松本 省二

PURPOSE: Prasugrel is not approved for patients treated with flow diverters, which have a high metal coverage ratio. However, robust antiplatelet therapy with prasugrel may prevent thromboembolic complications. We administered prasugrel and aspirin to all patients treated with flow diverters and reported the safety of the antiplatelet therapy regimen. METHODS: This retrospective, single-center study evaluated the angiographic and clinical data of consecutive patients treated with flow diverters for cerebral unruptured aneurysms between June 2020 and May 2022. All patients received dual antiplatelet therapy, including prasugrel and aspirin. The administration of prasugrel ended 3 or 6 months after the procedure, whereas aspirin use continued for at least 12 months. Periprocedural complications (< 30 days post-procedure) and delayed complications (> 30 days post-procedure) were recorded. RESULTS: During the study period, 120 unruptured aneurysms were treated with flow diverters in 110 patients. All patients, except one, survived longer than 12 months after the procedure. The rate of thromboembolic complications was 6.4%, and more than half of the patients had transient symptoms; one (0.9%) had a major ischemic stroke. One patient (0.9%) each had an asymptomatic, small subarachnoid hemorrhage and significant hemorrhagic complications with melena. The rate of permanent neurological deficits was 1.8%, and the mortality rate was 0.9%. CONCLUSIONS: Dual antiplatelet therapy comprising routine use of prasugrel and aspirin for flow diverter-implanted patients possibly contributed to a low rate of thromboembolic complications and low risk of hemorrhagic complications.

OBJECTIVE: This retrospective study aimed to investigate factors associated with inhibition of early aneurysm obliteration after flow diverter (FD) treatment. We also created the early obliteration inhibition (EOI) score for pre-operative evaluation. METHODS: We examined 110 cerebral aneurysms in 104 patients who underwent FD treatment. The following parameters were investigated: age, sex, symptoms, aneurysm location and type, maximum aneurysm diameter, parent vessel diameter, neck diameter, and dome-neck ratio. We also noted aneurysm location relative to the curvature of the parent artery and any branches arising from the aneurysm dome. Procedural factors such as FD diameter and length, number of FDs placed, type of FD, and use of adjunctive coiling were also investigated. Aneurysm obliteration was evaluated using digital subtraction angiography 3 months after the procedure. Adequate obliteration was defined as grade C or D on the O'Kelly-Marotta scale. RESULTS: The following factors inhibited early obliteration: 1) extradural location, 2) saccular aneurysm, 3) aneurysm neck located at the outer convexity of the parent artery, and 4) arterial branch arising from the aneurysm dome. Odds ratios were used to create an EOI score. Receiver operating characteristic curve analysis showed that the optimal cut-off EOI score for adequate obliteration was 1.5 (area under the curve, 0.81; 95% confidence interval, 0.73-0.9; sensitivity, 0.9; specificity, 0.57). CONCLUSION: The EOI score, which is based on factors that inhibit early obliteration, may predict early treatment outcomes of FD placement.

PURPOSE: Optimal size selection is important for successful Woven EndoBridge (WEB) treatment. Conventional recommendations for WEB sizing based on aneurysm width and height sometimes require device exchange. We aimed to design a novel volume-based parameter, the ideal WEB-aneurysm volume (iWAVe) ratio, for optimal WEB sizing. METHODS: Consecutive patients who underwent WEB treatment for wide-neck bifurcation aneurysms between January 2021 and May 2022 were retrospectively reviewed. Aneurysm volume was automatically calculated using software. We measured the aneurysm volume based on the expected position of the device within the aneurysm. The WAVe ratio was defined as the ratio of the aneurysm volume to WEB volume. We dichotomized aneurysms treated with a successful sizing or unsuccessful sizing for WEB (successful group and unsuccessful group, respectively). RESULTS: Thirty-five patients were eligible for study enrollment. Ten patients (28.6%) needed to exchange the WEB on the first attempt and required another WEB on the second attempt resulting in deployment success. Hence, 35 aneurysms were in the successful group and 10 were in the unsuccessful group. The median WAVe ratio was 1.0 (range 0.76-1.31) in the successful group and 1.27 (0.58-1.89) in the unsuccessful group. Using logistic regression, iWAVe ratio was from 0.90-1.16 to secure a >80% probability of success by the 95% lower confidence limit. The sensitivity and specificity of the iWAVe ratio for optimal size selection on the first attempt were 0.60 and 1.00, respectively. CONCLUSION: Decision-making based on aneurysm width and the iWAVe ratio could promote optimal WEB sizing.

