Mechanical thrombectomy for in-hospital stroke: data from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: The benefit, safety, and time intervals of mechanical thrombectomy (MT) in patients with in-hospital stroke (IHS) are unclear. We sought to evaluate the outcomes and treatment times for IHS patients compared with out-of-hospital stroke (OHS) patients receiving MT. METHODS: We analyzed data from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) between 2015 and 2019. We compared the functional outcomes (modified Rankin Scale (mRS) scores) at 3 months, recanalization rates, and symptomatic intracranial hemorrhage (sICH) after MT. Time intervals from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were recorded for both groups, as were door-to-imaging and door-to-groin for OHS. A multivariate analysis was performed. RESULTS: Of 5619 patients, 406 (7.2%) had IHS. At 3 months, IHS patients had a lower rate of mRS 0-2 (39% vs 48%, P<0.001) and higher mortality (30.1% vs 19.6%, P<0.001). Recanalization rates and sICH were similar. Time intervals (min, median (IQR)) from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were favorable for IHS (60 (34-106) vs 123 (89-188.5); 150 (105-220) vs 220 (168-294); 227 (164-303) vs 293 (230-370); all P<0.001), whereas OHS had lower door-to-imaging and door-to-groin times compared with stroke onset-to-imaging and onset-to-groin for IHS (29 (20-44) vs 60 (34-106), P<0.001; 113 (84-151) vs 150 (105-220); P<0.001). After adjustment, IHS was associated with higher mortality (aOR 1.77, 95% CI 1.33 to 2.35, P<0.001) and a shift towards worse functional outcomes in the ordinal analysis (aOR 1.32, 95% CI 1.06 to 1.66, P=0.015). CONCLUSION: Despite favorable time intervals for MT, IHS patients had worse functional outcomes than OHS patients. Delays in IHS management were detected.

The Role of Bypass Surgery for the Management of Complex Intracranial Aneurysms in the Anterior Circulation in the Flow-Diverter Era: A Single-Center Series.

Despite the increasing popularity of flow diverters (FDs) as an endovascular option for intracranial aneurysms, the treatment of complex aneurysms still represents a challenge. Combined strategies using a flow-preservation bypass could be considered in selected cases. In this study, we retrospectively reviewed our series of patients with complex intracranial aneurysms submitted to bypass. From January 2015 to May 2022, 23 patients were selected. We identified 11 cases (47.8%) of MCA, 6 cases (26.1%) of ACA and 6 cases (26.1%) of ICA aneurysms. The mean maximal diameter was 22.73 ± 12.16 mm, 8 were considered as giant, 9 were fusiform, 8 presented intraluminal thrombosis, 10 presented wall calcification, and 18 involved major branches or perforating arteries. Twenty-five bypass procedures were performed in 23 patients (two EC-IC bypasses with radial artery graft, seventeen single- or double-barrel STA-MCA bypasses and six IC-IC bypasses in anterior cerebral arteries). The long-term bypass patency rate was 94.5%, and the total aneurysm exclusion was 95.6%, with a mean follow-up of 28 months. Median KPS values at last follow-up was 90, and a favorable outcome (KPS ≥ 70 and mRS ≤ 2) was obtained in 87% of the cases. The use of bypass techniques represents, in selected cases, a valid therapeutic option in the management of complex anterior circulation aneurysms when a simpler direct approach, including the use of FD, is considered not feasible.

Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

OBJECTIVE: The objective of this paper was to explore the utility of time to maximum concentration (Tmax )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT). METHODS: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves. RESULTS: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). Tmax  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A Tmax  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73). INTERPRETATION: Tmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888.

Endovascular treatment beyond 24 hours from the onset of acute ischemic stroke: the Italian Registry of Endovascular Thrombectomy in Acute Stroke (IRETAS).

