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Background Safety and efficacy in surgical treatment of cerebral arteriovenous malformations (AVMs) are dictated by thorough understanding of angioarchitectural features, intraoperative identification of feeding vessels, and appreciation of surrounding eloquent areas. Our aim was to describe the preliminary results of combined application of color Doppler ultrasound (CDUS) and contrast-enhanced ultrasound (CEUS) in a consecutive surgical series of AVM. We pointed out the tool's efficacy in distinguishing feeding from bystander vessels and in identifying pattern of venous drainage. We examined its role as an adjunct for semiquantitative evaluation of the nidus inflow. Methods We used combined CDUS and CEUS in patients surgically treated for cerebral AVMs. We adopted these techniques following a designed protocol to guide safer AVM resection as an adjunct to indocyanine green videoangiography. Intraoperative assessment by ultrasound was performed before, during, and following nidus resection. Results Four surgically treated cerebral AVMs availed of the ultrasound protocol. Postoperative conventional angiography showed complete resection of the AVMs. CDUS and CEUS proved to be valuable adjunctive tools to indocyanine green videoangiography and micro-Doppler in properly navigating and discerning vascular structures, especially vessel feeders from bystanders. The protocol allows us to identify flow direction, estimate blood velocity within the nidus, and appreciate flow modifications following temporary clipping. Ultimately, it allows us to evaluate the degree of nidus deafferentation, residual flow, restoration of venous drainage and absence of arteriovenous shunts. Conclusions The CDUS and CEUS protocol is safe and repeatable and works as real-time imaging, further supporting complete surgical resection of AVMs.

Background and Objective Clipping is still considered the treatment of choice for middle cerebral artery (MCA) aneurysms due to their angioarchitectural characteristics as they are often bifurcation dysplasias, needing a complex reconstruction rather than a simple exclusion. Thus, maintaining this surgical expertise is of paramount importance to train of young cerebrovascular surgeons. To balance for the increasingly limited experience due the worldwide general inclination toward the endovascular approaches, it is important to provide to the young neurosurgeons rules and operative nuances to guide this complex surgery. We describe the technical algorithm we use to teach our residents to approach ruptured and unruptured MCA aneurysms, which may help to develop a procedural memory useful to perform an effective and safe surgery. Materials and Methods We reviewed our last 10 years' institutional experience of about 400 cases of ruptured and unruptured MCA aneurysms clipping, analyzing our technical refinements and the difficulties in residents and young neurosurgeons teaching, to establish fundamental key-points and design a didactic algorithm that includes operative instructions and safety rules. Results We recognized seven pragmatic technical key points regarding craniotomy, sylvian fissure opening, basal cisternostomy, proximal vessel control, lenticulostriate arteries preservation, aneurysm neck microdissection, and clipping to use as a didactic algorithm for teaching residents, and as operative instructions for inexperienced neurosurgeons. Conclusion In the setting of clipping MCA aneurysms, respect for surgical rules is of paramount importance to perform an effective and safe procedure, ensure the best aneurysm exclusion, and preserve the flow in collaterals and perforators.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Several hundred variants have been identified in these HHT-causing genes, including deletions, missense and nonsense mutations, splice defects, duplications, and insertions. In this study, we have analyzed retrospectively collected images of magnetic resonance angiographies (MRA) of the brain of HHT patients, followed at the HHT Center of our University Hospital, and looked for the distribution of cerebrovascular phenotypes according to specific gene variants. We found that cerebrovascular malformations were heterogeneous among HHT patients, with phenotypes that ranged from classical arteriovenous malformations (AVM) to intracranial aneurysms (IA), developmental venous anomalies (DVA), and cavernous angiomas (CA). There was also wide heterogeneity among the variants of the ENG and ACVRL1 genes, which included known pathogenic variants, variants of unknown significance, variants pending classification, and variants which had not been previously reported. The percentage of patients with cerebrovascular malformations was significantly higher among subjects with ENG variants than ACVRL1 variants (25.0% vs. 13.1%, p < 0.05). The prevalence of neurovascular anomalies was different among subjects with different gene variants, with an incidence that ranged from 3.3% among subjects with the c.1231C > T, c.200G > A, or c.1120C > T missense mutations of the ACVRL1 gene, to 75.0% among subjects with the c.1435C > T missense mutation of the ACVRL1 gene. Further studies and larger sample sizes are required to confirm these findings.

Background Anterior communicating artery (AComA) aneurysms are the most common intracranial aneurysm, accounting for 25 to 38% of all cases. In spite of the advent of modern neurointerventional treatments, they still represent a strong indication for clipping in certain anatomical and clinical conditions. However, AComA aneurysms are the deepest located aneurysms of the anastomotic circle of Willis, with a complex spatial orientation, and they are fed by bilateral branches of the anterior circulations. Although, on one hand, these aneurysms represent the most complex ones of the anterior circulation, on the other hand, the experience of young neurosurgeons is increasingly limited. Therefore, respecting operative guidelines is crucial to achieve the best aneurysm exclusion and avoid fatal intraoperative complications. Study Objective We describe the technical algorithm we use to teach young neurosurgeons how to approach AComA aneurysms and help them to develop a procedural memory needed to perform an efficient and safe surgery. Materials and Methods We reviewed our last 10 years of institutional experience of > 200 cases of clipping ruptured and unruptured AComA aneurysms, analyzing our technical refinements and the difficulties in teaching residents and young neurosurgeons how to establish fundamental key points and design a didactic algorithm that includes operative instructions and safety rules. Results We identified seven pragmatic technical key points regarding craniotomy, cisternostomy, gyrus rectus corticectomy, proximal control, perforators and Heubner preservation, aneurysm neck dissection, and clipping to use in a didactic algorithm for teaching residents and as operative instructions for inexperienced neurosurgeons. Conclusion In the setting of clipping AComA aneurysms, respect for surgical rules is of paramount importance to perform an efficacious and safe procedure and ensure the best aneurysm exclusion and preservation of neurovascular structures.

Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker αSMA, with direct connections between αSMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans.

Background In the surgical treatment of spinal dural arteriovenous fistulas (DAVFs), intraoperative definition of anatomic characteristics of the DAVF and identification of the fistulous point is mandatory to effectively exclude the DAVF. Case Description Intraoperative ultrasound and contrast-enhanced ultrasound integrated with color Doppler ultrasound was applied in the surgical setting for a cervical DAVF to identify the fistulous point and evaluate correct occlusion of the fistula. Conclusions Integration of intraoperative ultrasound and contrast-enhanced ultrasound is a simple, cost-effective technique that provides an opportunity for real-time dynamic visualization of DAVF vascular patterns, identification of the fistulous point, and assessment of correct exclusion. Compared with other intraoperative tools, such as indocyanine green videoangiography, it allows the surgeon to visualize hidden anatomic and vascular structures, minimizing surgical manipulation and guiding the surgeon during resection.

