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The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

The localized, extremely low-flow condition that was observed in the dome of aneurysms with aspect ratios of more than 1.6 is a common flow characteristic in the geometry of ruptured aneurysms, so great care should be taken for patients with unruptured intracranial aneurysms with aspect ratios of more than 1.6.

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.

Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the genetic determinants. We report here a genomewide linkage study of IA in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for IA. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81x10-6), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39. These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7.

The present study was undertaken to analyze the roles of brain cations and of the blood-brain barrier (BBB) to albumin in the development of ischemic brain edema. Using the rat middle cerebral artery (MCA) occlusion model, changes in the brain water, sodium, and potassium contents were followed for a period of seven days. The permeability of the BBB to proteins was also followed by 125I-albumin transfer from the blood into the brain. A significant edema developed as early as three hours after MCA occlusion. This progressed rapidly to reach a maximum on the third day, gradually regressing thereafter. The increase in the brain water contents showed a parallel time course to the increase in the sodium and decrease in the potassium contents. A significant increase in the BBB permeability to albumin occurred 72 hours after MCA occlusion. However, there was no correlation between the brain water content and BBB permeability to albumin in the hemispheres studied 72 hours after MCA occlusion. The correlation between the brain water and sodium contents was not clear during the first six hours, but became highly significant thereafter. The data suggest that an increase in the BBB permeability to sodium occurred 12-48 hours after MCA occlusion, which, together with an antecedent intracellular shift of sodium, resulted in a massive influx of water and sodium into the brain. The BBB permeability change to sodium, not to proteins, seems to play a predominant role in the pathogenesis underlying ischemic brain edema.

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Background and Purpose-The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. Methods-Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. Results-Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (Pϭ.023, Wilcoxon rank sum test) but not at 3 months (Pϭ.056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores. Conclusions-Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent. (Stroke. 1998;29:12-17.)