中枢神经系统李斯特菌感染患者的临床和脑脊液二代测序结果分析

Clinical data and next-generation sequencing results analysis of central nervous system infection with listeria

目的评价脑脊液二代测序在中枢神经系统（CNS）李斯特菌感染诊断中的潜在应用价值.方法为明确2017年6—11月在河南省人民医院神经内科住院的5例CNS感染患者的致病微生物,采用血液与脑脊液常规、生化、细胞学、培养、革兰染色等实验室检测方法,应用BGISEQ-100测序平台进行脑脊液病原测序,同时收集患者的相关临床资料,对患者的临床、实验室与辅助检查结果进行综合分析.结果在5例患者中,男性1例,女性4例,年龄26-61岁,发病前3例有免疫抑制剂治疗史,3例前驱期有消化道症状,CNS受累后均有发热、头痛,脑膜刺激征,影像学表现为脑膜、脑干或脑室周围受累,脑脊液细胞数〉500×10^6/L,脑脊液二代测序检测到单核增生性李斯特菌的核酸序列数57-2611条,基因覆盖度为0.23％-14.00％,PCR验证结果支持5例患者的CNS李斯特菌感染临床诊断成立.结论脑脊液二代测序技术可准确判断CNS李斯特菌感染,有利于及时治疗.

Objective To evaluate the potential value of next-generation sequencing （ NGS） as a diagnostic method for listeria infection in central nervous system （ CNS ） . Methods To identify the potentially pathogenic microorganisms （ PPMs） of the five patients with CNS infection in the Department of Neurology, People＇s Hospital of Zhengzhou University from June 2017 to November 2017, blood or cerebrospinal fluid （ CSF ） was detected not only using common laboratory tests , including routine , biochemical, cytologic, culture and Gram-staining methods, etc, but also using the BGISEQ-100 sequencing platform to identify the PPMs of CSF .Concomitantly , we collected concurrent clinical data , then performed a comprehensive analysis of their clinical , laboratory , and auxiliary examination data .Results Of the five cases （male ：female： 1：4, age ranges： 26 -61 years）, the disease mainly occurred in summer.Three patients received immunosuppressants treatment before infection , and three patients had gastrointestinal syndrome in the prodromal period .Infection of CNS led to fever , headache and meningeal irritation sign in all the patients.The medical imaging examinations showed the invasion of meninges , brainstem, and the periventricular gray matter.The cell count of CSF was more than 500 ×10^6/L.NGS techniques showed listeria genome sequence ranged from 57 to 2611, and the coverage of listeria varied from 0.23% to 14.00%, and PCR results supported the existence of listeria .Conclusion NGS is beneficial to make the diagnosis of listeria infection in CNS , and can help guide early treatment .