Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Short-Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State.

OBJECTIVE: It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. METHODS: Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. RESULTS: We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. INTERPRETATION: We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Effects of Dose Titration on Dipyridamole-Induced Headache: A Randomized, Double-Blind Clinical Trial.

PURPOSE: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. RESULTS: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different. CONCLUSION: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache.

Interpretation of fluid-attenuated inversion recovery vascular hyperintensity in stroke.

Fluid-attenuation inversion recovery (FLAIR) vascular hyperintensity (FVH) is a common presentation on brain magnetic resonance images of patients with acute ischemic stroke. This sign is known as a sluggish collateral flow. Although FVH represents the large ischemic penumbra and collateral circulation, the clinical significance of FVH has not been established. Varying protocols for FLAIR, treatment differences, and heterogeneity of endpoints across studies have complicated the interpretation of FVH in patients with acute stroke. In this review article, we describe the mechanism of FVH, as well as its association with functional outcome, perfusion-weighted images, and large artery stenosis. In addition, we review the technological variables that affect FVH and discuss the future perspectives.

Association Between the Risk for Cardiovascular Events and Antiviral Treatment for Herpes Zoster.

BACKGROUND: Cardiovascular risk increases following herpes zoster. We investigated whether treatment with antiviral agents, steroids, and common cardiovascular medications was associated with the risk of postherpetic cardiovascular events. METHODS: This was a nationwide population-based, retrospective, cohort study using the National Health Insurance Service health claims data in Korea. We included patients with a first-ever diagnosis of herpes zoster in 2003-2014 and no prior cardiovascular event. The primary outcome was the occurrence of composites of myocardial infarction (International Statistical Classification of Diseases, Tenth Revision, code I21) and stroke (codes I60-I63) since the herpes zoster. We analyzed the exposure (intravenous or oral administration) to antiviral agents, steroids, antithrombotics, and statins within ±7 days from the index date of herpes zoster diagnosis. Follow-up was performed until occurrence of the primary outcome, death, or 31 December 2015, whichever came first. RESULTS: Of 84 993 patients with herpes zoster, the proportions of patients who received the treatment with antiviral agents, steroids, antithrombotics, and statins were 90.5%, 48.0%, 9.1%, and 7.9%, respectively. During the mean (standard deviation) follow-up period of 5.4 (3.1) years, 1523 patients experienced the primary outcome. Multivariate Cox regression analysis demonstrated that treatment with antiviral agents (adjusted hazard ratio, 0.82; 95% confidence interval, .71-.95) and statins (0.71; .59-.85) were significantly associated with the lower risk of primary outcome. Use of antithrombotics and steroids were not associated with the risk. CONCLUSIONS: After herpes zoster, treatment with antiviral agents was significantly associated with lower risk of cardiovascular events. We need more information on the cardiovascular protective role of herpes zoster treatments.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Clinical impact of estradiol/testosterone ratio in patients with acute ischemic stroke.

BACKGROUND: Sex hormones may be associated with a higher incidence of ischemic stroke or stroke-related events. In observational studies, lower testosterone concentrations are associated with infirmity, vascular disease, and adverse cardiovascular risk factors. Currently, female sexual hormones are considered neuroprotective agents. The purpose of this study was to assess the role of sex hormones and the ratio of estradiol/testosterone (E/T) in patients with acute ischemic stroke (AIS). METHODS: Between January 2011 and December 2016, 146 male patients with AIS and 152 age- and sex-matched control subjects were included in this study. Sex hormones, including estradiol, progesterone, and testosterone, were evaluated in the AIS patient and control groups. We analyzed the clinical and physiological levels of sex hormones and hormone ratios in these patients. RESULTS: The E/T ratio was significantly elevated among patients in the stroke group compared to those in the control group (P = 0.001). Categorization of data into tertiles revealed that patients with the highest E/T ratio were more likely to have AIS [odds ratio (OR) 3.084; 95% Confidence interval (CI): 1.616-5.886; P < 0.001) compared with those in the first tertile. The E/T ratio was also an independent unfavorable outcome predictor with an adjusted OR of 1.167 (95% CI: 1.053-1.294; P = 0.003). CONCLUSIONS: These findings support the hypothesis that increased estradiol and reduced testosterone levels are associated with AIS in men.

