International Journal of Stroke最新文献

Background: Observational studies have shown that selective serotonin reuptake inhibitors are associated with an increased risk of bone fractures, but the association can be confounded by indication and other sources of systematic bias that can be minimized in randomized controlled trials (RCTs).

Aim: Our aim was to report the rate, site, context, and predictors of fractures after stroke, and whether the fractures modified the effect of fluoxetine on modified Rankin scale (mRS) at 6 months in an individual patient data meta-analysis of 5907 patients enrolled in three RCTs of fluoxetine (20 mg for 6 months) for stroke recovery.

Methods: We classified fractures by treatment allocation, site (and thus likelihood of osteoporosis), and context, then performed multivariable analyses to explore the independent predictors of fractures. We explored whether the trend toward a poorer mRS at 6 months was explained by a fracture excess. Risk of bias was assessed using GRADE.

Results: Among 5907 patients randomized at a mean of 6.6 days (SD 3.6) post-stroke onset and followed for 6 months, the number of fractures at 6 months was 93 (3.15%) in the fluoxetine group versus 41 (1.39%) in the control group (difference 1.76, 95% CI 0.10-2.51). However, 128 patients with fractures were suitable for further analyses. Of these, 102 (80%) were in sites typically affected by osteoporosis; 115 (90%) were associated with falls and 1 (1%) with a seizure. Independent fracture risk factors were female sex (hazard ratio (HR) 1.96; 95% CI 1.37-2.81, p = 0.0002), age > 70 years (HR 2.30, 95% CI 1.52-3.49, p < 0.001), previous fractures (HR 0.63 for no previous fractures, 95% CI 0.42-0.94, p = 0.0227), and randomized treatment (fluoxetine) (HR 2.39; 95% CI 1.64-3.49, p < 0.001). The common odds ratio for the effect of fluoxetine on mRS at 6 months was unchanged after excluding fracture patients. Risk of bias was high for imprecision.

Conclusion: Fractures were more common in the fluoxetine group but the absolute risk of fractures was small and risk estimates were imprecise. Most fractures occurred with a fall, and in osteoporotic locations. Fractures did not modify the effect of fluoxetine on functional outcome.

Background: Acetylsalicylic acid (aspirin) is known to increase the risk of bleeding throughout the body. However, there is also evidence to suggest that acetylsalicylic acid may have a protective role in the formation and rupture of intracranial aneurysms. Previous studies investigating acetylsalicylic acid and subarachnoid hemorrhage (SAH) have so far provided conflicting results.

Aims: The aim of this study was to analyze the Nurse's Health Study (NHS) using serial assessments to evaluate differences in rates of SAH in those participants taking acetylsalicylic acid and those not taking acetylsalicylic acid while considering dose, frequency, and duration as well as different types of SAH.

Methods: The NHS is a prospective population-based cohort study of female nurses. Information on acetylsalicylic acid was first reported in 1980 until 2016 and included acetylsalicylic acid use, dose, frequency, and duration. All stroke cases were classified by physicians. Cox proportional-hazards regression models were used to estimate the hazard ratio (HR) associated with acetylsalicylic acid use.

Results: A total of 117,648 NHS participants were eligible for analysis with 357 cases of SAH observed over 4,091,239 years of follow-up. There was no association between acetylsalicylic acid use and SAH (HR = 1.02; 95% confidence interval (CI) = [0.82, 1.28], p = 0.85), aneurysmal SAH (1.04; 95% CI = [0.78, 1.39], p = 0.78), or idiopathic SAH (HR = 0.94; 95% CI = [0.65, 1.34], p = 0.72). The number of acetylsalicylic acid tablets per week was associated with SAH (HR = 1.03; 95% CI = [1.00, 1.06], p = 0.02), specifically fatal SAH (HR = 1.04 [1.00, 1.08], p = 0.03). There was no association between frequency and SAH (HR = 1.06; 95% CI = [0.99, 1.13], p = 0.07).

Conclusion: There was no evidence to support a protective association between acetylsalicylic acid and either SAH or aneurysmal SAH in female participants. In fact, there was some evidence to suggest increased SAH risk with increased acetylsalicylic acid dose in some but not all analyses.

Data access statement: Data are available by request from the Brigham and Women's Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health.

Background: In patients with an acute ischemic stroke, the penumbra is defined as ischemic tissue that remains salvageable when reperfusion occurs. However, the expected clinical recovery congruent with penumbral salvage is not always observed.

Aims: We aimed to determine whether the magnetic resonance imaging (MRI)-defined penumbra includes irreversible neuronal loss that impedes expected clinical recovery after reperfusion.

