Minimally invasive craniotomy for putaminal hemorrhage using a tubular retractor: A technical note.

Background: Minimally invasive endoscopic and stereotactic surgery have been established as surgical treatments for putaminal hemorrhage. However, facilities that do not have equipment for endoscopic or stereotactic surgery will likely have to perform conventional craniotomy. Using a tubular retractor, we were able to perform minimally invasive surgery, such as endoscopic surgery. Methods: A craniotomy was performed for left putaminal hemorrhage after cerebral infarction treatment. A 3-4 cm craniotomy centered at Kocher's point was performed under general anesthesia. A 2 cm incision was made in the cortex, and a tubular retractor was inserted under a microscope. The hematoma was reached at a position 4-5 cm from the cortex. Results: Thanks to the tubular retractor, it was relatively easy to observe the hematoma, and it was possible to remove it and confirm hemostasis without difficulty. Brain injury caused by the retractor insertion cavity was small, and no hemostasis was required. The surgery was completed by dura mater closure, bone flap fixation, and wound closure as per the standard. Most of the putaminal hemorrhage could be removed, and there was no rebleeding after the operation. The patient is still undergoing rehabilitation because of aphasia and muscle weakness. Manual Muscle Testing was at three points in the upper limb, and four points in the lower limb remained. Conclusion: For putaminal hemorrhage, microscopic craniotomy was performed using a tubular retractor and an approach such as endoscopic surgery. Craniotomy, hematoma removal, and hemostasis operations are also considered to be minimally invasive surgeries.

A Review of Current Flow Diverters.

Flow diverter (FD) devices are new-generation stents placed in the parent artery at the aneurysmal neck to obstruct intra-aneurysmal blood flow, thus favoring intra-aneurysmal thrombosis. In Japan, about eight years have passed since health insurance approval was granted for FD devices, and FD placement to treat aneurysms has become widespread. Treatment indications have also been expanded with the introduction of novel devices. At present, three types of FD (Pipeline, FRED, and Surpass Streamline) are available in Japan. This report represents a compilation of available FD technologies and describes the current consensus on this treatment.

Comparison between transradial and transfemoral mechanical thrombectomy for ICA and M1 occlusions: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: The role for the transradial approach for mechanical thrombectomy is controversial. We sought to compare transradial and transfemoral mechanical thrombectomy in a large multicenter database of acute ischemic stroke. METHODS: The prospectively maintained Stroke Thrombectomy and Aneurysm Registry (STAR) was reviewed for patients who underwent mechanical thrombectomy for an internal carotid artery (ICA) or middle cerebral artery M1 occlusion. Multivariate regression analyses were performed to assess outcomes including reperfusion time, symptomatic intracerebral hemorrhage (ICH), distal embolization, and functional outcomes. RESULTS: A total of 2258 cases, 1976 via the transfemoral approach and 282 via the transradial approach, were included. Radial access was associated with shorter reperfusion time (34.1 min vs 43.6 min, P=0.001) with similar rates of Thrombolysis in Cerebral Infarction (TICI) 2B or greater reperfusion (87.9% vs 88.1%, P=0.246). Patients treated via a transradial approach were more likely to achieve at least TICI 2C (59.6% vs 54.7%, P=0.001) and TICI 3 reperfusion (50.0% vs 46.2%, P=0.001), and had shorter lengths of stay (mean 9.2 days vs 10.2, P<0.001). Patients treated transradially had a lower rate of symptomatic ICH (8.0% vs 9.4%, P=0.047) but a higher rate of distal embolization (23.0% vs 7.1%, P<0.001). There were no significant differences in functional outcome at 90 days between the two groups. CONCLUSIONS: Radial and femoral thrombectomy resulted in similar clinical outcomes. In multivariate analysis, the radial approach had improved revascularization rates, fewer cases of symptomatic ICH, and faster reperfusion times, but higher rates of distal emboli. Further studies on the optimal approach are necessary based on patient and disease characteristics.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Repeat thrombectomy after large vessel re-occlusion: a propensity score matched analysis of technical and clinical outcomes.

