Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia

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.info:eu-repo/semantics/publishedVersio

The Italian Validation of the Social Skills Program PEERS® in Adolescents with Autism Spectrum Disorders (ASD): A Randomized Controlled Trial during COVID-19

Background. Social difficulties are a lifespan characteristic of the autism spectrum disorder (ASD), targeted in interventions for preschoolers and children, while evidence of their effectiveness in adolescents is lacking. The Program for the Education and Enrichment of Relational Skills (PEERS®) is an internationally recognized parent-assisted program on social skills, but in Italy there is no validated adaptation of this specific intervention. Objectives. A two-arm Randomized Controlled Trial to evaluate the effectiveness of the PEERS® intervention in the Italian context was conducted. Methods. The study was conducted according to CONSORT guidelines (Schulz et al., 2010) and registered in Clinical Trial (NCT05473104) (Figure 1). Adolescents with ASD (Level 1) were recruited through national stakeholders and public clinical services. Participants were randomly assigned to two groups stratified by gender and age: the experimental group (TG), attending training immediately, and the delay treatment group (WL), which participated after 14 weeks. Evaluation of primary (social abilities) and secondary outcomes (co-occurring conditions, executive functions) (Figure 2) was performed at 4 time-points: T0 (baseline), T1 (TG post-intervention and WL second baseline), T2 (TG follow-up and WL post-intervention), T3 (WL follow-up). A total of 99 teleconference interviews were conducted by an expert clinician, and 55 participants were excluded. Due to COVID-19, PEERS® training was delivered via telehealth (January-July 2021) and only questionnaires to multi-informant assessors (adolescents, parents, and teachers) were administered, with teachers blinded about the group allocation. Results. Of the 44 participants, 3 in the TG and 4 in the WL dropped out and were not replaced. Therefore, the sample was composed by 37 participants (Mage=15.3; SDage=2.0; range age:12.2-18.2), with 11 girls (29.7%) (TG=18; WL=19). There was no attrition in the outcome measures, except for 1 participant assigned to WL (T0 unavailable). No differences were found at T0 between TG and WL groups in baseline characteristics and primary outcomes. Significant groups differences emerged instead between T0 vs. T1 on primary (TASSK-R, F(1,22) = 40.79, p < .001, η2p = .65; QSQ-Social Initiative Scale parent version z = -3.412, p < .001; adolescent version z = -3.086, p = .002) and secondary outcomes (BRIEF-2 Emotion Regulation Index, F(1,22) = 15.20, p < .001, η2p = .41). To test additional treatment-related effects, we evaluated the changes in overall group (TG+WL) among pre- and post-intervention, and follow-up. Further changes from pre- to post-intervention emerged in secondary outcomes -(BRIEF- Global Executive Composite Score; CBCL-Youth version internalizing, externalizing, total problems; CDI-2 Functional Problems). All the improvements detected in post-treatment were also maintained at a 3-months follow-up. Conclusions. The efficacy of the Italian version of PEERS®– with minor changes to the original content's program – was ascertained on primary and secondary outcomes. Innovative findings on emotion regulation and depression symptoms have also emerged. Study limitations are due to blinding outcome assessors' bias and the absence of qualitative measures. Future studies should confirm the PEERS’ efficacy in community settings with traditional administration methods. Keywords: Autism spectrum disorder; Social skills training; Adolescents; validation; PEERS

Repeated reperfusion treatment in recurrent ischemic stroke. A retrospective single-center case series

Data regarding repeated reperfusion therapy (rRT) in acute ischemic stroke (AIS), including intravenous thrombolysis and endovascular treatment (EVT), are quite poor. To date, there are only few case reports and five larger studies on repeated EVT. We aimed to report our single-center experience and describe different clinical scenarios of recurrent AIS with emergent large vessel occlusion (LVO), for which the decision-making process could be challenging in the emergency setting. We retrospectively reviewed 765 consecutive AIS patients with LVO, who underwent reperfusion procedures at our comprehensive stroke center, from 2014 to 2020, and identified rRT patients. We identified and reviewed the medical records of eight patients (1.05%), who repeated reperfusive treatment for recurrent stroke within 30 days (early arterial reocclusion, EAR) and after 30 days (late arterial reocclusion, LAR). We assigned collected data to three clinical scenarios, each divided into EAR and LAR cases. All patients had recurrent emergent LVO in the same vessel territory previously affected, both in EAR and LAR patients. A good clinical outcome has been achieved in EAR patients (modified Rankin Score ≤ 2). Artery-to-artery embolic mechanism was more common in the EAR group, while LAR was more frequently associated with cardioembolic source. RRT appears to be an effective treatment option for recurrent LVO, and it should not be withheld in carefully selected patients. EVT should be considered, including aspiration-only and stenting procedures in patients with AIS and recurrent LVO after previous reperfusive treatments, even after a very short time

