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Background: various prospective clinical trials on high-grade gliomas were performed in the last years but patient (PTS) characteristics and outcome may be different in real clinical practice. We performed a retrospective analysis to evaluate the real-life experience in Padua Neuro-Oncology center. Matherials and Methods: retrospectively, we reviewed the medical records of PTS admitted to our observation from June 2010 to June 2015 with a diagnosis of AA or GBM. We analyzed clinical outcome with prognostic factors. Results: we analyzed 592 PTS with a diagnosis of CNS primary tumor. Among these, we enrolled 395 PTS: 33 (8.4%) with a histological diagnosis of AA, 293 (74%) with a histological diagnosis of GBM and 69 (17.4%) with a radiological diagnosis of GBM. At diagnosis, median age was 63.2 (range 24-88), 61.8% were male; 80% of PTS had an ECOG PS 0-2. Among PTS who underwent surgery, 48% had a radical surgery; 279 PTS (70.6%) performed RT in association to chemotherapy. 17% of PTS performed a second surgery at relapse and 45% a second-line treatment. MGMT was analyzed in all PTS who underwent surgery: it was methylated in 38.7% of PTS, IDH1 was mutated in 6%. GBM PTS with ECOG PS 0-2 and >2 had a median OS of 21.1 and 7.2 ms, respectively. GBM PTS with met and unmet MGMT had a mOS of 22.7 and 13.7 ms (p=0.005). AA PTS with met and unmet MGMT had a mOS of 29.5 and 16.6 ms (p=0.03). Considering all high-grade gliomas, PTS with met MGMT + mutIDH1 reported a mOS of 23.1ms, PTS with metMGMT + wtIDH1 had a mOS of 20.9 ms and PTS with unmetMGMT + wtIDH1 showed a mOS of 12.6ms (p

Background: MGMT gene promoter methylation status is acknowledged as a prognostic factor and predictive marker for temozolomide (TMZ) treatment. Although MGMT status determined by pyrosequencing was showed to correlate with progression free survival (PFS) and overall survival (OS), it is still unclear a cut-off value that discriminates between methylated and unmethylated patient (pts) and its correlation with the patient clinical outcome. Matherials and Methods: We analyzed the tissue samples from 128 PTS diagnosed with GBM from November 2009 to December 2015. All PTS underwent treatment with RT + TMZ and had an ECOG-PS 0-2. Methylation percentage for each sample was obtained by calculating the average methylation of all 10CpG sites (75-84) of MGMT promoter by pyrosequencing analysis. PTS with 0-6% of methylation were classified as unmethylated (UM), PTS with 7-24% as low methylated (LM) and PTS with ≥ 25% as high methylated (HM). 25% was the median value of methylation of our PTS having >6% of methylation. Results: Median age was 60 yrs (range 25-84), 60.9% were male, 74.2% had an ECOG PS 0-1, 50.8% underwent radical surgery, 85 PTS were dead at the time of analysis. 75 PTS were UM, 26 PTS were LM and 27 PTS were HM. On univariate analysis HM, LM and UM showed a PFS of 15.8, 10 and 9.1 ms, respectively (p=0.1). OS was 38.7, 21 and 18.8ms (p= 0.06). On multivariate analysis UM and LM PTS had a statistically lower PFS vs HM PTS (HR=2.57; p=0.001; HR= 2.5; p=0.007, respectively) and statistically lower OS (HR=3.47; p

The α-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson's disease (PD). Particularly triplication, but also duplication, of the SNCA is associated with early-onset rapidly progressing parkinsonism with increased risk of cognitive impairment. There is no report about the effect and safety of Deep Brain Stimulation (DBS) in carriers of this mutation and, in general, data in patients with genetic parkinsonism are scarce. We report a one-year prospective follow-up of subthalamic nucleus (STN) DBS in a 46-year old female carrier of SNCA duplication who developed PD at the age of 41 years, and rapidly showed disabling motor fluctuations and dyskinesias refractory to pharmacological strategies. One year after surgery there was a clinically relevant improvement in motor features with a reduction of 64% in UPDRS III in "off medication" and a complete abolition of peak dose dyskinesias. Patient did not report procedure-related adverse events following STN-DBS except for stimulation-induced right foot dystonia relieved by modulating stimulation parameters. Postoperative cognitive testing showed a decline in executive functions, mostly verbal fluency and attention shifting, compared with presurgical assessment. STN-DBS is safe and effective in patients with SNCA duplication showing a clinical pattern similar to idiopathic PD. Our case suggests that clinical phenotype rather genotype is the main predictor for DBS outcome.

BACKGROUND: Mutation of IDH1 gene is a prognostic factor and a diagnostic hallmark of gliomas. Mutant IDH1 enzyme can convert α-KG into 2-Hydroxyglutarate(2HG); mutated gliomas have elevated amounts of intracellular 2HG. We analyzed 2HG concentration in plasma and urine in glioma patients(PTS) to identify a biomarker of IDH1 gene mutation METHODS: All PTS had a prior histological confirmation of glioma, a recent brain MRI (within 2 weeks) showing the neoplastic lesions. The exclusion criteria were any chemotherapy performed within 28 days prior, other neoplastic and metabolic diseases. Plasma and urine samples were taken from all PTS and 2HG concentrations determined by liquid chromatography tandem mass spectrometry; Mann-Whitney test was used to test for differences in metabolite concentrations. ROC curve was used to evaluate the cut off value of 2HG biomarker. RESULTS: 84 PTS were enrolled: 38 with IDH1 mutated and 46 IDH1 wild-type. Among PTS with mutant IDH1 we had 21 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG); among PTS with IDH1 wild-type we had 35 HGG and 11 LGG. In all PTS we analyzed the mean 2HG concentration in plasma (P_2HG), in urine (U_2HG) and the ratio between P_2HG and U_2HG (R_2HG). We found an important significant difference in R_2HG between PTS with and without IDH1 mutation: 24.9 versus 15.3, respectively. The optimal cut-off value of R_2HG to identify glioma PTS with and without IDH1 mutation was 19 with sensitivity (S) 63%, specificity (SP) 76% and accuracy (A) 70%.; in only PTS with HGG the optimal cut-off value was 20 (S 76%, SP 89%, A 84%, PPV 80%, NPV 86%). No association between the grade or size of tumor and R_2HG were found. In 7 out of 7 HGG PTS, we found a correlation between R_2HG value and response to treatment. CONCLUSIONS: By analyzing the R_2HG derived from individual plasma and urine 2HG levels is possible discriminate glioma PTS with and without IDH1 mutation. A larger samples need to be analyzed to investigate this method to monitor treatment efficacy.

