Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Extraovarian Dysgerminoma Involving the Uterine Cervix: A Rare Case Report With Literature Review.

Primary extraovarian dysgerminoma (EOD) is a very rare disease. There is no literature about primary EOD involving the uterine cervix. We herein present details of a unique case of primary EOD involving the uterine cervix. A 46-year-old woman with uterine cervical tumor was referred to our institution with atypical genital bleeding. A polypoid tumor localized to the uterine cervix was found. Cervical biopsy detected malignant components of likely nonepithelial cell origin. Preoperative imaging examinations showed a uterine cervical tumor measuring ~5 cm, suggestive of malignancy without distant or lymph node metastases. The patient underwent abdominal radical hysterectomy with pelvic lymph node dissection according to the standard treatment for stage IB3 cervical cancers. The pathological diagnosis was dysgerminoma involving the uterine cervix and the right fallopian tube. Immunohistochemical results were as follows: SALL4 (+), octamer-binding transcription factor 4 (+), D2-40 (+), and c-Kit (+). She received 3 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. The disease did not recur up to 14 months after surgery. This is the first-ever published case of primary EOD involving the uterine cervix among previously reported EOD cases. Reported cases of EOD in female genital tract are also reviewed. Our case provides more extensive insights for pathologists to consider the differential diagnosis of cervical lesions. In our case, combination therapy involving a surgical approach-according to cervical cancers and adjuvant chemotherapy as used for ovarian dysgerminomas-was effective. Future verification is needed regarding the best approach for treating uterine cervical dysgerminomas.

Long-term outcome and factors associated with restenosis after combination therapy of balloon angioplasty and stenting for symptomatic intracranial stenosis.

BACKGROUND: The optimal treatment for intracranial artery stenosis (ICAS) has not been established. We retrospectively examined the initial and long-term outcomes associated with restenosis of a combination therapy of balloon angioplasty and stenting for symptomatic atherosclerotic ICAS. METHODS: Consecutive patients who underwent balloon angioplasty and/or stenting for ≥ 70% ICAS between 2006 and 2020 were analyzed. Patients within 48 h of stroke onset were excluded. The following procedures were established as standards at our institution: (1) primary balloon angioplasty alone was initially performed; (2) stenting for insufficient dilatation, recoiling, or dissection was conducted; and (3) stenting was considered for restenosis. Intracranial ischemic and hemorrhagic complications within 30 days after treatment were used to evaluate periprocedural safety. Recurrent ischemic events, restenosis and restenosis related factors were used to be evaluate the long-term outcome. RESULTS: A total of 160 patients were recruited. Initial treatment consisted of balloon angioplasty (n = 101) and stenting (n = 59). Intracranial complications within 30 days after treatment were ischemic in five (3.1%) and hemorrhagic in four patients (2.5%). The incidence of these complication was 3.1% in the stenting group and 2.5% in the balloon angioplasty group. The mean follow-up period was 53.9 months. Restenosis was found in 42 patients (26%). Recurrent ischemic events during follow-up were noted in 14 patients (8.8%), of which six patients had TIA and eight patients had ischemic stroke. Restenosis-associated factors included diabetes, coronary artery disease, percent stenosis after treatment, and balloon angioplasty in logistic univariate analysis. Multivariate Cox regression analysis showed that diabetes (HR: 2.084, CI: 1.039-4.180, p = 0.0386), length of lesion (HR; 1.358, CI: 1.174-1.571, p < 0.0001), and balloon angioplasty (HR: 4.194, CI: 1.083-16.239, p = 0.0379) were independent predictors for restenosis. CONCLUSION: Combination therapy of balloon angioplasty and stenting for symptomatic ICAS had a low perioperative stroke rate and may improve long-term outcome. Balloon angioplasty, diabetes, and length of lesion were significantly associated with restenosis.

Carotid Ultrasound Using Superb Microvascular Imaging to Identify Patients Developing In-Stent Restenosis After CAS.

