A large growing occipital meningocele with Dandy-Walker syndrome: A case report and review of the literature.

Background: Dandy-Walker syndrome (DWS) is a well-known developmental anomaly. An occipital meningocele (OMC) is recognized as a malformation that is relatively often associated with DWS, but the association of DWS with OMC has been reported in approximately 40 cases. We present herein a rare clinical course of DWS with OMC, in which the sac was small at birth and became progressively larger. Case Description: A 5-day-old baby boy was referred to our hospital due to OMC. He was born at 33 gestational weeks due to premature rupture of the membranes. He was diagnosed as having DWS associated with OMC. The OMC was covered with skin and its maximum diameter at birth was 3 cm. Magnetic resonance imaging showed an occipital bone defect and continuity of the fourth ventricle, posterior fossa cyst, and OMC sac. The aqueduct was patent, and no hydrocephalus was found. The OMC sac increased progressively with moderate hydrocephalus and reached 7 cm at the age of 54 days when his weight was 2508 g. A cystoperitoneal shunt and repair were performed after sinus venography by contrast computed tomography (CT). At the age of 1 year and 8 months, he had moderate developmental disabilities. Conclusion: In most cases reported, the OMC was relatively small, and large and giant sizes were reported in only six cases. Almost all cases remained the same size as at birth and underwent surgical intervention as early as possible. It was possible to understand the relationship between the occipital bone defect and abnormal running of sinuses such as the superior sagittal sinus, torcular Herophili, and transverse sinus preoperatively from the CT venography (CTV) image. CTV may be an effective and important method for safely performing repair and shunt.

Management for a patient of moyamoya disease presenting with ischemic stroke in the first trimester of pregnancy.

We report an extremely rare case of a 27-year-old woman presenting with ischemic stroke as an initial manifestation of moyamoya disease in the first trimester of pregnancy. We conducted an artificial abortion when her neurological symptoms rapidly became refractory to optimal antithrombotic treatments. The progression of neurologic deficits stopped immediately after abortion, resulting in recovery to independence, with slight motor aphasia and right hemiparesis due to improved cerebral flow. We highlight rapid artificial abortion combined with antithrombotic treatment for patients of moyamoya disease with pregnancy-associated ischemic stroke as an appropriate treatment to correct hemodynamic instability and suppress the progression of neurological symptoms.

Combined morphological, immunohistochemical and genetic analyses of medulloepithelioma in the posterior cranial fossa.

Medulloepithelioma is a rare and highly malignant primitive neuroectodermal tumor that usually occurs in childhood. The diagnosis of this entity required only morphological analysis until the World Health Organization classification of central nervous system (CNS) tumors was revised, and now genetic analysis is necessary. We report a case of medulloepithelioma in the posterior cranial fossa that was diagnosed by both morphological and genetic analyses based on this classification. A 10-month-old girl was admitted to our hospital with consciousness disturbance and vomiting. Neuroimaging revealed a partially calcified mass and cyst formation in the posterior cranial fossa. Partial resection of the tumor was performed and histological findings revealed multilayered rosettes with LIN28A staining, but genetic analysis showed no amplification of the C19MC microRNA cluster at 19q14.32. Therefore, we diagnosed the tumor as medulloepithelioma belonging to other CNS embryonal tumors. The patient was immediately treated with systemic high-dose chemotherapy. Follow-up neuroimaging 10 months later showed no signs of recurrence. Medulloepitheliomas are difficult to diagnose by routine HE staining and require combined morphological, immunohistochemical and genetic analyses to provide an accurate diagnosis.

[A Case of Ruptured Distal Anterior Choroidal Artery Aneurysm Associated with a Twig-Like Middle Cerebral Artery, Treated with Single-Stage Aneurysm Clipping and STA-MCA Double Anastomoses in the Acute Phase].

We report the case of a patient who has progressed well over 5 years following single-stage aneurysm clipping and superficial temporal artery-middle cerebral artery(STA-MCA)double anastomoses in the acute phase, for a ruptured distal anterior choroidal artery(AChA)aneurysm accompanied by a twig-like MCA. The patient was a 49-year-old female who developed a sudden severe headache and disturbance of consciousness due to subarachnoid hemorrhage and intraventricular hemorrhage(IVH). Cerebral angiography showed a right twig-like MCA associated with an abnormal vascular network and a ruptured aneurysm in the distal AChA. A day after emergency ventricular drainage for acute hydrocephalus, right frontotemporal craniotomy enabled distal AChA aneurysm clipping, together with removal of the IVH via transchoroidal fissure approach, in addition to STA-MCA double anastomoses to prevent recurrence of hemorrhage. The IVH resolved after surgery and no new infarct area was observed. Cerebral angiography revealed the disappearance of the aneurysm, good patency of the double bypass, and reduction of the abnormal vascular network. The patient gradually recovered without any neurological deficits, except for mild memory disturbance. Five years after the surgery, the patient has experienced no recurrence. The single-stage operation of aneurysm clipping and STA-MCA double anastomoses was made possible by devising an approach for a ruptured cerebral aneurysm, even in the acute stage. The successful improvement of cerebral circulation and prevention of cerebral hemorrhage from an early stage could serve as a reference for the treatment of similar hemorrhagic cases.

