脑脊液宏基因组学第二代测序辅助诊断中枢神经系统链球菌感染二例

doi:10.3969/j.issn.1672-6731.2024.04.008

摘要/Abstract

关键词: 脑膜炎，肺炎球菌性, 脑脓肿, 脑脊髓液, 宏基因组学, 基因检测, 病例报告

Key words: Meningitis, pneumococcal, Brain abscess, Cerebrospinal fluid, Metagenomics, Genetic testing, Case reports

狄晓萌, 王佳伟, 段泽君, 刘磊. 脑脊液宏基因组学第二代测序辅助诊断中枢神经系统链球菌感染二例[J]. 中国现代神经疾病杂志, 2024, 24(4): 245-252.

Xiao-meng DI, Jia-wei WANG, Ze-jun DUAN, Lei LIU. Metagenomic next-generation sequencing assisted diagnosis of Streptococcal infection of central nervous system: two cases report[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2024, 24(4): 245-252.

https://journal11.magtechjournal.com/cjcnn/CN/Y2024/V24/I4/245

图/表 5

图 1 例1重复送检冻存于-80 ℃冰箱的脑脊液样本mNGS测序显示，肺炎链球菌基因组的总碱基数为2 110 968 bp，序列覆盖的总长度为8951 bp，覆盖度为0.424%，平均深度为1 ×

Figure 1 mNGS in Case 1 (re-tested CSF samples stored at -80 ℃ refrigerator) showed Streptococcus pneumoniae was detected by mNGS in CSF, the total number of bases in the sequence was 2 110 968 bp, the total length of the sequence coverage was about 8951 bp, the genome coverage was 0.424%, and the average sequencing depth was 1 ×.

图 2 例1头部MRI检查所见 2a 横断面DWI显示双侧侧脑室枕角高信号，提示液-液平（箭头所示） 2b 横断面增强T₁WI未见右侧侧脑室强化征象，可见左侧侧脑室枕角室管膜轻度线样强化（箭头所示） 2c 横断面DWI显示第三脑室后部高信号，提示液-液平（箭头所示） 2d 横断面增强T₁WI未见第三脑室后部异常强化征象

Figure 2 Cranial MRI findings of Case 1 Axial DWI showed hyperintensity in bilateral occipital horn of the lateral ventricles, suggesting fluid-fluid planes (arrows indicate, Panel 2a). Axial enhanced T₁WI showed no enhancement in the occipital horn of the right lateral ventricle but mild rim-like ependymal enhancement in the horn of the left lateral ventricle (arrow indicates, Panel 2b). Axial DWI showed hyperintensity in the posterior portion of the third ventricle, suggesting fluid-fluid planes (arrow indicates, Panel 2c). Axial enhanced T₁WI showed no signs of abnormal enhancement of the posterior portion of the third ventricle (Panel 2d).

图 3 例2重复送检冻存于-80 ℃冰箱的脑脊液样本mNGS测序显示，中间链球菌基因组的总碱基数为1 932 951 bp，序列覆盖的总长度为26 463 bp，覆盖度为1.369%，平均深度为1.014 ×

Figure 3 mNGS in Case 2 (re-tested CSF samples stored at-80 ℃ refrigerator) showed Streptococcus intermedius was detected by mNGS in CSF, the total number of bases in the sequence was 1 932 951 bp, the total length of the sequence coverage was about 26 463 bp, the genome coverage was 1.369%, and the average sequencing depth was 1.014 ×.

