Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin; Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin.
Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin.
Biol Psychiatry. 2016 May 1;79(9):727-734. doi: 10.1016/j.biopsych.2015.02.024. Epub 2015 Feb 26.
The majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis suffer from persistent memory impairment despite unremarkable routine clinical magnetic resonance imaging. With improved acute care in these patients, neurocognitive impairment represents the major contributor to long-term morbidity and has thus become a focus of attention.
Forty patients with anti-NMDAR encephalitis after the acute disease stage and 25 healthy control subjects underwent multimodal structural imaging that combined volumetry of hippocampal subfields with analysis of hippocampal microstructural integrity. Verbal and visuospatial memory performance was assessed in all patients and correlation and mediation analyses were performed to examine associations between hippocampal structural integrity, memory performance, and disease severity.
Hippocampal volumes were significantly reduced in patients and hippocampal subfield analysis revealed bilateral atrophy of the input and output regions of the hippocampal circuit. Microstructural integrity was impaired in both hippocampi in patients. Importantly, hippocampal volumetric and microstructural integrity measures correlated with memory performance and disease severity and duration. Mediation analysis revealed that hippocampal microstructure mediated the effect of disease severity on memory performance.
Data from this largest cohort of anti-NMDAR encephalitis patients that underwent extensive multimodal magnetic resonance imaging demonstrate that structural hippocampal damage and associated memory deficits are important long-term sequelae of the encephalitis. Correlation with disease duration and severity highlights the need for rapid diagnosis and adequate immunotherapy to prevent persistent damage to the hippocampus. Advanced imaging protocols may allow a more detailed analysis of structural damage to assess disease progression in clinical routine examinations and for therapy evaluation in prospective trials.
尽管常规临床磁共振成像无明显异常，但大多数抗 N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者仍存在持续性记忆障碍。随着这些患者急性护理水平的提高，神经认知障碍是导致长期发病率的主要原因，因此成为关注的焦点。
40 例抗 NMDAR 脑炎患者在急性发病期后和 25 例健康对照者接受了多模态结构成像，该成像结合了海马亚区容积测量和海马微观结构完整性分析。所有患者均进行了言语和视觉空间记忆能力评估，并进行了相关性和中介分析，以检查海马结构完整性、记忆能力和疾病严重程度之间的关联。
患者的海马体积明显减小，海马亚区分析显示海马环路的输入和输出区域双侧萎缩。患者的双侧海马微观结构完整性受损。重要的是，海马容积和微观结构完整性测量值与记忆能力和疾病严重程度和持续时间相关。中介分析显示，海马微观结构介导了疾病严重程度对记忆能力的影响。
这项对接受广泛多模态磁共振成像检查的最大抗 NMDAR 脑炎患者队列的研究数据表明，结构海马损伤和相关的记忆缺陷是脑炎的重要长期后遗症。与疾病持续时间和严重程度的相关性突出了快速诊断和充分免疫治疗的必要性，以防止海马持续损伤。先进的成像方案可能允许更详细地分析结构损伤，以在临床常规检查中评估疾病进展，并在前瞻性试验中评估治疗效果。
