1. |
- Nordanstig, Annika, 1974, et al.
(författare)
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Very Urgent Carotid Endarterectomy is Associated with an Increased Procedural Risk: The Carotid Alarm Study
- 2017
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 54:3, s. 278-286
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Tidskriftsartikel (refereegranskat)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.
(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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3. |
- 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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4. |
- 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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5. |
- 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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6. |
- Alsholm, Linda, et al.
(författare)
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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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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279.
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Tidskriftsartikel (refereegranskat)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.
(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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8. |
- 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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9. |
- Bager, Johan-Emil, et al.
(författare)
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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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Ingår i: Journal of hypertension. - 1473-5598. ; 39:8, s. 1670-1677
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: European stroke journal. - 2396-9873 .- 2396-9881. ; 9:1, s. 154-161
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Self-rated health over the first five years after stroke
- 2020
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 20:1
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Tidskriftsartikel (refereegranskat)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.
(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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13. |
- 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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14. |
- Bonkhoff, A. K., et al.
(författare)
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Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome
- 2022
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Ingår i: NEUROLOGY. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:13
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Tidskriftsartikel (refereegranskat)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.
(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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16. |
- 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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17. |
- Bonkhoff, A. K., et al.
(författare)
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Sex-specific lesion pattern of functional outcomes after stroke
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:2
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Tidskriftsartikel (refereegranskat)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.
(författare)
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The relevance of rich club regions for functional outcome post-stroke is enhanced in women.
- 2023
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Ingår i: Human brain mapping. - : Wiley. - 1097-0193 .- 1065-9471. ; 44:4, s. 1579-1592
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Tidskriftsartikel (refereegranskat)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.
(författare)
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MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes
- 2021
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 15
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke.
- 2023
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 100:8
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. - 2385-2011.
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Bmj Open. - 2044-6055. ; 13:5
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Tidskriftsartikel (refereegranskat)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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26. |
- Ekker, Merel, et al.
(författare)
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Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
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27. |
- Erlandsson, Malin, 1972, et al.
(författare)
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Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis
- 2019
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Ingår i: BMC Med. - : Springer Science and Business Media LLC. - 1741-7015. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesSince low insulin-like growth factor (IGF) 1 is often linked to inflammation, we analyze whether serum levels of IGF1 are associated with cardiovascular disease (CVD) in rheumatoid arthritis (RA) in a longitudinal observational study.MethodsA CVD risk was estimated (eCVR) in 184 female RA patients (mean age 52years) and in 132 female patients after ischemic stroke (mean age 56years) with no rheumatic disease, using the Framingham algorithm. The median level of IGF1 divided the cohorts in IGF1(high) and IGF1(low) groups. A 5-year prospective follow-up for new CVD events was completed in all RA patients. The Mantel-Cox analysis and event-free survival curves were prepared. Unsupervised clustering of proteins within the IGF1 signaling pathway was employed to identify their association with eCVR.ResultsLow IGF1 resulted in a higher eCVR in RA patients (7.2% and 3.3%, p=0.0063) and in stroke (9.3% and 7.1%, p=0.033). RA had higher rate for new CVD events at prospective follow-up (OR 4.96, p=0.028). Hypertension was the major risk factor associated with low IGF1 in RA and stroke. In hypertension, IGF1 was no longer responsible for intracellular activation and lost its correlation to IRS1/2 adaptor proteins. The clustering analysis confirmed that combination of low IGF1 and IRS1/2 with high IL6, insulin, and glucose predisposed to high eCVR and emphasized the functional role of serum IGF1.ConclusionsLow serum IGF1 precedes and predicts development of early CVD events in female RA patients. Hypertension and aberrant IGF1 receptor signaling are highlighted as the important contributors to IGF1-related CVD events.
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28. |
- 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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29. |
- Fitzgerald, Seán, et al.
(författare)
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Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.
- 2021
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Ingår i: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. - : Elsevier BV. - 1532-8511. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization.As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3.A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109mm2, Cardioembolic=52mm2, Cryptogenic=47mm2 and Other=52mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups.The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.
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30. |
- Fitzgerald, Seán, et al.
(författare)
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Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition.
- 2021
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Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 13, s. 1111-1116
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Tidskriftsartikel (refereegranskat)abstract
- Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots.To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass.As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated.Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1-3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes.LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.
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31. |
- Frid, Petrea, et al.
(författare)
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Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 649-658
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Tidskriftsartikel (refereegranskat)abstract
- Objective Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. Methods Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. Results PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. Conclusion Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.
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32. |
- Frid, P., et al.
(författare)
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Migraine-associated common genetic variants confer greater risk of posterior vs. anterior circulation ischemic stroke☆
- 2022
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Ingår i: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 31:8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. Methods: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. Results: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01–0.03) and decreased risk of ACiS (p=0.010–0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008–0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001–0.010) and migraine without aura (p=0.032–0.048). Migraine with aura PRS did not show a differential association in our analyses. Conclusions: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.
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33. |
- Gadd, Gustaf, et al.
(författare)
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A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.
