Spinal intravascular papillary endothelial hyperplasia. Case report and review of the literature.

Intravascular papillary endothelial hyperplasia (Masson's vegetated hemangioendothelioma) is a rare condition affecting the neuroaxis. In the literature, only eight cases of this lesion involving the vertebral canal with spinal cord compression has been reported. We present a 37-year-old man with thoracic location mimicking schwannoma. Differential diagnosis, management, and review of literature are discussed in this short report.

Central Nervous System Strongyloides Stercoralis. A Case Report.

Strongyloidiasis is an infestation caused by the intestinal nematode Strongyloides stercoralis. It is potentially fatal in immunocompromised hosts due to its capacity to cause an overwhelming hyperinfestation however infested healthy individuals are usually asymptomatic. Hyperinfestation is extremely rare in the Central Nervous System (CNS) and usually limited to the gastrointestinal tract or lungs. CNS involvement in strongyloidiasis has only been seen in patients with hyperinfestation syndrome and may be fatal when misdiagnosed. In this report, we describe an unusual case of a 13-year-old girl presented with epileptic fits, multiple brain lesions and diagnosed as Strongyloides stercoralis infestation. Suitable frontal lesion biopsied and diagnosed as Strongyloides infestation and vasculitis. MRI features were totally regressed after the treatment with oral Albendazole for 3 months.

Expression profiling of RE1-silencing transcription factor (REST), REST corepressor 1 (RCOR1), and Synapsin 1 (SYN1) genes in human gliomas.

PURPOSE: The repressor element 1 (RE-1) silencing transcription factor (REST) is a transcription factor which represses the expression of neuronal differentiation-related genes including SYN1 gene. CoREST, encoded by RCOR1 gene, binds to the REST protein for remodeling of chromatin structure. Although there is a relation among REST, RCOR1, and SYN1 genes, the role of these genes in glioma tumors is still unclear. In this study, expressions of REST, RCOR1, and SYN1 genes were detected in primary cultures derived from tumor samples of diffuse astrocytoma (DA), anaplastic oligodendroglioma (AO), and glioblastoma multiforme (GBM) cases. METHODS: Expression profiles were analysed by RT-qPCR and the copy number variations were examined with qPCR in primary cultures. ChIP assay was performed to show binding characteristics of REST and CoREST proteins on promoter region of SYN1 gene. RESULTS: Means of relative expression for REST were as follows: 0.7898, 0.7606, and 0.7318 in DA, AO, and GBM groups, respectively. For RCOR1, expression means in DA, AO, and GBM groups were 0.7203, 0.7334, and 0.7230, respectively. SYN1 expression means were as follows: 0.3936, 0.3192, and 0.3197 in DA, AO, and GBM groups, respectively. Neither gain nor loss of copy numbers were detected for REST and RCOR1 genes in all groups. Copy loss for SYN1 was detected in primary culture of a DA case. REST and CoREST presented positive precipitation pattern on promoter region of SYN1 gene. CONCLUSIONS: Expressions of REST and RCOR1 genes may downregulate SYN1 expression in gliomas. Low expression pattern of SYN1 may maintain cancer stem-like phenotype which contributes to development of gliomas.

Management of Calvarial Tumors: A Retrospective Analysis and Literature Review.

AIM: Tumors of various organs that metastasize to bone do not neglect calvarium as a target. The aim of this study was to characterize the calvarial tumors. MATERIAL AND METHODS: We retrospectively reviewed 45 consecutive patients operated for calvarial masses from January 2002 till May 2012 at our hospital. Skull base tumors and patients ≤18 years were excluded. RESULTS: Three groups of lesions were found - calvarial metastases (15/45), primary tumors (5/45) and tumor-like lesions (25/45). Malignant lesions were equitable by gender distribution, higher age of onset (median age of primary =55; secondary = 60 years) and benign lesions by younger age (median = 35) and female bias (18/25). Calvarial metastases mostly presented with local swelling (10/15), local pain (6/15) and rarely neurologic deficit. There was associated dural sinus thrombosis (4/20 of malignant; 1/25 of benign lesions) and osteolysis (3/5 primary malignant, 13/15 secondary and 18/25 of benign lesions). Complete surgical excision was possible with minimal morbidity in all except one patient and nil mortality. CONCLUSION: Nearly half (20/45) of the calvarial lesions tend to be malignant with most of them presenting as silent painless masses. Surgical excision should be considered only after suitable investigation and appropriate neurosurgical set-up.

Downregulation of miR-195 via cyclosporin A in human glioblastoma cells.

