SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Putaala J.) srt2:(2020-2024)"

Sökning: WFRF:(Putaala J.) > (2020-2024)

  • Resultat 1-50 av 50
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Mishra, A., et al. (författare)
  • Stroke genetics informs drug discovery and risk prediction across ancestries
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
  •  
2.
  • Jaworek, T., et al. (författare)
  • Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke
  • 2022
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
  •  
3.
  • van de Munckhof, A., et al. (författare)
  • Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase
  • 2022
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
  •  
4.
  • Afifi, K., et al. (författare)
  • Features of intracranial hemorrhage in cerebral venous thrombosis
  • 2020
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 3292-3298
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. Aim To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. Methods We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. Results We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage,p = 0.4). Conclusion The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.
  •  
5.
  • Jaakonmäki, N., et al. (författare)
  • Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults
  • 2022
  • Ingår i: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 31:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. Materials and Methods: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. Results: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. Conclusions: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors. © 2022 The Author(s)
  •  
6.
  • Ken-Dror, G., et al. (författare)
  • Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis
  • 2021
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 90:5, s. 777-788
  • 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
  •  
7.
  • van de Munckhof, A., et al. (författare)
  • Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries
  • 2023
  • Ingår i: International Journal of Stroke. - 1747-4930. ; 18:9, s. 1112-1120
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.
  •  
8.
  •  
9.
  • Ranjan, R., et al. (författare)
  • Age of onset of cerebral venous thrombosis: the BEAST study
  • 2023
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 344-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged > 18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years (p < 0.001), respectively. However, the presence of antibiotic-requiring sepsis (p = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy (p < 0.001, 95% CI 29-34 years), puerperium (p < 0.001, 95% CI 26-34 years) and oral contraceptive use (p < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, similar to 12 years younger, in those with multiple (> 1) compared to '0' risk factors (p < 0.001, 95% CI 32-35 years). Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (> 1) risk factors suffer CVT similar to 12 years earlier compared to those with no identifiable risk factors.
  •  
10.
  • Scutelnic, A., et al. (författare)
  • Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19
  • 2023
  • Ingår i: European Stroke Journal. - 2396-9873. ; 8:4, s. 1001-1010
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x10(9)/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.
  •  
11.
  • van Kammen, M. S., et al. (författare)
  • Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic
  • 2021
  • Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 326:4, s. 332-338
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. OBJECTIVE To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. EXPOSURES Diagnosis of cerebral venous sinus thrombosis. MAIN OUTCOMES AND MEASURES Frequencies of admission thrombocytopenia (platelet count <150 x10(3)/mu L), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). RESULTS Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 x10(3)/mu L) in 52 (6.0%), moderate (50-99 x10(3)/mu L) in 17 (2.0%), and severe (<50 x10(3)/mu L) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. CONCLUSIONS AND RELEVANCE In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopeniawas uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodieswere rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.
  •  
12.
  • Broman, J., et al. (författare)
  • Long-term risk of recurrent vascular events and mortality in young stroke patients: Insights from a multicenter study
  • 2023
  • Ingår i: European Journal of Neurology. - 1351-5101. ; 30:9, s. 2675-2683
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although the incidence of stroke in the young is rising, data on long-term outcomes in these patients are scarce. We thus aimed to investigate the long-term risk of recurrent vascular events and mortality in a multicenter study. Methods: We followed 396 consecutive patients aged 18-55 years with ischemic stroke (IS) or transient ischemic attack (TIA) enrolled in three European centers during the period 2007-2010. A detailed outpatient clinical follow-up assessment was performed between 2018 and 2020. When an in-person follow- -up visit was not possible, outcome events were assessed using electronic records and registry data. Results: During a median follow-up of 11.8 (IQR 10.4-12.7) years, 89 (22.5%) patients experienced any recurrent vascular event, 62 (15.7%) had any cerebrovascular event, 34 (8.6%) had other vascular events, and 27 (6.8%) patients died. Cumulative 10-year incidence rate per 1000 person-years was 21.6 (95% CI 17.1-26.9) for any recurrent vascular event and 14.9 (95% CI 11.3-19.3) for any cerebrovascular event. The prevalence of cardiovascular risk factors increased over time, and 22 (13.5%) patients lacked any secondary preventive medication at the in-person follow-up. After adjustment for demographics and comorbidities, atrial fibrillation at baseline was found to be significantly associated with recurrent vascular events. Conclusions: This multicenter study shows a considerable risk of recurrent vascular events in young IS and TIA patients. Further studies should investigate whether detailed individual risk assessment, modern secondary preventive strategies, and better patient adherence may reduce recurrence risk.