BACKGROUND: Endovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat thrombectomy (rEVT) in recurrent LVO remains unclear. This study uses a large real-world patient cohort to study technical and clinical outcomes after rEVT. METHODS: This is a retrospective cohort study including patients who underwent thrombectomy between January 2013 and December 2022. Data were included from 21 comprehensive stroke centers globally through the Stroke Thrombectomy and Aneurysm Registry (STAR). Patients undergoing single EVT or rEVT within 30 days of LVO stroke were included in the study. Propensity score matching was used to compare patients undergoing single EVT versus rEVT. RESULTS: Out of a total of 7387 patients who underwent thrombectomy for LVO stroke, 90 (1.2%) patients underwent rEVT for the same vascular territory within 30 days. The median (IQR) time to re-occlusion was 2 (1-7) days. Compared with a matched cohort of patients undergoing a single EVT procedure, patients undergoing rEVT had a comparable rate of good functional outcome and mortality rate, but a higher rate of symptomatic intracranial hemorrhage (sICH). There was a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) score of patients who underwent rEVT at discharge compared with baseline (-4.8±11.4; P=0.006). The rate of successful recanalization was similar in the single thrombectomy and rEVT groups (78% vs 80%, P=0.171) and between index and rEVT performed on the same patient (79% vs 80%; P=0.593). CONCLUSION: Short-interval rEVT is associated with an improvement in the NIHSS score following large vessel re-occlusion. Compared with single thrombectomy, there was a higher rate of sICH with rEVT, but without a significant impact on rates of functional independence or mortality.

Impact of atherosclerotic etiology on technical and clinical outcomes of mechanical thrombectomy with a stent retriever: subanalysis of the Japan Trevo Registry.

BACKGROUND: The safety and effectiveness of stent retriever use for patients with acute large vessel occlusion (LVO) due to intracranial atherosclerotic disease (ICAD) is not well established. We investigated the differences in clinical outcomes in patients with and without ICAD. METHODS: We analyzed the Japan Trevo Registry, a nationwide registry which enrolled patients with acute LVO who underwent endovascular therapy (EVT) using the Trevo retriever alone or in combination with an aspiration catheter. We compared the technical and clinical outcomes of EVT between the ICAD and No-ICAD groups. The primary outcome was effective reperfusion and the secondary outcome was modified Rankin scale (mRS) score 0-2 at 90 days. Safety outcomes were worsening of neurologic symptoms within 24 hours, any intracranial hemorrhage within 24 hours, vessel dissection/vessel perforation related to using the Trevo retriever and mortality at 90 days. RESULTS: A total of 835 patients (45 in the ICAD group and 790 in the No-ICAD group) were analyzed. In the ICAD group, more men (68.9% vs 50.8%, P=0.02) and a lower median National Institutes of Health Stroke Scale score at admission (11 vs 18, P<0.0001) were observed. The primary outcome was significantly more common in the No-ICAD group (92.5%) than in the ICAD group (80.0%) (adjusted odds ratio (aOR) 0.21, 95% CI 0.09 to 0.50). The proportion of patients with mRS score 0-2 at 90 days was significantly lower in the ICAD group (44.4% vs 42.4%, aOR 0.49, 95% CI 0.23 to 1.00, P=0.0496). Other secondary and safety outcomes were not significantly different between the two groups. CONCLUSIONS: Patients with LVO with ICAD had a lower rate of effective reperfusion than those with No-ICAD.

Short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE): a multicenter, open-label, randomized clinical trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT. METHODS: Patients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141). RESULTS: A total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33). CONCLUSIONS: In this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

Perioperative Antiplatelet Management in the Flow-Diverter Treatment for Unruptured Cerebral Aneurysms: A Single-Center, Retrospective Analysis.

BACKGROUND: Although periprocedural antiplatelet therapy for the treatment of unruptured intracranial aneurysms (UIAs) using flow-diverter stents (FDSs) is necessary to avoid thromboembolic complications, a definite antiplatelet therapy has not been established. We aimed to evaluate the safety and efficacy of periprocedural antiplatelet management in UIA treatment with FDS. METHODS: A single-center retrospective analysis of consecutive patients with UIAs treated with FDSs between September 2013 and January 2022 was conducted. Patients received dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) for 14-day before and 3-6 months after FDS placement. Platelet aggregation was evaluated prior to treatment using light transmission aggregometry, which was classified into 3 grades; 1-3: promoted, 4-6: appropriate, and 7-9: non-responder, for adenosine diphosphate (ADP) and collagen. By this classification, the antiplatelet regimen was modified. Outcome included hemorrhagic and ischemic events. RESULTS: 193 patients with 200 UIAs underwent 213 FDSs placement. The median platelet aggregability grade before treatment was 5 for ADP and 4 for collagen. Antiplatelet therapy modification was performed in 62 patients (32.1%). The median postoperative DAPT duration was 94 days. Antiplatelet medicine-related hemorrhagic events occurred in 4 patients (2.1%) and ischemic events occurred in 6 patients (3.1%). These patients had no morbido-mortality. CONCLUSIONS: Periprocedural antiplatelet management based on the value of platelet aggregability was relatively safe and effective for treating UIA with FDS.

