Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Results of the pToWin Study: Using the pCONUS Device for the Treatment of Wide-Neck Intracranial Aneurysms.

Coil embolization has become a well-established option for the treatment of intracranial aneurysms. Yet, wide-neck bifurcation aneurysms (WNBAs) remain a challenge. The pCONUS is the first generation of a stent-like implant for the bridging of WNBAs to enable coiling. The pToWin study was a prospective, single-arm, multicenter study conducted to analyze the safety and efficacy of the pCONUS in the treatment of WNBAs. The primary effectiveness endpoint was the rate of adequate occlusion of the aneurysm at 3-6 and 7-12 months. The primary safety endpoint was the occurrence of major ipsilateral stroke or neurological death during the follow-up. A total of 115 patients were included. Aneurysm locations were the middle cerebral artery in 52 (45.2%), the anterior communicating artery in 35 (30.4%), the basilar artery in 23 (20%), the internal carotid artery terminus in three (2.6%), and the pericallosal artery in two (1.7%) patients. Treatment was successfully performed in all but one patient. The morbi-mortality rate was 1.9% and 2.3% at 3-6 and 7-12 months, respectively. Of the aneurysms, 75.0% and 65.6% showed adequate occlusion at 3-6 and 7-12 months, respectively. pCONUS offers a safe and reasonably effective treatment of WNBAs, demonstrated by acceptable adequate aneurysm occlusion and low rates of adverse neurologic events.

Endovascular Treatment of Posterior Circulation Saccular Aneurysms With the p64 Flow Modulation Device: Mid-and Long-Term Results in 54 Aneurysms From a Single Center.

Objective: Flow diverter (FD) stents have become one of the most common tools for treating intracranial aneurysms; however, their role in treating posterior circulation aneurysms is still discussed with controversy. In this study, we evaluated the safety and effectiveness of p64 FD for the treatment of saccular, unruptured aneurysms in the posterior circulation over a long-term follow-up period in a single center. Methods: From our prospectively maintained database, we retrospectively identified patients who underwent treatment of an intracranial saccular aneurysm arising from the posterior circulation with ≥1 p64 FD implanted or attempted between October 2012 and December 2019. Aneurysms could have been treated with prior or concomitant saccular treatment (e.g., coiling, intra-aneurysmal flow diversion). Aneurysms with parent vessel implants other than p64, fusiform aneurysms, and dissections were excluded. Peri- and postprocedural complications, clinical outcome, and clinical and angiographic follow-up results were evaluated. Results: In total, 54 patients (45 female, 9 male; mean age 55.1 years) with 54 intracranial aneurysms met the inclusion criteria. In 51 cases (94.4%), one p64 was implanted; in 2 cases (3.7 %), two p64s were implanted; in one case, deployment of the p64 was not feasible. Procedural complications occurred in 3.7% and postprocedural complications in 9.3 %, respectively. Hemorrhagic complications occurred in 2/54 patients (3.7%), thereof one fatal parenchymal hemorrhage. Ischemic complications were observed in 5/54 patients (9.3%). Early, mid-term, and long-term angiographic follow-up examinations showed complete or near-complete aneurysm occlusion, defined according to the O'Kelly -Marotta (OKM) scale as OKM C + D in 56, 75.6, and 82.9 %, respectively. Asymptomatic side vessel occlusions occurred in 3.8%, each during the first follow-up. Conclusions: The implantation of a p64 FD is a safe and effective device for endovascular treatment of posterior circulation saccular aneurysms with a high success rate and low morbi-mortality.

Flow Diversion for Reconstruction of Intradural Vertebral Artery Dissecting Aneurysms Causing Subarachnoid Hemorrhage-A Retrospective Study From Four Neurovascular Centers.