BACKGROUND <p lang="en">Reperfusion therapy for acute ischemic stroke efficacy is highly time dependent; therefore, stroke centers are required to further reduce the delays from hospital arrival to treatment efficiently. We developed a visual task management application, Task Calculation Stroke (Task Calc. Stroke: TCS), to facilitate hospital acute ischemic stroke treatment by supporting parallel staff task completion. We evaluated TCS for the reduction of reperfusion therapy delays and improvement of clinical outcomes. </p> METHODS <p lang="en">In this multicenter cohort study, patients were directly admitted to 4 comprehensive stroke centers in Japan and given intravenous tissue plasminogen activator and/or mechanical thrombectomy from June 2018 to December 2020. The research team visited each facility and instructed the staff on TCS use for acute ischemic stroke (training stage), after which the staff used TCS independently (TCS stage). We then compared door‐to‐needle time for intravenous tissue plasminogen activator, door‐to‐puncture time for mechanical thrombectomy, and clinical outcomes at discharge according to the modified Rankin Scale among patients treated before training (original stage), during the training stage, or the TCS stage. </p> RESULTS <p lang="en"> During the study period, 316 patients with acute ischemic stroke received reperfusion therapy; of these, 246 received intravenous tissue plasminogen activator and 162 mechanical thrombectomy (including 92 receiving both the treatments). The mean door‐to‐needle time was significantly reduced from 58.0 minutes in the original stage to 54.6 minutes in the training stage ( P =0.049) and 47.8 minutes in the TCS stage ( P &lt;0.001). The door‐to‐puncture time did not change during the training stage; however, in the TCS stage, it significantly reduced from 93.8 minutes in the original stage to 88.5 minutes ( P =0.004). The distribution of modified Rankin Scale scores at discharge significantly shifted favorably at the TCS stage ( P =0.003). </p> CONCLUSION <p lang="en">In this study, TCS application could reduce workflow time for reperfusion therapy and might have led to improved clinical outcomes. </p>

The posterior condylar vein is an emissary vein that connects the extracranial and intracranial venous systems through the posterior condylar canal (PCC). Dural arteriovenous fistulas (DAVF) of the PCC are rare, and only seven cases have been reported. Transvenous embolization (TVE) is the first-line treatment for PCC DAVF and is predominantly performed through the internal jugular vein. Herein, we report a case of PCC DAVF treated with TVE through the deep cervical vein. This is the first case report of a PCC DAVF treated with TVE through the deep cervical vein.

OBJECTIVES: This study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage. MATERIALS AND METHODS: We retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physician's discretion (previous dose group). After approval, we adopted the manufacturer's recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio <1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0-3 at discharge, and in-hospital mortality. RESULTS: Thirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio <1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p<0.001 and 100% vs. 68%, p = 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups. CONCLUSION: After prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage; however, there was no apparent difference in clinical outcomes.

OBJECTIVES: The benefit of mechanical thrombectomy for acute ischemic stroke is highly time dependent. However, time to treatment is longer for in-hospital stroke patients than community-onset stroke patients. This study aimed to clarify the cause of this difference. METHODS: A retrospective single-center study was performed to analyze patients with large vessel occlusion who underwent mechanical thrombectomy between January 2017 and December 2019. Patients were divided into in-hospital stroke and community-onset stroke groups. Clinical characteristics and treatment time intervals were compared between groups. RESULTS: One hundred four patients were analyzed: 17 with in-hospital stroke and 87 with community-onset stroke. Patient characteristics did not significantly differ between groups. Median door (stroke recognition)-to-computed tomography time (36 min vs. 14 min, P<0.01) and door-to-puncture time (135 min vs. 117 min, P=0.02) were significantly longer in the in-hospital stroke group than the community-onset stroke group. However, median computed tomography-to-puncture time (104 min vs. 104 min, P=0.47) and puncture-to-reperfusion time (53 min vs. 38 min, P=0.17) did not significantly differ. CONCLUSIONS: Longer door-to-puncture time in in-hospital stroke patients was mostly caused by longer door-to-computed tomography time, which is the initial part of the workflow. An in-hospital stroke protocol that places importance on early stroke specialist consultation and prompt transportation to the computed tomography scanner might hasten treatment and improve outcomes in patients with in-hospital stroke.

We report a case of vertebral artery dissecting aneurysm (VADA) that developed with subarachnoid hemorrhage and was found to be occluded based on subsequent digital subtraction angiography. Few reports have been published on ruptured VADA in which ipsilateral vertebral arteries are occluded. The proper management of this type of aneurysm is controversial. A 44-year-old woman developed a sudden onset headache. Computed tomography and three-dimensional computed tomography were immediately performed and showed subarachnoid hemorrhage and VADA distal to the right posterior inferior cerebellar artery bifurcation. We decided to treat the VADA immediately and performed digital subtraction angiography but found the VADA had spontaneously occluded. We performed coil embolization, including the aneurysm and the parent artery, with reference to the findings of three-dimensional computed tomography. On Day 16, recurrence was considered due to the finding of dilation of the distal end where the coil was embolized. An additional embolization was performed via the posterior communicating artery. No cases of endovascular treatment have been reported in VADA cases in which the rupture site is spontaneously occluded. In such cases, the treatment may be incomplete, so strict follow-up is required.

PURPOSE: The Flow Re-direction Endoluminal Device (FRED) has recently become available for flow diversion in Japan. We have encountered cases that failed to deploy the FRED. In this study, we report our initial experience with the FRED for cerebral aneurysms and clarify the causes of failed FRED deployment. METHODS: A retrospective data analysis was performed to identify patients treated with the FRED between June 2020 and March 2021. Follow-up digital subtraction angiography was performed at 3 and 6 months and assessed using the O'Kelly-Marotta (OKM) grading scale. RESULTS: Thirty-nine aneurysms in 36 patients (average age: 54.4 years) were treated with the FRED. The average sizes of the dome and neck were 9.9 mm and 5.2 mm, respectively. In nine patients, additional coiling was performed. In one patient (2.6%), proximal vessel injury caused direct carotid-cavernous fistula during deployment. Ischaemic complications were encountered in one patient (2.6%) with transient symptoms. Angiographic follow-up at 6 months revealed OKM grade C or D in 86.6% of patients. FRED deployment was successful in 35 (92.1%) procedures. In the failure group, the differences between the FRED and the minimum vessel diameter (P = 0.04) and the rate of the parent vessel having an S-shaped curve (P = 0.04) were greater than those in the success group. CONCLUSIONS: Flow diversion using the FRED is effective and safe for treating cerebral aneurysms. The use of the FRED for patients with an S-shaped curve in the parent vessel and oversizing of more than 2 mm should be considered carefully.

