Abstract

Objective: We sought to determine the prevalence, radiological characteristics, and clinical outcomes of intracerebral hemorrhage (ICH) of undetermined etiology. Methods: Systematic review and meta-analysis of studies involving patients with spontaneous ICH was conducted to assess the prevalence and clinical-radiological characteristics of undetermined ICH. Additionally, we assessed the rates for ICH secondary to hypertensive arteriopathy (HTN-A) and cerebral amyloid angiopathy (CAA). Subgroup analyses were performed based on the use of a) etiology-oriented ICH classification, b) detailed neuroimaging, and c) Boston criteria among CAA-ICH. Results: 24 studies were included (n=15,828; mean age: 64.8 years, males: 60.8%). The pooled prevalence of HTN-A ICH, undetermined ICH and CAA-ICH were 50% (95%CI: 43-58%), 18% (95%CI: 13-23%), and 12% (95%CI: 7-17%; p<0.001 between subgroups). The volume of ICH was largest in CAA-ICH 24.7mL (95%CI: 19.7-29.8mL), followed by HTN-A ICH 16.2mL (95%CI: 10.9-21.5mL) and undetermined ICH 15.4mL (95%CI: 6.2-24.5mL). Among patients with undetermined ICH, the rates of short-term mortality and intraventricular hemorrhage were 33% (95%CI: 25-42%) and 38% (95%CI: 28-48%), respectively. Subgroup analysis demonstrated a higher rate of undetermined ICH among studies that did not use an etiology-oriented classification (22%; 95%CI: 15-29%). No difference was observed between studies based on the completion of detailed neuroimaging to assess the rates of undetermined ICH (p=0.62). Conclusions: The etiology of spontaneous ICH remains undetermined among one in five patients in studies using etiology-oriented classification and among one in four patients in studies that avoid using etiology-oriented classification. The short-term mortality in undetermined ICH is high despite the relatively small ICH volume. Our findings suggest the use of etiology-oriented classification to approach ICH patients (Figure).

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