Posterior confluent white matter hyperintensities and intracerebral hemorrhage recurrence risk in patients with cerebral amyloid angiopathy

Background Cerebral amyloid angiopathy (CAA) is associated with a high risk of recurrence of intracerebral hemorrhage (ICH). This study aimed to identify risk factors of CAA-related ICH recurrence, especially focused on CAA-characteristic neuroimaging markers. Methods Consecutive survivors of spontaneous lobar ICH for probable CAA, possible CAA, and mixed cerebral small vessel disease (CSVD) were enrolled at Tianjin Huanhu Hospital between 2017 and 2024. Baseline clinical data and magnetic resonance imaging (MRI) findings were collected. Posterior confluent white matter hyperintensities (WMH-PC), which means WMHs predominantly posterior to the ventricular horns, extending more than 5 mm in the deep white matter. Other MRI features included multispot white matter hyperintensities (WMH-MS), cortical superficial siderosis (cSS), perivascular spaces (PVS), and acute convexity subarachnoid hemorrhage (cSAH) in the present study. Participants were prospectively followed for recurrent symptomatic ICH or death. Kaplan-Meier and Cox-regression models were used to assess associations with ICH recurrence risk. Results The cohort included 254 survivors of spontaneous ICH, with median age of 68.5 years (interquartile range [IQR]: 63.0–76.0) and 63.0% male. WMH-PC was present in 124 patients (48.8%). Hundred and seventy patients (66.9%) were probable CAA-related ICH. Over a median follow-up period of 20.0 months (IQR: 8.0–38.0), 53 patients (20.9%) experienced recurrent ICH. In the probable CAA-related ICH group, WMH-PC (adjusted hazard ratio [aHR]: 2.548; 95% confidence interval [CI]: 1.251–5.193); cSS (aHR: 2.340; 95% CI: 1.126–4.860); and CSO-PVS (aHR: 2.751; 95% CI: 1.219–6.207) were associated with increased risk of ICH recurrence; after adjusted for the MRI features, only CSO-PVS (aHR: 2.278; 95% CI: 1.075–4.828) remained independently associated with an increased risk of ICH recurrence. The effect of combined WMH-PC and cSS on the recurrence of ICH in cases of probable CAA was synergistic (aHR: 3.160; 95% CI: 1.579–6.325). Conclusions WMH-PC, cSS and CSO-PVS are risk factors associated with ICH recurrence and WMH-PC in combination with cSS demonstrates a synergistic effect on increased ICH recurrence risk in patients with probable CAA.