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Multidimensional Profiling of MRI ‐Negative Temporal Lobe Epilepsy Uncovers Distinct Phenotypes

Title: Multidimensional Profiling of MRI ‐Negative Temporal Lobe Epilepsy Uncovers Distinct Phenotypes
Authors: Ballerini, Alice; Casarini, Alessia; Biagioli, Niccolò; Mirandola, Laura; Ballotta, Daniela; Summers, Paul; Scolastico, Simona; Madrassi, Laura; Genovese, Maurilio; Malagoli, Marcella; Cantalupo, Gaetano; Giovannini, Giada; Pugnaghi, Matteo; Orlandi, Niccolò; Tassi, Laura; Cuccarini, Valeria; Aquino, Domenico; Tartara, Elena; Palesi, Fulvia; Didato, Giuseppe; Vitali, Paolo; null, null; Meletti, Stefano; Vaudano, Anna Elisabetta
Contributors: Ballerini, Alice; Casarini, Alessia; Biagioli, Niccolò; Mirandola, Laura; Ballotta, Daniela; Summers, Paul; Scolastico, Simona; Madrassi, Laura; Genovese, Maurilio; Malagoli, Marcella; Cantalupo, Gaetano; Giovannini, Giada; Pugnaghi, Matteo; Orlandi, Niccolò; Tassi, Laura; Cuccarini, Valeria; Aquino, Domenico; Tartara, Elena; Palesi, Fulvia; Didato, Giuseppe; Vitali, Paolo; Null, Null; Meletti, Stefano; Vaudano, Anna Elisabetta
Publication Year: 2026
Collection: Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS)
Subject Terms: amygdala enlargement; mri negative; temporal lobe epilepsy
Description: Objective: Although hippocampal sclerosis (TLE-HS) represents the most frequent cause of temporal lobe epilepsy (TLE), up to 30% of patients show no lesion on visual MRI inspection (TLE-MRIneg). These cases pose diagnostic and therapeutic challenges and are underrepresented in surgical series. We investigated whether TLE-MRIneg constitutes a distinct clinical and neuroanatomical entity compared to TLE-HS and aimed to identify subtypes within the TLE-MRIneg group. Methods: We analyzed MRI and clinical data from 209 patients with TLE and 102 healthy controls from the multicenter "3TLE project". Based on expert radiological review, 96 patients were classified as TLE-MRIneg and 76 as TLE-HS; the remaining 37 were excluded due to other focal lesions. We compared clinical characteristics and brain morphometry between TLE-MRIneg and TLE-HS and applied clustering techniques to detect TLE-MRIneg subtypes. Results: Compared with TLE-HS, TLE-MRIneg was associated with later onset, shorter disease duration, and milder clinical presentation. TLE-HS patients exhibited widespread cortical and subcortical atrophy, while TLE-MRIneg showed only subtle cortical thinning. Cluster analysis revealed two subtypes of TLE-MRIneg: one characterized by ipsilateral amygdala enlargement (AE) and the other by diffuse cortical atrophy. Interpretation: These findings demonstrate that TLE-MRIneg represents a distinct clinical-imaging entity from TLE-HS. The identification of morphologically defined subtypes, particularly AE, highlights the heterogeneity of TLE-MRIneg and its potential clinical relevance. This work supports the use of advanced imaging and data-driven methods to improve diagnosis and guide individualized management in non-lesional epilepsies.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/41873635; firstpage:1; lastpage:14; journal:ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY; https://hdl.handle.net/11380/1399829
DOI: 10.1002/acn3.70349
Availability: https://hdl.handle.net/11380/1399829; https://doi.org/10.1002/acn3.70349
Rights: info:eu-repo/semantics/openAccess ; license:[IR] creative-commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.224A37D3
Database: BASE