Objective: Dissecting aneurysms (DAs) of the vertebrobasilar territory manifesting with subarachnoid hemorrhage (SAH) are associated with significant morbi-mortality, especially in the case of re-hemorrhage. Sufficient reconstruction of the affected vessel is paramount, in particular, if a dominant vertebral artery (VA) is impacted. Reconstructive options include stent-assisted coiling and flow diversion (FD). The latter is technically less challenging and does not require catheterization of the fragile aneurysm. Our study aims to report a multicentric experience with FD for reconstruction of DA in acute SAH. Materials and Methods: This retrospective study investigated 31 patients (age: 30-78 years, mean 55.5 years) who had suffered from SAH due to a DA of the dominant VA. The patients were treated between 2010 and 2020 in one of the following German neurovascular centers: University Hospital Leipzig, Katharinenhospital Stuttgart, BG Hospital Bergmannstrost Halle/Saale, and Heinrich-Braun-Klinikum Zwickau. Clinical history, imaging, implanted devices, and outcomes were reviewed for the study. Results: Reconstruction with flow-diverting stents was performed in all cases. The p64 was implanted in 14 patients; one of them required an additional balloon-expandable stent to reconstruct severe stenosis in the target segment. One case demanded additional liquid embolization after procedural rupture, and in one case, p64 was combined with a PED. Further 13 patients were treated exclusively with the PED. The p48MW-HPC was used in two patients, one in combination with two additional Silk Vista Baby (SVB). Moreover, one patient was treated with a single SVB, one with a SILK+. Six patients died [Glasgow Outcome Scale (GOS) 1]. Causes of death were periprocedural re-hemorrhage, thrombotic occlusion of the main pulmonary artery, and delayed parenchymal hemorrhage. The remaining three patients died in the acute-subacute phase related to the severity of the initial hemorrhage and associated comorbidities. One patient became apallic (GOS 2), whereas two patients had severe disability (GOS 3) and four had moderate disability (GOS 4). Eighteen patients showed a complete recovery (GOS 5). Conclusion: Reconstruction of VA-DA in acute SAH with flow-diverting stents is a promising approach. However, the severity of the condition is reflected by high overall morbi-mortality, even despite technically successful endovascular treatment.

First-Pass Reperfusion by Mechanical Thrombectomy in Acute M1 Occlusion: The Size of Retriever Matters.

Introduction: Single-pass complete reperfusion using stent retrievers has been shown to improve functional outcome in patients with large vessel occlusion strokes. The aim of this study was to investigate the optimal size of stent retrievers to achieve one-pass complete reperfusion by mechanical thrombectomy. Methods: The study evaluated the results of aspiration-assisted mechanical thrombectomy of acute isolated occlusion of the middle cerebral artery in the M1 segment with a novel 5 × 40-mm stent retriever compared to the usual 4 × 20-mm device. Reperfusion status was quantified using the Thrombolysis In Cerebral Infarction (TICI) scale. We hypothesized that thrombectomy of M1 occlusions with 5 × 40-mm stent retriever yields higher rates of complete first-pass reperfusion (FP) (TICI ≥2c after one pass) and successful or modified FP (mFP) (TICI ≥2b after one pass) than thrombectomy with 4 × 20. We included isolated M1 occlusions treated with pRESET 5 × 40 (phenox) as first-choice device for thrombectomy and compared with M1 occlusions treated with pRESET 4 × 20. We excluded patients with additional occlusions or tandem stenosis or who received an intracranial stent or angioplasty as a part of the endovascular treatment. Results: One hundred thirteen patients were included in the 4 × 20 group and 57 patients in the 5 × 40 group. The 5 × 40 group achieved higher FP compared to 4 × 20 group [61.4% (35 of 57 patients) vs. 40.7% (46 of 113), respectively; adjusted odds ratio (OR) and 95% confidence interval (95% CI) = 2.20 (1.08-4.48), p = 0.030] and a higher mFP [68.4%, 39 of 57 patients vs. 48.7%, 55 of 113; adjusted OR (95% CI) = 2.11 (1.04-4.28), p = 0.037]. Frequency of successful reperfusion (TICI ≥2b) was similar in both groups (100 vs. 97.3%), but frequency of complete reperfusion (TICI ≥2c) was higher in the 5 × 40 group [82.5 vs. 61.9%, adjusted OR (95% CI) = 2.47 (1.01-6.04), p = 0.047]. Number of passes to achieve reperfusion was lower in the 5 × 40 group than in the 4 × 20 group [1.6 ± 1.1 vs. 2 ± 1.4, p = 0.033; adjusted incidence rate ratio (95% CI) = 0.84 (0.69-1.03), p = 0.096]. Modified Rankin scale at 90 days was similar in 5 × 40 and 4 × 20 groups. Conclusions: The size of stent retriever matters in acute M1 occlusions treated with aspiration-assisted mechanical thrombectomy. A longer stent retriever with a larger nominal diameter achieves a higher complete and successful FP and higher successful reperfusion compared to a shorter stent retriever.