Evaluation of serial changes on computed tomography and magnetic resonance imaging after implantation of carmustine wafers in patients with malignant gliomas for differential diagnosis of tumor recurrence.

Carmustine wafers are approved for localized treatment of malignant glioma. In this study, overall changes in computed tomography (CT) and magnetic resonance (MR) images of malignant glioma patients treated with carmustine wafer implantation were evaluated. The subjects were 25 patients undergoing craniotomy for malignant glioma resection and carmustine wafer implantation. Changes in the appearance of wafers, the resection cavity, and the adjacent parenchyma on CT and MR imaging were evaluated retrospectively. On CT, the wafers changed from an initially high-dense to an iso-dense appearance. All MR studies showed a low-intense wafer within 2 days. The wafers changed to a high- or iso-intense appearance on fluid attenuated inversion recovery and T1-weighted imaging, whereas they changed to an iso- to low-intense appearance on T2-weighted imaging. Gas in the cavity increased gradually after surgery, achieved a peak at 1 week postoperatively, and then disappeared in 1-3 months. Increased volume of the resection cavity was observed in 48% of patients. Regarding changes in the adjacent parenchyma, obvious contrast enhancement at the wall of the resection cavity was seen in 91% of cases at 1 month, but this disappeared gradually. Edema around the resection cavity was increased in 7 patients (28%), of whom only two experienced symptoms due to edema. We conclude that these radiological changes after carmustine wafer implantation should be carefully followed up, because these changes can easily be mistaken for infectious disease or recurrent tumors.

Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas.

The secreted protein acidic and rich in cysteine (SPARC) is a secreted glycoprotein that plays an essential role in promoting the motility of invasive tumor cells. In the present study, we investigated the role of SPARC in the motile and invasive activities of human glioma cells by silencing the SPARC gene. Introduction of SPARC-targeted small interfering RNA (siRNA) into glioma cell lines resulted in downregulation of SPARC expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with SPARC siRNA compared with those transfected with control siRNA. In an organotypic brain slice model, co-culture of glioma spheroids and rat brain slices showed that SPARC siRNA-transfected glioma cells failed to invade the surrounding normal brain tissue. In addition, intracerebral injection of glioma cells transfected with SPARC siRNA in nude mice resulted in the formation of a non-invasive tumor, whereas injection of cells transfected with control siRNA resulted in diffuse invasive tumors. Since SPARC was exclusively expressed in the invasive zone of the tumor margin and the area surrounding tumor necrosis, we investigated the relationship between SPARC expression and hypoxic stress. SPARC expression was upregulated under hypoxic stress of 1% oxygen concentration in glioma cells. Silencing hypoxia-inducible factor-1alpha with siRNA reduced the overexpression of SPARC induced under hypoxic conditions. These results suggest that SPARC plays an essential role in the invasive activity of human glioma cells, under hypoxic conditions. Downregulation of SPARC may be a novel anti-invasion therapeutic strategy for malignant gliomas.

Silencing hypoxia-inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas.

Malignant gliomas are characterized by active invasiveness, necrosis, and vascular proliferation. These pathological features have been speculated to be caused by tissue hypoxia. Hypoxia-inducible factor-1 (HIF-1), which is controlled by rapid stabilization of the HIF-1alpha subunit, is a pivotal transcriptional factor in the cellular response to hypoxia. Although many studies have described the relationship between tumor angiogenesis and hypoxic environment, the roles of HIF-1 in cell invasion have been barely elucidated in malignant gliomas. We investigated the role of HIF-1alpha in the motile and invasive activities of human glioma cells under hypoxia. Four malignant glioma cell lines, U87MG, U251MG, U373MG, and LN18, were cultured under 21 and 1% oxygen concentration. Expression of HIF-1alpha under hypoxia was observed to be much higher than that under normoxia in all cell lines. Introducing HIF-1alpha-targeted small interfering RNA (HIF-1alpha siRNA) into the glioma cell lines resulted in downregulation of HIF-1alpha expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with HIF-1alpha siRNA compared with those transfected with the control siRNA. Co-culture of glioma spheroids and rat brain slices showed that HIF-1alpha siRNA-transfected glioma cells failed to invade the surrounding normal brain tissue in an organotypic brain slice model. These effects of HIF-1alpha siRNA were more conspicuous under hypoxia than under normoxia. In addition, under hypoxic conditions, the level of matrix metalloproteinase (MMP)-2 mRNA was upregulated, and that of tissue inhibitor of metalloproteinase (TIMP)-2 was downregulated in all glioma cell lines. Treatment with HIF-1alpha siRNA resulted in downregulation of MMP-2 mRNA and upregulation of TIMP-2 mRNA. Furthermore, the enzyme activities of MMP-2 and MMP-9, both of which were activated by hypoxia, decreased with the introduction of HIF-1alpha siRNA. These findings suggest that overexpression of HIF-1alpha induced by hypoxic stress is an essential event in the activation of glioma cell motility through alteration of invasion-related molecules. Targeting the HIF-1alpha molecule may be a novel therapeutic strategy for malignant gliomas.