Methods: In the prospective French Acute Multimodal Imaging Study to Select Patients for Mechanical Thrombectomy (FRAME) and an observational cohort of patients with large vessel occlusions undergoing endovascular treatment, we quantified penumbral integrity by fluid-attenuated inversion recovery (FLAIR) changes. We studied the influence of recanalization status on the evolution of penumbral FLAIR changes and studied penumbral FLAIR changes as predictor of tissue fate and functional outcome on the 90-day modified Rankin Scale (mRS).

Results: Recanalization status did not modify the evolution of rFLAIR signal intensity (SI) over time in the total cohort, but was associated with lower SI in the FRAME subset (b = -0.06, p for interaction = 0.04). Median rFLAIR SI was higher at baseline in the subsequently infarcted penumbra compared to the salvaged (ratio = 1.07, standard deviation (SD) = 0.07 vs 1.03, SD = 0.06 p < 0.0001, n = 150). The severity and extent of rFLAIR SI changes did not predict 90-day functional outcome in univariate (p = 0.09) and multivariate logistic regression (p = 0.4).

Conclusions: Recanalization status did not influence the evolution of penumbral FLAIR changes. FLAIR SI changes in the baseline penumbra were associated with tissue fate, but not functional outcome.

Background: The visual outcome after central retinal artery occlusion (CRAO) is poor, but its relationship with early reperfusion (ER) is poorly known. We evaluated the incidence of ER in acute CRAO or branch retinal artery occlusion (BRAO), and its association with clinical outcome.

Methods: In this prospective observational multicenter study, we included patients with acute CRAO or macula-involving BRAO presenting within 24 hours from symptom onset. ER was evaluated within 24 hours after the initial clinical evaluation using indocyanine green angiography (ICGA). The primary outcome was the best-corrected visual acuity (BCVA) at 1 month.

Results: In all, 70 patients were enrolled, of whom 63 (90%) had CRAO. Median age was 71 years (interquartile range: 67-77), 63% were male, median time from symptom onset to presentation was 5.3 hours (interquartile range: 3.1-15.1), and 17% received intravenous fibrinolysis. ER was identified in 34 patients (49%), of whom 21 (30%) achieved complete reperfusion (100% filling of the 55° ICGA field). Patients with ER were less likely to have hypertension and diabetes mellitus (p < 0.001 and p = 0.046, respectively). At the 1-month follow-up, BCVA was significantly better in ER patients (median BCVA 1.3 logMAR vs 1.7 logMAR, p = 0.001), with greater benefit with complete reperfusion (p for trend < 0.001). ER was also associated with improved visual field and quality of life at the 1-month follow-up (both p < 0.05).

Conclusion: ER occurred in almost 50% of the patients and was associated with improved visual outcomes and quality of life. Therapies that increase ER in CRAO will likely improve clinical outcomes.

Clinical trial registration: This study was registered on ClinicalTrials.gov (identifier NCT03049514); https://classic.clinicaltrials.gov/ct2/show/NCT03049514.

Background: Increased time from symptom onset to puncture (TSOP) and time from puncture to reperfusion (TPTR) are associated with worse outcome in ischemic stroke patients treated with endovascular therapy (EVT) in the early time window (<6 h). However, these associations are less described in the late window (>6 h), where patients may benefit from EVT because of a more favorable imaging profile (late window paradox). We sought to compare the effect of these timeframes between these two periods on efficacy and safety outcomes.

Methods: The ETIS (Endovascular Treatment in Ischemic Stroke) registry is an ongoing, prospective, observational study in 21 centers that perform EVT in France. We included adult patients with an anterior occlusion, successfully treated by EVT (modified treatment in cerebral ischemia (mTICI) 2b-3) between January 2015 and June 2023, with a known time of stroke onset. The cohort was divided into two groups according to the TSOP (⩽6 h vs >6 h). Primary outcome was favorable outcome (modified Rankin Scale 0-2 at 90 days).

Results: In total, 7516 patients were included, with 5936 patients being treated ⩽6 h and 1580 >6 h. In the early window, TSOP and TPTR were associated with worse outcomes at 90 days (adjusted odds ratio (aOR) = 0.68 per hour; 95% confidence interval (CI) = 0.64-0.73; p < 0.001 and aOR = 0.92 per 10-min increment; 95% CI = 0.90-0.94, p < 0.001, respectively). TSOP was not associated with worse outcomes at 90 days in the late window (p = 0.955), but TPTR was associated with worse outcomes (aOR = 0.91 per 10-min increment; 95% CI = 0.86-0.96, p = 0.001), every 10 additional minutes in TPTR being associated with a 1.7% (95% CI = 0.6-2.7) decreased probability of favorable outcome.