Background. Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. Materials and Methods. All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. Results. A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment. Conclusion. Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which may rarely occurs as a complication of supratentorial procedures, and it shows a typical bleeding pattern defined "the zebra sign." However, its pathophysiology still remains unknown. We performed a comprehensive review collecting all cases of RCH after supratentorial craniotomies reported in literature in order to identify the most frequently associated procedures and the possible risk factors. We assessed percentages of incidence and 95 % confidence intervals of all demographic, neuroradiological, and clinical features of the patients. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 49 articles reporting 209 patients with a mean age of 49.09 ± 17.07 years and a male/female ratio 130/77. A RCH was more frequently reported as a complication of supratentorial craniotomies for intracranial aneurysms, tumors debulking, and lobectomies. In the majority of cases, RCH occurrence was associated with impairment of consciousness, although some patients remained asymptomatic or showed only slight cerebellar signs. Coagulation disorders, perioperative cerebrospinal fluid drainage, hypertension, and seizures were the most frequently reported risk factors. Zebra sign was the most common bleeding pattern, being observed in about 65 % out of the cases, followed by parenchymal hematoma and mixed hemorrhage in similar percentages. A multivariate analysis showed that symptomatic onset and intake of antiplatelets/anticoagulants within a week from surgery were independent predictors of poor outcome. However, about 75 % out of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless in the event of the occurrence of complications.

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which can be rarely observed as a complication of spine surgery. As well as for RCH reported after supratentorial procedures, it shows a characteristic bleeding pattern defined “zebra sign”. Nowadays, RCH pathophysiology still remains unknown. We performed a comprehensive review, collecting all cases of RCH after spine surgery reported in literature in order to identify the procedures most frequently associated with RCH and the possible risk factors. We assessed percentages of incidence and 95 % confidence interval of all demographic, neuroradiological, and clinical features. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 44 articles reporting 57 patients with mean age of 57.6 ± 13.9 years and a male/female ratio of 23/34. A RCH was more frequently reported as a complication of decompressive procedures for spinal canal stenosis, particularly when associated with instrumented fusion, followed by spinal tumor debulking and disc herniation removal. In the majority of cases, RCH occurrence was characterized by progressive impairment of consciousness, whereas some patients complained non-specific symptoms. Coagulation disorders, hypertension, and placement of postoperative subfascial drainages were the most frequently reported risk factors. The occurrence of intraoperative dural lesions was described in about 93 % of patients. Zebra sign was the most common bleeding pattern (about 43 % of cases) followed by parenchymal hematoma (37.5 %) and mixed hemorrhage (about 20 %). Impairment of consciousness at clinical onset and intake of anticoagulants/antiplatelets appeared associated with poor outcome at univariate analysis. However, more than 75 % of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless of the occurrence of complications.

Objective The incidence of chronic hydrocephalus requiring cerebrospinal fluid shunting was analyzed for a prospective series of 52 consecutive patients with ruptured cerebral aneurysms who underwent fenestration of the lamina terminalis during early microsurgical aneurysm repair. We hypothesized that, by creating an anterior ventriculocisternostomy, fenestration of the lamina terminalis would facilitate cerebrospinal fluid dynamics and decrease the risk of subsequent hydrocephalus. Methods Patients were enrolled according to the following criteria: 1) age more than 40 years; 2) admission Hunt and Hess Grade 2 to 4; 3) initial subarachnoid hemorrhage severity of Fisher Grade 3 or 4; and 4) early microsurgical repair of an anterior circulation aneurysm. Results The mortality rate in this series was 9.6%. Of the 47 surviving patients, 32 (68%) were discharged with a Glasgow Outcome Scale score of 5, 10 (21%) with a Glasgow Outcome Scale score of 4, and 5 (11%) with a Glasgow Outcome Scale score of 3. The follow-up period ranged from 12 to 60 months. Chronic hydrocephalus was radiographically and clinically evident in 3.8% of the total population. Shunt surgery was performed for two patients who exhibited symptoms resulting from hydrocephalus, corresponding to 4.2% of the surviving patients. Conclusion Estimates from the most recently published studies indicate that an incidence of chronic post-subarachnoid hemorrhage hydrocephalus (requiring shunt surgery) of 15 to 20% is representative for an average contemporary population of patients with aneurysmal subarachnoid hemorrhage. The lower incidence of chronic hydrocephalus observed in this series possibly reflects the favorable effect of lamina terminalis fenestration on cerebrospinal fluid dynamics.

OBJECTIVE: Cervical myelomeningocele is an extremely rare condition, accounting for only 1 to 5% of all neural tube defects. These lesions are usually diagnosed in childhood. Here, we report a case of a cervical myelomeningocele diagnosed and treated in adulthood. CLINICAL PRESENTATION: A 52-year-old man presented with a 3-year history of progressing weakness and paresthesia in his upper limbs. Physical examination revealed a posterior midline neck mass covered with normal skin. Magnetic resonance imaging showed a soft-tissue mass tethering the cord by a stalk extending from the dorsal spinal cord to the dome of the lesion. Syrinx was evident cranially and caudally to the origin of the posterior stalk. INTERVENTION: Surgical resection of the sac and intradural exploration were performed. The subdural space was explored, and the tethered structures were released. Histological examination showed small foci of meningothelial cells with psammoma bodies and rare thin fascicle of glial tissue dispersed in hyaline tissue. Immunohistochemical stains against glial fibrillary acidic protein and S100 confirmed the presence of bands of astrocytic tissue. The patient demonstrated early improvement of neurological deficits. Six months after surgery, he was asymptomatic and magnetic resonance imaging showed resolution of the syrinx. CONCLUSION: We believe the syrinx in this patient was caused by a blockade of flow in the central canal and around the spinal cord as a result of the tethered cord. The untethering procedure resulted in the collapse of the syrinx followed by resolution of neurological deficits.

