European Stroke Journal最新文献

Introduction: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated.

Patients and methods: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades.

Results: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group.

Discussion and conclusion: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis.

Introduction: In Moyamoya angiopathy (MMA), mechanisms underlying cognitive impairment remain debated. We aimed to assess the association of cognitive impairment with the degree and the topography of cerebral hypoperfusion in MMA.

Methods: A retrospective analysis of neuropsychological and perfusion MRI data from adults with MMA was performed. Ischemic and haemorrhagic lesion masks were created to account for cerebral lesions in the analysis of cerebral perfusion. Whole brain volume of hypoperfused parenchyma was outlined on perfusion maps using different Tmax thresholds from 4 to 12 s. Regional analysis produced mean Tmax values at different regions of interest. Analyses compared perfusion ratios in patients with and without cognitive impairment, with multivariable logistic regression analysis to identify predictive factors.

Results: Cognitive impairment was found in 20/48 (41.7%) patients. Attention/processing speed and memory were equally impaired (24%) followed by executive domain (23%). After adjustment, especially for lesion volume, hypoperfused parenchyma volume outlined by Tmax > 4 s or Tmax > 5 s thresholds was an independent factor of cognitive impairment (OR for Tmax > 4 s = 1.06 [CI 95% 1.008-1.123]) as well as attention/processing speed (OR for Tmax > 4 s = 1.07 [CI 95% 1.003-1.133]) and executive domains (OR for Tmax > 5 s = 1.08 [CI 95% 1.004-1.158]). Regarding cognitive functions, patients with processing speed and flexibility impairment had higher frontal Tmax compared to other ROIs and to patients with normal test scores.

Discussion: Cerebral hypoperfusion emerged as an independent factor of cognitive impairment in MMA particularly in attention/processing speed and executive domains, with a strong contribution of frontal areas.

Conclusion: Considering this association, revascularization surgery could improve cognitive impairment.

Introduction: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE.

Patients and methods: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE.

Results: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865).

Discussion and conclusion: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

Background: Ischaemic stroke and coronary artery disease share risk factors and stroke survivors experience a high rate of cardiac events. Recent work suggests a high burden of asymptomatic coronary artery disease (CAD) in ischaemic stroke survivors. Thus, we performed this systematic review and meta-analysis to A) estimate the prevalence of CAD in ischaemic stroke survivors without known CAD and B) evaluate the association between coronary atherosclerosis and future major adverse cardiovascular events (MACE) in stroke survivors.

Patients and methods: We conducted a systematic review and meta-analysis according to the PRISMA statement. We included studies investigating acute ischaemic stroke or transient ischaemic attack where participants underwent anatomical assessment of all coronary arteries. For objective B) we included studies that reported an association between coronary atherosclerosis and MACE. Two reviewers used the Newcastle-Ottawa Scale to assess risk of bias. We used random-effects modelling for our analyses.

Results: We identified 2983 studies of which 17 were included. These studies had a total of 6862 participants between 2008 and 2022. The pooled prevalence of any coronary atherosclerosis was 66.8% (95% CI 57.2%-75.1%) with substantial heterogeneity (I² = 95.2%). The pooled prevalence of obstructive (>50%) stenosis was 29.3% with substantial heterogeneity (I² = 91%). High-risk coronary anatomy (triple vessel disease or left main stenosis) was found in 7.0% (95% CI 4%-12%) with high heterogeneity I² = 72%. One study examined high-risk plaques and found a prevalence of 5.9%. Five studies reported the association of coronary atherosclerosis with future MACE. The presence of obstructive CAD confers a HR of 8.0 (95% CI 1.7-37.1, p = 0.007) for future MACE.

Discussion and conclusions: Asymptomatic CAD is common in ischaemic stroke survivors. The presence and severity of asymptomatic CAD strongly associates with the risk of future MACE. Further evaluation of the benefits of routine coronary assessment in ischaemic stroke is warranted.

Introduction: Hemorrhagic stroke may cause changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP), which may influence the prognosis of patients. The aim of this study was to investigate the relationship between early ICP, CPP, and 28-day mortality in the intensive care unit (ICU) of patients with hemorrhagic stroke.

Patients and methods: A retrospective study was performed using the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), including hemorrhagic stroke patients in the ICU with recorded ICP monitoring. The median values of ICP and CPP were collected for the first 24 h of the patient's monitoring. The primary outcome was 28-day ICU mortality. Multivariable Cox proportional hazards models were used to analyze the relationship between ICP, CPP, and 28-day ICU mortality. Restricted cubic regression splines were used to analyze nonlinear relationships.

Results: The study included 837 patients with a 28-day ICU mortality rate of 19.4%. Multivariable analysis revealed a significant correlation between early ICP and 28-day ICU mortality (HR 1.08, 95% CI 1.04-1.12, p < 0.01), whereas early CPP showed no correlation with 28-day ICU mortality (HR 1.00, 95% CI 0.98-1.01, p = 0.57), with a correlation only evident when CPP < 60 mmHg (HR 1.99, 95% CI 1.14-3.48, p = 0.01). The study also identified an early ICP threshold of 16.5 mmHg.

Discussion and conclusion: Early ICP shows a correlation with 28-day mortality in hemorrhagic stroke patients, with a potential intervention threshold of 16.5 mmHg. In contrast, early CPP showed no correlation with patient prognosis.

Introduction: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach.

Patients and methods: Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA (N = 2140 cases), ASAH (N = 5140) or the combined group, and liability to drug usage from 23 drug classes (N up to 320,000) independent of the risk factor high blood pressure. Next, we evaluated the causality and therapeutic potential of correlated drug classes using three different Mendelian randomization frameworks.

