Kim Albert E, Kang Peter, Bucelli Robert C, Ferguson Cole J, Schmidt Robert E, Varadhachary Arun S, Day Gregory S
Departments of Neurology.
Washington University in Saint Louis, St. Louis, MO.
Neurologist. 2018 Mar;23(2):55-59. doi: 10.1097/NRL.0000000000000171.
Indications for autoantibody testing in patients with rapid-onset cognitive impairment have expanded in step with the growing number of disease-associated autoantibodies and clinical syndromes. Although increased access to autoantibody testing has broadened our understanding of the spectrum of autoimmune encephalitis (AE), it has also produced new challenges associated with deciphering the contributions of disease-associated autoantibodies in patients with atypical clinical features and/or multiple autoantibodies. These challenges are illustrated through presentation of a patient with AE associated with autoantibodies against intracellular and cell-surface neuronal antigens. The implications of detection of multiple autoantibodies are considered in the context of relevant literature, and used to frame a diagnostic and therapeutic approach.
A previously well 67-year-old man presented with encephalopathy and psychosis, impaired visual fixation, and ataxia, emerging over 3 months. Hu, CRMP-5, and NMDAR autoantibodies were identified in the cerebrospinal fluid. No malignancy was discovered despite extensive investigations. An aggressive course of immunotherapy temporarily stabilized his course; however, the patient succumbed to his illness 10 months after symptom onset. Lack of sustained response to immunotherapy and neuropathologic findings suggested that AE associated with Hu antibodies was primarily responsible for this patient's progressive decline.
Multiple autoantibodies may be detected in patients with AE. When antibodies targeting intracellular and cell-surface antigens are detected together, investigation and treatment of syndromes associated with intracellular antibodies should be prioritized, acknowledging the link between these antibodies and irreversible neuronal injury. In paraneoplastic cases, prognosis may be tied to early detection and treatment of the underlying malignancy.
随着与疾病相关的自身抗体和临床综合征数量的增加，快速起病的认知障碍患者自身抗体检测的适应证也在不断扩大。尽管自身抗体检测的可及性增加拓宽了我们对自身免疫性脑炎（AE）谱系的认识，但它也带来了新的挑战，即解读疾病相关自身抗体在具有非典型临床特征和/或多种自身抗体的患者中的作用。通过介绍一名患有与针对细胞内和细胞表面神经元抗原的自身抗体相关的AE患者，阐述了这些挑战。在相关文献的背景下考虑检测到多种自身抗体的意义，并以此构建诊断和治疗方法。
一名67岁既往健康的男性在3个月内出现脑病、精神病、视觉注视障碍和共济失调。脑脊液中检测到Hu、CRMP - 5和NMDAR自身抗体。尽管进行了广泛检查，但未发现恶性肿瘤。积极的免疫治疗过程暂时稳定了他的病情；然而，患者在症状出现10个月后因病死亡。对免疫治疗缺乏持续反应以及神经病理学发现表明，与Hu抗体相关的AE是该患者病情逐渐恶化的主要原因。
AE患者可能检测到多种自身抗体。当同时检测到针对细胞内和细胞表面抗原的抗体时，应优先对与细胞内抗体相关的综合征进行调查和治疗，同时认识到这些抗体与不可逆神经元损伤之间的联系。在副肿瘤性病例中，预后可能与潜在恶性肿瘤疾病的早期检测和治疗相关。
