Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis
Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis
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DOI：
10.1136/jnnp-2018-320168
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发表时间：
2019-09-01
影响因子：
11
通讯作者：
Butler, Christopher R.
中科院分区：
文献类型：
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作者：
Loane, Clare;Argyropoulos, Georgios P. D.;Butler, Christopher R.
目的与抗电压门控钾通道复合物（VGKCC-Ab-LE）抗体相关的边缘系统脑炎常导致海马萎缩和持续性记忆障碍。它对海马体以外区域的长期影响以及脑损伤和认知结果之间的关系尚不清楚。我们研究了VGKCC-Ab-LE后脑结构和功能异常的性质及其在残留记忆损伤中的作用。24名VGKCC-Ab-LE患者（20名男性，4名女性;平均（SD）年龄63.86（11.31）岁）与年龄和性别匹配的健康对照组一起在急性后沿着招募，进行神经心理学评估、结构MRI和静息状态功能MRI（rs-fMRI）。结构异常，确定使用体积和体素为基础的形态学; rs-fMRI数据进行了分析，研究海马功能连接（FC）。结果患者表现为选择性记忆障碍。结构分析显示内侧颞叶内的局灶性海马萎缩，内侧背丘脑的相关萎缩，以及后内侧皮质的额外体积减少。区域卷和内存性能之间没有关联。相反，患者表现出减少后内侧皮质海马和海马间的FC，这与记忆评分相关（r = 0.553; r = 0.582，分别）。结论VGKCC-Ab-LE可导致持续性孤立记忆损害。患者海马萎缩，丘脑背内侧和后内侧皮质体积进一步减少。重要的是，剩余海马组织的FC减少与记忆功能的相关性比区域萎缩更密切。
Objective Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment.Method A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined.Results Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531).Conclusion VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.