Symptomatic hemorrhage associated with recurrent pilocytic astrocytoma with granulation tissue--case report.

A 51-year-old woman had been followed up for 10 years for recurrence of pilocytic astrocytoma 5 years after the initial treatment consisting of subtotal resection, chemotherapy, and radiation therapy. The patient presented with sudden onset of headache and vomiting. Computed tomography and T(2)*-weighted magnetic resonance imaging revealed hemorrhage in the tumor located in the right basal ganglia, thalamus, and hypothalamus. She underwent gross total resection of the lesion. Histological examination confirmed recurrent pilocytic astrocytoma with organizing hematoma and granulation tissue. Although neither symptomatic hemorrhage nor late benign recurrence is common, careful long-term follow up is necessary for patients with pilocytic astrocytoma.

The role of cerebral cyst formation in the intractability of epilepsy.

OBJECTIVES: The aims of the present study were: (1) to examine single focal, intractable epilepsy associated with gliotic changes and (2) to discuss the mechanisms underlying seizure intractability. PATIENTS AND METHODS: Records of 34 patients with surgically treated intractable epilepsy were analysed retrospectively. Thirteen out of 34 patients had single epileptic focus histologically identified as a gliotic change. Seizure types, neuroradiological findings including the location and size of the foci, the hemosiderin deposition and calcification, intra-operative findings, and pathological findings of 13 patients were analysed in this study. Whether cyst formation was presented was also recorded. Tailored resections of epileptogenic lesions were performed using electrocorticography and ultrasonography. RESULTS: Cyst formations were observed in 10 out of 13 patients. In eight of the patients with cyst formation, seizures initially were well controlled, but the subsequent seizures increased in both severity and frequency in a stepwise manner. All patients with cyst formation became seizure free after the removal of the cyst wall and surrounding gliotic tissue. CONCLUSIONS: Analyses of the clinical courses, pathological and hydrodynamic findings suggest that the gliotic changes secondarily induced by cystic changes in brain parenchyma appear to play an important role in seizure intractability. We adapted the 'Starling resistor model' of hydrodynamics as a hypothetical model for the intracranial cyst and fluid passage to explain the mechanisms of the formation of epileptogenic gliotic changes.

Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells.

Because the aberrantly activated phosphoinositide 3-kinase (PI3K)/Akt pathway renders tumor cells resistant to cytotoxic insults, including those related to anticancer drugs, inhibition of the pathway may possibly restore or augment the effectiveness of chemotherapy. Using the human malignant glioma cell lines U87, A172, LN18, and LN229, we examined effects of the PI3K inhibitor LY294002 on both apoptosis and cytotoxicity induced by chemotherapeutic agents, including antimicrotubule agents vincristine and paclitaxel, an alkylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea, a topoisomerase II inhibitor etoposide, and a DNA cross-linking agent cisplatin (cis-diamminedichloroplatinum), and we compared the LY294002-induced enhancement of effects of those agents. Ten to 20 micro M LY294002 augmented both apoptosis and caspase 3-like activity caused by antimicrotubule agents to a larger extent than induced by 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, and cisplatin in all four malignant glioma cell lines examined. The same doses of LY294002 enhanced cytotoxicity more efficiently with antimicrotubule agents than with other chemotherapeutic agents. Quantitative analyses using a modified isobologram and median effect plot method revealed that enhancement by LY294002 of vincristine- or paclitaxel-induced cytotoxicity was synergistic, whereas enhancement by the PI3K inhibitor of the other chemotherapeutic agent-induced cytotoxicity was additive. Our study indicates that the synergistic augmentation of the cytotoxicity by LY294002 occurs specifically with antimicrotubule agents, at least partially through an increase in caspase 3-dependent apoptosis, and we suggest that inhibitors of the PI3K/Akt pathway in combination with antimicrotubule agents may induce cell death effectively and be a potent modality to treat patients with malignant gliomas.

Brain stem glioblastoma with multiple large cyst formation and leptomeningeal dissemination in a 4-year-old girl.

