| 1. |
- Nordanstig, Annika, 1974, et al.
(author)
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Very Urgent Carotid Endarterectomy is Associated with an Increased Procedural Risk: The Carotid Alarm Study
- 2017
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 54:3, s. 278-286
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Journal article (peer-reviewed)abstract
- Objective/Background: The aim of the Carotid Alarm Study was to compare the procedural risk of carotid endarterectomy (CEA) performed within 48 hours with that after 48 hours to 14 days following an ipsilateral cerebrovascular ischaemic event. Methods: Consecutive patients with symptomatic carotid stenosis undergoing CEA were prospectively recruited. Time to surgery was calculated as time from the most recent ischaemic event preceding surgery. A neurologist examined patients before and, after CEA. The primary endpoint was the composite endpoint of death and/or any stroke within 30 days of the surgical procedure. The study was designed to include 600 patients, with 150 operated on within 48 hours. Results: From October 2010 to December 2015, 418 patients were included, of whom 75 were operated within 48 hours of an ischaemic event. The study was prematurely terminated owing to the slow recruitment rate in the group operated on within 48 hours. Patients undergoing CEA within 48 hours had a higher risk of reaching the primary endpoint than those operated on later (8.0% vs. 2.9%). Multivariate logistic regression analyses showed that CEA performed within 48 h (odds ratio [OR] 3.07; 95% confidence interval [CI] 1.04-9.09), CEA performed out of office hours (OR 3.65; 95% CI 1.14-11.67), and use of shunt (OR 4.02; 95% CI 1.36-11.93) were all independently associated with an increased risk of reaching the primary endpoint. Conclusion: CEA performed within 48 hours was associated with a higher risk of complications compared with surgery performed 48 hours-14 days after the most recent ischaemic event. (C) 2017 Published by Elsevier 'Ltd on behalf of European Society for Vascular Surgery.
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| 2. |
- Olsson, Sandra, 1976, et al.
(author)
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Genetic variation in complement component C3 shows association with ischaemic stroke.
- 2011
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In: 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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Journal article (peer-reviewed)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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| 3. |
- Stokowska, Anna, et al.
(author)
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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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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Journal article (peer-reviewed)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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| 4. |
- Stokowska, Anna, et al.
(author)
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Plasma c3 and c3a levels in cryptogenic and large-vessel disease stroke: associations with outcome.
- 2011
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In: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 32:2, s. 114-22
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Journal article (peer-reviewed)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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| 5. |
- Abzhandadze, Tamar, 1980, et al.
(author)
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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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In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977. ; 49:7, s. 550-557
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Journal article (peer-reviewed)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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| 6. |
- Alsholm, Linda, et al.
(author)
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Interrupted transport by the emergency medical service in stroke/transitory ischemic attack : A consequence of changed treatment routines in prehospital emergency care.
- 2019
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In: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279.
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Journal article (peer-reviewed)abstract
- BACKGROUND: The discovery that not all patients who call for the emergency medical service (EMS) require transport to hospital has changed the structure of prehospital emergency care. Today, the EMS clinician at the scene already distinguishes patients with a time-critical condition such as stroke/transitory ischemic attack (TIA) from patients without. This highlights the importance of the early identification of stroke/TIA.AIM: To describe patients with a final diagnosis of stroke/TIA whose transport to hospital was interrupted either due to a lack of suspicion of the disease by the EMS crew or due to refusal by the patient or a relative/friend.METHODS: Data were obtained from a register in Gothenburg, covering patients hospitalised due to a final diagnosis of stroke/TIA. The inclusion criterion was that patients were assessed by the EMS but were not directly transported to hospital by the EMS.RESULTS: Among all the patients who were assessed by the EMS nurse and subsequently diagnosed with stroke or TIA in 2015, the transport of 34 of 1,310 patients (2.6%) was interrupted. Twenty-five of these patients, of whom 20 had a stroke and five had a TIA, are described in terms of initial symptoms and outcome. The majority had residual symptoms at discharge from hospital. Initial symptoms were vertigo/disturbed balance in 11 of 25 cases. Another three had symptoms perceived as a change in personality and three had a headache.CONCLUSION: From this pilot study, we hypothesise that a fraction of patients with stroke/TIA who call for the EMS have their direct transport to hospital interrupted due to a lack of suspicion of the disease by the EMS nurse at the scene. These patients appear to have more vague symptoms including vertigo and disturbed balance. Instruments to identify these patients at the scene are warranted.
