一例接受帕博利珠单抗治疗的梅克尔细胞癌患者出现神经元中间丝神经系统自身免疫

文献信息

中文摘要

背景： 神经元中间丝（NIF）自身免疫是一种少见的副肿瘤性神经系统综合征，近年来逐渐被认识到与免疫检查点抑制剂（ICI）治疗相关。梅克尔细胞癌是与NIF抗体最常相关的恶性肿瘤之一，但已报道的病例仍然有限。
病例介绍： 一名55岁女性，患有IIIA期梅克尔细胞癌，在接受第二剂帕博利珠单抗治疗复发性疾病后，出现眩晕、步态不稳、构音障碍以及持续的右侧面部和颈部痉挛。脑MRI未见异常，而持续脑电图显示脑病，但无明确的脑电相关表现，提示可能存在皮层下肌阵挛。脑脊液（CSF）分析显示淋巴细胞性细胞增多、蛋白升高。CSF及细胞学检测显示NIF抗体阳性。停用帕博利珠单抗，患者接受大剂量糖皮质激素治疗，随后每月静脉注射免疫球蛋白，6个月后神经系统症状近乎完全缓解。
结论： 本病例拓展了ICI相关NIF副肿瘤性神经系统自身免疫合并梅克尔细胞癌的日益增多的谱系。据我们所知，持续性面部和颈部痉挛在此临床情境中鲜有报道。早期识别该综合征、及时进行抗体检测、停用ICI治疗并启动治疗，可能改善神经系统结局，同时为后续肿瘤管理提供信息。

英文摘要

BACKGROUND: Neuronal intermediate filament (NIF) autoimmunity is an uncommon paraneoplastic neurologic syndrome that has increasingly been recognized in association with immune checkpoint inhibitor (ICI) therapy. Merkel cell carcinoma is among the malignancies most frequently associated with NIF antibodies, although reported cases remain limited.
CASE PRESENTATION: A 55-year-old female with stage IIIA Merkel cell carcinoma developed vertigo, gait instability, dysarthria, and persistent right hemifacial and cervical spasms after receiving second dose of pembrolizumab for recurrent disease. Brain MRI was unremarkable, while continuous electroencephalography demonstrated encephalopathy without a definitive electrocerebral correlate, raising suspicion for subcortical myoclonus. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, elevated protein. CSF and positive NIF antibodies using cell-based assay. Pembrolizumab was discontinued, and the patient was treated with high-dose corticosteroids followed by monthly intravenous immunoglobulin, resulting in near complete resolution of her neurologic symptoms after 6 months.
CONCLUSION: This case expands the growing spectrum of ICI-associated NIF paraneoplastic neurologic autoimmunity complicating Merkel cell carcinoma. To our knowledge, persistent hemifacial and cervical spasm has rarely been reported in this clinical setting. Early recognition of this syndrome, prompt antibody testing, discontinuation of ICI therapy, and initiation of therapy may improve neurological outcomes while informing further oncologic management.