Neurologic Complications Associated With the Zika Virus in Brazilian Adults

Neurologic Complications Associated With the Zika Virus in Brazilian Adults
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DOI:
10.1001/jamaneurol.2017.1703
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发表时间:
2017-10-01
期刊:
影响因子:
29
通讯作者:
Moreira do Nascimento, Osvaldo Jose
Moreira do Nascimento, Osvaldo Jose
中科院分区:
医学1区
文献类型:
--
作者:
Ferreira da Silva, Ivan Rocha;Frontera, Jennifer A.;Moreira do Nascimento, Osvaldo Jose

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重要性 目前尚无评估成人寨卡病毒 (ZIKV) 感染继发神经系统症状的发生率和范围的前瞻性队列研究。 目的 评估因格林-巴尔综合征 (GBS)、脑膜脑炎或横贯脊髓炎住院患者的急性 ZIKV 感染率。 设计、环境和参与者 一项前瞻性、观察性队列研究是在神经系统疾病三级转诊中心进行的2015 年 12 月 5 日至 2016 年 5 月 10 日期间,巴西里约热内卢连续住院的患有新发急性副感染或神经炎症性疾病的成年人(> 18 岁)。所有参与者都接受了一系列虫媒病毒病测试。评估了三个月的功能结果。 干预措施 使用实时逆转录酶聚合酶链反应和 IgM 抗体捕获酶联免疫吸附测定法对血清和脑脊液样本进行 ZIKV 检测。收集临床、放射学(磁共振成像)、电生理学和 3 个月的功能结果数据。 主要结果和措施 ZIKV 感染继发的神经系统并发症的检测。 结果 纳入 40 名患者(15 名女性和 25 名男性;中位年龄,44 岁 [范围,22-72 岁]),其中 29 名患者(73%)患有 GBS(90% 布莱顿 1 级确定性),7 名患者(18%) 患有脑炎,3 例 (8%) 患有横贯性脊髓炎,1 例 (3%) 患有新诊断的慢性炎症性脱髓鞘性多发性神经病。其中,35 名患者 (88%) 的血清和/或脑脊液中有近期 ZIKV 感染的分子和/或血清学证据。在 ZIKV 感染阳性的患者中,27 例患有 GBS(18 例脱髓鞘性、8 例轴突性和 1 例米勒·费希尔综合征),5 例患有脑炎(3 例伴有急性神经肌肉疾病),2 例患有横贯性脊髓炎,1 例患有慢性炎症性脱髓鞘性多发性神经病。 9 名 ZIKV 感染阳性患者(26%)需要入住重症监护室,5 名患者(14%)需要机械通气。与2013年12月5日至2014年5月10日(巴西寨卡病毒爆发前)期间的入院人数相比,GBS入院人数从平均每月1.0人增加到每月5.6人,脑炎入院人数从每月0.4人增加到每月1.4人,横贯性脊髓炎入院人数保持稳定在每月0.6人。 3 个月时,2 名 ZIKV 感染阳性患者 (6%) 死亡(1 名 GBS 患者和 1 名脑炎患者),18 名患者 (51%) 患有慢性疼痛,幸存者的改良 Rankin 评分中位数为 2(范围为 0-5)。 结论和相关性 在这个巴西单中心队列中,ZIKV 感染与多种严重神经系统综合征的发病率增加相关。数据还表明,在发展中国家,使用血液和脑脊液样本进行血清学和分子检测可以作为一种更便宜的替代诊断策略,因为在这些国家,斑块减少中和测试是不切实际的。 (C) 2017 年美国医学会。版权所有。
IMPORTANCE There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.OBJECTIVE To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barr, syndrome (GBS), meningoencephalitis, or transversemyelitis.DESIGN, SETTING, AND PARTICIPANTS A prospective, observational cohort studywas conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (> 18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed.INTERVENTIONS Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase-polymerase chain reaction and an IgMantibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected.MAIN OUTCOMES AND MEASURES The detection of neurologic complications secondary to ZIKV infection.RESULTS Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transversemyelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transversemyelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, toMay 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5).CONCLUSIONS AND RELEVANCE In this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical. (C) 2017 American Medical Association. All rights reserved.