Residual and recurrent intracranial aneurysms after surgical clipping present a persistent risk of bleeding. Secondary coiling after incomplete clipping represents a strategy to occlude the residual sac: feasibility, bleeding risk and outcome were evaluated through a systematic review of literature along with the series of two tertiary referral neurovascular centres. Demographics, ruptured status, aneurysm morphology, topography, exclusion at surgery, timing of secondary coiling, complications, occlusion rate and outcome were analysed. Percentage of incidence and 95% CI were calculated for all variables. T test was used for continue variables, whereas Fisher's test (two-sided) is for categorical ones. Overall, 102 patients (92 cases from literature and 10 cases from institutional series) were included. Mean age at diagnosis was 52.94 ± 12.17 years, and male/female ratio 0.5; 3/4 of aneurysms involved the anterior circulation, whereas ¼ the posterior circulation. An aneurysmal neck remnant was described in 58.43% of cases, an aneurysmal sac remnant in 29.21% and a regrowth in 12.36%. Residual aneurysm rupture was reported in 22% of cases. Complete/near-complete occlusion after secondary coiling was observed in 70% of cases, a partial in 25.56% and a failure in 4.44%. Only one case of perforation was reported. Complications were comparable to standard endovascular procedures. Aneurysms remnants after clipping are often observed in cases difficult anatomical locations. Their bleeding risk is not negligible. Secondary coiling is a rescue strategy to effectively and safely secure the aneurysm remnant. Only in a minority of cases, it is a staged treatment after 'remodelling' of the aneurysm neck.

Background Ventriculoatrial (VA) shunt is a routine technique for the treatment of hydrocephalus. The correct position at the superior vena cava–right atrium junction is generally assessed by radiography. We present the first experience of an alternative, nonradiographic technique to assess the distal end of the VA shunts through an electrocardiographic (EKG) method. The technique has developed from the large experience of central venous catheters (CVC) worldwide; the EKG-guided method is a common and validated alternative to standard radiologic control of the location of the tip of any CVC. Methods Five consecutive patients underwent VA shunt with venous catheter positioned with the EKG-guided technique. The position of the catheter tip was verified by standard chest radiography. Results Four men and 1 woman (mean age, 45.4 years) underwent VA shunt for hydrocephalus with the EKG-guided technique. The side of internal jugular vein puncture was the right side in 4 cases and the left side in 1 case. As confirmed by radiography, all VA shunt tips were located within the correct range. There was no radiologic evidence of procedure-related complication or catheters that had to be replaced. Conclusions The EKG-guided technique for VA shunts is as accurate as fluoroscopy, but simpler, more readily available, less expensive, safer, and more cost effective. It reduces the need of radiography and radiologic exposition for both patients and operators. The EKG method may be a valid and cost-effective alternative to standard radiologic control in VA shunts, as for any central venous access device, and could become the preferential method for confirming tip position during VA shunt surgery.

Whether antithrombotic treatment is safe and/or affects the risk of intracranial bleeding in subjects with sporadic brain arteriovenous malformations (AVMs) is unknown. We conducted a retrospective analysis on the use of antithrombotics among patients affected by brain AVMs in follow-up at our institution. Attention was paid to the type of antithrombotic drug (either antiplatelets or anticoagulants), current or past use, dosage, and duration of treatment. Several clinical and angioarchitectural features of brain AVMs were also taken into consideration. The association between the use of antithrombotics and haemorrhagic onset was analyzed. A total of 77 patients were included in this study. Among them, ten patients were taking antithrombotic drugs at the time of AVM diagnosis. The rate of haemorrhagic onset was not significantly different between subjects who were and were not taking antithrombotic drugs (40 vs 55.2%, p = ns). Among the many clinical and angioarchitectural features analyzed, the only parameter that showed a statistically significant association with haemorrhagic onset was the size of the nidus. Patients who took antithrombotic treatments after being diagnosed with a brain AVM did not show an increased rate of intracranial haemorrhage over time considering a mean follow-up 4 years. In our study, antithrombotic treatment was not associated with increased intracranial bleeding among subjects with brain AVMs. In the presence of a strong clinical indication, antiplatelet and anticoagulant medications should not be denied a priori to patients with brain AVMs. Studies on larger populations are necessary to confirm these data.

Background High-grade dural arteriovenous fistulas (dAVFs) can present shunts with very different angio-architectural characteristics. Specific hemodynamic factors may affect clinical history and determine very different clinical courses. Objectives To evaluate the relationship between some venous angio-architectural features in high-grade dAVFs and clinical presentation. Specific indicators of moderate or severe venous hypertension were analyzed, such as altered configurations of the dural sinuses (by a single or a dual thrombosis), or overload of cortical vessels (restrictions of outflow, pseudophlebitic cortical vessels, and venous aneurysms). Methods The institutional series was retrospectively reviewed (49 cases), and the pattern of venous drainage was analyzed in relationship with clinical presentation (benign/aggressive/hemorrhage). Results Thirty-five of 49 cases displayed cortical reflux (high-grade dAVFs). This subgroup displayed a benign presentation in 31.42% of cases, an aggressive in 31.42%, and hemorrhage in 37.14%. Conclusions Our data confirm that within high-grade dAVFs, 2 distinct subpopulations exist according to severity of clinical presentation. Some indicators we examined showed correlation with aggressive nonhemorrhagic manifestations (outflow restriction and pseudophlebitic cortical vessels), while other showed a correlation with hemorrhage (dual thrombosis and venous aneurysms). Current classifications appear insufficient to identify a wide range of conditions that ultimately determine the organization of the cortical venous drainage. Intermediate degrees of venous congestion correlate better with the clinical risk than the simple definition of cortical reflux. The angiographic aspects of venous drainage presented in this study may prove useful to assess dAVF hemodynamic characteristics and identify conditions at higher clinical risk.

Background In spite of the advent of neurointerventional treatment, different clinical and anatomical features are still strong indications for clipping of posterior communicating artery (PComA) aneurysms. But the experience of young neurosurgeons is increasingly limited, and therefore providing technical operative guidelines is a fundamental prerequisite to achieve the best aneurysm exclusion and avoid perioperative complications. Study Objective We describe a technical algorithm we use to teach young neurosurgeons how to approach carotid aneurysms that may help them develop a procedural memory and thus perform an efficient and safe surgery. Material and Methods We reviewed our last 10 years of institutional experience of > 150 cases of clipping ruptured and unruptured PComA aneurysms, analyzing our technical refinements and the difficulties in teaching residents and young neurosurgeons how to establish fundamental key points and design a didactic algorithm that includes operative instructions and safety rules. Results We recognized seven pragmatic technical key points regarding craniotomy, cisternostomy, proximal and distal control, aneurysm neck dissection, preservation of neurovascular structures, and clipping to use in a didactic algorithm for teaching residents and as operative instructions for inexperienced neurosurgeons. Conclusion In the setting of clipping PComA aneurysms, respect for surgical rules is of paramount importance to perform an efficacious and safe procedure and ensure the best aneurysm exclusion and preservation of neurovascular structures.

