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Multidimensional Profiling of MRI-Negative Temporal Lobe Epilepsy Uncovers Distinct Phenotypes.

Alice Ballerini1, Alessia Casarini1, Niccolò Biagioli1

  • 1Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Annals of Clinical and Translational Neurology
|March 24, 2026
PubMed
Summary

Temporal lobe epilepsy without visible MRI lesions (TLE-MRIneg) is distinct from hippocampal sclerosis (TLE-HS), with milder symptoms. TLE-MRIneg subtypes include amygdala enlargement or diffuse atrophy, aiding personalized epilepsy management.

Keywords:
amygdala enlargementmri negativetemporal lobe epilepsy

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Area of Science:

  • Neurology
  • Radiology
  • Epilepsy Research

Background:

  • Hippocampal sclerosis (TLE-HS) is the most common cause of temporal lobe epilepsy (TLE).
  • Up to 30% of TLE patients lack visible lesions on standard MRI (TLE-MRIneg), posing diagnostic challenges.
  • TLE-MRIneg cases are underrepresented in surgical studies, necessitating further investigation.

Purpose of the Study:

  • To determine if TLE-MRIneg is a distinct clinical and neuroanatomical entity compared to TLE-HS.
  • To identify potential subtypes within the TLE-MRIneg group.
  • To improve diagnosis and management of non-lesional epilepsies.

Main Methods:

  • Analysis of MRI and clinical data from 209 TLE patients and 102 controls (3TLE project).
  • Classification of patients into TLE-MRIneg (n=96) and TLE-HS (n=76) based on expert radiological review.
  • Comparison of clinical characteristics and brain morphometry; application of clustering techniques for TLE-MRIneg subtypes.

Main Results:

  • TLE-MRIneg patients presented with later onset, shorter disease duration, and milder symptoms than TLE-HS patients.
  • TLE-HS showed widespread cortical/subcortical atrophy; TLE-MRIneg exhibited subtle cortical thinning.
  • Cluster analysis identified two TLE-MRIneg subtypes: ipsilateral amygdala enlargement (AE) and diffuse cortical atrophy.

Conclusions:

  • TLE-MRIneg is a distinct clinical-imaging entity separate from TLE-HS.
  • Morphologically defined subtypes, especially AE, reveal TLE-MRIneg heterogeneity and clinical relevance.
  • Advanced imaging and data-driven methods can enhance diagnosis and personalize management for non-lesional epilepsies.