The authors report a 4-year-old girl who developed brain stem glioblastoma. Meningeal irritation was present at onset. Magnetic resonance imaging revealed intracranial and intraspinal leptomeningeal dissemination, which progressed faster than the original tumor. Multiple large cysts developed at the interhemispheric and prepontine cisterns, resulting in progressive obstructive hydrocephalus. The patient survived only 5 months after presentation. Histology was verified by autopsy.

Unusual progression of pleomorphic adenoma of the lacrimal gland: case report.

A 72-year-old female complained of acute pain on left eye movement followed by progressive exophthalmos. Neuroimaging revealed a large well-demarcated lesion consisting of solid and cystic parts, as well as bone destruction and hemorrhage, within the left orbital cavity. The preoperative diagnosis was pleomorphic adenoma with or without malignant transformation, or cavernous angioma. En bloc excision including adjacent tissues was planned to resolve the progressive symptoms and to obtain a histological diagnosis. The transcranial route was chosen since tumor invasion to the cranial base was possible. The histological diagnosis was pleomorphic adenoma. Pathological and preoperative radiological examinations indicated that repeated intratumoral hemorrhage had caused the orbital bone destruction and acute orbital pain. Neoplasms should be differentiated from a wide spectrum of other possible pathologies. Accurate clinical diagnosis of neoplasm in the orbital cavity is important for correct therapeutic management. Malignancy is generally suspected if painful and progressive signs and symptoms are associated with an orbital mass lesion. The present case suggests that pleomorphic adenoma should also be considered in the differential diagnosis. The therapeutic strategy for lacrimal gland tumors remains controversial, so a flexible management approach is required.

Unusual variant of the anterior cerebral artery.

A rare abnormality of the A1 segment of the anterior cerebral artery (ACA) is reported. The right ACA bifurcated into two parts at the middle point of the A1 segment, and these segments did not rejoin. The superior right A1 segment connected with the left A1 and formed a single pericallosal artery. The inferior right A1, from which the right ophthalmic artery originated, had no connection with the left A1.

Experimental appraisal of the lack of antitumor natural killer cell-mediated immunosurveillance in response to lymphomas growing in the mouse brain.

OBJECT: Natural killer (NK) cell-mediated immunosurveillance in the brain is currently obscure, in contrast with the intracerebral immune reaction of cytotoxic T lymphocytes (CTLs) to tumor cells. The goal of this study, in which a controlled tumor model was used, was to investigate a relationship between NK cells and major histocompatibility complex (MHC) Class I gene expression in intracerebral tumor-bearing hosts. METHODS: A matched set of two cloned tumor cell lines (lymphoma+ and lymphoma-), which differ only in MHC Class I gene expression, was established from the parental YAC-1 cell line (a target widely accepted as being sensitive to murine NK cells). An in vivo rapid elimination assay (REA) was performed using tumor cells labeled with [125I] 5-iodo-2-deoxyuridine to evaluate intracerebral NK cell-mediated defense immunity. There was no difference in the in vitro growth rate and c-myc gene expression between lymphoma+ and lymphoma- cells. An in vitro cytotoxicity assay showed that the lymphoma+ cell line was sensitive to MHC Class I-restricted CTL-mediated lysis, whereas the lymphoma- line was refractory to it. Both were susceptible to NK cell-mediated lysis, comparable to the level shown by YAC-1 cells. Flow cytometry revealed that lymphoma+ reacted positively for cell-surface MHC Class I molecules, whereas lymphoma- had no reaction. Four- to 72-hour REAs, performed using either cell line, disclosed no clearance of radiolabeled tumor cells from the brain in independent groups of untreated and T cell-depleted mice; this contrasted with eradication of radioactivity from the lungs. In NK cell-depleted mice, however, there was no elimination of radiolabeled tumor cells from the brain or lungs. The MHC Class I expression on lymphoma+ cells was enhanced after intracerebral inoculation, rendering them less sensitive to NK cells. By contrast, lymphoma- cells remained negative for cell-surface MHC expression, being sensitive to NK cells and refractory to CTLs after intracerebralinoculation. These results indicate the absence of NK cell-mediated lytic activity in the brain. This allows even NK cell-sensitive tumor cells to escape intracerebral immunosurveillance. CONCLUSIONS: These experiments have refined the information that the brain may lack NK cell-mediated defense immunity against intracerebrally growing tumors, representing a characteristic aspect of this immunologically privileged organ.