Thrombosed aneurysms of the middle cerebral artery (MCA) usually show large dimension and complex morphology with neck sclerosis and perforating vessels originating from the sac. Only limited experiences from case reports or small mixed series including thrombosed aneurysms in different locations are available in literature. To systematically review all the pertinent literature, a comprehensive literature review with the search terms "MCA, aneurysm, and thrombosis" and a pooled analysis including our institutional series were performed. We evaluated demographics, ruptured status, aneurysm morphology, topography and size, thrombosis extension, treatment, complications, final occlusion rate, and clinical outcome at follow-up. Data were individually extracted for each patient and included in a pool for the statistical analysis. Forty-two articles published between 1992 and 2016 were selected, including a total of 115 patients. Most of thrombosed aneurysms were saccular (67.6%), large or giant (86.7%), and located at the MCA bifurcation (67.3%). The treatment of choice was surgery in more than 80% of cases compared with the endovascular techniques, though the overall percentage of complications reported in the two groups was similar and around 20% of cases. Clinical outcome was favorable in more than 85% of patients after treatment. This is the first systematic review focusing on treatment and outcome of thrombosed MCA aneurysms. Our data depict their main angioarchictectural and clinical characteristics, proving the feasibility of their treatment with good prognosis in a high percentage of patients. However, complication and mortality rates of about 20 and 3.5%, respectively, are not negligible.

INTRODUCTION A fenestration is an anatomical variation that most commonly involves vessels of the posterior circulation, which can predispose the formation of aneurysms and represents a further technical challenge for treatment. There are no large series and the incidence of complications is unknown. This paper is a systematic review on this topic. EVIDENCE ACQUISITION The relevant English literature was reviewed and the data was extracted for each patient and collected in a pool. Demographics, localization of fenestration, morphology and aneurysm topography, admission and follow-up clinical status, treatments, complications and occlusion rate were recorded. EVIDENCE SYNTHESIS We analyzed 62 articles published between 1992 and 2016 including 120/133 patients/aneurysms. The most commonly involved segment was the vertebro-basilar junction (82.5%), followed by the basilar trunk (10%). About 96.6% of reported aneurysms were saccular and 80.3% were ruptured. The preferred treatment was endovascular (86.67%) and a surgical clipping was reported in just over 13% of patients. A complete/almost complete occlusion was obtained in about 80% of cases, with a global rate of complications of 12.5%. A serious clinical condition at onset has been independently associated with poor outcome at multivariate analysis (P

Background Recently, the lateral supraorbital (LSO) keyhole variant of the standard pterional (PT) approach has been popularized for anterior skull base surgery, because it provides good anatomic exposition, reduced complications, and better aesthetic and functional results. However, these aspects have been formally compared only by a limited number of studies. We reviewed our experience with 50 consecutive anterior communicating artery (AComA) and A1/A2 aneurysms. Of these 50 patients, 25 had undergone the standard PT approach and 25, the LSO variant. We report the results in terms of exclusion of the aneurysm, postoperative complications, functional/masticatory outcomes, and aesthetic and patient satisfaction. Methods From January 2014 to December 2015, 25 patients with unruptured AComA and A1/A2 aneurysms underwent the standard PT craniotomy. From January 2016 to March 2017, another 25 patients underwent the LSO technique. Results No statistically significant differences were observed in the aneurysmal exclusion rate at angiographic follow-up or major complications. A statistically significant difference in the clinical outcome (Glasgow Outcome Scale) was evident only for the immediate postoperative time and was not significant during the follow-up period. The hospital stay was shorter in the LSO group. Minor complications, patient satisfaction, aesthetics, and functional and masticatory outcomes were significantly better statistically in the LSO group. Conclusions The LSO approach demonstrated a lower rate of early clinical minor complications, with a reduction in hospitalization. The LSO approach provides better results for patient satisfaction, masticatory comfort, and cosmetic results. In our experience, the LSO approach is a safe and effective substitute to the standard PT craniotomy to treat unruptured AComA and A1/A2 aneurysms.

Epidermoid cysts (ECs) are benign and slow-growing lesions that account for about 0.2%–2% of all intracranial tumors. Symptoms appear slowly and tumors may have already grown to giant proportions when patients receive their first diagnosis. The optimal treatment for ECs is surgical removal, which includes the total resection of the entire capsule of the lesion in order to minimize the risk of malignant transformation associated with partial removal. However, considering the giant size that the ECs can reach at the time of the diagnosis, and their adherence to the surrounding structures, the risks and benefits of total versus subtotal resections in the short- and long-term patients' outcome are still under debate. Here, we report a case of an extensive giant EC and offer a discussion of its characteristics, surgical management, and postoperative outcome, taking a cue to argue about the recent literature based in the latest case studies.

Pterional craniotomy (PT) has long been the standard approach for the treatment of middle cerebral artery (MCA) aneurysms, even though it may cause temporalis muscle atrophy, facial nerve injury, and masticatory difficulties. Minipterional craniotomy (MPT) is an alternative approach that may provide the same surgical corridor, limiting the risk of postoperative esthetic and functional complications. From January 2011 to December 2014 we consecutively performed 68 craniotomies for surgical treatment of unruptured MCA aneuryms: 37 were standard PT and 31 were MPT. There were no significant differences in mean age, sex, and aneurysm topography between the two groups. The mean skin incision length was 14 cm in the PT group and 6 cm in the MPT group. According to the Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS), there were no significant differences in clinical outcome at discharge or follow-up between the two groups. Also, the rates of complete aneurysm exclusion were comparable. However, the number of patients complaining of masticatory disorders was higher among those treated with PT. Finally, the number of complications observed in the PT group was higher than that in the MPT group, but only the differences in mean hospitalization length and necessity for a dural patch for reconstruction were statistically significant. In conclusion, the MPT approach is a safe and effective alternative to the standard PT for the treatment of unruptured MCA aneurysms.

Giant aneurysms of the basilar artery are rare and are frequently associated with obstructive hydrocephalus and brainstem compression. Treatment still remains a challenge both for neurosurgeons and for interventional neuroradiologists. Cases reported in the literature are anecdotal and, overall, their outcomes are poor. We present the case of a patient with a giant aneurysm of the basilar artery tip, involving the origin of both the posterior cerebral and superior cerebellar arteries, who underwent coiling and ventriculoperitoneal shunting for associated obstructive hydrocephalus. A pCONus ® stent (Phenox; Bochum, Germany) was detached with its petals opened over the ostia of the parent vessels, with the aim being to reconstruct the neck of the aneurysm and to preserve the flow in the parent vessel. Moreover, the presence of the stent was useful to maintain the coils within the dome of the aneurysm. The pCONus is a new neurovascular device that is also useful for treating cases of complex basilar artery aneurysms when the ostia of the parent vessel origin is at the level of the aneurysm neck.