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| 7. |
- Andersson, Malin E, 1978, et al.
(author)
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Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease.
- 2007
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In: International journal of molecular medicine. - 1107-3756 .- 1791-244X. ; 20:2, s. 233-9
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Journal article (peer-reviewed)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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| 8. |
- Ay, Hakan, et al.
(author)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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In: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Journal article (peer-reviewed)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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| 9. |
- Bager, Johan-Emil, et al.
(author)
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Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and oral anticoagulants: results from The Swedish Primary Care Cardiovascular Database of Skaraborg.
- 2021
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In: Journal of hypertension. - 1473-5598. ; 39:8, s. 1670-1677
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Journal article (peer-reviewed)abstract
- To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs).We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130mmHg as reference.There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145-180mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130mmHg.In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145-180mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130mmHg. This suggests that lowering SBP to below 145mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation.
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| 10. |
- Bager, Johan-Emil, et al.
(author)
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Long-term risk-factor control and secondary prevention are insufficient after first TIA: Results from QregPV.
- 2023
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In: European stroke journal. - 2396-9873 .- 2396-9881. ; 9:1, s. 154-161
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Journal article (peer-reviewed)abstract
- Long-term risk-factor control and secondary prevention are not well characterized in patients with a first transient ischemic attack (TIA). With baseline levels as reference, we compared primary-care data on blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), smoking, and use of antihypertensives, statins and antiplatelet treatment/oral anticoagulation (APT/OAC) during 5years after a first TIA.Patients in QregPV, a Swedish primary-care register for the Region of Västra Götaland, with a first TIA discharge diagnosis from wards proficient in stroke care 2010 to 2012 were identified and followed up to 5years. BP, LDL-C, smoking, use of antihypertensives, statins, APT/OAC, and achievement of target levels were calculated. We used logistic mixed-effect models to analyze the effect of follow-up over time on risk-factor control and secondary prevention treatment.We identified 942 patients without prior cerebrovascular disease who had a first TIA. Compared to baseline, the first year of follow-up was associated with improvements in concomitant attainment of BP <140/90mmHg, LDL-C<2.6mmol/L and non-smoking, which rose from 20% to 33% (OR 2.08, 95% CI 1.38-3.13), but then stagnated in years 2-5. In the first year of follow-up, 47% of patients had complete secondary prevention treatment (antihypertensives, APT/OAC and statin), but continued follow-up was associated with a yearly decrease in secondary prevention treatment (OR 0.94, 95% CI 0.94-0.98).Risk-factor control was inadequate, leaving considerable potential for improved secondary prevention treatment after a first TIA in Swedish patients followed up to 5years.
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| 11. |
- Bjalkefur, K., et al.
(author)
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Self-rated health over the first five years after stroke
- 2020
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In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 20:1
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Journal article (peer-reviewed)abstract
- Background Self-rated health (SRH) focuses on the patient's own perception, and represents an important patient-reported outcome. The aim was to investigate SRH one to 5 years after stroke, follow the development over time and search for factors associated with SRH. Methods Consecutive stroke patients admitted to Stroke Units at the Skaraborg Hospital, Sweden were included 2007-2009 (n = 2190). Patient-reported outcomes were collected annually over 5 years using a postal questionnaire. SRH was assessed by the question about general health from SF-36. Factors associated with SRH were investigated by multiple logistic regression analysis. Results Response-rate was > 90% at all time points. Overall, 40.2, 41.9, 40.7, 45.0 and 46.3% of the patients reported good SRH, 1 to 5 years after stroke. Performance in activities of daily living (ADL) was strongly associated with good SRH; 49.8 and 14.7% after 1 year in independent and dependent survivors respectively, p < 0.001. In independent survivors 1 year after stroke, good SRH was positively associated with female sex (OR = 2.0; p = < 0,001), physical activity (OR = 2.14; p = < 0,001), car driving (OR = 2.25; p = < 0,001), and negatively associated with age (OR = 0.99; p = < 0,001), pain (OR = 0.49; p = < 0,001), depression (OR = 0.30; p = < 0,001), and self-perceived unmet care needs (OR = 0.39; p = < 0,001). In dependent survivors, depression (OR = 0.23; p = < 0,001) and age (OR = 0.96; p = < 0,05), were negatively associated with good SRH 1 year after stroke. Similar patterns were observed throughout the follow-up. Conclusion The proportion stroke survivors reporting their health as good is slightly increasing over time. After stroke, SRH is associated with pain, depression, ability to perform activities and self-perceived unmet care needs, indicating that efforts to support stroke survivors in the chronic phase after stroke should concentrate on targeting these factors.
