Ford Hannah, Seery Nabil, Tan Tracie, Gardner Logan, Box Jeffrey, Wesselingh Robb, Bosco Julian, Monif Mastura
Department of MS and Neuroimmunology, Alfred Hospital, Melbourne, Victoria, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Brain Behav. 2025 Aug;15(8):e70779. doi: 10.1002/brb3.70779.
Autoimmune encephalitis (AE) and paraneoplastic syndromes (PNS) are rare disorders with distinct phenotypes. They are increasingly considered in patients with diverse neurologic symptoms, but the clinical context remains critical for diagnosis. Commercial diagnostic assays for AE and PNS are embedded as available tests, however the diagnostic yield and clinical impact of autoantibody testing remain uncertain.
This single-center study analyzed all cerebrospinal fluid (CSF) and serum neuronal cell-surface antigen antibody (NCSAA) and intracellular neuronal antigen antibody (INAA) tests requested as part of routine care between 2019 and 2022. Data was collected retrospectively on clinical indications, supportive investigations, diagnosis, and management.
2161 antibody tests (1371 serum, 790 CSF) from 491 patients were reviewed. The most frequent testing indications were cognitive (26.5%, 130) and psychiatric (20.6%, 101) syndromes, 56.9% (74) and 18.8% (19) of which had associated focal neurology/seizures, respectively. Other common indications included neuropathy, seizures, movement disorders, ataxia, visual symptoms, myelitis, and motor neuron syndromes. Only 1.6% (34) of all autoantibody tests were positive, 38.2% of which were true positives (seven NCSAA, six INAA) and 61.8% (21) were false positives (one NCSAA, twenty INAA). Most false positives (95.2%, 20) were tested in serum only. 0.8% (4) of patients were diagnosed with seropositive AE (LGI1, NMDAR) and 0.8% (4) with INAA-associated syndromes (CRMP5, Yo, GAD65). All had focal neurology/seizures or supportive paraclinical investigations. 98.4% (2127) of antibody tests were negative, 99.1% (2107) of which were true negatives and 0.9% (20) were false negatives (19 seronegative AE, one seronegative PNS). 24% (118) of patients received immunosuppression, 93.2% (110) of whom were antibody negative.
Our findings demonstrate that indications for autoantibody testing are heterogenous, with a low true positive yield and frequent INAA false positives. This underscores the importance of clinical phenotyping and supportive investigations to prevent inappropriate widespread autoantibody testing.
自身免疫性脑炎（AE）和副肿瘤综合征（PNS）是具有不同表型的罕见疾病。在患有各种神经系统症状的患者中，它们越来越受到关注，但临床背景对于诊断仍然至关重要。AE和PNS的商业诊断检测作为可用测试已被纳入，但自身抗体检测的诊断率和临床影响仍不确定。
这项单中心研究分析了2019年至2022年期间作为常规护理一部分所要求的所有脑脊液（CSF）和血清神经元细胞表面抗原抗体（NCSAA）以及细胞内神经元抗原抗体（INAA）检测。回顾性收集了有关临床指征、辅助检查、诊断和管理的数据。
对来自491名患者的2161项抗体检测（1371项血清检测，790项脑脊液检测）进行了审查。最常见的检测指征是认知综合征（26.5%，130例）和精神综合征（20.6%，101例），其中分别有56.9%（74例）和18.8%（19例）伴有局灶性神经功能障碍/癫痫发作。其他常见指征包括神经病变、癫痫发作、运动障碍、共济失调、视觉症状、脊髓炎和运动神经元综合征。所有自身抗体检测中只有1.6%（34项）呈阳性，其中38.2%为真阳性（7项NCSAA，6项INAA），61.8%（21项）为假阳性（1项NCSAA，20项INAA）。大多数假阳性（95.2%，20项）仅在血清中检测到。0.8%（4例）患者被诊断为血清阳性AE（LGI1、NMDAR），0.8%（4例）患者被诊断为与INAA相关的综合征（CRMP5、Yo、GAD65）。所有患者均有局灶性神经功能障碍/癫痫发作或辅助性临床检查支持。98.4%（2127项）抗体检测为阴性，其中99.1%（2107项）为真阴性，0.9%（20项）为假阴性（19例血清阴性AE，1例血清阴性PNS）。24%（118例）患者接受了免疫抑制治疗，其中93.2%（110例）抗体为阴性。
我们的研究结果表明，自身抗体检测的指征是异质性的，真阳性率低，且INAA假阳性频繁。这突出了临床表型分析和辅助检查对于防止不适当广泛进行自身抗体检测的重要性。