Conclusion: Only EVT procedural time is associated with unfavorable outcomes at 90 days in late window patients. These results highlight how the late window paradox may end at the start of EVT and underscore the need for timely management, particularly for the EVT, even for late window patients with a presumed more favorable imaging profile.

Background: Intensive blood pressure (BP) management within 24 h after successful reperfusion following endovascular thrombectomy (EVT) is associated with worse functional outcomes than conventional BP management in Asian randomized controlled trials. Given the high prevalence of intracranial atherosclerotic stenosis (ICAS) in Asia, ICAS may influence these outcomes.

Aims: We aimed to assess whether ICAS affects the outcomes of intensive BP management after successful EVT.

Methods: We conducted a secondary analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, which enrolled participants from June 2020 to November 2022. Patients with anterior circulation large vessel occlusion (LVO) were stratified into ICAS-related and embolic LVO groups. Clinical outcomes for intensive (target systolic BP < 140 mm Hg) and conventional BP management (target systolic BP = 140-180 mm Hg) were analyzed in each group. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included symptomatic intracerebral hemorrhage within 36 h and stroke-related death within 3 months.

Results: Among 192 patients, 59 were in the ICAS-related LVO group, and 133 were in the embolic LVO group. In the ICAS-related LVO group, the rate of achieving a favorable outcome at 3 months was 37.5% with intensive BP management and 55.6% with conventional management (adjusted odds ratio (OR) = 0.49 (95% confidence interval (CI) = 0.14 to 1.75); P = 0.27). In the embolic LVO group, these rates were 29.9% and 42.4%, respectively (adjusted OR = 0.64 (95% CI = 0.28 to 1.45); P = 0.29). No significant interaction was found (P for interaction = 0.68). In addition, the ICAS-related LVO group receiving intensive BP management had lower rates of successful reperfusion at 24 h compared to conventional management (67.7% vs. 91.7%; P = 0.03), while no significant difference was found in the embolic LVO group. A significant interaction effect on successful reperfusion at 24 h was observed between ICAS-related and embolic LVO groups (P for interaction = 0.04). No significant differences in safety outcomes were observed between intensive BP management and conventional management within both ICAS-related LVO and embolic LVO groups.

Conclusions: ICAS did not significantly affect outcomes of intensive BP management within 24 h after successful EVT. After successful reperfusion by EVT, intensive BP management should be avoided regardless of ICAS presence.

Data access statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Background: Intravenous thrombolysis (IVT) is the cornerstone treatment for the acute ischemic stroke (AIS) within 4.5 h after onset. Current guidelines recommend administering antiplatelet medications 24 h after IVT. However, vascular reocclusion is a common occurrence after IVT. Tirofiban, a platelet glycoprotein IIb/IIIa antagonist, can help deter macrovascular reocclusion, prevent microvascular thrombosis, and enhance cerebral blood flow.

Objective: This trial aims to assess whether early administration of tirofiban can improve clinical outcomes in patients with AIS who received IVT.

Methods and design: The Advancing Stroke Safety and Efficacy through Early Tirofiban Administration after Intravenous Thrombolysis (ASSET IT) Trial is an investigator-initiated, randomized, placebo-controlled, double-blind, multicenter study. Up to 832 eligible patients will be consecutively randomized in a 1:1 ratio to receive either intravenous tirofiban or placebo over a period of 2 years across 38 stroke centers in China.

Outcomes: The primary endpoint is excellent functional status at day 90, defined as a modified Rankin Score of 0-1. Primary safety endpoints include symptomatic intracerebral hemorrhage at 24 h and mortality at 90 days.

Trial registry number: NCT06134622 (clinicaltrials.gov).

Background: Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes. The role of endovascular therapy (EVT) in the management of CVT remains controversial and variations in practice patterns are not well known.

Aims: Here, we present a comprehensive, international characterization of practice patterns and perspectives on the use of EVT for CVT.

Methods: A comprehensive 42-question survey was distributed to stroke clinicians globally from May to October 2023, asking about practice patterns and perspectives on the use of EVT for CVT.