First-in-human trial of a self-expandable, temporary dilation system for intracranial atherosclerotic disease in patients presenting with acute ischemic stroke.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) significantly contributes to ischemic stroke, especially among Asian populations. Large vessel occlusion (LVO) due to underlying ICAD accounts for 15-35% of acute ischemic stroke cases requiring endovascular therapy. However, the successful recanalization rate of ICAD-related LVO remains lower. The TG dilator is a self-expandable device, temporarily dilating ICAD-related blocked blood vessels. OBJECTIVE: To demonstrate TG dilator safety and efficacy for ICAD-related acute ischemic stroke. METHODS: This was a single-arm, open-label, non-randomized, prospective, multicenter, and investigator-initiated trial that involved patients undergoing TG dilator application for acute ischemic stroke caused by ICAD-related LVO or severe stenosis. RESULTS: We enrolled 10 patients in this trial between November 2022 and April 2023. The median (IQR) age was 68 (59.3-75.3) years. Before using the dilator, seven patients received stent retriever treatment. All 10 patients were prescribed a loading dose of aspirin with prasugrel. The median application time was 10 (10-12) min. At the end of the procedure, we achieved significant recanalization immediately in all patients. The stenosis/occlusion decreased from 100% (100-100) to 68% (56.3-75.3). No patient experienced recurrent ischemic stroke or reocclusion within 90 days. We achieved a modified Rankin scale score of 0-2 in 8 patients by day 90. We detected no cases of intracranial hemorrhage, equipment failure, distal embolism, vasospasm, dissection, or perforation requiring intervention. CONCLUSIONS: Acute revascularization using the TG dilator on patients with ICAD-related LVO or severe stenosis did not cause any significant adverse event, and consistently improved blood flow at 90 days.

Outcomes of mechanical thrombectomy in stroke patients with extreme large infarction core.

BACKGROUND: Recent clinical trials have demonstrated that patients with large vessel occlusion (LVO) and large infarction core may still benefit from mechanical thrombectomy (MT). In this study, we evaluate outcomes of MT in LVO patients presenting with extremely large infarction core Alberta Stroke Program Early CT Score (ASPECTS 0-2). METHODS: Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) was interrogated. We identified thrombectomy patients presenting with an occlusion in the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery and extremely large infarction core (ASPECTS 0-2). A favorable outcome was defined by achieving a modified Rankin scale of 0-3 at 90 days post-MT. Successful recanalization was defined by achieving a modified Thrombolysis In Cerebral Ischemia (mTICI) score ≥2B. RESULTS: We identified 58 patients who presented with ASPECTS 0-2 and underwent MT . Median age was 70.0 (59.0-78.0) years, 45.1% were females, and 202 (36.3%) patients received intravenous tissue plasminogen activator. There was no difference regarding the location of the occlusion (p=0.57). Aspiration thrombectomy was performed in 268 (54.6%) patients and stent retriever was used in 70 (14.3%) patients. In patients presenting with ASPECTS 0-2 the mortality rate was 4.5%, 27.9% had mRS 0-3 at day 90, 66.67% ≥70 years of age had mRS of 5-6 at day 90. On multivariable analysis, age, National Institutes of Health Stroke Scale on admission, and successful recanalization (mTICI ≥2B) were independently associated with favorable outcomes. CONCLUSIONS: This multicentered, retrospective cohort study suggests that MT may be beneficial in a select group of patients with ASPECTS 0-2.

Mechanical thrombectomy for the treatment of primary and secondary anterior cerebral artery occlusions: insights from STAR.

