ObjectEndoscopic surgery is routinely used to treat intracranial arachnoid cysts. However, the indications and results with respect to the different cyst locations, compared with those of microsurgical fenestration and cyst shunting, deserve to be discussed.MethodsThe authors review 18 patients with intracranial arachnoid cysts treated by pure endoscopic technique in their neurosurgical department. There were 10 male and 8 female patients ranging in age from 2 months to 48 years (median age 19.4 years). The cyst location was suprasellar in 5 cases, quadrigeminal in 5, cortical hemispheric in 2, sylvian region in 3, and posterior fossa in 3. The authors also reviewed the literature, comprising 61 reports for an overall number of 645 patients with intracranial arachnoid cysts treated by different surgical techniques. These techniques included microsurgical excision or fenestration by craniotomy, cyst shunting, and endoscopic fenestration. The surgical results of the different techniques according to the different cyst locations underwent statistical analysis.ResultsThe overall success rate (complete or partial clinical remission) in the authors' endoscopic series was 83.3% (15 of 18 cases), which is rather similar to that of 222 patients treated endoscopically and reported on in the literature (84.2%). In the overall endoscopic group, a higher success rate was found for cysts in the suprasellar (89.7%), quadrigeminal (88.5%), and posterior cranial fossa (83.3%) regions compared with sylvian (70%) and cortical and interhemispheric (75%) regions. The statistical comparison of the results of the endoscopic series with those of craniotomy and shunting revealed no significant differences for suprasellar, quadrigeminal, or posterior cranial fossa cysts, whereas the success rate of endoscopy is lower than that of other techniques for sylvian and cortical cysts.ConclusionsEndoscopy is a safe and effective therapeutic modality for patients with intracranial arachnoid cysts. Cysts of the suprasellar and quadrigeminal regions and posterior fossa are the best indications for neuroendoscopy; on the other hand, cortical cysts are best treated by microsurgical fenestration or shunting. For sylvian cysts, the endoscopic procedure may be advocated in most cases.
Malignant gliomas are highly dependent on the isoprenoid pathway for the synthesis of lipid moieties critical for cell proliferation. The isoprenoid derivative N6-isopentenyladenosine (iPA) displays pleiotropic biological effects, including a direct anti-tumor activity in several tumor models. The antiglioma effects of iPA was then explored in U87MG cells both in vitro and grafted in mice and the related molecular mechanism confirmed in primary derived patients' glioma cells. iPA powerfully inhibited tumor cell growth and induced caspase-dependent apoptosis through a mechanism involving a marked accumulation of the pro-apoptotic BIM protein and inhibition of EGFR. Indeed, activating AMPK following conversion into its iPAMP active form, iPA stimulated EGFR phosphorylation and ubiquitination along a proteasome-mediated pathway which was responsible for receptor degradation and its downstream signaling pathways inhibition, including the STAT3, ERK and AKT cascade. The inhibition of AMPK by compound C prevented iPA-mediated phosphorylation of EGFR, known to precede receptor loss. As expected the block of EGFR degradation, by exposure to the proteasome inhibitor MG132, significantly reduced iPA-induced cell death. Given the importance of receptor degradation in iPA-mediated cytotoxicity, we also documented that the EGFR expression levels in a panel of primary glioma cells confers them a high sensitivity to iPA treatment. In conclusion our study provides the first evidence of iPA antiglioma effect. Indeed, as glioma is driven by aberrant signaling of growth factor receptors, particularly the EGFR, iPA, alone or in association with EGFR targeted therapies, might be a promising therapeutic tool to achieve a potent anti-tumoral effect.
Glioblastoma (GBM), the most aggressive brain cancer, is highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical for cell proliferation but the function and regulation of key intermediate enzymes like farnesyl-diphosphate synthase (FDPS), up to now, remained unknown. A deregulated expression and activity of FDPS was the central research idea of the present study. FDPS mRNA, protein and enzyme activity were analyzed in a cohort of stage III-IV glioma patients (N = 49) and primary derived cells. FDPS silencing helped to clarify its function in the maintenance of malignant phenotype. Interestingly, compared to tumor-free peripheral (TFB) brain and normal human astrocytes (NHA), FDPS protein expression and enzyme activity were detected at high degree in tumor mass where a correlation with canonical oncogenic signaling pathways such as STAT3, ERK and AKT was also documented. Further, FDPS knockdown in U87 and GBM primary cells but not in NHA, enhanced apoptosis. With the effort to develop a more refined map of the connectivity between signal transduction pathways and metabolic networks in cancer FDPS as a new candidate metabolic oncogene in glioblastoma, might suggest to further target MVA pathway as valid therapeutic tool.
The relatively high rate of success of ETV in various forms of hydrocephalus and the intraoperative finding of mobility of the third ventricle floor after the stomy suggest that the first mechanism of the ETV is the restoration of pulsatility of the ventricular walls. This results in restoration of the CSF flow from the ventricular system into the subarachnoid spaces and normalization of the CSF dynamics. Accordingly, ETV is not only an internal shunt, but it primarily influences the capacity of the brain pulsatility to ensure CSF flow.
In our experience, the 3-D endoscope represents a critical development in visualization, thus enabling improved hand-eye coordination and depth perception, which are mandatory for the management of complex intradural neurovascular structures during tumor removal surgery.
There is no effective alternative to surgery in the treatment of the symptomatic cases of chiari malformation. Nonetheless, in literature there is no unanimous consensus about what is the surgical "gold standard" and which are the candidates for surgery. No doubt that intracranial hypertension and ventricular dilatation have to be investigated and treated before considering decompression. It is also very important to keep in mind that a surgery does not guarantee a complete recovery from every symptoms. We report our experience about who are the candidates for surgery, which is the most appropriate surgical technique and when is the correct time for surgery along the natural history of the disease.
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