抗IgLON5抗体相关脑病三例分析

Encephalopathy associated with anti-IgLON5 antibody： report of three cases

目的通过抗神经元抗体检测筛查抗IgLON家族蛋白5（IgLON5）抗体相关脑病患者，对抗IgLON5抗体阳性者进行临床观察，描述其临床特点。 方法收集北京协和医院2015年12月至2017年6月收治的150例伴有明显睡眠障碍的帕金森综合征患者，或者多系统萎缩样表现的患者，对患者的血清和脑脊液进行抗IgLON5抗体检测，对抗体阳性者继续进行HLA－DRB1、HLA－DQB1基因检测，并进行临床评估、免疫治疗与随诊。结果3例患者抗IgLON5抗体阳性，其中女性1例，男性2例，年龄61～64岁。神经系统临床表现：例1口唇不适伴不自主运动、行走不稳和失眠；例2失眠、睡眠行为异常和精神异常伴吞咽困难；例3失眠、睡眠行为异常、构音障碍、震颤伴有流涎。脑脊液细胞学检查：2例可见轻度淋巴细胞性炎症并可见浆细胞，1例未见异常。多导睡眠监测：例1和例2可见睡眠呼吸暂停，例2和例3严重失眠，例2可见睡眠行为异常。基因检测3例均HLA－DQB1＊0501阳性，2例伴HLA－DRB1＊1001阳性，1例HLA－DRB1＊1001阴性。3例均接受免疫治疗，1例有效。结论抗IgLON5抗体相关脑病是一种少见的抗神经元抗体相关的自身免疫性脑病，具有较为特征性的临床表现。尽管本病具有tau蛋白相关神经变性疾病的病理改变，但免疫治疗仍具有潜在价值。

ObjectiveTo report the clinical and paraclinical features of a case series with anti-IgLON5 antibody related encephalopathy. MethodsOne hundred and fifty patients with sleep disorders and subacute or chronic onset of movement disorders, parkinsonism or bulbar palsy were included. The serum and cerebrospinal fluid specimens of these patients were screened for anti-IgLON5 antibody. The clinical and paraclinical features of patients with seropositive anti-IgLON5 antibody were summarized.ResultsThree patients with seropositive anti-IgLON5 antibody were identified, with one female and two males. The onset age ranged from 61 to 64 years. Case 1 presented with symptoms of involuntary movement, unsteady walk and insomnia; case 2 with symptoms of insomnia, sleep behavioral disorder, psychiatric behavior and dysphagia; case 3 with symptoms of insomnia, sleep behavioral disorder, dysarthria, and tremor. When examined by polysomnography, obstructive sleep apnea syndrome was revealed in cases 1 and 2, serious insomnia was found in cases 2 and 3, and sleep behavioral disorder was revealed in case 2. All three patients were positive for HLA-DQB1＊0501, and cases 2 and 3 were positive for HLA-DRB1＊1001. All three patients received immunotherapy and only one patient （case 1） responded well to immunotherapy with intravenous immunoglobulin, steroids and mycophenolate mofetil.ConclusionsAnti-IgLON5-related encephalopathy is a rare disease with distinct clinical features of both autoimmune disorders and neurodegeneration disorders. These patients may benefit from immunotherapy.