Olfactory groove meningiomas may attain surprisingly large size. The subfrontal approach is currently the route preferred by most neurosurgeons for their excision. The pterional-transsylvian route represents an alternate exposure for microsurgery of frontobasal tumors. Although this approach has been already described for olfactory meningiomas, tumors of giant size were not specifically addressed in the literature. We report the application of the pterional-transsylvian approach in six patients with giant olfactory meningiomas. This series is unique because it includes only patients with tumors exceeding 6 cm in diameter with bilateral symmetrical development. A radical removal was achieved in all patients and all of them made a full recovery. To investigate the relevance of the pterional-transsylvian approach for minimizing surgical morbidity, a magnetic resonance imaging protocol was designed to characterize even subtle postoperative frontal lobe structural changes. These changes, limited to the frontal lobe ipsilateral to exposure and localized in specific anatomical domains of the prefrontal area, included cystic degenerative alterations, parenchymal gliosis, and associated persistent white matter edema. Results from the present series strengthen the usefulness of the pterional-transsylvian approach as a safe surgical route for lesions affecting the anterior skull base, even with huge bilateral symmetrical expansion, such as giant olfactory meningiomas.

Objective To present a case carrying a chromosomal rearrangement of the 6p25.3 locus and diagnosed with Moyamoya syndrome. Methods A Caucasian 4 years-and-9-months-old girl was admitted to a peripheral hospital for vomiting and acute left hemiparesis, followed by left arm clonic seizures, aphasia and confusion. Phenytoin stopped the crisis, but hemiparesis persisted. EEG documented widespread slow waves, mainly on the right hemisphere. Computed tomography (third day) showed hypodensity of the entire right hemisphere. Past history was characterized by prematurity (born at 32 g.w.), cardiac defects (atrial septal defect, patent ductus arteriosus), surgically corrected at 3 years old. High resolution karyotype showed this rearrangement: 46, XX, der(6)dup(6) (p24p23)del(6)(p25). Cognitive level was borderline. On day 4 the girl was transferred to our Child Neurology Unit where she underwent a complete workup. Results Echocardiogram: normal; carotid doppler ultrasound: bilateral stenosis of internal carotid arteries; brain magnetic resonance imaging (MRI): ischemic areas in territories supplied by right middle and anterior cerebral arteries; brain angio-MRI: bilateral multiple stenosis of anterior and posterior cerebral arteries and collateral circulation consistent with Moyamoya syndrome. Therefore, after a digital angiography, the patient underwent an encephalo-duro-arterial-myo-sinangiosis. The post-operative period was uneventful. Conclusion Moyamoya syndrome is known to be associated to some genetic conditions (such as Neurofibromatosis type 1, Alagille syndrome and Trisomy 21). To date, only one pediatric case with Moyamoya syndrome and chromosomal rearrangement of 6p25.3 has been reported, similar to our patient. Therefore, all patients presenting with a chromosomal rearrangement involving the 6p25.3 locus should be studied with brain angio-MRI; moreover this genetic region should be investigated to identify possible disease-specific genes for Moyamoya syndrome.

Object. The radical scavenger (±)-N,N′-propylenedinicotinamide (AVS) was shown recently to ameliorate delayed neurological deficits resulting from ischemia in patients who have had an aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of AVS administration after experimental SAH on 1) behavioral deficits; 2) angiographically confirmed basilar artery (BA) spasm; and 3) blood-brain barrier (BBB) permeability changes. Methods. These parameters were measured by 1) using a battery of well-characterized chronic assessment tasks over a 5-day observation period; 2) assessing in vivo the mean vessel diameter 2 days after SAH; and 3) evaluating the extravasation of protein-bound Evans Blue dye by using a spectrophotofluorimetric technique 2 days after SAH. Groups of eight to 10 rats received injections of 400 µl of autologous blood into the cisterna magna. Within 5 minutes after the surgical procedures were completed the rats were treated with an intravenously administered continuous infusion of saline (Group III) or AVS (1 mg/kg/minutes, Group IV). Results were compared with those in sham-operated animals treated with intravenously administered saline (Group I) or AVS (Group II). The AVS-treated rats had significantly improved balance beam scores on Days 1 to 2 (p < 0.05), shorter beam traverse times on Day 1 (p < 0.05), and better beam walking performance on Days 1 to 4 (p < 0.01), but no significant effect was seen in terms of SAH-related changes in body weight. Treatment with AVS also attenuated the SAH-induced BA spasm (p < 0.05) and decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices, and in the subcortical and cerebellar gray matter and brainstem (p < 0.01). Conclusions. These results demonstrate useful antivasospastic and brain-protective actions of AVS after induction of experimental SAH and provide support for observations of beneficial effects of AVS made in the clinical setting.

Injury to peripheral nerves can occur as a result of various surgical procedures, including oral and maxillofacial surgery. In the case of nerve transaction, the gold standard treatment is the end-to-end reconnection of the two nerve stumps. When it cannot be performed, the actual strategies consist of the positioning of a nerve graft between the two stumps. Guided nerve regeneration using nano-structured scaffolds is a promising strategy to promote axon regeneration. Biodegradable electrospun conduits composed of aligned nanofibers is a new class of devices used to improve neurite extension and axon outgrowth. Self assembled peptide nanofibrous scaffolds (SAPNSs) demonstrated promising results in animal models for central nervous system injuries, and, more recently, for peripheral nerve injury. Aims of this work are (1) to review electrospun and self-assembled nanofibrous scaffolds use in vitro and in vivo for peripheral nerve regeneration; and (2) its application in peripheral nerve injuries treatment. The review focused on nanofibrous scaffolds with a diameter of less than approximately 250 nm. The conjugation in a nano scale of a natural bioactive factor with a resorbable synthetic or natural material may represent the best compromise providing both biological and mechanical cues for guided nerve regeneration. Injured peripheral nerves, such as trigeminal and facial, may benefit from these treatments.