BACKGROUND: The safety and efficacy of mechanical thrombectomy (MT) for the treatment of acute anterior cerebral artery (ACA) occlusions have not clearly been delineated. Outcomes may be impacted based on whether the occlusion is isolated to the ACA (primary ACA occlusion) or occurs in conjunction with other cerebral arteries (secondary). METHODS: We performed a retrospective review of the multicenter Stroke Thrombectomy and Aneurysm (STAR) database. All patients with MT-treated primary or secondary ACA occlusions were included. Baseline characteristics, procedural outcomes, complications, and clinical outcomes were collected. Primary and secondary ACA occlusions were compared using the Mann-Whitney U test and Kruskal-Willis test for continuous variables and the χ2 test for categorical variables. RESULTS: The study cohort comprised 238 patients with ACA occlusions (49.2% female, median (SD) age 65.6 (16.7) years). The overall rate of successful recanalization was 75%, 90-day good functional outcome was 23%, and 90-day mortality was 35%. There were 44 patients with a primary ACA occlusion and 194 patients with a secondary ACA occlusion. When adjusted for baseline variables, the rates of successful recanalization (68% vs 76%, P=0.27), 90-day good functional outcome (41% vs 19%, P=0.38), and mortality at 90 days (25% vs 38%, P=0.12) did not differ between primary and secondary ACA occlusion groups. CONCLUSION: Clinical and procedural outcomes are similar between MT-treated primary and secondary ACA occlusions for select patients. Our findings demonstrate the need for established criteria to determine ideal patient and ACA stroke characteristics amenable to MT treatment.

Comparison of balloon guide catheter versus non-balloon guide catheter for mechanical thrombectomy in patients with distal medium vessel occlusion.

BACKGROUND: Several studies have established the safety and efficacy of balloon guide catheters (BGCs) for large vessel occlusions. However, the utility of BGCs remains largely unexplored for distal medium vessel occlusions (DMVOs). In this study, we aim to compare the outcomes of BGC vs. Non-BGC in patients undergoing mechanical thrombectomy (MT) for DMVO. METHOD: This retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) encompassed adult patients with acute anterior cerebral artery, posterior cerebral artery, and middle cerebral artery-M2-3-4 occlusions. Procedure times, safety, recanalization, and neurological outcomes were compared between the two groups, with subgroup analysis based on first-line thrombectomy techniques. RESULTS: A total of 1508 patients were included, with 231 patients (15.3%) in the BGC group and 1277 patients (84.7%) in the non-BGC group. The BGC group had a lower modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2C (43.2% vs 52.7%, P=0.01), longer time from puncture to intracranial access (15 vs 8 min, P<0.01), and from puncture to final recanalization (97 vs 34 min, P<0.01). In the Solumbra subgroup, the first pass effect (FPE) rate was lower in the BGC group (17.4% vs 30.7%, P=0.03). Regarding clinical outcomes, the BGC group had a lower rate of distal embolization (8.8% vs 14.9%, P=0.03). CONCLUSION: Our study found that use of BGC in patients with DMVO was associated with lower mTICI scores, decreased FPE rates, reduced distal embolization, and longer procedure times.

Intravenous alteplase before endovascular therapy for acute large vessel occlusion with large ischemic core: subanalysis of a randomized clinical trial.

BACKGROUND: The efficacy of endovascular therapy (EVT) in patients with large ischemic core has been reported, but it remains unclear whether IV alteplase (IVT) has beneficial effects in addition to EVT in such patients. We evaluated the efficacy and safety of EVT with or without IVT. METHODS: The RESCUE-Japan LIMIT was an open-label, prospective, multicenter, randomized clinical trial to evaluate the efficacy and safety of EVT in stroke patients with large ischemic core, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5. This subanalysis evaluated the differences in the effects of EVT with medical care (EVT group) compared with medical care alone (No-EVT group) between those who received IVT (IVT stratum) and those who did not (No-IVT stratum) before EVT. RESULTS: Among 202 enrolled patients, 147 (73%) did not receive IVT. In the No-IVT stratum, the modified Rankin Scale (mRS) score of 0-3 at 90 days was significantly higher in the EVT group than in the No-EVT group (31.1% vs 12.3%, OR 3.21 (95% CI 1.37 to 7.53)). In the IVT stratum, the mRS score of 0-3 was 30.8% in the EVT group and 13.8% in the No-EVT group (OR 2.78 (95% CI 0.72 to 10.7)) (interaction p=0.77). The incidence of symptomatic intracranial hemorrhage was not different between the two groups in the No-IVT stratum (OR 1.20 (95% CI 0.35 to 4.12)), but it was significantly higher in the EVT group than in the No-EVT group in the IVT stratum (11.5% vs 0%, p=0.03). CONCLUSIONS: There was no difference in efficacy of EVT with or without IVT, while IVT before EVT might increase symptomatic intracranial hemorrhage in patients with large ischemic core. TRIAL REGISTRATION INFORMATION: NCT03702413.

