International Journal of Stroke最新文献

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized.

Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021.

Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76.

Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

Background: Recombinant prourokinase (rhPro-UK) is a specific plasmin activator, which has been approved to treat acute myocardial infarction in China.

Aim: This phase 3 trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset.

Methods and design: RhPro-UK in AIS within 4.5 h of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasmin activator (rt-PA)-controlled, phase 3 trial. A total of 1552 patients who are eligible for intravenous thrombolytic therapy from 72 clinical sites will be randomly assigned to receive either rhPro-UK 35 mg (15 mg bolus + 20 mg infusion/30 min) or rt-PA 0.9 mg/kg (10% bolus + 90% infusion/1 h).

Study outcomes: The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary efficacy outcomes include the proportion of patients with mRS score of 0-2, the distribution of mRS, self-care ability in daily life on the Barthel Index at 90 days, the proportion of subjects with ⩾ 4 points decrease in National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score ⩽ 1 from baseline at 24 h and 7 days after treatment. Safety outcomes are symptomatic intracranial hemorrhage (sICH) and major systematic bleeding within 7 days as well as death from all causes within 90 days.

Discussion: The results from the PROST-2 trial will comprehensively elucidate the efficacy and safety profile of rhPro-UK as a potential alternative agent for stroke thrombolysis.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591.

Background: This study aimed to compare direct aspiration, stent retriever, and the combined thrombectomy technique on clinical, safety, and technical outcomes in late-window stroke patients included in the MR CLEAN-LATE trial.

Methods: This post hoc analysis of the MR CLEAN-LATE trial included patients treated with direct aspiration, stent retriever, or combined thrombectomy technique as first-line approach. Primary outcome was the modified Rankin Scale (mRS) score at 90 days follow-up, and compared between the three groups with ordinal logistic regression analysis. Secondary outcomes included mortality at 90 days, total technique switches, procedure time, recanalization rate measured with the expanded thrombolysis in cerebral infarction (eTICI) score, and symptomatic intracranial hemorrhage (sICH). Predefined variables were used for adjustments.

Results: In the MR CLEAN-LATE trial, 258 patients underwent endovascular treatment and 232 were included in our analyses. The mRS at 90 days did not differ (stent retriever vs. direct aspiration: adjusted common odds ratio (acOR) = 1.35, 95% confidence interval (CI) = 0.73 to 2.50; stent retriever vs. combined: acOR = 1.13, 95% CI = 0.64 to 2.00; direct aspiration vs. combined: acOR = 1.19, 95% CI = 0.64 to 2.21). Direct aspiration thrombectomy was accompanied with more switches to another technique compared to the stent retriever (adjusted odds ratio (aOR) = 6.50, 95% CI = 2.52 to 16.8) or combined group (aOR = 4.67, 95% CI = 1.80 to 12.1) and with higher sICH rates compared to the combined technique (13% vs. 2.5%; aOR = 8.19, 95% CI = 1.49 to 45.1). Mortality, procedure time, and eTICI did not differ.

Conclusion: Stent retriever, direct aspiration, or the combined thrombectomy technique as first-line approach showed no differences in clinical outcome in late-window stroke patients. Direct aspiration was accompanied with higher sICH rates and more switcher to another technique compared to the combined group.

Background: Insulin resistance (IR) is of growing concern yet its association with white matter integrity remains controversial. We aimed to investigate the association between IR and white matter integrity in nondiabetic adults.

Methods: This cross-sectional analysis was conducted based on the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study. A total of 1709 nondiabetic community-dwelling adults with available diffusion-weighted imaging based on brain magnetic resonance imaging and completed oral glucose tolerance test were included. IR was measured noninvasively by insulin sensitivity indices (ISI), including ISIcomposite and ISI_0,120, as well as homeostasis model assessment of insulin resistance (HOMA-IR). White matter microstructure abnormalities were identified by diffusion-weighted imaging along with tract-based spatial statistical analysis to compare diffusion metrics between groups. The multivariable linear regression models were applied to measure the association between white matter microstructure abnormalities and IR.

Results: A total of 1709 nondiabetic individuals with a mean age of 60.8 ± 6.4 years and 54.1% female were included. We found that IR was associated with a significant increase in mean diffusivity, axial diffusivity, and radial diffusivity extensively in cerebral white matter in regions such as the anterior corona radiata, superior corona radiata, anterior limb of internal capsule, external capsule, and body of corpus callosum. The pattern of associations was more marked for ISIcomposite and ISI_0,120. However, the effect of IR on white matter integrity was attenuated after, in addition, adjustment for history of hypertension and cardiovascular disease and antihypertensive medication use.