BACKGROUND AND PURPOSE: In-stent restenosis (ISR) caused by in-stent intimal hyperplasia (ISH) may develop after carotid artery stenting (CAS), and often necessitates re-stenting. We investigated whether new ultrasound technique is useful for detecting carotid artery plaques prone to ISR. PURPOSE: Superb micro-vascular imaging (SMI) is a new color Doppler imaging technique for assessing low velocity blood flow such as neovascularization in carotid artery plaques. In this study, we attempted to identify associations between findings from carotid ultrasonography with SMI performed prior to CAS and in-stent restenosis after 6 months of CAS. METHODS: This study investigated 19 patients (18 men; mean age, 72.4 years). Preoperative plaque evaluation was performed by magnetic resonance imaging, ultrasonography, and carotid angiography. Follow up angiography was performed in all patients at 6 months after CAS. ISR was defined as ISH resulting in >50% stenosis based on European Carotid Surgery Trialists criteria. We investigated whether SMI was useful as a predictor of ISR by chi-square test. RESULTS: Preoperative mean stenosis rate according to North American Symptomatic Carotid Endarterectomy Trial methods in 19 patients was 61.3%. Neovascularization was observed on SMI in 10 patients (52.6%). Carotid angiography at 6 months after CAS revealed ISR in 4 patients, all of whom had shown neovascularization on SMI. A significant association was seen between findings of neovascularization on SMI and development of ISR (p = 0.033). In predicting ISR, neovascularization findings on SMI offered 100.0% sensitivity and 60.0% specificity. CONCLUSIONS: Preprocedural plaque characterization by carotid ultrasound with SMI appears useful for predicting ISR at 6 months after CAS.

Outcomes of Balloon Angioplasty and Stenting for Symptomatic Intracranial Atherosclerotic Stenosis at a High Volume Center.

PURPOSE: This study investigated the periprocedural complication rates, long-term outcome, and restenosis of endovascular treatment for intracranial atherosclerotic stenosis (ICS) at our hospital. METHODS: We retrospectively analyzed the clinical data of 217 patients comprising 256 endovascular treatments for high-grade symptomatic ICS. The lesion was located in the internal carotid artery in 77, the middle cerebral artery in 111, the basilar artery in 29, and the vertebral artery in 39. Patients were divided into two groups, before (early-phase group, 1999-2013) and after approval of Wingspan (late-phase group, 2014-2017). RESULTS: In the early-phase group (n = 163), 157 lesions were treated by balloon angioplasty and 31 (17%) by coronary stenting. In the late-phase group (n = 54), 33 lesions were treated by balloon angioplasty and 35 (52%) by Wingspan stenting. Overall technical success rates were 96% in the balloon angioplasty and 100% in stenting groups. The 30-day rate of stroke, TIA, and death were 4.8% in the early-phase group and 4.4% in the late-phase group. There was one minor stroke and two TIAs during the follow-up period in the late-phase group. CONCLUSIONS: Endovascular treatment for symptomatic ICS in this study appeared to be safe and effective if patients are properly selected. However, future well-designed randomized trials with different techniques and modified patients selection criteria are certainly warranted.

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial.

IMPORTANCE: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. OBJECTIVE: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. INTERVENTIONS: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). MAIN OUTCOMES AND MEASURES: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. RESULTS: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). CONCLUSIONS AND RELEVANCE: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000021488.

Sex Differences in Blood Pressure-Lowering Therapy and Outcomes Following Intracerebral Hemorrhage: Results From ATACH-2.

BACKGROUND AND PURPOSE: Evidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)-lowering therapy. METHODS: Eligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110-139 mm Hg) or standard (140-179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored. RESULTS: In total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02-1.37, P=0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74-1.13) in women versus 1.13 (95% CI, 0.92-1.39) in men (P for interaction=0.11), with inconclusive Gail-Simmon test (P=0.16). CONCLUSIONS: Women had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565.

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

Preprocedural Carotid Plaque Echolucency as a Predictor of In-Stent Intimal Restenosis after Carotid Artery Stenting.

