Clinical presentation and treatment of distal anterior inferior cerebellar artery aneurysms.

Aneurysms located at the distal portion of the anterior inferior cerebellar artery (AICA) are rare, and their clinical features are not fully understood. We report the clinical features and management of nine distal AICA aneurysms in nine patients treated during the past decade at Kagoshima University Hospital and affiliated hospitals. Our series includes seven women and two men. Of their nine aneurysms, eight were ruptured and one was unruptured; six were saccular and three were dissecting aneurysms. The most prevalent location was the meatal loop (n = 5) followed by the postmeatal (n = 3) and premeatal segment (n = 1) of the AICA, suggesting hemodynamic stress as an etiology of these distal AICA aneurysms. Of the nine patients, five presented with angiographic features suggestive of increased hemodynamic stress to the AICA and the common trunk of the posterior inferior cerebellar artery, with vertebral artery stenosis, marked laterality, and a primitive hypoglossal artery. We addressed eight aneurysms (eight patients) surgically; one aneurysm in one patient disappeared in the course of 3 months without surgical treatment. Of the eight surgically treated aneurysms, seven were ruptured and one was unruptured, five were clipped via lateral suboccipital craniotomy, two were trapped via lateral suboccipital craniotomy, and one was embolized. Good outcomes were obtained in six of the eight patients who underwent operation (75 %). We consider increased hemodynamic stress attributable to anatomic variations in the AICA and related posterior circulation to be the predominant contributor to the development of distal AICA aneurysms. Direct clipping and trapping yielded favorable outcomes in our series.

Germinoma with syncytiotrophoblastic giant cells arising in the corpus callosum.

A previously healthy 31-year-old Japanese man presented with a very rare germinoma of the corpus callosum without other intracranial lesions manifesting as transitory speech disturbance. Magnetic resonance (MR) imaging revealed a heterogeneously enhanced mass in the corpus callosum extending into the cavity of the septum pellucidum. A tumor specimen obtained by stereotactic biopsy revealed a two-cell pattern germinoma containing human chorionic gonadotropin (HCG)-beta-positive giant cells. The cerebrospinal fluid and serum levels of HCG and HCG-beta subunit were measurable. The diagnosis was germinoma with syncytiotrophoblastic giant cells. Three cycles of chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by radiation therapy achieved complete remission, and 5 cycles of chemotherapy with carboplatin and etoposide were added. MR imaging performed 40 months after the diagnosis showed a cicatricial cyst in the body of the corpus callosum, the original tumor site. All 11 previously reported cases of germinoma in the corpus callosum were associated with synchronous or metachronous intracranial lesions. These patients tended to be older than patients with general intracranial germinoma. Germinoma should be included in the differential diagnosis of corpus callosum tumors, especially in young adult males.

Changes in tissue factor and the effects of tissue factor pathway inhibitor on transient focal cerebral ischemia in rats.

INTRODUCTION: To determine the contribution of tissue factor (TF) to focal cerebral ischemia/reperfusion injury, we investigated the changes in TF in rat brains with transient focal cerebral ischemia and also assessed the effect of TF pathway inhibitor (TFPI). MATERIALS AND METHODS: Spontaneous hypertensive rats were subjected to 90-min of middle cerebral artery occlusion (MCAO) and then were reperfused for up to 24 h. Immediately after MCAO, recombinant human TFPI (rhTFPI) (50 or 20 microg/kg/min) was administered by means of a continuous intravenous injection for 4.5 h. RESULTS AND CONCLUSIONS: TF immunoreactivity decreased or scattered in the ischemic area after reperfusion, however, an increased TF expression was observed in the microvasculature with the surrounding brain parenchyma and it peaked at 3 to 6 h, which coincided with the start of fibrin formation. On the other hand, total TF protein in ischemic area continued to exist and did not remarkably change until 24 h after reperfusion. At 24 h after reperfusion, the total infarct volume in the group treated with 50 microg/kg/min rhTFPI was significantly smaller than that in the controls (saline). Western blotting and immunohistochemical studies showed that rhTFPI treatment resulted in a decrease of fibrin in the ischemic brains and microvasculature. TF-mediated microvascular thrombosis is thus considered to contribute to focal cerebral ischemia/reperfusion injury. The continuous infusion of rhTFPI until a peak of TF-mediated microvascular thrombosis therefore attenuates the infarct volume by reducing fibrin deposition in the cerebral microcirculation.

