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
Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Neuroscience Research Center, University Magna Græcia, Catanzaro, Italy.
Neurology. 2025 Sep 23;105(6):e213688. doi: 10.1212/WNL.0000000000213688. Epub 2025 Aug 22.
Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of gray and white matter structures. Evidence supports a progressive condition, although the temporal evolution of TLE is poorly defined. In this ENIGMA-Epilepsy study, we aim to investigate structural alterations in gray and white matter across the adult lifespan in patients with TLE by charting both gray and white matter changes and explore the covariance of age-related alterations in both compartments.
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 scores of all patients. Covariance analyses examined the coupled correlations of gray and white matter lifespan curves for each region.
We studied 769 patients with TLE and 885 healthy controls across an age range of 17-73 years. Robust ( < 0.05) gray matter thickness/volume decline ( < -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 ( < -0.3, < 0.05) and mean diffusivity measures ( > 0.3, < 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.
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.
颞叶癫痫（TLE）通常与颞叶内侧病变以及灰质和白质结构的广泛改变相关。有证据支持这是一种进行性疾病，尽管TLE的时间演变尚不清楚。在这项ENIGMA - 癫痫研究中，我们旨在通过绘制灰质和白质的变化情况，研究TLE患者在成年期整个寿命过程中灰质和白质的结构改变，并探索两个脑区中与年龄相关改变的协方差。
对来自18个国际研究点的TLE患者的分割T1加权和扩散MRI数据进行荟萃分析，并与健康对照进行比较。我们将按年龄中位数分组的组间比较与横断面滑动年龄窗口分析相结合，以探索灰质（皮质厚度、皮质下体积）和白质微观结构（各向异性分数、平均扩散率）与年龄相关的变化。根据所有患者的平均得分构建五年范围的年龄窗口。协方差分析检查每个区域灰质和白质寿命曲线的耦合相关性。
我们研究了年龄在17 - 73岁之间的769例TLE患者和885例健康对照。在整个成年期，TLE患者在广泛的皮质 - 皮质下区域出现了显著的（<0.05）灰质厚度/体积下降（<-0.20），范围超出了颞叶内侧。白质变化也广泛存在于多个纤维束中，在颞叶边缘纤维的各向异性分数（<-0.3，<0.05）和平均扩散率测量值（>0.3，<0.05）方面有峰值效应。这些变化跨越了成年时间窗口，在皮质厚度、皮质下体积和扩散测量水平上，其影响超过了与典型衰老相关的过程，尤其是在55岁以上的患者中。协方差分析显示，在颞叶边缘系统内外的多个白质束、皮质下结构和皮质区域之间存在强关联。
本研究强调，TLE患者在整个寿命过程中表现出更明显和广泛的灰质和白质萎缩。我们研究的横断面性质限制了关于所显示的萎缩是否为进行性的明确结论，但强调了对患者进行及时诊断和干预的重要性。总体而言，我们的结果促使未来进行纵向研究，以阐明耐药性癫痫的后果。