- 2024
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Ingår i: International journal of molecular sciences. - 1661-6596 .- 1422-0067. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.
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34. |
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35. |
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36. |
- Gerafi, Joel, et al.
(författare)
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Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke
- 2017
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 24:11, s. 1407-1415
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 EAN Background and purpose: Visuospatial inattention (VSI) and language impairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. Methods: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1–5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian Stroke Scale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. Results: The regression model significantly explained variance in the modified Rankin scale (R 2 = 0.435, P < 0.001) and identified VSI (P = 0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for Frenchay Activities Index was also significant (R 2 = 0.269, P < 0.001) with VSI (P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. Conclusions: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.
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37. |
- Gerafi, Joel, et al.
(författare)
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The presence and prediction of lateralized inattention 7 years post-stroke
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:5, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- Objective Lateralized inattention is a typical sign of neglect and related to poor functional outcome. Knowledge of the long-term course of this phenomenon is limited. The purpose of this study was to investigate presence and predictors for signs of lateralized inattention 7 years after stroke. Methods From a cohort of acute ischemic stroke patients, aged 18-69 years (n = 297), a consecutive series of 188 survivors without recurrent stroke at follow-up 7 years later were included. Within the first week after stroke onset, stroke severity was assessed according to the Scandinavian Stroke Scale. Target omissions, asymmetry of omissions, and perceptual speed according to Star- and Letter Cancellation Tests were also assessed. Presence of lateralized inattention at the 7-year follow-up was investigated with the Star- and Letter Cancellation Tests and with the neglect item in the National Institutes of Health Stroke Scale. Results At the follow-up, 22 (11.7%) participants had lateralized inattention and the multivariable regression showed that independent significant baseline predictors were total omissions in target cancellations (P < .001) and inferior baseline performance on visual processing speed (P = .008). Conclusion About one of ten individuals exhibited signs of lateralized inattention 7 years after stroke. Baseline performance in perceptual processing speed and target omissions independently predicted presence of late signs of lateralized inattention. This is the first time processing speed is recognized as a significant predictor of lateralized inattention several years after the stroke incidence, indicating that the longitudinal course of processing speed following stroke is a critical subject for future research.
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38. |
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39. |
- Gidlöf, Olof, et al.
(författare)
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A Common Missense Variant in the ATP Receptor P2X7 Is Associated with Reduced Risk of Cardiovascular Events
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies. Methods: Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model. Results: The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively). Conclusions: A common loss-of-function missense variant in the gene encoding the P2X7 receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.
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40. |
- Gummesson, Christina, et al.
(författare)
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Entrustable professional activities (EPAs) for undergraduate medical education : development and exploration of social validity
- 2023
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Ingår i: BMC Medical Education. - : BioMed Central (BMC). - 1472-6920. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders.Aim: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs.Method and material: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater’s perception of the present graduates’ required level of supervision when performing the activity. Free-text comments were also included and analyzed.Results: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as “important” by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported “independent”. The three themes of the free text comments were: ‘relevant target areas and content’; ‘definition of the activities’; and ‘clinical practice and learning’.Conclusion: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.
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41. |
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42. |
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43. |
- Hanson, Ellen, et al.
(författare)
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Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmö Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach. The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample ≤70 years. We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals.
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44. |
- Hanson, Ellen, et al.
(författare)
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No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes
- 2012
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:3, s. 339-342
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The ABO blood group system is encoded by one gene, ABO. Previous studies have reported an association between blood group non-O (i.e. phenotype A, B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is associated with ischemic stroke and/or etiologic subtypes of ischemic stroke. Materials and methods: The study was performed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke before the age of 70 years, and 600 matched controls. Patients were classified according to the TOAST criteria. Results: There was no significant association between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also true for blood group O vs. A and O vs. B. Furthermore, no association between ABO genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis was confined to large-vessel disease, small-vessel disease, cardioembolic stroke and cryptogenic stroke. In this analysis, there was no significant association between any ischemic stroke subtype and ABO phenotype or genotype. Conclusions: The findings in this study suggest that ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes.
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45. |
- Hanson, Ellen, et al.
(författare)
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Plasma factor VII-activating protease antigen levels and activity are increased in ischemic stroke.
- 2012
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Ingår i: Journal of thrombosis and haemostasis : JTH. - : Elsevier BV. - 1538-7836 .- 1538-7933. ; 10:5, s. 848-56
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Tidskriftsartikel (refereegranskat)abstract
- Factor VII-activating protease (FSAP) is a recently discovered plasma protease with a role in the regulation of hemostasis and vascular remodeling processes. Higher levels and activity of FSAP have been reported in patients with deep vein thrombosis, but there are no data on plasma FSAP in ischemic stroke (IS).
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46. |
- Hanson, Ellen, et al.
