Seizures in Cerebral Amyloid Angiopathy: A Systematic Review and Meta-Analysis

Cerebral amyloid angiopathy (CAA) is a disease of the cerebral vasculature that can result in microhemorrhages, as well as intraparenchymal and subarachnoid hemorrhage, superficial siderosis (SS), and/or secondary infarct/inflammation. CAA may be encountered as an isolated pathology or with Alzheimer disease and has been demonstrated to be associated with an increased risk of seizures. However, the overall rates of seizures and specific pathologies related to CAA and their subsequent risk of seizures have not been elucidated.

Prior studies of CAA and seizures are predominantly case reports or small case series, and larger studies have focused primarily on smaller subgroups of patients with CAA. Only 2 prior studies assessed larger heterogeneous populations of patients with CAA. One study focused on long-term outcomes and evaluated the impact of seizures on cognitive and survival outcomes retrospectively, although it did not delineate the effects of acute and chronic seizure disorders (epilepsy) and did not find an association. Long-term prospective or retrospective studies on outcomes regarding seizures/epilepsy and CAA are therefore lacking.

A total of 1,376 articles were identified, with 48 (34 case reports/series and 14 cohort studies) included in this review. Acute symptomatic seizures (ASyS) and epilepsy were poorly defined, and the overall prevalence of seizures in cohort studies was 22.8%, with significant heterogeneity (I ² = 77%; p < 0.01). Epilepsy was diagnosed in 34.4% and ASyS in 10.6% of patients in heterogeneous cohorts. Most of the studies assessed seizures in specific subgroups of CAA with variable prevalence, including CAA with related inflammation (CAA-ri): 56.9%; lobar intracranial hemorrhage (ICH): 17.1%; and cortical SAH (cSAH) or SS: 8.7%. In heterogeneous cohorts, SS (p < 0.001 and p = 0.03, respectively) and CAA-ri (p = 0.005 and p = 0.04, respectively) were significantly associated with epilepsy/seizures. In 1 study, cSAH (p = 0.03) and acute lobar ICH (p = 0.002) were associated with seizures, likely related to inclusion of ASyS. Status epilepticus (14/125) and drug resistance (6/89) were infrequent. Clinical pathologic entities associated with a risk of seizures include cSAH, CAA-ri, SS, and acute ICH.