Diffusion MRI biomarkers for predicting treatment outcomes in infantile epileptic spasms syndrome with non-lesional MRI

Abstract

Background

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) and patients exhibit diffuse white matter alterations and structural remodeling. However, the correlation between these structural changes and brain network properties, or their effect on the efficacy of treatment outcomes in MRI non-lesional IESS patients is not clear.

Method

This retrospective study was conducted on IESS patients using fixel-based analysis (FBA) of diffusion MRI and graph theory analysis of structural connectivity, involving 26 non-lesional IESS patients aged 2 to 12 months and 120 age-matched controls. We further examined the differences between antiseizure medication (ASM) responders and non-responders within the IESS cohort. FBA was performed across three age groups (2–5, 6–7, and 8–12 months) to evaluate white matter integrity at the micro- and macroscale using fiber density (FD), fiber cross-section (FC), and combined fiber density and cross-section (FDC). Graph theory analysis was used to assess global and local network properties.

Results

When compared to the control group, IESS patients exhibited significantly lower FD, FC, and FDC across major white matter tracts, including the corticospinal tract, corpus callosum, superior longitudinal fasciculus, optic radiations, and thalamic radiations (family-wise error-corrected, p < 0.05). Graph theory analysis revealed significant alterations in brain network properties, particularly in the age group of 2–5 months, where IESS patients exhibited a significantly lower mean clustering coefficient (p < 0.001, d = -0.74) and global efficiency (p = 0.001, d = -0.69. Small-world network analysis demonstrated a shift toward a more randomized network structure in IESS patients, particularly in the age group of 6–7 months (p = 0.001, d = -0.6182). In the secondary analysis, ASM treatment responders showed higher FD values in regions critical for seizure control, such as the hippocampus. Meanwhile, the ASM treatment non-responders exhibited increased FC in areas such as the pons and brainstem. Although subgroup differences did not achieve statistical significance, trends suggest that white matter integrity and network organization may influence treatment outcomes.

Conclusion

The results highlight widespread changes in white matter integrity and network connectivity in non-lesional IESS patients, with preliminary evidence suggesting a relationship between structural brain differences and treatment responsiveness. These findings underscore the potential of advanced neuroimaging analyses to guide personalized interventions in IESS.