| 1. |
- Olsson, Sandra, 1976, et al.
(författare)
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Genetic variation in complement component C3 shows association with ischaemic stroke.
- 2011
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Ingår i: European journal of neurology : the official journal of the European Federation of Neurological Societies. - : Wiley. - 1468-1331. ; 42, s. 214-16
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The aim of this study was to investigate whether genetic variation at the third complement component (C3) locus is associated with ischaemic stroke (IS). Methods: The Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 patients with IS, and 668 healthy controls. Sixteen SNPs were analyzed. Results: Two SNPs, rs2277984 and rs3745565, showed a significant association with overall IS. The SNP rs2277984 also showed association with the IS subtype cryptogenic stroke. These associations were independent of hypertension, diabetes, and smoking. The independent association between rs3745565 and overall IS withstands correction for multiple testing. Conclusion: In this sample of patients with IS, genetic variation in C3 is associated with IS.
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| 2. |
- Stokowska, Anna, et al.
(författare)
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Cardioembolic and Small Vessel Disease Stroke Show Differences in Associations between Systemic C3 Levels and Outcome
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the complement system has been proposed to play a role in the pathophysiology of stroke. As the specific involvement of the complement proteins may be influenced by stroke etiology, we compared plasma C3 and C3a levels in patients with cardioembolic (CE) and small vessel disease (SVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at three months and two years. Methodology/Principal Findings: Plasma C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and at three months after stroke, and age- and sex-matched control subjects from The Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assesed with modified Rankin Scale. In the CE group, plasma C3 levels were elevated only in the acute phase, whereas C3a was elevated at both time points. The follow-up phase plasma C3 levels in the upper third were associated with an increased risk of unfavorable outcome at three months (OR 7.12, CI 1.72-29.46, P = 0.007) as well as after two years (OR 8.25, CI 1.61-42.28, P = 0.011) after stroke. These associations withstand adjustment for age and sex. Conversely, three-month follow-up plasma C3a/C3 level ratios in the middle third were associated with favorable outcome after two years both in the univariate analysis (OR 0.19, CI 0.05-0.82, P = 0.026) and after adjustment for age and sex (OR 0.19, CI 0.04-0.88, P = 0.033). In the SVD group, plasma C3 and C3a levels were elevated at both time points but showed no significant associations with outcome. Conclusions: Plasma C3 and C3a levels are elevated after CE and SVD stroke but show associations with outcome only in CE stroke.
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| 3. |
- Stokowska, Anna, et al.
(författare)
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Plasma c3 and c3a levels in cryptogenic and large-vessel disease stroke: associations with outcome.
- 2011
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Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 32:2, s. 114-22
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Inflammation seems to be a key player in the pathophysiology of stroke. In this study, we compared plasma C3 and C3a levels in cryptogenic and large-vessel disease (LVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at 3 months and 2 years. Methods: C3 and C3a levels in plasma of 79 cryptogenic stroke and 73 LVD stroke patients, sampled within 10 days and at 3 months after stroke, and age- and sex-matched control subjects from the Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assessed with the modified Rankin Scale. Results: Plasma C3 was increased in both stroke groups at both time points. Systemic elevation of C3a was limited to the acute phase in the cryptogenic stroke group, whereas plasma C3a levels in the LVD group were also elevated at the 3-month follow-up. In the LVD group, plasma C3 levels in the upper third at the 3-month follow-up were associated with an unfavorable outcome after 3 months independently of age and sex: odds ratio (OR) 5.56; 95% confidence interval (CI) 1.03-29.93; p = 0.045; as well as after 2 years: OR 4.75; 95% CI 1.11-20.30; p = 0.036. In the cryptogenic stroke group, high plasma C3a levels in the acute phase were associated with an unfavorable outcome after 3 months: OR 3.75; 95% CI 1.01-13.96; p = 0.049 in univariate analysis but not after adjustment for age and sex (p = 0.050). Conclusions: Plasma C3 and C3a levels are elevated in cryptogenic and LVD stroke and the predictive value of these markers may depend on stroke subtype. Further studies on the role of the complement system in ischemic stroke outcome based on larger patient populations and controlling for the effect of infections, are clearly warranted.
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| 4. |
- Abzhandadze, Tamar, 1980, et al.
(författare)
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LIFE SATISFACTION IN SPOUSES OF STROKE SURVIVORS AND CONTROL SUBJECTS: A 7-YEAR FOLLOW-UP OF PARTICIPANTS IN THE SAHLGRENSKA ACADEMY STUDY ON ISCHAEMIC STROKE
- 2017
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 49:7, s. 550-557
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate life satisfaction in spouses of middle-aged stroke survivors from the long-term perspective and to identify factors that explain their life satisfaction. Subjects: Cohabitant spouses of survivors of ischaemic stroke aged < 70 years at stroke onset (n = 248) and spouses of controls (n = 246). Methods: Assessments were made 7 years after inclusion to the study. Spouses' life satisfaction was assessed with the Fugl-Meyer's Life Satisfaction Check-List (LiSAT 11). Stroke-related factors were examined with the National Institutes of Health stroke scale, Mini-Mental State Examination, Barthel Index and modified Rankin Scale. Results: Spouses of stroke survivors had significantly lower satisfaction with general life, leisure, sexual life, partner relationship, family life, and poorer somatic and psychological health than spouses of controls. Caregiving spouses had significantly lower scores on all life domains except vocation and own activities of daily living than non-caregiving spouses. Spouses' satisfaction on different life domains was explained mainly by their age, sex, support given to the partner, and the survivor's level of global disability, to which both physical and cognitive impairments contributed. Conclusion: Seven years after stroke, spouses of stroke survivors reported lower life satisfaction compared with spouses of controls. Life satisfaction in stroke survivors' spouses was associated with spouses' age, sex, giving support, and the stroke survivors' level of global disability.
