| 1. |
- Aked, Joseph, et al.
(författare)
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Attitudes to Stem Cell Therapy among Ischemic Stroke Survivors in the Lund Stroke Recovery Study
- 2017
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:8, s. 566-572
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that stem cell therapy (SCT) may improve poststroke recovery, and clinical trials investigating safety are ongoing. However, knowledge about patients' attitudes to SCT in stroke is limited. We evaluated the knowledge and attitudes to this therapeutic approach as well as possible factors influencing this among stroke patients potentially suitable for SCT. Consecutive first-ever acute ischemic stroke patients aged 20-75 years with NIH stroke scale scores 1-18 were included. Exclusion criteria were severe comorbidities or infratentorial stroke. Clinical follow-up after 3-5 years assessed severity of residual stroke symptoms, cognitive function, functional status, patient-reported outcome, and comorbidity, and after receiving standardized information, the participants also completed an eight-item questionnaire on knowledge and attitudes about SCT. The relationships between clinical variables and positive attitude to SCT were assessed with logistic regression analyses. Of 108 patients included at baseline, 84 participated at follow-up and completed the questionnaire. In total, 12% had prior knowledge of SCT. When informed, 63% were positive toward it and 36% reported willingness to participate in SCT trials. Only 5%-8% expressed ethical considerations regarding different stem cell sources. Positive attitudes to SCT were associated with male gender (OR: 3.74; 95% CI: 1.45-9.61; P < 0.01) and better patient-reported outcome (OR: 1.02; 95% CI: 1.00-1.04; P < 0.05). In conclusion, stroke patients had limited prior knowledge of SCT, yet attitudes were positive among the majority after receiving standardized and neutral information. Gender and degree of stroke recovery may influence attitudes to SCT, indicating a need for targeted information to improve knowledge about SCT.
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| 2. |
- Aked, Joseph, et al.
(författare)
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Completeness of case ascertainment in Swedish hospital-based stroke registers
- 2020
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:2, s. 148-155
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a worldwide development toward using data from hospital-based stroke registers to estimate epidemiological trends. However, incomplete case ascertainment may cause selection bias. We examined the completeness of case ascertainment and selection bias in two hospital-based Swedish stroke registers. Methods: First-ever stroke cases between March 2015 and February 2016 in the catchment area of Skåne University Hospital, Lund, Sweden, were included from multiple overlapping sources: two hospital-based stroke registers, Riksstroke-Lund and Lund Stroke Register (LSR); local outpatient and inpatient registers; primary care registers; and autopsy registers. The resulting population-based cohort was used as reference to assess completeness of case ascertainment and patient characteristics in Riksstroke-Lund and LSR. Results: In total, 400 stroke patients were identified. Riksstroke-Lund detected 328 (82%) patients, whereas LSR detected 363 (91%). Patients undetected by hospital-based registers had higher 28-day case fatality than those detected (44% vs 9%; P =.001). Patients only detected in primary care (n = 11) more often lived in healthcare facilities compared with those detected by hospital-based registers (57% vs 7%; P =.001). Patients not detected by Riksstroke-Lund, but detected by population-based sources, had less severe strokes (median NIHSS 3 vs 5; P =.013). Conclusions: Some first-ever stroke patients, such as those with high early case fatality and those with mild stroke, may go undetected with hospital-based screening used in clinical stroke registers. This can result in selection bias due to not identifying specific groups of patients including some with high early case fatality and those living in healthcare facilities.
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| 3. |
- Aked, Joseph, et al.