Comprehensive analysis of the impact of procedure time and the 'golden hour' in subpopulations of stroke thrombectomy patients.

OBJECTIVE: To evaluate the effect of procedure time on thrombectomy outcomes in different subpopulations of patients undergoing endovascular thrombectomy (EVT), given the recently expanded indications for EVT. METHODS: This multicenter study included patients undergoing EVT for acute ischemic stroke at 35 centers globally. Procedure time was defined as time from groin puncture to successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) or abortion of procedure. Patients were stratified based on stroke location, use of IV tissue plasminogen activator (tPA), Alberta Stroke Program Early CT score, age group, and onset-to-groin time. Primary outcome was the 90-day modified Rankin Scale (mRS) score, with scores 0-2 designating good outcome. Secondary outcome was postprocedural symptomatic intracranial hemorrhage (sICH). Multivariate analyses were performed using generalized linear models to study the impact of procedure time on outcomes in each subpopulation. RESULTS: Among 8961 patients included in the study, a longer procedure time was associated with higher odds of poor outcome (mRS score 3-6), with 10% increase in odds for each 10 min increment. When procedure time exceeded the 'golden hour', poor outcome was twice as likely. The golden hour effect was consistent in patients with anterior and posterior circulation strokes, proximal or distal occlusions, in patients with large core infarcts, with or without IV tPA treatment, and across age groups. Procedures exceeding 1 hour were associated with a 40% higher sICH rate. Posterior circulation strokes, delayed presentation, and old age were the variables most sensitive to procedure time. CONCLUSIONS: In this work we demonstrate the universality of the golden hour effect, in which procedures lasting more than 1 hour are associated with worse clinical outcomes and higher rates of sICH across different subpopulations of patients undergoing EVT.

Endovascular therapy for acute intracranial large vessel occlusion due to atherothrombosis: Multicenter historical registry.

BACKGROUND: Atherothrombotic stroke-related large vessel occlusion (AT-LVO) is caused by two etiologies, the intracranial artery occlusion due to in situ occlusion (intracranial group) or due to embolism from cervical carotid occlusion or stenosis (tandem group). The prognosis and reocclusion rate of each etiology after endovascular therapy (EVT) is unclear. METHODS: We conducted a historical multicenter registry study at 51 Japanese centers to compare the prognoses of AT-LVO between two etiologies. The primary outcome was the incidence of recurrent ischemic stroke or reocclusion of the treated vessels within 90 days after EVT. Each of the primary outcome means the incidence of recurrent ischemic stroke and reocclusion of the treated vessels within 90 days after EVT. RESULTS: We analyzed 582 patients (338 in the intracranial group and 244 in the tandem group). Patients in the intracranial group were younger (mean 71.9 vs 74.5, p=0.003), more of them were female and fewer of them were current smokers than those in the tandem group. In the tandem group, the patients' National Institutes of Health Stroke Scale score on admission was higher (13 vs 15, p=0.006), onset to puncture time was shorter (299 [145-631] vs 232 [144-459] minutes, p=0.03) and Alberta Stroke Program Early CT Score (ASPECTS) was lower (8 [7-9] vs 8 [6-9], p=0.0002). The primary outcome was higher in the intracranial group (22.5% vs 8.2%, p<0.0001). However, any ICH and death were not significantly different in the two groups. CONCLUSIONS: The incidence of recurrent ischemic stroke or reocclusion after EVT for AT-LVO was higher in the intracranial group.

Clinical Significance of Early Venous Filling Detected via Preoperative Angiography in Glioblastoma.

Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between 1 April 2013 and 31 March 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of the 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angiography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, p = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.

Relation between duration of dual antiplatelet therapy and risk of ischemic stroke after stent-assisted treatment of cerebral aneurysm (DAPTS ACE-registry).

