Mild Acute Ischemic Stroke Research Articles

Dual Antiplatelet Versus Alteplase for Early Neurologic Deterioration in Minor Stroke With Versus Without Large Vessel Occlusion: Prespecified Post Hoc Analysis of the ARAMIS Trial.

Dual antiplatelet therapy (DAPT) was noninferior to alteplase in minor nondisabling strokes in the ARAMIS trial (Antiplatelet Versus R-tPA for Acute Mild Ischemic Stroke); however, early neurological deterioration (END) associated with vessel stenosis may benefit from DAPT. We investigated whether the efficacy of DAPT was greater than alteplase in minor strokes with no large vessel occlusion (LVO). This study was a prespecified post hoc analysis of the ARAMIS trial and included patients with responsible vessel examination in the as-treated analysis set of the ARAMIS trial who were divided into LVO group and non-LVO group. In each group, patients were further classified into DAPT and intravenous alteplase treatments. Primary outcome was END at 24 hours defined as more than or equal to 4-point National Institutes of Health Stroke Scale score increase compared with baseline, and safety outcomes were symptomatic intracerebral hemorrhage and bleeding events during study. The primary analysis was estimated with a risk difference calculated by a generalized linear model including adjusted different baseline characteristics between treatments. Of 723 patients from the ARAMIS trial, 480 patients were included: 36 were categorized into LVO group and 444 into non-LVO group, of whom 20 patients had END. Compared with intravenous alteplase, a lower proportion of END was found after DAPT treatment in the non-LVO group (adjusted risk difference, -4.8% [95% CI, -6.9% to -2.6%]; P<0.001), but not in the LVO group (adjusted risk difference, 2.3% [95% CI, -17.6% to 22.3%]; P=0.82). The interaction was marginally significant between groups (P=0.06). In the non-LVO group, a lower proportion of bleeding events was found after DAPT treatment than intravenous alteplase (adjusted risk difference, -6.4% [95% CI, -8.9% to -3.9%]; P<0.001). Other safety outcomes were similar between the 2 treatments. Among minor nondisabling acute ischemic stroke without LVO, DAPT may be superior to intravenous alteplase regarding preventing END with a better safety profile. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03661411.

Efficacy and safety of P2Y12 inhibitors plus aspirin versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: a meta-analysis of randomized controlled trials

Abstract Background Patients with mild ischemic stroke or transient ischemic attack (TIA) have an increased risk of recurrent stroke within 90 days after the onset of the initial thrombotic event. Antiplatelet therapy plays an essential role in reducing the risk of stroke recurrence. However, data regarding the efficacy and safety of dual antiplatelet therapy (DAPT) with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy is limited. Purpose We performed an updated systematic review and meta-analysis to evaluate the effectiveness of DAPT versus aspirin monotherapy in patients with mild ischemic stroke or TIA in the light of new published evidence. Moreover, we investigated whether antiplatelet therapy started within 72 hours is effective in reducing recurrent stroke as compared to the conventionally used 24-hour time window for initiating DAPT. Methods PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT with aspirin plus clopidogrel to aspirin alone started within 24 hours or 72 hours in patients with acute mild ischemic stroke or high-risk TIA from inception to December 31st, 2023. A random-effects model was used to pool risk ratios (RRs) and 95% confidence intervals (CIs) for clinical endpoints. Results Five RCTs with 27,563 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 23% (RR: 0.77; 95% CI: 0.70-0.83; p&amp;lt;0.00001), ischemic stroke by 26% (RR: 0.74; 95% CI: 0.68-0.81; p&amp;lt;0.00001), and major adverse cardiovascular events (MACE) by 23% (RR: 0.77; 95% CI: 0.71-0.84; p&amp;lt;0.00001). However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 2.19; 95% CI: 1.38-3.48; p=0.0009) and hemorrhagic stroke (RR: 2.08; 95% CI: 1.13-3.82; p=0.02). No significant differences were observed for all-cause death (RR: 1.28; 95% CI: 0.95-1.71; p=0.10), cardiovascular death (RR: 1.38; 95% CI: 0.81-2.33; p=0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p=0.20). We performed sensitivity analysis based on the hazard ratio reported by RCTs which showed comparable results. Subgroup analysis based on treatment onset time (therapy initiation within 24 hours of thrombotic event vs therapy initiation within 72 hours of thrombotic event) showed that both strategies were effective in reducing the risk of recurrent stroke. Subgroup analysis based on the duration of DAPT (21 days vs. 90 days) showed that DAPT for 90 days was associated with an increased risk of moderate or severe bleeding as compared to therapy lasting for 21 days. Conclusion DAPT with P2Y12 inhibitors and aspirin reduces the risk of recurrent stroke and MACE but is associated with an increased risk of moderate or severe bleeding.