Seasonal patterns and associations in the incidence of acute ischemic stroke requiring mechanical thrombectomy.

BACKGROUND: In order to identify risk periods with an increased demand in technical and human resources, we tried to determine patterns and associations in the incidence of acute ischemic stroke due to embolic large vessel occlusions (eLVO) requiring mechanical thrombectomy (MT). METHODS: We conducted a time series analysis over a 9-year period (2010-2018) based on observational data in order to detect seasonal patterns in the incidence of MT due to eLVO (n = 2628 patients). In a series of sequential negative binominal regression models, we aimed to detect further associations (e.g., temperature, atmospheric pressure, air pollution). RESULTS: There was a 6-month seasonal pattern in the incidence of MT due to eLVO (p = 0.024) peaking in March and September. Colder overall temperature was associated with an increase in MT due to eLVO (average marginal effect [AME], [95% CI]: -0.15 [-0.30-0.0001]; p = 0.05; per °C). A current increase in the average monthly temperature was associated with a higher incidence of MT due to eLVO (0.34 [0.11-0.56]; p = 0.003). Atmospheric pressure was positively correlated with MT due to eLVO (0.38 [0.13-0.64]; p = 0.003; per hectopascal [hPa]). We could detect no causal correlation between air pollutants and MT due to eLVO. CONCLUSIONS: Our data suggest a 6-month seasonal pattern in the incidence of MT due to eLVO peaking in spring and early autumn. This might be attributed to two different factors: (1) a current temperature rise (comparing the average monthly temperature in consecutive months) and (2) colder overall temperature. These results could help to identify risk periods requiring an adaptation in local infrastructure.

Endovascular Treatment of Anterior Circulation Aneurysms With the p64 Flow Modulation Device: Mid- and Long-Term Results in 617 Aneurysms From a Single Center.

BACKGROUND: Flow diverters have become an important tool in the treatment of intracranial aneurysms, especially when dealing with difficult-to-treat or complex aneurysms. The p64 is the only fully resheathable and mechanically detachable flow diverter available for clinical use. OBJECTIVE: To evaluate the safety and effectiveness of p64 for the treatment of intracranial saccular unruptured aneurysms arising from the anterior circulation over a long-term follow-up period. METHODS: We retrospectively reviewed our prospectively maintained database to identify all patients who underwent treatment for an intracranial saccular (unruptured or beyond the acute hemorrhage phase) aneurysm arising from the anterior circulation with ≥1 p64 between December 2011 and December 2019. Fusiform aneurysms and dissections were excluded. Aneurysms with prior or concomitant saccular treatment (eg, coiling and clipping) were included. Aneurysms with parent vessel implants other than p64 were excluded. Anatomic features, intraprocedural complications, clinical outcome, as well as clinical and angiographic follow-ups were all recorded. RESULTS: In total, 530 patients (388 females; median age 55.9 yr) with 617 intracranial aneurysms met the inclusion criteria. The average number of devices used per aneurysm was 1.1 (range 1-3). Mean aneurysm dome size was 4.8 mm (range 1-27 mm). Treatment-related morbimortality was 2.4%. Early, mid-term, and long-term angiographic follow-up showed complete or near-complete aneurysm occlusion in 76.8%, 89.7%, and 94.5%, respectively. CONCLUSION: Treatment of intracranial saccular unruptured aneurysms of the anterior circulation using p64 is a safe and effective treatment option with high rate of occlusion at long-term follow-up and low morbimortality.