(författare)
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Survival, causes of death and recurrence up to 3 years after stroke : A population-based study
- 2021
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:12, s. 4060-4068
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Up-to-date population-based information about long-term survival, causes of death and recurrence after stroke is needed. Methods: Four hundred consecutive individuals in a population-based cohort of first-ever stroke between 2015 and 2016 in Lund, Sweden, were followed up to 3 years regarding (i) survival (Swedish Population Register); (ii) causes of death (Swedish Causes of Death Register); and (iii) stroke recurrence (interview and medical chart review). Index and recurrent ischaemic stroke cases were classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and Oxfordshire Community Stroke Project; and comorbidities were classified using the Charlson Comorbidity Index. Cox regression was used to determine predictors for 3-year mortality. Survival rates were compared with three local studies over a 30-year timespan. Results: Amongst 400 first-ever stroke patients, 265 (66%) survived 3 years post-stroke. Age (hazard ratio [HR] 1.09; 95% confidence interval [CI] 1.06–1.11), stroke severity (HR 1.11; 95% CI 1.08–1.13) and comorbidities (HR 1.36; 95% CI 1.22–1.53) were independently related to 3-year mortality. Amongst index ischaemic stroke patients, survival was lowest amongst those with cardio-aortic embolism (51/91; 56%). Cerebrovascular disease (54/135; 40%) and ischaemic heart disease (25/135; 19%) were the most common causes of death. Within 3 years, 30 (8%) had recurrent stroke. Amongst patients with index ischaemic stroke, 16/29 (55%) had a different TOAST pathogenetic mechanism or hemorrhagic stroke upon recurrence. Stroke survival improved between 1983–1985 and 2015–2016 (p = 0.002), but no significant change was observed between 2001–2002 and 2015–2016 (p = 0.48). Conclusions: Stroke survival rates are relatively high, but their improvement over recent decades may be slowing down, possibly due to the composition of the first-ever stroke population. The common occurrence of changed pathogenetic mechanisms between first-ever and recurrent stroke highlights the value of reassessment in recurrent stroke.
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| 4. |
- Aked, Joseph, et al.
(författare)
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Temporal Trends of Stroke Epidemiology in Southern Sweden : A Population-Based Study on Stroke Incidence and Early Case-Fatality
- 2018
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 50:3-4, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Up-to-date epidemiological stroke studies are important for healthcare planning and evaluating prevention strategies. This population-based study investigates temporal trends in stroke incidence and case-fatality in southern Sweden. Methods: First-ever stroke cases in the local catchment area of Skåne University Hospital in Lund, Sweden, between March, 2015 and February, 2016, were included from several sources, including 2 prospective hospital-based registers, retrospective screening of primary care visits, and autopsy registers. Stroke incidence and 28-day case-fatality rates were compared with data from this area obtained through similar methodology between March, 2001 and February, 2002. Results: Altogether, 456 and 413 first-ever stroke patients were identified during the earlier and later time periods respectively. The age- and sex-standardized stroke incidence rates decreased from 246 (95% CI 224–270) to 165 (95% CI 149–182) per 100,000 people. However, incidence remained unaltered among those <65 years. Early case-fatality decreased from 14 to 11% (p = 0.165). Conclusion: First-ever stroke incidence in southern Sweden has decreased to 33% since the beginning of this millennium. Incidence rates have decreased among the elderly but remain unchanged among younger age groups. Our findings warrant further studies on trends in risk factor profiles and effects of prevention strategies, and heightened focus on stroke in the young.
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| 5. |
- 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 16 954 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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| 6. |
- Bellenguez, Celine, et al.
(författare)
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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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| 7. |
- Delavaran, Hossein
(författare)
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Clinical Findings and Outcome after Stroke. Including a Translational Stem Cell Therapy Perspective.
