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OBJECTIVEThe introduction of flow-diverter devices (FDDs) has revolutionized the endovascular treatment of intracranial aneurysms. Here the authors present their Italian multicenter experience using the flow re-direction endoluminal device (FRED) in the treatment of cerebral aneurysms, evaluating both short- and long-term safety and efficacy of this device.METHODSBetween February 2013 and December 2014, 169 consecutive aneurysms treated using FRED in 166 patients were entered into this study across 30 Italian centers. Data collected included patient demographics, aneurysm location and characteristics, baseline angiography, adverse event and serious adverse event information, morbidity and mortality rates, and pre- and posttreatment modified Rankin Scale scores, as well as angiographic and cross-sectional CT/MRI follow-up at 3–6 months and/or 12–24 months per institutional standard of care. All images were reviewed and adjudicated by an independent core lab.RESULTSOf the 169 lesions initially entered into the study, 4 were later determined to be extracranial or nonaneurysmal by the core lab and were excluded, leaving 165 aneurysms in 162 patients treated in 163 procedures. Ninety-one (56.2%) patients were asymptomatic with aneurysms found incidentally. Of the 165 aneurysms, 150 (90.9%) were unruptured. One hundred thirty-four (81.2%) were saccular, 27 (16.4%) were fusiform/dissecting, and the remaining 4 (2.4%) were blister-like. One hundred thirty-seven (83.0%) arose from the anterior circulation.FRED deployment was impossible in 2/163 (1.2%) cases, and in an additional 4 cases (2.5%) the device was misdeployed. Overall mortality and morbidity rates were 4.3% and 7.3%, respectively, with rates of mortality and morbidity potentially related to FRED of up to 2.4% and 6.2%, respectively. Neuroimaging follow-up at 3–6 months showed complete or nearly complete occlusion of the aneurysm in 94% of cases, increasing to 96% at 12–24 months’ follow-up. Aneurysmal sac shrinkage was observed in 78% of assessable aneurysms.CONCLUSIONSThis preliminary experience using FRED for endovascular treatment of complex unruptured and ruptured aneurysms showed a high safety and efficacy profile that is comparable to those of other FDDs currently in use.

In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months.A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate.The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.).

OBJECTIVE To assess the feasibility, safety and preliminary efficacy of intra-arterial thrombolysis (IAT) compared with standard intravenous thrombolysis (IVT) for acute ischemic stroke. METHODS Eligible patients with ischemic stroke, who were devoid of contraindications, started IVT within 3 h or IAT as soon as possible within 6 h. Patients were randomized within 3 h of onset to receive either intravenous alteplase, in accordance with the current European labeling, or up to 0.9 mg/kg intra-arterial alteplase (maximum 90 mg), over 60 min into the thrombus, if necessary with mechanical clot disruption and/or retrieval. The purpose of the study was to determine the proportion of favorable outcome at 90 days. Safety endpoints included symptomatic intracranial hemorrhage (SICH), death and other serious adverse events. RESULTS 54 patients (25 IAT) were enrolled. Median time from stroke onset to start to treatment was 3 h 15 min for IAT and 2 h 35 min for IVT (p

Background Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT). Methods We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO+ cells) and NET content (citH3+ area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus. Results Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = −6.19, 95%CI = −11.69 to −1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62). Conclusion Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.

Background: Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR). Methods: A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36months, were included in the study. Results: Data of 191 patients were evaluated. After a mean follow-up of 80months (range 37–173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22Gy (P =.019, OR = 2.39, 95% CI 1.15–4.97) and flow rate dichotomized into high vs non-high (P

