| 21. |
- Baturova, Maria A., et al.
(author)
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Non-permanent atrial fibrillation and oral anticoagulant therapy are related to survival during 10years after first-ever ischemic stroke
- 2017
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 232, s. 134-139
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Journal article (peer-reviewed)abstract
- Background: Atrial fibrillation (AF) detection in ischemic stroke patients triggers initiation of oral anticoagulant therapy (OAC). However, little is known regarding whether the persistency of AF affects long-term prognosis after ischemic stroke. We aimed to assess the impact of AF types and OAC on the outcome during a 10-year follow-up (FU) after first-ever ischemic stroke. Material and methods: The study sample comprised 336 first-ever ischemic stroke patients (median age 76, interquartile range 25-75% (IQR) 67-82. years, 136 female) included in the Lund Stroke Register (LSR) in 2001-2002. At baseline, 109 patients had either permanent (n = 44) or recurrent (n = 65) AF. OAC was assessed using the Lund University Hospital anticoagulation database. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register. Results: During FU, 200 patients died. AF independently predicted all-cause mortality (hazard ratio (HR) 1.52 95% CI 1.14-2.04, p = 0.005); the worst prognosis was observed for permanent AF (HR 1.86 95% CI 1.29-2.69, p = 0.001). Patients with recurrent AF receiving OAC had similar survival rates to patients without AF (HR 0.73 95% CI 0.38-1.39, p = 0.333), while prognosis was worst for patients with permanent AF without OAC (HR 2.28 95% CI 1.38-3.77, p = 0.001) and intermediate for patients with permanent AF on OAC (HR 1.57 95% CI 0.92-2.67, p = 0.099). Conclusion: All-cause mortality was independently associated with AF and was the greatest in stroke patients with permanent AF. Patients with recurrent AF receiving OAC have the most favorable outcome, similar to those without AF and significantly better than OAC-treated patients with permanent AF.
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| 22. |
- Bellenguez, Celine, et al.
(author)
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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
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Journal article (peer-reviewed)abstract
- Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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| 23. |
- Bonkhoff, A. K., et al.
(author)
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Sex-specific lesion pattern of functional outcomes after stroke
- 2022
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In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:2
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Journal article (peer-reviewed)abstract
- Relying on neuroimaging and clinical data of 822 acute stroke patients, Bonkhoff et al. report substantially more detrimental effects of lesions in left-hemispheric posterior circulation regions on functional outcomes in women compared to men. These findings may motivate a sex-specific clinical stroke management to improve outcomes in the longer term. Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
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| 24. |
- Bonkhoff, Anna K, et al.
(author)
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The relevance of rich club regions for functional outcome post-stroke is enhanced in women.
- 2023
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In: Human brain mapping. - : Wiley. - 1097-0193 .- 1065-9471. ; 44:4, s. 1579-1592
-
Journal article (peer-reviewed)abstract
- This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS>2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.
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| 25. |
- Bourached, Anthony, et al.