PURPOSE: Cyclosporin A (CsA) is a potent immunosuppressive agent. MicroRNAs (miRs) which post-transcriptionally regulate gene expression are non-coding RNAs. The aim of this study was to investigate the effects of CsA on 88 miRs expression changes in glioma cells (U-87 MG). METHODS: CsA was used in U-87 MG glioma cells in doses of 10, 30 and 60 µM. Cytotoxic assays and determination of IC50 dose of CsA were performed. Relative quantification of 88 miRs was performed by real time RT-PCR. The fold changes of miRs determined and alterations in the miR expressions were compared with CsA-treated and CsA- free U-87 MG glioma cells. RESULTS: In U-87 MG cells treated with CsA, the IC50 dose was 10 µM. Seventeen of 88 human miRs were downregulated compared to the untreated control group by using miRs array. It was found that the expression levels of several miRs, in particular miR-195, was significantly decreased in CsA-treated U-87 MG cells. CONCLUSION: This study revealed a significant role of miR-195 in the molecular pathology of glioma cells which can also implicate potential application of miR-195 in cancer therapy. Rather than downregulation of miR-195 alone to exhibit cytotoxicity, treatment with CsA could be more effective especially on temozolomide-resistant cells.

Primary glioblastoma of the medulla spinalis: a report of three cases and review of the literature.

Primary spinal glioblastoma multiforme (spinal GBM) is not a very common entity. This paper presents an outline of this rare neoplasm, its clinical presentation, course, management and outcome and reports a 3-case series of spinal GBM. In this 3-case series with spinal GBM, one of the patients was operated for hydrocephalous 10 months later following the tumor surgery and another patient had cerebral metastasis after the surgery. In the postoperative period, two of the cases received radiotherapy and one received combined radiotherapy and chemotherapy with steroid therapy together following the tumor surgery. The review of the pertinent literature has revealed that due to the scarcity of the reported cases of primary spinal GBMs, this issue requires a closer look. GBM behaves more aggressive in medulla spinalis than it behaves when it originates from cerebrum. It may disseminate to the cerebrum during its course and it may cause hydrocephalus due to this dissemination (metastasis).

Assessment of genetic markers and glioblastoma stem-like cells in activation of dendritic cells.

Glioblastoma (GBM) is the most common and aggressive intraparenchymal primary brain tumor in adults. The principal reasons for the poor outcomes of GBM are the high rates of recurrence and resistance to chemotherapy. The aim of this study was to determine the role of tailored cellular therapy for GBM with a poor prognosis and compare the activity of dendritic cells (DCs) that have encountered GBM cells. Detecting the correlations between methylation and expression of MGMT and PTEN genes and GBM cancer stem cells (CSCs) markers after co-cultures with a mononuclear cell cocktail are also aims for this study. Allogenic umbilical cord blood (UCB)-derived DCs were labeled with the CD11a and CD123 for immature DCs, and CD80 and CD11c for mature DCs. CD34, CD45, and CD56 cells were isolated from allogenic UCB for using in DCs maturation. GBM CSCs were detected with CD133/1 and CD111 antibodies after co-culture studies. DC activation was carried out via GBM cells including CD133 and CD111 cells and a mononuclear cells cocktail including CD34, CD45, and CD56 natural killer cells. Real-time PCR was performed to detect the expression and promoter methylation status of PTEN and MGMT genes. The expression of CSCs markers was found in all GBM cases, and a statistically significant correlation was found among them after co-culture studies. The most pronounced affinity of DCs to GBM cells was observed at dilutions between 1/4 and 1/256 in co-cultures. There was a statistically significant correlation between cellularity and granularity ratios for CD123 and CD11c. PTEN and MGMT gene expression and methylation values were evaluated with respect to CSCs expression and no statistical significance was found. Activation of DCs might associate with CSCs and the mononuclear cells cocktail including CD34, CD45, and CD56 cells which were obtained from allogenic UCB.

Protein S deficiency, epileptic seizures, sagittal sinus thrombosis and hemorrhagic infarction after ingestion of dimenhydrinate.

Congenital protein S deficiency is associated with an increased risk of venous thrombosis. A14-year-old boy presented with epileptic seizures and thrombosis of the superior sagittal sinus and frontal hemorrhagic venous infarction after ingestion of 50 mg of dimenhydrinate, an antiemetic drug. The patient was found to be heterozygous for the factor V Leiden mutation and had a functional protein S deficiency. He recovered completely within a month after conservative treatment. Dimenhydrinate may have disrupted a subclinical pre-existing condition in this case.

Intravascular papillary endothelial hyperplasia of the central nervous system--four case reports.