<bold>Background:</bold> Coronavirus Disease 2019 (COVID-19) has spread worldwide with collateral damage and therefore might affect the behavior of stroke patients with mild symptoms seeking medical attention. <bold>Methods:</bold> Patients with ischemic stroke who were admitted to hospitals within 7 days of onset were retrospectively registered. The clinical characteristics, including onset-to-door time (ODT), of patients with a transient ischemic attack (TIA)/mild stroke (National Institutes of Health Stroke Scale [NIHSS] score of ≤ 3 on admission) or moderate/severe stroke were compared between those admitted from April 2019 to March 2020 (pre-COVID-19 period) and from April to September 2020 (COVID-19 period). Multivariable regression analysis was performed to identify factors associated with the ODT. <bold>Results:</bold> Of 1,100 patients (732 men, median age, 73 years), 754 were admitted during the pre-COVID-19 period, and 346 were admitted during the COVID-19 period. The number and proportion of patients with TIA/minor stroke were 464 (61.5%) in the pre-COVID-19 period and 216 (62.4%) during the COVID-19 period. Among patients with TIA/mild stroke, the ODT was longer in patients admitted during the COVID-19 period compared with that of the pre-COVID-19 period (median 864 min vs. 508 min, <italic>p</italic> = 0.003). Multivariable analysis revealed the COVID-19 period of admission was associated with longer ODT (standardized partial regression coefficient 0.09, <italic>p</italic> = 0.003) after adjustment for age, sex, route of arrival, NIHSS score on admission, and the presence of hypertension, diabetes mellitus, and wake-up stroke. No significant change in the ODT was seen in patients with moderate/severe stroke. <bold>Conclusions:</bold> The COVID-19 epidemic might increase the ODT of patients with TIA/mild stroke.

<sec id="sec001"> <title>Background and purpose</title> The impact of the paraoxonase-1 (<italic>PON1</italic>) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of <italic>PON1</italic> Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. </sec> <sec id="sec002"> <title>Methods</title> Post-clopidogrel platelet reactivity was measured using a VerifyNow^® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for <italic>PON1</italic> Q192R and <italic>CYP2C19*2</italic> and <italic>*3</italic> (no function alleles), and <italic>*17</italic>. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 <italic>PON1</italic> 192R allele and HPR defined as original and corrected PRU ≥208. </sec> <sec id="sec003"> <title>Results</title> Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 <italic>PON1</italic> 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 <italic>PON1</italic> 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 <italic>CYP2C19</italic> no function allele. </sec> <sec id="sec004"> <title>Conclusions</title> Carrying ≥1 <italic>PON1</italic> 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded. </sec>

Background The World Federation of Neurosurgical Societies (WFNS) scale is widely accepted for predicting outcomes for subarachnoid hemorrhage (SAH) patients. However, it is difficult to definitely predict outcomes for the most poor grade, WFNS grade 5. The present study aimed to investigate the prognostic ability of a novel classification using computed tomography perfusion (CTP) findings, called the cortical blood flow insufficiency (CBFI) scores. Methods CTP was performed on admission for aneurysmal SAH followed by radical treatments within 72 hours of onset. Twenty-four cerebral cortex regions of interest (ROIs) were defined. CBFI was defined as Tmax > 4 s in each ROI, and CBFI scores were calculated based on the total number of ROIs with CBFI. Using the optimal cutoff value based on receiver operating characteristics (ROC) analysis to predict patient functional outcomes, CBFI scores were divided into "high" or "low" CBFI scores. Patient functional outcomes at 90 days were categorized based on modified Rankin Scale scores (0-3, favorable group; 4-6 unfavorable group) (0-4, non-catastrophic group; 5-6, catastrophic group). Results Fifty-seven patients were included in this study, of whom 21 (36.8%) and 13 (22.8%) were in the unfavorable and the catastrophic groups, respectively. A factor predicting unfavorable and catastrophic outcomes was CBFI score cutoff value of 7 points (area under the curve, 0.73 and 0.81, respectively). In multivariable logistic regression analysis for unfavorable outcome, high CBFI scores (odds ratio (OR), 8.6; 95% confidence interval (CI), 1.1-65.4;P = 0.04) and WFNS grade 5 (OR, 30.0; 95% CI, 4.5-201.0;P < 0.001) remained as independent predictors, while for catastrophic outcome, high CBFI scores (OR, 25.3; 95% CI, 3.3-194.0;P = 0.002) and age (OR, 1.1; 95% CI, 1.0-1.2;P = 0.02) remained as independent predictors. Conversely, WFNS grade 5 was not an independent predictor of catastrophic outcomes (OR, 3.8; 95% CI, 0.6-24.0;P = 0.15). In high CBFI scores, the OR of the delayed cerebral ischemia (DCI) occurrence was 9.6 (95% CI, 1.5-61.4;P = 0.02) after adjusting for age. Conclusion High CBFI scores could predict unfavorable and catastrophic outcomes for aneurysmal SAH patients and DCI occurrence.