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| 12. |
- Blomgren, Charlotte, et al.
(author)
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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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In: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 25:2, s. 119-126
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Journal article (peer-reviewed)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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| 13. |
- Blomgren, Charlotte, et al.
(author)
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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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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 14:5
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Journal article (peer-reviewed)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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| 14. |
- Bonkhoff, A. K., et al.
(author)
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Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome
- 2022
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In: NEUROLOGY. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:13
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Journal article (peer-reviewed)abstract
- Background and Objectives To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. Methods MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs lowWMHburden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. Results A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. Discussion Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.
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| 15. |
- Bonkhoff, A. K., et al.
(author)
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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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In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-453X .- 1662-4548. ; 16
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Journal article (peer-reviewed)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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| 16. |
- Bonkhoff, A. K., et al.
(author)
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Outcome after acute ischemic stroke is linked to sex-specific lesion patterns
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)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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| 17. |
- 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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| 18. |
- 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
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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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| 19. |
- Bretzner, M., et al.
(author)
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MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes
- 2021
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In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 15
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Journal article (peer-reviewed)abstract
- Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes. Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA). Results: Radiomic features were predictive of WMH burden (R-2 = 0.855 +/- 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-values(CV1-6) < 0.001, p-value(CV7) = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes. Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.
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| 20. |
- Bretzner, Martin, et al.
(author)
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Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke.
- 2023
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In: Neurology. - 1526-632X .- 0028-3878. ; 100:8
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Journal article (peer-reviewed)abstract
- While chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age." We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors and worse functional outcomes.We extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison with chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs and a logistic regression model of favorable functional outcomes taking RBA as input.We reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age = 62.8 years, 42.0% female patients). T2-FLAIR radiomics predicted chronological ages (mean absolute error = 6.9 years, r = 0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted odds ratios: 0.58, 0.76, 0.48, 0.55; all p-values < 0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes.T2-FLAIR radiomics can be used to predict brain age and derive RBA. Older-appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke.
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| 21. |
- Brinjikji, Waleed, et al.
(author)
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Endotheliitis and cytokine storm as a mechanism of clot formation in COVID-19 ischemic stroke patients: A histopathologic study of retrieved clots.
- 2023
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In: Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. - 2385-2011.
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Journal article (peer-reviewed)abstract
- Studies during the COVID-19 pandemic have demonstrated an association between COVID-19 virus infection and the development of acute ischemic stroke, particularly large vessel occlusion (LVO). Studying the characteristics and immunohistochemistry of retrieved stroke emboli during mechanical thrombectomy for LVO may offer insights into the pathogenesis of LVO in COVID-19 patients. We examined retrieved COVID-19 emboli from the STRIP, EXCELLENT, and RESTORE registries and compared their characteristics to a control group.We identified COVID-positive LVO patients from the STRIP, RESTORE, and EXCELLENT studies who underwent mechanical thrombectomy. These patients were matched to a control group controlling for stroke etiology based on Trial of Org 10172 in Acute Stroke Treatment criteria. All clots were stained with Martius Scarlet Blue (MSB) along with immunohistochemistry for interleukin-6 (IL-6), C-reactive protein (CRP), von Willebrand factor (vWF), CD66b, fibrinogen, and citrullinated Histone H3. Clot composition was compared between groups.Nineteen COVID-19-positive patients and 38 controls were included. COVID-19-positive patients had a significantly higher percentage of CRP and vWF. There was no difference in IL-6, fibrin, CD66b, or citrullinated Histone H3 between groups. Based on MSB staining, there was no statistically significant difference regarding the percentage of red blood cells, white blood cells, fibrin, and platelets.Our study found higher concentrations of CRP and vWF in retrieved clots of COVID-19-positive stroke patients compared to COVID-19-negative controls. These findings support the potential role of systemic inflammation as indicated by elevated CRP and endothelial injury as indicated by elevated vWF as precipitating factors in thrombus development in these patients.