Background and Objectives Laser-based repairing techniques offer several advantages respect to standard suturing in microsurgery. In this work we evaluate the applicability and feasibility of two innovative laser-based approaches for microvascular repair and anastomoses: (1) laser-assisted vascular repair (LAVR); (2) laser-assisted end-to-end vascular anastomosis (LAVA). All these procedures have been executed by the use of diode laser irradiation and chitosan-patches infused with Indocyanine Green (ICG). Study Design/Materials and Methods Experiments were performed on 30 rabbits. Twenty animals underwent LAVR and 10 end-to-end LAVA procedures. In the LAVR group, a 5-mm longitudinal cut was performed on the common carotid artery (CCA), then an ICG-infused chitosan patch was topically applied and laser-soldered over the arterial lesion. In the LAVA group the end-to-end anastomosis was executed on CCA by means of application of the three interrupted sutures and subsequent laser soldering of the ICG-infused patch. Animals underwent different follow-up periods (2, 7, 30, and 90 days). At the end of every follow-up, the animals were re-anesthetized and a microdoppler analysis was performed in order to check patency of the treated vessels. Then soldered segments were excised and subjected to histological and ultrastructural evaluations. Results At the end of surgery no bleeding from the treated segment was observed; all the treated vessels were patent. At the end of follow-up periods, no signs of perivascular haemorrhage were found. An intraoperative microdoppler evaluation assessed the patency of all the treated vessels. Histology showed a good reorganization of the vascular wall structures and an early endothelial regeneration was observed by SEM. Conclusions Our study demonstrated the efficacy of laser tissue soldering by means of ICG-infused chitosan patches for the in vivo repairing of microvascular lesions and end-to-end anastomoses. This approach offers several advantages over conventional suturing methods and is technically easy to perform, minimizing the surgical trauma to vessels. Lasers Surg. Med. 45:318–325, 2013. © 2013 Wiley Periodicals, Inc.

Background Single nucleotide polymorphisms (SNPs) on chromosome 9p21 have been recently associated with intracranial aneurysms and stroke. In this study, we tested the association between the rs1333040C>T polymorphism on the 9p21 locus and sporadic brain arteriovenous malformations (BAVMs). Methods We studied 78 patients with sporadic BAVMs and 103 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T polymorphism was assessed by PCR–restriction fragment length polymorphism using the BsmI restriction endonuclease. Results We found that the distribution of the three genotypes (TT/TC/CC) of the rs1333040 polymorphism was significantly different between cases and controls (p=0.02). Using dominant, recessive and additive genetic models, we found that the TT genotype and the T allele were significantly more common in the BAVM group than in controls. We also evaluated whether the rs1333040 polymorphism was associated with prototypical angio-architectural features of BAVMs (such as nidus size, venous drainage pattern and Spetzler–Martin grading) and with the occurrence of seizures and bleeding. We detected a significant association between the homozygous T allele in the recessive model and BAVMs with a nidus >4 cm in diameter. Deep venous drainage was significantly more frequent among subjects carrying at least one T allele in the dominant model. Patients with seizures showed a significant association with the TT genotype and the T allele in all genetic models examined whereas those who experienced intracranial bleeding showed a significant association with the T allele in the trend model. Conclusions This is the first study demonstrating an association between an SNP of the 9p21 region and sporadic BAVMs. Our results emphasise the relevance of this chromosomal locus as a common risk factor for various forms of cerebrovascular diseases.

article Although several descriptions of the angioarchitectural features of brain arteriovenous malformations (AVMs) associated with higher hemorrhagic risk have been reported, the prognostic value of the different bleeding pat- terns still needs to be elucidated. This study evaluated the influence on clinical appearance and outcome of the parenchymal and non- parenchymal (subarachnoid hemorrhage—SAH—and intraventricular hemorrhage—IVH) bleedings associated with ruptured AVMs. Clinical records and neuroradiological examinations of 30 patients with hemorrhagic AVMs were reviewed in order to identify their angioarchitectural features and the associated bleeding pattern. These data along with demographic characteristics and treatment modality were dichotomized and their relationship with clinical status at admission and follow-up was tested. IVH as well as parenchymal hematomas larger than 20 cm 3 appeared associated with a severe clinical status at admission, whereas SAH involving basal cisterns was significantly associated with unfavorable outcome. Age, sex and angioarchitectural features did not show significant association with the severity of the prognosis. However, none of these bleeding patterns appeared as an independent risk factor of poor outcome at multi- variate analysis. In conclusion, our data emphasized the possibility that non-parenchymal bleeding may worsen the outcome of patients with hemorrhagic AVMs.

BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium.METHODS: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with pRESULTS: The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal pCONCLUSIONS: We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution.

Background Endovascular treatment of posterior cerebral artery aneurysms is challenging because of the particular features of posterior circulation vessels. We performed a systematic review of the literature, to assess safety and efficacy associated to their endovascular treatment. Methods Through a literature search, we identified 20 studies that met our inclusion criteria. We also performed a retrospective analysis of patients treated at our institution during the last 10 years. Demographics, angiographic features, clinical presentation, and outcome were extracted from each study. Data were combined using a random effects model and heterogeneity was assessed by I2. Results We retrieved 7 patients from our institutional series and 246 from the literature. Overall, 253/259 patients/aneurysms were included in this study. A selective coiling was performed in 27% of cases, a stent-assisted coiling in 2%, and a parent artery occlusion in 62%. Immediate complete/near-complete occlusion was obtained in 96% of cases and maintained in 90% at follow-up. No differences were observed between ruptured and unruptured aneurysms. Ischemic complications were reported in 15% of cases, although the most frequent was a hemianopsia in 7%; a hemiparesis was reported in only 2% of cases. Mortality was overall 1%. Ischemic complications were more frequent among patients who underwent nonselective treatment (P Conclusions Endovascular treatment of posterior cerebral artery aneurysms is associated with increased degree of occlusion and low recurrence rate. However, a parent artery occlusion implies complications, even although most of them are minor events such as hemianopsia.

We report on a symptomatic case in which the whole intracranial blood supply was provided by a single vertebral artery as both internal carotid arteries were occluded and the contralateral vertebral artery was severely hypoplasic. The patient was treated by a flow-augmentation extracranial-intracranial bypass. Preoperative perfusion studies were essential in tailoring surgical strategy. Keypoints of the paper are contralateral perfusion changes after unilateral bypass surgery. The patient experienced a total recovery from symptoms and a bilateral improvement in brain perfusion, probably as consequence of post-operative hemodynamic rearrangement.