BACKGROUND: Clinical trials and observational studies have demonstrated the benefit of thrombectomy up to 16 or 24 hours after the patient was last known to be well. This study aimed to evaluate the outcome of stroke patients treated beyond 24 hours from onset. METHODS: We analyzed the outcome of 34 stroke patients (mean age 70.7±12.3 years; median National Institutes of Health Stroke Scale (NIHSS) score 13) treated with endovascular thrombectomy beyond 24 hours from onset who were recruited in the Italian Registry of Endovascular Thrombectomy in Acute Stroke. Selection criteria for patients were: pre-stroke modified Rankin scale (mRS) score of ≤2, non-contrast CT Alberta Stroke Program Early CT score of ≥6, good collaterals on single phase CT angiography (CTA) or multiphase CTA, and CT perfusion mismatch with an infarct core size ≤50% of the total hypoperfusion extent or involving less than one-third of the extent of the middle cerebral artery territory evaluated by visual inspection. The primary outcome measure was functional independence assessed by the mRS at 90 days after onset. Safety outcomes were 90 day mortality and the occurrence of symptomatic intracranial hemorrhage (sICH). RESULTS: Successful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was present in 76.5% of patients. Three month functional independence (mRS score 0-2) was observed in 41.1% of patients. The case fatality rate was 26.5%. and the incidence of sICH was 8.8%. CONCLUSIONS: These findings suggest that, in a real world setting, very late endovascular therapy is feasible in appropriately selected patients.

Salvage transorbital approach for the endovascular treatment of carotid cavernous fistulas.

PURPOSE: Carotid cavernous fistulas (CCFs) are abnormal connections between the cavernous sinus (CS) and carotid arteries. In direct CCFs, a transarterial route is often the preferred vascular access; in case of indirect CCFs, the complex anatomy of the feeder vessels and their extra-intracranial anastomosis makes the transarterial embolization challenging and often ineffective. The aim of this study was to review our experience with the transorbital approach to treat patients affected by CCF who have already experienced an endovascular failure procedure, in order to assess this salvage technique feasibility, by analyzing possible risks and complications. METHODS: We performed a retrospective study of all patients affected by CCFs who underwent transorbital embolization between February 2017 and February 2019 at our institution. RESULTS: All patients (3 cases) tolerated both the retrograde embolization and the direct surgical approach with clinical improvement; the closure of the fistula was complete and verified intraoperatively by angiography. Esthetic result was acceptable in all cases with reduction of the proptosis and the intraocular pressure, and increased visual acuity. There were no complications or clinical recurrence. CONCLUSION: Transorbital approach for the endovascular treatment of CCFs is a feasible and safe salvage procedure, which can find indication after other endovascular access failures.

Persistent trigeminal artery aneurysms: case report and systematic review.

BACKGROUND: The persistent trigeminal artery (PTA) is an adult carotid-basilar anastomosis with debated pathologic aspects, such as its association with brain aneurysms. True trigeminal artery aneurysms are rare vascular anomalies, reported in a few case reports. OBJECTIVE: To report our experience with a ruptured trigeminal artery aneurysm and to provide a systematic review of the literature in order to analyse potential links between the anatomic configuration of the PTA and PTA aneurysm (PTAA) type, and implications of each PTAA type for the diagnostic and therapeutic approach. METHODS: We reviewed the medical literature on trigeminal artery aneurysms according to the PRISMA guidelines. Population characteristics, aneurysms features, and PTA type and side were assessed. RESULTS: 40 previously published cases of PTAAs were included in the analysis. The mean age of subjects was 55 years, with a strong female predominance (77%). Four PTAAs were accidentally discovered, while 16 caused compressive symptoms and 20 were ruptured. Successful endovascular treatment was performed in 62% of cases. CONCLUSIONS: PTAAs are rare vascular anomalies, underdiagnosed in the presence of a trigemino-cavernous fistula. Parent vessel occlusion seems to be the best therapeutic option for ruptured or symptomatic unruptured PTAAs in Saltzman type II and III PTAs. Patency of the parent vessel is the main target in Saltzman type I PTA.

Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry.

INTRODUCTION: Endovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT. METHODS: A multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (≥90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up. RESULTS: A total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259±120 min vs 305±202 min; p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b-3 reperfusion was lower in the EICA occlusion group (70% vs 81%; p=0.03). The favorable outcome (90-day mRS 0-2), intracerebral hemorrhage and procedural complications were similar in both groups. CONCLUSION: Atherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b-3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis.