A new, miniature ultrasonic surgical aspirator with a handpiece designed for transsphenoidal surgery. Technical note.

The authors describe an innovative surgical instrument designed to remove hard fibrous masses from the pituitary region, which cannot be completely removed using standard transsphenoidal surgical procedures. The innovative features of the instrument include a miniature ultrasonic surgical aspirator and an extra-long bayonet handpiece with a 1.9-mm-diameter translucent tip. Intraoperative use of this refined device may increase the effectiveness of the removal of fibrous lesions within a narrow operative field, while also preserving surgical safety.

Experimental validation of deuterium oxide-mediated antitumoral activity as it relates to apoptosis in murine malignant astrocytoma cells.

OBJECT: Deuterium oxide (D2O), or heavy water, affects a variety of biological activities different from those of water. The authors examined the antitumoral effect of D2O on brain neoplasms and demonstrated D2O-mediated cytotoxicity by using a Rous sarcoma virus-induced murine malignant astrocytoma cell line, RSVM. The mechanism of the observed cytotoxicity may involve D2O-induced apoptosis and cell-cycle modulation. METHODS: The authors performed an assay with methylthiazol tetrazolium bromide and a trypan blue dye exclusion test to confirm in vitro D2O-mediated cytotoxicity for RSVM cells. At D2O concentrations of 10 to 50%, the cytotoxic effect was dose and time dependent. Flow cytometry analysis revealed programmed cell death (apoptosis) and the accumulation of RSVM cells during the G2/M phase. By applying the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method, fluorescein isothiocyanate-annexin V and propidium iodide double staining, and caspase-family protease activity analysis, the authors demonstrated both DNA fragmentation and enhancement of caspase activity after a 48-hour treatment with D2O, thus indicating that D2O induces apoptosis in RSVM cells. Apoptotic DNA fragmentation was completely abolished by the caspase inhibitor Z-VAD-FMK (benzyloxycarbonil-Val-Ala-Aps-fluoromethylketone). The findings indicate that the caspase activation pathway may be involved in D2Oinduced apoptosis. CONCLUSIONS: The authors found that D2O is cytotoxic to malignant astrocytoma cells. The mechanism of D2O-mediated cytotoxicity involved the induction of apoptosis and cell accumulation during the G2/M phase. This D2O-induced apoptosis is modulated through the caspase activation pathway.

Growth inhibition of human malignant glioma cells induced by the PI3-K-specific inhibitor.

OBJECT: The phosphatase and tensin homolog deleted from chromosome 10 (PTEN) functions as a tumor suppressor by negatively regulating the growth/survival signals of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. The PI3-K/Akt pathway in PTEN-deficient tumors may be one of the key targets for anticancer therapy. The authors examined the effects of the PI3-K inhibitor 2-(4-morpholinyl)-8-phenylchromone (LY294002) on human malignant glioma cells, and compared these effects on PTEN-deficient cells with those on PTEN-wild-type (PTEN-wt) cells. METHODS: Using human malignant glioma cell lines, including the PTEN-deficient cells A172 and U87MG and the PTEN-wt cells LN18 and LN229, the effects of LY294002 on cell growth, apoptosis, and chemotherapeutic agent-induced cytotoxicity were evaluated. The LY294002 inhibited the growth of U87MG cells associated with reduced phosphatidylinositol 3,4,5,-trisphosphate and phosphorylated Akt, and also induced growth inhibition in three other cell lines. Although LY294002 caused apoptosis in all four cell lines, apoptosis seemed to contribute to only a small portion of growth inhibition induced by LY294002. There was no link between the status of PTEN and the median inhibitory concentration values for LY294002 or between the gene status and the extent of LY294002-induced apoptosis. The LY294002 significantly augmented the cytotoxicity induced by etoposide in PTEN-deficient cells, but not in PTEN-wt cells. Enhancement of 1,3-bis(2-chloroethyl)-1-nitrosourea- and cisplatin-induced cytotoxicity by LY294002 was not linked to the status of PTEN. No marked difference in the amounts of phosphorylated Akt was found between PTEN-deficient and PTEN-wt cells. CONCLUSIONS: The findings show that PI3-K is a possible target for therapy in patients with gliomas, and PI3-K inhibitors in combination with chemotherapeutic agents could be potent therapeutic modalities for patients with malignant gliomas.