Objectives Dural arteriovenous fistulas (DAVFs) are a challenging condition in vascular neurosurgery. Disease natural history and its management is still debated. In the present paper we report our center series on DAVFs over a period of 10 years. Our data were compared with relevant literature. Patient and methods Our series includes 45 cases: 14 cavernous sinus, 11 transverse-sigmoid, 8 patients tentorial, 6 anterior cranial fossa, 5 patients spinal, 1 patient foramen magnum. Results and conclusions DVAFs distribution, clinical presentation and hemorrhagic risk are discussed. Cavernous sinus DAVFs are the most common site in our series. Other locations in order of frequency are transverse-sigmoid sinus, tentorial, anterior cranial fossa, spinal and foramen magnum. The majority of patients presented with non-aggressive symptoms. 18% presented with intracranial hemorrhage: all the hemorrhages occurred in high-grade DAVFs. For most patients, endovascular treatment, transarterial or transvenous, was the first option. Surgery was performed for the anterior cranial fossa DAVFs and other complex lesions draining mostly transverse-sigmoid sinus and tentorium. In 7% of cases a combination of endovascular + surgical treatment was used. Our series has been carefully analyzed in comparison ‘side by side’ with most relevant literature on DVAFs, focusing particularly on management strategies, therapeutic options and risks related to treatment.

✓ Extraaxial cavernous hemangiomas are rare intracranial lesions that can be located in different cranial compartments. Extension across different tissue planes such as the subcutaneous tissue, skull, orbital cavity, intracranial dura mater, and extracranial trigeminal divisions within the same patient has not been previously reported. This 32-year-old woman suffered left exophthalmos, left sixth nerve palsy, and trigeminal neuropathy. Magnetic resonance imaging studies revealed an extensive multicompartmental lesion, with enhancement following Gd administration. A left orbitopterional approach allowed removal of several cavernomatous lesions located in the orbit, frontotemporal dura, and lateral wall of the cavernous sinus. A histologically based diagnosis of extraaxial cavernous hemangioma was made. In the postoperative period the patient experienced a regression of her symptoms. The authors report on a case of cavernous hemangioma with a unique extension to different intracranial/extracranial compartments. Although radical removal of the lesion was not feasible, partial excision allowed for satisfactory clinical control of the patient's symptoms.

In order to understand the oncogenic properties of retinoblastoma-interacting zinc-finger (RIZ) gene products, we produced an MCF-7-derived cell line expressing a fusion protein containing the zinc-finger (aa 359–497) domain of RIZ protein (MCF-7/znf). The Zn-finger domain contains three of the eight putative Zn-finger motifs and is located in proximity of the E1A-like domain containing the Rb protein-binding motif. The MCF-7/znf cells showed a higher growth rate than the parental or the control cell lines, both in hormone-deprived conditions or upon estrogen stimulation. Furthermore, they were less sensitive to the growth inhibitory effect of anti-estrogens and showed a higher level of expression of cyclin D1 and A. The expressed Zn-finger domain recombinant product was localized in the nucleus and in the nucleoli and its expression modified the pattern of actin staining in the cytoplasm. In conclusion the presented results indicated that the Zn-finger domain could be endowed with the putative oncogenic activity of RIZ2 gene product.

I recenti progressi della neurochirurgia e della neuroradiologia permettono di affrontare i problemi relativi alle malformazioni arterovenose cerebrali secondo diverse modalità terapeutiche anche tra loro combinate. Ci riferiamo in particolare al trattamento diretto microneurochirurgico, alla riduzione od esclusione della malformazione vascolare dal circolo mediante trattamento endovascolare anche ripetuto nel tempo ed al trattamento radiochirurgico. Diversi fattori sono stati correlati alla valutazione del rischio chirurgico, quali la sede, le dimensioni, l'angio-architettura, con particolare riferimento alla presenza di aneurismi arteriosi o venosi ed al pattern del drenaggio venoso. Altri fattori che influenzano il rischio chirurgico sono quelli relativi al quadro generale del paziente ed alle sue condizioni neurologiche. L'indicazione al trattamento di una malformazione vascolare si pone se il rischio dell'opzione terapeutica è considerato “accettabile”, ossia inferiore rispetto a quello della storia naturale. Gli Autori espongono i risultati della casistica personale relativa a 20 pazienti trattati con modalità chirurgica ed endovascolare.

Objective Indocyanine green video angiography (ICG-VA) is a non invasive, easy to use and a very useful tool for various neurosurgical procedures. Initially introduced in vascular neurosurgery since 2003, it’s applications have broadened over time, both in vascular applications and in other neurosurgical fields. The objective of our study is to review all published literature about ICG-VA, cataloguing its different applications. Methods A systematic review of all pertinent literature articles published from January 2003 to May 2014 using Pubmed access was performed using pertinent keywords; cross check of references of selected articles was performed in order to complete bibliographical research. Results of research were grouped by pathology. Results and conclusions The paper systematically analyses ICG-VA different applications in neurosurgery, from vascular neurosurgery to tumor resection and endoscopic applications, focusing on reported advantages and disadvantages, and discussing future perspectives.

Background: The chromosomal locus 9p21 is a novel genetic marker for a variety of cardiovascular and cerebrovascular diseases. In a recent study, we have demonstrated an association between the single nucleotide polymorphism (SNP) rs1333040C>T on chromosome 9p21 and sporadic brain arteriovenous malformations (BAVMs). Here, we extended our analysis to an additional SNP on chromosome 9p21 (rs7865618A>G) and increased our sample size including BAVMs from two different Italian neurosurgical centers. Methods: We studied 206 patients with sporadic BAVMs and 171 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T and rs7865618A>G polymorphisms were assessed by PCR-RFLP using the BsmI and MspI restriction endonucleases, respectively. For each SNP, we performed dominant, recessive, and additive genetic models. Results: The distribution of the three possible genotypes of rs1333040 (TT, TC and CC) was statistically different between cases and controls (p = 0.0008). The TT genotype was significantly associated with BAVMs both in the dominant (p = 0.013) and recessive (p = 0.012) models. The T allele was significantly associated with BAVMs in the additive model (p = 0.002). Also the distribution of the three possible genotypes of rs7865618 (GG, AG and AA) was statistically different between cases and controls (p = 0.005), and the GG genotype and G allele were significantly associated with BAVMs in the dominant (p = 0.032), recessive (p = 0.007), and additive models (p = 0.009). We also detected a significant association between BAVMs with large nidus size and the GG genotype and G allele of rs7865618 and the TT genotype of rs1333040. A deep venous drainage was instead associated with the TT genotype of the rs1333040 and the GG genotype of the rs7865618. The occurrence of bleeding was associated with the TT genotype and T allele of rs1333040, while the presence of seizures appeared associated with the GG genotype of rs7865618. Conclusions: SNPs of the 9p21 region, in addition to be genetic markers for coronary artery disease, stroke, and intracranial aneurysms, are associated with sporadic BAVMs. These results extend and strengthen the role of the 9p21 chromosomal region as a common risk factor for cerebrovascular diseases.

