| 1. |
- Tolvanen, A. D., et al.
(författare)
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TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10 min or shorter
- 2017
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1663, s. 166-173
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Tidskriftsartikel (refereegranskat)abstract
- Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24 h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30 min, n = 6-8 per group) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24 h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5 min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10 min of ischemia followed up to 1 week after reperfusion remained free of infarction and any MRI signal change. Thus, 10 min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. (C) 2017 Elsevier B.V. All rights reserved.
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| 2. |
- Aarnio, Karoliina, et al.
(författare)
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Outcome of pregnancies and deliveries before and after ischaemic stroke
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:4, s. 346-355
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Limited data exist on the outcome of pregnancies and deliveries in women with ischaemic stroke. We investigated the incidence of pregnancy- and delivery-related complications in women with ischaemic stroke before and after pregnancy compared with stroke-free matched controls. Patients and methods: Of our 1008 consecutive patients aged 15–49 years with first-ever ischaemic stroke, 1994– 2007, we included women with pregnancy data before or after stroke recorded in the Medical Birth Register (MBR) (n¼152), and for them searched stroke-free controls matched by age, parity, year of birth, residential area and multiplicity (n¼608). Data on hospital admissions and deaths (1987–2014) came from national health registries. Poisson regression mixed models allowed comparison of the incidence of complications. Results: A total of 124 stroke mothers had 207 singleton pregnancies before and 45 mothers 68 pregnancies after stroke. The incidence rate ratio (IRR) for the composite outcome of pregnancy and delivery complications adjusted for socioeconomic status and maternal smoking was 1.43 (95% confidence interval [CI] 1.00–2.03, p¼0.05) for pre-stroke mothers, and 1.09 (95% CI 0.66–1.78) for post-stroke mothers, compared with matched controls. Similarly, the adjusted IRR for post-stroke hospital admission during pregnancy was 1.85 (95% CI 1.03–3.31). The IRR for perinatal death of the child was 3.43 (95% CI 0.57–20.53) before and 8.88 (95% CI 0.81–97.95) after stroke. Discussion and conclusions: Compared with stroke-free mothers, we found a higher incidence of pregnancy- and delivery-related complications in mothers with ischaemic stroke. Larger studies are needed to verify our results.
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| 3. |
- Acciarresi, M., et al.
(författare)
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Prestroke CHA(2)DS(2)-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study
- 2017
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 26:6, s. 1363-1368
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS < 3 or >= 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.
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| 4. |
- Antonenko, Kateryna, et al.
(författare)
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Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods: Data were analyzed from the ‘‘Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation’’ (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p<0.001) and younger (p<0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p¼0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p¼0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.411.7 days for men versus 6.512.4 days for women, p¼0.902). Men presented with more severe strokes at onset (mean NIHSS 9.26.9 versus 8.17.5, p<0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p¼0.28 and p¼0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p<0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes.
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| 5. |
- Gensicke, H, et al.
(författare)
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Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.
- 2017
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 24:2, s. 262-269
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Tidskriftsartikel (refereegranskat)abstract
- Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined.In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated.Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)].Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.
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| 6. |
- Grond-Ginsbach, C., et al.
(författare)
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Genetic Imbalance in Patients with Cervical Artery Dissection
- 2017
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Ingår i: Current Genomics. - : Bentham Science Publishers Ltd.. - 1389-2029. ; 18:2, s. 206-213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) = 1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107). Conclusion: The findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.
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| 7. |
- Hagg-Holmberg, S., et al.
(författare)
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Prognosis and Its Predictors After Incident Stroke in Patients With Type 1 Diabetes
- 2017
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:10, s. 1394-1400
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Although patients with type 1 diabetes have a poor prognosis after a stroke, predictors of survival after an incident stroke in these patients are poorly studied. In this observational study, a total of 144 patients of 4,083 with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study suffered an incident stroke in 1997-2010, and were followed for a mean 3.4 6 +/- 3.1 years after the stroke. Information was recorded on hard cardiovascular events and death as a result of cardiovascular or diabetes-related cause, collectively referred to as vascular composite end point. Information was collected from medical records, death certificates, and the National Care Register of Health Care. Predictors at the time of the incident stroke were studied for the end points. During follow-up, 104 (72%) patients suffered a vascular composite end point. Of these, 33 (32%) had a recurrent stroke, 33 (32%) a hard cardiovascular event, and 76 (53%) died of cardiovascular or diabetes-related causes, with an overall 1-year survival of 76% and 5-year survival of 58%. The predictors of a vascular composite end point were hemorrhagic stroke subtype (hazard ratio 2.03 [95% CI 1.29-3.19]), as well as chronic kidney disease stage 2 (2.48 [1.17-5.24]), stage 3 (3.04 [1.54-6.04]), stage 4 (3.95 [1.72-9.04]), and stage 5 (6.71 [3.14-14.34]). All-cause mortality increased with deteriorating kidney function. Patients with type 1 diabetes with an incident stroke have a poor cardiovascular prognosis and a high risk of all-cause mortality. In particular, hemorrhagic stroke subtype and progression of diabetic kidney disease conveys worse outcome.
