Brain trauma causes the onset of an inflammatory process within the dural border cell layer; high levels of inflammatory cytokines were significantly correlated with recurrence and layering CSDH. A prolonged postoperative antiinflammatory medicine given as prophylaxis may help prevent the recurrence of a CSDH.

To contribute to a better understanding of the prognostic differences between atypical and malignant meningiomas as defined by the World Health Organization (WHO) and the influence of the grade of initial surgical excision on postoperative course, 42 cases of atypical and 29 of malignant meningioma were studied, along with long-term follow up. The two groups were compared with respect to long-term survival, recurrence-free survival, and median time to recurrence. The prognostic significance of the Simpson grade of surgical resection and tumor location was also considered. Survival at 5 and 10 years was recorded in 95% and 79%, respectively, of patients with atypical meningioma and in 64.3% and 34.5% of patients with malignant meningioma (p = 0.001). Recurrence-free survival and median time to recurrence were also significantly longer in patients with atypical than in those with malignant meningiomas: 11.9 versus 2 years (p = 0.001) and 5 versus 2 years (p < 0.0041), respectively. Six (26%) of the 23 recurring atypical meningiomas became malignant. Simpson Grade I resection and location in the cerebral convexity, which were closely related, were found to be associated with a significantly better clinical course in the entire series (p < or = 0.0016). Patients with atypical meningiomas fared better than those with malignant meningiomas after incomplete surgical excision (Simpson Grades II-III), but the difference was not statistically significant. Multivariate analysis using the Cox model indicated that radical extirpation (Simpson Grade I vs. II-III) and histological findings (atypical meningioma vs. malignant meningioma) were significantly related to prolonged survival (p < 0.0003 and p < 0.0388, respectively). In conclusion, the current study shows that for most patients with atypical meningioma the prognosis was less severe than for those with malignant meningioma, but the risk of a downhill course resulting from malignancy after incomplete resection and recurrence was not negligible (26%). In addition, the WHO classification was found to be inadequate for a minority of the atypical meningioma cases, which currently have the same unfavorable course as cases of malignant meningioma. The results also indicate that objective Simpson Grade I extirpation of convexity meningiomas can be successful despite histological findings of malignancy.

The precise localizations of the neural substrates of voluntary inhibition are still debated. It has been hypothesized that, in humans, this executive function relies upon a right-lateralized pathway comprising the inferior frontal gyrus and the presupplementary motor area, which would control the neural processes for movement inhibition acting through the right subthalamic nucleus (STN). We assessed the role of the right STN, via a countermanding reaching task, in 10 Parkinson's patients receiving high-frequency electrical stimulation of the STN of both hemispheres (deep brain stimulation, DBS) and in 13 healthy subjects. We compared the performance of Parkinson's patients in 4 experimental conditions: DBS-ON, DBS-OFF, DBS-OFF right, and DBS-OFF left. We found that 1) inhibitory control is improved only when both DBS are active, that is, the reaction time to the stop signal is significantly shorter in the DBS-ON condition than in all the others, 2) bilateral stimulation of STN restores the inhibitory control to a near-normal level, and 3) DBS does not cause a general improvement in task-related motor function as it does not affect the length of the reaction times of arm movements, that is, in our experimental context, STN seems to play a selective role in response inhibition.

3Fondazione 'Carlo Ferri' per la prevenzione e la cura dei tumori, via Edmondo Riva 42, 00015 Monterotondo, Italy AbstractGermline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (nZ103), including 17 with AIP mutations (AIP mut ). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P!0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (PZ0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (PZ0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP mut PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.

Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high infiltration in the brain parenchyma rendering the tumor difficult to eradicate by neurosurgery. Efforts to identify molecular targets involved in the invasive behavior of GBM suggested ion channel inhibition as a promising therapeutic approach. To determine if the Ca2+-dependent K+ channel KCa3.1 could represent a key element for GBM brain infiltration, human GL-15 cells were xenografted into the brain of SCID mice that were then treated with the specific KCa3.1 blocker TRAM-34 (1-((2-chlorophenyl) (diphenyl)methyl)-1H-pyrazole). After 5 weeks of treatment, immunofluorescence analyses of cerebral slices revealed reduced tumor infiltration and astrogliosis surrounding the tumor, compared with untreated mice. Significant reduction of tumor infiltration was also observed in the brain of mice transplanted with KCa3.1-silenced GL-15 cells, indicating a direct effect of TRAM-34 on GBM-expressed KCa3.1 channels. As KCa3.1 channels are also expressed on microglia, we investigated the effects of TRAM-34 on microglia activation in GL-15 transplanted mice and found a reduction of CD68 staining in treated mice. Similar results were observed in vitro where TRAM-34 reduced both phagocytosis and chemotactic activity of primary microglia exposed to GBM-conditioned medium. Taken together, these results indicate that KCa3.1 activity has an important role in GBM invasiveness in vivo and that its inhibition directly affects glioma cell migration and reduces astrocytosis and microglia activation in response to tumor-released factors. KCa3.1 channel inhibition therefore constitutes a potential novel therapeutic approach to reduce GBM spreading into the surrounding tissue.