Hideo Osada

Increased xCT expression correlates with tumor invasion and outcome in patients with glioblastomas.

BACKGROUND xCT is a light chain of the cystine/glutamate antiporter system xc. Glutamate that is released by system xc plays an important role in the infiltration of glioblastoma (GBM) cells. Furthermore, increased glutathione synthesis by system xc may protect tumor cells against oxidative stress induced by radiotherapy and chemotherapy. OBJECTIVE To investigate whether the levels of xCT expression correlated with infiltrative imaging phenotypes on magnetic resonance imaging and outcomes in patients with GBMs. METHODS Forty patients with histologically confirmed primary GBMs were included in the study. Patient charts were retrospectively reviewed for age, sex, Karnofsky Performance Status Scale score, Mini-Mental State Examination score, magnetic resonance imaging features, xCT expression, isocitrate dehydrogenase 1 R132H expression, O-methylguanine-DNA methyltransferase promoter methylation status, type of surgery, progression-free survival, and overall survival. RESULTS In invasive margins, xCT expression was weak in 20 patients and strong in 20 patients. A Cox regression model revealed that a Karnofsky Performance Status Scale score less than 60 (hazard ratio [HR]: 4.525; P = .01), partial removal (HR: 2.839; P = .03), and strong xCT expression (HR: 4.134; P < .001) were significantly associated with shorter progression-free survival and that partial removal (HR: 2.865; P = .03), weak isocitrate dehydrogenase 1 R132H expression (HR: 15.729; P = .01), and strong xCT expression (HR: 2.863; P = .04) were significantly associated with shorter overall survival. CONCLUSION These findings suggest that xCT is an independent predictive factor in GBMs.

Surgical management for glossopharyngeal neuralgia associated with cardiac syncope: two case reports

Two patients with glossopharyngeal neuralgia associated with cardiac syncope were treated with temporary cardiac pacemakers for cardiac syncope and then microvascular decompression. The offending arteries were the posterior inferior cerebellar artery in one patient and the anterior inferior cerebellar artery in the other. The offending arteries were attached to the glossopharyngeal nerve and the vagal nerve at the root entry zones. After surgery, the patients were free from neuralgia and cardiac syncope did not occur after the pacemakers were extracted. Implantation of a temporary cardiac pacemaker in the perioperative period ensures safe microvascular decompression.

Sulfasalazine and temozolomide with radiation therapy for newly diagnosed glioblastoma

BACKGROUND A recent phase 1/2 clinical trial argued for caution for the use of sulfasalazine in progressive glioblastoma (GBM). However, the study enrolled patients with recurrent or progressive high-grade glioma indicating that patients recruited probably had severe disease. Thus, the study may not accurately reflect the effectiveness of sulfasalazine for GBM and we hypothesized that earlier sulfasalazine administration may lead to anticancer effects. AIM The aim of this study was to investigate whether sulfasalazine can improve the outcomes of patients with newly diagnosed GBM. SUBJECTS AND METHODS A total of 12 patients were treated with temozolomide and sulfasalazine with radiation therapy after surgery. Twelve patients with primary GBM treated with temozolomide and radiation therapy formed the control group. Progression-free survival (PFS), overall survival (OS) and seizure-free survival (SFS) curves were obtained using the Kaplan-Meier method. The survival curves were compared using the log-rank test. RESULTS The median OS, PFS and SFS did not differ between the groups. Grade 3 or 4 adverse events occurred over the duration of the study in nine (75%) patients. The median SFS was 12 months in nine patients who received sulfasalazine administration for more than 21 days, which was strongly but not significantly longer than the 3 months observed in the control group (P = 0.078). CONCLUSIONS Sulfasalazine treatment with temozolomide plus radiotherapy for newly diagnosed primary GBM is associated with a high rate of discontinuation due to hematologic toxic effects. This treatment may have no effect on OS or PFS, although it may improve seizure control if an adequate dose can be administered.

IgG4-Related Intracranial Hypertrophic Pachymeningitis : A Case Report and Review of the Literature

Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater. Recently, the possibility that IgG4-related sclerosing disease may underlie some cases of intracranial hypertrophic pachymeningitis has been suggested. We herein report the tenth case of IgG4-related intracranial hypertrophic pachymeningitis and review the previous literature. A 45-year-old male presented with left-sided focal seizures with generalization. Magnetic resonance imaging (MRI) revealed a diffuse thickening and enhancement of the right convexity dura matter and falx with focal nodularity. The surgically resected specimens exhibited the proliferation of fibroblast-like spindle cells and an infiltration of mononuclear cells, including predominantly plasma cells. The ratio of IgG4-positive plasma cells to the overall IgG-positive cells was 45% in the area containing the highest infiltration of plasma cells. On the basis of the above findings, IgG4-related sclerosing disease arising from the dura mater was suspected. IgG4-related sclerosing disease should be added to the pachymeningitis spectrum.