图 4 例2头部CT检查所见 4a 横断面CT显示，右侧枕叶及左侧丘脑、基底节区多发低密度影 4b 横断面CT显示，左侧额叶低密度影（箭头所示） 图 5 例2头部MRI检查所见 5a 横断面T₁WI显示，右侧枕叶、左侧丘脑和额叶多发类圆形囊性病变，囊液呈低信号 5b 横断面T₂-FLAIR成像显示，右侧枕叶、左侧丘脑多发类圆形囊性病变，囊液呈稍高信号，周围可见高信号水肿区 5c 横断面DWI显示，右侧枕叶、左侧丘脑多发类圆形囊性病变，囊液呈高信号

Figure 4 Cranial CT findings of Case 2 Axial CT showed multiple hypodensities in the right occipital lobe, left thalamus and basal ganglia (Panel 4a). Axial CT showed a hypodensity lesion in the left frontal lobe (arrow indicates, Panel 4b). Figure 5 Cranial MRI findings of Case 2 Axial T₁WI showed multiple rounded hyperintensities in the right occipital lobe, left thalamus and frontal lobe (Panel 5a). Axial T₂-FLAIR showed multiple rounded cystic lesions in the right occipital lobe and left thalamus with slightly hyperintensity in the central part and hyperintense edema in the periphery (Panel 5b). Axial DWI showed multiple rounded cystic lesions with hyperintense cystic fluid in the right occipital lobe and left thalamus (Panel 5c).

图 6 例2左侧基底节病变光学显微镜观察所见 × 400 6a 水肿脑组织内散在小血管周围淋巴细胞“套袖”形成 HE染色 6b 脑实质内可见星形胶质细胞增生及散在淋巴细胞浸润 HE染色 6c 炎性细胞主要为CD3⁺T细胞免疫组化染色（EnVision二步法） 6d 仅见个别CD20⁺B细胞免疫组化染色（EnVision二步法）

Figure 6 Light microscopy findings of left basal ganglia of Case 2 × 400 There was brain edema with scattered perivascular lymphocytic cuffing (Panel 6a). HE staining Astrocyte infiltration and scattered lymphocytic infiltration were noted in the brain parenchymal lesions (Panel 6b). HE staining The main component inflammatory cells were CD3⁺T lymphocytes (Panel 6c). Immunohistochemical staining (EnVision) There were few CD20⁺B lymphocytes (Panel 6d). Immunohistochemical staining (EnVision)