<sec><title>Background</title>Thromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel. </sec><sec><title>Methods</title>Patients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU &lt;240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint. </sec><sec><title>Results</title>The tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group. </sec><sec><title>Conclusion</title>The results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications. </sec>

OBJECTIVE: Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction. METHODS: In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients' clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247-0.987, p < .001) and IDI (0.068, 95% CI: 0.021-0.116, p = .005). CONCLUSIONS: Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.

Mechanical thrombectomy using a retrograde approach is performed for tandem occlusion of the internal carotid artery (ICA). In our patient, a guiding catheter was easily passed by the stenosed lesion despite severe stenosis at the ICA origin. Therefore, we aimed to recanalize the occlusion of the terminal ICA without angioplasty for the stenosed lesion. When contrast was injected, a massive extravasation of contrast from the C2 portion of the ICA was observed. It was speculated that the bleeding was caused by rupture of an aneurysm at that site due to increased intra-arterial pressure caused by the contrast injection to a blind alley, which was created by a wedged guiding catheter at severe stenosis at the ICA origin and the occlusion of the terminal ICA. Our simulation experiment using a silicon vascular model in this situation demonstrated that the elevation of intra-arterial pressure in such blind alley reached over 50, 100, and 200 mmHg by injection of contrast from a microcatheter, a 4-Fr inner catheter, and a 9-Fr balloon-guiding catheter, respectively. When a retrograde approach is planned for tandem occlusion of the ICA, even when the proximal lesion is easily passed, prior angioplasty for the proximal lesion should be considered to avoid wedging by catheter.

Background and Purpose: In the acute phase of ischemia-reperfusion, hypoperfusion associated with ischemia and reperfusion in microvascular regions and disruption of the blood-brain barrier (BBB) contribute to post-ischemic brain injury. We aimed to clarify whether brain injury following transient middle cerebral artery occlusion (tMCAO) is ameliorated in Transient receptor potential vanilloid 4 knockout (Trpv4-/- ) mice. Methods: tMCAO was induced in wild-type (WT) and Trpv4-/- mice aged 8-10 weeks. Ischemia-induced lesion volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining at 24 h post-tMCAO. Tissue water content and Evans blue leakage in the ipsilateral hemisphere and a neurological score were evaluated at 48 h post-tMCAO. Transmission electron microscopy (TEM) was performed to assess the morphological changes in microvasculature in the ischemic lesions at 6 h post-tMCAO. Results: Compared with WT mice, Trpv4-/- mice showed reduced ischemia-induced lesion volume and reduced water content and Evans blue leakage in the ipsilateral hemisphere alongside milder neurological symptoms. The loss of zonula occludens-1 and occludin proteins in the ipsilateral hemisphere was attenuated in Trpv4-/- mice. TEM revealed that parenchymal microvessels in the ischemic lesion were compressed and narrowed by the swollen endfeet of astrocytes in WT mice, but these effects were markedly ameliorated in Trpv4-/- mice. Conclusion: The present results demonstrate that TRPV4 contributes to post-ischemic brain injury. The preserved microcirculation and BBB function shortly after reperfusion are the key neuroprotective roles of TRPV4 inhibition, which represents a promising target for the treatment of acute ischemic stroke.

Early neurological deterioration (END) following intravenous recombinant tissue plasminogen activator (rt-PA) treatment is a serious clinical event that can be caused by hemorrhagic or ischemic insult. We investigated the differences in predictive factors for END due to hemorrhagic and END due to ischemic insults. Consecutive patients from four hospitals who received 0.6 mg/kg intravenous rt-PA for acute ischemic stroke were retrospectively recruited. END was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within 24 h compared with baseline. END was classified into those due to hemorrhagic (ENDh) or ischemic (ENDi) insult based on computed tomography (CT) or magnetic resonance imaging. Risk factors associated with ENDh and ENDi were investigated by comparison with non-END cases. A total of 744 patients (452 men, median 75 years old) were included. END was observed in 79 patients (10.6%), including 22 ENDh (3.0%) and 57 ENDi (7.7%), which occurred within a median of 7 h after treatment. Multivariate analyses showed that higher pretreatment NIHSS score (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00-1.13) and pretreatment with antiplatelets (OR 2.84, 95% CI 1.08-7.72) were associated with ENDh. Extensive early ischemic change (Alberta Stroke Program Early CT Score ≤ 7 on CT or ≤ 6 on diffusion-weighted imaging; OR 2.80, 95% CI 1.36-5.64) and large artery occlusions (OR 3.09, 95% CI 1.53-6.57) were associated with ENDi. Distinct factors were predictive for the END subtypes. These findings could help develop preventative measures for END in patients with the identified risk factors.

