and the Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group 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 PARTICIPANTSThis 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 RELEVANCEIn 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.
ObjectiveTo 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.MethodsWe defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into pre-diagnosis and solely post-diagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS, and association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression.ResultsOf 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 post-diagnosis 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 were independently associated with outcome.ConclusionASS occurred in 1/3 of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In absence of pre-diagnosis ASS, no subgroup was identified with sufficient risk of post-diagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.
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 PARTICIPANTSThis 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,
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 twelve hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >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 one or more LS (incidence rate for first LS 30 per 1,000 person-years, 95%CI 25-35). Median time to first LS was 5 months (IQR 1-16). Baseline predictors of LS included status epilepticus in the acute phase (Hazard Ratio [HR] 7.0, 95%CI 3.9-12.6), acute seizure(s) without status epilepticus (HR 4.1, 95%CI 2.5-6.5), intracerebral hemorrhage (HR 1.9, 95%CI 1.1-3.1), subdural hematoma (HR 2.3, 95%CI 1.1-4.9) and decompressive hemicraniectomy (HR 4.2, 95%CI 2.4-7.3). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received anti-epileptic drug treatment after the first LS.Conclusion:During a median follow-up of two years, approximately one in ten patients with CVT had LS. Patients with baseline intracranial bleeding, 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.
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