参考文献 30

1	van de Beek D , Brouwer M , Hasbun R , Koedel U , Whitney CG , Wijdicks E . Community-acquired bacterial meningitis. Nat Rev Dis Primers, 2016, 2: 16074. doi: 10.1038/nrdp.2016.74
2	Sun DB , Wang M , Guo Y . Distribution and drug resistance of cerebrospinal fluid pathogenic bacteria in hospitalized patients. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2020, 20: 455- 459. URL
	孙登彬, 王猛, 郭烨. 住院患者脑脊液病原菌分布及其耐药分析. 中国现代神经疾病杂志, 2020, 20: 455- 459. URL
3	van de Beek D , Brouwer MC , Koedel U , Wall EC . Community-acquired bacterial meningitis. Lancet, 2021, 398: 1171- 1183. doi: 10.1016/S0140-6736(21)00883-7
4	McGill F , Heyderman RS , Panagiotou S , Tunkel AR , Solomon T . Acute bacterial meningitis in adults. Lancet, 2016, 388: 3036- 3047. doi: 10.1016/S0140-6736(16)30654-7
5	Gil E , Wall E , Noursadeghi M , Brown JS . Streptococcus pneumoniae meningitis and the CNS barriers. Front Cell Infect Microbiol, 2023, 12: 1106596. doi: 10.3389/fcimb.2022.1106596
6	Marra A , Brigham D . Streptococcus pneumoniae causes experimental meningitis following intranasal and otitis media infections via a nonhematogenous route. Infect Immun, 2001, 69: 7318- 7325. doi: 10.1128/IAI.69.12.7318-7325.2001
7	Koelman DLH , Brouwer MC , Ter Horst L , Bijlsma MW , van der Ende A , van de Beek D . Pneumococcal meningitis in adults: a prospective nationwide cohort study over a 20-year period. Clin Infect Dis, 2022, 74: 657- 667. doi: 10.1093/cid/ciab477
8	Martín-Cerezuela M , Aseginolaza-Lizarazu M , Boronat-García P , Asensio-Martín MJ , Alamán-Laguarda G , Álvarez-Lerma F , Roa-Alonso D , Socias L , Vera-Artázcoz P , Ramírez-Galleymore P , Grupo de Trabajo en Infección y Sepsis (GTEIS) from the Sociedad Española de Medicina Intensiva y Unidades Coronarias (SEMICYUC) . Severe community-acquired Streptococcus pneumoniae bacterial meningitis: clinical and prognostic picture from the intensive care unit. Crit Care, 2023, 27: 72. doi: 10.1186/s13054-023-04347-3
9	Klein M , Abdel-Hadi C , Bühler R , Grabein B , Linn J , Nau R , Salzberger B , Schlüter D , Schwager K , Tumani H , Weber J , Pfister HW . German guidelines on community-acquired acute bacterial meningitis in adults. Neurol Res Pract, 2023, 5: 44. doi: 10.1186/s42466-023-00264-6
10	Buchholz G , Koedel U , Pfister HW , Kastenbauer S , Klein M . Dramatic reduction of mortality in pneumococcal meningitis. Crit Care, 2016, 20: 312. doi: 10.1186/s13054-016-1498-8
11	Jensen A , Hoshino T , Kilian M . Taxonomy of the Anginosus group of the genus Streptococcus and description of Streptococcus anginosus subsp. whileyi subsp. nov. and Streptococcus constellatus subsp. viborgensis subsp. nov. Int J Syst Evol Microbiol, 2013, 63 (Pt 7): 2506- 2519.
12	Issa E , Salloum T , Tokajian S . From normal flora to brain abscesses: a review of Streptococcus intermedius. Front Microbiol, 2020, 11: 826. doi: 10.3389/fmicb.2020.00826
13	Mishra AK , Fournier PE . The role of Streptococcus intermedius in brain abscess. Eur J Clin Microbiol Infect Dis, 2013, 32: 477- 483. doi: 10.1007/s10096-012-1782-8
14	Brouwer MC , Tunkel AR , McKhann GM 2nd , van de Beek D . Brain abscess. N Engl J Med, 2014, 371: 447- 456. doi: 10.1056/NEJMra1301635
15	Menon S , Bharadwaj R , Chowdhary A , Kaundinya DV , Palande DA . Current epidemiology of intracranial abscesses: a prospective 5 year study. J Med Microbiol, 2008, 57 (Pt 10): 1259- 1268.
16	Sakushima K , Hayashino Y , Kawaguchi T , Jackson JL , Fukuhara S . Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: a meta-analysis. J Infect, 2011, 62: 255- 262. doi: 10.1016/j.jinf.2011.02.010
17	Nemescu RE , Iancu LS , Dorneanu OS , Ursu RG , Dorobăţ CM . Influence of antibiotic therapy prior to admission on the efficacy of classical methods for the diagnosis of meningococcal disease. Rev Med Chir Soc Med Nat Iasi, 2014, 118: 497- 502.