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between duration of DAPT and incidence of ischemic stroke in patients with cerebral aneurysm. METHODS: We registered patients with cerebral aneurysm who underwent SACE in 27 hospitals in Japan. Those treated with DAPT (aspirin and clopidogrel) were eligible for inclusion in a previously reported randomized control trial (RCT). Patients who were ineligible or refused to participate to the RCT were followed-up for 15 months after SACE as the non-RCT cohort. Our study examined both the RCT and non-RCT cohorts. The primary and secondary outcomes were ischemic stroke and hemorrhagic events. RESULTS: Among the 313 patients registered, 296 were included for analysis (of these, 136 were RCT patients and 160 were non-RCT patients). Patients who were treated with DAPT for more than 6 months (n=191) were classified as the long-term DAPT group. Those treated less than 6 months (n=105) were classified as the short-term group. The incidence of ischemic stroke did not significantly differ between the long-term group (2.5 per 100 person-years) and the short-term group (3.2 per 100 person-years); nor did incidence of hemorrhagic events (0.8 and 3.2 per 100 person-years, respectively). The period of DAPT was not significantly associated with incidence rates of ischemic stroke or hemorrhagic events. CONCLUSIONS: Duration of DAPT was not associated with the incidence of ischemic stroke in the first 15 months after SACE.

Outcomes of Intramedullary Spinal Cord Tumor Surgery in Older Versus Younger Adults: A Multicenter Subanalysis Study by the Neurospinal Society of Japan.

OBJECTIVE: Intramedullary spinal cord tumors (IMSCTs) are uncommon and difficult to treat. Studies examining the efficacy of rare IMSCT surgery in the elderly are limited. We conducted a subanalysis using multicenter retrospective-historical data provided by the Japan Neurospinal Society to compare surgical outcomes between older and younger adults with IMSCTs. METHODS: We classified patients with IMSCTs into younger (aged 18-64 years) or older ( ≥ 65 years) groups. The primary outcomes of "improved" or "worsened" from the preoperative period to 6 months after surgery were evaluated using the modified McCormick scale (mMCs). A favorable outcome was defined as an mMCs grade of I/II at 6 months. RESULTS: Among 841 patients registered, there were 658 younger (78.2%) and 183 older patients (21.8%) evaluated using mMCs at 6 months. Median preoperative mMCs grades were significantly worse in older patients than in younger patients. Neither the "improved" nor "worsened" rate differed significantly between the groups (28.1% vs. 25.1%; crude odds ratio [cOR], 0.86; 95% confidence interval [CI], 0.59-1.25; adjusted OR [aOR], 0.84; 95% CI, 0.55-1.28; 16.9% vs. 23.0%; cOR, 1.47; 95% CI, 0.98-2.20; aOR, 1.28; 95% CI, 0.83-1.97). Favorable outcomes were significantly less common among older adults in the univariate analysis but were not significant in the multivariate analysis (66.4% vs. 53.0%; cOR, 0.57; 95% CI, 0.41-0.80; aOR, 0.77; 95% CI, 0.50-1.19). In both younger and older patients, preoperative mMCs accurately predicted favorable outcomes. CONCLUSION: Age alone is not a sufficient reason to prohibit surgery for IMSCTs.

Optimal duration of dual antiplatelet therapy for stent-assisted coiling or flow diverter placement.

BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary to prevent thromboembolic complications after stent-assisted coiling (SAC) or flow-diversion (FD) for cerebral aneurysms, but the optimal antiplatelet regimen remains unclear. OBJECTIVE: To determine the optimal DAPT duration in patients with SAC/FD. METHODS: This multicenter cohort study enrolled patients who received SAC/FD for cerebral aneurysms at seven Japanese institutions between January 2010 and December 2020. The primary outcome was the time from procedure to the occurrence of a composite of target vessel-related thromboembolic events, procedure-unrelated major bleeding events, or death. The cumulative event-free survival rates were analyzed using a Kaplan-Meier curve, and the differences in each outcome between the groups dichotomized by the duration of DAPT were analyzed using the log-rank test. RESULTS: Of 632 patients (median observational period, 646 days), primary outcome occurred in 63 patients (10.0%), most frequently within 30 days after the procedure. The cumulative event-free survival rates at 30 days, 1 year, and 2 years after the procedure were 93.3% (91.4 to 95.3%), 91.5% (89.3 to 93.7%), and 89.5% (87.0 to 92.0%), respectively. The cumulative event-free survival rates after switching to monotherapy were similar for the >91 and <90 days DAPT groups in the population limited to patients who were switched from DAPT to monotherapy without major clinical events. CONCLUSIONS: Thromboembolic events rarely occurred beyond 30 days after SAC/FD. The duration of DAPT may be shortened if patients have a periprocedural period without events. Further prospective studies are warranted to determine the optimal duration of antiplatelet therapy. TRIAL REGISTRATION NUMBER: UMIN000044122 :https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050384.

Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke.

We recently demonstrated that injury/ischemia-induced multipotent stem cells (iSCs) develop within post-stroke human brains. Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients.