Clinical phenotype modulates brain's myelin and iron content in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is associated with brain pathology extending beyond temporal lobe structures. We sought to look for informative patterns of brain tissue properties in TLE that go beyond the established morphometry differences. We hypothesised that volume differences, particularly in hippocampus, will be paralleled by changes in brain microstructure. The cross-sectional study included TLE patients (n = 25) from a primary care center and sex-/age-matched healthy controls (n = 55). We acquired quantitative relaxometry-based magnetic resonance imaging (MRI) data yielding whole-brain maps of grey matter volume, magnetization transfer (MT) saturation, and effective transverse relaxation rate R2* indicative for brain tissue myelin and iron content. For statistical analysis, we used the computational anatomy framework of voxel-based morphometry and voxel-based quantification. There was a positive correlation between seizure activity and MT saturation measures in the ipsilateral hippocampus, paralleled by volume differences bilaterally. Disease duration correlated positively with iron content in the mesial temporal lobe, while seizure freedom was associated with a decrease of iron in the very same region. Our findings demonstrate the link between TLE clinical phenotype and brain anatomy beyond morphometry differences to show the impact of disease burden on specific tissue properties. We provide direct evidence for the differential effect of clinical phenotype characteristics on processes involving tissue myelin and iron in mesial temporal lobe structures. This study offers a proof-of-concept for the investigation of novel imaging biomarkers in focal epilepsy.