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and Purpose: Stroke is one of the dominant causes of death and adult disability in the world. There is a need for novel therapeutic approaches to improve functional recovery and outcome after stroke, and experimental studies have shown that stem cell-based therapies (SCT) hold much potential in this regard. This thesis, comprising 5 papers, aims to explore and describe clinical symptoms, lesion appearance, and outcome after stroke to provide guidance and enhance possibilities for future clinical implementation of SCT. Methods: In Paper I, a consecutive series of first-ever ischemic stroke patients (n=108) were examined ≤4 days of stroke onset regarding: (i) neuroradiological characteristics, and (ii) stroke severity measured with National Institutes of Health Stroke Scale (NIHSS). In Papers II and V, available survivors (n=84) from Paper I were assessed after 3-5 years regarding: (i) the frequency and recovery of upper extremity motor impairment (UEMI) measured with NIHSS arm and hand motor items; ii) the relation of UEMI to activity limitations measured with modifed Rankin Scale (mRS) and participation restrictions evaluated with Stroke Impact Scale (SIS); and iii) their knowledge and attitude about SCT using a questionnaire on SCT for stroke. In Papers III and IV, 10-year survivors (n=145) from a population-based group of 416 first-ever stroke patients in the Lund Stroke Register were assessed regarding: (i) functional status measured with mRS and Barthel Index (BI); (ii) patient-reported outcome using the European Quality of Life-5 Dimensions (EQ-5D) and Short-Form 36 Health Survey (SF-36), and iii) cognitive function using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), including comparisons with age- and sex-matched non-stroke control persons (n=354) from the population study Gott Åldrande i Skåne.Results: In Paper I, the distance between the nearest margin of the infarct(s) to the subventricular zone (a known neurogenic area in the brain) was 0-2 mm in 51/102 patients with visible ischemic lesions on DW-MRI. Only 8 patients had infarcts predominantly confined to striatum (a commonly used lesion site in pre-clinical stroke studies with SCT), causing mild deficits with a median NIHSS of 3 (range 1-5). In Paper II, 56 (52%) of the stroke patients had UEMI (NIHSS arm/hand score ≥1) in the first days after stroke onset. Morever, 10/41 stroke survivors with UEMI at baseline and without recurrent stroke displayed residual UEMI after 3-5 years, whereas 31/41 individuals showed complete recovery. Post-stroke UEMI correlated to mRS (rs=0.49, p<0.001) and the SIS participation domain (rs=-0.38, p=0.001). In Paper III, 103 (71%) of the 10-year stroke survivors had mRS≤2, 106 (73%) had a BI score of 95-100, 105 (72%) reported no problems with self-care according to EQ-5D, and 90 (62%) had positive views about their general health status according to SF-36. In Paper IV, 75 (61%) out of 122 stroke survivors who completed the MoCA had a score of MoCA<25. The odds of having severe cognitive impairment (MMSE<23) were higher among stroke survivors than the controls (education-adjusted OR 2.48; 95% CI: 1.34-4.59; p=0.004). In Paper V, only 10 (12%) of the stroke survivors had prior knowledge of SCT, but 53 (63%) of the participants expressed positive attitudes towards SCT after having received standardized and neutral written information. Positive attitudes to SCT were associated with male gender (crude OR 3.74; 95% CI: 1.45-9.61; p=0.006) and higher degree of self-perceived stroke recovery according to the SIS (crude OR 1.02; 95% CI: 1.00-1.04; p=0.034).Conclusions: Optimized endogenous neurogenesis may have a therapeutic potential, and striatum should probably not be the primary target for SCT aiming for neuronal replacement. SCT targeting post-stroke UEMI may be clinically valuable, and UEMI recovery may be a suitable outcome in later-phase pivotal stroke trials studying the efficacy of SCT. A majority of long-term stroke survivors have a relatively good prognosis accompanied by positive self-perceptions about their health, and would probably not have been in need of SCT to improve functional outcome. However, early prognostic assessments are needed to detect stroke patients with poor expected functional recovery and outcome where SCT may be beneficial. Cognitive impairment is common among long-term stroke survivors and should be taken into account both in pre-clinical studies and in future clinical trials with SCT. Targeted patient information on SCT for stroke may be valuable to facilitate recruitment to clinical trials and reduce risks of selection bias.
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| 8. |
- Delavaran, Hossein, et al.
(författare)
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Proximity of brain infarcts to regions of endogenous neurogenesis and involvement of striatum in ischaemic stroke.
- 2012
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical stroke trials with stem cell-based approaches aiming for trophic actions, modulation of inflammation and neuroprotection are ongoing. However, experimental studies also suggest that neuronal replacement by grafted neural stem cells (NSCs) and possibly by endogenous NSCs from the subventricular zone (SVZ) may restore function in the stroke-damaged striatum. To evaluate the potential clinical impact of these findings, we analyzed the spatial relationship of infarcts to the SVZ and the proportion of individuals with striatal lesions in a consecutive series of ischaemic stroke patients. METHODS: Patients aged 20-75 years with first-ever ischaemic stroke underwent DW-MRI of the brain within 4 days after stroke onset. We analyzed location, size, number of acute focal ischaemic abnormalities and their spatial relationship to the SVZ. Stroke severity was assessed using NIH Stroke Scale (NIHSS). RESULTS: Of 108 included patients, the distance from the nearest margin of the infarct(s) to the SVZ was ≤2 mm in 51/102 patients with visible ischaemic lesions on DW-MRI. Twenty-four patients had involvement of striatum. Eight of these had predominantly striatal lesions, that is >50% of the total ischaemic lesion volume was located in caudate nucleus and/or putamen. These 8 patients had a median NIHSS of 3. CONCLUSIONS: Many stroke patients have infarcts located close to the SVZ, providing some supportive evidence that optimized endogenous neurogenesis may have therapeutic potential. However, predominantly striatal infarcts are rare and tend to give mild neurological deficits, indicating that striatum should not be the primary target for neuronal replacement efforts in humans.
