Multivariate white matter alterations are associated with epilepsy duration

TL;DR

This study introduces a multivariate approach using Mahalanobis distance to better understand white matter alterations related to epilepsy duration, revealing more robust associations than traditional univariate methods.

Contribution

The paper demonstrates that multivariate analysis captures white matter changes in epilepsy more effectively than univariate approaches, providing a more comprehensive understanding of disease progression.

Findings

Multivariate analysis shows significant associations with epilepsy duration in white matter tracts.

Univariate analysis failed to detect some associations identified by multivariate methods.

Multivariate approach yields more robust and non-overlapping results.

Abstract

Previous studies investigating associations between white matter alterations and duration of temporal lobe epilepsy (TLE) have shown differing results, and were typically limited to univariate analyses of tracts in isolation. In this study we apply a multivariate measure (the Mahalanobis distance), to capture the distinct ways white matter may differ in individual patients, and relate this to epilepsy duration. Diffusion MRI, from a cohort of 94 subjects (28 healthy controls, 33 left-TLE and 33 right-TLE), was used to assess associations between tract fractional anisotropy (FA) and epilepsy duration. Using ten white matter tracts, we analysed associations using traditional univariate analyses (z-scores) and a complementary multivariate approach (Mahalanobis distance), incorporating multiple white matter tracts into a single unified analysis. In patients with right-TLE, FA was not significantly associated with epilepsy duration for any tract studied in isolation. In patients with left-TLE, the FA of two limbic tracts (ipsilateral fornix, contralateral cingulum gyrus) was significantly negatively associated with epilepsy duration (Bonferonni corrected p<0.05). Using a multivariate approach we found significant ipsilateral positive associations with duration in both left, and right-TLE cohorts (left-TLE: Spearman's rho=0.487, right-TLE: Spearman's rho=0.422). Extrapolating our multivariate results to duration equals zero (i.e. at onset) we found no significant difference between patients and controls. Associations using the multivariate approach were more robust than univariate methods. The multivariate distance measure provides non-overlapping and more robust results than traditional univariate analyses. Future studies should consider adopting both frameworks into their analysis in order to ascertain a more complete understanding of epilepsy progression, regardless of laterality.