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used for the assessment of early ischemic changes (EICs) before thrombolysis. However, for symptomatic intracerebral hemorrhage (sICH) following intravenous recombinant tissue plasminogen activator (rt-PA), the prediction abilities of CT-ASPECTS, diffusion-weighted imaging (DWI)-ASPECTS, and DWI-ASPECTS including EICs in deep white matter (DWI-ASPECTS + W) are unclear. We investigated associations between each score and sICH following intravenous rt-PA. Data from consecutive patients who received intravenous rt-PA for acute ischemic stroke from 2005 to 2015 in four hospitals were retrospectively screened. We included data from patients who had undergone both CT and magnetic resonance imaging before thrombolysis and without evidence of posterior circulation stroke. We analyzed the ability of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W to predict sICH, accompanied by an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 within the initial 36 h. Of 455 patients (273 men, median 75 years old), sICH occurred in 15 patients (3.3%). Receiver operating characteristics curve analysis showed that the optimal cut-offs of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W for predicting sICH were ≤ 9 (sensitivity 60.0%, specificity 59.8%, c-statistic 0.625), ≤ 6 (sensitivity 53.3%, specificity 80.9%, c-statistic 0.718), and ≤ 8 (sensitivity 86.7%, specificity 55.9%, c-statistic 0.756), respectively. A DWI-ASPECTS + W of ≤ 8 was independently associated with sICH (odds ratio 5.21, 95% confidence interval 1.30-35.31) after adjustment for pretreatment with antithrombotic agents, pretreatment NIHSS score, and large artery occlusions. DWI-ASPECTS + W predicted sICH in patients with acute anterior circulation stroke receiving intravenous rt-PA.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rt-PA) has become a common treatment for acute ischemic stroke and has highly time-dependent benefits. We aimed to clarify temporal trends regarding the frequency and characteristics of patients receiving rt-PA and explore factors associated with door-to-needle time (DNT) in Japanese emergency hospitals. METHODS: Consecutive patients who received intravenous rt-PA for acute ischemic stroke from October 2005 to December 2015 were retrospectively registered from 4 hospitals. Temporal trends in the frequency and characteristics of patients receiving rt-PA and factors associated with DNT were investigated. RESULTS: A total of 750 patients, including 688 (420 men, median 75 years old) with out-of-hospital stroke, were registered. The frequency of patients receiving intravenous rt-PA for acute ischemic stroke continuously increased from 1.8% in 2005 to 9.5% in 2015. The proportion of patients who were elderly or had prestroke disability increased over time, while pretreatment stroke severity declined. The DNT gradually decreased (median 105 minutes in 2005, 61 minutes in 2015). According to multivariate regression analysis with correction for multiple comparisons, activation of a code stroke system (standardized partial regression coefficient (β) -.50, P < .001, q < .001), onset-to-door time (β -.15, P < .001, q < .001), pretreatment with antithrombotic agents (β .12, P < .001, q = .001), and year of treatment (β .11, P = .007, q = .011) were associated with DNT. CONCLUSIONS: Intravenous rt-PA was widely adopted in Japanese emergency hospitals. Characteristics of patients receiving intravenous rt-PA have changed over the past decade. Several factors, including the year of treatment, were associated with DNT, which has shortened over time.

Background: To maximize the effect of intravenous (IV) thrombolysis and/or endovascular therapy (EVT) for acute ischemic stroke (AIS), stroke centers need to establish a parallel workflow on the basis of a code stroke (CS) protocol. At Kokura Memorial Hospital (KMH), we implemented a CS system in January 2014; however, the process of information sharing within the team has occasionally been burdensome. Objective: To solve this problem using information communication technology (ICT), we developed a novel application for smart devices, named "Task Calc. Stroke" (TCS), and aimed to investigate the impact of TCS on AIS care. Methods: TCS can visualize the real-time progress of crucial tasks for AIS on a dashboard by changing color indicators. From August 2015 to March 2017, we installed TCS at KMH and recommended its use during normal business hours (NBH). We compared the door-to-computed tomography time, the door-to-complete blood count (door-to-CBC) time, the door-to-needle for IV thrombolysis time, and the door-to-puncture for EVT time among three treatment groups, one using TCS ("TCS-based CS"), one not using TCS ("phone-based CS"), and one not based on CS ("non-CS"). A questionnaire survey regarding communication problems was conducted among the CS teams at 3 months after the implementation of TCS. Results: During the study period, 74 patients with AIS were transported to KMH within 4.5 h from onset during NBH, and 53 were treated using a CS approach (phone-based CS: 26, TSC-based CS: 27). The door-to-CBC time was significantly reduced in the TCS-based CS group compared to the phone-based CS group, from 31 to 19 min (p = 0.043). Other processing times were also reduced, albeit not significantly. The rate of IV thrombosis was higher in the TCS-based CS group (78% vs. 46%, p = 0.037). The questionnaire was correctly filled in by 34/38 (89%) respondents, and 82% of the respondents felt a reduction in communication burden by using the TCS application. Conclusions: TCS is a novel approach that uses ICT to support information sharing in a parallel CS workflow in AIS care. It shortens the processing times of critical tasks and lessens the communication burden among team members.

An elevated end-diastolic (ED) ratio of the common carotid artery (CCA) is an indicator of occlusive lesions of the distal portion of the internal carotid artery. We report 2 cases of cerebral arteriovenous malformation (AVM) showing an elevated ED ratio of the CCA, which decreased after surgery. Case 1 was a 28-year-old man with chronic recurrent headache with aura, and case 2 was a 29-year-old woman with sudden-onset headache and intracerebral hemorrhage without neurologic abnormality. In both cases, digital subtraction angiography revealed a Spetzler-Martin Grade IV AVM, which was mainly fed by branches of the left middle cerebral artery with venous drainage into superficial and deep cerebral veins. Preoperative carotid ultrasonography showed an elevated CCA ED ratio (1.38 in case 1 and 1.47 in case 2; left > right) without atherosclerotic lesions. Patients' AVMs were successfully resected. In both cases, the ED ratio was decreased after surgery (to 1.05 in case 1 and 1.20 in case 2). A decrease in vascular resistance on 1 side caused by cerebral AVM can result in an increase in the CCA ED ratio comparable to that of carotid axis occlusion.