As reported earlier, p53 antibodies are detected in the sera of patients with different types of cancer, including lung cancer. In contrast, in the serum of healthy subjects the presence of anti-p53 antibodies is extremely rare. We collected the venous blood samples of 109 patients affected with lung cancer (LC): 57 patients (46 M, 11 F) with non-small-cell carcinoma (NSCLC), 52 others (40 M, 12 F) with small-cell carcinoma (SCLC). Serum p53 antibodies were assayed using ELISA method and all positive sera were confirmed by Western-blot method. In addition, using IRMA methods we assayed serum CEA, TPA, CYFRA21-1 and NSE. Serum p53Ab are detectable (p53Ab-positive) in 35/109 (32.1%) patients with lung cancer. About 17/57 (29.8%) patients affected with NSCLC and 18/52 (34.6%) with SCLC were p53Ab-positive. CEA, TPA, CYFRA21-1 and NSE sensitivity in LC patients (NSCLC+SCLC) is 50.5%, 58.7%, 42.2%, 35.8%, respectively. The lower sensitivity (32.1%) of serum p53Ab is connected with the higher specificity and diagnostic accuracy (100% and 69%, respectively). Out of 35 patients p53Ab-positive, five (14.3%) exhibit only serum p53Ab, while serum values of the established tumor markers were lower than cut-off. Serum p53Ab assessment is a simple and a low-cost assay with a good specificity and diagnostic accuracy that in LC patients can be used at least in association with established tumor markers.

The aim of this study was to investigate the expression of estrogen receptor (ER) beta and alpha genes in normal (N) and malignant (C) primary cultures of human prostate epithelial cells (PEC) and fibroblasts (PFC) and in the prostate tissue donors. Both ERbeta and ERalpha messenger ribonucleic acids were found by RT-PCR analysis in six NPECs and normal prostate tissues and in only one of six CPECs and in the respective cancer tissue donor. The other five CPECs and related cancer tissue donors and all normal and cancer PFCs expressed ERalpha messenger ribonucleic acid alone. Immunoblot analysis, using a polyclonal anti-ERbeta (C-terminal) antibody, demonstrated ERbeta protein in all NPEC lysates and in one of the six CPECS: ERalpha protein was expressed in both NPECs and CPECs when a polyclonal antibody directed against the ERalpha N-terminal domain was used. In contrast, ERalpha protein was not detected in two of the six CPEC lysates when ERalpha C-terminal monoclonal antibodies were used. Using a set of primers designed to amplify the region from exons 6-8, RT-PCR analysis demonstrated the absence of the expected transcript in these cells. The present study shows that the ERbeta gene is expressed together with ERalpha in normal prostates and NPECs, whereas it is barely detectable in prostate cancer and CPECS: Moreover, in some CPECs, the ERalpha gene may be transcribed in a changed protein, resulting from the expression of a deletion variant. Together, these data suggest that prostate malignancy is associated with a potential disorder of ER-mediated pathways.

A 47-year-old man underwent surgery for syncytial meningioma. Twelve months later neuroimaging demonstrated recurrence, showing an intra-axial ring-enhanced cystic lesion in the site of previous surgery. High-grade glioma was suspected. Neuropathologist's diagnosis was 'intraparenchymal rhabdoid meningioma'. The case raises questions about behaviour of meningiomas and their differential diagnosis with gliomas.

The purpose of this review article is to summarize the epidemiology, pertinent anatomy, mechanisms of injury, and classification systems of occipital condylar fractures (OCFs), as well as their clinical presentation and screening, the importance of computed tomography (CT) for detection, and current treatment options. The authors emphasize the rate of occurrence of OCFs, which may be detected in as many as 16% of patients with craniocervical injury. Clinical presentation is not specific, and OCF is not readily diagnosed at physical examination. Failure to diagnose may result in substantial morbidity, and thus accurate diagnosis is mandatory for both therapeutic and medicolegal implications. The diagnosis is most likely to be made with CT. Thin-section CT technique is the method of choice to evaluate the traumatized craniocervical junction. OCFs should be suspected in all patients sustaining high-energy blunt trauma to the head and/or upper cervical spine, resulting from axial loading, lateral bending and/or rotation, and/or direct blow. Besides a CT study assessing potential intracranial injuries, these patients require CT of the craniocervical junction. Radiologists should be aware of the types of OCFs and associated injuries.

An unusual case of rotational occlusion of a non-dominant vertebral artery (VA) is presented. This clinical syndrome is associated for the first time with a complex craniovertebral junction malformation. Rotational occlusion of the VA is usually asymptomatic, vertebro-basilar insufficiency has been rarely observed in cases of involvement of a dominant VA, and concomitant occlusion or hypoplasia of the contralateral artery. Diagnosis of rotational VA occlusion is based on haemodynamic demonstration of the effects of head rotation. The importance of the awareness of this syndrome is stressed.

Prostaglandins of the E series are immunomodulatory agents which exert inhibitory as well as stimulatory effects on a variety of immune responses. Since it is known that PGE2is able to increase cAMP levels, we investigated whether it can affect gene expression through the activation of the transcription factors which bind enhancer elements in the promoter regions of cAMP-regulated genes. Using electrophoretic mobility shift assay, we demonstrated that a short treatment of human T lymphocytes with PGE2induces specific binding activity to CRE and AP-2, but not AP-1, DNA elements. Since the okadaic acid, a potent protein phosphatase inhibitor, prolongs the induction of the binding activity, phosphorylation events are likely to occur. This activity seems to be due to increased cAMP levels because forskolin and IBMX mimic the effects of PGE2. More interestingly, transfection experiments with CRE–CAT plasmide show that PGE2activates the transcription of a CRE-containing promoter. These data support the positive role for PGE2on some immune functions.