  •  
13.
  • Krzywicka, K., et al. (författare)
  • Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination
  • 2022
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 98:7
  • 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.
  •  
14.
  • Krzywicka, K., et al. (författare)
  • Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency
  • 2021
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:11, s. 3656-3662
  • 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.
  •  
15.
  • van de Munckhof, A., et al. (författare)
  • Declining mortality of cerebral venous sinus thrombosis with thrombocytopenia after SARS-CoV-2 vaccination
  • 2022
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:1, s. 339-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose High mortality rates have been reported in patients with cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) after vaccination with adenoviral vector SARS-CoV-2 vaccines. The aim of this study was to evaluate whether the mortality of patients with CVST-VITT has decreased over time. Methods The EudraVigilance database of the European Medicines Agency was used to identify cases of CVST with concomitant thrombocytopenia occurring within 28 days of SARS-CoV-2 vaccination. Vaccines were grouped based on vaccine type (adenoviral or mRNA). Cases with CVST onset until 28 March were compared to cases after 28 March 2021, which was the day when the first scientific paper on VITT was published. Results In total, 270 cases of CVST with thrombocytopenia were identified, of which 266 (99%) occurred after adenoviral vector SARS-CoV-2 vaccination (ChAdOx1 nCoV-19, n = 243; Ad26.COV2.S, n = 23). The reported mortality amongst adenoviral cases with onset up to 28 March 2021 was 47/99 (47%, 95% confidence interval 37%-58%) compared to 36/167 (22%, 95% confidence interval 16%-29%) in cases with onset after 28 March (p < 0.001). None of the four cases of CVST with thrombocytopenia occurring after mRNA vaccination died. Conclusion The reported mortality of CVST with thrombocytopenia after vaccination with adenoviral vector-based SARS-CoV-2 vaccines has significantly decreased over time, which may indicate a beneficial effect of earlier recognition and/or improved treatment on outcome after VITT.
  •  
16.
  • Broman, J., et al. (författare)
  • Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke
  • 2022
  • Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 54:1, s. 1757-1766
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. Patients and methods The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. Results Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. Conclusions In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding. KEY MESSAGES Initiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Patients starting antidepressants after IS should be followed up more closely in case of recurrent events. Future studies are needed to verify the results and to further study the nature of this finding.
  •  
17.
  • Broman, J., et al. (författare)
  • Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study
  • 2022
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 269, s. 956-965
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. Methods: Helsinki Young Stroke Registry includes patients aged 15–49years with first-ever IS, 1994–2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. Results: We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48–4.31) and during later follow-up among those with silent infarcts (2.04; 1.27–3.28), prior use of antidepressants (2.09; 1.26–3.46) and moderate versus mild stroke (2.06; 1.18–3.58). The relative difference in the hazard rate for moderate–severe limb paresis persisted both within the first 100days (3.84, 2.12–6.97) and during later follow-up (4.54; 2.51–8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11–1.97) as well as lower (1.78; 1.25–2.54) and upper white-collar workers (2.00; 1.24–3.23) compared to blue-collar workers. Conclusion: One-fourth of young adults started PSADs within 1year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up. © 2021, The Author(s).
  •  
18.