Effects of intravenous infusion of hydrogen-rich fluid combined with intra-cisternal infusion of magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

BackgroundThe failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage.MethodsThis study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers.DiscussionThe present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy.Trial registrationUMIN-CTR: UMIN000014696

Intravenous tissue plasminogen activator treatment for ischemic stroke in dabigatran-treated patients

Vergouwen et al. reported that intravenous tissue plasmin-ogen activator (IV tPA) treatment was not associated withan increased risk of secondary intracerebral hemorrhage orgastrointestinal hemorrhage in patients with acute ischemicstroke taking warfarin with an international normalizedratio (INR) <1.7 [6]. These results mean that IV tPAtreatment should not be discouraged in patients takingwarfarin with INR <1.7.Recently, dabigatran, a new oral anticoagulant, wasapproved by the FDA. In the Randomized Evaluation ofLong-Term Anticoagulant Therapy trial, dabigatran wasshown to be as effective as warfarin in prevention of systemicembolism and future stroke, with lower risk of majorhemorrhage [2]. Additionally, dabigatran does not needmonitoring (differently from warfarin). Therefore, the numberof dabigatran-treated patients presenting with ischemic strokemay increase in the future. However, there is no guidelinewhether dabigatran-treated patients presenting with ischemicstroke can be considered eligible for IV tPA treatment or not.Only two case reports demonstrated the safety of IV tPAtreatment for acute ischemic stroke in dabigatran-treatedpatient [3, 5]. On the other hand, Ammollo et al. reportedthat dabigatran enhanced the susceptibility of plasma clots totPA-induced lysis in in vitro study [ 1]. Based on Ammollo’sresults, we can hypothesize that dabigatran may also enhancethebleedingriskcausedbytPA.Although we recognize the lack of data on IV tPAtreatment for acute ischemic stroke in dabigatran-treatedpatients, we need provisional guidelines of the topic, asearly as possible, in order to avoid confusion. Some tests,such as activated partial thrombin time and ecarin clottingtime, which have been reported as correlated with dabiga-tran concentrations, can be helpful for clinicians todetermine the indication of IV tPA for such patients [4].

Temporal profile of plasma adiponectin level and delayed cerebral ischemia in patients with subarachnoid hemorrhage.

Adiponectin affects nitric oxide production, and low plasma adiponectin levels are associated with impaired endothelium-dependent vasorelaxation. However, adiponectin pathophysiology in the acute phase after stroke, especially subarachnoid hemorrhage, is not well understood. The present study evaluated the changes in plasma adiponectin concentrations in patients with subarachnoid hemorrhage and investigated the relationship between plasma adiponectin and delayed cerebral ischemia. Serial plasma samples from 27 patients with subarachnoid hemorrhage were obtained on day 0 or 1 after hemorrhage, and days 3, 7, 10, 14, and 21. As a control, plasma samples were obtained from 26 healthy volunteers. Differences between patients with and without delayed cerebral ischemia were assessed to investigate the relationship between plasma adiponectin concentrations and the occurrence of delayed cerebral ischemia. There were no significant differences in the clinical characteristics of patients with and without delayed cerebral ischemia. The plasma adiponectin concentrations were significantly lower in patients on days 3 and 7 compared with controls. Plasma adiponectin concentrations in patients with delayed cerebral ischemia were significantly lower than in those without delayed cerebral ischemia on days 3, 7, 10, and 14. The present results indicate that low plasma adiponectin concentrations from day 3 to day 14 might be associated with the development of delayed cerebral ischemia.

Surgical Results After Primary Decompressive Craniectomy in Poor-Grade Aneurysmal Subarachnoid Hemorrhage

It is well known that patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) have poor outcomes owing to significant mass effect and brain stem compression. On the other hand, decompressive craniectomy (DC) has shown efficacy in reducing morbidity and mortality in patients with intracranial hypertension. Here, we study the efficacy of DC in poor-grade SAH with attention to surgical outcome. A total of 38 consecutive patients with poor-grade SAH was treated in our hospital between 1 August 2005 and 30 July 2010. Among these 38 patients, we involved 15 patients with DC in the present study. We retrospectively reviewed medical charts and radiological findings. Glasgow Outcome Scale score on discharge showed good response in 1 (6.7 %), moderate disability in 6 (40.0 %), severe disability in 4 (28.1 %), vegetative state in 2 (1.3 %), and death in 2 (13.3 %). In particular, 3 grade IV patients (50.0 %) had a favorable outcome. Recent several experimental studies also indicated that DC significantly improves outcome owing to increased perfusion pressure or reduced intracranial pressure. We suggest that the DC provided the efficacy in reducing mortality in poor-grade SAH patients.

Infratentorial arteriovenous malformation associated with persistent primitive hypoglossal artery.

Background: We report a case of infratentorial arteriovenous malformation (AVM) associated with persistent primitive hypoglossal artery (PPHA). To our knowledge, this is the second reported case of these combined anomalies in the English literature. We discuss the embryological relationship between these two congenital vascular anomalies. Case Description: An 18-year-old girl, who suddenly developed severe headache and vomiting followed by loss of consciousness, was admitted to our hospital. A computed tomography scan showed intracerebellar hemorrhage with obstructive hydrocephalus. Digital subtraction angiography revealed an AVM in the left cerebellar hemisphere and an ipsilateral PPHA. After the intracranial pressure was stabilized, the AVM was surgically removed. AVMs develop during the 4th to 8th week of embryonic life. In contrast, carotid-basilar anastomoses (CBAs) including primitive hypoglossal arteries appear and close spontaneously by the 6th week of embryonic life. Thus, AVMs precede CBAs, and a large amount of blood flows into the adjoining AVM via ipsilateral CBAs. As a result, spontaneous closure of a CBA may be disturbed. Conclusion: We speculate that coexistence of infratentorial AVMs and ipsilateral CBAs is not incidental but inevitable.

Surgical resection of developmental venous anomaly causing massive intracerebral haemorrhage: A case report

Abstract Cerebral developmental venous anomalies (DVAs) very rarely cause massive haematoma, but should be included in the differential diagnosis of atypical massive intracerebral haematoma (ICH). We describe a case of massive ICH caused only by a DVA and successfully treated by haematoma evacuation with surgical resection of the DVA.