18	Diallo K , Feteh VF , Ibe L , Antonio M , Caugant DA , du Plessis M , Deghmane AE , Feavers IM , Fernandez K , Fox LM , Rodrigues CMC , Ronveaux O , Taha MK , Wang X , Brueggemann AB , Maiden MCJ , Harrison OB . Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: a narrative review. EbioMedicine, 2021, 65: 103274. doi: 10.1016/j.ebiom.2021.103274
19	Abdeldaim GM , Strålin K , Korsgaard J , Blomberg J , Welinder-Olsson C , Herrmann B . Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. BMC Microbiol, 2010, 10: 310. doi: 10.1186/1471-2180-10-310
20	Lin CX , Yang H , Zhang H . Cerebral infarction associated with Aspergillus infection in the central nervous system: a case report. Zhong Feng Yu Shen Jing Ji Bing Za Zhi, 2022, 39: 1027- 1029.
	林彩秀, 杨卉, 张灏. 中枢神经系统曲霉菌感染相关脑梗死病例1例报告. 中风与神经疾病杂志, 2022, 39: 1027- 1029.
21	Meng C , Li R , Liu L , Wang JW . Infection of nocardia farcinica in central nervous system: one case report. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2021, 391- 394. URL
	孟超, 李然, 刘磊, 王佳伟. 中枢神经系统鼻疽奴卡菌感染一例. 中国现代神经疾病杂志, 2021, 21: 391- 394. URL
22	Zhang LH , Luo S , Xu ST , Li SJ , Hu WX , Xie HL . Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus diagnosed by cerebrospinal fluid next-generation sequencing test twice. Shen Zang Bing Yu Tou Xi Shen Yi Zhi Za Zhi, 2022, 31: 595- 600.
	张丽华, 罗松, 许书添, 李世军, 胡伟新, 谢红浪. 两次脑脊液宏基因二代测序诊断系统性红斑狼疮并发进行性多灶性白质脑病. 肾脏病与透析肾移植杂志, 2022, 31: 595- 600.
23	Tian P , Yang L , Fu JM , Liang HM , Fan XW . Diagnosis of AIDS combined with toxoplasmic encephalitis by cerebrospinal fluid next-generation sequencing: a case report. Zhong Feng Yu Shen Jing Ji Bing Za Zhi, 2020, 37: 378- 379. URL
	田盼, 杨丽, 付建敏, 梁花敏, 范学文. 脑脊液二代测序诊断艾滋病合并弓形虫脑炎1例报告. 中风与神经疾病杂志, 2020, 37: 378- 379. URL
24	Boolchandani M , D'Souza AW , Dantas G . Sequencing-based methods and resources to study antimicrobial resistance. Nat Rev Genet, 2019, 20: 356- 370.
25	Brown JR , Bharucha T , Breuer J . Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases. J Infect, 2018, 76: 225- 240. doi: 10.1016/j.jinf.2017.12.014
26	Li ZY , Dang D , Wu H . Next-generation sequencing of cerebrospinal fluid for the diagnosis of unexplained central nervous system infections. Pediatr Neurol, 2021, 115: 10- 20. doi: 10.1016/j.pediatrneurol.2020.10.011
27	Gu W , Miller S , Chiu CY . Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol, 2019, 14: 319- 338. doi: 10.1146/annurev-pathmechdis-012418-012751
28	Wilson MR , O'Donovan BD , Gelfand JM , Sample HA , Chow FC , Betjemann JP , Shah MP , Richie MB , Gorman MP , Hajj-Ali RA , Calabrese LH , Zorn KC , Chow ED , Greenlee JE , Blum JH , Green G , Khan LM , Banerji D , Langelier C , Bryson-Cahn C , Harrington W , Lingappa JR , Shanbhag NM , Green AJ , Brew BJ , Soldatos A , Strnad L , Doernberg SB , Jay CA , Douglas V , Josephson SA , DeRisi JL . Chronic meningitis investigated via metagenomic next-generation sequencing. JAMA Neurol, 2018, 75: 947- 955. doi: 10.1001/jamaneurol.2018.0463
29	Wilson MR , Sample HA , Zorn KC , Arevalo S , Yu G , Neuhaus J , Federman S , Stryke D , Briggs B , Langelier C , Berger A , Douglas V , Josephson SA , Chow FC , Fulton BD , DeRisi JL , Gelfand JM , Naccache SN , Bender J , Dien Bard J , Murkey J , Carlson M , Vespa PM , Vijayan T , Allyn PR , Campeau S , Humphries RM , Klausner JD , Ganzon CD , Memar F , Ocampo NA , Zimmermann LL , Cohen SH , Polage CR , DeBiasi RL , Haller B , Dallas R , Maron G , Hayden R , Messacar K , Dominguez SR , Miller S , Chiu CY . Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. N Engl J Med, 2019, 380: 2327- 2340. doi: 10.1056/NEJMoa1803396
30	Barlas O , Sencer A , Erkan K , Eraksoy H , Sencer S , Bayindir C . Stereotactic surgery in the management of brain abscess. Surg Neurol, 1999, 52: 404- 410. doi: 10.1016/S0090-3019(99)00118-4