  • Elmegiri, M., et al. (författare)
  • MRI Characterization of Non-traumatic Intracerebral Hemorrhage in Young Adults
  • 2020
  • Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: Non-traumatic intracerebral hemorrhage (ICH) in younger population is a relatively rare event but is associated with considerable mortality and poor functional outcome. Imaging plays a crucial role in determining the underlying cause and guide treatment of ICH. In up to 41% of patients in prior studies, the underlying cause remained elusive. However, the usage of MRI as part of diagnostic work-up was scanty. We aimed to analyze MRI findings of ICH in younger patients and assess specificity and sensitivity of MRI in detecting structural or local underlying causes of ICH. Methods: We included patients aged 15-49 years with first-ever ICH identified from a prospective hospital discharge registry, 2000-2010. All study patients underwent MRI within 3 months of ICH. Imaging data was analyzed by a senior neuroradiologist blinded to final clinical diagnosis. We calculated the diagnostic accuracy of MRI in detecting structural/local underlying causes. Results: Of our 116 patients (median age, 39; 67% males), structural/local causes were the leading causes of ICH (50.0%), and of these, bleeding cavernomas (23.3%) were the most frequent followed by arteriovenous malformations (12.9%), cerebral venous thrombosis (CVT) (7.8%), brain tumors (5.2%), and moyamoya disease (0.9%). Lobar location of ICH was more prevalent in younger patients. MRI was highly sensitive (90.0%; 95% confidence interval, 79.5-96.2%) for detection of structural/local causes compared with angiographic imaging (55.6%; 95% CI, 40.0-70.4%), while MRI was less specific (87.3%; 95% CI, 75.5-94.7%) for structural/local causes, compared with angiographic imaging (97.4%; 95% CI, 86.5-99.9%). Conclusion: MRI was highly sensitive for the detection of structural and local causes underlying ICH in young adults. Thus, MRI should be considered in the diagnostic work-up of all young ICH patients to enable targeted secondary prevention.
  •  
19.
  • Inkeri, J., et al. (författare)
  • Carotid intima-media thickness and arterial stiffness in relation to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes
  • 2021
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 58:7, s. 929-937
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To determine if arterial functional and structural changes are associated with underlying cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes. Methods We enrolled 186 individuals (47.8% men; median age 40.0, IQR 33.0-45.0 years) with type 1 diabetes (median diabetes duration of 21.6, IQR 18.2-30.3 years), and 30 age- and sex-matched healthy controls, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. All individuals underwent a biochemical work-up, brain magnetic resonance imaging (MRI), ultrasound of the common carotid arteries and arterial tonometry. Arterial structural and functional parameters were assessed by carotid intima-media thickness (CIMT), pulse wave velocity and augmentation index. Results Cerebral microbleeds (CMBs) were present in 23.7% and white matter hyperintensities (WMHs) in 16.7% of individuals with type 1 diabetes. Those with type 1 diabetes and CMBs had higher median (IQR) CIMT 583 (525 - 663) mu m than those without 556 (502 - 607) mu m, p = 0.016). Higher CIMT was associated with the presence of CMBs (p = 0.046) independent of age, eGFR, ApoB, systolic blood pressure, albuminuria, history of retinal photocoagulation and HbA(1c). Arterial stiffness and CIMT were increased in individuals with type 1 diabetes and WMHs compared to those without; however, these results were not independent of cardiovascular risk factors. Conclusions Structural, but not functional, arterial changes are associated with underlying CMBs in asymptomatic individuals with type 1 diabetes.
  •  
20.
  •  
21.
  • Inkeri, J., et al. (författare)
  • Glycemic control is not related to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes
  • 2022
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 59, s. 481-490
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To determine if medium- and long-term blood glucose control as well as glycemic variability, which are known to be strong predictors of vascular complications, are associated with underlying cerebral small vessel disease (cSVD) in neurologically asymptomatic individuals with type 1 diabetes. Methods A total of 189 individuals (47.1% men; median age 40.0, IQR 33.0-45.2 years) with type 1 diabetes (median diabetes duration of 21.7, IQR 18.3-30.7 years) were enrolled in a cross-sectional retrospective study, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA(1c)) values were collected over the course of ten years before the visit including a clinical examination, biochemical sampling, and brain magnetic resonance imaging. Markers of glycemic control, measured during the visit, included HbA(1c), fructosamine, and glycated albumin. Results Signs of cSVD were present in 66 (34.9%) individuals. Medium- and long-term glucose control and glycemic variability did not differ in individuals with signs of cSVD compared to those without. Further, no difference in any of the blood glucose variables and cSVD stratified for cerebral microbleeds (CMBs) or white matter hyperintensities were detected. Neither were numbers of CMBs associated with the studied glucose variables. Additionally, after dividing the studied variables into quartiles, no association with cSVD was observed. Conclusions We observed no association between glycemic control and cSVD in neurologically asymptomatic individuals with type 1 diabetes. This finding was unexpected considering the large number of signs of cerebrovascular pathology in these people after two decades of chronic hyperglycemia and warrants further studies searching for underlying factors of cSVD.
