抗 NMDAR 脑炎患者 12 个月时脑脊液抗体持续存在的预后价值。
Prognostic Value of Persistent CSF Antibodies at 12 Months in Anti-NMDAR Encephalitis.
机构信息
From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., M.R., S.M.-C., V.W., A.V., M.V.G., A.F., D.G., G.P., V.R., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; SynatAc Team (N.L.C.-P., M.R., S.M.-C., V.W., A.V., M.V.G., A.F., D.G., G.P., V.R., B.J., J.H.), Institute MeLis, INSERM U1314/CNRS UMR 5284, Université de Lyon, Université Claude Bernard Lyon 1, France; Neuroimmunology and Neuroinflammation Group (N.L.C.-P., B.O.-M., P.J.S.-C.), Institute of Biomedical Research of Málaga - IBIMA; Andalusian Network of Clinical and Translational Research in Neurology (NeuroRECA) (N.L.C.-P., B.O.-M., P.J.S.-C.); Universidad de Málaga (N.L.C.-P., P.J.S.-C.), Andalucía Tech, Facultad de Medicina, Campus de Teatinos s/n, Spain; Service de Biostatistique - Bioinformatique (A.K., D.M.-B.), Pôle Santé Publique, Hospices Civils de Lyon; Laboratoire de Biométrie et Biologie Évolutive (A.K., D.M.-B.), Équipe Biostatistique-Santé, CNRS, UMR5558, Université Lyon 1, Université de Lyon, Villeurbanne; Immunology Department (D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Department of Cellular Biology, Genetics, and Physiology (B.O.-M.), Faculty of Sciences, University of Málaga, Spain.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2023 May 5;10(4). doi: 10.1212/NXI.0000000000200108. Print 2023 Jul.
BACKGROUND AND OBJECTIVES
Anti-NMDA receptor (NMDAR) encephalitis is defined by the presence of antibodies (Abs) targeting the NMDAR in the CSF. This study aimed to determine the prognostic value of persistent CSF NMDAR-Abs during follow-up.
METHODS
This retrospective observational study included patients diagnosed with anti-NMDAR encephalitis in the French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis and for whom CSF samples were obtained at diagnosis and >4 months of follow-up to evaluate CSF NMDAR-Ab persistence. Because patients were tested for CSF NMDAR-Abs at different time points, samples were stratified into different periods of follow-up (i.e., 12 months was considered for the 9- to 16-month follow-up period).
RESULTS
Among the 501 patients diagnosed with anti-NMDAR encephalitis between January 2007 and June 2020, 89 (17%) were tested between 4 and 120 months for CSF NMDAR-Abs after clinical improvement and included in the study (75/89 women, 84%; median age 20 years, interquartile range [IQR] 16-26). During follow-up, 21 of 89 (23%) patients had a relapse after a median time of 29 months (IQR 18-47), and 20 of 89 (22%) had a poor outcome (mRS ≥3) after a median last follow-up of 36 months (IQR 19-64). Most patients (69/89, 77%) were tested at the 12-month follow-up period, and 42 of 69 (60%) of them had persistent CSF NMDAR-Abs. When comparing patients with persistent or absent CSF NMDAR-Abs at 12 months, poor outcome at the last follow-up was more frequent in the former (38% vs 8%, = 0.01), who had relapses more often (23% vs 7%), which also appeared earlier in the course of the disease (90% during the following 4 years of follow-up vs 20%), although no significant difference was observed at long-term follow-up ( = 0.15). In addition, patients with persistent CSF NMDAR-Abs at 12 months had higher titers of CSF NMDAR-Abs at diagnosis.
DISCUSSION
In this study, patients with persistent CSF NMDAR-Abs at 12 months were more likely to have subsequent relapses and a poor long-term outcome. However, these findings should be interpreted with caution because of the variability in the time of sampling of this study. Future prospective studies are required to validate these results in larger cohorts.
背景与目的
抗 N- 甲基-D- 天冬氨酸受体（NMDAR）脑炎的定义是脑脊液中存在针对 NMDAR 的抗体（Abs）。本研究旨在确定随访期间脑脊液中持续存在 NMDAR-Abs 的预后价值。
方法
本回顾性观察性研究纳入了在法国神经副肿瘤综合征和自身免疫性脑炎参考中心诊断为抗 NMDAR 脑炎的患者，且在诊断时和随访>4 个月时获得了脑脊液样本，以评估脑脊液 NMDAR-Ab 的持续存在情况。由于患者在不同时间点检测脑脊液 NMDAR-Abs，因此将样本分为不同的随访期（即，9-16 个月的随访期考虑为 12 个月）。
结果
在 2007 年 1 月至 2020 年 6 月期间诊断的 501 例抗 NMDAR 脑炎患者中，有 89 例（17%）在临床改善后进行了 4 至 120 个月的脑脊液 NMDAR-Abs 检测，其中 75/89 例为女性（84%），中位年龄为 20 岁（四分位距 [IQR] 16-26）。在随访期间，21/89 例（23%）患者在中位时间 29 个月（IQR 18-47）后复发，20/89 例（22%）患者在中位末次随访 36 个月（IQR 19-64）后预后较差（mRS≥3）。大多数患者（69/89，77%）在 12 个月随访期进行了检测，其中 69/69 例（60%）患者的脑脊液 NMDAR-Abs 持续存在。在比较 12 个月时脑脊液 NMDAR-Abs 持续存在或不存在的患者时，前者在末次随访时预后较差的发生率更高（38%比 8%， = 0.01），前者更常复发（23%比 7%），且前者复发更早（90%在随访的 4 年内，而 20%在以后），尽管在长期随访中未观察到显著差异（ = 0.15）。此外，12 个月时脑脊液 NMDAR-Abs 持续存在的患者在诊断时脑脊液 NMDAR-Abs 的滴度更高。
讨论
在本研究中，12 个月时脑脊液 NMDAR-Abs 持续存在的患者更有可能随后复发和预后不良。然而，由于本研究采样时间的差异，这些发现的解释应谨慎。需要前瞻性研究在更大的队列中验证这些结果。
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