NIHSS Score Prognostic Effect of Mechanical Thrombectomy in Patients with Acute Mild Ischemic Stroke Complicated with Large Vessel Occlusion

NIHSS Score Prognostic Effect of Mechanical Thrombectomy in Patients with Acute Mild Ischemic Stroke Complicated with Large Vessel Occlusion

Association of perfusion variables with functional outcome in acute mild ischemic stroke patients or transient ischemic attack

ObjectiveSome patients with acute minor stroke or transient ischemic attack (TIA) are at risk for a poor prognosis. There are a limited number of studies that have investigated the functional prognosis of acute mild ischemic stroke or TIA based on imaging indicators. This study aims to explore the relationship between Perfusion Variables and poor prognosis in patients with mild ischemic stroke or TIA. Materials and methodsA retrospective analysis was conducted on a cohort of 344 patients with mild ischemic stroke or TIA, who were admitted and treated at the First Affiliated Hospital of Soochow University between January 2016 and March 2022. The criteria were National Institutes of Health Stroke Scale (NIHSS) scores of ≤5. Poor outcome was defined as a modified Rankin Scale (mRS) score of ≥2 points at 90 days. Multivariate logistic regression was performed to identify the risk factors associated with clinical outcomes. The receiver operating characteristic (ROC) analysis was used to explore the cutoff value of factors. ResultsFollowing a 3-month follow-up period, 49 (12.4 %) out of the 344 patients with mild stroke or TIA demonstrated a poor prognosis. Multivariable regression analysis identified mismatch volume as independent predictors of a poor 90-day prognosis. The ROC curve analysis indicated that a mismatch volume exceeding 16.5 ml was associated with a higher risk of unfavorable functional outcomes. ConclusionA mismatch volume of ≥16.5mL predicted poor functional outcome in mild stroke or TIA patients.

Neuraxial anesthesia for non-neurological emergency surgery in a patient with acute ischemic stroke: a case report

BackgroundThe recent guidelines recommend delaying elective non-neurological surgery after an index stroke, but there is a lack of consensus regarding emergency surgery in patients with a recent stroke. Impaired cerebral autoregulation and altered baroreceptor function elevate the risk of recurrent stroke in this group. Moreover, the impact of anesthesia type (general vs. regional) for non-cardiovascular, non-neurological surgery in patients with an index stroke remains inconclusive.Case presentationA 67-year-old male with an acute mild ischemic stroke underwent emergency surgery for an obstructed right-sided direct inguinal hernia under combined spinal-epidural anesthesia. Pre-operative assessment showed stable hemodynamics, and perioperative measures were taken to ensure stable blood pressure. Neuraxial anesthesia was employed successfully, and the patient remained hemodynamically stable throughout the surgery and postoperative period. No neurological deficits were observed post-surgery, and follow-up up to 3 months revealed no cognitive impairment or neurological decline.ConclusionsNeuraxial anesthesia can be considered for patients with acute mild strokes requiring urgent non-neurological surgery, provided they are hemodynamically stable and without coagulopathy. However, the choice of anesthesia should be individualized based on factors such as neurological status, stroke severity, coagulation, and existing disabilities. This case highlights the importance of a personalized approach to anesthesia in emergency surgery for stroke patients.

