Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature

Abstract

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.