central nervous system infections

中枢神经系统感染
  • 文章类型: Case Reports
    第一次精神病发作可能与神经系统疾病有关,尤其是感染性或自身免疫性脑炎。值得注意的是,由确认的亚急性细菌性脑膜炎引发的免疫介导的脑炎被记录在案,这就是我们将要介绍的情况。
    一名22岁女性,没有既往病史,免疫能力强,三个月的行为,情感和认知症状,随后出现感官知觉和精神病的妥协。脑脊液检查显示肺炎链球菌FilmArray®阳性的炎症体征。患者接受抗精神病药物和抗生素治疗2周,临床症状无改善。具有免疫介导性精神病的脑后综合征被认为是一种诊断,在症状完全缓解的情况下,开始使用皮质类固醇和血浆置换进行免疫抑制治疗。随访一年后,未发现神经系统复发。
    脑炎是一种神经综合征,由于脑实质损伤,可导致精神症状,包括精神病和行为改变。其原因通常是感染性(通常是病毒性)或自身免疫性(抗NMDA,AMPA,LGI1或其他)。细菌性脑膜炎的精神病在抗生素治疗下没有改善是显着的,其存在应提示一种免疫介导的感染后综合征,即使在未鉴定自身免疫性脑炎相关抗体的情况下,该综合征也可能对免疫调节剂的使用产生应答.文献中没有类似病例的报道。
    免疫介导的精神病可能是与细菌性脑膜炎相关的脑炎后综合征的表现,在使用抗精神病药和抗生素没有改善的情况下,用免疫抑制剂治疗可能会带来益处。
    UNASSIGNED: A first psychotic episode may be related to neurological diseases, especially encephalitis of infectious or autoimmune origin. It is remarkable that an immune-mediated encephalitis triggered by a confirmed subacute bacterial meningitis is documented, and this is the case we will present.
    UNASSIGNED: A 22-year-old woman with no previous medical history, immunocompetent, with three months of behavioral, affective and cognitive symptoms with subsequent compromise of sensory perception and psychosis. Examination of cerebrospinal fluid showed inflammatory signs with positive FilmArray© for Streptococcus pneumoniae. She received anti-psychotic and antibiotic treatment for 2 weeks without clinical improvement. Postencephalitic syndrome with immune-mediated psychosis was considered as a diagnosis, and immunosuppressive management with corticosteroid and plasmapheresis was initiated with complete resolution of symptoms. After one year of follow-up no neurological relapse has been identified.
    UNASSIGNED: Encephalitis is a neurological syndrome due to brain parenchymal damage that can result in psychiatric symptoms including psychosis and behavioral changes. Its causes are usually infectious (usually viral) or autoimmune (Anti NMDA, AMPA, LGI1 or others). A psychiatric condition in bacterial meningitis without improvement with antibiotic treatment is remarkable, its presence should suggest an immune-mediated post-infectious syndrome that may respond to the use of immunomodulators even in the absence of identification of autoimmune encephalitis-associated antibodies. No similar cases have been reported in the literature.
    UNASSIGNED: Immune-mediated psychosis may be a manifestation of post-encephalitic syndrome associated with bacterial meningitis and its treatment with immunosuppressants may offer benefit in cases where the use of antipsychotics and antibiotics shows no improvement.
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  • 文章类型: Case Reports
    脑膜炎仍然是中枢神经系统感染的重要原因。特别是在婴儿中,需要高度怀疑。虽然可以开始使用经验性抗生素,指导治疗必须采取诊断措施。此类病例的通知有助于监测数据和决定向人群提供疫苗。
    N meningiditis remains an important cause of central nervous system infection. A high index of suspicion is required especially in infants. While empirical antibiotics may be initiated, diagnostic measures must be adopted for guided therapy. Notification of such cases contributes to surveillance data and deciding on providing vaccines to the population.
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  • 文章类型: Journal Article
    宏基因组下一代测序(mNGS)在确定重症监护病房的医院中枢神经系统(CNS)感染中的应用仍未得到充分研究。
    我们通过mNGS和常规检查对院内CNS感染患者的脑脊液(CSF)样本进行了微生物学结果的回顾性分析。这项研究的目的是评估医院mNGS在该人群中的临床诊断效果。
    本研究共纳入26例院内中枢神经系统感染病例。共有69.2%(18/26)的样本检测mNGS呈阳性,显著大于通过常规技术检测到的7.7%(2/26;p<0.05)。在培养前施用抗生素很可能是CSF培养率低的原因。通过标准测试错过了25个致病菌株。通过常规测试,与mNGS结果一致的三种病原体呈阳性。由于低病原体CSF滴度,8例mNGS阴性。与传统测试相比,mNGS在诊断中枢神经系统感染方面表现出100%的敏感性和33.3%的特异性。30天死亡率为26.9%(7/26)。
    常规的微生物检测常常不能检测所有的神经侵入性病原体。我们的研究表明,mNGS提供了一种检测院内CNS感染的替代方法。通过将mNGS应用于脑膜炎或脑炎患者的CSF样本,我们能够提高诊断医院神经系统感染的能力。
    UNASSIGNED: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.
