Zubal Richard, Velicky Buecheler Matus, Sone Daichi, Postma Tjardo, De Tisi Jane, Caciagli Lorenzo, Winston Gavin P, Sidhu Meneka K, Long Lili, Xiao Bo, Mcevoy Andrew William, Miserocchi Anna, Vos Sjoerd B, Baumann Christian R, Duncan John S, Koepp Matthias J, Galovic Marian
Department of Neuroradiology, Inselspital, Bern University Hospital and University of Bern, Switzerland.
Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Neurology. 2025 Jan 28;104(2):e210182. doi: 10.1212/WNL.0000000000210182. Epub 2024 Dec 23.
Mesial temporal lobe epilepsy (mTLE) is generally associated with focal brain atrophy, but little knowledge exists on possible disease-related hypertrophy of brain structures. We hypothesized that repeated seizures or adaptive plasticity may lead to focal brain hypertrophy and aimed to investigate associated clinical correlates.
In this cohort study, we included patients with mTLE undergoing detailed epilepsy evaluations and matched healthy volunteers (HVs) from 2 tertiary centers (discovery and validation cohorts). We assessed areas of brain hypertrophy and their clinical correlates using whole-brain voxel-based or surface-based morphometry (VBM, SBM), subcortical volumetry, and shape analysis of T1-weighted MRI data by fitting linear models. We evaluated the functional implications of the findings on memory encoding using fMRI.
We included 135 patients with mTLE with neuropathology-confirmed hippocampal sclerosis (77 left, 58 right; 82 women; mean age 37 ± 11 years) and 47 HVs (29 women, mean age 36 ± 11 years) in the discovery cohort. VBM detected increased gray matter volume of the contralateral amygdala in patients with both left ( = 8.7, < 0.001) and right ( = 7.9, < 0.001) mTLE. We confirmed the larger volume of the contralateral amygdala using volumetry (left mTLE 1.74 ± 0.16 mL vs HVs 1.64 ± 0.11, < 0.001; right mTLE 1.79 ± 0.18 mL vs HVs 1.70 ± 0.11, = 0.002) and shape analysis (left mTLE ≤ 0.005; right mTLE = 0.006). We validated the hypertrophy of the contralateral amygdala in the validation cohort (mTLE, n = 18, 1.91 ± 0.20 mL; HVs, n = 18, 1.75 ± 0.13; = 0.009). In left mTLE, contralateral amygdala hypertrophy was associated with poorer verbal memory and, in right mTLE, with more frequent focal-to-bilateral tonic-clonic seizures. A larger volume of the contralateral amygdala correlated with increased functional activation of the right parietal memory encoding network in a subgroup (44/135 patients with mTLE, 26/47 HVs) receiving fMRI.
Unilateral mTLE due to hippocampal sclerosis is associated with hypertrophy of the contralateral amygdala. This may represent plasticity to compensate for verbal memory deficits or may be the consequence of seizure spread to the contralateral hemisphere.
内侧颞叶癫痫（mTLE）通常与局灶性脑萎缩相关，但对于可能与疾病相关的脑结构肥大了解甚少。我们推测反复癫痫发作或适应性可塑性可能导致局灶性脑肥大，并旨在研究相关的临床关联。
在这项队列研究中，我们纳入了来自2个三级中心（发现队列和验证队列）接受详细癫痫评估的mTLE患者以及匹配的健康志愿者（HV）。我们通过拟合线性模型，使用基于全脑体素或表面的形态测量法（VBM、SBM）、皮质下容积测量以及T1加权MRI数据的形状分析，评估脑肥大区域及其临床关联。我们使用功能磁共振成像（fMRI）评估这些发现对记忆编码的功能影响。
在发现队列中，我们纳入了135例经神经病理学证实为海马硬化的mTLE患者（左侧77例，右侧58例；女性82例；平均年龄37±11岁）和47例HV（女性29例，平均年龄36±11岁）。VBM检测到左侧（t = 8.7，P < 0.001）和右侧（t = 7.9，P < 0.001）mTLE患者对侧杏仁核灰质体积增加。我们使用容积测量法（左侧mTLE 1.74±0.16 mL vs HV 1.64±0.11，P < 0.001；右侧mTLE 1.79±0.18 mL vs HV 1.70±0.11，P = 0.002）和形状分析（左侧mTLE P ≤ 0.005；右侧mTLE P = 0.006）证实了对侧杏仁核体积增大。我们在验证队列中验证了对侧杏仁核肥大（mTLE，n = 18，1.91±0.20 mL；HV，n = 18，1.75±0.13；P = 0.009）。在左侧mTLE中，对侧杏仁核肥大与较差的言语记忆相关，而在右侧mTLE中，与更频繁的局灶性至双侧强直阵挛发作相关。在接受fMRI的一个亚组（135例mTLE患者中的44例，47例HV中的26例）中，对侧杏仁核体积增大与右侧顶叶记忆编码网络的功能激活增加相关。
由于海马硬化导致的单侧mTLE与对侧杏仁核肥大相关。这可能代表了一种可塑性，以补偿言语记忆缺陷，或者可能是癫痫发作扩散至对侧半球的结果。
