Changes in Gray Matter Morphology and White Matter Microstructure Across the Adult Lifespan in People With Temporal Lobe Epilepsy.
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Chen Judy, Ngo Alexander, Rodriguez-Cruces Raul, Royer Jessica, Caligiuri Maria Eugenia, Gambardella Antonio, Concha Luis, Keller Simon Sean, Cendes Fernando, Yasuda Clarissa Lin, Alvim Marina Koutsodontis Machado, Bonilha Leonardo, Gleichgerrcht Ezequiel, Focke Niels K, Kreilkamp Barbara A K, Domin Martin, Von Podewils Felix, Langner Soenke, Rummel Christian, Wiest Roland, Martin Pascal, Kotikalapudi Raviteja, Bender Benjamin, O'Brien Terence J, Sinclair Benjamin, Vivash Lucy, Kwan Patrick, Desmond Patricia, Lui Elaine, Duma Gian Marco, Bonanni Paolo, Ballerini Alice, Vaudano Anna Elisabetta, Meletti Stefano, Tondelli Manuela, Alhusaini Saud, Doherty Colin P, Cavalleri Gianpiero, Delanty Norman, Kalviainen Reetta, Jackson Graeme D, Kowalczyk Magdalena, Mascalchi Mario, Semmelroch Mira K H G, Thomas Rhys H, Soltanian-Zadeh Hamid, Davoodi-Bojd Esmaeil, Zhang Junsong, Lenge Matteo, Guerrini Renzo, Bartolini Emanuele, Hamandi Khalid, Foley Sonya, Rüber Theodor, Bauer Tobias, Weber Bernd, Caldairou Benoit, Depondt Chantal, Absil Julie, Carr Sarah J A, Abela Eugenio, Richardson Mark P, Devinsky Orrin, Pardoe Heath R, Severino Mariasavina, Striano Pasquale, Tortora Domenico, Kaestner Erik, Hatton Sean N, Arienzo Donatello, Vos Sjoerd B, Ryten Mina, Taylor Peter N, Duncan John S, Whelan Christopher D, Galovic Marian, Winston Gavin P, Thomopoulos Sophia I, Thompson Paul M, Sisodiya Sanjay M, Labate Angelo, Mcdonald Carrie, Caciagli Lorenzo, Bernasconi Neda, Bernasconi Andrea, Lariviere Sara, Schrader Dewi Victoria, Bernhardt Boris C
Аннотация
METHODS: Mega-analysis of parcellated T1-weighted and diffusion MRI data across 18 international sites for patients with TLE was compared against healthy controls. We combined median-age split groupwise comparisons with cross-sectional sliding age-window analyses to explore gray (cortical thickness, subcortical volume) and white matter microstructure (fractional anisotropy, mean diffusivity) age-related changes. Five-year range age windows were constructed from mean z scores of all patients. Covariance analyses examined the coupled correlations of gray and white matter lifespan curves for each region.
RESULTS: We studied 769 patients with TLE and 885 healthy controls across an age range of 17-73 years. Robust (pFDR < 0.05) gray matter thickness/volume decline (d < -0.20) was seen across a broad cortico-subcortical territory, extending beyond the mesiotemporal lobe throughout the adult lifespan in patients with TLE. White matter changes were also widespread across multiple fiber tracts with peak effects in temporolimbic fibers in fractional anisotropy (d < -0.3, pFDR < 0.05) and mean diffusivity measures (d > 0.3, pFDR < 0.05). Changes spanned the adult time window and effects exceeded typical aging-related processes in patients at the level of cortical thickness, subcortical volume, and diffusion measures, particularly in patients older than 55 years. Covariance analyses revealed strong associations across multiple white matter tracts, subcortical structures, and cortical regions within and beyond the temporolimbic system.
DISCUSSION: This study highlights that patients with TLE exhibit more pronounced and widespread gray and white matter atrophy across the lifespan. The cross-sectional nature of our study limits definitive conclusions on whether the atrophy shown is progressive but emphasizes the importance of prompt diagnosis and intervention in patients. Collectively, our results motivate future longitudinal studies to clarify consequences of drug-resistant epilepsy.