Choroid plexus tumors (CPTs) are intraventricular lesions originating from ventricular neuroepithelium and represent up to 4 % of brain neoplasms affecting pediatric population. They are more frequently benign papillomas, but malignant carcinomas can sometimes occur. The authors present a description of surgical approach for CPTs, particularly focusing on the complications related to the cerebrospinal fluid (CSF) circulation, which may affect outcome. Microsurgical resection represents the first line treatment for CPTs. The goal is the complete removal of the tumor and the restoration of a physiological CSF circulation.

IntroductionStem cell based intervertebral disc (IVD) regeneration is quickly moving toward clinical applications.1 However, many aspects need to be investigated to routinely translate this therapy...

IntroductionTo study the efficacy of novel regenerative strategies is necessary to develop new models that do not implement annulus fibrosus (AF) damage. We hypothesize an ideal preclinical model t...

SummaryVenous thromboembolism (VTE) may complicate the clinical course of glioblastoma multiforme (GBM). Circulating microparticles (MPs) have been associated with cancer-related VTE. Sixty-one consecutive patients with GBM undergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy were prospectively evaluated. MPs numbers according to cellular origin and the procoagulant activity of annexin V positive (AV+) MPs (MP-activity) were measured before surgery and then 1 week and 1, 4, and 7 months after surgery. Glial (GFAP+) and endothelial (CD62E+) derived MPs, AV+ and tissue factor-bearing (TF+) MPs were measured using flow cytometry. Baseline levels of GFAP+/TF-, TF+/GFAP-, and GFAP+/TF+ MPs were significantly higher in GBM patients than in healthy controls, and significantly increased at each time point after surgery; at 7 months, a further significant increase over the level found a week after surgery was only seen in the subtotally resected patients. The number AV+/CD62E- MPs increased in GBM patients and correlated with MP activity. TF+/GFAP- MPs numbers were significantly higher in 11 GBM patients who developed VTE than in those who did not (p 0.04). TF+/GFAP- MPs levels above the 90th percentile (calculated in GBM patients without VTE) were associated with a higher risk of VTE (RR 4.17, 95% CI 1.57–11.03). In conclusion, the numbers of glial-derived and/or TF-bearing MPs were high in GBM patients both before and even more after the neoplasm was treated, especially in patients with subtotal resection likely according to disease progression. A contribution of TF+/GFAP- MPs to the risk of VTE is suggested.

The paper from Iacoangeli and his colleagues from Ancona and Rome in this issue of Acta Neurochirurgica is timely given the continuing controversy on best treatment options for vestibular schwannomas. Their report is on the preliminary experience with an old approach integrated with the endoscope. The case material includes ten cases of small and medium sized sporadic acoustic neuromas (five cases of 8 and 10 mm, five cases of 11–25 mm), selected on the basis of a favourable anatomy of the temporal bone. It is noteworthy, and rather exceptional in comparison to other’s experiences, that only three cases out of ten had a preoperative normal facial nerve function, while four cases of 11–25 mm had a House-Brackmann (HB) grade 3 and three cases of 10 and 20 mm had a HB grade 2, which makes 70 % of preoperative facial dysfunction in small and medium-size tumors. The surgical outcome was outstanding, with unchanged postoperative facial function (with the exception of the case with preoperative radiotherapy), only one case experiencing a hearing loss from AAORLHNS class B to C, and no instances of deafness. The removal of tumors from the internal auditory canal without a drill meatotomy in this series might have been favoured by a limited extension into the canal. The results on the hearing and facial nerve are superior to the results reported in the literature.

Gliomas are devastating tumors of the brain resistant to therapies. Although some therapies can prolong the survival time among the affected persons, gliomas are not curable and new therapeutic approaches need to be investigated. Oncolytic viruses seem to represent an interesting alternative, because anticancer agents and new viral agents have to be explored to identify the one with the best characteristics. Bovine herpesvirus type 4 (BoHV-4) is a gammaherpesvirus with a striking tropism and permissive replication toward cancer cells and rat, mouse, and human glioma cells. However, BoHV-4 does not replicate into the normal brain parenchyma. The BoHV-4 genome was cloned as a bacterial artificial chromosome to easily manipulate this large genome and be used as a viral vector platform. In the present study, a herpes simplex virus type 1 thymidine kinase suicide gene–armed BoHV-4 was constructed, characterized, and proven to be highly efficient in killing by apoptosis glioma cells in vitro when co-administered with the pro-drug ganciclovir (GCV). When the armed BoHV-4/GCV therapeutic approach was tested in immunocompetent orthotopic syngenic mouse and rat glioma models in vivo, a significant increase in survival among the treated animals was achieved, and some animals were completely cured. The BoHV-4–based vector represents a promising alternative oncolytic virus for glioma and, perhaps, other types of cancer treatment that merit further investigation. This article represents the result of a mutual interaction between human medical science and veterinary science, a combination of scientific knowledge often neglected.