(author)
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Scaling behaviours of deep learning and linear algorithms for the prediction of stroke severity
- 2023
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In: BRAIN COMMUNICATIONS. - 2632-1297. ; 6:1
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Journal article (peer-reviewed)abstract
- Deep learning has allowed for remarkable progress in many medical scenarios. Deep learning prediction models often require 105-107 examples. It is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller. Such stroke outcome predictions however could be particularly instrumental in guiding acute clinical and rehabilitation care decisions. We here compared the capacities of classically used linear and novel deep learning algorithms in their prediction of stroke severity. Our analyses relied on a total of 1430 patients assembled from the MRI-Genetics Interface Exploration collaboration and a Massachusetts General Hospital-based study. The outcome of interest was National Institutes of Health Stroke Scale-based stroke severity in the acute phase after ischaemic stroke onset, which we predict by means of MRI-derived lesion location. We automatically derived lesion segmentations from diffusion-weighted clinical MRI scans, performed spatial normalization and included a principal component analysis step, retaining 95% of the variance of the original data. We then repeatedly separated a train, validation and test set to investigate the effects of sample size; we subsampled the train set to 100, 300 and 900 and trained the algorithms to predict the stroke severity score for each sample size with regularized linear regression and an eight-layered neural network. We selected hyperparameters on the validation set. We evaluated model performance based on the explained variance (R2) in the test set. While linear regression performed significantly better for a sample size of 100 patients, deep learning started to significantly outperform linear regression when trained on 900 patients. Average prediction performance improved by similar to 20% when increasing the sample size 9x [maximum for 100 patients: 0.279 +/- 0.005 (R2, 95% confidence interval), 900 patients: 0.337 +/- 0.006]. In summary, for sample sizes of 900 patients, deep learning showed a higher prediction performance than typically employed linear methods. These findings suggest the existence of non-linear relationships between lesion location and stroke severity that can be utilized for an improved prediction performance for larger sample sizes. Bourached et al. contrast linear and deep learning-based algorithms in their prediction performances of stroke severity depending on the training set sample sizes. They find that linear regression outperforms deep learning-based algorithms for smaller training samples comprising lesion location information of 100 patients, while deep learning excels in the case of larger samples (N = 900).
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| 26. |
- Canhao, P C, et al.
(author)
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Causes and predictors of death in cerebral venous thrombosis
- 2005
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 36:8, s. 1720-1725
-
Journal article (peer-reviewed)abstract
- Background and Purpose - The causes of death of patients with cerebral venous thrombosis (CVT) have not been systematically addressed in previous studies. We aimed to analyze the causes and predictors of death during the acute phase of CVT in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) to identify preventable or treatable causes. Methods - ISCVT is a multinational, prospective, observational study including 624 patients with CVT occurring between May 1998 and May 2001, in which 27 patients (4.3%) died during the acute phase, 21 (3.4%) within 30 days from symptom onset. Inclusion forms and a questionnaire assessing the causes of death were analyzed. A logistic regression analysis was performed to identify the predictors of death within 30 days from symptom onset of CVT. Results - Median time between onset of symptoms and death was 13 days and between diagnosis and death, 5 days. Causes of death were mainly transtentorial herniation due to a unilateral focal mass effect (10 patients) or to diffuse edema and multiple parenchymal lesions (10 patients). Independent predictors of death were coma (odds ratio [OR], 8.8; 95% confidence interval [CI], 2.8 to 27.7), mental disturbance (OR, 2.5; 95% CI 0.9 to 7.3), deep CVT thrombosis (OR, 8.5; 95% CI, 2.6 to 27.8), right intracerebral hemorrhage (OR, 3.4; 95% CI, 1.1 to 10.6), and posterior fossa lesion (OR, 6.5; 95% CI, 1.3 to 31.7). Worsening of previous focal or de novo focal deficits increased the risk of death. Conclusions - The main causes of acute death were neurologic, the most frequent mechanism being transtentorial herniation.
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| 27. |
- Cheng, Yu-Ching, et al.
(author)
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Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.
- 2016
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In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 47:2, s. 307-16
-
Journal article (peer-reviewed)abstract
- Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years.
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| 28. |
- Cortez, Daniel, et al.
