抗 NMDAR 脑炎与原发性精神病性精神病中神经丝轻链水平的研究
Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis.
机构信息
From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (M.G., L.S., M.B., T.A., E.M.-H., J.L., E.M., A.M.-L., A.S., J.C.-F., F.G., E.P., J.D.), Hospital Clínic, Universitat de Barcelona; Neurology Department (M.G., E.M.-H., A.M.-L., A.S., J.D.), Barcelona Clínic Schizophrenia Unit (BCSU) (M.B., E.P.), Department of Child and Adolescent Psychiatry and Psychology (T.A., J.C.-F.), Institute of Neuroscience, and Medical Statistics Core Facility (R.B.), Hospital Clínic, Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (M.G., L.S., E.M.-H., L.Q., J.D.), Madrid; Department of Neurology (L.M.-A., L.Q.), Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Department of Medicine (M.B., A.S., J.C.-F., E.P.), University of Barcelona; Centro de Investigación Biomédica en Red, Salud Mental (CIBERSAM) (M.B., J.C.-F., E.P.), Madrid; Department of Neurology (T.A.), Pediatric Neuroimmunology Unit, Sant Joan de Déu (SJD) Children's Hospital, University of Barcelona, Spain; Department of Neurology (J.D.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Catalan Institute for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
出版信息
Neurology. 2022 Apr 5;98(14):e1489-e1498. doi: 10.1212/WNL.0000000000200021. Epub 2022 Feb 10.
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/µL) 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, whereas only 5 of 33 (15%) with NMDARe with isolated psychosis were below this cutoff (risk estimation NMDARe vs pFEP: odds ratio 120.4 [95% CI 21.8-664], < 0.001). None of the patients with HSE and 35 of 36 (97%) HC had sNfL<15 pg/mL.
DISCUSSION
NfL measured at diagnosis of NMDARe associated with features of disease severity but not with long-term outcome. Young patients with FEP and 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.
背景与目的
诊断抗 N- 甲基-D- 天冬氨酸受体（NMDAR）脑炎（NMDARe）的一个重要挑战是将其与由精神疾病引起的首发精神病（FEP）（pFEP）区分开来。CSF 抗体检测可区分这些疾病，但在精神科医疗机构中很难进行腰椎穿刺。另一个问题是缺乏 NMDARe 严重程度和预后的生物标志物。在这里，我们评估了神经丝轻链（NfL）检测在这些环境中的性能。
方法
在这项观察性研究中，使用单分子阵列测定了 NMDARe、pFEP、单纯疱疹性脑炎（HSE）和健康参与者（HC）患者的 NfL 水平，后两组用作对照。进行了接收器操作特征（ROC）分析，以评估血清 NfL（sNfL）水平对 NMDARe 和 pFEP 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（33 例首发时伴有单纯精神病）、45 例 pFEP 患者、36 例 HSE 患者和 36 例 HC 患者。与无这些特征的 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 CSF 白细胞增多（>20 个白细胞/μL）且无早期免疫治疗的 NMDARe 患者的 NfL（主要在 CSF 中）水平更高。NMDARe 患者在发病时的 NfL 水平与 1 年随访时使用改良 Rankin 量表评估的结局无相关性。与 pFEP 和 HC 患者相比，NMDARe 患者的 sNfL 显著升高，与 HSE 患者相比，sNfL 显著降低。sNfL 在 NMDARe 伴单纯精神病与 pFEP 之间的 ROC 分析提供了 0.93（95%CI 0.87-0.99）的曲线下面积和 15pg/mL 以上的 sNfL 截止值以区分这些疾病（敏感性 85%，特异性 96%，阳性似然比 19.3）。45 例 pFEP 患者中有 43 例（96%）的 sNfL<15pg/mL，而 33 例伴有单纯精神病的 NMDARe 患者中仅有 5 例（15%）低于该截止值（NMDARe 与 pFEP 的风险估计：比值比 120.4[95%CI 21.8-664]，<0.001）。无 HSE 患者和 36 例 HC 中有 35 例（97%）的 sNfL<15pg/mL。
讨论
NMDARe 发病时测定的 NfL 与疾病严重程度的特征相关，但与长期结局无关。FEP 且 sNfL≥15pg/mL 的年轻患者患 NMDARe 的几率比 pFEP 患者高 120 倍。该截止值正确分类了 96%的 pFEP 患者和 85%的 NMDARe 伴单纯精神病患者。FEP 病因不明且 sNfL≥15pg/mL 的患者应进行 CSF NMDAR 抗体检测。
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