Purpose: Arteriovenous malformations’ (AVMs) obliteration depends on several factors; among the many factors that must be considered to obtain a high rate of obliteration and a low rate of complications, Flickinger-Pollock Score (FPS) seems to have an important role but still have to be validated in the pediatric population while Paddick-Conformity Index (PCI) still has no demonstration of its utility on the outcome and is considered only as a treatment quality marker. Methods: We retrospectively analyzed 33 consecutive children (2–18years) with an AVM, treated with stereotactic radiosurgery Gamma Knife (SRS-GK) from 2001 to 2014 in our institution. We assess angiographic (DSA) Obliteration Rate (OR) as well FPS and PCI to draw conclusions. Results: DSA-OR was 60.6% with a rate of hemorrhage of 0%. median target volume (TV) was 3.60cc (mean 4.32 ± 3.63; range 0.15–14.2), median PD was 22Gy (mean 21.4± 2.6; range 16.5–25). Median percentage of coverage was 98% (mean 97 ± 3; range 84–100). The median modified FPS was 0.78 (mean 0.89 ± 0.52; range 0.21–2.1) and highly correlate with OR (p = 0.01). The median PCI was 0.65 (mean 0.65 ± 0.14; range 0.34–0.95) A PCI lower than 0.57 highly correlates with final OR (p = 0.02). Conclusion: SRS-GK was safe and gradually effective in children. A prescription dose-like that used in adult population (i.e. > 18 and between 20 and 25Gy) is essential to achieve obliteration. A PD of 23Gy and 22Gy did impact OR, respectively (p= 0.02) and (p = 0.05). FPS and PCI are valuable scores that seem to correlate with the OR also in the pediatric population although further prospective studies are needed to confirm these observations.

"Background: The reported AVMs obliteration rate after Gamma Knife radiosurgery (GKS) ranges from 70 to 94 %. The objective of the present study was to assess prognostic factors predictive for cerebral AVMs obliteration in 127 patients who underwent GKS. Methods: The AVMs were classified according to the Spetzler-Martin classification. Twenty-one cases (16.5 %) were classified as grade I, 46 cases (36.2 %) as grade II, 51 cases (40.1 %) as grade III, and nine cases (7.1 %) as grade IV-V. The AVMs were deeply located in 16.5 % of patients. The peripheral prescription dose ranged from 16 to 30 Gy (mean 22.3 Gy). The AVMs volume ranged from 0.1 to 13 cc (mean 2.7 cc). Results: In 72 patients out of the 104 (69.2 %) with a radiological follow-up, MRI showed the AVM obliteration; in 54 cases (60 %) out of the 90 that performed a DSA, a complete AVM obliteration was achieved (average closure time 48.5 months). The volume of the nidus (p = 0.001), the prescription dose (p = 0.004), the 2002 Pollock-Flickinger classification (p = 0.031), and their 2008 revised classification (p = 0.025) were found to be statistically significant in predicting the probability of AVM closure. In the multivariate analysis, only the prescription dose was found to be an independent prognostic factor (p = 0.009) for AVM obliteration. Conclusions: The volume of the nidus and the prescription dose significantly influence the outcome of radiosurgical treatment. The Pollock-Flickinger classification was found to be a reliable scoring system in predicting the AVM closure and an important tool for selection of patients candidate for GKS. © 2013 Springer-Verlag Wien."

Purpose To report a favorable outcome of branch retinal artery occlusion (BRAO) treated by means of early administration of tirofiban, a glycoprotein IIb-IIIa platelet receptor inhibitor. Methods Case report. Results A 65-year-old woman developed dramatic visual impairment in her left eye secondary to BRAO after left internal carotid artery endovascular reconstruction with flow diverter stent implant; visual acuity was hand motion. A dose of intravenous tirofiban was injected 10 minutes after symptoms onset. Fourteen hours after drug infusion, retinal fluorescein angiography revealed a well-perfused macula with a partial reperfusion of the inferior temporal branch of the central retinal artery; visual acuity was 20/20 in both eyes. Conclusions This case supports the effectiveness of tirofiban in secondary BRAO in neurosurgery and may open its usage to further research.

BACKGROUND AND PURPOSE: Our aim was to compare contrast-enhanced MR angiography (CE-MRA) and 3D time-of-flight (TOF) MRA at 3T for follow-up of coiled cerebral aneurysms. MATERIALS AND METHODS: Fifty-two patients treated with Guglielmi detachable coils for 54 cerebral aneurysms were evaluated at 3T MRA. 3D TOF MRA (TR/TE = 23/3.5; SENSE factor = 2.5) and CE-MRA by using a 3D ultrafast gradient-echo sequence (TR/TE = 5.9/1.8; SENSE factor = 3) enhanced with 0.1-mmol/kg gadobenate dimeglumine were performed in the same session. Source images, 3D maximum intensity projection, 3D shaded surface display, and/or 3D volume-rendered reconstructions were evaluated in terms of aneurysm occlusion/patency and artifact presence. RESULTS: In terms of clinical classification, the 2 MRA sequences were equivalent for 53 of the 54 treated aneurysms: 21 were considered fully occluded, whereas 16 were considered to have a residual neck and 16 were considered residually patent at follow-up MRA. The remaining aneurysm appeared fully occluded at TOF MRA but had a residual patent neck at CE-MRA. Visualization of residual aneurysm patency was significantly ( P = .001) better with CE-MRA compared with TOF MRA for 10 (31.3%) of the 32 treated aneurysms considered residually patent with both sequences. Coil artifacts were present in 5 cases at TOF MRA but in none at CE-MRA. No relationship was apparent between the visualization of patency and either the size of the aneurysm or the interval between embolization and follow-up. CONCLUSION: At follow-up MRA at 3T, unenhanced TOF and CE-MRA sequences are similarly effective at classifying coiled aneurysms as occluded or residually patent. However, CE-MRA is superior to TOF MRA for visualization of residual patency and is associated with fewer artifacts.

