Interictal blood–brain barrier dysfunction in piriform cortex of people with epilepsy

Objective: The piriform cortex is considered to be highly epileptogenic. Its resection during epilepsy surgery is a predictor for postoperative seizure freedom in temporal lobe epilepsy. Epilepsy is associated with a dysfunction of the blood–brain barrier. We investigated blood–brain barrier dysfunction in the piriform cortex of people with temporal lobe epilepsy using quantitative T1-relaxometry. Methods: Gadolinium-based contrast agent was administered ictally and interictally in 37 individuals before undergoing quantitative T1-relaxometry. Postictal and interictal images were co-registered, and subtraction maps were created as biomarkers for peri-ictal (∆qT1_{interictal-postictal}) and interictal (∆qT1_{noncontrast-interictal}) blood–brain barrier dysfunction. Values were extracted for the piriform cortex, hippocampus, amygdala, and the whole cortex. Results: In temporal lobe epilepsy (n = 14), ∆qT1_{noncontrast-interictal} was significantly higher in the piriform cortex than in the whole cortex (p = 0.02). In extratemporal lobe epilepsy (n = 23), ∆qT1_{noncontrast-interictal} was higher in the hippocampus than in the whole cortex (p = 0.05). Across all individuals (n = 37), duration of epilepsy was correlated with ∆qT1_{noncontrast-interictal} (ß = 0.001, p < 0.001) in all regions, while the association was strongest in the piriform cortex. Impaired verbal memory was associated with ∆qT1_{noncontrast-interictal} only in the piriform cortex (p = 0.04). ∆qT1_{interictal-postictal} did not show differences in any region. Interpretation: Interictal blood–brain barrier dysfunction occurs in the piriform cortex in temporal lobe epilepsy. This dysfunction is linked to longer disease duration and worse cognitive deficits, emphasizing the central role of the piriform cortex in the epileptogenic network of temporal lobe epilepsy.