Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination

Objective 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. Methods 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. Results 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). Conclusions In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022Peer reviewe

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

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) 50x109/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.</p

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

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) 50x109/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.</p

Abstract 3932: High Rate Of Radiographic Stroke Recurrence In Cryptogenic TIA And Minor Stroke Patients: A Prospective Imaging Study

Introduction: Cryptogenic stroke (CS) mechanism in patients with TIA/Minor stroke has a recurrent stroke risk of 1-6% within 3 months. There is some evidence to suggest that an occult embolic phenomenon would be a likely cause of stroke in many patients with CS. It is likely that radiographic event rates are higher than clinical event rates which may potentially be a therapeutic target for proof of concept prevention trials. We sought to determine clinical and radiographic event rates in patients with cryptogenic mechanisms in a TIA/minor stroke population. Methods: Patients with TIA/Minor stroke (NIH Stroke Scale ≤ 3) were prospectively enrolled and imaged within 24 hours of symptom onset as part of two prospective imaging cohorts. [VISION (V) and CATCH (C)]. Patients were included if their baseline modified Rankin scale (mRS) was ≤1. All patients were followed clinically for 3 months to document any clinical recurrence and had a repeat MRI either at day 30 (V) or at day 90 (C). Stroke mechanisms were categorized as per TOAST criteria after parenchymal and vascular imaging and cardiac investigations. Patients were labelled as cryptogenic only after standard etiological workup for ischemic stroke including at least vascular imaging, transthoracic echocardiogram and holter monitoring was completed. Follow up imaging was assessed for any new lesions in comparison to baseline imaging. Results: Among patients enrolled in both prospective studies 380/844(45%) had cryptogenic stroke mechanisms. Of these, 215 patients had follow up imaging. There were 132 (61%) males. Intracranial occlusions was seen in 23/215 (10.6%) with baseline DWI abnormality documented in 66/215 (30.6%). In the VISION dataset, 5/76 (6.6%, 95%CI 2.2-15%) patients had new lesions on follow-up MRI at day 30. In the CATCH dataset 19/131 (14.5%: 9-22%) of patients had new lesions on follow-up MRI at day 90. Baseline DWI abnormalities was a significant predictor of new radiological lesions on follow-up imaging [p=0.003 OR 4.75 95% CI: 1.67-13.2]. Overall clinical recurrence was seen in 10/215 (4.6%: 2.2-8.4%) of patients. Baseline DWI abnormality was not a significant predictor of clinical recurrence (p=0.96). Conclusion: TIA/Minor stroke patients with cryptogenic mechanism show evidence of silent radiological accumulation of disease on follow up imaging at a higher rate than clinical recurrence. Repeat brain imaging at 3 months or potentially later may be a useful surrogate marker for disease activity in treatment trials in this population. There is a need for randomized controlled trials using novel anticoagulants with follow-up imaging as a surrogate marker of disease activity to improve treatment of cryptogenic minor stroke/TIA. </jats:p

Abstract 3968: Eloquence Of Region And Extent Of Brain Ischemia Detected By DWI Predicts Degree Of 24h Nihss Score Improvement After Arterial Recanalization In Ischemic Stroke

Introduction Improvement in NIHSS score at 24 hrs or delta NIHSS change (ΔNIHSS) is an early measure of response to recanalization treatment and has been associated with good outcome. We hypothesized that ΔNIHSS achieved with arterial recanalization may be influenced by eloquence of region involved within a vascular territory on baseline imaging. Methods Patients from prospectively collected Keimyung University stroke database, [2005-2009] were analyzed. Patients with proximal anterior circulation occlusions (ICA, MCA M1, proximal M2) who recanalized after IV tPA/IV tPA+endovascular therapy (TIMI 2/3) on DSA / MRA were included for final analysis.Detailed clinical and biochemical data collected prospectively was analyzed. Imaging analysis was done in University of Calgary. Two readers evaluated baseline DWI imaging and graded ischemic infarcts in16 anatomical regions(cortical MCA-M1,M2,M3,M4,M5,M6, insula; subcortical MCA- corona radiata -C1,C2,C3, basal ganglia; posterior limb of internal capsule; ACA- A1,A2 and PCA-P1,P2). Depending on the number of infarct regions involved, patients were categorized into three groups: mild - (0-3 infarct regions), moderate-(4-6), large and extensive (7-16). Improvement of 10 point in NIHSS score was labeled as treatment responders. ΔNIHSS change per point was the primary outcome. Results Among 265 patients in database, 101 patients who recanalized (TIMI2/3,) were analyzed. ΔNIHSS ≥10 was seen in 24 (24%) of subjects. There were 56% males. The mean age of patients was 65+-11.2yrs, Baseline median NIHSS was: 14 (IQR -11-16) and 24 hrs median NIHSS was 7 (IQR 6-9). There was no neurological improvement (ΔNIHSS) in patients with greater than 6 areas of involvement (p&lt;0.001).Glucose was significantly higher in patients without ΔNIHSS compared to patients with ΔNIHSS (p=0.01). The most eloquent regions as measured by absence of delta NIHSS&gt;10 despite recanalization were basal ganglia (OR 0.03 95%CI 0.004-0.25, p=0.001),posterior limb of internal capsule (OR 0.10 95%CI 0.01-0.85, p&lt;0.001) ,M2 ( OR 0.06 95%CI 0.01-0.25, p&lt;0.001)and C2 (core of corona radiata)(OR 0.12 95%CI 0.04-0.35 p&lt;0.001). Conclusions ΔNIHSS at 24 hours after recanalization is high in a situation when more anatomical regions are involved. Patients with more than six infarcted regions had no improvement in ΔNIHSS. Patients with baseline involvement (ischemic core) of the corona radiata (C2), M2 (temporal lobe), basal ganglia and internal capsule have the least chance for significant ΔNIHSS improvement. </jats:p

Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke

Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke