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Background Unruptured intracranial aneurysms (UIAs) are increasingly identified and are an important health-care burden; in the past they were commonly treated by surgical clipping, but nowadays endovascular coil embolization is increasingly employed as an alternative. Methods The Unruptured Aneurysms Italian Study (UAIS) is a multicentric cooperative prospective study aimed to delineate the "State of the Art" of UIAs treatment in Italy. 51 Italian Neurosurgical and Neuroradiological Units, representatives of all 20 Italian regions are involved in the Study. Results UAIS started on June 2003 and ended on July 2007. 1138 patients were collected by that date, but 181 were ruled-out due to severe violation of the protocol; 957 had complete data and could be statistically evaluated. Conclusions UAIS demonstrates that the treatment of UAs, as performed in Italy as a Nation, is effective in improving long-term outcome vs. natural history, particularly in aneurysms larger than 7 mm.

article i nfo Objective: Current methods of calculating Intracranial Elastance Index (IEI) depend from CSF pulse-wave, whose shape may deeply change during ICP rising. The main aim of this study was to evaluate the reliability and specificity of a novel method to calculate IEI (method C), based on the integral of the CSF pulse-wave area. Method: Twenty ventricular infusion-tests of patients with idiopathic NPH were re-evaluated. We have compared method C with the most widely used methods to calculate IEI: a modified Szewczykowski method (diastolic ICP against CSF pulse-wave amplitude-method A) and a modified Czosnyka method (diastolic ICP against the fundamental harmonic-method B). R-squared (R 2 ) was calculated for each test. Means were compared through ANOVA and t-test. Results: Mean R 2 values for methods A, Ba nd Cw ere 0.91 ±0 .06,0.9 ± 0.06 and 0.96 ± 0.03, respectively. Mean R 2 values obtained through method Av s Ca nd through method Bv s Cw ere significantly different (p = .006 and p = .001, respectively), while values obtained through method A vs B were not (p = 1). Analysis of ICP tracks demonstrated that 9 patients showed no different shape of the ICP wave during the infusion test, while the remaining 11 did. The mean R2 values obtained through method A vs C and through methodBvsCweresignificantly different (p b .001 for both) for patients showing a different shape of the ICP wave during the infusion test. Conclusions: Method C seems to be the most reliable method to calculate IEI, as it is independent from CSF pulse wave modifications.

Malignant gliomas represent the most common primary brain tumor: more than 50% of them are glioblastoma multiforme (GBM). Photodynamic therapy may offer a very good chance of targeted destruction of infiltrating GBM cells, thus increasing the survival time and recurrence-free interval of GBM patients. Among photosensitizing agents, meta-tetrahydroxyphenylchlorin (m-THPC) is promising for the treatment of brain tumors. In previous studies, we investigated the transfection activity of dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) liposomes, containing a cationic gemini surfactant, loaded with m-THPC on human colon adenocarcinoma and glioblastoma cell lines. In this paper, the uptake and the intracellular distribution of m-THPC, loaded in several formulations of cationic liposomes, were analyzed, by making a comparison with those obtained using the same chlorin in the pharmaceutical form (Foscan(R)). Moreover, by cloning efficiency assay the potential therapeutic efficiency of chlorin delivered by liposome formulations was compared with that of the pharmaceutical compound, before and after irradiation with laser light at 652 nm. The obtained results indicated that cationic liposomes (i) transferred m-THPC in glioblastoma cells more efficiently than pharmaceutical formulation; (ii) significantly (p < 0.001) increased the m-THPC cytotoxic effect after laser irradiation; (iii) seemed to exert their cytotoxic action in the early phase of interaction with the cells, during adhesion to the plasma membrane.

We report a rare bone-leptomeningeal metastasis from an adrenal cortical carcinoma (ACC). ACC is a rare malignancy and represents one of the most unusual sources of intracranial metastases (0-0.2%); the localization to the skull bone and meninges is uncommon. A 45-year-old man underwent surgery for a non-functioning ACC; 4 months later he developed a soft left frontal mass. The CT scans and MRI showed a large tumor with bone and leptomeningeal involvement. Despite chemotherapy, the lesion increased in volume, which led to local pain and right hemiparesis. Thus, the patient underwent excision of the mass; histopathological diagnosis confirmed that it was an ACC metastasis. The patient underwent standard radiation therapy after surgery. At post-operative follow-up, the patient was in a good neurological condition with no radiological evidence of a cranial recurrence; however, there was a voluminous abdominal regrowth of the primary tumor. To our knowledge, this is the second case of bone and leptomeningeal metastasis arising from an ACC. This patient report confirms the effectiveness of aggressive surgery for management of large intracranial metastases, particularly those that arise from primary tumors that are resistant to radiotherapy and chemotherapy. In our opinion, surgery represents the most appropriate treatment for voluminous intracranial metastasis - even when there are no neurological signs.