Conclusion: Our findings indicate a significant association between IR and white matter microstructural abnormalities in nondiabetic middle-aged community residents, while these associations were greatly influenced by the history of hypertension and cardiovascular disease, and antihypertensive medication use. Further investigation is needed to clarify the role of IR in white matter integrity, whereas prophylactic strategies of maintaining a low IR status may ameliorate disturbances in white matter integrity.

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

Background: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain.

Aims: This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups.

Methods: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140-180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months.

Results: Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups.

Conclusions: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

Background: Stroke risks associated with rapid climate change remain controversial due to a paucity of evidence.

Aims: To examine the risk of subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), and ischemic stroke (IS) associated with meteorological parameters.

Methods: In this time-stratified case-crossover study, adult patients hospitalized for their first stroke between 2011 and 2020 from the insurance claims data in Taiwan were identified. The hospitalization day was designated as the case period, and three or four control periods were matched by the same day of the week and month of each case period. Daily mean and 24-h variations in ambient temperature, relative humidity, air pressure, and apparent temperature were measured. Conditional logistic regression models were applied to assess the risk of stroke associated with exposure to weather variables, using the third quintile as a reference, controlling for air pollutant levels.

Results: There were 7161 patients with SAH, 40,426 patients with ICH, and 107,550 patients with IS. There was an inverse linear relationship between mean daily temperature and apparent temperature with ICH. Elevated mean daily atmospheric pressure was associated with an increased risk of ICH. A greater decrease in apparent temperature over a 24-h period was associated with increased risk of ICH but decreased risk of IS (odds ratio (95% confidence interval) for the first vs. third quintile of changes in apparent temperature, 1.141 (1.053-1.237) and 0.946 (0.899-0.996), respectively).

Conclusions: There were considerable differences in short-term associations between meteorological parameters and three main pathological types of strokes.

Data access statement: The authors have no permission to share the data.

Background: Return-to-work is a major goal achieved by fewer than 50% stroke survivors. Evidence on how to support return-to-work is lacking.

Aims: To evaluate the clinical effectiveness of Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care (UC) (i.e. usual NHS rehabilitation) versus UC alone for helping people return-to-work after stroke.

Methods: This pragmatic, multicentre, individually randomised controlled trial with embedded economic and process evaluations, compared ESSVR with UC in 21 NHS stroke services across England and Wales. Eligible participants were aged ≥18 years, in work at stroke onset, hospitalised with new stroke and within 12-weeks of stroke. People not intending to return-to-work were excluded. Participants were randomised (5:4) to individually-tailored ESSVR delivered by stroke-specialist occupational-therapists for up to 12-months or usual National Health Service rehabilitation. Primary outcome was self-reported return-to-work for ≥2 hours per week at 12-months. Primary and safety analyses were done in the intention-to-treat population.

Results: Between 1st June-2018, and 7th March-2022, 583 participants (mean age 54.1 years [SD 11.0], 69% male) were randomised to ESSVR (n=324) or UC (n=259). Primary outcome data were available for 454(77.9%) participants. Intention-to-treat analysis showed no evidence of a difference in the proportion of participants returned-to-work at 12-months (165/257[64.2%] ESSVR vs 117/197[59.4%] UC; adjusted odds ratio 1.12 [95%CI 0.8 to 1.87],p=0.3582). There was some indication that older participants and those with more post-stroke impairment were more likely to benefit from ESSVR (interaction p=0.0239 and p=0.0959 respectively).

Conclusions: To our knowledge, this is the largest trial of a stroke VR intervention ever conducted. We found no evidence that ESSVR conferred any benefits over UC in improving return-to-work rates 12-months post-stroke. Return-to-work (for at least 2 hours per week) rates were higher than in previous studies (64.2% ESSVR versus 59.4% UC) at 12-months and more than double that observed in our feasibility trial (26%). Interpretation of findings was limited by a predominantly mild-moderate sample of participants and the Covid-19 pandemic. The pandemic impacted the trial, ESSVR and UC delivery, altering the work environment and employer behaviour. These changes influenced our primary outcome and the meaning of work in people's lives; all pivotal to the context of ESSVR delivery and its mechanisms of action.

Data access: Data available on reasonable request.

Registration: ISRCTN12464275.

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.