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| 9. |
- Delavaran, Hossein, et al.
(författare)
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Spontaneous Recovery of Upper Extremity Motor Impairment After Ischemic Stroke : Implications for Stem Cell-Based Therapeutic Approaches
- 2017
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Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 8:4, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that stem cell therapy (SCT) may improve sensorimotor recovery after stroke. Upper extremity motor impairment (UEMI) is common after stroke, often entailing substantial disability. To evaluate the feasibility of post-stroke UEMI as a target for SCT, we examined a selected sample of stroke patients potentially suitable for SCT, aiming to assess the frequency and recovery of UEMI, as well as its relation to activity limitations and participation restrictions. Patients aged 20–75 years with first-ever ischemic stroke, and National Institutes of Health Stroke Scale (NIHSS) scores 1–18, underwent brain diffusion-weighted MRI within 4 days of stroke onset (n = 108). Survivors were followed up after 3–5 years, including assessment with NIHSS, Fugl-Meyer assessment of upper extremity (FMA-UE), modified Rankin Scale (mRS), and Stroke Impact Scale (SIS). UEMI was defined as NIHSS arm/hand score ≥1. UEMI recovery was evaluated with change in NIHSS arm/hand scores between baseline and follow-up. Of 97 survivors, 84 were available to follow-up. Among 76 subjects (of 84) without recurrent stroke, 41 had UEMI at baseline of which 10 had residual UEMI at follow-up. The FMA-UE showed moderate-severe impairment in seven of 10 survivors with residual UEMI. UEMI was correlated to mRS (rs = 0.49, p < 0.001) and the SIS social participation domain (rs = −0.38, p = 0.001). Nearly 25% of the subjects with UEMI at baseline had residual impairment after 3–5 years, whereas about 75% showed complete recovery. Most of the subjects with residual UEMI had moderate-severe impairment, which correlated strongly to dependency in daily activities and social participation restrictions. Our findings suggest that SCT targeting post-stroke UEMI may be clinically valuable with significant meaningful benefits for patients but also emphasize the need of early prognostication to detect patients that will have residual impairment in order to optimize patient selection for SCT.
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| 10. |
- Jönsson, Ann-Cathrin, et al.
(författare)
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Falls After Stroke : A Follow-up after Ten Years in Lund Stroke Register
- 2021
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1532-8511 .- 1052-3057. ; 30:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate incidence of self-reported falls and associated factors in a ten-year perspective after stroke.METHODS: From a population-based cohort of first-ever stroke patients (n = 416) included in the Lund Stroke Register between March 1, 2001, and February 28, 2002, we performed a follow up of all 145 survivors ten years after stroke. We collected data on age, gender, main stroke type, living and housing situation, general health status (question 1 in the Short Form Health Survey (SF-36), dizziness, physical activity, Barthel Index, mobility aids, moving ability inside/outside, and health-related quality of life as defined by the EuroQol 3 dimension scale (EQ-5D-3L). Factors that may relate to falls were compared between those who had experienced falls after stroke or not.RESULTS: Ten years after stroke, 49 patients (34 %) reported falls and 96 patients (66 %) reported no falls. Compared to patients with no falls, those who reported falls were older (median age 83.3 years vs 75.6 years; p < 0.001), more often lived alone, were more dependent in daily living, had less physical activity, poorer general health status, more often needed mobility aids, were more often unable to move alone outside, and had poorer health-related quality of life in all items in EQ-5D-3L except pain/discomfort.CONCLUSIONS: Falls had occurred in approximately one third of the participants ten years after the stroke, and were strongly associated with several measures of frailty. Our results indicate that fall prevention should in particular focus on those at high risk of falls.
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