| 21. |
- Delavaran, Hossein, et al.
(författare)
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Spontaneous Recovery of Upper Extremity Motor Impairment After Ischemic Stroke : Implications for Stem Cell-Based Therapeutic Approaches
- 2017
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Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 8:4, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that stem cell therapy (SCT) may improve sensorimotor recovery after stroke. Upper extremity motor impairment (UEMI) is common after stroke, often entailing substantial disability. To evaluate the feasibility of post-stroke UEMI as a target for SCT, we examined a selected sample of stroke patients potentially suitable for SCT, aiming to assess the frequency and recovery of UEMI, as well as its relation to activity limitations and participation restrictions. Patients aged 20–75 years with first-ever ischemic stroke, and National Institutes of Health Stroke Scale (NIHSS) scores 1–18, underwent brain diffusion-weighted MRI within 4 days of stroke onset (n = 108). Survivors were followed up after 3–5 years, including assessment with NIHSS, Fugl-Meyer assessment of upper extremity (FMA-UE), modified Rankin Scale (mRS), and Stroke Impact Scale (SIS). UEMI was defined as NIHSS arm/hand score ≥1. UEMI recovery was evaluated with change in NIHSS arm/hand scores between baseline and follow-up. Of 97 survivors, 84 were available to follow-up. Among 76 subjects (of 84) without recurrent stroke, 41 had UEMI at baseline of which 10 had residual UEMI at follow-up. The FMA-UE showed moderate-severe impairment in seven of 10 survivors with residual UEMI. UEMI was correlated to mRS (rs = 0.49, p < 0.001) and the SIS social participation domain (rs = −0.38, p = 0.001). Nearly 25% of the subjects with UEMI at baseline had residual impairment after 3–5 years, whereas about 75% showed complete recovery. Most of the subjects with residual UEMI had moderate-severe impairment, which correlated strongly to dependency in daily activities and social participation restrictions. Our findings suggest that SCT targeting post-stroke UEMI may be clinically valuable with significant meaningful benefits for patients but also emphasize the need of early prognostication to detect patients that will have residual impairment in order to optimize patient selection for SCT.
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| 22. |
- Divakar, Pradeep K., et al.
(författare)
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Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi
- 2015
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1217-1226
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Tidskriftsartikel (refereegranskat)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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| 23. |
- Fava, Cristiano, et al.
(författare)
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A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case-control study
- 2015
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23, s. 969-974
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other ‘traditional risk factors’, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case–control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029–1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967–1.140); P=0.25), MDC (1.168 (1.060–1.288); P=0.002) and SAHLSIS (1.124 (0.997–1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case–control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
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| 24. |
- Franceschini, N, et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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| 25. |
- Giese, Anne Katrin, et al.
(författare)
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Design and rationale for examining neuroimaging genetics in ischemic stroke : The MRI-GENIE study
- 2017
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Ingår i: Neurology: Genetics. - 2376-7839. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI-GENetics Interface Exploration (MRI-GENIE) study. Methods: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributedMRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants. Neuroimaging analyses include themanual and automated assessments of established MRI markers. A high-throughputMRI analysis pipeline for the automated assessment of cerebrovascular lesions on clinical scans will be developed in a subset of scans for both acute and chronic lesions, validated against gold standard, and applied to all available scans. The extracted neuroimaging phenotypes will improve characterization of acute and chronic cerebrovascular lesions in ischemic stroke, including CCS subtypes, and their effect on functional outcomes after stroke. Moreover, genetic testing will uncover variants associated with acute and chronic MRI manifestations of cerebrovascular disease.Conclusions: The MRI-GENIE study aims to develop, validate, and distribute the MRI analysis platform for scans acquired as part of clinical care for patients with AIS, which will lead to (1) novel genetic discoveries in ischemic stroke, (2) strategies for personalized stroke risk assessment, and (3) personalized stroke outcome assessment.
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| 26. |
- Gill, Dipender, et al.
(författare)
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Genetically Determined Risk of Depression and Functional Outcome After Ischemic Stroke
- 2019
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Ingår i: Stroke. - 1524-4628. ; 50:8, s. 2219-2222
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods- Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. Results- There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81; 95% CI, 0.98-3.35; P=0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P=0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57; 95% CI, 1.05-6.25; P=0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81; 95% CI, 0.95-3.46; P=0.08). Conclusions- We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.
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| 27. |
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| 28. |
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| 29. |
- Grönholm, Erik, et al.
(författare)
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Predominance of caudate nucleus lesions in acute ischemic stroke patients with impairments in language and speech
- 2016
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 23:1, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose. Whereas traditional views of language processing in the brain have assumed that the language function is concentrated to a limited number of cortical areas (Broca’s and Wernicke’s areas), current knowledge points at a much more complex system of language and speech processing involving many brain areas, both cortical and subcortical. The purpose of the current study was to make an unbiased assessment of which cerebral areas are affected in first-ever acute ischemic stroke patients identified as having language and speech impairments according to the National Institute of Health Stroke Scale (NIHSS). Methods. Data from thirty-four patients with language and speech impairments, with a score of 1-3 on item 9 on the NIHSS, following ischemic stroke was collected from the Lund Stroke Register. MRI images acquired up to 20 days after stroke onset were used to create an overlap lesion image using MRIcron software. Results. The classical language areas, Wernicke’s and Broca’s area, were affected in less than one fourth of the patients. The most frequently affected region was a subcortical region - the left caudate nucleus and the adjacent corona radiata. Conclusions. These findings contribute to the growing body of evidence that the basal ganglia have a crucial role in the control over language and speech processing.
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| 30. |
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