The woven endoBridge (WEB) for endovascular therapy of intracranial aneurysms : update of a systematic review with meta-analysis.

Endovascular treatment of wide-neck intracranial aneurysms (IAs) is challenging, especially in bifurcation location. The intra-saccular flow-disruptor Woven EndoBridge (WEB) offers a new concept of endovascular therapy for wide-neck IAs. We performed an update of a systematic review aimed to report the feasibility, effectiveness and safety of WEB device therapy. A systematic review was conducted using several electronic databases (including PUBMED and EMBASE), searching for studies published between October 2015 and December 2017 (those published between January 2010 and September 2015 were included in our initial systematic review). Outcomes were: success of implantation, peri-procedural complications, mortality, and adequate occlusion (complete occlusion or neck remnant). In total (initial review + update), 12 uncontrolled case-series studies were included, reporting outcomes for 940 patients (68.6% female; mean age, 57 years) harboring 962 IAs. Most IAs were wide-neck bifurcation aneurysms (75%-100%), mainly at middle cerebral artery (37%) and anterior communicating artery (24.6%). Feasibility was 97% (95% confidence interval [CI], 95%-99%), and 9% (95%CI, 5%-14%) of cases required additional treatment. There were 14% (95%CI, 9%-19%) peri-procedural complications. After a median clinical follow-up of 7 months, mortality was 5% (95%CI, 1%-10%) and was higher in series with larger proportions of ruptured IAs. At last angiographic follow-up (median, 7 months; range, 3-27.9 months), adequate occlusion rate was 81% (95%CI, 73%-88%). Although WEB showed high rates of adequate aneurysm occlusion at mid-term, procedure-related complications and mortality rates were not negligible. Future studies should compare the WEB device with other treatment options. [Abstract copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Use of the Enterprise™ Intracranial Stent for Revascularization of Large Vessel Occlusions in Acute Stroke

Background and Purpose:: Major cerebral thromboembolism often resists recanalization with currently available techniques. The authors present their initial experience with a self-expanding stent for use in intracranial vascular reconstruction, permitting immediate recanalization of acute thromboembolic occlusions of the anterior circulation. Patients and Methods:: Patients treated with the Cordis Enterprise™ self-expanding intracranial stent system for acute thromboembolic occlusion of the major anterior cerebral arteries were included. Treatment comprised systemic and intraarterial thrombolysis, mechanical thrombectomy, and stent placement. Stent deployment, recanalization rate by means of Thrombolysis In Cerebral Infarction (TICI) scores and the clinical outcome were all assessed. Results:: Six patients presenting with acute carotid T (n = 2) or proximal middle cerebral artery occlusion (n = 4) were treated. The mean National Institutes of Health Stroke Scale (NIHSS) score at presentation was 14; the mean age was 57 years. Successful stent deployment and immediate recanalization were achieved in all six with a TICI score of ≥ 2. Neither distal emboli nor any procedure-related complications were encountered. One patient developed symptomatic intracerebral hemorrhage and two patients needed decompressive craniectomy after treatment. The mean NIHSS score at 10 days was 10, but only one patient showed a complete recovery at 3 months. Conclusion:: Intracranial placement of the Enterprise™ self-expanding stent has proven to be feasible and efficient in achieving immediate recanalization of occluded main cerebral arteries. The use of antiplatelet therapy after treatment may, however, increase the risk of reperfusion intracerebral hemorrhag

Treatment of intracranial dural fistulas with Onyx : a prospective cohort, systematic review, and meta-analysis