(författare)
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Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke
- 2011
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:2, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- Background: Compared with coronary artery disease, there are few studies on von Willebrand factor (VWF) in ischemic stroke (IS). Moreover, there is little information on VWF in the etiologic subtypes of IS. Objectives: The aim of the present study was to investigate VWF in IS and in the etiologic subtypes of IS. Patients/methods: The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) is a case-control study comprising 600 patients and 600 matched controls. Etiologic IS subtype was defined according to the TOAST criteria. Blood sampling was performed in the acute phase and after 3 months. Results: The levels of VWF were increased in overall IS, at both time-points. The 3-month VWF levels were increased in the subtypes of large-vessel disease (LVD), cardioembolic (CE) stroke and cryptogenic stroke, but not in the subtype of small-vessel disease (SVD), as compared with the controls. The acute phase VWF levels were significantly increased in all four subtypes. In the multivariate regression analysis, with vascular risk factors as covariates, the 3-month VWF levels were associated with CE stroke and cryptogenic stroke, and the acute phase VWF levels with all subtypes. There were significant subtype-specific differences in VWF, with the highest levels in LVD and CE stroke. Conclusions: The present results show that VWF levels are increased in patients with IS. Furthermore, the VWF levels differ between etiologic IS subtypes and thus, it is important to consider etiologic subtypes in future studies of VWF in patients with IS.
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47. |
- Hofgren, Caisa, 1952, et al.
(författare)
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Cognitive screen and employment long-term after infratentorial stroke
- 2022
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 145:5, s. 610-618
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Motor problems are well-described neurological deficits that occur commonly after an infratentorial ischemic stroke. However, the brain stem and cerebellum are also part of the neural interconnections responsible for cognition, emotions, and behavioral responses. We lack studies on long-term cognitive outcomes and patient employment after an infratentorial stroke. In the present study, we described and compared long-term poststroke cognitive outcomes and employment between patients that experienced infratentorial and supratentorial ischemic strokes. Materials and Methods: We included consecutive patients that experienced an acute ischemic stroke at <= 58 years of age. Patients were classified according to the stroke location. At seven years poststroke, surviving participants were assessed for neurological deficits (National Institutes of Health Stroke Scale [NIHSS]), functional outcome (modified Rankin Scale [mRS]), cognitive function Barrow Neurological Institute Screen (BNIS), and employment. Results: Among 141 participants, 25 (18%) had infratentorial and 116 (82%) had supratentorial strokes. At the 7-year poststroke follow-up, there was no significant difference in BNIS total scores; with a median of 43 (IQR 40.5-46) and 41 (IQR 38-46) in the infratentorial and supratentorial groups, respectively. This result indicated that cognitive dysfunction occurred frequently in both groups. Similar employment rates were observed in the infratentorial (48%) and supratentorial (55%) groups. Both groups had a median NIHSS score of 0 and a median mRS score of 2 at the 7-year follow-up. Conclusion: Patients who survived an infratentorial or supratentorial ischemic stroke had similar rates of long-term cognitive dysfunction and difficulties in returning and/or remaining at work.
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48. |
- Holmegaard, Lukas, et al.
(författare)
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Long-term progression of white matter hyperintensities in ischemic stroke
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 138:6, s. 548-556
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Studies on long-term progression of white matter hyperintensities (WMH) after ischemic stroke are scarce. Here, we sought to investigate this progression and its predictors in a cohort presenting with ischemic stroke before 70 years of age. Materials and methods Participants in the Sahlgrenska Academy Study on Ischemic Stroke who underwent magnetic resonance imaging (MRI) of the brain at index stroke were examined by MRI again after 7 years (n = 188, mean age 53 years at index stroke, 35% females). WMH at index stroke and progression were assessed according to Fazekas' grades and the WMH change scale. Stroke subtype was classified according to TOAST. Results Marked WMH at index stroke were present in 20% of the participants and were significantly associated with age, hypertension, and subtype. Progression of WMH after 7 years was observed in 63% and 35% of the participants for subcortical and periventricular locations, respectively. Significant independent predictors of progression were age and marked WMH at baseline for both locations, whereas no significant associations were detected for vascular risk factors or subtype in multivariable analyses. In participants with no or only mild WMH at baseline, 20% showed marked WMH at follow-up. Age and hypertension, but not subtype, were independently associated with this acquisition of marked WMH. Conclusions Age and marked WMH at index stroke, but not stroke subtype, predicted long-term WMH progression after ischemic stroke before 70 years of age, whereas age and hypertension predicted acquisition of marked WMH in those with no or only mild WMH at baseline.
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49. |
- Holmegaard, Lukas, et al.
(författare)
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Proinflammatory protein signatures in cryptogenic and large artery atherosclerosis stroke
- 2021
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 143:3, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle-aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke.Blood was collected in the acute phase and after 3months from cryptogenic (n=162) and LAA (n=73) stroke patients aged 18-69years and once from age-matched controls (n=235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C-statistics.We identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs≥0.85). For both subtypes, RANTES, IL-4, and IFN-γ contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs≥0.76), and here eotaxin and MCP-1 contributed the most.The protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL-4, and IFN-γ in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP-1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause.
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50. |
- Hong, S. M., et al.
(författare)
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Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (beta = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.
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