Dear Editor, There is emerging evidence of Gemella morbillorum (GM) as a pathogen capable of causing potentially lifethreatening central nervous system (CNS) infections. We document the first case of intracranial epidural abscess (EA) caused by this pathogen, and emphasize the need to consider potential neurological involvement in patients with chronic sinus disease from whom GM is isolated. A 14-year-old boy presented with a 2-week history of headache and fever. His past medical history was only significant for sinusitis 2 years earlier. He was initially treated in the community for acute sinusitis by the family physician. Upon admission, he appeared mildly distressed, with a body temperature of 38.5 °C, complained of frontal headache, and vomited twice during clinical examination. Neurological examination was unremarkable, and blood investigations documented a CRP of 260 mg/l and an ESR of 99 mm/h. He was therefore empirically administered a large-spectrum antibiotic therapy. Over the following day, he remained pyrexial and his headache and vomiting worsened: a CT head scan showed frontal and left-sided maxillary and ethmoidal sinuses opacification, with extensive epidural frontal collection. A contrast-enhanced MRI scan revealed frontal epidural empyema and superior sagittal sinus compression with no evidence of dural sinuses thrombosis (Fig. 1, top). The patient underwent an urgent frontobasal bilateral craniotomy. A bicoronal flap was raised and an initial burr hole was placed in the frontal parasagittal area, yielding copious purulent debris under pressure. After craniotomy was performed, a purulent collection extending from the frontal sinuses up to the coronaric suture was noted. The frontal sinuses were opened and drained, with subsequent cranialization and closure with a galeal flap. The post-operative course was uneventful and our patient has remained apyrexial ever since the operation, with normalization of inflammatory markers. Intraoperative cultures from purulent material grew a metronidazole-resistant strain of Gemella morbillorum. He received a total of 14 days of intravenous antibiotics and was discharged on the 15th postoperative day, in good clinical condition. Gammainterferon and IL-12 serum levels were normal. A contrastenhanced MRI head scan carried out 3 months after surgery was unremarkable (Fig. 1, bottom).

We recently described a three-layer concentric model of a glioblastoma (GBM) related to a specific distribution of molecular and phenotypic characteristics driven by the intratumoral hypoxic gradient in which the cancer stem cells niche is located in the hypoxic necrotic core of the tumour. The purpose of this study was to investigate the relationship between O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and MGMT expression in GBM samples collected according to the three-layer concentric model. Multiple tissue samples were obtained, by means of image-guided surgery, from the three concentric layers of newly diagnosed GBM. Two samples from each layer were collected from 12 patients (total 72 samples). Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tissue samples. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. In all tumours, MGMT protein expression decreased progressively from the inner to the outer layer, and methylation of the MGMT promoter was unrelated to tumour layer. In particular, the MGMT promoter was unmethylated in all layers in 41.7% of tumours, methylated in all layers in 25%, and variably methylated in the three layers in 33.3%. We recorded concordance between MGMT expression and MGMT promoter methylation status within the GBM in only 58.8% of the samples collected. Our data suggest that both MGMT expression and promoter methylation data may be variable throughout GBM and that they may, consequently, depend on the site of surgical sample collection, even in the same patient. However, whereas MGMT expression is pre-operatively predictable when sampling is performed according to the three-layer concentric model, MGMT promoter methylation is not. These results must be considered when sample collection is performed for assessment of MGMT data.

✓ Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation have not been fully elucidated in the literature. The authors employed the [14C]-2-deoxy-D-glucose autoradiography method to investigate the effect of whole-brain x-irradiation on local cerebral glucose utilization in the rat brain. The animals were exposed to conventional fractionation (200 ± 4 cGy/day, 5 days/week for a total dose of 4000 cGy), and the effects of this regimen were assessed at 2 weeks and 3 months postirradiation. In rats evaluated 2 weeks after treatment, statistically significant decreases in cerebral metabolic activity were found in 13 of the 27 regions studied, compared to control animals. In rats studied 3 months after treatment, additional metabolic suppression and statistically significant decreases in cerebral metabolic activity were found in 11 of the 27 regions, compared to rats studied 2 weeks after treatment. A weighted-average rate for the brain as a whole was approximately 15% and approximately 25% below that of control animals 2 weeks and 3 months after exposure, respectively. Although the difference in species is significant enough so that direct extrapolation to humans may not be appropriate, the data reported here may have potential clinical implications for the evaluation of the risk-benefit ratio for radiotherapy. This model can be used reproducibly for further investigations, including evaluation of therapies that may reduce irradiation-induced brain injury.

Symptomatic spinal cord compression caused by an epidural mass of extramedullary hematopoietic tissue in patients with beta-thalassemia is a rare occurrence, that becomes exceptional in childhood and adolescence. The literature is not uniform about the optimal treatment of these patients and different modes of therapy have been proposed so far, including surgical excision or decompressing laminectomy followed by local irradiation and/or hypertransfusional regimens. We report the successful treatment of such a complication in an adolescent with homozygous beta-thalassemia by surgery followed by repeated blood transfusions aimed at maintaining hematocrit at normal levels.

Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype) were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes.

In this short case-illustrated review we aimed to analyse the possible nuances of hemifacial spasm (HFS) as the presenting symptom of a tumour of the fourth ventricle. The issue is remarkable since HFS can be secondary to a fourth ventricle tumour, even when no other neurological signs are reported. In addition, the possible presentation with only upper facial muscle involvement, as in the presented case, can be deceitful because this is characteristic of the benign and much more frequent "typical" form. Based on our intra-operative data and on the previously reported cases, we think that pathogenesis could be referable to the facial nerve nucleus involvement and that clinical nuances could be related to the specific somatotropy of the nucleus under the fourth ventricle floor that, as in our case, can be infiltrated by tumour. Resolution of the disorder can usually be obtained after the complete resection of the tumour that in the reported case resulted a subependymoma (WHO grade I), so far never described in literature associated with HFS.

Anticonvulsant therapy is usually recommended before surgery in all patients affected by high grade glioma who are planned to be treated with Carmustine 1,3-bis [2 chloroetyl]-1-nitrosurea, or BCNU) wafers. In fact, phase III studies have reported a risk of seizures higher than 30% in this group of patients. The aim of the study was the evaluation of rate type time of occurrence of seizures in BCNU-treated patients in the postoperative period as well as the investigation into possible risk factors for seizure occurrence in this population. From April 2007 to September 2010, 55 patients underwent surgical removal of malignant glioma and BCNU wafers implantation at the Department of Neurosurgery of Padova. All patients were given antiepileptic prophylaxis for 3 months after surgery. Clinical data (including preoperative seizure history), radiological data, surgical treatment, antiepileptic treatment were retrospectively reviewed. Nine percent of the patients treated with BCNU wafers presented seizures in the postoperative course. Seizures were partial in 80% of cases; they occurred within 30 days after surgery and in 80% of cases within the first 7 days. Patients with preoperative seizures presented more frequently postoperative epilepsy than patients who were preoperatively seizure-free [P = 0.0006; OR = 48 (2,4;945)]. Postoperative seizures were more common among patients affected by one or more wafers related adverse event than among patients without adverse events [P = 0.006; OR = 21 (2,06;213)]; however, they did not appear associated to the number of implanted wafers. Patients with a sub-therapeutic level of AED at the seventh day after surgery presented a higher seizure occurrence [P = 0.02; OR = 11 (1,5;79,8)]. In our experience, postoperative seizures in BCNU-treated patients were less frequent than expected. Careful patient selection and postoperative monitoring could probably play a role in order to decrease seizure occurrence.

