Temporal and Spatial Clustering of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy

Abstract

Objectives: Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH.

Methods: We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI.

Results: In 682 included patients (median age 68 years, 40.3% female, median follow-up time 4.1 years), 18 (2.6%) had an early recurrent ICH, which was associated with higher age and CAA. In patients with probable CAA, the risk of early recurrent ICH was increased 5-fold within the first 3 months compared with during months 4-12 (hazard ratio 5.41, 95% CI 2.18-13.4) while no significant difference was observed in patients without CAA. In patients with an ICH cluster, we observed spatial clustering (recurrent ICH within close proximity of index ICH in 63.0%) and a tendency for multiple sequential hemorrhages (≥3 ICH foci within 3 months in 44.4%).

Discussion: Our data provide evidence of both temporal and spatial clustering of ICH in CAA, suggesting a transient and localized active bleeding-prone process.

Figure 1. Temporal Changes in Risk of Recurrent Intracerebral Hemorrhage

Figure 2. Neuroimaging Findings in 2 Exemplary Patients With ICH Clusters

(A) A patient in their seventies with index right parietal intracerebral hemorrhage. On index CT, 2 additional separate foci of convexity subarachnoid hemorrhage were visible (right parietal, left frontal). 48 days after the index ICH, the patient suffered a recurrent ICH in the right frontal lobe. On MRI after clinical worsening 6 days later, an additional large left frontal ICH was visible, as were disseminated cortical superficial siderosis and numerous lobar microbleeds. This patient did not have any further recurrent ICH over a follow-up period of 9 years (with several CT scans performed in the follow-up period). (B) Another patient in their seventies with right occipital intracerebral hemorrhage. T2* MRI sequences did not show additional chronic hemorrhagic lesions. 6 years later, the patient suffered a left frontal hemorrhage. After initial stabilization, MRI depicted bilateral parietal acute convexity subarachnoid hemorrhage and extensive cortical superficial siderosis. 53 days after the second ICH, the patient had a large right frontal ICH and died shortly thereafter. ICH = intracerebral hemorrhage.