Many efforts and much research have been dedicated to the field of non-invasive angiographic techniques in the past few years. Thanks first to magnetic resonance angiography (MRA) and subsequently to computed tomographic angiography (CTA), very interesting results have been obtained in the diagnosis of cerebrovascular diseases. Neck vessels are most successfully evaluated by both MRA and CTA, and the need for digital subtraction angiography (DSA) examinations in patients at risk for vascular occlusions has significantly decreased. The role and the diagnostic accuracy of these non-invasive modalities in intracranial vascular pathology is still under investigation, and several studies have been and are being performed. Both techniques have a better spatial resolution and sensitivity in detecting cerebrovascular malformations than DSA. In the diagnosis of cerebral aneurysms, both MRA and CTA - due to their high sensitivity - have become screening techniques in the population at risk for subarachnoid hemorrhage, these techniques may become basic diagnostic modalities in treatment planning. The results are less satisfying in the evaluation of brain arteriovenous malformations and in the different steps of pre- and post-therapeutic evaluation.

To compare three-dimensional (3D) time-of-flight (TOF) MR angiography, contrast-enhanced MR angiography, digital subtraction angiography (DSA), and rotational angiography for depiction of stenosis.The study had Ethics Committee approval, and each patient gave written informed consent. Forty-nine patients (18 women, mean age, 67.2 years +/- 9.1 [+/- standard deviation], and 31 men, mean age, 63.1 years +/- 8.0) with symptomatic stenosis of internal carotid artery (ICA) diagnosed at duplex ultrasonography underwent transverse 3D TOF MR angiography with sliding interleaved kY acquisition and coronal contrast-enhanced MR angiography, followed by DSA and rotational angiography within 48 hours. MR angiography was performed at 1.5-T with a cervical coil. Contrast-enhanced MR angiograms were obtained after a bolus injection of 20 mL of gadobenate dimeglumine. Maximum ICA stenosis on maximum intensity projection and source images was quantified according to NASCET criteria. Correlations for 3D TOF MR angiography, contrast-enhanced MR angiography, DSA, and rotational angiography were determined by means of cross tabulation, and accuracy for detection and grading of stenoses were calculated. Data were evaluated with analysis of variance, Wilcoxon signed rank test, and McNemar test, all at significance of P.05.Ninety-eight ICAs were evaluated at contrast-enhanced MR angiography, DSA, and rotational angiography, and 97 were evaluated at 3D TOF MR angiography. Correlations for contrast-enhanced MR angiography, 3D TOF MR angiography, and DSA relative to rotational angiography were r2 = 0.9332, r2 = 0.9048, and r2 = 0.9255, respectively. Lower correlation (r2 = 0.8593) was noted for contrast-enhanced MR angiography and DSA. Respective sensitivity and specificity for detection of hemodynamically relevant stenosis relative to rotational angiography were 100% and 90% for contrast-enhanced MR angiography, 95.5% and 87.2% for 3D TOF MR angiography, and 88.6% and 100% for DSA. Four of 31 severe stenoses were underestimated at DSA, and three were underestimated at contrast-enhanced MR angiography. Three severe stenoses were underestimated at 3D TOF MR angiography, and one was misclassified as occluded. Of 13 moderate (50%-69%) stenoses, one was overestimated at contrast-enhanced MR angiography, two were underestimated and three overestimated at 3D TOF MR angiography, and two were underestimated at DSA.DSA results in an underestimation of ICA stenosis compared with rotational angiography. Contrast-enhanced MR angiography correlates best with rotational angiography.