Four rare cases of intracranial intravascular papillary endothelial hyperplasia (IPEH) manifesting as cranial nerve disturbances occurred in 16-, 18-, 24-, and 28-year-old females. Magnetic resonance imaging showed all lesions as isointense with strong enhancement on T1-weighted images, and as hyperintense on T2-weighted images. All lesions were removed via craniotomies. Histological examination found vascular structures and papillary spaces lined with endothelial cells showing immunoreactivity for CD31. Complete removal was curative in two cases, whereas incomplete removal resulted in cure in one case and residual deficits in one case. Iatrogenic deficits should be avoided in IPEH treatment by surgery. Differentiation from neoplasm such as angiosarcoma depends on histological characteristics.

Secretory meningiomas.

Secretory meningiomas are a rare meningioma subtype. Among meningiomas, the frequency of secretory meningiomas is 1.6%. Unlike other meningioma types, most of the patients were female (ratio 3:1). No recurrence was reported during the 24-180 months follow-up period of our secretory meningiomas in which, a low level of 0.3% Ki-67 proliferative index was reported. In this meningioma subtype, the percentage of cases with positive progesterone receptor is 33%. With carcinoembryonic antigen, cytokeratin and epithelial membrane antigen, in all the cases positivity was observed in both, the inclusions and the cells surrounding them. With human milk fat globulin 2, a high ratio (92%) of positivity was observed. Majority of the cases were negative with CA125, only three of the cases had suspicious positivity. Distribution of inclusions was irregular and their positive reactions showed varying staining features. Positivity with alpha-1-antitripsin was seen not only in the inclusions but also in some meningothelial cells as well. Ubiquitin was positive in inclusions of the 83% of cases. Staining features of the inclusions pointed out the possibility of them being in a varying age and/or content. Secretory meningiomas are a different type compared to other meningiomas, not only with their histological features but also with their clinical features as well.

Online electrochemical monitoring of nitric oxide during photodynamic therapy.

Photodynamic therapy (PDT), as a novel treatment modality, is based on the use of a photosensitizing agent with an excitation light source for the treatment of various malignancies. Its effect is mediated through reactive oxygen species and nitric oxide (NO), which are shown to be present in apoptosis. Individual differences among patients and even in different areas of the same tumor in one patient may cause a major problem with PDT: dose calculation during application of the light. An electrochemical sensor is proposed for online monitoring of NO generation as a solution of this problem. 5-Aminolevulinic acid (ALA) was administered as the photosensitizer in rat cerebellum. An amperometric sensor, selective to NO, was designed and tested both in vitro and in vivo during PDT. ALA-mediated PDT resulted in rapid generation of NO, starting as early as the application of light on the tissue. Simultaneous amperometric recordings have been carried out for 5 min during PDT. The progressive increase in NO concentration peaked at 1.10 min and then the response current began to decrease until it reached a plateau at around 70% of its peak value. This study, for the first time, electrochemically demonstrates the generation of NO during PDT. Rapid and stable responses obtained by the experimental setup confirmed that this method could be used as an online monitoring system for PDT-mediated apoptosis.

Local interstitial chemotherapy with sustained release bucladesine in de novo glioblastoma multiforme: a preliminary study.

This clinical study was designed to evaluate the safety and efficacy of the sustained release form of dibutryl adenosine-3',5'-cyclic monophosphate (dB-cAMP, bucladesine) placed in the tumor resection cavity at the time of recurrence of the de novo glioblastoma multiforme (GBM) patients. In a randomized prospective manner, 40 patients who were diagnosed as GBM in their first operations were included in this study. Four different therapy protocols were used: First group of 10 patients had tumor resection only. Second group assessed had only systemic chemotherapy as six i.v. infusions of fotémustine after tumor resection. Third group had implantation of bucladesine-loaded biodegradable polymeric sustained release (bcl-SR) pellets while the last group received six i.v. infusions of systemic fotémustine as in the second group in addition to local implantation of bcl-SR pellets. A biodegradable polymer, poly-DL-lactide-co-glycolide with molecular weight of 80000, was used as carrier matrix for the drug with an approximately 4-5 months of release time. Maximal doses of 20 mg of bucladesine with a mean dose of 15.5 mg were implanted. No bone marrow suppression occurred and there were no wound infections as far as the local bucladesine-loaded polymer therapy is concerned. In this randomized prospective trial of local interstitial chemotherapy with long acting bcl-SR did show a statistically significant delay of recurrence on the treatment of GBM patients. Best treatment results obtained from the local bcl-SR + systemic fotémustine treated group in which survival rate estimated by the Kaplan-Meier method was 70% in de novo GBM at 12 months.