Left Deep Frontal Cavernous Angioma Mimicking a Glioma in an Adult Patient.

Cerebral cavernous angiomas are vascular malformations characterized by large adjacent vessels. Usually, these lesions are smaller than 3 cm, the mean age at presentation occurs between 20 and 40 years, and the neuroradiological findings are well described, especially for magnetic resonance imaging, where the "popcorn balls" appearance is due to the presence of locules containing blood. Among these, the giant cavernous angiomas are very rare, particularly in adults. We collected clinical and neuroradiological data from clinical file and hospital diagnostic archive. A comprehensive review of similar cases was performed. We describe the clinical, diagnostic, and surgical management of a giant cerebral cavernous angioma located in the left deep frontal lobe mimicking a high-grade glioma in an adult Chinese patient. Giant cerebral cavernous angioma may be misdiagnosed and should be considered as differential diagnosis.

The LUNA aneurysm embolization system for intracranial aneurysm treatment: short-term, mid-term and long-term clinical and angiographic results.

BACKGROUND AND PURPOSE: Intrasaccular aneurysm flow disruption represents an emerging endovascular approach to treat intracranial aneurysms. The purpose of this study was to determine the clinical and angiographic outcomes of using the LUNA aneurysm embolization system (AES) for treatment of intracranial aneurysms. MATERIALS AND METHODS: The LUNA AES Post-Market Clinical Follow-Up study is a prospective, multicenter, single-arm study that was designed to evaluate device safety and efficacy. Bifurcation and sidewall aneurysms were included. Aneurysm occlusion was assessed using the Raymond-Roy classification scale. Disability was assessed using the Modified Rankin Scale (mRS). Morbidity was defined as mRS >2 if baseline mRS ≤2, increase in mRS of 1 or more if baseline mRS >2, or mRS >2 if aneurysm was ruptured at baseline. Clinical and angiographic follow-up was conducted at 6, 12 and 36 months. RESULTS: Sixty-three subjects with 64 aneurysms were enrolled. Most aneurysms were unruptured (60/63 (95.2%)); 49 were bifurcation or terminal (49/64 (76.6%)). Mean aneurysm size was 5.6±1.8 mm (range, 3.6-14.9 mm), and mean neck size was 3.8±1.0 mm (range, 1.9-8.7 mm). Though immediate postoperative adequate occlusion was low (11/63, 18%), adequate occlusion was achieved in 78.0% (46/59) and 79.2% (42/53) of the aneurysms at 12 months and 36 months, respectively. Four patients were retreated by the 12-month follow-up (4/63 (6.3%)) and three patients were retreated by the 36-month follow-up (3/63 (4.8%)). There were two major strokes (2/63 (3.2%)), one minor stroke (1/63 (1.6%)) and three incidents of intracranial hemorrhage in two subjects (2/63 (3.2%)) prior to the 12-month follow-up. There was one instance of mortality (1/63, 1.6%). Morbidity was 0% (0/63) and 1.8% (1/63) at the 12-month and 36-month follow-ups, respectively. CONCLUSIONS: LUNA AES is safe and effective for the treatment of bifurcation and sidewall aneurysms. CLINICAL TRIAL REGISTRATION: ISRCTN72343080; Results.

Ferroportin Expression in Adipocytes Does Not Contribute to Iron Homeostasis or Metabolic Responses to a High Calorie Diet.