Initial Stroke Severity in Patients With Atrial Fibrillation According to Antithrombotic Therapy Before Ischemic Stroke.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the leading cause of ischemic stroke. Preventive antithrombotic use, especially for anticoagulation, reduces the incidence of ischemic stroke in patients with AF. Using data from the nationwide multicenter stroke registry, we investigated the trends of preceding antithrombotic medication use in patients with acute ischemic stroke (AIS) with AF and its association with initial stroke severity and in-hospital outcomes. METHODS: This study included 6786 patients with AIS with known AF before stroke admission across 39 hospitals between June 2008 and December 2018. We collected the data on antithrombotic medication use (no antithrombotic/antiplatelet/anticoagulant) preceding AIS. Initial stroke severity was measured using the National Institutes of Health Stroke Scale, and in-hospital outcome was determined by modified Rankin Scale score at discharge. RESULTS: During the study period, anticoagulant use continued to increase. However, nearly one-third of patients with AIS with known AF did not receive antithrombotics before stroke. Initial National Institutes of Health Stroke Scale scores varied according to preceding antithrombotic therapy (P<0.001). It was higher in patients who did not receive antithrombotics than in those who received antiplatelets or anticoagulants (median National Institutes of Health Stroke Scale score: 8 versus 7 and 8 versus 6, respectively). Favorable outcome at discharge (modified Rankin Scale score, 0-2) was more prevalent in patients who received antiplatelets or anticoagulants (P<0.001). Use of antiplatelets (odds ratio, 1.23 [95% CI, 1.09-1.38]) and anticoagulants (odds ratio, 1.31 [95% CI, 1.15-1.50]) was associated with a mild initial neurological deficit (National Institutes of Health Stroke Scale score ≤5) in patients with AIS with AF. CONCLUSIONS: Throughout the study period, the proportion of patients taking anticoagulants increased among patients with AIS with known AF. However, a large portion of AF patients still did not receive antithrombotics before AIS. Furthermore, prehospitalization use of anticoagulants was associated with a significantly higher likelihood of a mild initial neurological deficit and favorable outcome at discharge.

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach.

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = -0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

Characteristics of Intracranial Aneurysms According to Levels of Coronary Artery Calcium.

Background and Purpose- Several vascular risk factors are known to be associated with the occurrence of intracranial aneurysms (IAs). Coronary artery calcium (CAC), which reflects the atherosclerotic burden of the coronary arteries, is a known predictor of cardiovascular events and stroke. We investigated the relationship between IA and CAC. Methods- We retrospectively enrolled Korean subjects at a single university hospital who had both brain magnetic resonance angiography and cardiac computed tomography as part of health examinations from January 2010 to July 2017. Subjects were categorized into 4 groups according to CAC score as assessed by cardiac computed tomography: zero (0), low (1-99), intermediate (100-399), or high (≥400). Then, the prevalence of IA in each CAC score group was assessed. We also performed subgroup analysis by age, sex, and location of IA. Results- A total of 4934 subjects (mean age, 54.1±9.8 years; %women, 42.2%) were included for analysis. IAs were detected in 258 subjects (5.23%). The prevalence of IA significantly increased as the CAC score increased (4.8%, 5.4%, 6.4%, and 11.1%, respectively; P for trend, 0.004). In subjects over the age of 50 years, this correlation was more prominent in women than in men (7.1% versus 3.7%, 8.8% versus 4.4%, 8.6% versus 6.3%, and 21.1% versus 10.0%, respectively). Subgroup analysis for the aneurysm location showed that nonbifurcation aneurysm was associated with a high CAC score but bifurcation aneurysm was not. Multivariate logistic regression showed high CAC score was an independent risk factor for the presence of IA compared with zero CAC score (adjusted odds ratio, 2.16; 95% CI, 1.18-3.95). Conclusions- A high CAC score was associated with the presence of IA. This relationship was more prominent in females and nonbifurcation aneurysms.

Significance of hyperintense arteries on Gd-enhanced 3D T1W black-blood imaging in acute stroke.

OBJECTIVES: To elucidate the pathogenesis of hyperintense arteries on Gd-enhanced 3D T1W BB FSE and their clinical significance in acute middle cerebral artery (MCA) stroke. METHODS: We retrospectively reviewed 20 patients with MCA infarction. We measured the contrast-to-noise ratio between hyperintense artery and adjacent grey matter on T2-FLAIR and Gd-enhanced 3D T1W BB FSE and compared them by using Student's t test. The agreement of positive hyperintense artery between T2 FLAIR and Gd-enhanced 3D T1WI BB FSE was estimated with intraclass correlation coefficient. Our cohort was dichotomised into two groups depending on hyperintense artery scores, and clinical data were compared between two groups by using Student's t test and chi-square test. RESULTS: The contrast between hyperintense artery and grey matter on Gd-enhanced 3D T1W BB FSE was significantly higher than that on T2-FLAIR (2.27 ± 1.65 versus 0.94 ± 0.86, p = 0.01). Overall, agreement of hyperintense arteries on T2-FLAIR and Gd-enhanced 3D T1W BB FSE was excellent (ρ = 0.76, p < 0.01). Patients with higher hyperintense artery scores had higher perfusion deficits that those with lower hyperintense artery scores (196.7 ± 41.4 vs 100.1 ± 130.1, p = 0.03). CONCLUSION: Hyperintense arteries on Gd-enhanced 3D T1W BB FSE in acute MCA stroke may be associated with slow collateral flows. Their territories corresponded to those of FLAIR, but had a better contrast. The patients with hyperintense arteries in a wider territory showed larger perfusion deficit than those with hyperintense arteries in a narrower territory. KEY POINTS: • Hyperintense arteries on Gd-enhanced 3D T1W BB FSE are slow collateral flows. • Hyperintense arteries on Gd-enhanced 3D T1W BB FSE are well matched with FLAIR hyperintense vessels. • Hyperintense arteries are associated with perfusion deficit in stroke patients.

Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke.

Background and Purpose- We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods- This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results- In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm3; P<0.001). In the multivariate analysis, thrombus volume was independently associated with nonrecanalization ( P<0.001). The cutoff for predicting nonrecanalization was calculated as 200 mm3. In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions- Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Rescue Stenting for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Multicenter Experience.

BACKGROUND AND PURPOSE: Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients. METHODS: This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015. We identified the patients who underwent MT but failed to recanalize intracranial internal carotid artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2 groups: patients with RS and without RS after MT failure. Clinical and laboratory findings and outcomes were compared between the 2 groups. It was tested whether RS is associated with functional outcome. RESULTS: MT failed in 148 (25.0%) of the 591 patients with internal carotid artery or middle cerebral artery M1 occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left without further treatment (no stenting group). Recanalization was successful in 64.6% (31 of 48 patients) of RS group. Compared with no stenting group, RS group showed a significantly higher rate of good outcome (modified Rankin Scale score, 0-2; 39.6% versus 22.0%; P=0.031) without increasing symptomatic intracranial hemorrhage (16.7% versus 20.0%; P=0.823) or mortality (12.5% versus 19.0%; P=0.360). Of the RS group, patients who had recanalization success had 54.8% of good outcome, which is comparable to that (55.4%) of recanalization success group with MT. RS remained independently associated with good outcome after adjustment of other factors (odds ratio, 3.393; 95% confidence interval, 1.192-9.655; P=0.022). Follow-up vascular imaging was available in the 23 (74.2%) of 31 patients with recanalization success with RS. The stent was patent in 20 (87.0%) of the 23 patients. Glycoprotein IIb/IIIa inhibitor was significantly associated with stent patency but not with symptomatic intracranial hemorrhage. CONCLUSIONS: RS was independently associated with good outcomes without increasing symptomatic intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal carotid artery or middle cerebral artery M1 occlusion.

Number of Stent Retriever Passes Associated With Futile Recanalization in Acute Stroke.

Background and Purpose- Stent retriever (SR) thrombectomy has become the mainstay of treatment of acute intracranial large artery occlusion. However, it is still not much known about the optimal limit of SR attempts for favorable outcome. We evaluated whether a specific number of SR passes for futile recanalization can be determined. Methods- Patients who were treated with a SR as the first endovascular modality for their intracranial large artery occlusion in anterior circulation were retrospectively reviewed. The recanalization rate for each SR pass was calculated. The association between the number of SR passes and a patient's functional outcome was analyzed. Results- A total of 467 patients were included. Successful recanalization by SR alone was achieved in 82.2% of patients. Recanalization rates got sequentially lower as the number of passes increased, and the recanalization rate achievable by ≥5 passes of the SR was 5.5%. In a multivariable analysis, functional outcomes were more favorable in patients with 1 to 4 passes of the SR than in patients without recanalization (odds ratio [OR] was 8.06 for 1 pass; OR 7.78 for 2 passes; OR 6.10 for 3 passes; OR 6.57 for 4 passes; all P<0.001). However, the functional outcomes of patients with ≥5 passes were not significantly more favorable than found among patients without recanalization (OR 1.70 with 95% CI, 0.42-6.90 for 5 passes, P=0.455; OR 0.33 with 0.02-5.70, P=0.445 for ≥6 passes). Conclusions- The likelihood of successful recanalization got sequentially lower as the number of SR passes increased. Five or more passes of the SR became futile in terms of the recanalization rate and functional outcomes.

Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea.