Background Implantation of carmustine (1,3-bis (2 chloroetyl)-1-nitrosurea [BCNU]) wafers is an approved local treatment after surgical removal of high-grade gliomas. Safety data have been largely reported by phase III studies. The communication between the final surgical cavity and the ventricular cavities is supposed to be a relative contraindication for positioning of the wafers because of the possible development of hydrocephalus. However, at present there are neither data about this topic published with the exception of a few case reports, nor any proposals for selection criteria for wafer implantation in such circumstances. Furthermore, there are no technical suggestions in literature put forward for the surgical repairing of ventricular defects. Our study was particularly focused on addressing these 3 issues. Methods Forty-three patients affected by a high-grade glioma underwent surgical removal and BCNU wafer implantation between March 2007 and September 2009 at the Department of Neurosurgery of Padua. Among them, we retrospectively reviewed clinical, surgical, and radiological data of 9 patients who had been treated with carmustine wafers after surgical repair of communication between the surgical cavity and the ventricular cavities. We also focused on the technical details concerning wafers positioning in this particular situation. Results Ventricular defects were present in the atrium in 4, frontal horn in 3, and temporal horn in 2 cases. The maximum diameter of the defect was between 6 and 10 mm. In all cases, the defect was intraoperatively repaired in the same way, and up to 8 wafers were implanted in the surgical cavity. In the series reported, no cases of hydrocephalus were detected. Conclusions In our experience, integrity of wafers, size of ventricular wall defect, and accuracy in repairing the defect were crucial issues. Nevertheless, more experience and prospective studies would be helpful to clarify both in what measure ventricular opening affects safety data and the best reliable way of repairing ventricular defects when BCNU wafers are implanted.

Study design A case report and literature review of the treatment of "noncommunicating" syringomyelia. OBJECTIVE.: The aim of this report is to document the timing and the treatment of hydromyelia holocord after surgical treatment for both tethering and retethering of spinal lipoma. Summary of background data Syringomyelia associated with spinal lipoma presents a different pathogenesis and treatment in comparison to the "communicating" hydromyelia in the myelomeningocele. After the primary retethering operation performed in symptomatic patients, recurrent retethering can occur with an increase of the syringomyelia signs and symptoms. Methods Syringomyelia treated with a thin silastic tube passed from the syrinx to the subarachnoidal space for drainage and decompression. Prior operations were: (1) initial untethering at birth, (2) second untethering at 5 years of age, (3) posterior fossa and cervical decompression. Results Magnetic resonance imaging 6 months post shunt operation demonstrated decompression of the hydromyelia holocord and syringobulbia with improvement of motor function of the legs and improvement in sensory symptoms. Conclusion Usefulness of syrinx-subarachnoidal shunt is demonstrated in this case report after unsuccessful decompression and detethering. When the enlargement of the ependymal channel is greater than 50% of the spinal cord's diameter, neurologic, and urological symptoms are evident and the patient benefitted from cord untethering and syrinx drainage. (1) The terminal "noncommunicating" syringomyelia in lumbar sacral lipoma has been reported to be associated with retethering in spinal lipoma in the 25% of the cases. (2) The rise of distal syringomyelia isn't only linked to the kind of the spinal lipoma, but also to the difficulty to obtain the untethering and a smooth cerebrospinal fluid flow between the subarachnoidal space and the ependymal canal. (3) In patients with hydromyelia holocord greater than the 50% of the spinal cord's diameter a myelotomy and insert an ependymal channel/syrinx to the subarachnoidal space shunt can resolve of the syrinx. In this case, the enlargement of the ependymal channel in "noncommunicating" syringomyelia associated with lumbosacral lipoma is greater than 50% of the spinal cord's diameter; neurologic and urological symptoms occurred and the patient benefited from cord untethering and concurrent syrinx drainage.

Glioblastoma multiforme (GBM) are highly proliferative tumors currently treated by surgical removal, followed by radiotherapy and chemotherapy, which are counteracted by intratumoral hypoxia. Here we exploited image guided surgery to sample multiple intratumoral areas to define potential cellular heterogeneity in correlation to the oxygen tension gradient within the GBM mass. Our results indicate that more immature cells are localized in the inner core and in the intermediate layer of the tumor mass, whereas more committed cells, expressing glial fibrillary acidic protein and β-III-tubulin, are distributed along the peripheral and neo-vascularized area, where Smad1/5/8 and Stat3 result to be activated. Moreover, GBM stem cells, identified with the stem cell marker CD133, express high level of DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT) known to be involved in chemotherapy resistance and highly expressed in the inner core of the tumor mass. Importantly, these cells and, particularly, CD133+ cells result to be resistant to temozolomide (TMZ), the most used oral alkylating agent for the treatment of GBM, which specifically causes apoptosis only in GBM cells derived from the peripheral layer of the tumor mass. These results indicate a correlation between the intratumoral hypoxic gradient, the tumor cell phenotype, and the tumor resistance to chemotherapy leading to a novel concentric model of tumor stem cell niche, which may be useful to define the real localization of the chemoresistant GBM tumor cells in order to design more effective treatment strategies.