OBJECTIVES: In-stent intimal restenosis (ISR) caused by neointimal hyperplasia can develop <24 months after carotid artery stenting (CAS). The utility of plaque imaging by carotid ultrasonography (US) or magnetic resonance imaging (MRI) has been investigated for the prediction of ipsilateral stroke. We aimed to investigate whether these imaging techniques are useful for detecting carotid plaques prone to ISR. MATERIALS AND METHODS: We examined 133 patients (mean age of 72.1 ± 8.4 years old) that received CAS at a single hospital from 2014 to 2018. A pre-CAS carotid plaque evaluation was performed by carotid angiography, duplex carotid US, and black-blood carotid artery MRI (BB-MRI). The mean stenosis rate was 71.0 ± 12.3% by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) methods. Follow-up carotid angiography was performed 6 months after CAS in all patients according to a predefined protocol. ISR was defined as in-stent intimal hyperplasia more than 50% stenosed based on the NASCET criteria. The selection of the stent type was at the discretion of the treating physician. Predictors of ISR were determined by multivariate logistic regression analysis. RESULTS: Follow-up angiography demonstrated ISR in 33 patients (24.8%). In 44 patients, more than two stents were deployed. Univariate logistic regression analyses demonstrated echolucent lesion, floating plaque, complete occlusive or pseudo-occlusive lesion, and closed-cell stent use as significantly associated with ISR (>50%). Multivariate logistic regression analysis demonstrated that echolucent lesion (OR 4.667, 95% CI 1.849-11.779) and closed-cell stent use (OR .378, 95% CI .148-.968) were significantly associated with ISR. CONCLUSIONS: Preprocedural plaque characterization by carotid US appeared to be useful to predict ISR 6 months after CAS.

Characterization of nucleolar localization and exclusion signals in terminal deoxynucleotidyltransferase interacting factor 2/estrogen receptor α-binding protein.

Terminal deoxynucleotidyltransferase interacting factor 2/estrogen receptor α-binding protein (TdIF2/ERBP) is a multifunctional nucleolar protein. The nucleolar localization of TdIF2/ERBP is important for its functions because it promotes ribosomal RNA transcription. However, signal sequences that direct TdIF2/ERBP to the nucleolus are not well characterized. We examined the TdIF2/ERBP sequence using truncation and mutation analyses to determine whether the nucleosome binding and C-terminal domains of TdIF2/ERBP possess nucleolar localization signals (NoLSs). In these domains, four NoLSs that could direct the mCherry protein to the nucleolus were detected. In addition, a short stretch of hydrophobic residues (VLLVL) in the center of TdIF2/ERBP acted as a nucleolar exclusion signal, which reduced the nucleolar accumulation of mCherry-NoLS fusion proteins. These results would contribute to improving the prediction of NoLSs from protein sequences. The short, transferrable localization signals would be valuable tools for understanding the association between localization and functions of nucleolar proteins. Abbreviations TdIF2: terminal deoxynucleotidyltransferase interacting factor 2; ERBP: estrogen receptor α-binding protein; EGFP: enhanced green fluorescent protein; NLS: nuclear localization signal; NoLS: nucleolar localization signal; NoES: nucleolar exclusion signal; DAPI: 4',6-diamidino-2-phenylindole.

Contrast-enhanced transoral carotid ultrasonography for the evaluation of plaque protrusion after carotid artery stenting.

A 67 year-old man was admitted to our hospital because of mild left hemiparesis and was diagnosed with cerebral infarction caused by right internal carotid artery stenosis. He was treated with dual antiplatelet therapy and scheduled for carotid artery stenting 14 days after onset. The preoperative right carotid angiogram showed 60% stenosis by the NASCET criteria, with an ulcer. The postoperative angiogram suggested protrusion in the stent, which could not be seen on conventional carotid ultrasonography because of its high location. On transoral carotid ultrasonography, clear delineation of the lesion was not possible due to color blurs. Contrast-enhanced transoral carotid ultrasonography (CETOCU) clearly demonstrated the protrusion and delineated the lumen within the stent.

Long-Term Outcome of Balloon Angioplasty Without Stenting for Symptomatic Middle Cerebral Artery Stenosis.

PURPOSE: A recent randomized controlled trial demonstrated that aggressive medical management was superior to angioplasty with stenting for intracranial stenosis. The purpose of this study was to assess initial and long-term outcomes of balloon angioplasty without stenting for symptomatic middle cerebral artery (MCA) stenosis. METHODS: We retrospectively analyzed the clinical data of 72 patients (mean age, 58.9 years old) with 84 balloon angioplasties without stenting for high-grade (>70%) atherosclerotic stenosis of the main trunk of the MCA. All patients had experienced recurrent transient ischemic attack or minor stroke resistant to medical treatment. We assessed perioperative and long-term outcomes such as restenosis and the recurrence of strokes. The follow-up period was a median of 63 months (range, 6-171 months). RESULTS: Balloon angioplasty was successful in 97% of procedures. During the 30-day perioperative period, a total of 3 patients suffered from stroke (4.2%) without death. A total of 23 (31.9%) patients had restenosis at a time point that varied from 6 to 111 months. Diabetes mellitus (DM) was noted significantly more often in the restenosis group (39%) than in the nonrestenosis group (13%). Multivariate logistic regression analysis revealed DM (odds ratio, 4.84; 95% confidence interval, 1.196-19.62; P = .027) as an independent predictor of restenosis. Restenosis and DM were indicated as independent predictors of the recurrence of ischemic stroke and transient ischemic attack. CONCLUSIONS: Balloon angioplasty without stenting for symptomatic MCA stenosis can be performed with a high successful rate and a low risk of complications. Long-term outcome data suggest that this procedure reduces the risk of further strokes.