Integrin-linked kinase (ILK) regulation of the cell viability in PTEN mutant glioblastoma and in vitro inhibition by the specific COX-2 inhibitor NS-398.

We report the increased activity and expression of the ILK protein in human glioblastomas and demonstrate that ILK activity is regulated by PTEN. The transfection of wild type-PTEN into the glioblastoma cell line U-251 MG altered the localization of ILK in the cell membrane; transfection with PTEN down-regulated PKB/Akt-Ser-473 phosphorylation via the inhibition of ILK-signaling. Our results suggest that ILK is critical for the PTEN-sensitive regulation of PKB/Akt-dependent cell survival. The selective COX-2 inhibitor NS-398 was found capable of down-regulating ILK and PKB/Akt phosphorylation. Our data indicate that inhibition of ILK signaling may be beneficial in the treatment of PTEN-deficient glioblastoma.

Postoperative regression of desmoplastic infantile gangliogliomas: report of two cases.

OBJECTIVE AND IMPORTANCE: Desmoplastic infantile gangliogliomas (DIGs) are extremely rare tumors that respond well to treatment. However, their biological behavior remains to be clarified. We describe two patients whose DIGs spontaneously regressed after surgery, without adjuvant therapy. CLINICAL PRESENTATION: A 9-month-old girl presented with left hemiparesis, and a 6-month-old boy presented with increasing head circumference. For both patients, neuroimaging demonstrated a huge cystic tumor that included a solid portion and was widely attached to the dura. Gadolinium-diethylenetriamine penta-acetic acid produced strong enhancement. INTERVENTION: One patient underwent partial and the other subtotal tumor removal. Histologically, both tumors were diagnosed as DIGs. Postoperatively, the residual tumors were monitored without adjuvant therapy, and both regressed in several months. CONCLUSION: Our experience suggests that DIGs may include a subgroup of tumors with a tendency for spontaneous regression, possibly attributable to the induction of apoptosis.

Tumefactive myelinoclastic diffuse sclerosis--case report.

A 6-year-old boy presented with mental disturbance and progressive left hemiparesis. Magnetic resonance imaging demonstrated large intracranial mass lesions with ring-like enhancement. His neurological condition deteriorated rapidly. Open biopsy via craniotomy was performed under the suspicion of tumor. Histological examination showed massive demyelination and axon preservation, but no tumor cells. The diagnosis was myelinoclastic diffuse sclerosis (MDS). He was treated with high-dose methylprednisolone and improved dramatically. MDS is a rare demyelinating disorder of the central nervous system that affects mainly children and may mimic a brain tumor. MDS must be included in the differential diagnosis in young patients with a brain tumor with atypical radiological appearance.

Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK).

To investigate the biological effect of cerivastatin on glioblastoma cells, we exposed them to various concentrations of cerivastatin. Cerivastatin exhibited dual effects on glioblastoma cells in a dose-dependent manner. Immunofluorescence microscopy showed disruption of actin stress fibers and focal adhesion plaques even at nanomolar concentrations. Matrigel assay demonstrated marked inhibition of glioblastoma cell invasion. Immunoblot analysis using a phosphospecific antibody against focal adhesion kinase (FAK) showed that inhibition of migration was associated with the down-regulation of tyrosine phosphorylation of FAK. Our data suggest that cerivastatin may be beneficial for combination therapy with conventional anti-cancer drugs by inhibiting the invasion of glioblastoma.