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| 5. |
- Andersson, Malin E, 1978, et al.
(författare)
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Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease.
- 2007
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Ingår i: International journal of molecular medicine. - 1107-3756 .- 1791-244X. ; 20:2, s. 233-9
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Tidskriftsartikel (refereegranskat)abstract
- Kinesin is a microtubule-associated motor protein that transports Alzheimer-associated amyloid precursor protein (APP) in neurons. In animal models, impaired kinesin-mediated APP transport seems to enhance formation of the neurotoxic 42 amino acid fragment of beta-amyloid (A beta 42). In man, one study suggests that a polymorphism (rs8702, 56,836G>C) in the kinesin light chain 1 gene (KNS2) may affect the risk of Alzheimer's disease (AD). To further assess KNS2 as a susceptibility gene for AD we analyzed 802 patients with sporadic AD and 286 controls, 134 longitudinally followed patients with mild cognitive impairment (MCI) and 39 cognitively stable controls for the rs8702 polymorphism. The rs8702 polymorphism did not influence risk of AD (p=0.46). However, rs8702 interacted with APOE epsilon 4 carrier status in AD (p=0.006) and influenced cerebrospinal fluid levels of hyperphosphorylated tau in MCI patients who converted to AD during follow-up (p=0.018). These findings support earlier indications that genetic variability in the KNS2 gene may play a role during early stages of AD pathogenesis.
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| 6. |
- Ay, Hakan, et al.
(författare)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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Ingår i: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 7. |
- Blomgren, Charlotte, et al.
(författare)
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Long-term performance of instrumental activities of daily living (IADL) in young and middle-aged stroke survivors: Results from SAHLSIS outcome
- 2018
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Ingår i: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 25:2, s. 119-126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although stroke prevalence is increasing and large proportions of stroke survivors are expected to live many years after stroke onset, research on the long-term consequences of stroke for instrumental activities of daily living (IADL) is limited. Aim: To explore performance of IADL seven years post-stroke onset and identify predictors of long-term IADL performance based on commonly employed acute measures and demographic characteristics in young and middle-aged stroke survivors. Methods: Data on stroke survivors were collected from SAHLSIS. IADL performance was assessed at 7 years using the Frenchay Activities Index (FAI). Demographic data and baseline measures were assessed as predictors of FAI outcome, using logistic regression. Results: 237 stroke survivors with a median age of 63 at follow-up were included. Participants had predominantly suffered a mild stroke and > 90% lived at home with no community services. Mean FAI was 25.7(score range 0-45), indicating reduced levels of participation in IADL. Frequency of performance of IADL was lowest for work/leisure activities. Gender, cohabitation status, initial stroke severity and baseline score on mRS were independently associated with IADL outcome. Conclusions: Reduced levels of participation in IADL persist many years after stroke onset and indicate a need to adapt a long-term perspective on stroke rehabilitation.
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| 8. |
- Blomgren, Charlotte, et al.
(författare)
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Long-term performance of instrumental activities of daily living in young and middle-aged stroke survivors-Impact of cognitive dysfunction, emotional problems and fatigue.
- 2019
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- With an upward trend in the number of people who return home to independent living after stroke, the ability to perform more complex activities is becoming an increasingly important long-term outcome after stroke. Although associations between Instrumental Activities of Daily Living (IADL) and cognitive dysfunction, emotional problems, and fatigue have been reported, less is known about the long-term impact of these stroke consequences on the performance of everyday activities in young and middle-aged stroke survivors.To explore the impact of cognitive dysfunction, emotional problems, and fatigue on long-term performance of instrumental activities of daily living in young and middle-aged stroke survivors.Data on stroke survivors, aged 18-69 at index stroke, were collected from the Sahlgrenska Academy Study on Ischaemic Stroke. IADL outcome was assessed using the Frenchay Activities Index (FAI), and the impact of chosen variables was assessed using Spearman´s rank-order correlation and logistic regression.Seven years after index stroke, 296 stroke survivors (median age of 64) were included in this study. Cognitive dysfunction showed the strongest correlations with FAI outcome and independently explained worse outcome on FAI summary score and the domain of work/leisure activities. Fatigue was independently explanatory of worse outcome on FAI summary score and domestic chores, while depressive symptoms independently explained worse outcome on work/leisure activities. In a subgroup with only those participants who had no or minimal residual neurological deficits at follow-up (NIHSS score 0), cognitive dysfunction independently explained worse outcome on FAI summary score and work/leisure activities. Depressive symptoms independently explained worse outcome on FAI summary score and domestic chores.Our results show that in young and middle-aged stroke survivors, cognitive dysfunction, depressive symptoms, and fatigue negatively impact performance of IADL even at seven years post stroke onset. Further, we have shown that an impact of both cognitive dysfunction and depressive symptoms can be found also among stroke survivors with mild or no remaining neurological deficits.
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| 9. |
- Bonkhoff, A. K., et al.
(författare)
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Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics
- 2022
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-453X .- 1662-4548. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. ResultsWe analyzed 2,466 patients (age = 63.4 +/- 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio similar to 1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, p(FDR) < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, p(FDR) = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL. ConclusionMultiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.
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| 10. |
- Bonkhoff, A. K., et al.
(författare)
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Outcome after acute ischemic stroke is linked to sex-specific lesion patterns
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n=503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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