Effects of Pretreatment Cerebral Blood Volume and Time to Recanalization on Clinical Outcomes in Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Faster time to recanalization leads to better clinical outcomes in patients treated with endovascular thrombectomy. Whether the association between time to recanalization and clinical outcomes depends on cerebral blood volume (CBV) obtained from pretreatment computed tomography (CT) perfusion (CTP) imaging was investigated. METHODS: In consecutive patients with acute ischemic stroke who achieved recanalization by endovascular thrombectomy for intracranial internal carotid artery or M1 occlusion, the effects on clinical outcome of time to recanalization and the relative CBV value (rCBV) assessed by pretreatment CTP were evaluated. The patient population was divided into 2 groups according to rCBV: normal rCBV group (rCBV ≥ .9) and low rCBV group (rCBV < .9). In each group, time to recanalization was compared between the good and the poor clinical outcome groups. RESULTS: Sixty-four patients were eligible for this study. Twenty-six patients (40.6%) achieved good clinical outcomes. In the normal rCBV group, no association was found between clinical outcome and time to recanalization. In the low rCBV group, time to recanalization from CTP (101 minutes versus 136 minutes, P = .040) was significantly shorter in the good clinical outcome group. On binary logistic regression modeling, CTP to recanalization time (odds ratio 1.035 [1.004-1.067], P = .025) was an independent predictor of good clinical outcome only in the low rCBV group. CONCLUSIONS: The association between time to recanalization and clinical outcomes depends on rCBV obtained from pretreatment CTP. Time to recanalization is more important for good clinical outcomes in patients with low rCBV than in patients with normal rCBV.

Revisiting Current Golden Rules in Managing Acute Ischemic Stroke: Evaluation of New Strategies to Further Improve Treatment Selection and Outcome.

OBJECTIVE: Advanced stroke imaging has generated much excitement for the early diagnosis of acute ischemic stroke (AIS) and facilitation of intervention. However, its therapeutic impact has not matched its diagnostic utility; most notably, lacking significant contributions to recent major AIS clinical trials. It is time to reexamine the fundamental hypotheses from the enormous body of imaging research on which clinical practices are based and reassess the current standard clinical and imaging strategies, or golden rules, established over decades for AIS. In this article, we will investigate a possible new window of opportunity in managing AIS through a better understanding of the following: first, the potential limitations of the golden rules; second, the significance of imaging-based parenchymal hypoperfusion (i.e., lower-than-normal relative cerebral blood flow [rCBF] may not be indicative of ischemia); third, the other critical factors (e.g., rCBF, collateral circulation, variable therapeutic window, chronicity of occlusion) that reflect more individual ischemic injury for optimal treatment selection; and, fourth, the need for penumbra validation in successfully reperfused patients (not in untreated patients). CONCLUSION: Individual variations in the therapeutic window, ischemic injury (rCBF), and chronicity of vascular lesion development have not been comprehensively incorporated in the standard algorithms used to manage AIS. The current established imaging parameters have not been consistently validated with successfully reperfused patients and rCBF to quantitatively distinguish between oligemia and ischemia and between penumbra and infarct core within ischemic tissue. A novel paradigm incorporating rCBF values or indirectly incorporating relative rCBF values with higher statistically powered imaging studies to more reliably assess the severity of ischemic injury and differentiate reversibility from viability within the area of imaging-based parenchymal hypoperfusion may provide a more personalized approach to treatment, including no treatment of infarction core, to further enhance outcomes.

Prediction of cerebral hyperperfusion syndrome after carotid artery stenting by CT perfusion imaging with acetazolamide challenge.