Background Cerebral hyperperfusion syndrome (CHS) is known to be a rare but devastating complication of carotid artery revascularization. Because patients with acute ischemic stroke due to acute major cerebral and/or cervical artery occlusion treated with endovascular reperfusion therapy may have impaired autoregulation in the cerebral vasculature, these patients may also develop CHS. Despite the growing number of endovascular reperfusion procedures for acute ischemic stroke, this complication has only rarely been reported. Case Description A 77-year-old man developed acute cerebral infarction as the result of occlusions of the right internal carotid artery and right middle cerebral artery. After systemic intravenous injection of recombinant tissue-type plasminogen activator, endovascular reperfusion therapy was initiated. The occluded arteries were successfully recanalized with thrombectomy by using a stent retriever for the middle cerebral artery and stent placement for the origin of the internal carotid artery. However, head computed tomography obtained 12 hours after treatment showed acute intracranial hemorrhage that did not involve the ischemic lesions. Under evaluation with transcranial near-infrared spectroscopy and single-photon emission computed tomography, the hemorrhage was considered to have been caused by CHS after reperfusion therapy. Conclusions CHS may lead to unfavorable outcomes after reperfusion therapy for acute ischemic stroke. Recognizing clinical deterioration caused by CHS can be challenging in patients with neurologic disorders of acute ischemic stroke. Therefore, it is important to perform routine monitoring of regional cerebral oxygen saturation by using near-infrared spectroscopy, perform single-photon emission computed tomography promptly to evaluate cerebral blood flow, and maintain strict antihypertensive therapy to prevent CHS after reperfusion therapy.

Background: End-diastolic ratio, calculated by the side-to-side ratio of end-diastolic flow velocities of the common carotid arteries, is an indicator for large artery intracranial occlusive disease. However, the diagnostic ability of end-diastolic ratios derived from different measurement conditions is unclear. Methods: End-diastolic ratios were measured twice by single carotid duplex ultrasonography. End-diastolic ratio(1st) was calculated from separate end-diastolic flow velocities measured during routine assessment. End-diastolic ratio(2nd) was calculated almost simultaneously without head rotation. For each end-diastolic ratio, the measurement conditions and prediction ability for occlusions of the internal carotid artery or proximal portion of the middle cerebral artery using an established cutoff of 1.4 or greater were compared. Results: Two hundred thirty-three patients (147 men, median 67 years) were registered, with available intracranial artery information in 158 patients (67.8%) and occlusions detected in 7 patients (4.4%). End-diastolic ratio1(st) was significantly higher than end-diastolic ratio2(nd) (median 1.21 versus 1.08, P &lt; .001). Compared with end-diastolic ratio1(st), end-diastolic ratio2nd had a significantly shorter time interval (median 709 versus 28 seconds, P &lt; .001) and smaller pulse rate difference (1.54 +/- 5.10 versus.25 +/- 4.63 beats per minute, P = .004). To predict occlusions, the sensitivity, specificity, and overall accuracy for end-diastolic ratio1(st) of 1.4 or greater were 85.7%, 70.9%, and 71.5%, respectively, and for end-diastolic ratio2(nd) of 1.4 or greater were 85.7%, 98.0%, and 97.5%, respectively. End-diastolic ratio2(nd) had better specificity and overall accuracy than end-diastolic ratio1st (P &lt;.001). Conclusions: End-diastolic ratio varies with measurement conditions. Combined end-diastolic flow velocities measurement may improve diagnostic ability for large artery intracranial occlusive disease.

Background. Previous reports have shown significant delays in treatment of in-hospital stroke (IHS). We developed and implemented our IHS alert protocol in April 2014. We aimed to determine the influence of implementation of our IHS alert protocol. Methods: Our implementation processes comprise the following four main steps: IHS protocol development, workshops for hospital staff to learn about the protocol, preparation of standardized IHS treatment kits, and obtaining feedback in a monthly hospital staff conference. We retrospectively compared protocol metrics and clinical outcomes of patients with IHS treated with intravenous thrombolysis and/or endovascular therapy between before (January 2008 March 2014) and after implementation (April 2014 December 2016). Results: Fifty-five patients were included (pre, 25; post, 30). After the implementation, significant reductions occurred in the median time from stroke recognition to evaluation by a neurologist (30 vs. 13.5 min, p &lt; 0.01) and to first neuroimaging (50 vs. 26.5 min, p &lt; 0.01) and in the median time from first neuroimaging to intravenous thrombolysis (45 vs. 16 min, p = 0.02). The median time from first neuroimaging to endovascular therapy had a tendency to decrease (75 vs. 53 min, p = 0.08). There were no differences in the favorable outcomes (modified Rankin scale score of 0-2) at discharge or the incidence of symptomatic intracranial hemorrhage between the two periods. Conclusion: Our IHS alert protocol implementation saved time in treating patients with IHS without compromising safety.