BACKGROUND Onyx is important embolic material in the endovascular treatment of intracranial dural arteriovenous fistula (DAVF). However, its impact on DAVF occlusion rates, morbidity, mortality, and complication rates is not fully examined. OBJECTIVE To improve understanding of safety and effectiveness profiles associated with transarterial endovascular treatment using Onyx for intracranial DAVF METHODS We analyzed data from our prospective clinical registry and conducted a systematic review of all previous transarterial embolization studies using Onyx published between January 2005 and December 2015 in MEDLINE and EMBASE. RESULTS In the prospective study, 41 transarterial procedures were performed in 33 consecutive patients harboring 36 DAVFs. Complete initial exclusion was obtained in 32 of 36 (88.9%) fistulas; 31 fistulas were followed up showing 4 (12.9%) recurrences. Procedure-related morbidity and mortality were 3% and 0%, respectively. The literature review identified 19 studies involving a total of 425 patients with 463 DAVFs. Meta-analysis, including our registry data, showed an initial complete occlusion rate of 82% (95% confidence interval [CI]: 74%, 88%; I2, 70.6%), and recurrence rate at midterm of 2% (95% CI: 0%, 5%; I2, 21.5%). Pooled postoperative neurological deficit, procedure-related morbidity, and mortality rates were 4% (95% CI: 2%, 6%; I2, 0%), 3% (95% CI: 1%, 5%; I2, 0%), and 0%, respectively. CONCLUSION This meta-analysis suggests that transarterial embolization with Onyx is a safe treatment modality for DAVFs. Although Onyx showed a low recurrence rate at midterm, the long-term risk is poorly addressed in our study and should warrant a longer follow-up

Impact of Emergent Cervical Carotid Stenting in Tandem Occlusion Strokes Treated by Thrombectomy: A Review of the TITAN Collaboration

Introduction: Endovascular therapy has been shown to be an effective and safe treatment for tandem occlusion. The endovascular therapeutic strategies for tandem occlusions strokes have not been adequately evaluated and the best approach is still controversial. The TITAN (Thrombectomy in TANdem occlusions) registry was a result of a collaborative effort to identify the best therapeutic approach for acute ischemic stroke due to tandem lesion. In this review, we aim to summarize the main findings of the TITAN study and discuss the challenges of treatment for tandem occlusion in the era of endovascular thrombectomy.Methods: A review of the data from the multicenter international observational and non-randomized TITAN registry was performed. The TITAN registry included acute ischemic stroke patients with tandem lesions (proximal intracranial occlusion and cervical carotid artery occlusion or stenosis>90%) who were treated with thrombectomy with or without carotid artery stenting.Results: Prior intravenous thrombolysis and emergent cervical carotid stenting were associated with higher reperfusion (mTICI 2b-3 and mTICI 3) rates at the end of the intervention. Poor outcome did not occur more frequently after stenting than after conservative treatment of the cervical carotid lesion. Emergent carotid stenting with antithrombotic agents and intracranial thrombectomy yielded higher reperfusion rate and good outcome (90 day mRS 0–2) compared to other strategies (carotid artery stenting and thrombectomy without antithrombotic, angioplasty and thrombectomy, or thrombectomy alone). Pretreatment intravenous thrombolysis was not associated with increased risk of hemorrhagic complications. Likewise, periprocedural unfractionated heparin did not modify the efficacy and safety results. Etiology of carotid artery lesion (atherosclerosis vs. dissection) did not emerge as predictor of outcome or recanalization.Conclusion: Emergent stenting of the cervical carotid lesion with antithrombotic agents in conjunction to thrombectomy appears to be the best treatment strategy for acute ischemic strokes with tandem lesions. These findings will be further investigated in the ongoing randomized controlled TITAN trial

The efficacy of multimodal treatment for symptomatic vertebral hemangiomas: A report of 27 cases and a review of the literature

INTRODUCTION: Vertebral hemangiomas (VH) represent the most common primary bone tumor of the spine and are rarely symptomatic. Currently, there is no consensus for treatment and many therapeutic options are available, alone or in combination including cementoplasty, sclerotherapy, surgery, embolization and/or radiotherapy. OBJECTIVE: To evaluate the clinical and radiological outcome of a multimodal management for symptomatic VH. METHODS: A consecutive prospective and retrospective multicenter study was conducted to review cases of symptomatic VHs between 2005 and 2015. Clinical and radiological aspects, treatment modalities and complications were evaluated preoperatively; postoperatively and at last follow-up. We also reviewed the literature of studies concerning case series of VH, published after 1990 and involving more than 10 patients. RESULTS: Twenty-seven VHs were included in our series (mean age at diagnosis: 47.9 years), out of which 26 were symptomatic. Ten presented with neurologic deficit (37%). An epidural extension was noted in 13 patients (48%). Eleven patients (41%) underwent multimodal treatments. In the multimodal group, eradication was observed in 6 patients (54%), stable residue in 5 cases (46%) with no recurrence versus 3 eradication (23%), 9 stable residue (69%) and no recurrence in the monomodal group, (P>0.05). The literature comprised 14 studies including 458 patients. Only 4 studies were focused on multimodal treatments. CONCLUSION: Based on this study, the multimodal management of symptomatic VHs appeared safe and effective. Finally, we propose an algorithm for symptomatic VHS management based on the severity of epidural extension and fracture risk.Les auteurs n'ont aucun support financier à déclare

