Cerebral small vessel disease burden in late-onset epilepsy of unknown aetiology: insights from a prospective multicenter cohort

BACKGROUND: Late-onset epilepsy of unknown aetiology (LOEU) represents a prevalent and often disabling neurological disorder. Existing studies indicate that cerebral small vessel disease (cSVD) may play a significant role in the pathogenesis of epilepsy within this population; however, prospective investigations are currently lacking. We aimed to systematically describe the burden and qualitative aspects of cSVD in a LOEU population. METHODS: Patients with LOEU were prospectively included across three university hospitals (Nancy, Lille and Reims, France). Patients were systematically assessed for clinical, cardiovascular, neurophysiological (EEG, polygraphy/polysomnography), neuropsychological, and radiological features (brain MRI and FDG-PET). cSVD was assessed using MRI only. A composite score evaluating WMH, microbleeds, EPVS, and lacunar infarcts was used. Moderate-to-severe cSVD was defined as a score of 2 4. RESULTS: A total of 55 patients were enrolled, predominantly male (63.6%), with a median age of 71yo (IQR 12.7) and multiple cardiovascular risk factors. Moderate-to severe cSVD was infrequent in this cohort (23.6%). No significant association was observed between cSVD score and epilepsy characteristics. Objective cognitive impairment was prevalent but was not associated with a higher burden of cSVD. Multivariate logistic regression identified advanced age as the sole significant factor associated with moderate-to-severe cSVD. CONCLUSION: In this thoroughly characterized cohort, moderate-to-severe cSVD was infrequent, with age identified as the sole risk factor. These findings support the hypothesis that cSVD may serve as a biomarker of brain aging. Further research is required to substantiate these results.