Malignant gliomas, with an incidence of 5 cases per 100,000 population per year, represent the most common primary brain tumour. They have an overall survival length of less than 2 years. Many different adjuvant therapies have been developed. Among them, Photodynamic Therapy (PDT), that is based on photochemical reactions between light and tumoral tissue selectively labelled with exogenous photosensitizing agents. Among photosensitizers, m-THPC (Temoporfin), seems to be the most promising one for the treatment of brain tumors, but, unfortunately, it causes problems of high skin photosensitivity. To by-pass this problem, we devised an intratumoral route of administration of this photosensitizer. The aim of this study is to investigate and compare the uptake of m-THPC in brain tumor and normal tissue after systemic and intratumoral administration of the drug. 30 female Wistar rats received m-THPC 12 days after C6 tumor implantation. Temoporfin was administered intratumorally in 24 rats at two different concentrations. 6 rats constituted the control group and received m-THPC by means of an intraperitoneal injection. The brains were extracted at 4 h, 24 h and 96 h after Temoporfin injection. The samples were examined with a confocal laser scanning microscope. All samples showed high fluorescence emission exclusively in the tumour area, without appreciable differences between the samples taken at the different times of sacrifice and the two routes of administration. No fluorescence whatsoever was detected among normal brain tissue surrounding the tumour. The intratumoral route appears to give comparable results to the systemic one, regarding intracellular uptake efficiency and tumour - normal tissue ratio, with the advantage of a much shorter time needed to reach optimal intratumoural concentration - that is just four hours from m-THPC injection.

In this study we investigated the feasibility of mixed liposomes formed by dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and cationic gemini surfactant (Gemini 1) loaded with the chlorin m-tetrahydroxyphenylchlorin (m-THPC), in photodynamic therapy (PDT) for glioma. To this aim, an in vitro study was carried out by employing various human glioblastoma cell lines (A172, DBTRG, LN229, U118). The following liposomal formulations were tested: (i) DMPC and Gemini 1; (ii) m-THPC in DMPC in the absence or (iii) in the presence of Gemini 1 in the molar ratio 8:2; 7:3, and 6:4. The presence of Gemini 1 significantly increased the intracellular uptake of chlorin in all cell tested although with a different extent: LN229 > U118 > A172 > DBTRG. The cytotoxicity of chlorin-loaded liposomes was then tested by cloning efficiency performed on different cultures, before and after irradiation with laser light at 652 nm, at a Fluence Rate of 200 mW/s for 100 s, with a total Fluence of 20 J/cm−2. In the absence of irradiation, the different liposomal formulations induced a cytotoxicity in less than 30% of glioblastoma cells. On the contrary, irradiation induced total destruction of all cultures treated with m-THPC/DMPC + Gemini 1 in the ratios 8:2, or 7:3, or 6:4.

Spinal cord injury often results in irreversible and permanent neurologic deficits below the lesion level. Nowadays, treatment is limited to drugs and/or physiotherapy aimed at compensating disability. New experimental studies focus on the transplantation of cells capable of surviving, regenerating tissue, recovering functions and/or improving symptoms. A review of such type of studies on spinal cord reconstruction published between 1991 and 2004 is presented. In the latter years, cell transplantation appeared as the most promising approach in spinal cord regeneration research. To date, this promise has not been maintained, despite the appearance of new attractive cell populations for grafting, such as neural stem cells. The demonstration that stem cells exist in the adult brain and that they can be isolated and expanded in vitro offers the possibility to test such interesting cells in the paraplegic rat. Some neurotrophic factors can facilitate axonal regeneration and neuronal survival. Therefore, the development of strategies, such as implanting neural stem cells engineered to secrete neurotrophic factors directly in the lesion site, could be important to promote regeneration in the injured spinal cord. Despite all the strategies used till now, the problem of the paraplegic rat remains. Only the solution of such problem will authorize studies in higher mammals and, finally, the clinical application in human patients. The paraplegic adult rat with a T8 spinal cord transection should be considered the standard experimental model to be used in spinal cord reconstruction studies. Function and anatomic results are undisputed only after spinal cord transection.

Infectious aneurysm is a rare event, especially after the introduction of antibiotic therapy. However, its early detection is very important for timely treatment with antibiotics and surgical intervention. This pathology may generally be due to mycotic endocarditis or septic embolization, prevailing in the preantibiotic era, and to aortitis, whose incidence is actually increasing, mainly in subjects with preexisting large-vessel atherosclerosis and intimal defects. This clinical entity is usually defined as microbial arteritis and recognizes Salmonella spp as the microorganism most frequently isolated from blood or vascular tissue cultures. The authors present the case of a 56-year-old man with a history of hypertension that some weeks before admission manifested as hyperpyrexia and episodic lumbar pain, associated with hepatosplenomegaly and with a pulsing mass in the periumbilical region. Abdominal computed tomography (CT) scan documented a voluminous infrarenal aortic aneurysm with a markedly reduced and irregular vessel wall. The patient underwent surgical excision of the aneurysm, during which marked periaortic inflammation phenomena, complete absence of the posterior aortic wall for a length of 5-6 cm, and the exposure of the correspondent vertebral bodies were observed. Histopathologic examination of the aneurysmal tissue showed atheromatous and thrombotic aspects and confirmed strong signs of inflammation. This case may suggest that the occurrence of microbial aortitis, especially from Salmonella spp, should be taken into account in the presence of a septic status associated with back, abdominal, or thoracic pain.