Outcome in acute ischemic stroke patients with large-vessel occlusion and initial mild deficits

BackgroundThe management of patients with initially mild acute ischemic stroke (AIS), defined by the National Institutes of Health Stroke Scale (NIHSS) scores 0–5, remains ambiguous despite advances in stroke treatment. The early identification of patients likely to deteriorate is critical in preventing lasting disability.AimsWe investigated the frequency and early predictors of poor functional outcomes in AIS patients with large-vessel occlusion (LVO) and initial mild deficits.MethodsWe performed a retrospective observational study of consecutive AIS patients admitted to a single comprehensive stroke center between 2018 and 2021. The inclusion criteria were a diagnosis of AIS, an arrival NIHSS score of 0–5, imaging-confirmed LVO, and arrival within 24 h of the last-known-well time. The primary outcome was the change in the discharge-modified Rankin Score (ΔmRS) from baseline, categorized as 0–1 (stable outcome) or &amp;gt;1 (poor outcome). Early neurological deterioration was defined as a mean NIHSS score increase of &amp;gt;1 in the first 24-h period. Univariate and multivariable regression analyses were performed. The mean daily NIHSS scores were compared between groups using an analysis of variance (ANOVA).ResultsOf 4,410 stroke admissions, 120 patients met the study inclusion criteria, with 71 (59.2%) patients having a ΔmRS of 0–1 and 49 (40.8%) patients having a ΔmRS of &amp;gt; 1. The mean arrival NIHSS score was similar between groups. However, the mean first-24-h NIHSS score was significantly higher in the poor outcome group vs. the stable outcome group (2.13 vs. 0.95, p &amp;lt; 0.001). A demographic-adjusted multivariable logistic regression revealed that a higher mean first-24-h NIHSS score was the sole early predictor of poor outcome (odds ratio [OR] of 1.65 and a 95% confidence interval [CI] of [1.18, 2.48]). The only association with early neurological deterioration was vertebral artery occlusion, with an OR of 0.35 and a 95% CI of [0.14, 0.81]. The trending mean daily NIHSS scores revealed that patients with poor outcomes deteriorate within 24 h, a significant difference from the stable group (p &amp;lt; 0.001).ConclusionPoor outcomes occurred in a significant proportion of LVO patients with initial mild deficits. The only association was early neurological deterioration. To prevent poor outcomes, rapid identification of any clinical deterioration should prompt consideration of thrombectomy.

Association of α-HBDH levels with the severity and recurrence after acute ischemic stroke

Objectiveα-HBDH serves as a biomarker of myocardial damage and is implicated in adverse outcomes across various critical illnesses. Our study aimed to assess the correlation between α-HBDH levels, and severity and recurrence of acute ischemic stroke (AIS).MethodsWe enrolled patients with mild-to-moderate AIS within 72 h of onset. Based on the baseline score of the National Institutes of Health Stroke Scale (bNIHSS) at registration, patients were categorized into mild (bNIHSS ≤ 4 points) and moderate AIS groups (4 < bNIHSS ≤ 10 points). Subsequently, based on the normal upper limit of α-HBDH, patients were divided into low-level α-HBDH (≤ 180 U/L) and high-level α-HBDH (> 180 U/L) groups. Multivariate logistic regression analysis and Cox proportional hazard regression analysis were employed to evaluate the relationship between α-HBDH levels and bNIHSS scores as well as the risk of recurrent AIS within 90 days.ResultsWe observed a significant association between higher baseline levels of α-HBDH and increased bNIHSS scores, indicating a more severe AIS (odds ratio = 24.449; 95% confidence interval [CI], 8.749–68.324; p < 0.01). Additionally, the risk of recurrent AIS within 90 days was 4.666 times higher in the high-level α-HBDH group compared to the low-level group (hazard ratio = 4.666; 95% CI, 2.481–8.777; p < 0.01).ConclusionsThe baseline level of α-HBDH is significantly correlated with the severity of AIS and the risk of recurrent AIS within 90 days.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia

Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. ClinicalTrials.gov Identifier: NCT03635749.

Sex Differences in the Dual Antiplatelet Therapy Versus Alteplase for Patients with Minor Nondisabling Acute Ischemic Stroke: A Secondary Analysis of the ARAMIS Study.