Integration of ultrasonography and endoscopy into transsphenoidal surgery with a "picture-in-picture" viewing system--technical note.

A technique to integrate ultrasonography and endoscopy is described for transsphenoidal surgery to prevent intraoperative internal carotid artery (ICA)-related, life-threatening complications such as aneurysmal formation and carotid-cavernous fistula. The ultrasound unit helps avoid direct injury to the ICA. The technical advantage of this system is the miniature 1-mm diameter microvascular probe, which does not disturb the operative field. An arterial or venous flow source of even an invisible vessel can be detected easily, noninvasively, and reproducibly. Real-time information with a 100% detection rate for the ICA is helpful for predicting localization even in the intracavernous portion, where the ICA is invisible. The endoscope unit can visualize the dead angle areas of the operating microscope by varying the endoscopic gateways and display on a "picture-in-picture" system. The advantage of both devices is the integration with a video processor, so that the real-time information from each unit can be switched intraoperatively onto the display as required. This method is of particular help for removing lesions with intracavernous invasion or encasement of the ICA.

[Evaluation of brain tumors by simultaneous dual isotope SPECT with 201Tl-chloride and 99mTc-MIBI].

Single photon emission computed tomography (SPECT) is useful for detecting brain tumors. In this study, we evaluated the utility of simultaneous dual SPECT with 201Tl-Chloride (Tl) and 99mTc-MIBI (MIBI) for diagnosis of brain tumors. We evaluated 20 cases, including 2 glioblastomas, 7 anaplastic astrocytomas, 2 oligodendrogliomas, 2 anaplastic ependymomas, 2 medulloblastomas, 2 meningiomas, 1 malignant meningioma, 1 pituitary adenoma, and 1 craniopharyngioma. We analyzed the uptake ratio (T/N ratio) of tracers in both Tl and MIBI at max counts/pixels ratio in the region of interest. The T/N ratios in early and delayed images were described as early ratios (ER) and delay ratios (DR), respectively. The retention index (RI) was calculated as the DR/ER ratio. Significant correlations were found between ER and DR for both Tl (DR = 0.797 * ER + 0.359, r = 0.871), and MIBI (DR = 0.961 * ER - 0.191, r = 0.784). Next, we analyzed the correlations between Tl and MIBI SPECT, for ER, DR, and RI. ER values for the two were strongly correlated (r = 0.791), DR values were weakly correlated (r = 0.556), and RI exhibited no correlation between them (r = 0.328). There were no correlations between tumor volume and T/N ratio for the two (ER-Tl; r = 0.0095, DR-TI; r = 0.0050, ER-MIBI; r = 0.036, DR-MIBI; r = 0.254). Lastly no correlation was found between RI-Tl and RI-MIBI (r = 0.328). We discuss the difference in the mechanism of accumulation of two tracers and the significance of simultaneous dual SPECT using them for the differential diagnosis of pituitary tumors, regrowth of oligodendrogliomas, and multidrug resistance of chemotherapy. Dual SPECT with Tl and MIBI appears to be useful for the diagnosis of brain tumor.

Rathke's cleft cyst with non-hemorrhagic rupture resulting in alteration of signal intensity for a short period: a case report.

In a case of 23-year-old female with Rathke's cleft cyst (RCC), unusual changes with size and morphology on computed tomography (CT) and magnetic resonance images (MRI) were noted in a short period of 3 weeks after spontaneous rupture. The CT noted that the intracystic isodensity was changed to hyperdensity. And MRI showed not only a decrease in size of the lesion but also changing from hypo- and hyperintensity in T1- and T2-weighted images to hyperintensity in both T1- and T2-weighted images. The intraoperative findings disclosed that the cyst content was milky-like, but not hemorrhagic. We considered that the leakage of cyst content to the cerebrospinal fluid pathway caused not only inflammatory reaction but also waxing and waning of both the cyst size and intralesional protein concentration, which resulted in unusual changing CT and MR appearance. We should take into consideration that the nature of RCC can be altered by not only intracystic hemorrhage but also non-hemorrhagic rupture even for a short period.