BACKGROUND: Increasing evidence suggest that statin therapy has a diabetogenic effect. Individual types of statin may have a different effect on glucose metabolism. Using the repeated nationwide population-based health screening data in Korea, we investigated the longitudinal changes in fasting glucose level of non-diabetic individuals by use of statins. METHODS: From the National Health Screening Cohort, we included 379,865 non-diabetic individuals who had ≥ 2 health screening examinations with fasting blood glucose level measured in 2002-2013. Using the prescription records of statins in the database, we calculated the proportion of days covered (PDC) and average number of defined daily doses per day (anDDD) by statins. We constructed multivariate linear mixed models to evaluate the effects of statins on the changes in fasting glucose (Δglu). RESULTS: High PDC by statins had a significant positive effect on Δglu (coefficient for PDC 0.093 mmol/L, standard error 0.007, p < 0.001). anDDD by statins was also positively associated with Δglu (coefficient for anDDD 0.119 mmol/L, standard error 0.009, p < 0.001). Unlike statins, the PDC by fibrate and ezetimibe were not significantly associated with Δglu. There was no significant interaction effect on Δglu between time interval and statin. Considering individual types of statins, use of atorvastatin, rosuvastatin, pitavastatin, and simvastatin were significantly associated with increase of Δglu. Pravastatin, lovastatin, and fluvastatin were also positively associated with Δglu, but were not statistically significant. CONCLUSIONS: More adherent and intensive use of statins was significantly associated with an increase in fasting glucose of non-diabetic individuals. In subgroup analysis of individual statins, use of atorvastatin, rosuvastatin, pitavastatin and simvastatin had significant association with increase in fasting glucose. Pravastatin, lovastatin, and fluvastatin had non-significant trend toward an increased fasting glucose. Our findings suggest the medication class effect of statins inducing hyperglycemia.

Can FLAIR hyperintense vessel (FHV) signs be influenced by varying MR parameters and flow velocities? A flow phantom analysis.

BACKGROUND: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) have been used to assess leptomeningeal collateral flow in acute ischemic stroke. However, prior FHVs studies showed inconsistent results, which may be ascribable to different magnetic resonance (MR) parameters used. PURPOSE: To evaluate whether FHVs could be influenced by varying MR parameters and flow velocities, using a flow phantom. MATERIAL AND METHODS: A total of 512 sets of FLAIRs were performed with varying parameters and flow velocities, using a flow phantom. Flow phantom was manufactured with 3.5% agarose solution, an 8-mm inner diameter silicone tube and non-pulsatile pump. Varying MR parameters were repetition time (TR)/inversion time (TI), echo time (TE), flip angle (FA) of refocusing pulse, and periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER). The signal intensity of flow were measured and regarded as the degree of FHVs. Simple and multiple linear regression analyses were applied to evaluate the association between the degree of FHVs and varying MR parameters as well as flow velocities. RESULTS: On univariate analysis, PROPELLER technique (R(2 )= 0.448) demonstrated strongest correlation with the degree of FHV, followed by flow velocities (R(2 )= 0.204), FA (R(2 )= 0.126), and TE (R(2 )= 0.031), whereas TR/TI showed no significant correlations. On multivariate analysis, TE, FA, PROPELLER technique, and flow velocities were independent factors influencing the degree of FHVs (<0.001). CONCLUSION: Flow velocities, FA of refocusing pulse, TE, and PROPELLER technique significantly affected the degree of FHVs. Optimized MR parameters should be used consistently in future studies, which may provide more reliable results.

Left Atrial Volume Index Predicts Recurrence of Stroke in Patients with Nonsustained Atrial Tachycardia.

BACKGROUND: Nonsustained atrial tachycardia (NSAT) is known to appear more frequently in patients with paroxysmal atrial fibrillation (AF). Enlarged left atrium (LA) is considered to be an independent risk factor for newly diagnosed AF. METHODS: We investigated the risk factors for predicting the stroke recurrence in NSAT patients. In total, 252 patients (114 women, mean 70 ± 11 years) with acute ischemic stroke and documented NSAT in 24-hour Holter monitoring were enrolled and followed. All patients underwent echo-Doppler evaluations. RESULTS: During a mean follow-up period of 35 ± 31 months, the stroke recurrence rate was 11.1% (28 of 252). The patients with recurrence (n = 28) had higher left atrium volume index (LAVI, P < .001) and higher E/e' (P = .028) compared with those without recurrence (n = 224). On the Kaplan-Meier survival analysis, stroke recurrence rate was significantly higher in patients with enlarged LA (LAVI >28 mm3/m2; P < .001 by the log-rank test), and it remained significant in multivariate analysis (hazard ratio, 1.154; 95% confidence interval [CI], 1.099-1.212, P < .001). CONCLUSIONS: In patients with acute ischemic stroke and NSAT, enlarged LA predicts an increased risk of stroke recurrence. This study supports the necessity of prolonged rhythm monitoring in stroke patients with NSAT and enlarged LA to detect undiagnosed AF and consequently considering anticoagulation therapy.

Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

BACKGROUND: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. METHODS: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. RESULTS: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm(3)). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤ 4.9 cm(3) (p = 0.002). Significant treatment effects were observed in the cilostazol group. CONCLUSIONS: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.