Background: The transmission of amyloid β (Aβ) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. Aims: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. Methods: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. Results: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4–18, range = 0–26 years) years. The median symptom latency was 39 years (IQR = 34–41, range = 28–49). The median age at symptom onset was 49 years (IQR = 43–55, range = 32–70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. Conclusions: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

Background and Purpose: Idarucizumab achieves instant reversal of anticoagulation and enables intravenous thrombolysis (IVT) in dabigatran-treated acute ischemic stroke (AIS) patients. AIS in dabigatran-treated patients is a rare event, therefore the experience is limited. A review of all published cases was performed to evaluate the safety and effectiveness of this therapeutic strategy.Methods: We searched PubMed and Scopus for all published cases of IVT after reversal with idarucizumab in dabigatran-treated AIS patients. The outcomes were safety assessed by hemorhagic transformation (HT), symptomatic intracranial hemorrhage (SICH) and death, and efficacy assessed by National Institutes of Health Stroke Scale (NIHSS) reduction.Results: We identified 251 AIS patients (39,9% females) with an average age of 74 years. HT, SICH, and death were reported in 19 (7.6%), 9 (3.6%), and 21 (8.4%) patients, respectively. Patients experiencing HT presented with more severe strokes (median NIHSS on admission: 21 vs. 8, p < 0.001; OR: 1.12, 95% CI: 1.05–1.20). After IVT there was a significant NIHSS reduction of 6 points (IQR:3–10, p < 0.001) post-stroke and linear regression revealed a correlation of admission NIHSS to NIHSS reduction (p < 0.001).Conclusions: In this systematic review of all published cases of IVT in dabigatran-treated AIS patients after reversal with idarucizumab the rates of HT, SICH and mortality, as well as NIHSS reduction, were comparable with previous studies in non-anticoagulated patients. This provides reassuring evidence about the safety and efficacy of this therapeutic strategy.

BACKGROUND: Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain. METHODS: Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of ≥2, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0–2 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake. RESULTS: Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73–86) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake <12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, −2.1% [95% CI, −5.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes. CONCLUSIONS: This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.