| 1. |
- Altersberger, V. L., et al.
(författare)
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Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration
- 2022
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Ingår i: Stroke. - 1524-4628. ; 53:12, s. 3557-3563
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.
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| 2. |
- Ken-Dror, G., et al.
(författare)
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Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis
- 2021
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 90:5, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 x 10(-16)). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with individuals with blood group O. Interpretation We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021
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| 3. |
- Krzywicka, K., et al.
(författare)
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Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 98:7, s. E759-E768
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Cerebral venous sinus thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. Methods We estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of a first dose of 4 SARS-CoV-2 vaccinations using data from the European Medicines Agency's EudraVigilance database (until June 13, 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. Results The absolute risk of CVST within 28 days of first-dose vaccination was 7.5 (95% confidence interval [CI] 6.9-8.3), 0.7 (95% CI 0.2-2.4), 0.6 (95% CI 0.5-0.7), and 0.6 (95% CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95% CI 3.9-4.9), 0.7 (95% CI 0.2-2.4), 0.0 (95% CI 0.0-0.1), and 0.0 (95% CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18- to 24-year-old group (7.3 per million, 95% CI 2.8-18.8 and 3.7 per million, 95% CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group >= 70 years (0.2, 95% CI 0.0-1.3). Age <60 years compared to >= 60 years was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79, 95% CI 2.98-11.24, p < 0.001). Discussion The risk of CVST with thrombocytopenia within 28 days of first-dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines.
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| 4. |
- Krzywicka, Katarzyna, et al.
(författare)
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Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.
- 2023
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 30:5, s. 1335-1345
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored.Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included.Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent.Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.
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| 5. |
- Krzywicka, K., et al.
(författare)
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Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency
- 2021
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:11, s. 3656-3662
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Cerebral venous sinus thrombosis (CVST) has been described after vaccination against SARS-CoV-2. The clinical characteristics of 213 post-vaccination CVST cases notified to the European Medicines Agency are reported. Methods Data on adverse drug reactions after SARS-CoV-2 vaccination notified until 8 April 2021 under the Medical Dictionary for Regulatory Activities Term 'Central nervous system vascular disorders' were obtained from the EudraVigilance database. Post-vaccination CVST was compared with 100 European patients with CVST from before the COVID-19 pandemic derived from the International CVST Consortium. Results In all, 213 CVST cases were identified: 187 after AstraZeneca/Oxford (ChAdOx1 nCov-19) vaccination and 26 after a messenger RNA (mRNA) vaccination (25 with Pfizer/BioNTech, BNT162b2, and one with Moderna, mRNA-1273). Thrombocytopenia was reported in 107/187 CVST cases (57%, 95% confidence interval [CI] 50%-64%) in the ChAdOx1 nCov-19 group, in none in the mRNA vaccine group (0%, 95% CI 0%-13%) and in 7/100 (7%, 95% CI 3%-14%) in the pre-COVID-19 group. In the ChAdOx1 nCov-19 group, 39 (21%) reported COVID-19 polymerase chain reaction tests were performed within 30 days of CVST symptom onset, and all were negative. Of the 117 patients with a reported outcome in the ChAdOx1 nCov-19 group, 44 (38%, 95% CI 29%-47%) had died, compared to 2/10 (20%, 95% CI 6%-51%) in the mRNA vaccine group and 3/100 (3%, 95% CI 1%-8%) in the pre-COVID-19 group. Mortality amongst patients with thrombocytopenia in the ChAdOx1 nCov-19 group was 49% (95% CI 39%-60%). Conclusions Cerebral venous sinus thrombosis occurring after ChAdOx1 nCov-19 vaccination has a clinical profile distinct from CVST unrelated to vaccination. Only CVST after ChAdOx1 nCov-19 vaccination was associated with thrombocytopenia.
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| 6. |
- Lindgren, Erik, 1993, et al.
(författare)
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A scoring tool to predict mortality and dependency after cerebral venous thrombosis.
- 2023
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Ingår i: European journal of neurology. - 1468-1331. ; 30:8, s. 2305-2314
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Tidskriftsartikel (refereegranskat)abstract
- We developed a prognostic score to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials..We used data from the International CVT Consortium. We excluded patients with pre-existent functional dependency. We used logistic regression to predict poor outcome (modified Rankin Scale 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunken using Ridge regression to adjust for optimism in internal validation.Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, we derived the SI2 NCAL2 C score utilizing the following components: absence of female Sex-specific risk factor, Intracerebral hemorrhage, Infection of the central nervous system, Neurologic focal deficits, Coma, Age, lower Level of hemoglobin (g/L), higher Level of glucose (mmol/L) at admission, and Cancer. C-statistics were 0.80 (95%CI 0.75-0.84), 0.84 (95%CI 0.80-0.88) and 0.84 (95%CI 0.80-0.88) for the poor outcome, 30 days and 1 year mortality model, respectively. Calibration plots indicated good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com.The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.
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| 7. |
- Lindgren, Erik, 1993, et al.
(författare)
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Acute symptomatic seizures in cerebral venous thrombosis
- 2020
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 95:12, s. E1706-E1715
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium. Methods We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression. Results Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome. Conclusion ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.
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| 8. |
- Lindgren, Eric, 1997, et al.
