Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies
Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies
复制标题
DOI：
10.1001/jamaneurol.2016.4226
复制
发表时间：
2017-01-01
期刊：
影响因子：
29
通讯作者：
Bartsch, Thorsten
中科院分区：
文献类型：
--
作者：
Finke, Carsten;Pruess, Harald;Bartsch, Thorsten
边缘脑炎伴富含亮氨酸的胶质瘤失活1（LGI 1）抗体是自身免疫性脑炎最常见的变体之一，抗体靶向神经元表面抗原。然而，神经影像学模式和长期的认知outcome.Objective研究抗LGI 1脑炎患者的认知结果和结构磁共振成像（MRI）的改变。设计，设置，和参与者一个横断面研究在Charite大学柏林和大学医院石勒苏益格-荷尔斯泰因，基尔，德国的神经科进行。从2013年6月1日至2015年2月28日，收集了30名抗LGI 1脑炎患者和27名年龄、性别和教育水平相匹配的健康对照个体的数据。主要结果和指标临床评估、认知测试和高分辨率MRI数据，包括全脑、海马和基底神经节体积测定;白色物质完整性结果：30例患者中，19例为男性（63%），平均（SD）年龄为65.7（12.3）岁。抗LGI 1脑炎患者恢复不完全，（平均[SE] Rey听觉言语学习测试[RAVLT]，延迟回忆：患者，6.52 [1.05];对照组，11.78 [0.56]，P < .001）和视觉空间（Rey-Osterrieth复杂图形测试[ROCF]，延迟回忆：患者，16.0 [1.96];对照组，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，包括亚区角氨2/3（CA 2/3）和CA 4/齿状回（DG），以及受损的海马微结构的完整性。更高的疾病严重程度与更大的言语记忆缺陷相关（RAVLT延迟回忆，r = -0.40; P = .049），左侧海马体积减少（r = -0.47; P = .02）和左侧CA 2/3（r = -0.41; P = 0.04）和CA 4/DG（r = -0.43; P = 0.03）亚区，左海马微结构完整性受损（r = 0.47; P = 0.01）。反过来，左侧CA 2/3子区体积减少（RAVLT延迟回忆，r = 0.40; P = 0.047）和左侧海马微结构完整性受损（RAVLT识别，r = -0.41; P = 0.04）与言语记忆缺陷相关。仅1例患者观察到基底节MRI信号异常，但面臂张力障碍性癫痫发作持续时间较长与苍白球体积减少相关（r = -0.71; P = .03）。相比之下，未发现皮质灰质或白色质异常。疾病发作和开始免疫治疗之间的潜伏期与言语显着相关（干扰后RAVLT回忆，r = -0.48; P = .02）和视觉空间（ROCF延迟回忆，r = -0.46; P = .03）记忆缺陷。LGI 1脑炎与海马记忆系统结构损伤导致的认知缺陷和残疾有关。这种损伤可以通过早期免疫治疗来预防。
IMPORTANCE 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.OBJECTIVE 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 Charite-Universitatsmdizin 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.MAIN OUTCOMES AND MEASURES 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).RESULTS 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.CONCLUSIONS AND RELEVANCE 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.