BACKGROUND: Definitive preoperative predictors of cerebral hyperperfusion following carotid artery stenting are yet to be established. OBJECTIVE: To determine the preprocedural risk factors for cerebral hyperperfusion phenomenon (CHP) following carotid artery stenting. METHODS: Patients undergoing preprocedural single-photon emission computed tomography (SPECT) and cerebral angiography prior to their first carotid artery stenting were monitored for occurrence of CHP. In addition to patient characteristics, we investigated imaging parameters, such as cerebral blood flow, cerebral vasoreactivity, and asymmetry index on SPECT, and presence of near occlusion and leptomeningeal anastomosis on cerebral angiography. RESULTS: Out of 100 patients (mean age: 73.0 +/- 7.6 years; 85 men), 9 developed CHP. On multivariate logistic regression analysis, asymmetry index (%) on SPECT (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.70-0.93, P = .003) and presence of leptomeningeal anastomosis on cerebral angiography (OR 72.1, 95% CI 3.52-1480, P = .006) were independent predictors of CHP. CONCLUSION: Combined use of cerebral angiography and SPECT may obviate the need for acetazolamide challenge to predict the risk of CHP following carotid artery stenting.

Aim: Atrial fibrillation (AF)-related cardioembolic stroke is a serious problemin the aging society. The present study examined the clinical characteristics and outcomes of AF-related cardioembolic stroke in patients aged &gt;= 80 years. Methods: Between September 2011 and April 2014, consecutive patients with ischemic stroke and AF were retrospectively extracted from the multicenter database. Clinical characteristics were compared between patients aged &gt;= 80 years and &lt;80 years. Multivariate cox proportional hazard models were used to estimate hazard ratios and 95% confidential intervals on 90-day mortality for age of &gt;= 80 years. Results: A total of 253 patients aged &gt;= 80 years (87 men, 86.4 +/- 5.0 years) and 196 patients aged &lt;80 years (134 men, 70.4 +/- 7.1 years) were included. Patients aged &gt;= 80 years were more frequently female, and more likely to have higher premorbid modified Rankin Scale score (mRS), lower body mass index, previous history of stroke, prior antiplatelet therapy, congestive heart failure, and persistent AF. Patients aged &gt;= 80 years had higher initial National Institutes of Health Stroke Scale score and were more likely to have occlusion of the cervicocephalic arteries, but less likely to receive thrombolysis. Patients aged &gt;= 80 years had a higher mRS and mortality after 3 months. Age of &gt;= 80 years was a significant predictor of 90-day mortality after adjustment for sex (hazard ratio 2.20, 95% confidential interval 1.25-4.09), but was no longer significant after further adjustment for other clinical characteristics and stroke severity. Conclusions: In AF-related cardioembolic stroke, patients aged &gt;= 80 years had different clinical characteristics and poorer outcome compared with patients aged &lt;80 years.

Background and purpose Hemorrhagic complications during neurointerventional procedures have various etiologies and can result in severe morbidity and mortality. This study investigated the possible association between low platelet reactivity measured by the VerifyNow assay and increased hemorrhagic complications during elective neurointervention under dual antiplatelet therapy. Methods From May 2010 to April 2013 we recorded baseline characteristics, P2Y12 reaction units (PRU), and aspirin reaction units using VerifyNow. The primary endpoint was post-procedural hemorrhagic complications. Results A total of 279 patients were enrolled and 31 major hemorrhagic complications (11.1%) were identified. From receiver-operating characteristic curve analysis, PRU values could discriminate between patients with and without major hemorrhagic complications (area under the curve 0.63). Aspirin reaction unit values had no association with the primary outcome. The optimal cut-off for the primary outcome (PRU &lt;= 175) was used to identify the low platelet reactivity group. The incidence of hemorrhagic complications was 20.0% in this group and 8.9% in the non-low platelet reactivity group. Multivariate analysis identified low platelet reactivity as an independent predictor for hemorrhagic complications. Conclusions The risk of hemorrhagic complications during elective neurointervention including cerebral aneurysm coil embolization and carotid artery stenting under dual antiplatelet therapy is associated with the response to clopidogrel but not to aspirin. A PRU value of &lt;= 175 discriminates between patients with and without hemorrhagic complications. Future prospective studies are required to validate whether a specific PRU value around 170-180 is predictive of hemorrhagic complications.

41歳男。突然発症の左上下肢のしびれを主訴とした。非外傷性右頸部内頸動脈解離およびそれに起因する動脈原性塞栓症の診断でアスピリン内服下に経過観察していた。初回脳梗塞発症から5ヵ月後に傾眠状態となり、頭部MRI DWIで新規脳梗塞を認めた。脳血管内治療にて急性期血行再建を行ったが、頸動脈ステントを留置した内頸動脈に茎状突起が近接しており、茎状突起過長症に伴う内頸動脈解離と判明した。また、脳血管撮影時の動態撮影では頭位の変化に伴って頸動脈が圧迫されており、ステント内血栓症からの脳梗塞再発を予防する目的で茎状突起摘出を行い、術後は脳梗塞の再発を認めていない。

Objective: We report a rare case of cervical internal carotid artery aneurysm associated with Marfan syndrome and the technical details of endovascular trapping. Case Presentations: A 23-year-old male who had been diagnosed with Marfan syndrome presented with dysphagia due to an enlarged left cervical pulsating mass. Imaging studies revealed a non-thrombosed, giant cervical internal carotid fusiform aneurysm measuring approximately 3–4 cm extending to the skull base. After bypass surgery between the superficial temporal artery and the middle cerebral artery, endovascular trapping of the cervical internal carotid artery at both sides of the aneurysm was performed under flow control without positioning any coils inside the aneurysm itself. A 6F distal access catheter technique through the aneurysm and double or triple microcatheter technique were useful for tight and short-length occlusion of the artery combined with a proximal balloon guiding catheter. Dysphagia resolved after treatment due to alleviation of the compression on the recurrent nerve and disappeared completely within 3 weeks. Conclusion: Distal access catheter and multiple microcatheters under proximal flow control can be useful for endovascular trapping of both sides of a cervical fusiform aneurysm.

Background: We aimed to determine the predictive factors for excellent or extremely poor functional outcome in patients with first-ever atrial fibrillation (AF)-related cardioembolic stroke. Methods: Retrospective observational study from a database. Patients with AF-related cardioembolic stroke with a premorbid modified Rankin Scale (mRS) score of 0 or 1 and without a previous history of stroke were included. Results: Factors associated with excellent functional outcome (mRS scores of 0 or 1; n = 77; 30.4% of patients) included age &gt;78 years (OR 0.31, 95% CI 0.15-0.61), male sex (OR 2.16, 95% CI 1.04-4.60), absence of hypertension (OR 0.46, 95% CI 0.22-0.94) and initial National Institutes of Health Stroke Scale (NIHSS) score of &gt;9 (OR 0.08, 95% CI 0.03-0.16). Factors associated with extremely poor functional outcome (mRS scores of 5 or 6; n = 63; 24.9%) included age &gt;78 years (OR 3.30, 95% CI 1.54-7.39), initial NIHSS score of &gt;9 (OR 12.38, 95% CI 5.40-32.56), congestive heart failure (OR 4.82, 95% CI 2.00-12.19) and ischemic heart disease (OR 4.02, 95% CI 1.18-14.69). Conclusions: Predictive factors exist to delineate excellent and extremely poor functional outcomes after a first-time stroke associated with AF. (C) 2016 S. Karger AG, Basel

【目的】頸動脈ステント留置術(CAS)後の再狭窄による脳梗塞発症リスクと,再狭窄発生の独立予測因子につき検討する.【方法】2009年1月から2014年9月までに当科でCASを施行し180日以上経過観察した症例において,NASCET 70%以上の再狭窄の頻度,同側脳梗塞発症について後方視的検討を行った.【結果】250例が解析対象となった.周術期以降の同側脳梗塞は9例(3.6%),再狭窄は19例(7.6%)に認め,再狭窄に合併した同側脳梗塞は3例であった.Cox比例ハザードモデルでは,再狭窄を有する群に有意に同側脳梗塞が多い結果であった(hazard ratio[HR],5.98;95% confidence interva[CI],1.19-24.47;p=0.032).また,多変量解析にてclosed cell stentの使用(HR5.12,95% CI 1.30-34.34;P=0.017)のみが再狭窄発生に関連する独立予測因子であった.【結論】再狭窄が同側脳梗塞発症に関連し,再狭窄発生にはclosed cell stentの使用が関連していることが示唆された.(著者抄録)

Background: We examined the association between pre-admission risk scores and severity on admission and functional outcome in acute ischemic stroke with atrial fibrillation (AF). Methods: Between September 2011 and April 2014, we retrospectively extracted consecutive ischemic stroke patients with AF whose pre-admission modified Rankin Scale (mRS) score was 2 or less from our prospective database. Pre-admission CHADS(2), CHA(2)DS2-VASc, and R(2)CHADS(2) scores were calculated in each patient, and their association with the National Institutes of Health Stroke Scale (NIHSS) score on admission or unfavorable outcome (mRS &gt;= 3 at 3 months from the onset) was assessed. Results: A total of 344 patients (189 were men; age, 77.7 +/- 10.0 years) were included in the analysis. The median pre-admission CHADS(2), CHA(2)DS(2)-VASc, and R(2)CHADS(2) scores were 2, 4, and 4, respectively. NIHSS score on admission was positively correlated with pre-admission CHADS(2) (rho = .116, P = .031), CHA(2)DS(2)-VASc (rho = .166, P = .020), and R(2)CHADS(2) scores (rho = .106, P = .049). Receiver operating characteristic (ROC) curve analysis revealed that pre-admission CHADS(2) score of 2 or more (sensitivity, 80%; specificity, 45%; area under the ROC curve [AUC], .654), CHA(2)DS(2)-VASc score of 3 or more (sensitivity, 86%; specificity, 44%; AUC, .683), and R(2)CHADS(2) score of 4 or more (sensitivity, 61%; specificity, 62%; AUC, .657) were associated with unfavorable outcome. The pre-admission CHA(2)DS(2)-VASc score was better than the pre-admission CHADS(2) score in estimating unfavorable outcome (P = .017). In multivariate analysis, cutoffs of these scores, female sex, higher NIHSS score, and internal carotid artery occlusion were associated with unfavorable outcome. Conclusions: Pre-admission CHADS(2), CHA(2)DS(2)-VASc, and R(2)CHADS(2) scores were associated with onset severity and functional outcome in acute ischemic stroke with AF. (C) 2015 by National Stroke Association