(författare)
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calorine: A Python package for constructing and sampling neuroevolution potential models
- 2024
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Ingår i: Journal of Open Source Software. - 2475-9066. ; 9:95, s. 6264-6264
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Tidskriftsartikel (refereegranskat)abstract
- Molecular dynamics (MD) simulations are a key tool in computational chemistry, physics, and materials science, aiding the understanding of microscopic processes but also guiding the development of novel materials. A MD simulation requires a model for the interatomic interactions. To this end, one traditionally often uses empirical interatomic potentials or force fields, which are fast but inaccurate, or ab-initio methods based on electronic structure theory such as density functional theory, which are accurate but computationally very expensive (Müser et al., 2023). Machine-learned interatomic potentials (MLIPs) have in recent years emerged as an alternative to these approaches, combining the speed of heuristic force fields with the accuracy of ab-initio techniques (Unke et al., 2021). Neuroevolution potentials (NEPs), implemented in the GPUMD package, in particular, are a highly accurate and efficient class of MLIPs (Fan et al., 2021, 2022; Fan, 2022). NEP models have already been used to study a variety of properties in a range of materials, with recent examples including radiation damage in tungsten (Liu et al., 2023), phase transitions (Fransson, Wiktor, et al., 2023) and dynamics of halide perovskites (Fransson, Rosander, et al., 2023) as well as thermal transport in two-dimensional materials (Sha et al., 2023). Here, we present calorine, a Python package that simplifies the construction, analysis and use of NEP models via GPUMD.
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| 9. |
- Lindgren, Erik, 1993
(författare)
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Cerebral Venous Thrombosis - Complications and Outcomes
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral venous thrombosis (CVT) is a relatively rare cause of stroke, which predominantly affects working-aged adults and particularly women. The clinical course is highly miscellaneous. Data from large cohorts are scarce and knowledge on CVT complications and outcomes are limited. The overarching aim of this thesis was to investigate prognostic factors affecting clinical outcome after CVT. We investigated adult patients consecutively diagnosed with CVT from a local registry, the Sahlgrenska CVT Registry (study I), and from a newly established large international cohort from, in total, 17 hospitals, the International CVT Consortium (study II-V). Among 62 working-aged adults included from the Sahlgrenska CVT Registry, functional outcome was good as 87% were independent at long-term follow-up. However, 29% were unable to return to work and merely 19% were asymptomatic (study I). In study II-V, patients were included from the International CVT Consortium. Acute symptomatic seizure(s) occurred in 441/1,281 (34%) patients, predicted by variables related to parenchymal injury adjacent to the cerebral cortex (study II). Of 123/1,127 (11%) experiencing a first late seizure (>7 days after diagnosis), seizure recurrence rate was 70% (study III). A dural arteriovenous fistula was detected in 29/1,218 (2.4%) patients, most commonly concomitant or subsequently to the diagnosis of CVT (study IV). Acute symptomatic seizures, status epilepticus in the acute phase and dural arteriovenous fistulas were not associated with worse functional outcome (study II and IV). From risk factors affecting clinical outcome, we developed the combined SI2NCAL2C risk score to calculate individual risks of dependency or mortality at 6 months, mortality at 30-days and mortality at 1 year. The model showed promising performance in internal validations (study V). This thesis indicates that although most patients recover well and achieve independency after CVT, residual symptoms are frequent and one-quarter of working-aged adults are unable to return to work. Seizures frequently complicate the acute phase and every tenth patient experiences late seizures after CVT. The high risk of late seizure recurrence supports the diagnosis of epilepsy at time of a first late seizure. Dural arteriovenous fistulas are infrequent and mostly appear simultaneously or after CVT. The SI2NCAL2C risk score can be used with information available in routine clinical practice, to predict dependency or mortality at 6 months, mortality at 30-days and mortality at 1 year, but warrant external validation prior to implementation in clinical practice.
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| 10. |
- Lindgren, Erik, 1993, et al.
(författare)
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Dural arteriovenous fistulas in cerebral venous thrombosis Data from the International Cerebral Venous Thrombosis Consortium
- 2022
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:3, s. 761-770
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population. Methods We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up. Results dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8 (5-23) months. Patients with dAVF were older (median [IQR] 53 [44-61] vs. 41 [29-53] years; p < 0.001), more frequently male (69% vs. 33%; p < 0.001), more often had chronic clinical CVT onset (>30 days: 39% vs. 7%; p < 0.001) and sigmoid sinus thrombosis (86% vs. 51%; p < 0.001), and less frequently had parenchymal lesions (31% vs. 55%; p = 0.013) at baseline imaging. Clinical outcome at last follow-up did not differ between patients with and without dAVF. Additionally, five patients were confirmed with dAVF from non-consecutive CVT cohorts. Among all patients with CVT and dAVF, 17/34 (50%) had multiple fistulas and 23/34 (68%) had cortical venous drainage. Of 34 patients with dAVF with 36 separate CVT events, 3/36 fistulas (8%) were diagnosed prior to, 20/36 (56%) simultaneously and 13/36 after (36%, median 115 [IQR 38-337] days) diagnosis of CVT. Conclusions Dural arteriovenous fistulas occur in at least 2% of CVT patients and are associated with chronic CVT onset, older age and male sex. Most CVT-related dAVFs are detected simultaneously or subsequently to diagnosis of CVT.
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