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| 8. |
- Huber, Roman, et al.
(författare)
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Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study.
- 2017
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Ingår i: Stroke. - 1524-4628. ; 48:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO.We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0-). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns.PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P<0,001); subdivision of cryptogenic strokes revealed a PFO in 24% of 978 ASCO 3 patients (n.s. versus ASCO 1 and 2) and a higher prevalence of 36% in 750 ASCO 0 cases (P<0.001 versus ASCO 3 and versus ASCO 1 and 2). PFO was more commonly observed in ASCO 0- (n=271) than in ASCO 0+ patients (n=479; 48 versus 29%; P<0.001). There was no PFO-associated magnetic resonance imaging lesion pattern.Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.
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| 9. |
- Maguire, Jane M., et al.
(författare)
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GISCOME – Genetics of Ischaemic Stroke Functional Outcome network : A protocol for an international multicentre genetic association study
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:3, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Genome-wide association studies have identified several novel genetic loci associated with stroke risk, but how genetic factors influence stroke outcome is less studied. The Genetics of Ischaemic Stroke Functional outcome network aims at performing genetic studies of stroke outcome. We here describe the study protocol and methods basis of Genetics of Ischaemic Stroke Functional outcome. Methods: The Genetics of Ischaemic Stroke Functional outcome network has assembled patients from 12 ischaemic stroke projects with genome-wide genotypic and outcome data from the International Stroke Genetics Consortium and the National Institute of Neurological Diseases Stroke Genetics Network initiatives. We have assessed the availability of baseline variables, outcome metrics and time-points for collection of outcome data. Results: We have collected 8831 ischaemic stroke cases with genotypic and outcome data. Modified Rankin score was the outcome metric most readily available. We detected heterogeneity between cohorts for age and initial stroke severity (according to the NIH Stroke Scale), and will take this into account in analyses. We intend to conduct a first phase genome-wide association outcome study on ischaemic stroke cases with data on initial stroke severity and modified Rankin score within 60–190 days. To date, we have assembled 5762 such cases and are currently seeking additional cases meeting these criteria for second phase analyses. Conclusion: Genetics of Ischaemic Stroke Functional outcome is a unique collection of ischaemic stroke cases with detailed genetic and outcome data providing an opportunity for discovery of genetic loci influencing functional outcome. Genetics of Ischaemic Stroke Functional outcome will serve as an exploratory study where the results as well as the methodological observations will provide a basis for future studies on functional outcome. Genetics of Ischaemic Stroke Functional outcome can also be used for candidate gene replication or assessing stroke outcome non-genetic association hypotheses.
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| 10. |
- Mattila, O S, et al.
(författare)
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Ultra-acute diagnostics for stroke: Large-scale implementation of prehospital biomarker sampling.
- 2017
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 136:1, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based biomarkers could enable early and cost-effective diagnostics for acute stroke patients in the prehospital setting to support early initiation of treatments. To facilitate development of ultra-acute biomarkers, we set out to implement large-scale prehospital blood sampling and determine feasibility and diagnostic timesavings of this approach.Emergency medical services (EMS) personnel of the Helsinki metropolitan area were trained to collect prehospital blood samples from thrombolysis candidates using a cannula adapter technique. Time delays, sample quality, and logistics were investigated between May 20, 2013 and May 19, 2014.Prehospital blood sampling and study recruiting were successfully performed for 430 thrombolysis candidates, of which 50% had ischemic stroke, 14.4% TIA, 13.5% hemorrhagic stroke, and 22.1% stroke mimics. A total of 66.3% of all samples were collected during non-office hours. The median (interquartile range) emergency call to prehospital sample time was 33minutes (25-41), and the median time from reported symptom onset or wake-up to prehospital sample was 53minutes (38-85; n=394). Prehospital sampling was performed 31minutes (25-42) earlier than hospital admission blood sampling and 37minutes (30-47) earlier than admission neuroimaging. Hemolysis rate in serum and plasma samples was 6.5% and 9.3% for EMS samples, and 0.7% and 1.6% for admission samples.Prehospital biomarker sampling can be implemented in all EMS units and provides a median timesaving of more than 30minutes to first blood sample. Large prehospital sample sets will enable development of novel ambulance biomarkers to improve early differential diagnosis and treatment of thrombolysis candidates.
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