INTRODUCTION: Cerebral hyperperfusion syndrome (HPS) is an uncommon but serious complication of carotid artery stenting (CAS). The purpose of this study was to investigate the efficacy of CT perfusion imaging (CTP) with acetazolamide challenge to identify patients at risk for HPS after CAS. METHODS: We retrospectively analyzed 113 patients who underwent CTP with rest and acetazolamide challenge before CAS. CTP maps were assessed for absolute and relative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and change of each parameter before and after acetazolamide challenge. Patients were divided into two groups according to the HPS after the CAS. Receiver-operating characteristic (ROC) curve analysis was performed to determine the most accurate CTP parameter for the prediction of HPS. RESULTS: Nine of 113 patients had HPS. There were significant differences for absolute and relative values of resting CBF (p = 0.001 and p = 0.026), resting MTT (p < 0.001 and p = 0.004), post-acetazolamide CBF (p < 0.001 and p = 0.001), post-acetazolamide MTT (p < 0.001 and p = 0.002), and % changes of CBF (p = 0.009) between the HPS and non-HPS groups. ROC curve analysis showed that the CTP parameters with the maximal area under the receiver-operating characteristic curve (AUC) for HPS was the absolute value of post-acetazolamide MTT (AUC 0.909) and the absolute value of resting MTT (AUC 0.896). CONCLUSION: Pretreatment CTP with acetazolamide challenge could identify patients at risk for HPS after CAS. Although the CTP parameter that most accurately identified patients at risk for HPS was the absolute value of post-acetazolamide MTT, resting MTT was sufficiently accurate.

Quality assurance monitoring of a citywide transportation protocol improves clinical indicators of intravenous tissue plasminogen activator therapy: a community-based, longitudinal study.

BACKGROUND: Stroke-bypass transportation to the stroke center by paramedics is important to maximize the efficiency of intravenous tissue plasminogen activator (iv-tPA) therapy. To improve access to stroke thrombolysis, a citywide protocol was launched on January 2007 in Kawasaki City (population 1.4 million) using the Maria Prehospital Stroke Scale (MPSS), and quality assurance monitoring has been performed every 6 months. The aim was to identify whether the citywide quality assurance monitoring improves the process and outcome of iv-tPA therapy. METHODS: All of the MPSS-based transportation data prospectively recorded by the Kawasaki City Fire Department and the associated clinical data in the 11 hospitals that accept stroke-bypass transfers were merged every 6 months for the quality assurance monitoring. Clinical indicators such as ambulance call-to-door time, onset-to-needle time, door-to-needle time, frequency of thrombolytic use, and outcome of thrombolytic therapy were analyzed. These clinical indicators were also compared between patients transferred on weekdays and on weekends. RESULTS: A total of 2049 patients was registered from April 2009 to March 2013. Their mean age was 70.4 ± 13.2 (range, 24-98) years, and 64.3% were male. Ambulance call-to-door time decreased gradually from 37.5 ± 12.5 minutes to 33.9 ± 11.7 minutes over 4 years (P = .000, analysis of variance with the post hoc Dunnett test). Onset-to-needle time and door-to-needle time were similar over the 4 years. Good outcome (modified Rankin Scale score <2) after iv-tPA therapy increased from 24.1% to 35.3% (P = .045, 2010 vs. 2012). No deleterious effect of weekend admission was observed based on these clinical indicators. CONCLUSIONS: A citywide MPSS-based transportation protocol significantly decreased the delay in the ambulance call-to-door time. The implementation of standardized cross-institutional quality assurance programs for acute stroke therapy may improve the process and outcome of iv-tPA therapy in the community.

Improvement of cerebral blood flow after balloon angioplasty and stenting for symptomatic middle cerebral artery stenosis.

OBJECTIVE: Although reports of endovascular treatment for intracranial arterial stenosis have been increasing recently, their efficacy remains to be elucidated. This study aimed to investigate the changes in cerebral hemodynamics of severe middle cerebral artery (MCA) stenosis patients by performing CT perfusion (CTP) after endovascular treatment. METHODS: Subjects were those who underwent balloon angioplasty and stenting for symptomatic MCA M1 stenosis refractory to medical therapy at our hospital between 2008 and 2022. We included 36 patients (mean age 63.69 ± 15.24 years, 20 males) who underwent CTP before and within three weeks after treatment. The CTP parameters such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) were calculated as ipsilateral values divided by contralateral value. RESULTS: Endovascular treatment consisted of 26 balloon angioplasty and 10 stenting procedures performed at an average of 1 month from onset. CTP was performed at an average of 5.5 days postoperatively. The mean overall stenosis rate decreased from 79.0% to 30.3%. In the balloon angioplasty group, it decreased from 77.6% to 35.3%, and in the stent group, it decreased from 82.7% to 17.5%. After treatment, rCBF and rMTT measured by CTP improved significantly (both p < 0.001), whereas there was no significant change in rCBV. The improvement rates of rCBF and rMTT were mild higher in the stent group, but not significantly so. CONCLUSION: Balloon angioplasty and stenting for symptomatic MCA improved cerebral hemodynamics, resulting in significantly increased rCBF and decreased rMTT.

