Neuropathological Variability within a Spectrum of NMDAR-Encephalitis
Neuropathological Variability within a Spectrum of NMDAR-Encephalitis
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DOI：
10.1002/ana.26223
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发表时间：
2021-10-09
影响因子：
11.2
通讯作者：
Hoeftberger, Romana
中科院分区：
文献类型：
--
作者：
Zrzavy, Tobias;Endmayr, Verena;Hoeftberger, Romana
目的探讨N-甲基-D-天冬氨酸受体（NMDAR）脑炎的神经病理学特征。方法：我们检查了4例NMDAR脑炎患者的尸检; 2例未经治疗，3例合并症：小细胞肺癌、脑移植后淋巴组织增生性疾病（PTLD）和重叠脱髓鞘。结果两名未经治疗的患者在基底节、杏仁核和海马以及周围的白色物质中出现炎性浸润，主要由血管周围和实质CD 3（+）/CD 8（-）T细胞和CD 79 a（+）B细胞/浆细胞组成。结果显示，与疾病严重程度相关的NMDAR免疫反应性显著降低。患有NMDAR-脑炎和肾移植免疫抑制的患者发生了脑单形性PTLD。炎症变化与NMDAR-脑炎一致。此外，浆细胞在坏死肿瘤附近沿着巨噬细胞和活化的小胶质细胞聚集，这些细胞强烈表达促炎活化标志物HLA-DR、CD 68和IL 18。第四例患者在NMDAR脑炎后4年复发时发生脱髓鞘病变。这些病变表现出典型多发性硬化的特征，放射状扩张病变和无补体或免疫球蛋白沉积的髓鞘再生阴影斑块，与I型脱髓鞘相一致。NMDAR-脑炎患者炎症的地形分布反映了运动障碍、行为异常和记忆功能障碍的临床症状，炎症主要在基底节、杏仁核和海马中观察到，NMDAR-免疫反应性的丧失与疾病严重程度相关。共现的病理影响炎症的空间分布、组成和强度，这可能改变患者的临床表现和结果。ANN NEUROL 2021
Objective To describe the neuropathological features of N-methyl-D-aspartate receptor (NMDAR)-encephalitis in an archival autopsy cohort. Methods We examined four autopsies from patients with NMDAR-encephalitis; two patients were untreated, three had comorbidities: small cell lung cancer, brain post-transplant lymphoproliferative disease (PTLD), and overlapping demyelination. Results The two untreated patients had inflammatory infiltrates predominantly composed of perivascular and parenchymal CD3(+)/CD8(-) T cells and CD79a(+) B cells/plasma cells in basal ganglia, amygdala, and hippocampus with surrounding white matter. The hippocampi showed a significant decrease of NMDAR-immunoreactivity that correlated with disease severity. The patient with NMDAR-encephalitis and immunosuppression for kidney transplantation developed a brain monomorphic PTLD. Inflammatory changes were compatible with NMDAR-encephalitis. Additionally, plasma cells accumulated in the vicinity of the necrotic tumor along with macrophages and activated microglia that strongly expressed pro-inflammatory activation markers HLA-DR, CD68, and IL18. The fourth patient developed demyelinating lesions in the setting of a relapse 4 years after NMDAR-encephalitis. These lesions exhibited the hallmarks of classic multiple sclerosis with radially expanding lesions and remyelinated shadow plaques without complement or immunoglobulin deposition, compatible with a pattern I demyelination. Interpretation The topographic distribution of inflammation in patients with NMDAR-encephalitis reflects the clinical symptoms of movement disorders, abnormal behavior, and memory dysfunction with inflammation dominantly observed in basal ganglia, amygdala, and hippocampus, and loss of NMDAR-immunoreactivity correlates with disease severity. Co-occurring pathologies influence the spatial distribution, composition, and intensity of inflammation, which may modify patients' clinical presentation and outcome. ANN NEUROL 2021