  •  
22.
  •  
23.
  • Lindgren, Erik, 1993, et al. (författare)
  • Acute symptomatic seizures in cerebral venous thrombosis
  • 2020
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 95:12
  • 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.
  •  
24.
  • Lindgren, Erik, 1993, et al. (författare)
  • Dural arteriovenous fistulas in cerebral venous thrombosis Data from the International Cerebral Venous Thrombosis Consortium
  • 2022
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:3, s. 761-770
  • 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.
  •  
25.
  • Martinez-Majander, N., et al. (författare)
  • Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults
  • 2021
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 89:2, s. 242-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). Methods We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (+/- 5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. Results The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. Interpretation MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2020
  •  
26.
  • Martinez-Majander, N., et al. (författare)
  • Endothelial Dysfunction is Associated With Early-Onset Cryptogenic Ischemic Stroke in Men and With Increasing Age
  • 2021
  • Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 10:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (+/- 5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients >= 41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.
  •  
27.
  • Martinez-Majander, N., et al. (författare)
  • Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study
  • 2022
  • Ingår i: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 31:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. Methods: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. Results: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). Conclusions: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS. © 2022 The Author(s)
  •  
28.
  • Paciaroni, M., et al. (författare)
  • Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes
  • 2020
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
  •  
29.
  • Sánchez Van Kammen, Mayte, et al. (författare)
  • Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
  • 2021
  • Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
  •  
30.
  • van Kammen, M. S., et al. (författare)
  • Late seizures in cerebral venous thrombosis
  • 2020
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 95:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT. Methods We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with 7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS. Results We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced >= 1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS. Conclusion During a median follow-up of 2 years, approximate to 1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS.
  •  
31.
  •  
32.
  •  
33.
  • Eriksson, M. I., et al. (författare)
  • Haptoglobin genotype and its relation to asymptomatic cerebral small-vessel disease in type 1 diabetes
  • 2023
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 60:6, s. 749-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles’ association with SVD. Methods: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7years, diabetes duration 23 ± 10years, HbA1c 8.1 ± 3.2% [65 ± 12mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts). Results: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74–83], 75 [70–80], and 75 [72–81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46–2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. Conclusions: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.
  •  
34.
  •  
35.
  • Giustozzi, M., et al. (författare)
  • Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation
  • 2020
  • Ingår i: Stroke. - 0039-2499. ; 51:8, s. 2347-2354
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 Georg Thieme Verlag. All rights reserved.
  •  
36.
  • Ilinca, A., et al. (författare)
  • Whole-Exome Sequencing in 22 Young Ischemic Stroke Patients With Familial Clustering of Stroke
  • 2020
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 51:4, s. 1056-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • Backgrounds and Purpose-Although new methods for genetic analyses are rapidly evolving, there are currently knowledge gaps in how to detect Mendelian forms of stroke. Methods-We performed whole-exome sequencing in 22 probands, under 56 years at their first ischemic stroke episode, from multi-incident stroke families. With the use of a comprehensive stroke-gene panel, we searched for variants in stroke-related genes. The probands' clinical stroke subtype was related to clinical characteristics previously associated with pathogenic variants in these genes. Relatives were genotyped in 7 families to evaluate stroke-gene variants of unknown significance. In 2 larger families with embolic stroke of unknown source, whole-exome sequencing was performed in additional members to examine the possibility of identifying new stroke genes. Results-Six of 22 probands carried pathogenic or possibly pathogenic variants in genes reported to be associated with their stroke subtype. A known pathogenic variant in NOTCH3 and a possibly pathogenic variant in ACAD9 gene were identified. A novel JAK2:c.3188G>A (p.Arg1063His) mutation was seen in a proband with embolic stroke of undetermined source and prothrombotic status. However, penetrance in the family was incomplete. COL4A2:c.3368A>G (p.Glu1123Gly) was detected in 2 probands but did not cosegregate with the disease in their families. Whole-exome sequencing in multiple members of 2 pedigrees with embolic stroke of undetermined source revealed possibly pathogenic variants in genes not previously associated with stroke, GPR142:c.148C>G (p.Leu50Val), and PTPRN2:c.2416A>G (p.Ile806Val); LRRC1 c.808A>G (p.Ile270Val), SLC7A10c.1294dupG (p.Val432fs), IKBKB: c.1070C>T (p.Ala357Val), and OXGR1 c.392G>A (p.Arg131His), respectively. Conclusions-Screening with whole-exome sequencing using a comprehensive stroke-gene panel may identify rare monogenic forms of stroke, but careful evaluation of clinical characteristics and potential pathogenicity of novel variants remain important. In our study, the majority of individuals with familial aggregation of stroke lacked any identified genetic causes.