Use of pCONUS HPC for the treatment of unruptured wide-necked bifurcation aneurysms: early clinical experience using single antiplatelet therapy.

BACKGROUND: In recent years, a growing number of stents and stent-like devices have become available to facilitate the treatment of challenging aneurysms. However, the need for dual antiplatelet therapy can limit their use, especially in ruptured aneurysms. The hydrophilic polymer coating (pHPC, phenox) is a novel glycan-based multilayer polymer that reduces platelet adhesion. This study aims to report our initial experience using the pCONUS HPC device for the treatment of unruptured wide-necked bifurcation aneurysms (WNBA) using acetylsalicylic acid (ASA) as single antiplatelet therapy (SAPT). METHODS: We retrospectively identified all patients who were treated with the pCONUS HPC for unruptured WNBA in a multi-staged procedure using ASA as SAPT. Records were made of periprocedural complications, clinical outcome and angiographic and clinical follow-up. RESULTS: We identified 15 patients with 15 WNBA. The average age was 69 years old (range, 41-76). Seven aneurysms were located in the middle cerebral artery, five in the anterior communicating artery, two at the basilar tip and one in the posterior communicating artery. Immediate post-treatment angiography showed five aneurysms with modified Raymond-Roy classification (mRRC) grade I and four aneurysms with mRRC grade II. There were no haemorrhagic complications. Four patients developed thrombus formation during the second treatment session, all of them completely resolving after administration of glycoprotein IIb/IIIa antagonists. Angiographic follow-up data were available for 10 patients and showed adequate occlusion (mRRC I or II) in eight aneurysms (80%). In-stent stenosis was observed in one patient whereas two patients showed de novo stenosis in one of the efferent branches. CONCLUSIONS: This early experience on the use of the pCONUS HPC device suggests that it can be useful for treating unruptured WNBA under ASA as SAPT. Further investigation with a randomised treatment registry and larger cohort is needed.

The p48 MW flow modulation device for treatment of unruptured, saccular intracranial aneurysms: a single center experience from 77 consecutive aneurysms.

BACKGROUND: The p48 MW Flow Modulation Device (phenox, Bochum Germany) is a low profile flow diverter stent (FDS), designed for implantation into intracranial arteries with a diameter of less than 3.5 mm. OBJECTIVE: To evaluate the safety and efficacy of the p48 MW FDS in the treatment of unruptured aneurysms located at intracranial arteries with less than 3.5 mm diameter based on a retrospective analysis from a single tertiary neurovascular center. METHODS: A prospectively maintained database was retrospectively reviewed to identify all cases of intracranial saccular aneurysms treated electively with the p48 MW device. Records were made of basic demographics, aneurysmal characteristics, interventional procedures, adverse events, clinical outcomes and occlusion rates on angiographic follow-ups. RESULTS: A total of 77 aneurysms and 74 patients were included. The mean size of the treated aneurysms was 3.5 ± 2.4 mm and the mean aspect ratio was 1.3 ± 0.4. A total of 80 endovascular procedures were performed with a total of 12 (15%) adverse events leading to two (2.5%) permanent morbidities/mortalities. Technical issues were encountered in 3 (3.9%) cases. Adequate occlusion of the treated aneurysm was recorded in 55.6% and 63.9% on the first and latest available DSA follow-ups, respectively. There were no cases of side-branch occlusion. CONCLUSIONS: The p48 MW is an easy-to-use implant with very good safety margins. Side branch occlusion and significant in-stent stenosis are infrequently encountered. The time from implantation to sufficient aneurysm occlusion takes longer than with FDS with lower porosity.

The p48 Flow Modulation Device with Hydrophilic Polymer Coating (HPC) for the Treatment of Acutely Ruptured Aneurysms: Early Clinical Experience Using Single Antiplatelet Therapy.

