To determine whether CAA patients with amyloid spells have a higher risk of developing epilepsy compared with those without spells.

Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterized by progressive β-amyloid deposition within the walls of cortical and leptomeningeal vessels. Transient focal neurological episodes “amyloid spells” are increasingly recognized as an early and distinctive presentation of the disease. Although seizures are well described in CAA, the relationship between amyloid spells, and the risk of developing epilepsy remains poorly understood.

We retrospectively analyzed patients diagnosed with probable or definite CAA according to Boston Criteria 2.0 at a single center between 2015 and 2024. Clinical, laboratory, and MRI data were extracted and compared between patients with and without amyloid spells using chi-square and t-tests.

Among 375 patients with CAA (mean age 78 ± 6 years; 49.6% female), 127 (33.9%) experienced amyloid spells. Compared with those without spells, patients with spells were more likely to have a history of transient ischemic attack (18.6% vs 5.6%, p < 0.001) but did not differ in age, sex, vascular comorbidities, or laboratory markers. MRI analyses showed a nonsignificant trend toward greater cortical superficial siderosis in the spell group (p = 0.096), while lobar microbleed, white-matter hyperintensity, and small-vessel disease burdens were comparable. Epilepsy developed in 44.9% of patients with amyloid spells versus 2.4 % without (p < 0.001). Ischemic stroke was also more frequent among those with spells (33.1% vs 22.2%, p = 0.023), while intracerebral hemorrhage rates were similar (16.5% vs 19.4%, p = 0.505).

Amyloid spells are strong and independent predictor of future epilepsy in patients with CAA. These findings suggest that amyloid spells may represent an early biomarker of cortical hyperexcitability, highlighting the need for closer surveillance and early intervention in this subgroup.