change in the venous drainage pattern from Type 1 to Type 2 (n = 5), from Type 2 to Type 3 (n = 3), and from Type 1 to Type 3 (n = 3). One of 11 had a conversion into a lesion with cortical venous drainage. The remaining 6 dAVFs (4 with observational management, 2 with transarterial embolization) demonstrated closure of the fistula; in 5 of these, the affected cavernous sinus was not depicted on follow-up angiograms. Conclusion In some cavernous sinus dAVFs with palliative transarterial embolization or observational management, there was a change in the venous drainage patterns, consisting of a decrease in the number of venous drainage routes. There was a trend for the posterior route to close before the anterior drainage or cortical drainage route. This suggests the occurrence of a staged progression in a regular direction in cavernous sinus dAVFs. Without treatment aiming at a complete cure, most cavernous sinus dAVFs can behave benignly, with a low possibility of development of cortical venous reflux during follow-up.

A 64-year-old woman presented with a rare anaplastic ganglioglioma in the right cerebellopontine angle manifesting as dizziness persisting for 2 weeks. Preoperative magnetic resonance (MR) imaging revealed a partially enhanced cystic lesion of the right cerebellopontine angle. The tumor was subtotally removed through a right lateral suboccipital craniectomy. The tumor was thought to originate from the brain stem with exophytic growth into the right cerebellopontine angle. Histological examination showed neoplastic ganglional and glial cells with anaplastic features such as mitosis, pleomorphism, and endothelial proliferation. The MIB-1 labeling index of the glial components was 40% to 60%. The diagnosis was anaplastic ganglioglioma (World Health Organization grade IV). She received postoperative radiotherapy but died of respiratory failure with tumor recurrence 11 months after the operation. Gangliogliomas usually have a good prognosis. Histological features of anaplasia and a high MIB-1 labeling index may be predictive of a poor clinical outcome.

A 45-year-old woman presented with progressive stroke due to occlusion of the left internal carotid artery at the level of the cavernous portion (C3/C4). Revascularization was achieved by stent deployment following percutaneous transluminal angioplasty. Stent thrombosis occurred 7 days after primary stenting; it was successfully treated with the stent-in-stent technique. The patient was able to return to her independent life with no sequelae except for slight hemiparesis. In combination with appropriate antiplatelet treatment, the stent-in-stent technique should be considered as a rescue option in patients with re-occlusion of an intracranial stent.

There are few cases of spinal hemorrhagic disease compared to cerebral stroke. However, progress in diagnostic neuroradiology has shown that it is not such a rare disease. We report on cases of spinal hemorrhagic disease that were diagnosed as cerebral stroke. Subjects are 13 cases of spinal hemorrhagic disease that we treated from September 1998 to November 2003. Among these cases, 6 patients were initially diagnosed as cerebral stroke. These comprised 3 cases of spinal epidural hematoma, 1 case of spinal subdural hematoma and 2 cases of spinal subarachnoid hemorrhage. In most cases, they presented with neck, back or low back pain, but a few cases presented with hemiparesis and were not diagnosed as spinal disease. These cases are likely to misdiagnosed as cerebral stroke. Hematomas often occur on 1 side of spinal cord and lead to hemiparesis. Now we can easily and correctly diagnose spinal hemorrhagic disease using magnetic resonance imaging (MRI). Spinal hemorrhagic diseases are rare but a good prognosis can be expected with appropriate diagnosis and treatment.

The correlation between volume embolization ratio (VER), the percentage of aneurysm volume occupied by coils, and aneurysm stability after endovascular treatment with platinum coils was studied in 86 patients who underwent embolization of 88 cerebral saccular aneurysms with standard platinum coils between March 1997 and January 2003. Radiographic follow up was possible of 62 aneurysms with greater than 70% obliteration on immediate post-procedure angiograms for more than 6 months. Immediate post-procedure evaluation found that 12 of 14 small ( < 4 mm), 12 of 38 medium (4- < 10 mm), and two of 10 large (≥ 10 mm) aneurysms had high (≥ 25%) VER. In addition, the VER was high in 22 of 40 aneurysms with small (

We herein report unusual basal ganglia hyperintense lesions on noncontrast T1-weighted magnetic resonance imaging in a patient with central nervous system metastasis from lung adenocarcinoma that was treated with gefitinib. T2*-weighted magnetic resonance imaging showed no hypointense lesions, thereby excluding the possibility of calcification or haemorrhage. A stereotactic brain biopsy of the left basal ganglia lesions revealed atypical cells, some of which formed a glandular lumen with a micropapillary pattern. These cells were immunopositive for markers of lung adenocarcinoma, thereby confirming the diagnosis of metastasis. We speculate that proteins, including carcinoembryonic antigens from the adenocarcinoma cells in the basal ganglia, may have contributed to the hyperintensity observed on noncontrast T1-weighted magnetic resonance imaging.

Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p

Chordomas are thought to be tumors originating from notochord remnants characterized histologically by cohesive cells with epithelial features and by immunohistochemical expression of epithelial markers. To investigate the expression and distribution of cell adhesion molecules in chordomas, we immunohistochemically studied the expression of representative cell adhesion molecules, E-cadherin, P-cadherin, N-cadherin, beta-catenin, CD44, ICAM-1 (CD54), NCAM (CD56), and VCAM-1 (CD106) in 16 tumors from 16 patients (skull base, n=5; cervical, n=2; sacral, n=9) and 3 cases of fetal notochord. Of 16 tumors, 12 (75.0%) expressed membranous immunoreactivity for NCAM, 10 (62.5%) for VCAM-1, 9 (56.3%) for CD44, 8 (50.0%) for N-cadherin, 6 (37.5%) for beta-catenin, 4 (25%) for ICAM-1, and 1 (6.3%) for P-cadherin. Nuclear staining for E-cadherin was recognized in 11 (68.8%) tumors, and membranous staining for E-cadherin in 3 (18.8%); none of the tumors showed both nuclear and membranous staining. Intranuclear accumulation of beta-catenin was not found in any chordoma. One fetal notochord case showed immunoreactivity for N-cadherin, E-cadherin (some cells showed staining in both cytoplasm and nuclei), CD44 and beta-catenin. These results indicate that chordomas frequently express immunoreactivity for multiple adhesion molecules including VCAM, CD44 and N-cadherin, as well as for NCAM and E-cadherin, as previously reported. These molecules may participate in producing the cellular cohesion evident in tumor morphological structure. Although the precise underlying mechanisms remain to be elucidated, the high frequency of nuclear expression of E-cadherin (11 of 16 cases) may be diagnostically useful.

We evaluated the surgical and long-term follow-up results of VA-CCA transposition in patients with bilateral VA occlusive lesions. Indications for this operation are: 1) symptomatic patients with the infarction in the cerebellum, brain stem or occipital lobe, 2) symptomatic patients with more than 50% VA stenosis with contralateral VA occlusion, 3) symptomatic patients with more than 75% bilateral VA stenosis at origin. In 13 patients, there were no deaths and no major complications. During the follow-up period, 1 patient died of a cardiac event, and another patient had a reattack due to the restenosis of VA stenosis. Another 11 patients showed no reattacks and good patency of VA. Although there have been no prospective randomized studies for this disease, VA-CCA transposition is a safe and useful treatment for patients with bilateral VA origin occlusive lesions.