Estimated Disease Progression Trajectory of White Matter Disruption in Unilateral Temporal Lobe Epilepsy: A Data-Driven Machine Learning Approach

Background/Objectives: Although the involvement of progressive brain alterations in epilepsy was recently suggested, individual patients’ trajectories of white matter (WM) disruption are not known. Methods: We investigated the disease progression patterns of WM damage and its associations with clinical metrics. We examined the cross-sectional diffusion tensor imaging (DTI) data of 155 patients with unilateral temporal lobe epilepsy (TLE) and 270 age/gender-matched healthy controls, and we then calculated the average fractional anisotropy (FA) values within 20 WM tracts of the whole brain. We used the Subtype and Stage Inference (SuStaIn) program to detect the progression trajectory of FA changes and investigated its association with clinical parameters including onset age, disease duration, drug-responsiveness, and the number of anti-seizure medications (ASMs). Results: The SuStaIn algorithm identified a single subtype model in which the initial damage occurs in the ipsilateral uncinate fasciculus (UF), followed by damage in the forceps, superior longitudinal fasciculus (SLF), and anterior thalamic radiation (ATR). This pattern was replicated when analyzing TLE with hippocampal sclerosis (n = 50) and TLE with no lesions (n = 105) separately. Further-progressed stages were associated with longer disease duration (p < 0.001) and a greater number of ASMs (p = 0.001). Conclusions: the disease progression model based on WM tracts may be useful as a novel individual-level biomarker.