Predictive value of Tmax perfusion maps on final core in acute ischemic stroke: an observational single-center study

Purpose: To assess utility of computed tomography perfusion (CTP) protocols for selection of patients with acute ischemic stroke (AIS) for reperfusive treatments and compare the diagnostic accuracy (ACC) in predicting follow-up infarction, using time-to-maximum (Tmax) maps. Methods: We retrospectively reviewed consecutive AIS patients evaluated for reperfusive treatments at comprehensive stroke center, employing a multimodal computed tomography. To assess prognostic accuracy of CTP summary maps in predicting final infarct area (FIA) in AIS patients, we assumed the best correlation between non-viable tissue (NVT) and FIA in early and fully recanalized patients and/or in patients with favorable clinical response (FCR). On the other hand, the tissue at risk (TAR) should better correlate with FIA in untreated patients and in treatment failure. Results: We enrolled 158 patients, for which CTP maps with Tmax thresholds of 9.5 s and 16 s, presented sensitivity of 82.5%, specificity of 74.6%, and ACC of 75.9%. In patients selected for perfusion deficit in anterior circulation territory, CTP-Tmax > 16 s has proven relatively reliable to identify NVT in FCR patients, with a tendency to overestimate NVT. Similarly, CTP-Tmax > 9.5 s was reliable for TAR, but it was overestimated comparing to FIA, in patients with unfavorable outcomes. Conclusions: In our experience, Tmax thresholds have proven sufficiently reliable to identify global hypoperfusion, with tendency to overestimate both NVT and TAR, not yielding satisfactory differentiation between true penumbra and benign oligoemia. In particular, the overestimation of NVT could have serious consequences in not selecting potential candidates for a reperfusion treatment

Stroke network performance during the first COVID-19 pandemic stage: A meta-analysis based on stroke network models

Background: The effect of the COVID pandemic on stroke network performance is unclear, particularly with consideration of drip&ship vs. mothership models. Aims: We systematically reviewed and meta-analyzed variations in stroke admissions, rate and timing of reperfusion treatments during the first wave COVID pandemic vs. the pre-pandemic timeframe depending on stroke network model adopted. Summary of findings: The systematic review followed registered protocol (PROSPERO-CRD42020211535), PRISMA and MOOSE guidelines. We searched MEDLINE, EMBASE, and CENTRAL until 9 October 2020 for studies reporting variations in ischemic stroke admissions, treatment rates, and timing in COVID (first wave) vs. control-period. Primary outcome was the weekly admission incidence rate ratio (IRR = admissions during COVID-period/admissions during control-period). Secondary outcomes were (i) changes in rate of reperfusion treatments and (ii) time metrics for pre- and in-hospital phase. Data were pooled using random-effects models, comparing mothership vs. drip&ship model. Overall, 29 studies were included in quantitative synthesis (n = 212,960). COVID-period was associated with a significant reduction in stroke admission rates (IRR = 0.69, 95%CI = 0.61–0.79), with higher relative presentation of large vessel occlusion (risk ratio (RR) = 1.62, 95% confidence interval (CI) = 1.24–2.12). Proportions of patients treated with endovascular treatment increased (RR = 1.14, 95%CI = 1.02–1.28). Intravenous thrombolysis decreased overall (IRR = 0.72, 95%CI = 0.54–0.96) but not in the mothership model (IRR = 0.81, 95%CI = 0.43–1.52). Onset-to-door time was longer for the drip&ship in COVID-period compared to the control-period (+32 min, 95%CI = 0–64). Door-to-scan was longer in COVID-period (+5 min, 95%CI = 2–7). Door-to-needle and door-to-groin were similar in COVID-period and control-period. Conclusions: Despite a 35% drop in stroke admissions during the first pandemic wave, proportions of patients receiving reperfusion and time-metrics were not inferior to control-period. Mothership preserved the weekly rate of intravenous thrombolysis and the onset-to-door timing to pre-pandemic standards. © 2021 World Stroke Organization

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: 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. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: 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