Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis.
Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis.
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DOI：
10.1016/s1474-4422(18)30244-8
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发表时间：
2018-09
期刊：
影响因子：
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通讯作者：
Spanish Herpes Simplex Encephalitis Study Group
中科院分区：
文献类型：
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作者：
Armangue T;Spatola M;Vlagea A;Mattozzi S;Cárceles-Cordon M;Martinez-Heras E;Llufriu S;Muchart J;Erro ME;Abraira L;Moris G;Monros-Giménez L;Corral-Corral Í;Montejo C;Toledo M;Bataller L;Secondi G;Ariño H;Martínez-Hernández E;Juan M;Marcos MA;Alsina L;Saiz A;Rosenfeld MR;Graus F;Dalmau J;Spanish Herpes Simplex Encephalitis Study Group
单纯疱疹脑炎 (HSE) 可引发自身免疫性脑炎 (AE)，导致神经系统恶化。我们的目的是评估这种并发症的频率、综合征、危险因素和结果。对 2014 年 1 月 1 日至 2017 年 10 月 31 日期间诊断的 HSE 患者进行的前瞻性观察研究，由西班牙 19 个二级/三级中心的神经科医生、儿科医生和传染病专家（队列 A）进行。 2、6和12个月时进行门诊随访；前 3 周内死亡或招募延迟 > 10 天的患者被排除。对另一组患者在 HSE 后发生 AE 后进行回顾性研究（队列 B）。使用多变量二元逻辑回归模型评估 AE 的危险因素。 A 组包括 51 名患者（中位年龄 50 岁，IQR 6-68；29 名男性）； 14 例 (27%) 出现 AE，并且全部 (100%) 都有神经元抗体（9 例 NMDAR，5 例其他）；其他 37 例未出现 AE，11 例 (30%) 产生抗体（3 例 NMDAR，8 例其他）（p<0.001）。 HSE 后 3 周内的抗体检测通常预示着 AE（OR 11.5；95% CI2.7–48.8，p=0.001）。 HSE 后 2 个月内，AE 的抗体敏感性、特异性、阳性和阴性预测值分别为 100%、76%、61% 和 100%（如果仅考虑 NMDAR：64%、95%、82%、88%；在最小的儿童中：均为 100%）。 B 组包括 48 名患者（中位年龄 8.8 岁，IQR1.1-44.2；27 名男性），其中 44 名患有 AE（34 名 NMDAR，10 名其他患者）。在两个队列 (n=58 AE) 中，≥4 岁的患者经常出现精神病（18/31，58%；年龄较小的儿童无法评估）。 ≤4岁的患者 (27) 更有可能出现较短的 HSE-AE 间隔（中位 26 天 vs 43 天，p=0.0073）、舞蹈手足徐动症（27, 100% vs 0, p<0.001）、意识障碍（26, 96% vs 7, 23%, p<0.001）、NMDAR 抗体（24, 89% vs 19, 61%，p=0.033），1 年时结果更差（中位改良Rankin 量表，4 vs 2，p<0.001；癫痫发作，12/19 [63%] vs 3/23 [13%]，p=0.001）。 27% 的 HSE 患者发生 AE。它跟随神经元抗体的发展，通常在 HSE 后 3 个月内出现；这些症状与年龄有关，幼儿的结果更糟。及时诊断很重要，因为患者（主要是 4 岁以上的患者）对免疫疗法有反应。
Herpes simplex encephalitis (HSE) can trigger autoimmune encephalitis (AE) that leads to neurological worsening. We aimed to assess the frequency, syndromes, risk factors, and outcome of this complication. Prospective observational study of patients with HSE diagnosed between January 1st 2014 and October 31st 2017 by neurologists, pediatricians, and infectious disease specialists in 19 secondary/tertiary Spanish centers (Cohort-A). Outpatient follow-up was obtained at 2, 6 and 12 months; patients who died within the first 3 weeks or with delay in recruitment >10 days were excluded. Another group of patients was retrospectively studied after they developed AE post-HSE (Cohort-B). Multivariable binary logistic regression models were used to assess risk factors for AE. Cohort-A included 51 patients (median age 50 years, IQR 6–68; 29 male); 14 (27%) developed AE and all (100%) had neuronal antibodies (9 NMDAR, 5 other); the other 37 did not present AE and 11 (30%) developed antibodies (3 NMDAR, 8 other) (p<0.001). Antibody-detection within 3 weeks post-HSE often heralded AE (OR 11.5; 95% CI2.7–48.8, p=0.001). Within 2 months post-HSE, antibody sensitivity, specificity, positive and negative predictive values for AE were 100%, 76%, 61% and 100% (if only NMDAR considered: 64%, 95%, 82%, 88%; in youngest children: all 100%). Cohort-B included 48 patients (median age 8.8 years, IQR1.1–44.2; 27 male), 44 with AE (34 NMDAR, 10 other). In both Cohorts (n=58 AE), patients ≥4 years old frequently presented with psychosis (18/31, 58%; younger children not assessable). Patients ≤4 years (27) were more likely to have shorter HSE-AE intervals (median 26 vs 43 days, p=0.0073), choreoathetosis (27, 100% vs 0, p<0.001), impaired consciousness (26, 96% vs 7, 23%, p<0.001), NMDAR antibodies (24, 89% vs 19, 61%, p=0.033), and worse outcome at 1 year (median modified Rankin Scale, 4 vs 2, p<0.001; seizures, 12/19 [63%] vs 3/23 [13%], p=0.001). AE occurs in 27% of patients with HSE. It follows the development of neuronal antibodies and usually presents within 3 months post-HSE; the symptoms are age-dependent, and the outcome is worse in young children. Prompt diagnosis is important because patients, mainly those older than 4 years, respond to immunotherapy.