Brain arteriovenous malformations are characterized by a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation. They are known to occur either sporadically or in the context of well-defined genetic disorders. Haemorrhage represents the most severe clinical manifestation, whereas other common symptoms include headache, seizures and neurological deficits. Although sporadic forms do not recognize a specific genetic cause, in recent years, it has been hypothesized that genes involved in angiogenesis and inflammation or coding for proteins, such as fibronectins, laminins and integrins, may play a role in the pathophysiology of brain arteriovenous malformations. More recently, a new trend of genetic studies has investigated the association between sporadic arteriovenous malformations and single nucleotide polymorphisms, single base variations between genomes within members of a biological species or between paired chromosomes in an individual, which may determine the susceptibility to develop complex diseases and influence their natural history. Several polymorphisms in two different families of genes have been associated with disease susceptibly and increased haemorrhagic risk. These genes are mainly involved in the inflammatory cascade and in the regulation of angiogenesis. However, most of the investigated polymorphisms have been selected on the basis of candidate genes because of their potential functional role in the pathogenesis of brain arteriovenous malformations or in other cerebrovascular diseases. Only one hypothesis-free genome-wide association study in a small number of patients has been performed so far, but it was unable to identify significant associations between brain arteriovenous malformations and specific genetic loci. In this article, we review and analyse the polymorphisms investigated to date in association with sporadic brain arteriovenous malformations in the medical literature. We discuss the biological, pathophysiological and clinical implications of these studies, with particular attention to the prediction of haemorrhagic risk and the possibility of building genetic profiles capable of defining the architectural features of the malformations and predict their evolution and natural history. We also present a joint analysis of the risk estimates found by the studies in literature that have evaluated the association between single nucleotide polymorphisms and brain arteriovenous malformation susceptibility and risk of bleeding. This analysis shows a statistically significant association between the interleukin 6 -174G>C (odds ratio = 1.97; 95% confidence interval: 1.15-3.38) and the tumour necrosis factor α -238G>A (odds ratio = 2.19; 95% confidence interval: 1.25-3.83) gene polymorphisms and risk of intracranial haemorrhage and between the activin-like kinase 1 (also known as ACVRL1) intervening sequence 3 -35A>G (odds ratio = 2.42; 95% confidence interval: 1.54-3.8) gene polymorphism and disease susceptibility.

Epileptic seizures account for 24-40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs).We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P0.05.About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P0.001 and 48.9% vs. 23.5%; P = 0.002, respectively). No lobar predisposition was observed. A nidus4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26-6.31; P = 0.009) at logistic regression analysis.AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.

Laser-based approach for suturing biological tissues is emerging as a valid alternative to conventional techniques, because of its widely demonstrated advantages, such as immediate watertight closure of the wound, minimal inflammatory response and scar formation, and reduced wound healing time. Moreover the laser based techniques may provide suturing in hardly accessible sites (e.g. in microsurgery, endoscopic and minimally invasive surgery) or in thin tissues that are impossible to treat with staples and/or stitches (e.g. the lens capsule bag). Usually, the biological tissue is stained with a liquid or semisolid preparation of organic chromophores (indocyanine green - ICG): a near infrared laser light is locally absorbed and converted into a photothermal effect, thus inducing welding of the wound. Some limitations are ascribed to the use of organic chromophores, such as their poor photochemical stability, excessive diffusiveness in the biological matrices and inadequate stability when stored in an aqueous solution or dispersed in a physiological environment. To overcome these problems we proposed the use of chitosan matrices, properly stained with conventional chromophores (ICG). The Indocyanine Green (ICG) is included into the chitosan matrices: the matrix enwraps the chromophore particles, thus enhancing their stability, durability and effectiveness. The final product has thus the necessary optical and mechanical characteristics to design a safe and standard laser-based tissue closuring procedure. The ICG infused chitosan patches were used to perform Laser Assisted Vasular Repair (LAVR) and Anastomosis (LAVA) in an in vivo experimental study in carotid rabbits. An ICG-infused chitosan patch was used to wrap the artery in the lesion area. A diode laser emitting at 810 nm, equipped with a 300 °m diameter optical fiber was used to weld the patch onto the artery wall, by delivering single laser spots to induce local patch/tissue adhesion. The result is an immediate closure of the wound, with no bleeding at clamps release. The animals were observed during follow-up. All the anastomosis were patent, no bleeding signs were documented. The carotid samples underwent histological examinations. The advantages of the proposed technique are: simplification of the surgical procedure and shortening of the operative time; decreased foreign-body reaction; reduced inflammatory response and improved vascular healing process.

Sir, We read with great interest the article by Fierstra et al . (2011), recently published in your journal. This article reopens the debate regarding the unsolved problem of the origin of seizures in patients with brain arteriovenous malformations, the pathophysiology of which remains poorly understood. Although angiographic studies have shown some associations between different brain arteriovenous malformation angioarchitectural features and epilepsy, they have not elucidated the underlying pathophysiology (Turjman et al ., 1995 a , b ; Hoh et al ., 2002). Similarly, MRI studies have often shown gliosis and chronic ischaemic changes in peri-nidal tissue as well as in remote regions, but any significant correlation has been demonstrated between extent of gliosis and clinical symptoms (Essig et al ., 2000). The main pathophysiological hypotheses to date include: (i) focal cerebral ischaemia attributable to a steal phenomenon as described by Spetzler et al . (1992) and Taylor et al . (2002); (ii) gliosis, demyelination and haemosiderin deposits in peri-nidal tissue; and (iii) secondary epileptogenesis in ipsilateral temporomesial cortex (Yeh et al ., 1990), or at a distant site, attributable to a ‘kindling’ phenomenon, in which epileptic discharges are enhanced by excitatory synaptic connections from brain arteriovenous malformations (Hoh et al ., 2002). Bleeding was deemed responsible for triggering seizure activity by Turjman et al . (1995 a ) and Stein and Wolpert (1980); in contrast, in the study by Hoh et al . (2002), intracranial haemorrhage was not a statistically significant factor associated with epilepsy. Fierstra et al . (2011) studied in vivo the possible haemodynamic effect …

""The retinoblastoma protein-interacting zinc-finger (RIZ) gene, also known as PRDM2, encodes two protein products, RIZ1 and RIZ2, differing for the presence of a 202 aa domain, called PR domain, at the N-terminus of the RIZ1 molecule. While the histone H3 K9 methyltransferase activity of RIZ1 is associated with the negative control of cell proliferation, no information is currently available on either expression regulation of the RIZ2 form or on its biological activity. RIZ proteins act as ER co-activators and promote optimal estrogen response in female reproductive tissues. In estrogen-responsive cells, 17-beta estradiol modulates RIZ gene expression producing a shift in the balanced expression of the two forms. Here, we demonstrate that an estrogen-responsive element (ERE) within the RIZ promoter 2 is regulated in a ligand-specific manner by ERa, through both the AF1 and AF2 domains. The pattern of ERa binding, histone H4 acetylation, and histone H3 cyclical methylation of lysine 9 was comparable to other estrogen-regulated promoters. Association of topoisomerase II beta with the RIZ promoter 2 confirmed the transcriptional activation induced by estrogen. We hypothesize that RIZ2, acting as a negative regulator of RIZ1 function, mediates the proliferative effect of estrogen through regulation of survival and differentiation gene expression. J. Cell. Physiol. 227: 964975, 2012. (C) 2011 Wiley Periodicals, Inc.""