BACKGROUND & AIMS: Iron has an increasingly recognized role in the regulation of adipose tissue function, including the expression of adipokines involved in the pathogenesis of nonalcoholic fatty liver disease. The cellular iron exporter, ferroportin, has been proposed as being a key determinant of adipocyte iron homeostasis. METHODS: We studied an adipocyte-specific ferroportin (Fpn1) knockout mouse model, using an Adipoq-Cre recombinase driven Fpn1 deletion and fed mice according to the fast food diet model of nonalcoholic steatohepatitis. RESULTS: We showed successful selective deletion of Fpn1 in adipocytes, but found that this did not lead to increased adipocyte iron stores as measured by atomic absorption spectroscopy or histologically quantified iron granules after staining with 3,3'-diaminobenzidine-enhanced Perls' stain. Mice with adipocyte-specific Fpn1 deletion did not show dysregulation of adiponectin, leptin, resistin, or retinol-binding protein-4 expression. Similarly, adipocyte-specific Fpn1 deletion did not affect insulin sensitivity during hyperinsulinemic-euglycemic clamp studies or lead to histologic evidence of increased liver injury. We have shown, however, that the fast food diet model of nonalcoholic steatohepatitis generates an increase in adipose tissue macrophage infiltration with crown-like structures, as seen in human beings, further validating the utility of this model. CONCLUSIONS: Ferroportin may not be a key determinant of adipocyte iron homeostasis in this knockout model. Further studies are needed to determine the mechanisms of iron metabolism in adipocytes and adipose tissue.

The androgen receptor in bone marrow progenitor cells negatively regulates fat mass.

It is well established that testosterone negatively regulates fat mass in humans and mice; however, the mechanism by which testosterone exerts these effects is poorly understood. We and others have shown that deletion of the androgen receptor (AR) in male mice results in a phenotype that mimics the three key clinical aspects of hypogonadism in human males; increased fat mass and decreased bone and muscle mass. We now show that replacement of the Ar gene specifically in mesenchymal progenitor cells (PCs) residing in the bone marrow of Global-ARKO mice, in the absence of the AR in all other tissues (PC-AR Gene Replacements), completely attenuates their increased fat accumulation. Inguinal subcutaneous white adipose tissue and intra-abdominal retroperitoneal visceral adipose tissue depots in PC-AR Gene Replacement mice were 50-80% lower than wild-type (WT) and 75-90% lower than Global-ARKO controls at 12 weeks of age. The marked decrease in subcutaneous and visceral fat mass in PC-AR Gene Replacements was associated with an increase in the number of small adipocytes and a healthier metabolic profile compared to WT controls, characterised by normal serum leptin and elevated serum adiponectin levels. Euglycaemic/hyperinsulinaemic clamp studies reveal that the PC-AR Gene Replacement mice have improved whole-body insulin sensitivity with higher glucose infusion rates compared to WT mice and increased glucose uptake into subcutaneous and intra-abdominal fat. In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function.

Enterprise Deployment Through PulseRider To Treat Anterior Communicating Artery Aneurysm Recurrence.

BACKGROUND: PulseRider (Pulsar Vascular, Los Gatos, California, USA) is a new endovascular device designed to treat wide-neck bifurcation intracranial aneurysms. Deployment of a stent through a PulseRider to treat an aneurysm's recurrence has never been described before. CASE DESCRIPTION: We report the case of a 55-year-old man who underwent coiling of an 8-mm anterior communicating artery aneurysm with assistance of a PulseRider neck reconstruction device. The 6-month digital subtraction angiography control showed aneurysm recurrence, so we deployed an Enterprise 2 closed-cell stent (Codman, Miami Lakes, Florida, USA) in the A1-A2 segment passing across the previously implanted PulseRider. Enterprise correctly expanded and allowed for adequate coiling of the aneurysm. CONCLUSION: An Enterprise stent can be safely opened through a PulseRider in order to treat aneurysm recurrence.

Trigeminal Neuralgia Completely Relieved After Stent-Assisted Coiling of a Superior Cerebellar Artery Aneurysm.

BACKGROUND: Although secondary trigeminal neuralgia is usually due to tumors or multiple sclerosis, other major neurologic diseases, such as aneurysms, should be taken into account when the history or the symptoms suggest a secondary origin. CASE DESCRIPTION: A 67-year-old lady presented with a 6-month history of trigeminal neuralgia involving exclusively the right ophthalmic division. A dedicated 3-dimensional-magnetic resonance imaging-magnetic resonance angiography study documented rare contact with a wide-necked aneurysm of the superior cerebellar artery, which distorted the trigeminal root. The patient underwent an endovascular treatment by stent-assisted coiling with the complete disappearance of neuralgic pain attacks within 24 hours. CONCLUSION: The complete relief from the neuralgic paroxysms immediately after endovascular stent-assisted occlusion of a superior cerebellar artery aneurysm demonstrates the crucial role of a pulsating stimulus on the demyelinated nerve fibers in evoking the ectopically generated discharges.

CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke.

BACKGROUND: Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy. METHODS: Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals. RESULTS: Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0-2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome. CONCLUSIONS: CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.

Curative Transvenous Onyx Embolization of a Maxillary Arteriovenous Malformation in a Child: Report of a New Technique.

Endovascular management of maxillary arteriovenous malformation (AVMs) can be complex. Transarterial, transvenous, and direct puncture embolization has been described. The authors report the case of a 9-year-old girl with a hemorrhagic maxillary AVM, which has been treated by transvenous embolization after failure of transarterial embolization. The venous pouch was catheterized with a detachable tip microcatheter and occluded by slow Onyx injection. Onyx filled the pouch and retrogradely reached some arterial feeders, achieving complete occlusion. Bleeding episode ceased and at 6 months follow-up no recurrence was found. Maxillary AVMs can be successfully treated by transvenous Onyx embolization.

CT perfusion and angiographic assessment of pial collateral reperfusion in acute ischemic stroke: the CAPRI study.

BACKGROUND: The purpose of this study was to evaluate the correlation between a novel angiographic score for collaterals and CT perfusion (CTP) parameters in patients undergoing endovascular treatment for acute ischemic stroke (AIS). METHODS: 103 patients (mean age 66.7±12.7; 48.5% men) with AIS in the anterior circulation territory, imaged with non-contrast CT, CT angiography, and CTP, admitted within 8 h from symptom onset and treated with any endovascular approach, were retrospectively included in the study. Clinical, neuroradiological data, and all time intervals were collected. Careggi Collateral Score (CCS) was used for angiographic assessment of collaterals and the Alberta Stroke Program Early CT Score (ASPECTS) for semiquantitative analysis of CTP maps. Two centralized core laboratories separately reviewed angiographic data, whereas CT findings were evaluated by an expert neuroradiologist. Univariate and multivariate analysis were performed considering CCS both as an ordinal and a dichotomous variable. RESULTS: 37/103 patients (35.9%) received intravenous tissue plasminogen activator. Median (IQR) ASPECTS was 9 (6-10) for admission CT, 9 (5-10) for cerebral blood volume (CBV) maps, 3 (2-3) for mean transit time maps, 3 (2-4), for cerebral blood flow maps, and 5 (3-7) for CTP mismatch. Univariate analysis showed a significant correlation between CCS and ASPECTS for all CTP parameters. Multivariate analysis confirmed an independent association only between CCS and CBV (p=0.020 when CCS was considered as a dichotomous variable, p=0.026 with ordinal CCS). CONCLUSIONS: A correlation between angiographic assessment of the collateral circulation and CTP seems to be present, suggesting that CCS may provide an indirect evaluation of the infarct core volume to consider for patient selection in AIS.

Y-stent assisted coiling of bifurcation aneurysms with Enterprise stent: long-term follow-up.

BACKGROUND: Y-stent assisted coiling has been proposed for the treatment of wide-neck bifurcation aneurysms, but there are many technical variations. We report our single-center experience of Y-stent assisted coiling of bifurcation aneurysms with the closed cell Enterprise stent in order to evaluate the safety and long-term results of this technique. The literature on Y-stenting and its hemodynamic effects are reviewed. METHODS: Fifty-two consecutive patients with wide-neck bifurcation aneurysms underwent Y-stent assisted coiling with two Enterprise stents. The procedure was completed in 48 cases (92.3%) and technical failure occurred in 4 cases (7.3%). Cases performed with other stents were excluded. All procedures were performed under double antiplatelet therapy. Periodic clinical and neuroradiological follow-up was performed. RESULTS: Mean neuroradiological follow-up time was 26 months. Complete immediate occlusion was obtained in 87.5% of patients. Two remnants had regrown at follow-up and were recoiled, achieving complete occlusion. The late neuroradiological occlusion rate was: complete occlusion 93.6%, neck remnant 4.3%, sac remnant 2.1%. No in-stent stenosis was detected at follow-up. Among the 48 procedures, two complications occurred (4.2%). Mortality was 2.1%. No delayed ischemic stroke occurred. CONCLUSIONS: Y-stent assisted coiling has a high immediate occlusion rate and very good long-term stability. The procedure is relatively safe, although the complication and mortality rates are not negligible. Two Enterprise stents can be safely used for Y-stenting and, indeed, offer the advantage of easier catheterization, delivery and deployment into distal and tortuous vessels than open cell stents.