(author)
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Atrial time and voltage dispersion are both needed to predict new-onset atrial fibrillation in ischemic stroke patients
- 2017
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
-
Journal article (peer-reviewed)abstract
- Background: Atrial fibrillation (AF) is a known risk factor for ischemic stroke. Electrocardiographic predictors of AF in population studies such as the Framingham Heart Study, as well as in hypertensive patients have demonstrated a predictive value of the P-wave duration for development of AF. QRS vector magnitude has had a predictive value in ventricular arrhythmia development. We aimed to assess the value of the three-dimensional P-wave vector magnitude and its relationship to P-wave duration for prediction of new-onset AF after ischemic stroke. Methods: First-ever ischemic stroke patients without AF at inclusion in the Lund Stroke Register were included. Measurements of P wave duration (Pd), QRS duration, corrected QT interval, and PQ interval were performed automatically using the University of Glasgow 12-lead ECG analysis algorithm. The P-wave vector magnitude (Pvm) was calculated automatically as the square root of the sum of the squared P-wave magnitudes in leads V6, II and one half of the P-wave amplitude in V2 ( PV 6 2 + PII 2 + 0.5 PV 2 2 $$ \sqrt(PV(6)^2+(PII)^2+(\left((0.5)^(\ast )PV2\right))^2) $$ ), based on the P-wave magnitude (Pvm) as defined by the visually transformed Kors' Quasi-orthogonal method. Results: The median age was 73 (IQR 63-80) years at stroke onset (135 males, 92 females). Multivariate predictors of new-onset atrial fibrillation included age>65years, hypertension, and Pd/Pvm. A cut-off value of 870ms/mV gave sensitivity, specificity, positive and negative predictive values of 51, 79, 30 and 87%, respectively. The Pd/Pvm was the only ECG predictor of AF with a significant multivariate hazard ratio of 2.02 (95% CI 1.18 to 3.46, p=0.010). Conclusion: P-wave dispersion as measured by the Pd/Pvm was the only ECG parameter measured which independently predicted subsequent AF identification in a cohort of stroke patients. Further prospective studies in larger cohorts are needed to validate its clinical usefulness.
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| 29. |
- Divakar, Pradeep K., et al.
(author)
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Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi
- 2015
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1217-1226
-
Journal article (peer-reviewed)abstract
- We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes, Ascomycota), one of the largest families of lichen-forming fungi with complex and variable morphologies, also including several lichenicolous fungi. We assembled a six-locus data set including nuclear, mitochondrial and low-copy protein-coding genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle originated independently three times in lichenized ancestors within Parmeliaceae, and a new generic name is introduced for one of these fungi. In all cases, the independent origins occurred c. 24 million yr ago. Further, we show that the Paleocene, Eocene and Oligocene were key periods when diversification of major lineages within Parmeliaceae occurred, with subsequent radiations occurring primarily during the Oligocene and Miocene. Our phylogenetic hypothesis supports the independent origin of lichenicolous fungi associated with climatic shifts at the Oligocene-Miocene boundary. Moreover, diversification bursts at different times may be crucial factors driving the diversification of Parmeliaceae. Additionally, our study provides novel insight into evolutionary relationships in this large and diverse family of lichen-forming ascomycetes.
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| 30. |
- Dorvall, Malin, 1991, et al.
(author)
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Mosaic Loss of Chromosome Y Is Associated With Functional Outcome After Ischemic Stroke.
- 2023
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In: Stroke. - : Wolters Kluwer. - 1524-4628 .- 0039-2499. ; 54:9, s. 2434-2437
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Journal article (peer-reviewed)abstract
- Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke.The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735). We used binary logistic regression to analyze associations between LOY, determined by DNA microarray intensity data, and poor 3-month functional outcome (modified Rankin Scale score, >2) in each cohort separately and combined. Patients who received recanalization therapy were excluded from sensitivity analyses.LOY was associated with about 2.5-fold increased risk of poor outcome in univariable analyses (P<0.001). This association withstood separate adjustment for stroke severity and diabetes in both cohorts but not age. In sensitivity analyses restricted to the nonrecanalization group (n=987 in the combined cohort), the association was significant also after separate adjustment for age (odds ratio, 1.6 [95% CI, 1.1-2.4]) and when additionally adjusting for stroke severity and diabetes (odds ratio, 1.6 [95% CI, 1.1-2.5]).We observed an association between LOY and poor outcome after ischemic stroke in patients not receiving recanalization therapy. Future studies on LOY and other somatic genetic alterations in larger stroke cohorts are warranted.
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