Histopathologic substrate of drug-resistant epilepsy in older adults and the elderly undergoing surgery

Patients 60 years or older are one of the highest risk age groups for development of epilepsy. Clinical and neuroimaging analysis has typically accounted for etiology in two-thirds of these patients, while the data on histopathology are lacking. We provide the first analysis of the histopathological substrates underlying drug-resistant epilepsy (DRE) in older adults/elderly patients who underwent resective epilepsy surgery (RES) at Cleveland Clinic. A total of 78 patients (mean age ± standard deviation: 64.7 ± 3.7 years; 59% female) were included in the study. The most common pathologies included hippocampal sclerosis (HS; 35.9%; all visible on magnetic resonance imaging [MRI]), focal cortical dysplasia (FCD; 25.6%) and remote infarct/ischemic changes (12.8%). Underlying pathology did not differ significantly between the patients achieving a good seizure outcome (Engel class I; 77% [47 of 61 patients]) and the rest of the cohort. With one exception, all MRI-negative cases had FCD type Ib. A receiver-operating characteristic (ROC) curve analysis found a significant association (P = 0.002) between seizure-onset age and HS, whereby the odds of its presence were reduced by 4% for every 1 year increase in the age at seizure onset. The model showed that the age cutoff for seizure onset predicting HS was 43 years, with a negative predictive value of 81.6%. None of the 14 patients with late-onset epilepsy (≥60 years of age) were found to have HS; they mostly had acquired lesions. Our study provides histopathologic evidence for the diminished role of late-onset HS in DRE in older adults/elderly who undergo RES.