Assisted coiling of saccular wide-necked unruptured intracranial aneurysms: stent versus balloon.

BACKGROUND AND PURPOSE: Assisted coiling with stents or balloons enables a higher percentage of complete occlusions of saccular unruptured intracranial aneurysms to be achieved with a reasonable complication rate. The aim of this study was to compare stent-assisted coiling and the balloon remodeling technique in terms of efficacy, stability, and safety for the treatment of comparable unruptured saccular intracranial aneurysms. MATERIALS AND METHODS: 268 patients with 286 saccular unruptured wide-necked intracranial aneurysms were treated at our institution with stent- or balloon-assisted coiling and retrospectively reviewed. Statistical analysis was performed to assess significant differences between the two groups. RESULTS: The rate of complete occlusion at the end of the procedure was higher with stent-assisted coiling than with balloon-assisted coiling (86.8% vs 78%) and the same results were also observed after 6 months (92.1% vs 77.6%; p=0.05). About 50% of major recurrences occurred in large to giant aneurysms (p<0.001). The overall complication rate was similar in the stent-assisted and balloon-assisted groups (10.3% vs 9.3%). Independently of the technique, a higher complication rate was observed with bifurcational aneurysms, particularly in the middle cerebral artery (p=0.016). CONCLUSIONS: Stent-assisted coiling achieved better results in terms of complete occlusion and stability than balloon-assisted coiling with a lower rate of recurrence without being associated with a higher risk of intraprocedural complications. Bifurcational and large to giant aneurysms were associated with higher complication rates and higher recurrence rates, respectively, and still represent a challenge for both techniques.

Ubiquitous expression of the Pik3caH1047R mutation promotes hypoglycemia, hypoinsulinemia, and organomegaly.

Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of PI3K, are among the most common mutations found in human cancer and have also recently been implicated in a range of overgrowth syndromes in humans. We have used a novel inducible "exon-switch" approach to knock in the constitutively active Pik3ca(H1047R) mutation into the endogenous Pik3ca gene of the mouse. Ubiquitous expression of the Pik3ca(H1047R) mutation throughout the body resulted in a dramatic increase in body weight within 3 weeks of induction (mutant 150 ± 5%; wild-type 117 ± 3%, mean ± sem), which was associated with increased organ size rather than adiposity. Severe metabolic effects, including a reduction in blood glucose levels to 59 ± 4% of baseline (11 days postinduction) and undetectable insulin levels, were also observed. Pik3ca(H1047R) mutant mice died earlier (median survival 46.5 d post-mutation induction) than wild-type control mice (100% survival > 250 days). Although deletion of Akt2 increased median survival by 44%, neither organ overgrowth, nor hypoglycemia were rescued, indicating that both the growth and metabolic functions of constitutive PI3K activity can be Akt2 independent. This mouse model demonstrates the critical role of PI3K in the regulation of both organ size and glucose metabolism at the whole animal level.

Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction.

The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or accelerates metabolic dysfunction during obesity. In the current study, we sought to identify the effects of VEGF-A neutralization on parameters of glucose metabolism and insulin action in a dietary mouse model of obesity. Within only 72 h of administration of the VEGF-A-neutralizing monoclonal antibody B.20-4.1, we observed almost complete reversal of high-fat diet-induced insulin resistance principally due to improved insulin sensitivity in the liver and in adipose tissue. These effects were independent of changes in whole-body adiposity or insulin signaling. These findings show an important and unexpected role for VEGF in liver insulin resistance, opening up a potentially novel therapeutic avenue for obesity-related metabolic disease.