| 31. |
- Putaala, Jukka, et al.
(författare)
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Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:2, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
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| 32. |
- Redfors, Petra, et al.
(författare)
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Living alone predicts mortality in patients with ischemic stroke before 70 years of age: a long-term prospective follow-up study
- 2016
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377 .- 1471-2377. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Living alone is associated with increased mortality after myocardial infarction but little data is available about whether this applies to prognosis after stroke. We aimed to examine the association between living situation and long-term mortality in patients with ischemic stroke and a control group, and to explore whether this association is modified by patient gender. METHODS: This is a prospective case-control study of 600 patients with ischemic stroke before 70 years of age and 600 age- and sex-matched controls who have been included in the Sahlgrenska Study on Ischemic Stroke. Mortality data were collected through national registers and medical records. We used Cox regression models for identifying predictors of mortality. RESULTS: In the entire sample, mean age was 57 years, proportion of males 64 %, proportion living alone 28 %, and median follow-up 8.6 years. Mortality rates were 36 % among patients living alone, 17 % among cohabitant patients, 15 % among controls living alone, and 9 % among cohabitant controls. Living alone was an independent predictor of all-cause mortality in cases after adjustment for stroke severity, stroke subtype, and vascular risk factors including physical activity, alcohol consumption, and socioeconomic status. A significant interaction was found between gender and living situation; the adjusted hazard ratio for mortality was 3.47 (95 % Confidence Interval 2.13-5.65) in male patients living alone, whereas no significant association was observed in women. Living alone was also a predictor of vascular mortality among cases and of all-cause mortality among controls. CONCLUSIONS: Living alone is associated with increased long-term mortality after ischemic stroke in men. Further prospective studies are needed to confirm the observed gender difference and to identify modifiable factors underlying this increased risk.
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| 33. |
- Redfors, Petra, et al.
(författare)
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Long-term follow-up of post-stroke epilepsy after ischemic stroke: Room for improved epilepsy treatment.
- 2020
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Ingår i: Seizure. - : Elsevier BV. - 1532-2688 .- 1059-1311. ; 76, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- To assess long-term incidence and predictors of post-stroke epilepsy (PSE) and to evaluate the antiepileptic drug (AED) treatment in a well characterized cohort of middle-aged patients.The study is based on the Sahlgrenska Study on Ischemic stroke, and included 1066 adult patients with first-ever or recurrent acute ischemic stroke (AIS) before the age of 70. Early seizures (ES) were defined as seizures within one week and PSE as unprovoked seizures occurring more than one week from index stroke. Cardiovascular risk factors, subtype of AIS, and stroke severity were determined at baseline. ES, PSE, treatment with AEDs, recurrent stroke and mortality were assessed through national registers and medical records. Cox regression models were used for identifying predictors of PSE.Twenty-six patients (2.4 %) developed ES. After a median follow-up of 8.0 (IQR 4.1-10.9) years, 84 (7.9 %) had PSE, and 160 (15.0 %) had experienced a non-fatal recurrent stroke. Stroke location (total anterior and partial anterior circulation infarct, both P < 0.001), ES (P < 0.001), stroke recurrence (P < 0.001), artery dissection (P < 0.002), and previous coronary heart disease (P < 0.006) were independent predictors of PSE. Only 10 (11.9 %) had the first seizure more than four years after index stroke. In 24 (30 %) PSE patients, seizure control was not achieved.In addition to well-known risk factors for PSE development, our data also identified stroke recurrence, artery dissection and established coronary disease. Seizure control was less common than expected and in a significant proportion of patients AEDs had not been adjusted despite continuing seizures.
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| 34. |
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| 35. |
- Redfors, Petra, et al.
(författare)
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Stroke subtype predicts outcome in young and middle-aged stroke sufferers
- 2012
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 126:5, s. 329-335
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: There are few studies on long-term outcome after ischemic stroke (IS) for young and middle-aged stroke sufferers in relation to etiologic subtypes. Here, we report 2-year outcome in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). MATERIALS AND METHODS: SAHLSIS comprises 600 patients with IS before the age of 70 years. Etiologic subtype of IS was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST). Recurrent vascular events and death were registered using several overlapping methods. Functional outcome was assessed according to the modified Rankin Scale (mRS). RESULTS: After 2 years, 55 (9.2%) patients had suffered a recurrent stroke, 15 (2.5%) had a transient ischemic attack (TIA), 4 (0.7%) had a coronary event, and 24 (4.0%) had died. The number of recurrent stroke, TIA, and death differed significantly between etiologic stroke subtypes. The highest rates were observed in large-vessel disease (LVD), whereas small-vessel disease and cryptogenic stroke showed the lowest recurrence and mortality rates. LVD was a significant predictor of the composite outcome (recurrent stroke, TIA, coronary event and/or death) independently of cardiovascular risk factors and stroke severity. Stroke subtype also predicted functional outcome 2 years after index stroke, but this association was not retained after adjustment for stroke severity. CONCLUSIONS: In young and middle-aged stroke patients, stroke subtype predicts recurrent vascular events and/or death 2 years after index stroke independently of cardiovascular risk factors and stroke severity. Thus, it is important to take the etiologic subtype of IS in account when assessing the risk of recurrence both in the clinical setting and in future studies.
