[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones.
In a multicenter IVT-register-based cohort study, we compared previously dependent (prestroke modified Rankin Scale score, 3-5) versus independent (prestroke modified Rankin Scale score, 0-2) patients. Outcome measures were poor 3-month outcome (not reaching at least prestroke modified Rankin Scale [dependent patients]; modified Rankin Scale score of 3-6 [independent patients]), death, and symptomatic intracranial hemorrhage. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (OR [95% confidence interval]) were calculated.
Among 7430 IVT-treated patients, 489 (6.6%) were dependent and 6941 (93.4%) were independent. Previous stroke, dementia, heart, and bone diseases were the most common causes of preexisting dependency. Dependent patients were more likely to die (ORunadjusted, 4.55 [3.74-5.53]; ORadjusted, 2.19 [1.70-2.84]). Symptomatic intracranial hemorrhage occurred equally frequent (4.8% versus 4.5%). Poor outcome was more frequent in dependent (60.5%) than in independent (39.6%) patients, but the adjusted ORs were similar (ORadjusted, 0.95 [0.75-1.21]). Among survivors, the proportion of patients with poor outcome did not differ (35.7% versus 31.3%). After adjustment for age and stroke severity, the odds of poor outcome were lower in dependent patients (ORadjusted, 0.64 [0.49-0.84]).
IVT-treated stroke patients who were dependent on the daily help of others before stroke carry a higher mortality risk than previously independent patients. The risk of symptomatic intracranial hemorrhage and the likelihood of poor outcome were not independently influenced by previous dependency. Among survivors, poor outcome was avoided at least as effectively in previously dependent patients. Thus, withholding IVT in previously dependent patients might not be justified.
[Show abstract][Hide abstract] ABSTRACT: Importance
Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known.Objective
To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT.Design, Setting, and Participants
The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015.Main Outcomes and Measures
Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion.Results
Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours.Conclusion and Relevance
For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion.Trial Registration
trialregister.nl Identifier: NTR1804
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging.
Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH.
IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12-6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH.
In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.
[Show abstract][Hide abstract] ABSTRACT: Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between WMHs and markers of endothelial dysfunction and CBF by quantifying WMH volume on 3·0 Tesla MRI. We included 40 children with HbSS or HbSβ(0) thalassaemia, with a mean age of 12·1 ± 2·6 years. Boys demonstrated an increased risk for WMHs (odds ratio 4·5, 95% confidence interval 1·2-17·4), unrelated to glucose-6-phosphate dehydrogenase deficiency. In patients with WMHs, lower fetal haemoglobin (HbF) was associated with a larger WMH volume (regression coefficient = -0·62, R(2) = 0·25, P = 0·04). Lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower CBF in the white matter (regression coefficient = 0·07, R(2) = 0·15, P = 0·03), suggesting that endothelial dysfunction could potentially hamper CBF. The findings of our explorative study suggest that a high level of HbF may be protective for WMHs and that endothelial dysfunction may contribute to the development of WMHs by reducing CBF.
No preview · Article · Oct 2015 · British Journal of Haematology
[Show abstract][Hide abstract] ABSTRACT: Background:
In patients with a space-occupying middle cerebral artery (MCA) infarct surgical decompression reduces the risk of death, but increases the chance of survival with severe disability. We assessed quality of life (QoL), symptoms of depression, and caregiver burden at long-term follow-up.
Patients treated in two academic centres between 2007 and 2012 were included. Follow-up was at least six months. Patients and caregivers were interviewed separately. QoL was assessed with a visual analogue scale and the 36-item Short-Form health survey (SF-36); depression with the Hospital Anxiety and Depression Scale; and caregiver burden with the Caregiver Strain Index.
Twenty five patients were enrolled, of whom seven had an infarct in the dominant hemisphere. After a median follow-up of 26 months (IQR 11-46) the median SF-36 mental component score was 54.4 (IQR 45-60), indicating a mental QoL comparable to that in the general population. The median SF-36 physical component score was 32.7 (IQR 22-38), indicating a worse physical QoL. Dominance of the hemisphere did not influence QoL. 79 % of patients and 65 % of caregivers would, in retrospect, again choose for surgery. 26 % of patients had signs of depression and 64 % of caregivers were substantially burdened in their daily life.
Mental QoL after surgical decompression for space-occupying MCA infarct is comparable to that in the general population, whereas physical QoL is worse. Dominance of the hemisphere did not influence QoL. The majority of caregivers experience substantial burden. Most patients and caregivers stand by their decision for hemicraniectomy.
[Show abstract][Hide abstract] ABSTRACT: -We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in ischemic stroke patients on novel oral anticoagulants (NOAC, last intake <48hours) compared to patients (i) taking vitamin K-antagonists (VKA) or (ii) without prior anticoagulation (no-OAC).
-Multicenter cohort pilot study. Primary outcome measures were (i) occurrence of ICH in three categories - any intracranial hemorrhage (ICHany), symptomatic ICH according to the criteria of the ECASS-II (sICHECASS-II) and the NINDS thrombolysis trial (sICHNINDS); and (ii) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA-patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range [IQR] 8-22h). In VKA-patients, median pre-IVT/IAT INR was 1.3 (IQR 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9 % NOAC patients, compared to 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients compared to 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistical significant differences.
-IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both, IVT/IAT in patients on subtherapeutic VKA-treatment or in those without prior anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.
[Show abstract][Hide abstract] ABSTRACT: The fact that stroke prevention has become so much more effective over the last several decades calls for celebration. Improvements in understanding the benefits of encouraging a healthy lifestyle, more effective use of medications, and improved technique of preventive procedures account for the change. The systematic review by Munster et al.1 documents a 70% decline in the 30-day incidence of stroke or death associated with carotid endarterectomy (CEA) for 50%-99% asymptomatic carotid stenosis, from approximately 4% in the early 1990s to 1.2% in 2013. The rate of perioperative death alone fell 75% from approximately 1.3% to 0.4%. Measurements from 204,622 patients from 47 registries demonstrate these dramatic declines in the rates of devastating complications. Operative safety in research trials (mostly randomized trials) has shown similar magnitude improvements, but this failed to reach statistical significance due to smaller patient numbers (6 trials involving 4,431 procedures).
[Show abstract][Hide abstract] ABSTRACT: Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes.
The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes.
The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP.
Current controlled trials;
ISRCTN66140176. Date of registration: 6 April 2010.
[Show abstract][Hide abstract] ABSTRACT: In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH.
[Show abstract][Hide abstract] ABSTRACT: Background
In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci.DesignThe String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients.AimsThe study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies.
No preview · Article · Sep 2014 · International Journal of Stroke