Pitfalls in cervical spine surgery : , Pitfalls in cervical spine surgery : , کتابخانه دیجیتال جندی شاپور اهواز

The posterior approach through a midline longitudinal incision provides the most direct access to the posterior elements of the cervical spine. Through this approach, the posterior elements of the cervical spine can be removed, and access to the posterior aspect of the spinal cord and nerve roots from the occiput to C7 can be obtained. The posterior approach to the cervical spine allows excellent exposure to perform several surgical techniques, with or without internal fi xation. It can also be a useful rostral extension of a longer posterior thoracic spinal approach [1] . The posterior elements of the cervical spine play an important role in the stabilization of the cervical spine. Indeed, their removal in patients undergoing wide laminectomies (i.e., for the management of pathologies such as the spondylotic myelopathy, or extraor intra-medullary tumors) may cause subluxation, or severe kyphotic angulation of the spine (i.e., swan neck), causing increased compression of the neural elements and worsening of neurological defi cits [1] . In some patients, if necessary, with careful retraction and protection of the neural structures, it is possible to expose the anterior side of the spinal canal (actually the lateral side of the posterior wall of the vertebral body and the intervertebral disk space), the pedicles, and the posterior portion of the root canals. With this approach, however, the surgeon should not expect to be able to reach the central region of the posterior vertebral bodies [1] . This would involve particularly diffi cult (if not impossible) retraction or displacement of neural structures, which might produce severe neurological damage [2] . Complications Related to Posterior Approach

Spinal cord neoplasms are an uncommon cause of back pain, radicular pain, or sensorymotor defi cits. Primary tumors that involve the spinal cord or nerve roots may arise from glial cells located within the parenchyma of the cord, Schwann cells of the nerve roots, or meningeal cells covering the cord. Metastatic spinal cord tumor can result from dissemination of a primary systemic cancer or, more rarely, from drop metastasis of primary intracranial lesions. According to the literature, spinal tumors are divided on the basis of their location into three major groups: intradural intramedullary, intradural extramedullary, and extradural tumors. Intradural tumors are contained in the thecal sac and they can originate within the spinal cord tissue, classifi ed as intramedullary, or adjacent but extrinsic to the cord, classifi ed as extramedullary lesions.

The growing teratoma syndrome (GTS) consists of a mature teratoma paradoxically enlarging during or after chemotherapy for malignant nongerminomatous germ cell tumors.We report two cases of GTS occurring in association with NSGCT of the pineal gland. Although an unusual event, clinicians and radiologists should be aware of its natural history.When normalized tumor markers after chemotherapy are associated with imaging features of a growing mass, the hypothesis of GTS must be taken in consideration. When early diagnosed, GTS can be managed surgically with good results.

Trans-ethmoidal encephalo-meningocele is an extremely rare event among the adult population. It mainly affects young people who have previously reported a head injury. Even though early treatment is mandatory to avoid septic complications, the diagnosis is usually late because of the misleading symptomatology. We describe the unusual clinical history of an adult patient with a giant trans-ethmoidal encephalo-meningocele. A 61-year-old woman presented progressively more intense headache and rhinorrhea. No trauma was reported. We learned that she had a history of misunderstood spontaneous rhinorrhea beginning two years before, followed one year later by a lateral sinus thrombosis which worsened the cerebrospinal fluid leakage. Some months after stroke a new cerebral magnetic resonance scan revealed a giant trans-ethmoidal encephalo-meningocele. The brain herniation was surgically removed by a subfrontal intradural approach through a frontal craniotomy. Even rare, giant naso-ethmoidal encephalo-meningocele has to be considered in adult patients presenting with rhinorrhea even without a history of meningitis or neurological defects. Venous stroke can affect patients in whom prolonged CSF leakage occurs because of misunderstood cerebrospinal fistula. These patients must be monitored after stroke for the possible onset of an encephalo-meningocele.

The peculiar radiological and pathological findings of four pediatric cases admitted to the University Hospital of Padua between 1990 and 2007 are described. In all cases, the contrast-enhanced head and spine magnetic resonance images revealed thickened and abnormally enhancing subarachnoid spaces particularly at the level of basal cisterns and interhemispheric fissure. Furthermore, small cystic lesions scattered throughout the brain and mainly in the cerebellum were also visible. All patients were missing a well-defined intraparenchymal mass, although during the follow-up a small intramedullary lesion appeared within the cervical spine in two and subsequently in the frontal horn of the left lateral ventricle in one of those. All patients presented an indolent long-term follow-up. Histologically, the tumors were composed by a monotonous population of cells arranged in straight lines or in small lobules. The cells were characterized by round to oval nuclei with finely granular dispersed chromatin, inconspicuous nucleoli with oligodendrocyte-like features. The morphological and immunohistochemical findings suggested in all cases a "glioneuronal commitment" of the tumors. Because of the unique similar clinical and neuroradiological characteristics, we propose this small series of tumors as a new possible distinct pathological and clinical entity.

OBJECTIVE: In recent years, research on stem cells has been focused on the development of personalized cell-based therapies. Owing to their homing properties, adult human stem cells are a promising source of autologous cells to be used as therapeutic vehicles. Multiple potential sources for clinically useful stem and progenitor cells have been identified, including autologous and allogenic embryonic, fetal and adult somatic cells from neural, adipose and mesenchymal tissue. In the present report, we describe a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. METHODS: Adult stem cells isolated from skin and adipose tissue derived from the same adult donor were amplified under varying conditions related to the coating of the chamber slide and the presence of serum and/or growth factors, such as with EGF and FGF2. Neurospheres were then expanded and evaluated in terms of proliferation and gene expression. RESULTS: Adipose and skin derived neurospheres were comparable in size, quantity of cells and genes expressed. Cells from both types of tissue grew optimally without slide coating, in the presence of serum and with the combined addition of FGF2 and EGF. DISCUSSION: We describe a method for isolating and improving a population of multipotent adult precursor cells from the two most accessible adult tissue sources: skin and adipose tissue. This autologous adult stem cell population could be used for cell replacement or cell therapies.

SUMMARY: Hypophyseal triplication is malformation that has not been described previously. We present a child with midline abnormalities who underwent epignathus excision at birth. Brain MR imaging revealed 2 paired lateral pituitary glands and an oval midline gland, each with an independent stalk, connected to a thickened third ventricle floor. Because malformations represent a failure in embryogenesis, this case may provide interesting clues on the normal development of the hypophysis.

