Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia.

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.

Surgical Treatment of Middle Cerebral Artery Aneurysms: Hints and Precautions for Young Cerebrovascular Surgeons.

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.

Combined Use of Color Doppler Ultrasound and Contrast-Enhanced Ultrasound in the Intraoperative Armamentarium for Arteriovenous Malformation Surgery.

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.

Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo.

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.

Surgical Treatment of Anterior Communicating Artery Aneurysms: Hints and Precautions for Young Cerebrovascular Surgeons.

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.

Surgical Treatment of Posterior Communicating Artery Aneurysms: Hints and Precautions for Young Cerebrovascular Surgeons.

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.

Secondary coiling after incomplete surgical clipping of cerebral aneurysms: a rescue strategy or a treatment option for complex cases? Institutional series and systematic review.

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 » 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.

Intracranial aneurysms of the posterior circulation associated with a fenestration: a systematic review.

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<0.001). CONCLUSIONS: This systematic review has shown that endovascular occlusion is the treatment of choice for posterior circulation aneurysms associated with fenestrations, being highly effective, with an occlusion rate of about 80%, unchanged at follow-up. Although the presence of a fenestration can make more complex the aneurysm occlusion, and the occurrence of complications is not negligible, it is not considered a limiting condition for treatment.

Treatment and outcome of thrombosed aneurysms of the middle cerebral artery: institutional experience and a systematic review.

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.

Surgical Management of Intracranial Giant Epidermoid Cysts in Adult: A Case-Based Update.

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.

Antithrombotic therapy and intracranial bleeding in subjects with sporadic brain arteriovenous malformations: preliminary results from a retrospective study.

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.

Lateral Supraorbital Versus Pterional Approach: Analysis of Surgical, Functional, and Patient-Oriented Outcomes.

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.

Integration of Real-Time Intraoperative Contrast-Enhanced Ultrasound and Color Doppler Ultrasound in the Surgical Treatment of Spinal Cord Dural Arteriovenous Fistulas.

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.

Electrocardiographic-Guided Technique for Placement of Ventriculoatrial Shunts: A Valid and Cost-Effective Technical Simplification.

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.

Angio-Architectural Features of High-Grade Intracranial Dural Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and Hemorrhagic Risk.

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.

Minipterional Craniotomy for Treatment of Unruptured Middle Cerebral Artery Aneurysms. A Single-Center Comparative Analysis with Standard Pterional Approach as Regard to Safety and Efficacy of Aneurysm Clipping and the Advantages of Reconstruction.

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 Basilar Artery Aneurysm Involving the Origin of Bilateral Posterior Cerebral and Superior Cerebellar Arteries: Neck Reconstruction with pCONus-Assisted Coiling.

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.

Endovascular Treatment of the Posterior Cerebral Artery Aneurysms: Single-Center Experience and a Systematic Review.

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 I(2). 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 < 0.01). 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.

Genome-wide association study of sporadic brain arteriovenous malformations.

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 p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. RESULTS: 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 p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. CONCLUSIONS: 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.

Bilateral flow changes after extracranial-intracranial bypass surgery in a complex setting of multiple brain-feeding arteries occlusion: The role of perfusion studies.

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.