BACKGROUND: Flow diversion (FD) remains a potential treatment option following aneurysmal subarachnoid hemorrhage (aSAH) when standard options may not be feasible. However, it should not be considered a first-line treatment due to the need for dual antiplatelet therapy (DAPT). The hydrophilic polymer coating on the p48MW flow diverter (HPC, phenox) is a surface modification that inhibits platelet adhesion. This study aims to report on our early single-center experience using the p48MW HPC (phenox) flow diverter with single antiplatelet therapy (SAPT) following an aSAH. MATERIALS AND METHODS: We retrospectively identified all patients who had been treated with the p48MW HPC for aSAH under SAPT. All patients treated within 30 days following an aSAH were included. Any occurrence of thromboembolic and hemorrhagic complications was recorded alongside angiographic and clinical follow-up details. RESULTS: Eight patients were identified. The mean interval between aSAH and FD was 6 days. Of the eight ruptured aneurysms, one was blister-like, one saccular, one mycotic, and the remaining five were dissecting aneurysms. Intraprocedural transient thrombus formation was observed in four patients (50%). Stent thrombosis was observed in one patient (12.5%) on day 3 with spontaneous recanalization after being switched onto DAPT. None of the aneurysms rebled after treatment. Two patients died due to cerebral vasospasm. Complete aneurysm occlusion had been achieved in all but one patient at angiographic follow-up (average 6 months). CONCLUSIONS: This small series highlights the possibility and limitations of using the p48MW HPC with SAPT in ruptured aneurysms. Randomized trials with longer follow-up in larger cohorts are underway.

Use of the pCONus HPC as an adjunct to coil occlusion of acutely ruptured aneurysms: early clinical experience using single antiplatelet therapy.

BACKGROUND: Coil occlusion has become the standard treatment for many ruptured aneurysms. However, specific aneurysm structures pose technical difficulties and may require the use of adjunctive neck-bridging devices, which necessitate the use of dual antiplatelet therapy. The hydrophilic polymer coating (pHPC, phenox) is a surface modification that inhibits platelet adhesion. OBJECTIVE: To present initial experience with the pCONUS HPC device as an adjunct to coil embolization for ruptured aneurysms using single antiplatelet therapy (SAPT). METHODS: All patients who were treated with the pCONUS HPC for ruptured aneurysms using SAPT were retrospectively identified. The occurrence of thromboembolic and hemorrhagic complications was recorded together with the angiographic and clinical follow-up details. RESULTS: Fifteen patients were identified (nine female) with a median age of 54 years (range 27-81). Six aneurysms were located at the anterior communicating artery, five at the middle cerebral artery bifurcation, two at the basilar artery bifurcation, one at the posterior communicating artery, and one involving the intradural internal carotid artery. Ten patients (66.6%) achieved modified Raymond-Roy classification I or II at post-treatment angiography, with 45.5% of patients having adequate occlusion (defined as complete occlusion or neck remnant) at follow-up. All patients received acetylsalicylic acid (ASA) as SAPT before and after the procedure. Intraprocedural thrombus formation was seen in three patients (20%), resolving in two patients after a bolus dose of eptifibatide, and one treated with mechanical aspiration. No clinical or radiological consequences were seen. There were no recurrent aneurysm ruptures. One patient died owing to cerebral vasospasm. CONCLUSION: This initial clinical experience highlights the possibility and limitations of using the pCONUS HPC device in the treatment of complex ruptured aneurysm with ASA as SAPT. Randomized trials with longer follow-up in larger cohorts are underway.

Flow Diversion for Treatment of Acutely Ruptured Intracranial Aneurysms : A Single Center Experience from 45 Consecutive Cases.

BACKGROUND: Reports about the use of flow diverter stents (FDS) in the acute setting of subarachnoid hemorrhage (SAH) are limited. This article presents a single center experiences based on 45 consecutive cases with emphasis on complication rates and clinical and radiologic outcomes. METHODS: A prospectively maintained database of all cases treated with FDS as a stand-alone or adjunct device was retrospectively reviewed. All patients treated within 30 days of SAH were included. Records were made of clinical presentation, details of endovascular treatment, procedural complications, clinical outcome, and degree of occlusion on follow-up. RESULTS: In this study 45 patients (48.9% females; mean age 58.8 ± 12.4 years) were included. Flow diversion was performed after a median of 4 days. The procedural complication rate was 13.3% resulting in 2.2% permanent morbidities and 4.4% mortalities. No major hemorrhagic complications related to antiplatelet therapy were recorded. Immediate complete occlusion was achieved in 13.3%. Among survivors, complete occlusion was achieved in 94.6%. Excellent clinical outcome was recorded in 68.9% and 81.6% of the total population and survivors, respectively. There were no records of rebleeding from the target lesions. CONCLUSION: Flow diversion is an attractive alternative strategy for management of acutely ruptured aneurysms with high rates of delayed complete occlusion and acceptable complication rates.