  •  
37.
  • Krzywicka, Katarzyna, et al. (författare)
  • Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.
  • 2023
  • Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 30:5, s. 1335-1345
  • 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 28days 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 6months, 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.
  •  
38.
  • Lindgren, Erik, 1993, et al. (författare)
  • A scoring tool to predict mortality and dependency after cerebral venous thrombosis.
  • 2023
  • Ingår i: European journal of neurology. - 1468-1331. ; 30:8, s. 2305-2314
  • 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 30days 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, 30days 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.
  •  
39.
  • Roaldsen, M.B., et al. (författare)
  • Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial
  • 2023
  • Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 22:2, s. 117-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health. © 2023 Elsevier Ltd
  •  
40.
  • Scutelnic, Adrian, et al. (författare)
  • Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
  • 2022
  • Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
  •  
41.
  • Silvis, S. M., et al. (författare)
  • Anaemia at admission is associated with poor clinical outcome in cerebral venous thrombosis
  • 2020
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 27:4, s. 716-722
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose Anaemia is associated with poor clinical outcome after ischaemic and haemorrhagic stroke. The association between anaemia and outcome in patients with cerebral venous thrombosis (CVT) was examined. Methods Consecutive adult patients with CVT were included from seven centres. Anaemia at admission was scored according to World Health Organization definitions. Poor clinical outcome was defined as a modified Rankin Scale score 3-6 at last follow-up. A multiple imputation procedure was applied for handling missing data in the multivariable analysis. Using binary logistic regression analysis, adjustments were made for age, sex, cancer and centre of recruitment (model 1). In a secondary analysis, adjustments were additionally made for coma, intracerebral haemorrhage, non-haemorrhagic lesion and deep venous system thrombosis (model 2). In a sensitivity analysis, patients with cancer were excluded. Results Data for 952 patients with CVT were included, 22% of whom had anaemia at admission. Patients with anaemia more often had a history of cancer (17% vs. 7%, P < 0.001) than patients without anaemia. Poor clinical outcome (21% vs. 11%, P < 0.001) and mortality (11% vs. 6%, P = 0.07) were more common amongst patients with anaemia. After adjustment, anaemia at admission increased the risk of poor outcome [adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.5-3.7, model 1]. Model 2 revealed comparable results (aOR 1.9, 95% CI 1.2-3.2), as did the sensitivity analysis excluding patients with cancer (aOR 2.3, 95% CI 1.3-3.8, model 1). Conclusion The risk of poor clinical outcome is doubled in CVT patients presenting with anaemia at admission.
  •  
42.