Sex is associated with clinical outcome in stroke. The present study aimed to determine the effect of sex on efficacy of dual antiplatelet (DAPT) versus alteplase in ischemic stroke based on Antiplatelet versus recombinant tissue plasminogen activator (R-tPA) for Acute Mild Ischemic Stroke (ARAMIS) trial. In this secondary analysis of the ARAMIS study, eligible patients aged 18 years or older with minor nondisabling stroke who received dual antiplatelet therapy or intravenous alteplase within 4.5 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used. Of the 719 patients who completed the study, 31% (223) were women, and 69% (496) were men. There were no significant sex differences in excellent functional outcome (unadjusted p = 0.304 for men and p = 0.993 for women; adjusted p = 0.376 for men and p = 0.918 for women) and favorable functional outcome (mRS score of 0-2; unadjusted p = 0.968 for men and p = 0.881 for women; adjusted p = 0.824 for men and p = 0.881 for women). But for the secondary outcomes, compared with alteplase, DAPT was associated with a significantly decreased proportion of early neurological deterioration within 24 h in men {unadjusted odds ratio [OR] = 0.440 [95% confidence interval (CI), 0.221-0.878]; p = 0.020; adjusted OR = 0.436 [95% CI, 0.216-0.877]; p = 0.020}, but not in women [unadjusted OR = 0.636 (95% CI, 0.175-2.319), p = 0.490; adjusted OR = 0.687 (95% CI, 0.181-2.609), p = 0.581]. For the safety outcomes, compared with the DAPT group, alteplase was associated with a significantly increased proportion of any bleeding events in men [unadjusted OR = 3.110 (95% CI, 1.103-8.770); p = 0.032], but not in women [unadjusted OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; adjusted OR = 5.394 (95% CI, 0.592-49.112), p = 0.135]. Sex did not influence the effect of dual antiplatelet therapy versus intravenous alteplase in minor nondisabling stroke, but more early neurological deterioration and bleeding events occurred in men who received alteplase.

Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.

Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores. We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset). Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance. Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.

Abstract 1158: Antiplatelet Therapy Versus Intravenous Thrombolysis For Mild Nondisabling Acute Ischemic Stroke: A Living Systematic Review And Meta-analysis

Background: Previous studies have shown contradictory results between early application of antiplatelet therapy and intravenous thrombolysis (IVT) for mild nondisabling (defined as NIHSS score of 0 to 5) acute ischemic stroke (AIS). Objective: To compare the benefits and risks of antiplatelet therapy and IVT in patients with mild nondisabling AIS. Methods: A systematic search of MEDLINE, Embase, and Cochrane Library was conducted from database inception until July 26, 2023, without language restriction. Randomized clinical trials (RCTs) or observational studies were selected. The primary outcomes were 90-day functional outcomes, measured by the modified Rankin Scale (mRS) score. The protocol has been registered before data collection (PROSPERO CRD42023447862). Results: Two RCTs and four observational studies with relatively low risk of bias that enrolled 3975 patients were analyzed (2454 in antiplatelet therapy and 1521 in IVT therapy). There were no significant differences between antiplatelet therapy and IVT in 90-day functional outcomes (mRS 0-1, odds ratio [OR], 1.08 [95% CI, 0.73-1.58]; mRS 0-2, OR, 1.04 [95% CI, 0.63-1.73]), death (OR, 0.64 [95% CI, 0.19-2.13]), and stroke recurrence (OR, 0.71 [95% CI, 0.28-1.79]). Antiplatelet therapy was associated with a reduced risk of sICH compared with IVT (OR, 0.20 [95% CI, 0.06-0.69]). Conclusions: Among patients with mild nondisabling AIS, compared with IVT, early application of antiplatelet therapy was not significantly associated with improved functional outcomes, reduced mortality, or stroke recurrence, but was significantly associated with a reduced risk of sICH. Regular updates will provide the best available evidence as new researches are published.

Observation of the Therapeutic Effect of Dual Antiplatelet Therapy with Aspirin and Clopidogrel on the Incidence, Characteristics, and Outcome in Acute Ischemic Stroke Patients with Cerebral Microbleeds at a Teaching Hospital, China.

Cerebral microbleeds (CMBs) are an important risk factor for stroke recurrence and prognosis. However, there is no consensus on the safety of antiplatelet therapy in patients with ischemic stroke and CMBs. This study aimed to observe the effects of dual antiplatelet therapy with aspirin and clopidogrel on bleeding conversion in patients with different degrees of CMBs. An observational retrospective study was conducted on 160 patients with acute mild ischemic stroke admitted to the Stroke Center, Affiliated Hospital of Beihua University between March 2021 and December 2022. Patients were divided into the CMBs and non-CMB groups. The CMB group was then divided into the low, medium and high-risk groups. In two groups, all patients were administered dual antiplatelet therapy (aspirin 100 mg and clopidogrel 75 mg orally once a day for 21 days according to the Chinese Stroke Guidelines of 2018), and no other anticoagulant or antiplatelet drugs were administered during the treatment period. Head CT, National Institutes of Health Stroke Scale(NIHSS) and modified Rankin Scale (mRS) score were re-checked, and the number of bleeding conversions was calculated at 21 days. Five patients in the CMB group had intracranial hemorrhage (5/116, 4.3%), while no intracranial hemorrhage was observed in the non-CMB group. There were no differences in the conversion rate of cerebral hemorrhage, NIHSS score, or mRS score between two groups after dual antiplatelet therapy (p>0.05). The conversion rate of cerebral hemorrhage in the high-risk group was higher than that in the non-CMB group (p<0.05), but the NIHSS and mRS score showed no difference between the high-risk and non-CMB groups (p>0.05). Dual antiplatelet therapy with aspirin and clopidogrel does not significantly increase the risk of bleeding transformation; however, it improves neurological recovery or long-term prognosis in patients with acute ischemic cerebral stroke complicated by low-risk and middle-risk CMBs.

Association between short-term glucose fluctuations and cognition in patients with acute ischemic stroke complicated by type 2 diabetes mellitus

ObjectivesGlucose fluctuations are more harmful than persistent hyperglycemia for chronic complications of diabetes. However, the relationship between cognition and glucose fluctuations in patients with acute ischemic stroke (AIS) complicated by type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association between short-term glucose fluctuations and cognition in patients with AIS complicated by T2DM. DesignA cohort study with a 2-year follow-up. Setting and participantsWe included 554 patients with mild AIS (mean age: 62 years; 170 females and 384 males). MeasurementsGlucose variability (GV) was evaluated using glycated hemoglobin (HbA1c), stress hyperglycemia (SHR), standard deviation of blood glucose (SDBG), mean postprandial blood glucose (MPBG), mean amplitude of glycemic excursion (MAGE), and time in range (TIR). We evaluated the relationship between GV, fasting blood glucose (FBG) and cognition during the acute phase using linear regression analysis. We evaluated the relationship between GV, FBG and the occurrence of post-stroke cognitive impairment (PSCI) using a logistic regression model. Mediation analyses were fitted to explore whether the relationships of HbA1c with cognition were mediated by cerebral small vessel disease (CSVD). ResultsA clear pattern of age-related GV was observed. Higher SHR in middle-aged participants; higher HbA1c, and lower TIR in older participants; and higher MAGE, MPBG, and SDBG across a broad age range (50–80 years) were associated with cognitive impairment in the acute phase of AIS. Higher SHR and SDBG together with lower TIR in middle-aged participants, higher HbA1c in older participants, and higher FBG, MPBG, and MAGE across a broad age range (50–80 years) were associated with the occurrence of PSCI. The association between HbA1c and cognition was partially mediated (proportion: 7–16%) by CSVD. ConclusionsShort-term glucose fluctuations are associated with cognition and a higher risk of PSCI in patients with AIS complicated by T2DM. CSVD might play an important role in the relationship between short-term glucose fluctuations and cognition.

Relationship between Cognitive Impairment and Serum ALP after Light Acute Ischemic Stroke in the Elderly

Objective: To analyze the association between cognitive impairment and serum ALP levels in elderly patients who developed light acute ischemic stroke. Methods: 100 cases of elderly patients with mild acute ischemic stroke admitted from January 2022 to June 2023 were selected as the study subjects, and were divided into two groups according to whether or not they developed cognitive impairment within six months; those who did not develop cognitive impairment were classified into the control group, with a total of 62 cases, while those who developed cognitive impairment were classified into the case group, with a total of 38 cases. The general data and serum ALP levels of the two groups were compared, and the correlation between serum ALP levels and MoCA scores was analyzed. Results: There was no significant difference between the general information of the two groups of patients in the control group and the case group (P &gt; 0.05). The serum ALP level of the patients in the case group was higher than that of the control group (P &lt; 0.05), and there was a negative correlation between the serum ALP level and the total score of MoCA, the visuospatial and executive scores, and the memory score (P &lt; 0.05). Conclusion: The serum ALP levels of elderly patients with cognitive impairment after mild acute ischemic stroke were higher than those of elderly patients without cognitive impairment after mild acute ischemic stroke, so the risk of cognitive impairment can be predicted in advance by detecting serum ALP levels.