Results: Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09-2.39, p = 0.018) and ASAH (OR = 1.68, 95% CI = 1.07-2.65, p = 0.024) if they used antidepressant drugs. This effect was absent in non-users. For beta-blockers, additional analyses showed that this effect was not independent of blood pressure after all. A complex and likely pleiotropic relationship was found between genetic liability to chronic multisite pain, pain medication usage (paracetamol, acetylsalicylic acid, and opioids), and IA.

Conclusions: We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA.

Introduction: To support decisions about thrombectomy provision, we have previously estimated the annual UK population eligible for treatment as ∼10% of stroke admissions. Since then, eight further randomised trials that could alter the eligibility rate have reported in 2021-23. We updated our estimates of the eligible population from these trials and other recent studies.

Patients and methods: An updated decision tree describing the EVT eligible population for UK stroke admissions was produced. Decision criteria were derived from the highest level of evidence available. For nodes where no specific RCT data existed, evidence was obtained from the latest systematic review(s) or the highest quality observational data.

Results: We estimate that 15,420 (approximately 15%) of admitted UK stroke patients are now eligible for thrombectomy, or 14,930 if advanced brain imaging using MRI/CT perfusion or collateral assessment were used in all patients. This is a 54% increase in our previous estimate in 2021. Over 50% of LAO strokes are now potentially eligible for thrombectomy. The increase in eligibility is principally due to a much larger cohort of later presenting and/or larger ischaemic core patients.

Conclusion: Most previously independent LAO stroke patients presenting within 24 h, even in the presence of a large ischaemic core on initial non-contrast CT, should be considered for thrombectomy with use of advanced brain imaging in those presenting beyond 12 h to identify salvageable penumbral brain tissue. Treatment in most patients remains critically time-dependent and our estimates should be interpreted with this in mind.

Introduction: To improve our understanding of the relatively poor outcome after endovascular treatment (EVT) in women we assessed possible sex differences in baseline neuroimaging characteristics of acute ischemic stroke patients with large anterior vessel occlusion (LVO).

Patients and methods: We included all consecutive patients from the MR CLEAN Registry who underwent EVT between 2014 and 2017. On baseline non-contrast CT and CT angiography, we assessed clot location and clot burden score (CBS), vessel characteristics (presence of atherosclerosis, tortuosity, size, and collateral status), and tissue characteristics with the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). Radiological outcome was assessed with the extended thrombolysis in cerebral infarction score (eTICI) and functional outcome with the modified Rankin Scale score (mRS) at 90 days. Sex-differences were assessed with multivariable regression analyses with adjustments for possible confounders.

Results: 3180 patients were included (median age 72 years, 48% women). Clots in women were less often located in the intracranial internal carotid artery (ICA) (25%vs 28%, odds ratio (OR) 0.85;95% confidence interval: 0.73-1.00). CBS was similar between sexes (median 6, IQR 4-8). Intracranial (aOR 0.73;95% CI:0.62-0.87) and extracranial (aOR 0.64;95% CI:0.43-0.95) atherosclerosis was less prevalent in women. Vessel tortuosity was more frequent in women in the cervical ICA (aOR 1.89;95% CI:1.39-2.57) and women more often had severe elongation of the aortic arch (aOR 1.38;95% CI:1.00-1.91). ICA radius was smaller in women (2.3vs 2.5 mm, mean difference 0.22;95% CI:0.09-0.35) while M1 radius was essentially equal (1.6vs 1.7 mm, mean difference 0.09;95% CI:-0.02-0.21). Women had better collateral status (⩾50% filling in 62%vs 53% in men, aOR 1.48;95% CI:1.29-1.70). Finally, ASPECT scores were equal between women and men (median 9 in both sexes, IQR 8-10vs 9-10). Reperfusion rates were similar between women and men (acOR 0.94;95% CI:0.83-1.07). However, women less often reached functional independence than men (34%vs 46%, aOR 0.68;95% CI:0.53-0.86).

Discussion and conclusion: On baseline imaging of this Dutch Registry, men and women with LVO mainly differ in vessel characteristics such as atherosclerotic burden, extracranial vessel tortuosity, and collateral status. These sex differences do not result in different reperfusion rates and are, therefore, not likely to explain the worse functional outcome in women after EVT.

Rationale: Decompressive craniectomy (DC) is beneficial in people with malignant middle cerebral artery infarction. Whether DC improves outcome in spontaneous intracerebral haemorrhage (ICH) is unknown.

Aim: To determine whether DC without haematoma evacuation plus best medical treatment (BMT) in people with ICH decreases the risk of death or dependence at 6 months compared to BMT alone.

Methods and design: SWITCH is an international, multicentre, randomised (1:1), two-arm, open-label, assessor-blinded trial. Key inclusion criteria are age ⩽75 years, stroke due to basal ganglia or thalamic ICH that may extend into cerebral lobes, ventricles or subarachnoid space, Glasgow coma scale of 8-13, NIHSS score of 10-30 and ICH volume of 30-100 mL. Randomisation must be performed <66 h after onset and DC <6 h after randomisation. Both groups will receive BMT. Participants randomised to the treatment group will receive DC of at least 12 cm in diameter according to institutional standards.

Sample size: A sample of 300 participants randomised 1:1 to DC plus BMT versus BMT alone provides over 85% power at a two-sided alpha-level of 0.05 to detect a relative risk reduction of 33% using a chi-squared test.

Outcomes: The primary outcome is the composite of death or dependence, defined as modified Rankin scale score 5-6 at 6 months. Secondary outcomes include death, functional status, quality of life and complications at 180 days and 12 months.

Discussion: SWITCH will inform physicians about the outcomes of DC plus BMT in people with spontaneous deep ICH, compared to BMT alone.

Trial registration: ClinicalTrials.gov Identifier: NCT02258919.