Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany2Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany3Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany4German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
JAMA Neurol. 2017 Jan 1;74(1):50-59. doi: 10.1001/jamaneurol.2016.4226.
Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood.
To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis.
DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted at the Departments of Neurology at Charité-Universitätsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015.
Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy).
Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P < .001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; P < .001) memory deficits. These deficits were accompanied by pronounced hippocampal atrophy, including subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as impaired hippocampal microstructural integrity. Higher disease severity correlated with larger verbal memory deficits (RAVLT delayed recall, r = -0.40; P = .049), decreased volumes of left hippocampus (r = -0.47; P = .02) and left CA2/3 (r = -0.41; P = .04) and CA4/DG (r = -0.43; P = .03) subfields, and impaired left hippocampal microstructural integrity (r = 0.47; P = .01). In turn, decreased volume of the left CA2/3 subfield (RAVLT delayed recall, r = 0.40; P = .047) and impaired left hippocampal microstructural integrity (RAVLT recognition, r = -0.41; P = .04) correlated with verbal memory deficits. Basal ganglia MRI signal abnormalities were observed in only 1 patient, but a longer duration of faciobrachial dystonic seizures correlated with a reduction of pallidum volume (r = -0.71; P = .03). In contrast, no abnormalities of cortical gray matter or white matter were found. The latency between disease onset and initiation of immunotherapy was significantly correlated with verbal (RAVLT recall after interference, r = -0.48; P = .02) and visuospatial (ROCF delayed recall, r = -0.46; P = .03) memory deficits.
Anti-LGI1 encephalitis is associated with cognitive deficits and disability as a result of structural damage to the hippocampal memory system. This damage might be prevented by early immunotherapy.
重要性：富含亮氨酸的胶质瘤失活 1 抗体（LGI1）相关脑炎是抗神经元表面抗原自身免疫性脑炎最常见的变体之一。然而，神经影像学模式和长期认知结局尚不清楚。
目的：研究抗 LGI1 脑炎患者的认知结局和结构磁共振成像（MRI）改变。
设计、地点和参与者：这是一项在德国柏林夏洛蒂医科大学和石勒苏益格-荷尔斯泰因州基尔大学医院神经内科进行的横断面研究。从 2013 年 6 月 1 日至 2015 年 2 月 28 日，共收集了 30 例抗 LGI1 脑炎患者和 27 例年龄、性别和教育程度相匹配的健康对照者的数据。
主要结局和测量：临床评估、认知测试和高分辨率 MRI 数据，包括全脑、海马和基底节容积测量；白质完整性（弥散张量成像）；灰质密度（基于体素的形态测量）；和海马微观结构完整性（平均扩散系数和各向异性分数）。
结果：研究共纳入 30 例患者，其中 19 例为男性（63%）；平均（SD）年龄为 65.7（12.3）岁。抗 LGI1 脑炎患者存在不完全恢复，存在明显且持续的言语（ Rey 听觉言语学习测试 [RAVLT]，延迟回忆：患者为 6.52[1.05]，对照组为 11.78[0.56]，P<0.001）和视觉空间（ Rey-Osterrieth 复杂图形测试 [ROCF]，延迟回忆：患者为 16.0[1.96]，对照组为 25.86[1.24]，P<0.001）记忆缺陷。这些缺陷伴随着明显的海马萎缩，包括 Cornu Ammonis 2/3（CA2/3）和 CA4/齿状回（DG）在内的海马亚区，以及海马微观结构完整性受损。疾病严重程度与言语记忆缺陷程度更高相关（RAVLT 延迟回忆，r=-0.40；P=0.049），左侧海马（r=-0.47；P=0.02）和左侧 CA2/3（r=-0.41；P=0.04）和 CA4/DG（r=-0.43；P=0.03）亚区的体积减小，以及左侧海马微观结构完整性受损（r=0.47；P=0.01）。反过来，左侧 CA2/3 亚区体积减小（RAVLT 延迟回忆，r=0.40；P=0.047）和左侧海马微观结构完整性受损（RAVLT 识别，r=-0.41；P=0.04）与言语记忆缺陷相关。仅在 1 例患者中观察到基底节 MRI 信号异常，但面肩肱型肌张力障碍性癫痫发作的持续时间较长与苍白球体积减小相关（r=-0.71；P=0.03）。相比之下，没有发现皮质灰质或白质的异常。疾病发作与免疫治疗开始之间的潜伏期与言语（RAVLT 干扰后回忆，r=-0.48；P=0.02）和视觉空间（ROCF 延迟回忆，r=-0.46；P=0.03）记忆缺陷显著相关。
结论和相关性：抗 LGI1 脑炎与认知缺陷和残疾有关，这是由于海马记忆系统的结构损伤所致。早期免疫治疗可能预防这种损伤。