Urinary Immunoglobulin G Is a Novel Biomarker for Atherosclerotic Burden in Mild Acute Ischemic Stroke Patients.

Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS). Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h). The exclusion criteria were (1) on-admission NIHSS scores ＞10, (2) a modified Rankin Scale (mRS) score ≥ 2 prior to stroke onset, (3) incomplete data (no urinalysis ≤ 3 days after admission or no mRS score at 90 days from stroke onset), and (4) an active malignancy. Patients at 90 days post-discharge were divided into those with favorable mRS scores of 0-1 and those with unfavorable mRS scores of 2-6. Clinical backgrounds were compared for (1) patients with positive and negative urinary IgG results, and (2) patients with favorable and unfavorable outcomes. Of our study's 210 patients (164=male, median age=68, median eGFR=53.2 ml/min/1.73 m2), 30 (14%) presented with positive urinary IgG, which was associated with cardiovascular risk factors. Higher BNP, higher D-dimer, lower eGFR, and higher CAVI were associated with higher positive urinary IgG. The favorable group, comprising 155 (74%) patients, had higher negative urinary IgG than the unfavorable group (89% vs 76%, P=0.026). No statistical difference emerged regarding microalbuminuria (29% vs 29%, P=1.000). In MAIS, urinary IgG was associated with both the presence of atherosclerosis and an unfavorable outcome at 90 days after stroke onset.

Dual antiplatelet therapy after intravenous thrombolysis for patients with minor ischemic stroke：A meta-analysis

ObjectiveIntravenous thrombolysis (IVT) has been shown to effectively decrease both the disability rate and mortality associated with acute ischemic stroke, however, there is also a risk of vascular re-occlusion. Antiplatelet therapy can mitigate this risk. Nevertheless, there are no relevant guidelines recommending whether the administration of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel can be performed following thrombolysis. The aim of this study was to conduct a meta-analysis utilizing multiple studies in order to assess the effectiveness and safety of DAPT after IVT in cases of acute mild ischemic stroke (AMIS). MethodsA comprehensive search on English literature published was performed on databases including PubMed, Embase, Web of Science, and Cochrane up until September 1, 2023. All cases were ischemic stroke patients who underwent IVT within a 4.5-hour timeframe and had a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 (or 3) upon admission. The primary efficacy endpoint is the 90-day Modified Rankin Scale (mRS) Score (MRS score 0–1), while the primary safety endpoint encompassed the occurrence of symptomatic intracranial hemorrhage (SICH) and 90-day mortality. The study's secondary objective is the recurrence of any type of stroke (hemorrhagic and ischemic) within a 90-day period. The included studies underwent an evaluation of bias risk using the Newcastle Ottawa scale. Risk ratios (RRs) and CIs were calculated using a random effects model, and the findings and heterogeneity among the included studies were visually presented on a forest plot. (There was a protocol registration (PROSPERO):). ResultsOut of the 1081 studies that were obtained, only 3 met the criteria and were included in the meta-analysis (657 patients in total). The findings indicate that, there was a significant difference in the mRS of 0–1 between single antiplatelet therapy (SAPT) with only aspirin or clopidogrel and DAPT with aspirin and clopidogrel ((RR,1.11[95%CI,0.99–1.24];P=0.07;I2=55%), and no significant difference in stroke recurrence after 90 days or 1 year ((RR,0.94[95%CI,0.41–2.16];P=0.89;I2=30%); Regarding safety evaluation, the results showed no significant difference in the SICH (RR,0.65[95%CI,0.11–3.97];P=0.64;I2=0%) and the incidence of mortality (RR,0.97[95%CI,0.19–4.96];P=0.97;I2=0%) between the two groups. ConclusionsFor patients with acute mild ischemic stroke (AMIS), in conjunction with DAPT after IVT can improve the 90-day prognosis, without increasing the risk of intracranial hemorrhage and 90-day mortality. However, it cannot reduce the risk of stroke recurrence.

Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial.

Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset. Prourokinase in mild ischemic stroke is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Patients who had an acute ischemic stroke within 4.5 hours from symptom onset and with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 will be recruited. Patients will be randomly assigned (1:1) to receive intravenous rhPro-UK (35 mg) or standard medical treatment. The follow-up duration will be 90 days. The calculated sample size is 1446. Primary efficacy outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score ≤ 1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, mRS score ≤ 2 at 90 days, early neurological improvement at 24 hours (a decrease of NIHSS score ≥ 4 points compared with baseline or NIHSS score ≤ 1 point), Barthel index of 75-100 points at 90 days, quality of life at 90 days, and activities of daily living at 90 days. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours, mortality at 90 days, moderate and severe systematic bleeding at 90 days, and adverse events/serious adverse events within 90 days. This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset. NCT05507645.

Intravenous Thrombolysis is Effective in Mild Stroke Patients with an Admission NIHSS Score of 3 to 5.

The role of intravenous thrombolysis in patients with acute mild ischemic stroke remains highly controversial. Therefore, this study aims to analyze the efficacy and safety of intravenous thrombolysis in patients with mild ischemic stroke based on admission National Institutes of Health Stroke Scale (NIHSS) score. The present study enrolled 507 patients with acute mild ischemic stroke admitted within 4.5 hours of symptom onset with an admission NIHSS score of 0 to 5. Patients were assigned to two groups based on admission NIHSS scores of 0 to 2 and 3 to 5, and subsequent analyses compared functional outcomes between thrombotic and non-thrombotic patients within these groups. The primary outcome was a modified Rankin score (mRS) of 0 or 1 at 90 days, representing functional independence. The safety outcomes were symptomatic intracranial hemorrhage (sICH), early neurological deterioration (END), and the rate of stroke recurrence within 90 days. Among the 267 patients with NIHSS scores of 0 to 2, 112 (41.9%) patients received intravenous thrombolysis. Overall, thrombolysis administration did not significantly improve the patient's functional prognoses at 90 days (adjusted OR=1.046, 95%CI=0.587-1.863, p = 0.878). However, there was a marked increase in the risk of sICH (p = 0.030). Of the 240 patients with NIHSS scores of 3 to 5, 155 (64.6%) patients received intravenous thrombolysis, resulting in a significant improvement in 90-day functional prognosis (adjusted OR=3.284, 95%CI=1.876- 5.749, p < 0.001) compared to those that did not receive thrombolysis intervention. Importantly, there was no significant increase in sICH incidence (adjusted OR=2.770, 95%CI=0.313-24.51, p = 0.360). There were no statistically significant differences in END or the rate of stroke recurrence within 90 days between thrombotic and non-thrombotic groups. Intravenous thrombolysis is safe and effective in patients with baseline NIHSS scores of 3 to 5. In contrast, it did not improve 90-day functional outcomes in patients with NIHSS scores of 0 to 2 and instead increased the risk of sICH.

The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): Protocol for a Pragmatic, Stepped Wedge, Cluster Randomized Controlled Trial

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications. Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events. Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

Prognostic significance of serum globulin in patients with acute ischemic stroke

Background and PurposeWe investigated the association between serum globulin levels upon hospital admission and in-hospital short-term outcomes in acute ischemic stroke (AIS) patients. MethodsA total of 3,127 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into 4 groups according to their level of admission serum globulin: Q1 (<23.5 g/L), Q2 (23.5-26.4 g/L), Q3 (26.4-29.9 g/L), and Q4 (≥29.9 g/L). Logistic regression models were used to estimate the effect of serum globulin on the short-term outcomes, including all cause in-hospital mortality, poor outcome upon discharge (modified Rankin Scale score ≥3) and in-hospital pneumonia in AIS patients. ResultsThe median National Institutes of Health Stroke Scale (NIHSS) score was 4.0 (IQR, 2.0-7.0). The risk of in-hospital mortality was significantly higher in patients with highest serum globulin level (Q4) compared to those with lowest (Q1) (adjusted odds ratio [OR] 2.30; 95% confidence interval [CI], 1.12-4.70; P-trend =0.026). The highest serum globulin level (Q4) was associated with a 1.32-fold and 1.62-fold increase in the risk of poor outcome upon discharge (adjusted OR 1.32; 95% CI, 1.00-1.75; P-trend = 0.070) and in-hospital pneumonia (adjusted OR 1.62; 95% CI, 1.18-2.23; P-trend = 0.001) in comparison to Q1 after adjustment for potential covariates. ConclusionsA high level of serum globulin upon hospital admission was independently associated with all cause in-hospital mortality, poor outcome upon discharge and in-hospital pneumonia in relative mild AIS patients.