Laser welding of microvessels provides several advantages over conventional suturing techniques: surgical times reduction, vascular healing process improvement, tissue damage reduction. We present the first application of biopolymeric patches in an in vivo laser assisted procedure for vessel repair. The study was performed in 20 New Zealand rabbits. After anesthesia, a 3-cm segment of the right common carotid artery was exposed and clamped proximally and distally. A linear lesion 3 mm in length was carried out. We used a diode laser emitting at 810 nm and equipped with a 300 mu m diameter optical fiber. To close the cut, ICG-loaded chitosan films were prepared: chitosan is characterized by biodegradability, biocompatibility, antimicrobial, haemostatic and wound healing-promoting activity. ICG is an organic chromophore commonly used in the laser welding procedures to mediate the photothermal conversion at the basis of the welding effect. The membranes were used to wrap the whole length of the cut, and then they were welded in the correct position by delivering single laser spots to induce local patch/tissue adhesion. The result is an immediate closure of the wound, with no bleeding at clamps release. The animals were observed during follow-up and sacrificed after 2, 7, 30 and 90 days. All the repaired vessels were patent, no bleeding signs were documented. The carotid samples underwent histological examinations. The advantages of the proposed technique are: simplification of the surgical procedure and shortening of the operative time; good strength of the vessel repair; decreased foreign-body reaction, reduced inflammatory response and improved vascular healing process.

"Growing evidence supports the concept that dynamic intra-and inter-chromosomal links between specific loci contribute to the creation of cell type-specific gene expression profiles. Therefore, analysis of the establishment of peculiar functional correlations between sites, also distant on linear DNA, that govern the transcriptional process appears to be of fundamental relevance. We propose here an experimental approach showing that 17 beta-estradiol-induced transcription associates to formation of loops between the promoter and termination regions of hormone-responsive genes. This strategy reveals as a tool to be also suitably used, in conjunction with automated techniques, for an extensive analysis of sites shared by multiple genes for induced expression."

Laser assisted vascular repair is a new optimized technique based on the use of ICG-infused chitosan patch to close a vessel wound, with or even without few supporting single stitches. We present an in vivo experimental study on an innovative end-to-end laser assisted vascular anastomotic (LAVA) technique, performed with the application of ICG-infused chitosan patches. The photostability and the mechanical properties of ICG-infused chitosan films were preliminary measured. The in vivo study was performed in 10 New Zealand rabbits. After anesthesia, a 3-cm segment of the right common carotid artery was exposed, thus clamped proximally and distally. The artery was then interrupted by means of a full thickness cut. Three single microsutures were used to approximate the two vessel edges. The ICG-infused chitosan patch was rolled all over the anastomotic site and welded by the use of a diode laser emitting at 810 nm and equipped with a 300 mu m diameter optical fiber. Welding was obtained by delivering single laser spots to induce local patch/tissue adhesion. The result was an immediate closure of the anastomosis, with no bleeding at clamps release. Thus animals underwent different follow-up periods, in order to evaluate the welded vessels over time. At follow-up examinations, all the anastomoses were patent and no bleeding signs were documented. Samples of welded vessels underwent histological examinations. Results showed that this technique offer several advantages over conventional suturing methods: simplification of the surgical procedure, shortening of the operative time, better re-endothelization and optimal vascular healing process

A clinical diagnosis of typical trigeminal neuralgia does not rule out the possibility of a space-occupying lesion compressing the nerve along its course from the brainstem to Meckel's cave. 4 cases of typical trigeminal neuralgia, treated medically for several years and seen here recently before a space-occupying lesion was found in the posterior cranial fossa, point up the need for thorough neurological and neuroradiological examination of all patients with the typical symptoms. Lesion removal resulted in total relief from pain in 3 patients. In the fourth patient the pain was controlled by percutaneous surgery with thermocoagulation of the gasserian ganglion.

Midbrain multiloculated cystic formations can rarely origin by enlargement of Virchow-Robin spaces surrounding mesencephalo-thalamic artery and branches of the collicular and accessory collicular arteries. They can determine several pictures of midbrain syndrome and obstructive hydrocephalus. The authors describe a 38 year-old man affected by a Benedikt's syndrome related to a midbrain multicystic formation. Clinical course, differential diagnosis, and therapeutic choice are here also briefly discussed.

408 Positional cerebral ischemia (PCI) is an extremely rare condition in which dramatic central nervous system deficits are triggered by standing in patients with severe stenosis or occlusion of the major brain-supplying blood vessels [1] . Because PCI is generally associated with orthostatic hypotension [2, 3] , a hemodynamic mechanism has been proposed [4] . However, PCI has been reported even in patients without orthostatic hypotension [1] . The treatment is medical, but surgery can be considered in refractory cases (endarterectomy for carotid artery stenosis or either highor low-flow extra-intracranial bypass – for carotid occlusion) [3] . We report a case of PCI associated with middle cerebral artery (MCA) occlusion and without orthostatic hypotension treated by lowflow extra-intracranial bypass. The patient, a 58-year-old male with a history of hypertension, suffered an ischemic stroke in the left hemisphere with sudden onset of speech disturbance and right hemiparesis in 1992. He experienced complete neurological recovery in approximately 1 month. Aspirin was the medical treatment. In December 2004, while the patient was still on aspirin, he presented with several stereotyped TIAs with acute onset of right-sided hemiparesis and paresthesias, and mild motor aphasia. Symptoms that were always triggered by standing presented nearly daily and rapidly improved (within few minutes) on returning to the supine position. Brain MRI showed multiple chronic ischemic lesions in the territory of the left MCA. Dual antiplatelet therapy with clopidogrel plus aspirin was started, followed by reduction in the frequency of the TIAs. In May 2005, recurrent episodes of right hemiparesis were associated with incomplete recovery when lying down, and he was hospitalized. General examination was normal and there were no hematological abnormalities. The supine blood pressure ranged between 130/80 and 150/90 mm Hg. There was no significant orthostatic hypotension and only occasionally was a slight reduction ( ! 10 mm Hg) in systolic blood pressure observed on standing. However, just a few blood pressure evaluations were performed on standing because of the worsening of neurological symptoms in this condition. MRI showed multiple ischemic areas in the territory of the left MCA ( fig. 1 A), whereas MR angiography demonstrated the occlusion of the left MCA ( fig. 1 B). A cerebral angiogram confirmed the occlusion of the left MCA at the M1 segment and a hypovascularized area in the left parietal region ( fig. 1 C). SPECT scans revealed a severe impairment of regional cerebral perfusion throughout the left hemisphere involving both deep and superficial territories; a marked reduction in 99m Tc ECD uptake was detected in the frontal and temporal cortices, while absence of radiotracer uptake was found in the parietal and occipital cortices ( fig. 1 E, F). Screening for vasculitis, Cerebrovasc Dis 2010;29:408–409 DOI: 10.1159/000288055