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| 36. |
- Redfors, Petra, et al.
(författare)
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The Barrow Neurological Institute Screen for Higher Cerebral Functions in Cognitive Screening after Stroke
- 2014
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 23:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) in screening for cognitive dysfunction at longterm follow-up after stroke in young and middle-aged patients. Within the Sahlgrenska Academy Study on Ischemic Stroke Outcome, the BNIS and the Mini-Mental State Examination (MMSE) were administered to 295 consecutive surviving patients seven years after ischemic stroke. All participants were less than 70 years at index stroke. BNIS score less than 47 and an MMSE score less than 29 were chosen to indicate cognitive dysfunction. Two hundred eighty-one (95%) patients completed both tests. The 2 test scores were moderately correlated, and both tests correlated to disability as measured by the modified Rankin Scale. The distribution of the MMSE score was skewed toward the top scores, with a marked ceiling effect, whereas the BNIS score was more normally distributed. Most BNIS subscales showed mean performance around the mid of the scale without ceiling effects. Both tests identified a large proportion of the subjects as cognitive impaired, however, with a substantially larger proportion for the BNIS (89%) compared with the MMSE (65%). We conclude that the BNIS may be a useful screening instrument for cognitive dysfunction after ischemic stroke and that a large proportion of young and middle-aged ischemic stroke survivors showed signs of cognitive dysfunction long after index stroke. Further validations of BNIS against formal neuropsychological testing and studies of the determinants and consequences of long-term cognitive outcome in this patient group are warranted.
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| 37. |
- Rossi, R., et al.
(författare)
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Correlation between acute ischaemic stroke clot length before mechanical thrombectomy and extracted clot area: Impact of thrombus size on number of passes for clot removal and final recanalization
- 2021
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 6:3, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We assessed the correlation between thrombus size before and after mechanical thrombectomy, measured as length by Computed Tomography Angiography/Non-Contrast Computed Tomography (CTA/NCCT) and Extracted Clot Area, ECA, respectively. We also assessed the influence of thrombus size on the number of passes required for clot removal and final recanalization outcome. Materials and methods: Acute ischaemic stroke (AIS) thrombi retrieved by mechanical thrombectomy from 500 patients and data of clot length by CTA/NCCT were collected from three hospitals in Europe. ECA was obtained by measuring the area of the extracted clot. Non-parametric tests were used for data analysis. Results: A strong positive correlation was found between clot length on CTA/NCCT and ECA (rho = 0.619,N = 500, P < 0.0001*). Vessel size influences clot length on CTA/NCCT (H2 = 98.6, P < 0.0001*) and ECA (H2 = 105.6,P < 0.0001*), but the significant correlation between CTA/NCCT length and ECA was evident in all vessels. Poorer revascularisation outcome was associated with more passes (H5 = 73.1, P < 0.0001*). More passes were required to remove longer clots (CTA/NCCT; H4 = 31.4, P < 0.0001*; ECA; H4 = 50.2, P < 0.0001*). There was no significant main association between recanalization outcome and length on CTA/NCCT or ECA, but medium sized clots (ECA 20-40 mm(2)) were associated with least passes and highest revascularisation outcome (N = 500, X-2 = 16.2, P < 0.0001*). Conclusion: Clot length on CTA/NCCT strongly correlates with ECA. Occlusion location influences clot size. More passes are associated with poorer revascularisation outcome and bigger clots. The relationship between size and revascularisation outcome is more complex. Clots of medium ECA take less passes to remove and are associated with better recanalization outcome than both smaller and larger clots.
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| 38. |
- Rossi, Rosanna, et al.
(författare)
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Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry.
- 2022
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 269:4, s. 1913-1920
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Tidskriftsartikel (refereegranskat)abstract
- There is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone.We collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal-Wallis tests were used for statistical analysis.451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P=0.895), FIB% (P=0.458) and PTL% (P=0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8-64.9) versus 36.8 (20.1-79.8) mm2, N=1000, H1=7.679, P=0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29-32.06) versus 14.97 (4.93-39.80) mm2, H1=3.637, P=0.056] and significantly less fibrin [9.10 (4.62-17.98) versus 10.54 (5.57-22.48) mm2, H1=7.920, P=0.005*] and platelets/other [5.04 (2.26-11.32) versus 6.54 (2.94-13.79) mm2, H1=9.380, P=0.002*] than MT-alone clots.Our results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components.
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| 39. |
- Rossi, Rosanna, et al.
(författare)
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Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.
- 2024
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Ingår i: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 25:5
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Tidskriftsartikel (refereegranskat)abstract
- The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.
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| 40. |
- Rossi, Rosanna, et al.
(författare)
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S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages.
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Post-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.We analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.PTIH was associated with higher S100b levels in clots (0.33 [0.08-0.85] vs. 0.07 [0.02-0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0-23.0] vs. 14.0 [10.5-19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1-4] vs. 1 [1-2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.Higher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.
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