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[伪狂犬病病毒所致脑炎的临床经验及二代测序分析]

[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].

作者信息

Zhao W L, Wu Y H, Li H F, Li S Y, Fan S Y, Wu H L, Li Y J, Lü Y L, Han J, Zhang W C, Zhao Y, Li G L, Qiao X D, Ren H T, Zhu Y C, Peng B, Cui L Y, Guan H Z

机构信息

Department of Neurology, the Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia Autonomous Region 024005, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2018 Apr 17;98(15):1152-1157. doi: 10.3760/cma.j.issn.0376-2491.2018.15.006.

Abstract

To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities. Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity. The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)×10(6)/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up. PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.

摘要

在中国,检测病因不明的脑炎患者中包括伪狂犬病病毒在内的潜在病原体,并描述新型脑炎实体。临床疑似感染性脑炎患者被纳入一项多中心研究,以确定北京协和医院脑炎项目中的病原体。对2016年至2017年纳入的病因不明的脑炎患者使用脑脊液(CSF)的二代测序(NGS)。对诊断为伪狂犬病病毒脑炎的患者进行研究以描述这一新型实体。这4例患者(3例男性,1例女性,38 - 54岁)在从事猪肉生产或销售工作时职业暴露于生猪肉,且至少1人在切猪肉时受伤。其中2例通过CSF的NGS确诊,3例血清可用于血清学分析的患者抗伪狂犬病病毒抗体呈阳性。他们均在1至4天内急性起病,出现发热、惊厥、意识丧失和呼吸衰竭,即使经过广泛治疗病情仍迅速恶化。所有患者均需入住重症监护病房,3例需要机械通气。2例患者还患有双侧视网膜炎。神经影像学显示对称的灰质病变,包括边缘系统、基底神经节和中脑,无明显出血。腰椎穿刺显示颅内压升高,CSF淋巴细胞增多[(6 - 64)×10⁶/L]。患者对阿昔洛韦联合静脉注射免疫球蛋白和类固醇治疗无反应。末次随访时,4例患者的改良Rankin评分分别为3分、5分、5分和6分(死亡)。伪狂犬病病毒可能是严重脑炎的病因。疑似伪狂犬病脑炎(PRE)的患者需要及时检测伪狂犬病病毒DNA。职业暴露患者出现累及边缘系统、基底神经节、丘脑和中脑双侧的严重脑炎提示这种新发感染性脑炎。

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