  • Tatlisumak, Turgut, et al. (författare)
  • Comparison of Manual Cross-Sectional Measurements and Automatic Volumetry of the Corpus Callosum, and Their Clinical Impact: A Study on Type 1 Diabetes and Healthy Controls
  • 2020
  • Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Degenerative change of the corpus callosum might serve as a clinically useful surrogate marker for net pathological cerebral impact of diabetes type 1. We compared manual and automatic measurements of the corpus callosum, as well as differences in callosal cross-sectional area between subjects with type 1 diabetes and healthy controls. Materials and methods: This is a cross-sectional study on 188 neurologically asymptomatic participants with type 1 diabetes and 30 healthy age- and sex-matched control subjects, recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent clinical work-up and brain MRI. Callosal area was manually measured and callosal volume quantified with FreeSurfer. The measures were normalized using manually measured mid-sagittal intracranial area and volumetric intracranial volume, respectively. Results: Manual and automatic measurements correlated well (callosal area vs. volume: ρ = 0.83, p < 0.001 and mid-sagittal area vs. intracranial volume: ρ = 0.82, p < 0.001). We found no significant differences in the callosal measures between cases and controls. In type 1 diabetes, the lowest quartile of normalized callosal area was associated with higher insulin doses (p = 0.029) and reduced insulin sensitivity (p = 0.033). In addition, participants with more than two cerebral microbleeds had smaller callosal area (p = 0.002). Conclusion: Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1. © Copyright © 2020 Claesson, Putaala, Shams, Salli, Gordin, Liebkind, Forsblom, Summanen, Tatlisumak, Groop, Martola and Thorn.
  •  
43.
  • Van De Munckhof, Anita, et al. (författare)
  • Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase
  • 2022
  • Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization.Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization).Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed).Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
  •  
44.
  • Eltoft, Agnethe, et al. (författare)
  • Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)
  • 2022
  • Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.
  •  
45.
  • Ilinca, A., et al. (författare)
  • MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
  • 2021
  • Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke. Methods We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses. Results Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease. Conclusions Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
  •  
46.
  • Raty, S., et al. (författare)
  • Occipital intracerebral hemorrhage-clinical characteristics, outcome, and post-ICH epilepsy
  • 2021
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 143:1, s. 71-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Posterior location affects the clinical presentation and outcome of ischemic stroke, but little is known about occipital intracerebral hemorrhage (ICH). We studied non-traumatic occipital ICH phenotype, outcome, and post-ICH epilepsy. Materials and Methods Occipital ICH patients were retrospectively identified from the Helsinki ICH Study registry of 1013 consecutive ICH patients treated in our tertiary center in 2005-2010. They were compared to non-occipital ICH patients to evaluate the effect of location on functional outcome at discharge (dichotomized modified Rankin Scale, mRS), 3- and 12-month mortality, and incidence of epilepsy. Results We found 19 occipital ICH patients (5.3% of lobar and 1.9% of all ICH). Compared to non-occipital lobar ICHs, they were younger (median age 63 vs 71 years,P= .007) and had lower National Institutes of Health Stroke Scale on admission (1 vs 8,P< .001), smaller hematoma volume (6.3 vs 17.7 ML,P= .008), and more frequently structural etiology underlying the ICH (26% vs 7%,P= .01). Mortality at both 3 and 12 months was 6%, whereas 84% reached favorable outcome (mRS 0-2) at discharge. Occipital location was associated with favorable outcome at discharge in lobar ICH (OR 11.02, 95% CI 1.55-78.20). Incidence of post-ICH epilepsy (median follow-up 2.7 years) was 18%, equaling to that of non-occipital lobar ICH. Conclusions Occipital ICH patients are younger, have less severe clinical presentation, smaller hematoma volume, more often structural etiology, and better outcome than other ICH patients. They exhibit a similar risk of epilepsy as non-occipital ICHs.
  •  
47.
  • Sobowale, Oluwaseun A., et al. (författare)
  • Baseline perihematomal edema, C-reactive protein, and 30-day mortality are not associated in intracerebral hemorrhage
  • 2024
  • Ingår i: FRONTIERS IN NEUROLOGY. - 1664-2295. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood.Objective Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH.Methods Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality.Results We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively).Conclusion Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.
  •  
48.
  • van de Munckhof, Anita, et al. (författare)
  • Direct oral anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study
  • 2023
  • Ingår i: FRONTIERS IN NEUROLOGY. - 1664-2295. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Current guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3-12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking.Methods: DOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting.Discussion: DOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT.
  •  
49.
  • Weller, Johannes, et al. (författare)
  • Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia
  • 2024
  • Ingår i: EUROPEAN STROKE JOURNAL. - 2396-9873 .- 2396-9881. ; 9:1, s. 105-113
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. Patients and methods: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. Results: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). Discussion and conclusion: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.
  •  
50.
  • Woock, Malin, et al. (författare)
  • Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach.
  • 2022
  • Ingår i: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 50

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy