The relevance of rich club regions for functional outcome post-stroke is enhanced in women

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 similar to 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 dub regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.Peer reviewe

Cardioembolic and small vessel disease stroke show differences in associations between systemic C3 levels and outcome.

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

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

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. Design: Cross-sectional, case-control study. 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

Stroke survivors long-term QALY-weights in relation to their spouses QALY-weights and informal support: a cross-sectional study

Background: Healthcare interventions that have positive effects on the stroke survivors health-related quality of life (HRQoL) and quality-adjusted life-years (QALYs) might also have positive effects for their spouses in terms of improved HRQoL and/or reduced spousal informal support. However, knowledge about stroke survivors HRQoL and QALY and the consequences for their spouses HRQoL and QALY is limited. Therefore, the aim of this study was to describe the HRQoL and QALY-weights in dyads of stroke survivors in comparison with dyads of healthy controls, and to study the relationship between the stroke survivors QALY-weights and consequences for spouses in terms of QALY-weight and annual cost of informal support, using a long-term perspective. Methods: Data on stroke survivors, controls, and spouses were collected from the seven-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). HRQoL was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. The magnitude of the support was assessed with a study specific time-diary. An ordinary least squares (OLS) regression was used to estimate the association between stroke survivors and spouses QALY-weights. A two-part econometric model was used to estimate the association between stroke survivors QALY-weights and the time spent and cost of spouses informal support. Results: Cohabitant dyads of 248 stroke survivors aged amp;lt;70 at stroke onset and 245 controls were included in the study. Stroke survivors had lower HRQoL in the SF-36 domains physical functioning, physical role, general health, vitality (P amp;lt; 0. 001), and social functioning (P = 0.005) in comparison with their cohabitant spouses. There was no significant difference in HRQoL for the dyads of controls. The results from the regression analyses showed that lower QALY-weights of the stroke survivors were associated with lower QALY-weights of their spouses and increased annual cost of spousal informal support. Conclusion: Our results show that the QALY-weights for stroke survivors had consequences for their spouses in terms of annual cost of spousal informal support and QALY-weights. Hence, economic evaluation of interventions that improve the HRQoL of the stroke survivors but ignore the consequences for their spouses may underestimate the value of the intervention.Funding Agencies|Swedish Research Council [K2014-64X-14, 605-12-5]; Sahlgrenska University hospital [ALFGBG-429981, ALFGBG-71890]; Swedish Heart and Lung Foundation [20130315]; Swedish Stroke Association; Rune and Ulla Amlovs Foundation; John and Brit Wennerstroms Foundation; Gothenburg Foundation</p

Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction

Background and purpose: Neurofilament light chain (NfL) is a marker of neuroaxonal damage. We aimed to study associations between serum NfL (sNfL) concentrations at different time points after ischemic stroke and outcomes. Methods: We prospectively included ischemic stroke cases (n = 595, mean age 59\ua0years, 64% males) and assessed outcomes by both the modified Rankin Scale (mRS) and the NIH stroke scale (NIHSS) at 3\ua0months and by mRS at 2\ua0years. In a subsample, long-term (7-year) outcomes were also assessed by both mRS and NIHSS. We used the ultrasensitive single-molecule array assay to measure sNfL in the acute phase (range 1–14, median 4\ua0days), after 3\ua0months and 7\ua0years in cases and once in controls (n = 595). Results: Acute-phase sNfL increased by the time to blood-draw and highest concentrations were observed at 3\ua0months post-stroke. High sNfL associated to stroke severity and poor outcomes, and both associations were strongest for 3-month sNfL. After adjusting for age, previous stroke, stroke severity, and day of blood draw, 3-month sNfL was significantly associated to both outcomes at all time points (p &lt; 0.01 throughout). For all main etiological subtypes, both acute phase and 3-month sNfL were significantly higher than in controls, but the dynamics of sNfL differed by stroke subtype. Conclusions: The results from this study inform on sNfL in ischemic stroke and subtypes over time, and show that sNfL predicts short- and long-term neurological and functional outcomes. Our findings suggest a potential utility of sNfL in ischemic stroke outcome prediction

Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors

The aim of this study was to investigate whether the dependency of midlife stroke survivors had any long-term impact on their spouses QALY-weights. Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. Health-related quality of life was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. Spouses of dependent and independent stroke survivors were categorized according to their scores on the modified Rankin Scale. An ordinary least squares regression analysis was used to evaluate whether the dependency of the stroke survivors had any impact on the spouses QALY-weights. Cohabitant dyads of 247 stroke survivors aged amp;lt; 70 at stroke onset and 245 dyads of controls were included in the study. Spouses of dependent stroke survivors (n = 50) reported a significant lower mean QALY-weight of 0.69 in comparison to spouses of independent stroke survivors (n = 197) and spouses of controls, (n = 245) who both reported a mean QALY-weight of 0.77. The results from the regression analysis showed that higher age of the spouse and dependency of the stroke survivor had a negative association with the spouses QALY-weights. The QALY-weights for spouses of dependent midlife stroke survivors were significantly reduced compared to spouses of independent midlife stroke survivors. This indicates that the inclusion of spouses QALYs in evaluations of early treatment and rehabilitation efforts to reduce stroke patients dependency would capture more of the total effect in dyads of stroke survivors.Funding Agencies|Swedish Research Council [K2014-64X-14605-12-5]; Sahlgrenska University hospital [ALFGBG-429981, ALFGBG-71890]; Swedish Heart and Lung Foundation [20130315]; Swedish Stroke Association; Rune and Ulla Amlovs Foundation for Neurological Research; John and Brit Wennerstroms Foundation for Neurological Research; Gothenburg Foundation for Neurological Research; Stroke-Riksforbundet</p

Genetic Variation Within the Interleukin-1 Gene Cluster and Ischemic Stroke

Background and Purpose-Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to investigate whether genetic variation in the interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes (IL1A, IL1B, and IL1RN) is associated with IS and/or any etiologic subtype of IS. Methods-Twelve tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 844 patients with IS and 668 control subjects. IS subtypes were defined according to the Trial of Org 10172 in Acute Stroke Treatment criteria in SAHLSIS. The Lund Stroke Register and the Malmo Diet and Cancer study were used as a replication sample for overall IS (in total 3145 patients and 1793 control subjects). Results-The single nucleotide polymorphism rs380092 in IL1RN showed an association with overall IS in SAHLSIS (OR, 1.21; 95% CI, 1.02-1.43; P = 0.03), which was replicated in the Lund Stroke Register and the Malmo Diet and Cancer study sample. An association was also detected in all samples combined (OR, 1.12; 95% CI, 1.04 -1.21; P = 0.03). Three single nucleotide polymorphisms in IL1RN (including rs380092) were nominally associated with the subtype of cryptogenic stroke in SAHLSIS, but the statistical significance did not remain after correction for multiple testing. Furthermore, increased plasma levels of interleukin-1 receptor antagonist were observed in the subtype of cryptogenic stroke compared with controls. Conclusion-This comprehensive study, based on a tagSNP approach and replication, presents support for the role of IL1RN in overall IS. (Stroke. 2012; 43: 2278-2282.

Correlations between plasma levels of C3 and C3a, hsCRP, and SSS.

<p>Values represent Spearman’s correlation coefficients (ρ) with significance levels denoted as follows:</p>*<p><i>P<</i>0.05;</p>**<p><i>P</i><0.01;</p>***<p><i>P</i><0.001.</p>§<p>variable measured at the same time point as the respective indicated measurements of C3 or C3a.</p><p>–indicates non-relevant correlation.</p><p>hsCRP – high sensitivity C-reactive protein; SSS – Scandinavian Stroke Scale score; CE- cardioembolic; SVD – small vessel disease.</p

Features of TOAST classification of ischemic stroke subtypes.

<p>Adapted from Adams and colleagues <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072133#pone.0072133-Adams1" target="_blank">[28]</a>.</p><p>LVD – large vessel disease; SVD – small vessel disease; CE- cardioembolic.</p