Recanalization of Emergent Large Intracranial Vessel Occlusion through Intravenous Thrombolysis: Frequency, Clinical Outcome, and Reperfusion Pattern.

BACKGROUND: According to a recent meta-analysis, 1 out of 10 patients with emergent large intracranial vessel occlusion (ELVO) causing stroke have recanalization after intravenous thrombolysis (IVT) alone. However, rate, clinical outcome, and recanalization pattern of this phenomenon are poorly understood. OBJECTIVES AND METHODS: Patients with ELVO recanalized only by IVT were analyzed, and frequency of recanalization, clinical outcome, safety variables, and reperfusion pattern were assessed. These patients were compared to a group of patients with ELVO who underwent endovascular thrombectomy with or without prior IVT. RESULTS: Successful or sufficient recanalization after IVT alone occurred in 81 of 760 patients (10.6%) with ELVO who had been referred for endovascular thrombectomy. These 81 patients (group 1) were compared to a group of patients receiving endovascular thrombectomy with prior IVT (group 2) or without (group 3). A good clinical outcome at 90 days was seen in 61.7% of patients in group 1, 32.2% in group 2, and 34.5% in group 3 (p < 0.001). The 3 groups had no significant differences in intracranial hemorrhage. IVT was not independently associated with symptomatic intracranial hemorrhage, parenchymal hematoma, or subarachnoid hemorrhage. Mortality at 90 days was 9.9% in group 1, 20.7% in group 2, and 29.6% in group 3 (p < 0.001). After adjusting for all relevant variables, outcome and mortality differences were nonsignificant. No difference in the rate of successful reperfusion (modified treatment in cerebral ischemia [mTICI] 2b/3) was found. A reperfusion mTICI 3 was achieved in 18.5% in group 1, 60.7% in group 2, and 57.1% in group 3 (p < 0.001). Patients in group 1 had lower chance of achieving a complete recanalization (mTICI 3) compared to patients in group 2, OR 0.15 (95% CI 0.08-0.29) and in group 3, OR 0.17 (95% CI 0.09-0.32; p < 0.001). CONCLUSIONS: Primary IVT in ELVO caused a recanalization rate of 10.6%, making endovascular treatment either unnecessary or impossible. Early recanalization of ELVO with only IVT is associated with a 61.7% independence rate at 90 days and similar successful reperfusion rates (mTICI2b/3) compared to ELVO treated with endovascular treatment, with or without previous IVT. However, recanalization only through IVT achieves a lower rate of mTICI 3 reperfusion when compared to endovascular treatment.

Predictors of Outcome After Endovascular Thrombectomy in Acute Basilar Artery Occlusion and the 6hr Time Window to Recanalization.

