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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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cerebral venous outflow may play a decisive role in acute ischemic stroke. Here, we assessed the relation of cerebral sinus vein characteristics with clinical and imaging surrogates of early outcome in acute ischemic stroke. We evaluated cerebral vein characteristics in 212 patients with the middle cerebral artery (MCA) occlusive stroke confirmed by CT angiography CTA within 6 h from symptom onset. Readout parameters included volume and density of the sigmoid sinus (SS) and density of the superior sagittal sinus (SupSagS). These were correlated with early clinical outcome defined as hospital death (HD), final infarct volume (FIV), and National Institute of Health Stroke Scale (NIHSS) at discharge. We found a correlation for the volume of the right SS and the FIV when the M1 segment of the MCA of either side was occluded (p = 0.002, Rho = 0.206, n = 134). A decrease in SS density was more pronounced in the subgroup with unfavorable outcome (NIHSS > 15 + HD) but only when the left hemisphere was affected (p = 0.026, n = 101). On stepwise logistic regression analysis, adjusted for on-admission NIHSS, age at presentation, and FIV, smaller SS volume was independently associated with lower odds for hospital death (n = 183, OR 0.13, 95 % CI 0.02-0.94, p = 0.043). A larger right SS and a decrease in density increase the risk of unfavorable early clinical and imaging outcome in AIS. This finding of an outflow pattern independent of the stroke site implicates an involvement of the cerebral venous drainage system in the pathophysiology of ischemic stroke.

The aim of our study was to assess whether cerebral artery clots undergo time-dependent morphological and compositional changes in acute ischemic stroke. We performed a retrospective chart review of patients admitted within 5 h from symptom onset to three European stroke centers and evaluated non-contrast-enhanced CT (NECT) for hyperdense artery signs (HAS) in 2565 scans. The occlusion site, density of HAS expressed in Hounsfield units (HU), area of HAS, and relative density (rHU) (HU clot/HU non-affected artery) were studied and related to time from symptom onset, clinical severity, stroke etiology, and laboratory parameters. A HAS was present in the middle cerebral artery (MCA) in 185 (7.2%) and further explored. The mean time from symptom onset to CT was 100 min (range 17-300). We found a time-dependent loss of density in the occluded M1 segment within the first 5 h ( N = 118, 95% CI [-15, -2], p = 0.01). Further, the thrombus area in the M2 segment decreased with time (cubic trend N = 67, 95% CI [-63, -8], p = 0.02). Overall, and especially in the M2 segment, a lower clot area was associated with higher fibrinogen (-21.7%, 95% CI [-34.8, -5.8], p = 0.009). In conclusion, our results disclosed time-dependent changes of intracranial thrombi with regard to occlusion site, density and area., Competing Interests: The authors declare no conflict of interest.

We explored whether clot density in middle cerebral artery (MCA) occlusion is related to clinical variables, stroke etiology, blood constituents, and prestroke medication. We performed a retrospective chart review of patients with acute ischemic stroke of the anterior circulation admitted to two Central European stroke centers. The acquisition of non-contrast enhanced CT (NECT) and CT angiography (CTA) within 4.5 h of symptom onset was obligatory. We assessed the site of MCA occlusion as well as density, area, and length of the clot in 150 patients. The Hounsfield unit values for the clot were divided with contralateral MCA segment to yield relative Hounsfield Unit ratio (rHU). The site of the vessel occlusion (M1 vs. M2) and antiplatelet usage, but not stroke etiology, significantly influenced rHU. We found an inverse correlation of rHU with erythrocyte count (p < 0.001). The multivariate analysis revealed that a higher rHU (i.e., clot being more hyperdense) was more likely with the use of antiplatelets (OR 4.24, CI 1.10-16.31, p = 0.036). Erythrocyte (OR 0.18, CI 0.05-0.55, p = 0.003), and thrombocyte counts (OR 0.99, CI 0.98-0.99, p = 0.029) were associated with odds for more hypodense clots (lower rHU). Our study disclosed that antiplatelet therapy impacts the composition of intracranial clots of the anterior circulation., Competing Interests: The authors declare no conflicts of interest.