Results: The overall response rate was 31% (863 respondents of 2744 invited) across 61 countries. The majority of respondents (74%) supported the use of EVT for CVT in certain clinical situations. Key considerations for decision-making in using EVT favored clinical over radiographic/procedural factors and included worsening level of consciousness (86%) and worsening neurological deficits (76%). In the past 3 years, 56% of respondents used EVT for the treatment of CVT, with most (49.5%) involved in two to five cases. Among interventionalists, significant variability existed in the techniques used for EVT (p < 0.001), with aspiration thrombectomy (56%) and stent retriever (51%) being the most used overall. Regionally, interventionalists from China predominantly used intra-sinus heparin (56%), while this technique was most commonly ranked as "never indicated" throughout the rest of the world (23%). Post-procedure, low molecular weight heparin was the most used anticoagulant (83%), although North American respondents favored unfractionated heparin (37%), while imaging was primarily split between magnetic resonance (71.8%) and computed tomography (65.9%) arteriography or venography.

Conclusion: Our survey reveals significant heterogeneity in approaches to EVT for CVT, and provides a comprehensive characterization of indications, techniques, and long-term management used by clinicians internationally. This resource will aid in optimizing patient selection and endovascular treatments for future trials.

Background: Non-contrast cranial computed tomography (NCCT) and CT angiogram (CTA) have become essential for endovascular treatment (EVT) in acute stroke. Patient selection may improve when CT perfusion (CTP) imaging is also added for patient selection. We aimed to analyze the effects of implementing CTP in acute ischemic stroke (AIS) patients' treatment to assess whether stroke outcomes differ in the late window.

Methods: We searched the PubMed, Embase, and Web of Sciences databases to obtain articles related to CTA and CTP in EVT. Collected patient data were split into two groups: the CTP and control (NCCT + CTA) cohorts. Primary outcomes evaluated were modified Rankin Scale (mRS) scores, symptomatic intracranial hemorrhages (sICHs), mortality, and successful recanalization.

Results: There were 14 studies with 5809 total patients in the final analysis: 2602 received CTP and 3202 were in the control group. CTP/CTA patients showed significantly lower rates of 90-day stroke-related mortality (odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.60-0.87, p < 0.01) and significantly higher successful recanalization (OR = 1.42, 95% CI = 1.06-1.94, p < 0.01) compared with CTA-only patients. Analysis of other outcomes including functional independence (mRS = 0-2), critical times, and intracranial hemorrhages was non-significant (p > 0.05).

Conclusion: The study highlights the usefulness of CTP-guided therapy as a supplementary tool in EVT selection in the late window. Although the addition of CTP resulted in lower mortality, the favorable outcomes did not improve. Further evidence is required to establish a clearer understanding of the potential advantages or limitations of incorporating CTP in stroke imaging.

Background: Several prehospital scales have been designed to aid paramedics in identifying stroke patients in the ambulance setting. However, external validation and comparison of these scales are largely lacking.

Aims: To compare all published prehospital stroke detection scales in a large cohort of unselected stroke code patients.

Methods: We conducted a systematic literature search to identify all stroke detection scales. Scales were reconstructed with prehospital acquired data from two observational cohort studies: the Leiden Prehospital Stroke Study (LPSS) and PREhospital triage of patients with suspected STrOke (PRESTO) study. These included stroke code patients from four ambulance regions in the Netherlands, including 15 hospitals and serving 4 million people. For each scale, we calculated the accuracy, sensitivity, and specificity for a diagnosis of stroke (ischemic, hemorrhagic, or transient ischemic attack (TIA)). Moreover, we assessed the proportion of stroke patients who received reperfusion treatment with intravenous thrombolysis or endovascular thrombectomy that would have been missed by each scale.

Results: We identified 14 scales, of which 7 (CPSS, FAST, LAPSS, MASS, MedPACS, OPSS, and sNIHSS-EMS) could be reconstructed. Of 3317 included stroke code patients, 2240 (67.5%) had a stroke (1528 ischemic, 242 hemorrhagic, 470 TIA) and 1077 (32.5%) a stroke mimic. Of ischemic stroke patients, 715 (46.8%) received reperfusion treatment. Accuracies ranged from 0.60 (LAPSS) to 0.66 (MedPACS, OPSS, and sNIHSS-EMS), sensitivities from 66% (LAPSS) to 84% (MedPACS and sNIHSS-EMS), and specificities from 28% (sNIHSS-EMS) to 49% (LAPSS). MedPACS, OPSS, and sNIHSS-EMS missed the fewest reperfusion-treated patients (10.3-11.2%), whereas LAPSS missed the most (25.5%).

Conclusions: Prehospital stroke detection scales generally exhibited high sensitivity but low specificity. While LAPSS performed the poorest, MedPACS, sNIHSS-EMS, and OPSS demonstrated the highest accuracy and missed the fewest reperfusion-treated stroke patients. Use of the most accurate scale could reduce unnecessary stroke code activations for patients with a stroke mimic by almost a third, but at the cost of missing 16% of strokes and 10% of patients who received reperfusion treatment.