[1]	梅月昕, 陈歆然, 陈红兵. 急性直窦血栓形成血管内治疗一例[J]. 中国现代神经疾病杂志, 2024, 24(8): 684-688.
[2]	王时强, 何小燕, 耿涛, 彭昌兴. 颅内多发动脉瘤长期随访一例[J]. 中国现代神经疾病杂志, 2024, 24(8): 689-694.
[3]	何平, 徐欣, 凌至培. 早发型帕金森病丘脑底核脑深部电刺激术后长期随访一例[J]. 中国现代神经疾病杂志, 2024, 24(7): 555-558.
[4]	赵亚楠, 李梦, 方艳博, 邓文静. 以肌张力障碍为发病特点的脊髓小脑性共济失调2型一例[J]. 中国现代神经疾病杂志, 2024, 24(7): 579-582.
[5]	王冬欣, 卢海丽, 陈娜. 成人副肿瘤性眼阵挛-肌阵挛-共济失调综合征一例[J]. 中国现代神经疾病杂志, 2024, 24(7): 583-588.
[6]	苏高健, 崔倩倩, 高杰, 朱栋梁, 吴楚伟, 黄贤键. 脑脊液宏基因组学第二代测序在颅内感染诊断与治疗中的应用[J]. 中国现代神经疾病杂志, 2024, 24(6): 435-441.
[7]	赵浩, 曲鑫, 王宁, 尚峰, 徐跃峤, 齐猛. 脑积水腰大池-腹腔分流术预后影响因素分析[J]. 中国现代神经疾病杂志, 2024, 24(6): 450-454.
[8]	荣轩, 苏高健, 吴佳宁, 赵世光, 黄贤键. 重度颅内感染集束化疗效分析[J]. 中国现代神经疾病杂志, 2024, 24(6): 471-477.
[9]	袁于青, 占青青, 谢亮. Ⅱ型亚历山大病一例[J]. 中国现代神经疾病杂志, 2024, 24(6): 502-506.
[10]	程婧, 张炜炜, 周勤明, 孟环宇, 何璐, 陈晟. 抗神经丝重链抗体相关脑炎一例并文献复习[J]. 中国现代神经疾病杂志, 2024, 24(5): 359-364.
[11]	董美学, 胡玲, 李涛. 笑气滥用致周围神经损害二例[J]. 中国现代神经疾病杂志, 2024, 24(5): 365-369.
[12]	胡宇静, 张莹, 代大伟, 姜宏佺. 抗神经节苷脂GD3抗体阳性慢性炎性脱髓鞘性多发性神经根神经病一例[J]. 中国现代神经疾病杂志, 2024, 24(5): 370-374.
[13]	解燕昭, 韩凝, 赵景茹, 魏娜. 肺动静脉畸形致急性脑梗死一例[J]. 中国现代神经疾病杂志, 2024, 24(5): 398-402.
[14]	彭玉晶, 史晓红, 王佳伟. 伴脑膜炎和（或）脑炎的Vogt-小柳-原田综合征临床特征分析[J]. 中国现代神经疾病杂志, 2024, 24(4): 217-223.
[15]	徐金梅, 刘兵舰, 关鸿志, 单萍, 陈国华, 梅俊华. 重度发热伴血小板减少综合征脑炎一例[J]. 中国现代神经疾病杂志, 2024, 24(4): 253-257.

选择文件类型/文献管理软件名称

选择包含的内容

2 脑脊液宏基因组学第二代测序辅助诊断中枢神经系统链球菌感染二例

Metagenomic next-generation sequencing assisted diagnosis of Streptococcal infection of central nervous system: two cases report

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 30

相关文章 15

编辑推荐

Metrics

本文评价

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 脑脊液宏基因组学第二代测序辅助诊断中枢神经系统链球菌感染二例

Metagenomic next-generation sequencing assisted diagnosis of Streptococcal infection of central nervous system: two cases report

RichHTML

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 30

相关文章 15

编辑推荐

Metrics

本文评价