| 1. |
- 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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| 2. |
- 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, s. e822-e833
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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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| 3. |
- Carrera, Caty, et al.
(författare)
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Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA.
- 2019
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Ingår i: Neurology. - 1526-632X. ; 93:9, s. e851-e863
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Tidskriftsartikel (refereegranskat)abstract
- To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10-6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10-4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009).The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.
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| 4. |
- Curtze, Sami, et al.
(författare)
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Cerebral white matter lesions and post-thrombolytic remote parenchymal hemorrhage.
- 2016
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:4, s. 593-9
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Tidskriftsartikel (refereegranskat)abstract
- Parenchymal hematoma (PH) following intravenous thrombolysis (IVT) in ischemic stroke can occur either within the ischemic area (iPH) or as a remote PH (rPH). The latter could be, at least partly, related to cerebral amyloid angiopathy, which belongs to the continuum of cerebral small vessel disease. We hypothesized that cerebral white matter lesions (WMLs)-an imaging surrogate of small vessel disease-are associated with a higher rate of rPH.We analyzed 2,485 consecutive patients treated with IVT at the Helsinki University Hospital. Blennow rating scale of 5 to 6 points on baseline computed tomographic head scans was considered as severe WMLs. An rPH was defined as hemorrhage that-contrary to iPH-appears in brain regions without visible ischemic damage and is clinically not related to the symptomatic acute lesion site. The associations between severe WMLs and pure rPH versus no PH, pure iPH versus no PH, and pure rPH versus pure iPH were studied in multivariate logistic regression models.rPHs were mostly (74%) located in lobar regions. After adjustments, the presence of severe WMLs was associated with pure rPH (odds ratio [OR] = 6.79, 95% confidence interval [CI] = 2.57-17.94) but not with pure iPH (OR = 1.45, 95% CI = 0.83-2.53) when compared to patients with no PH. In direct comparison of pure rPH with pure iPH, severe cerebral WMLs were further associated with higher iPH rates (OR = 3.60, 95% CI = 1.06-12.19).Severe cerebral WMLs were associated with post-thrombolytic rPH but not with iPH within the ischemic area. Ann Neurol 2016;80:593-599.
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| 5. |
- Maguire, Jane M., et al.
(författare)
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GISCOME – Genetics of Ischaemic Stroke Functional Outcome network : A protocol for an international multicentre genetic association study
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:3, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Genome-wide association studies have identified several novel genetic loci associated with stroke risk, but how genetic factors influence stroke outcome is less studied. The Genetics of Ischaemic Stroke Functional outcome network aims at performing genetic studies of stroke outcome. We here describe the study protocol and methods basis of Genetics of Ischaemic Stroke Functional outcome. Methods: The Genetics of Ischaemic Stroke Functional outcome network has assembled patients from 12 ischaemic stroke projects with genome-wide genotypic and outcome data from the International Stroke Genetics Consortium and the National Institute of Neurological Diseases Stroke Genetics Network initiatives. We have assessed the availability of baseline variables, outcome metrics and time-points for collection of outcome data. Results: We have collected 8831 ischaemic stroke cases with genotypic and outcome data. Modified Rankin score was the outcome metric most readily available. We detected heterogeneity between cohorts for age and initial stroke severity (according to the NIH Stroke Scale), and will take this into account in analyses. We intend to conduct a first phase genome-wide association outcome study on ischaemic stroke cases with data on initial stroke severity and modified Rankin score within 60–190 days. To date, we have assembled 5762 such cases and are currently seeking additional cases meeting these criteria for second phase analyses. Conclusion: Genetics of Ischaemic Stroke Functional outcome is a unique collection of ischaemic stroke cases with detailed genetic and outcome data providing an opportunity for discovery of genetic loci influencing functional outcome. Genetics of Ischaemic Stroke Functional outcome will serve as an exploratory study where the results as well as the methodological observations will provide a basis for future studies on functional outcome. Genetics of Ischaemic Stroke Functional outcome can also be used for candidate gene replication or assessing stroke outcome non-genetic association hypotheses.
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| 6. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 7. |
- Pihlasviita, Saana, et al.
