Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis
Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis
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DOI：
10.1212/wnl.0000000000200021
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发表时间：
2022-04-05
期刊：
影响因子：
9.9
通讯作者：
Dalmau, Josep
中科院分区：
文献类型：
--
作者：
Guasp, Mar;Martin-Aguilar, Lorena;Dalmau, Josep
背景与目的诊断抗nmda受体（NMDAR）脑炎（NMDARe）的一个重要挑战是将其与精神疾病（pFEP）引起的首发精神病（FEP）区分开来。脑脊液抗体测试可区分这些疾病，但在精神病院很难获得脊髓穿刺。另一个问题是缺乏NMDARe严重程度和结果的生物标志物。在这里，我们评估了神经丝轻链（NfL）测试在这些环境中的表现。方法采用单分子阵列检测NMDARe、pFEP、单纯疱疹性脑炎（HSE）和健康受试者（HC）的NfL水平，后2组为对照组。进行受试者工作特征（ROC）分析，以评估NMDARe和pFEP血清NfL （sNfL）水平的预测准确性，并获得临床有用的截止值。结果研究了118例NMDARe患者，其中33例首发时伴有孤立性精神病，45例伴pFEP， 36例伴HSE， 36例HC。与没有这些特征的NMDARe患者相比，伴有癫痫发作/癫痫持续状态、入住重症监护病房和脑脊液细胞增多（白细胞/ μ L）且未经早期免疫治疗的NMDARe患者更有可能出现更高的NfL（主要在脑脊液中）。NMDARe诊断时的NfL水平与用改良Rankin量表评估的1年随访结果不相关。NMDARe患者的sNfL明显高于pFEP和HC患者，低于HSE患者。对NMDARe伴孤立性精神病和pFEP的sNfL进行ROC分析，曲线下面积为0.93 (95% CI 0.87-0.99)， sNfL截断>= 15 pg/mL来区分这些疾病（敏感性85%，特异性96%，阳性似然比19.3）。45例sNfL= 15 pg/mL的pFEP患者中有43例（96%）发生NMDARe的几率是pFEP患者的120倍。这个临界值正确地将96%的pFEP患者和85%的NMDARe患者归类为孤立性精神病。病因不明且sNfL >= 15 pg/mL的FEP患者应进行CSF NMDAR抗体检测。
Background and Objectives An important challenge in diagnosing anti-NMDA receptor (NMDAR) encephalitis (NMDARe) is differentiating it from a first episode of psychosis (FEP) caused by a psychiatric disease (pFEP). CSF antibody testing distinguishes these diseases, but spinal taps are difficult to obtain in psychiatric facilities. A separate problem is the lack of biomarkers of NMDARe severity and outcome. Here we assessed the performance of neurofilament light chain (NfL) testing in these settings. Methods In this observational study, NfL levels were determined with single-molecule array in patients with NMDARe, pFEP, herpes simplex encephalitis (HSE), and healthy participants (HC), with the last 2 groups used as controls. Receiver operating characteristic (ROC) analyses were performed to assess the prediction accuracy of serum NfL (sNfL) levels for NMDARe and pFEP and to obtain clinically useful cutoffs. Results One hundred eighteen patients with NMDARe (33 with isolated psychosis at presentation), 45 with pFEP, 36 with HSE, and 36 HC were studied. Patients with NMDARe with seizures/status epilepticus, intensive care unit admission, and CSF pleocytosis (>20 white blood cells/mu L) and without early immunotherapy were more likely to have higher NfL (mainly in CSF) than individuals with NMDARe without these features. NfL levels at diagnosis of NMDARe did not correlate with outcome at 1-year follow-up assessed with the modified Rankin Scale. Patients with NMDARe had significantly higher sNfL than individuals with pFEP and HC and lower sNfL than patients with HSE. ROC analysis of sNfL between NMDARe with isolated psychosis and pFEP provided an area under the curve of 0.93 (95% CI 0.87-0.99) and an sNfL cutoff >= 15 pg/mL to distinguish these disorders (sensitivity 85%, specificity 96%, positive likelihood ratio 19.3). Forty-three of 45 (96%) patients with pFEP had sNfL= 15 pg/mL had a 120 times higher chance of having NMDARe than those with pFEP. This cutoff correctly classified 96% of patients with pFEP and 85% of patients with NMDARe with isolated psychosis. Patients with FEP of unclear etiology and sNfL >= 15 pg/mL should undergo CSF NMDAR antibody testing.