Table_3_Novel Surrogate Markers of CNS Inflammation in CSF in the Diagnosis of Autoimmune Encephalitis.docx

Background: Autoimmune encephalitis (AE) is an important cause of refractory epilepsy, rapidly progressive cognitive decline, and unexplained movement disorders in adults. Whilst there is identification of an increasing number of associated autoantibodies, patients remain with a high clinical probability of autoimmune encephalitis but no associated characterized autoantibody. These patients represent a diagnostic and treatment dilemma.
Objective: To evaluate routine and novel diagnostic tests of cerebrospinal fluid (CSF) in patients with a high probability of AE to attempt to identify better biomarkers of neuroinflammation.
Methods: Over 18 months (2016–2018), adult patients with a high clinical probability of AE were recruited for a pilot cross-sectional explorative study. We also included viral polymerase-chain-reaction (PCR) positive CSF samples and CSF from neurology patients with “non-inflammatory” (NI) diagnoses for comparison. CSF was examined with standard investigations for encephalitis and novel markers (CSF light chains, and cytokines).
Results and Conclusions: Thirty-two AE patients were recruited over 18 months. Twenty-one viral controls, 10 NI controls, and five other autoimmune neurological disease controls (AOND) were also included in the analysis. Our study found that conventional markers: presence of CSF monocytosis, oligoclonal bands, anti-neuronal immunofluorescence, and magnetic resonance imaging (MRI) changes could be suggestive of AE, but these investigations were neither sensitive nor specific. Promising novel makers of autoimmune encephalitis were the CSF cytokines IL-21 and IP10 which may provide better delineation between viral infections and autoimmune encephalitis than conventional markers, potentially leading to more immediate diagnosis and management of these patients.

研究背景：自身免疫性脑炎（Autoimmune encephalitis, AE）是成人难治性癫痫、快速进展性认知功能下降以及不明原因运动障碍的重要病因。尽管目前已识别出日益增多的相关自身抗体，但仍有部分患者临床高度疑似自身免疫性脑炎，却未检测到明确的特征性自身抗体，此类患者面临诊断与治疗的双重困境。
研究目的：旨在评估临床高度疑似自身免疫性脑炎患者的脑脊液（cerebrospinal fluid, CSF）常规及新型检测手段，以期发掘更优质的神经炎症生物标志物。
研究方法：在2016至2018年共计18个月的周期内，我们招募了临床高度疑似自身免疫性脑炎的成年患者，开展一项探索性横断面预实验。同时纳入病毒聚合酶链反应（polymerase-chain-reaction, PCR）阳性的脑脊液样本，以及神经内科诊断为“非炎症性（non-inflammatory, NI）”患者的脑脊液作为对照。对所有脑脊液样本均开展脑炎常规检测及新型标志物检测，包括脑脊液轻链与细胞因子。
结果与结论：本研究在18个月内共招募32例自身免疫性脑炎患者，同时纳入21例病毒感染对照、10例非炎症性对照以及5例其他自身免疫性神经疾病（autoimmune neurological disease, AOND）对照纳入分析。研究发现，常规检测指标如脑脊液单核细胞增多、寡克隆带、抗神经元免疫荧光结果及磁共振成像（magnetic resonance imaging, MRI）异常虽可提示自身免疫性脑炎，但此类检测手段的灵敏度与特异性均欠佳。本研究发现的潜在新型自身免疫性脑炎标志物为脑脊液细胞因子IL-21与IP10，相较于常规指标，二者可更清晰地鉴别病毒感染与自身免疫性脑炎，或有助于此类患者实现更及时的诊断与治疗。