(författare)
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Diagnosing cerebral ischemia with door-to-thrombolysis times below 20 minutes
- 2018
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 91:6, s. E498-E508
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To clarify diagnostic accuracy and consequences of misdiagnosis in the admission evaluation of stroke-code patients in a neurologic emergency department with less than 20-minute door-to-thrombolysis times. Accuracy of admission diagnostics was studied in an observational cohort of 1,015 stroke-code patients arriving by ambulance as candidates for recanalization therapy between May 2013 and November 2015. Immediate admission evaluation was performed by a stroke neurologist or a neurology resident with dedicated stroke training, primarily utilizing CT-based imaging. The rate of correct admission diagnosis was 91.1% (604/663) for acute cerebral ischemia (ischemic stroke/TIA), 99.2% (117/118) for hemorrhagic stroke, and 61.5% (144/234) for stroke mimics. Of the 150 (14.8%) misdiagnosed patients, 135 (90.0%) had no acute findings on initial imaging and 100 (67.6%) presented with NIH Stroke Scale score 0 to 2. Misdiagnosis altered medical management in 70 cases, including administration of unnecessary treatments (thrombolysis n = 13, other n = 24), omission of thrombolysis (n = 5), delays to specific treatments of stroke mimics (n = 13, median 56 [31-93] hours), and delays to antiplatelet medication (n = 14, median 1 [1-2] day). Misdiagnosis extended emergency department stay (median 6.6 [4.7-10.4] vs 5.8 [3.7-9.2] hours; p = 0.001) and led to unnecessary stroke unit stay (n = 10). Detailed review revealed 8 cases (0.8%) in which misdiagnosis was possible or likely to have worsened outcomes, but no death occurred as a result of misdiagnosis. Our findings support the safety of highly optimized door-to-needle times, built on thorough training in a large-volume, centralized stroke service with long-standing experience. Augmented imaging and front-loaded specialist engagement are warranted to further improve rapid stroke diagnostics.
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| 8. |
- Poli, Sven, et al.
(författare)
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Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF STROKE. - 1747-4930 .- 1747-4949. ; 19:1, s. 120-126
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.
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| 9. |
- Satopää, Jarno, et al.
(författare)
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Comparison of all 19 published prognostic scores for intracerebral hemorrhage.
- 2017
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Ingår i: Journal of the neurological sciences. - : Elsevier BV. - 1878-5883 .- 0022-510X. ; 379, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the accuracy of 19 published prognostic scores to find the best tool for predicting mortality after intracerebral hemorrhage (ICH).A retrospective single-center analysis of consecutive patients with ICH (n=1013). After excluding patients with missing data (n=131), we analyzed 882 patients for 3-month (primary outcome), in-hospital, and 12-month mortality. We analyzed the strength of the individual score components and calculated the c-statistics, Youden index, sensitivity, specificity, negative and positive predictive value (NPV and PPV) for the scores. Finally, we included every score component in a multivariable model to analyze the maximum predictive value of the data elements combined.Observed in-hospital mortality was 23.6%, 3-month mortality was 31.0%, and 12-month mortality was 35.3%. For in-hospital mortality, the National Institutes of Health Stroke Scale (NIHSS) performed equally good as the best score for the other outcomes, the ICH Functional Outcome Score (ICH-FOS). The c-statistics of the scores varied from 0.6293 (95% CI 0.587-0.672) to 0.8802 (0.855-0.906). With all variables from all the scores in a multivariable regression model, the c-statistics did not improve, being 0.89 (0.867-0.913). Using the Youden index cutoff for the ICH-FOS score, the sensitivity (73%), specificity (90%), PPV (76%), and NPV (88%) for the primary outcome were good.A plethora of scores exists to help clinicians estimate the prognosis of an acute ICH patient. The NIHSS can be used to quantify the risk of in-hospital death while the ICH-FOS performed best for the other outcomes.
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| 10. |
- Satopää, Jarno, et al.
(författare)
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Treatment of intracerebellar haemorrhage: Poor outcome and high long-term mortality.
- 2017
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Ingår i: Surgical neurology international. - : Scientific Scholar. - 2229-5097 .- 2152-7806. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Intracerebellar haemorrhage constitutes around 10% of all spontaneous, non-aneurysmal intracerebral haemorrhages (ICHs) and often carries a grim prognosis. In symptomatic patients, surgical evacuation is usually regarded the standard treatment. Our objective was to compare the in-hospital mortality and functional outcome at hospital discharge in either medically or surgically treated patients, and the impact of either treatment on long-term mortality after a cerebellar ICH.An observational, retrospective, single-centre consecutive series of 114 patients with cerebellar ICH. We assessed the effect of different demographic factors on functional outcome and in-hospital mortality using logistic regression. We also divided the patients in medical and surgical treatment groups based on how they had been treated and compared the clinical and radiological parameters, in-hospital, and long-term mortality in the different groups.In our series, 38 patients (33.3%) underwent haematoma evacuation and 76 (66.7%) received medical treatment. Glasgow coma scale <8, blocked quadrigeminal cistern, and severe hydrocephalus were associated with in-hospital death or poor functional outcome at discharge (modified Rankin scale 4-6). Surgically treated patients were younger, had larger haematomas both in volume and diameter, were in a worse clinical condition, and suffered more from hydrocephalus and brainstem compression. There were no statistically significant differences in in-hospital or long-term mortality. However, the surgically treated patients remained in a poor clinical condition.Surgical treatment of cerebellar ICH can be life-saving but often leads to a poor functional outcome. New studies are needed on long-term functional outcome after a cerebellar ICH.
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