Höftberger Romana, van Sonderen Agnes, Leypoldt Frank, Houghton David, Geschwind Michael, Gelfand Jeffrey, Paredes Mercedes, Sabater Lidia, Saiz Albert, Titulaer Maarten J, Graus Francesc, Dalmau Josep
From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
Neurology. 2015 Jun 16;84(24):2403-12. doi: 10.1212/WNL.0000000000001682. Epub 2015 May 15.
We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).
This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic techniques have been reported previously.
Patients' median age was 62 years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5-266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009).
Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome.
我们报告22例新确诊的抗α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）抗体患者的临床特征、合并症及预后情况。
这是一项对2009年5月至2014年3月间确诊患者的回顾性研究。免疫技术此前已有报道。
患者的中位年龄为62岁（范围23 - 81岁；14例女性）。共识别出四种综合征：12例（55%）患者表现为典型的边缘叶脑炎（LE），8例（36%）表现为边缘叶功能障碍伴多灶性/弥漫性脑病，1例先出现运动功能缺损后发生LE，1例表现为具有双相特征的精神病。14例患者（64%）经病理检查（5例肺癌、4例胸腺瘤、2例乳腺癌、2例卵巢畸胎瘤）或影像学检查（1例肺癌）发现有肿瘤。7例患者（3例抗神经元抗体、1例肿瘤相关抗体、2例细胞表面抗体、1例肿瘤相关及细胞表面抗体）出现其他抗体，所有这些患者均有神经系统症状或肿瘤，提示存在并发自身免疫。21例患者有治疗及预后信息（中位随访72周，范围5 - 266周）：5例对免疫治疗和肿瘤治疗反应良好，10例部分缓解，6例无改善。最终5例患者死亡；所有死亡患者均有肿瘤或与抗神经元抗体相关的副肿瘤症状。抗神经元抗体共存预示预后不良（p = 0.009）。
抗AMPAR脑炎通常表现为LE，也可出现其他症状或精神病，64%的病例为副肿瘤性。可出现完全且显著的神经功能改善，但大多数患者为部分恢复。筛查肿瘤及抗神经元抗体很重要，因为其检测结果会影响预后。