Background and Purpose: Decision algorithms for large vessel occlusions in the anterior circulation remain unconfirmed for acute basilar artery occlusion (aBAO). The aim of this study was to investigate procedural parameters, patient characteristics, functional outcome, and survival in dependency of the time window to recanalization from symptom onset. Furthermore predictors of outcome were identified. Materials and Methods: Retrospectively 231 patients with aBAO treated with endovascular treatment (EVT) between November 2008 and February 2019 were identified in a prospectively maintained single center stroke database. Baseline characteristics such as age, cardiovascular risk factors, NIHSS at admission, pre-interventional PC-ASPECTS, periprocedural parameters such as time to recanalization, duration of treatment, extent of reperfusion, collateral status, and occlusion patterns, as well as post-interventional 24 h NIHSS and post-interventional ICH were evaluated. Target variables were mRS at 90 days and mortality over 90 days. Results: Good outcome (mRS 0-2) was attained in 29.5% (n = 68) of patients, overall mortality was 36.8% (n = 85). In mulitivariate analyses patients with time to reperfusion beyond 6 h had a more than half fold decreased chance of good outcome [OR 0.47 95% CI (0.23-0.95) p < 0.05]. The odds for good outcome were reduced by almost 2/3 if post-interventional imaging revealed intracerebral hemorrhage [OR 0.28 95% CI (0.08-0.98)]. Unfavorable outcome was noted in 100% (n = 14) of patients with symptomatic ICH. Risk for death was reduced by more than 80% if collaterals were present [0.16 95% CI (0.03-0.87)] and if recanalization was successful (TICI 2b-3) [OR 0.19 95% CI (0.05-0.78)]. The odds for survival were 5-fold higher in patients with no post-interventional hemorrhages present [OR 5.35 95% CI (2.2-1.58)]. Conclusion: This study might contribute to explaining the ambiguous findings regarding the validity of the 6 h time window in aBAO, suggesting that collateral status impacts the odds of survival in the time window to recanalization beyond 6 h. In our study recanalization within 6 h from symptom onset was associated with good outcome. Successful recanalization (TICI 2b-3a) was necessary for good outcome and survival, post-interventional ICH was highly associated with unfavorable outcome. This might ease the decision making for EVT.

Anti-thrombogenic coatings for devices in neurointerventional surgery: Case report and review of the literature.

BACKGROUND: Stent-assisted coiling and extra-saccular flow diversion require dual anti-platelet therapy due to the thrombogenic properties of the implants. While both methods are widely accepted, thromboembolic complications and the detrimental effects of dual anti-platelet therapy remain a concern. Anti-thrombogenic surface coatings aim to solve both of these issues. Current developments are discussed within the framework of an actual clinical case. CASE DESCRIPTION: A 33-year-old male patient lost consciousness while doing sport and was administered 500 mg acetylsalicylic acid on site. Computed tomography revealed a massive subarachnoid haemorrhage, and digital subtraction angiography showed an aneurysm of the right middle cerebral artery. Stent-assisted coiling using a neck bridging device with a hydrophilic coating (pCONUS_HPC) was considered as an appropriate approach. Another 500 mg acetylsalicylic acid IV was given. After the single anti-platelet therapy was seen to be effective, a pCONUS_HPC was implanted, and the aneurysm sac subsequently fully occluded using coils. No thrombus formation was encountered. During the following days, 2 × 500 mg acetylsalicylic acid IV daily were required to maintain single anti-platelet therapy, monitored by frequent response testing. Follow-up digital subtraction angiography after 13 days confirmed the occlusion of the aneurysm and the patency of the middle cerebral artery. CONCLUSION: A variety of ways to reduce the thrombogenicity of neurovascular stents is discussed. Hydrophilic surface coatings are a valid concept to improve the haemocompatibility of neurovascular implants while avoiding the use of dual anti-platelet therapy. Phosphorylcholine and phenox hydrophilic polymer coating are currently the most promising candidates. This concept is supported by anecdotal experience. However, formalised registries and randomised trials are currently being established.

Management of a decompensated acute-on-chronic intracranial venous sinus thrombosis.