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| 22. |
- Brännmark, Cecilia, et al.
(author)
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FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke
- 2023
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In: Bmj Open. - 2044-6055. ; 13:5
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Journal article (peer-reviewed)abstract
- ntroduction Comprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, the FIND Stroke Recovery Study. We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery. Methods and analysis We recruit individuals with first-ever stroke at the stroke unit at the Sahlgrenska University Hospital, Sweden, to FIND. The inclusion started early 2018 and we aim to enrol minimum 500 patients. Neurological and cognitive impairments across multiple domains are assessed using validated clinical assessment methods, advanced neuroimaging is performed and blood samples for biomarker measuring (protein, RNA and DNA) at inclusion and follow-up visits at 3 months, 6 months, 1 year, 2 years and 5 years poststroke. At baseline and at each follow-up visit, we also register clinical variables known to influence outcomes such as prestroke functioning, stroke severity, acute interventions, rehabilitation, other treatments, socioeconomic status, infections (including COVID-19) and other comorbidities. Recurrent stroke and other major vascular events are identified continuously in national registers. Ethics and dissemination FIND composes a unique stroke cohort with detailed phenotyping, repetitive assessments of outcomes across multiple neurological and cognitive domains and patient-reported outcomes as well as blood and imaging biomarker profiling. Ethical approval for the FIND study has been obtained from the Regional Ethics Review Board in Gothenburg and the Swedish Ethics Review Board. The results of this exploratory study will provide novel data on the time course of recovery and biomarkers after stroke. The description of this protocol will inform the stroke research community of our ongoing study and facilitate comparisons with other data sets.
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| 23. |
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| 24. |
- Debette, Stéphanie, et al.
(author)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Journal article (peer-reviewed)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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| 25. |
- Drake, Mattias, et al.
(author)
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Diffusion-Weighted Imaging, MR Angiography, and Baseline Data in a Systematic Multicenter Analysis of 3,301 MRI Scans of Ischemic Stroke Patients-Neuroradiological Review Within the MRI-GENIE Study
- 2020
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Journal article (peer-reviewed)abstract
- Background:Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments of ischemic stroke patients in the Stroke Genetics Network, the results of the MRI-Genetics Interface Exploration (MRI-GENIE) study are described in this work. Methods:The MRI-GENIE study included patients with symptoms caused by ischemic stroke (N= 3,301) from 12 international centers. We established and used a structured reporting protocol for all assessments. Two neuroradiologists, using a blinded evaluation protocol, independently reviewed the baseline diffusion-weighted images (DWIs) and magnetic resonance angiography images to determine acute lesion and vascular occlusion characteristics. Results:In this systematic multicenter radiological analysis of clinical MRI from 3,301 acute ischemic stroke patients according to a structured prespecified protocol, we identified that anterior circulation infarcts were most prevalent (67.4%), that infarcts in the middle cerebral artery (MCA) territory were the most common, and that the majority of large artery occlusions 0 to 48 h from ictus were in the MCA territory. Multiple acute lesions in one or several vascular territories were common (11%). Of 2,238 patients with unilateral DWI lesions, 52.6% had left-sided infarct lateralization (P= 0.013 for chi(2)test). Conclusions:This large-scale analysis of a multicenter MRI-based cohort of AIS patients presents a unique imaging framework facilitating the relationship between imaging and genetics for advancing the knowledge of genetic traits linked to ischemic stroke.
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