Imaging blood–brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study

Objective: Blood–brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals. Methods: We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls. Results: Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10⁻⁷). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10). Significance: These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.