Perfusion Imaging to select patients with large ischemic core for mechanical thrombectomy

International audienceBackground and purpose: Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods: This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0-3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results: A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusion: s In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER clinicaltrials.gov NCT03192332

Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease

: Microtubules play fundamental roles in the maintenance of neuronal processes and in synaptic function and plasticity. While dynamic microtubules are mainly composed of tyrosinated tubulin, long-lived microtubules contain detyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination cycle is a key player in the maintenance of microtubule dynamics and neuronal homeostasis, conditions which go awry in neurodegenerative diseases. In the tyrosination/detyrosination cycle, the C-terminal tyrosine of α-tubulin is removed by tubulin carboxypeptidases and re-added by tubulin tyrosine ligase. Here we show that tubulin tyrosine ligase hemizygous mice exhibit decreased tyrosinated microtubules, reduced dendritic spine density, and both synaptic plasticity and memory deficits. We further report decreased tubulin tyrosine ligase expression in sporadic and familial Alzheimer's disease, and reduced microtubule dynamics in human neurons harboring the familial APP-V717I mutation. Finally, we show that synapses visited by dynamic microtubules are more resistant to oligomeric amyloid β peptide toxicity and that expression of tubulin tyrosine ligase, by restoring microtubule entry into spines, suppresses the loss of synapses induced by amyloid β peptide. Together, our results demonstrate that a balanced tyrosination/detyrosination tubulin cycle is necessary for the maintenance of synaptic plasticity, is protective against amyloid β peptide-induced synaptic damage, and that this balance is lost in Alzheimer's disease, providing evidence that defective tubulin retyrosination may contribute to circuit dysfunction during neurodegeneration in Alzheimer's disease

Impact of the Thrombectomy Trials on the Management and Outcome of Large Vessel Stroke: Data From the Lyon Stroke Center

Introduction: Randomized trials (RT) have recently validated the superiority of thrombectomy over standard medical care, including intravenous thrombolysis (IVT). However, data on their impact on routine clinical care remains scarce.Methods: Using a prospective observational registry, we assessed: (1) the clinical and radiological characteristics of all consecutive patients treated with thrombectomy; (2) the outcome of all patients with M1 occlusion (treated with thrombectomy or IVT alone). Two periods were compared: before (2013–2014) and after (2015–2016) the publication of RT.Results: Endovascular procedures significantly increased between the two periods (N = 82 vs. 314, p < 0.0001). In 2015–2016, patients were older (median [IQR]: 69 [57-80]; vs. 66 [53-74]; p = 0.008), had shorter door-to-clot times (69 [47-95]; vs. 110 [83-155]; p < 0.0001) resulting in a trend toward shorter delay from symptom onset to reperfusion (232 [185-300]; vs. 250 [200-339]; p = 0.1), with higher rates of reperfusion (71 vs. 48%; p = 0.0001). Conversely, no significant differences in baseline NIHSS scores, ASPECTS, delay to IVT or intracranial hemorrhage were found. In 2015–2016, patients with M1 occlusion were treated with thrombectomy more often than in 2013–2014 (87 vs. 32%, respectively; p < 0.0001), with a significant improvement in clinical outcome (shift analysis, lower modified Rankin scale scores: OR = 1.68; 95% CI: 1.10–2.57; p = 0.017).Conclusion: Following the publication of RT, thrombectomy was rapidly implemented with significant improvements in intrahospital delay and reperfusion rates. Treatment with thrombectomy increased with better clinical outcomes in patients with M1 occlusion

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