Yokota Yuki, Hara Makoto, Oshita Natsuki, Mizoguchi Tomotaka, Nishimaki Haruna, Hao Hiroyuki, Nakajima Hideto
Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Front Neurol. 2023 Jan 12;13:1048953. doi: 10.3389/fneur.2022.1048953. eCollection 2022.
We herein detail our experience with a unique patient with a primary central nervous system (PCNS) B-cell lymphoma concomitant with anti--methyl-d-aspartate receptor (NMDAR) antibodies that satisfied the criteria of "probable anti-NMDAR encephalitis (ProNMDARE)" based on the Graus criteria 2016.
A 73-year-old Japanese woman presented with acute pyrexia, agitation, and disturbance of consciousness. She gradually developed a reduction in speech frequency and truncal dystonia causing abnormal posture. Brain magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the bilateral frontal lobes, and her cerebrospinal fluid revealed mild pleocytosis. She was diagnosed with acute encephalitis and treated with acyclovir and intravenous dexamethasone; however, no improvement was observed. She was transferred to our hospital 6 weeks after the onset of her symptoms, and anti-NMDAR antibodies were identified in her cerebrospinal fluid through indirect immunolabeling with rat brain frozen sections and cell-based assays with NR1/NR2 transfected HEK cells. Follow-up MRI showed enlargement of the lesions in the right frontal lobe with gadolinium enhancement, suggesting a brain tumor. Stereotactic surgery was implemented, with subsequent pathological examination revealing that the tumor was consistent with diffuse large B-cell lymphoma (DLBCL) without evidence of systemic satellite lesions. Stereotactic irradiative therapies were then added to her treatment regimen, which partly improved her neurological symptoms with only mild cognitive dysfunction still remaining. A decrease in anti-NMDAR antibody titer was also confirmed after immunotherapy and tumor removal.
We herein report our experience with a novel case of PCNS-DLBCL masquerading as anti-NMDAR encephalitis that satisfied the diagnostic criteria of "proNMDARE." Treatment, including tumor removal, ameliorated disease severity and antibody titers of the patient. Our findings suggest that anti-NMDAR antibody-associated autoimmunity can be triggered by PCNS B-cell tumors, although primary brain tumors need to be excluded before establishing a diagnosis of autoimmune encephalitis.
我们在此详细介绍一位独特患者的病例，该患者患有原发性中枢神经系统（PCNS）B细胞淋巴瘤，并伴有抗N-甲基-D-天冬氨酸受体（NMDAR）抗体，根据2016年Graus标准，符合“可能的抗NMDAR脑炎（ProNMDARE）”的标准。
一名73岁的日本女性出现急性发热、烦躁和意识障碍。她逐渐出现言语频率降低和躯干肌张力障碍，导致姿势异常。脑部磁共振成像（MRI）显示双侧额叶有高强度病变，脑脊液显示轻度细胞增多。她被诊断为急性脑炎，并接受了阿昔洛韦和静脉注射地塞米松治疗；然而，未见改善。症状出现6周后，她被转到我院，通过用大鼠脑冰冻切片进行间接免疫标记和用NR1/NR2转染的HEK细胞进行细胞检测，在她的脑脊液中发现了抗NMDAR抗体。随访MRI显示右额叶病变增大，钆增强，提示脑肿瘤。实施了立体定向手术，随后的病理检查显示肿瘤与弥漫性大B细胞淋巴瘤（DLBCL）一致，无系统性卫星病变证据。然后在她的治疗方案中增加了立体定向放射治疗，这部分改善了她的神经症状，仅仍有轻度认知功能障碍。免疫治疗和肿瘤切除后，抗NMDAR抗体滴度也有所下降。
我们在此报告了一例伪装成抗NMDAR脑炎的PCNS-DLBCL新病例，该病例符合“proNMDARE”的诊断标准。包括肿瘤切除在内的治疗改善了患者的疾病严重程度和抗体滴度。我们的研究结果表明，PCNS B细胞肿瘤可引发抗NMDAR抗体相关的自身免疫，尽管在诊断自身免疫性脑炎之前需要排除原发性脑肿瘤。
