Milano Chiara, Saylam Ezgi, Papi Claudia, Marmolejo Laura, Sankovic Alexandra, Reinecke Raphael, Kerstens Jeroen, Pizzanelli Chiara, Simabukuro Mateus Mistieri, Benaiteau Marie, Joubert Bastien, Gastaldi Matteo, Dutra Lívia Almeida, Leypoldt Frank, Jansen Mareike, Kawachi Izumi, Akiyama Hisanao, Boy Nikolas, Bozzetti Silvia, Christensen Peter Broegger, Businaro Pietro, Dinoto Alessandro, Friedman-Korn Tal, Fujiwara Urara, Fukumoto Tatsuya, Fuse Kenshiro, Hooshmand Sam Ishmael, Hurst Lauren, Iorio Raffaele, Korn-Lubetzki Isabelle, Rodrigues André Filipe Lucchi, Mariotto Sara, Michael Johannes, Morimoto Yuko, Neuteboom Rinze Frederik, Piquet Amanda L, Rossetti Andrea O, Rumpler-Kreiner Sabine, Santoro Jonathan D, Schwendinger Florian, Shen Brenda, Syrbe Steffen, Troger Johannes, Wagner Ingrid, Bien Christian G, Martinez-Hernandez Eugenia, Armangue Thais, Höftberger Romana, Iizuka Takahiro, Titulaer Maarten J, Honnorat Jerome, Graus Francesc, Dalmau Josep O, Magaña Setty, Spatola Marianna
Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomédiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona, Spain.
Caixa Research Institute, Barcelona, Spain.
Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200453. doi: 10.1212/NXI.0000000000200453. Epub 2025 Jul 18.
Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (anti-AMPAR) encephalitis manifests as limbic encephalitis in adults and is often associated with cancer. Although some reports suggest that it may occur in children, the clinical features in this population, as well as the prognostic factors and long-term outcomes in children and adults, are unknown.
We performed a retrospective, international collaborative study of patients with anti-AMPAR encephalitis. Clinical information was reviewed, together with data from published pediatric patients. Clinical features of children and adults were compared with nonparametric tests. Survival rates (Kaplan-Meier curves) were compared using log-rank tests. Prognostic factors of poor outcome (modified Rankin Scale score >2) were identified using logistic regression models.
A total of 115 patients were included, of whom 84 (71 adults, 13 children) had only AMPAR antibodies and 31 (27 adults, 4 children) had additional concurrent neural antibodies. Among patients with AMPAR antibodies alone, tumors were identified in 37 adults (56%) and none of the children ( < 0.0001). Children were more likely than adults to have behavioral/psychiatric symptoms (5/13, 39%, vs 8/71, 11%, = 0.026) at onset, cerebellar dysfunction (6/13, 46%, vs 7/68, 10% = 0.005) or movement disorders (5/13, 39%, vs 8/67, 12%, = 0.032) during the disease course, and extratemporal brain MRI lesions (4/9, 44%, vs 5/44, 11%, = 0.035). Among 34 patients with prolonged follow-up (>24 months), long-term neurocognitive sequelae were reported in 23 (68%), all adults. Failure to respond to first-line immunotherapy at multivariable analysis predicted a poor outcome (OR 8.0, 95% CI 1.1-59.2, = 0.043). Among the 31 patients with concurrent neural autoantibodies, 22 (79%) had a tumor; those with high-risk antibodies had lower survival rates ( = 0.008).
Children and adults with anti-AMPAR encephalitis show distinct clinical-radiologic features. At long-term follow-up, 68% of patients, all adults, have neurologic sequelae, with failure to respond to first-line immunotherapy being associated with worse outcomes.
抗α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（抗AMPAR）脑炎在成人中表现为边缘性脑炎，且常与癌症相关。尽管一些报告表明其可能发生于儿童，但该人群的临床特征以及儿童和成人的预后因素与长期结局尚不清楚。
我们对患有抗AMPAR脑炎的患者进行了一项回顾性国际合作研究。回顾了临床信息以及已发表的儿科患者数据。采用非参数检验比较儿童和成人的临床特征。使用对数秩检验比较生存率（Kaplan-Meier曲线）。采用逻辑回归模型确定预后不良（改良Rankin量表评分>2）的预后因素。
共纳入115例患者，其中84例（71例成人，13例儿童）仅具有AMPAR抗体，31例（27例成人，4例儿童）同时存在其他神经抗体。在仅具有AMPAR抗体的患者中，37例成人（56%）发现肿瘤，而儿童均未发现（<0.0001）。儿童在发病时比成人更易出现行为/精神症状（5/13，39%，vs 8/71，11%，P=0.026）、在病程中出现小脑功能障碍（6/13，46%，vs 7/68，10%，P=0.005）或运动障碍（5/13，39%，vs 8/67，12%，P=0.032），以及颞叶外脑MRI病变（4/9，44%，vs 5/44，11%，P=0.035）。在34例随访时间延长（>24个月）的患者中，23例（68%）报告有长期神经认知后遗症，均为成人。多变量分析显示对一线免疫治疗无反应预示预后不良（OR 8.0，95%CI 1.1-59.2，P=0.043）。在31例同时存在神经自身抗体的患者中，22例（79%）有肿瘤；具有高风险抗体的患者生存率较低（P=0.008）。
抗AMPAR脑炎的儿童和成人表现出不同的临床-放射学特征。长期随访显示，68%的患者（均为成人）有神经后遗症，对一线免疫治疗无反应与更差的结局相关。