A 34-year-old female patient presented during the 10th week of her second gravidity with headache, nausea and vomiting 2 weeks before admission. Her medical history was remarkable for a heterozygous factor V Leiden mutation, elevated lipoprotein A, and a cerebral venous thrombosis (CVT) after oral contraceptive intake 15 years before. Magnetic resonance imaging (MRI) suggested acute and massive intracranial sinus thrombosis. Despite full-dose anticoagulation, the patient deteriorated clinically and eventually became comatose. Now, MRI/magnetic resonance angiography revealed vasogenic edema of both thalami, of the left frontal lobe, and of the head of the caudate nucleus, with venous stasis and frontal petechial hemorrhage. She was referred for endovascular treatment. Diagnostic angiography confirmed a complete superficial and deep venous sinus occlusion. Endovascular access to the straight and superior sagittal sinus was possible, but neither rheolysis nor balloon angioplasty resulted in recanalization of the venous sinuses. Monitored heparinization was continued and antiaggregation was initiated. The patient remained comatose for another 5 days and MRI showed progress of the cytotoxic edema. On day 6, infusion of eptifibatide at body-weight-adapted dosage was started. The following day, the patient improved and slowly regained consciousness. MRI confirmed regression of the edema. The eptifibatide infusion was continued for a total of 14 days. Thereafter two doses of 180 mg ticagrelor per os (PO) daily were started. The patient remained on acetylsalicylic acid (ASA), ticagrelor, and enoxaparin on an unchanged dosage regimen. She was discharged home 26 days after the endovascular treatment without serious neurological deficit, with the pregnancy intact. At the 30th week of pregnancy the dosage of ASA was reduced to 300 mg once PO daily. Cesarian delivery was carried out at the 38th week of pregnancy. The newborn was completely healthy. Ultima ratio therapeutic options for severe intracranial venous sinus thrombosis refractory to anticoagulation are discussed, with an emphasis on platelet-function inhibition.

Functional Outcome and Safety of Intracranial Thrombectomy After Emergent Extracranial Stenting in Acute Ischemic Stroke Due to Tandem Occlusions.

Background and Purpose: Various endovascular approaches to treat acute ischemic stroke caused by extra- intracranial tandem occlusions (TO) exist: percutaneous transluminal angioplasty with or without emergent extracranial carotid stenting (ECS) due to high-grade stenosis preceded or followed by intracranial mechanical and/or aspiration thrombectomy (MT). Which treatment strategy to use is still a matter of debate. Methods: From our ongoing prospective stroke registry we retrospectively analyzed 1,071 patients with anterior circulation stroke getting endovascular treatment within 6 h of symptom onset. ECS prior to intracranial MT for TO (n = 222) was compared to MT as standard of care (control group; acute intracranial vessel occlusion without concomitant ipsilateral ICA-occlusion or high-grade stenosis [C; n = 849]). Good functional outcome (mRS ≤ 2 at 3 months), mortality rates, frequencies of symptomatic intracranial hemorrhage (sICH) and successful recanalization (Thrombolysis in Cerebral Infarction Score [TICI] 2b or 3) were assessed. In subgroup analyses we tried to detect possible influences of stroke etiology, dual inhibition of platelet aggregation (IPA; clopidogrel [CLO]: n = 83; ticagrelor [TIC]: n = 137; in combination with Aspirin) and intravenous thrombolysis (IVT). Results: Functional outcome was superior in TO (mRS 0-2: 44.6%) when compared with controls (36.0%; OR [95% CI]: 3.49 [1.59-7.67]; p = 0.002). There was no difference in all-cause mortality at 3 months (TO: 21.6%; C: 27.7%; 0.78 [0.47-1.29]; p = 0.324), in-hospital mortality (0.76 [0.45-1.30]; p = 0.324), sICH (TO: 3.2%; C: 5.0%; 0.70 [0.30-1.59]; p = 0.389), and TICI 2b/3 (TO: 89.1%; C: 88.3%; p = 0.813). In subgroup-analysis, TIC and CLO did not differ in functional outcome (TIC: 45.3%; CLO: 44.6%; 1.04 [0.51-2.09]; p = 0.920) and mortality rates (all-cause mortality: TIC: 23.4%; CLO: 16.9%; 0.75 [0.27-2.13]; p = 0.594). sICH was more frequent in TIC (n = 7 [5.1%]) vs. CLO (n = 0; p = 0.048). Conclusion: In our pre-selected cohort, ECS prior to intracranial MT in TO allowed for a good functional outcome that was superior compared to a control population. Mortality rates did not differ. Despite a dual IPA in TO, there was no increase in sICH. CLO and TIC for dual IPA did not differ in terms out outcome and mortality rates. A significant increase in sICH was observed after initial loading with TIC.