Prediction of thrombolytic therapy after stroke-bypass transportation: the Maria Prehospital Stroke Scale score.

There is no prehospital stratification tool specifically for predicting thrombolytic therapy after transportation. We developed a new prehospital scale named the Maria Prehospital Stroke Scale (MPSS) by modifying the Cincinnati Prehospital Stroke Scale. Our objective is to evaluate its utility in a citywide bypass transportation protocol for intravenous (IV) tissue plasminogen activator (tPA). In the MPSS, facial droop, arm drift, and speech disturbance are tested by emergency medical technicians (EMTs). Facial droop is graded as normal (0) or abnormal (1), and the other 2 items are graded in 3 levels as normal (0), not severe (1), and severe (2). Thus, the total MPSS score ranges from 0 to 5. The predictive value of MPSS for thrombolytic therapy after bypass transportation was evaluated in 1057 patients. The MPSS scored by EMTs was significantly correlated with the National Institutes of Health Stroke Scale score in the emergency room (Spearman rho = .67, P = .000). The onset-to-door time was significantly longer with a low MPSS score (analysis of variance, F5,4.21 = .001). The rate of thrombolytic therapy was increased when the MPSS score increased from 0 to 5: 0%, 4.1%, 8.8%, 13.0%, 20.3%, and 31.5%, respectively. The areas under the receiver operating characteristic curve for the correct diagnosis of stroke and prediction of IV tPA therapy were calculated as .737 (95% confidence interval [CI]: .688-.786) and .689 (95% CI: .645-.732), respectively. Multivariate logistic regression analysis showed that the MPSS score and the detection-to-door time were independent predictors of tPA use after transportation. The MPSS is a novel prehospital stratification tool for the prediction of thrombolytic therapy after transportation.

Efficacy and safety of thrombectomy for acute ischaemic stroke in patients with pre-stroke mRS scores of 2-3: Real-world evaluation from an open-label, prospective, multicentre, observational study.

BACKGROUND: This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. METHODS: Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. RESULTS: After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. CONCLUSION: Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.

Ischemic stroke patients with low DWI ASPECTS scores require puncture to recanalization within 30 min for large vessel occlusion.

BACKGROUND: The clinical benefits of faster recanalization in acute large vessel occlusion are well recognized, but the optimal procedure time remains uncertain. The aim of this study was to identify patient characteristics that necessitate puncture-to-recanalization (P-R) time within 30 min to achieve favorable outcome. METHODS: We evaluated the patients from a prospective, multicenter, observational registry of acute ischemic stroke patients. The study included patients who underwent endovascular therapy for ICA or MCA M1 occlusion and achieved successful recanalization. Patients were categorized into subgroups based on pre-treatment characteristics and the frequency of favorable outcomes was compared between P-R time < 30 min and ≥ 30 min. Interaction terms were incorporated into the models to assess the correlation between each patient characteristic and P-R time. RESULTS: A total of 1053 patients were included in the study. Univariate analysis within each subgroup revealed a significant association between P-R < 30 min and favorable outcomes in patients with DWI ASPECTS ≤6, age > 85 and NIHSS ≥16. In the multivariable analysis, NIHSS, age, time from symptom recognition to puncture, and DWI ASPECTS were significant independent predictors of favorable outcomes. Notably, only DWI ASPECTS exhibited interaction terms with P-R < 30 min. The multivariable analysis indicated that P-R < 30 min was an independent predictor for favorable outcome in DWI ASPECTS ≤6 group, whereas not in DWI ≥7. CONCLUSIONS: P-R time < 30 min is predictive of favorable outcomes; however, the effect depends on DWI ASPECTS. Target P-R time < 30 min is appropriate for patients with DWI ASPECTS ≤6.