Microsurgical anatomy of the fourth ventricle has been comprehensively addressed by masterly reports providing classic descriptions of this complex region. Neuroendoscopy could offer a new, somewhat different perspective of the "inside" view of the fourth ventricle. The purpose of this study was to examine from the anatomical point of view the access to the fourth ventricle achieved by the endoscopic transaqueductal approach, to enumerate and describe the anatomically identifiable landmarks, and to compare them with those described during microsurgery.The video recordings of 52 of 75 endoscopic explorations of the fourth ventricle performed at the authors' institution for different pathological conditions were reviewed and evaluated to identify and describe every anatomical landmark. According to the microsurgical anatomy, at least 23 superficial structures are clearly identifiable in the fourth ventricle, and they represent the comparative basis of parallel endoscopic anatomy of the structures found during the fourth ventricle navigation.The following anatomical structures were identified in all cases: median sulcus, superior and inferior vela medullare, choroid plexus, inferior fovea, hypoglossal and vagal triangles, area postrema, obex, canalis medullaris, lateral recess, and the foramina of Luschka and Magendie. The median eminence, facial colliculus, striae medullaris, auditory tubercle, and inferior fovea were seen in the majority of cases. The locus caevruleus could never be seen.On the whole, 20 anatomical structures could consistently be identified by exploring the fourth ventricle with a fiberscope. Neuroendoscopy offers a quite different outlook on the anatomy of the fourth ventricle, and compared with the microsurgical descriptions it seems to provide a superior and detailed visualization, particularly of the structures located in the inferior triangle.

✓Astroblastoma is a rare primary brain neoplasm that accounts for 0.45–2.8% of brain gliomas. Intraventricular localization is extremely rare. The authors report a case of well-differentiated completely intraventricular astroblastoma in a 6-year-old girl and review the relevant literature. Their patient presented with a 5-week history of progressive nausea and vomiting. Magnetic resonance (MR) imaging revealed a large, well-demarcated, solid-cystic mass in the left temporooccipital ventricular horn. Macroscopic radical resection of the tumor was performed via the superior temporal sulcus. The postoperative course was uneventful and no adjuvant therapy was administered after surgery. No recurrence was detected at 9-months follow-up. Gross-total resection has the greatest impact on patient survival. In differentiated tumors, recurrence is usually local, and adjuvant therapy is recommended after repeated resection for the treatment of recurrence. In patients harboring anaplastic astroblastoma, gross-total resection and adjuvant therapy after the initial surgery seems to be the best choice. It is important to distinguish astroblastoma from ependymoma in clinical practice because of the differences in therapeutic approaches.

Object Microsurgical anatomy of the fourth ventricle has been comprehensively addressed by masterly reports providing classic descriptions of this complex region. Neuroendoscopy could offer a new, somewhat different perspective of the “inside” view of the fourth ventricle. The purpose of this study was to examine from the anatomical point of view the access to the fourth ventricle achieved by the endoscopic transaqueductal approach, to enumerate and describe the anatomically identifiable landmarks, and to compare them with those described during microsurgery. Methods The video recordings of 52 of 75 endoscopic explorations of the fourth ventricle performed at the authors' institution for different pathological conditions were reviewed and evaluated to identify and describe every anatomical landmark. According to the microsurgical anatomy, at least 23 superficial structures are clearly identifiable in the fourth ventricle, and they represent the comparative basis of parallel endoscopic anatomy of the structures found during the fourth ventricle navigation. Results The following anatomical structures were identified in all cases: median sulcus, superior and inferior vela medullare, choroid plexus, inferior fovea, hypoglossal and vagal triangles, area postrema, obex, canalis medullaris, lateral recess, and the foramina of Luschka and Magendie. The median eminence, facial colliculus, striae medullaris, auditory tubercle, and inferior fovea were seen in the majority of cases. The locus caevruleus could never be seen. Conclusions On the whole, 20 anatomical structures could consistently be identified by exploring the fourth ventricle with a fiberscope. Neuroendoscopy offers a quite different outlook on the anatomy of the fourth ventricle, and compared with the microsurgical descriptions it seems to provide a superior and detailed visualization, particularly of the structures located in the inferior triangle.

Mechanisms contributing to the rare but consistent neurotoxicity of contrast media currently in clinical use for the radiological examination of the subarachnoid space remain to be isolated. We assessed, by means of the (14C)-2-deoxy-D-glucose (2-DG) autoradiographic method, the effect of three non-ionic, low-osmolar contrast media, namely metrizamide, iopamidol and iohexol, on the local cerebral glucose utilization in the rat brain after intracisternal application. A significant (-30%) global reduction of the brain's metabolic activity occurred following intracisternal metrizamide injection. When compared with the mock-CSF control group the greater relative changes were observed in the supratentorial grey matter structures. In contrast, no significant changes were observed in metabolic brain activity in rats treated intracisternally with iopamidol and iohexol. These findings were consistent with the hypothesis that metrizamide is a competitive inhibitor of human brain hexokinase. The apparent lack of interference on neural tissue metabolism makes the second generation contrast media less neurotoxic and more suitable for neuroradiological subarachnoid investigations in clinical settings. The present experimental work establishes the 2-DG method as a viable laboratory approach to investigate aspects of neuronal dysfunction induced by contrast media.

Aneurysms of the vein of Galen are uncommon vascular malformations. They are most frequently seen in infants and children, leading to heart failure and hydrocephalus. Exceptionally, they are detected in adults. Several theories have been proposed to explain hydrocephalus in these patients: obstruction of the cerebral aqueduct, impaired absorption of CSF after subarachnoid hemorrhage, passive ex-vacuo mechanism, or thrombosis of an aneurysm. Hydrocephalus has been treated mainly with cerebrospinal shunt procedures, but also direct surgery, radiosurgery and embolisation of the malformation have proved to be effective. We report the case of a partially thrombosed ectasia of the vein of Galen in a 44-year-old male, with huge hydrocephalus successfully treated with an endoscopic third ventriculostomy.