    UNASSIGNED: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population.
    UNASSIGNED: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p<0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26).
    UNASSIGNED: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.
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  • 文章类型: Journal Article
    目的:诊断预测模型用于评估疑似脑膜炎的儿科患者发生细菌性脑膜炎(BM)的概率。为了评估这些模型在怀疑中枢神经系统(CNS)感染的广大儿童中的诊断准确性,我们进行了外部验证。
    方法:我们在Medline进行了系统的文献综述,以确定有关发展的文章,改进或验证BM的预测模型,并在0-18岁怀疑中枢神经系统感染的儿童的前瞻性队列中验证了这些模型。
    方法:我们计算了灵敏度,特异性,预测值,受试者工作特征曲线下面积(AUC),并评估用于诊断BM的模型的校准。
    结果:总计,在2012年至2015年期间纳入的450名疑似中枢神经系统感染患者的队列中,验证了23个预测模型。在75例患者(17%)中,最终诊断为CNS感染,包括30例BM(7%).总体AUC范围为0.69至0.94(中位数0.83,四分位距[IQR]0.79-0.87),年龄≥28天的儿童从0.74到0.96(中位数0.89,IQR0.82-0.92),新生儿从0.58到0.91(中位数0.79,IQR0.75-0.82)。
    结论:预测模型在排除儿童BM方面表现出良好至优异的测试特征,有助于对疑似中枢神经系统感染的儿科患者进行诊断检查。但不能取代完整的历史,体检和辅助测试。
    OBJECTIVE: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation.
    METHODS: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection.
    METHODS: We calculated sensitivity, specificity, predictive values, the area under the receiver operating characteristic curve (AUC) and evaluated calibration of the models for diagnosis of BM.
    RESULTS: In total, 23 prediction models were validated in a cohort of 450 patients suspected of a CNS infection included between 2012 and 2015. In 75 patients (17%), the final diagnosis was a CNS infection including 30 with BM (7%). AUCs ranged from 0.69 to 0.94 (median 0.83, interquartile range [IQR] 0.79-0.87) overall, from 0.74 to 0.96 (median 0.89, IQR 0.82-0.92) in children aged ≥28 days and from 0.58 to 0.91 (median 0.79, IQR 0.75-0.82) in neonates.
    CONCLUSIONS: Prediction models show good to excellent test characteristics for excluding BM in children and can be of help in the diagnostic workup of paediatric patients with a suspected CNS infection, but cannot replace a thorough history, physical examination and ancillary testing.
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  • 文章类型: Case Reports
    新生隐球菌是一种全球性的侵袭性真菌病,已知会导致大量的发病率和死亡率。通常观察到免疫系统受损的个体更容易发生隐球菌性脑膜炎。虽然眼部受累很少见,先前的研究表明,只有27%的中枢神经系统受累患者的眼部病变先于症状性脑膜炎。眼内感染通常表现为脉络膜视网膜病变和玻璃体炎症,常导致严重的视力丧失。在这种情况下,我们介绍了一名57岁免疫功能正常的女性的临床细节,她在四川大学华西医院眼科就诊,右眼视力逐渐丧失。经过全面评估,她被诊断为真菌性眼内炎,随后开始对隐球菌性脑膜脑炎进行适当的诱导抗真菌治疗。这个案例突出了早期识别和治疗的重要性,这可能会改善患者的预后。
    Cryptococcus neoformans is a global invasive mycosis that is known to cause significant morbidity and mortality. It is commonly observed that individuals with compromised immune systems are more prone to developing cryptococcal meningitis. Although ocular involvement is rare, previous studies have indicated that ocular lesions precede symptomatic meningitis in only 27 % of patients with central nervous system involvement. Intraocular infections typically manifest as chorioretinopathy and vitreous inflammation, often leading to severe vision loss. In this case, we present the clinical details of a 57-year-old immunocompetent woman who visited the ophthalmology department of West China Hospital of Sichuan University with a progressive loss of vision in her right eye. After a thorough evaluation, she was diagnosed with fungal endophthalmitis, and subsequently initiated on appropriate induction anti-fungal therapy for cryptococcal meningoencephalitis. This case highlights the importance of early recognition and treatment, which can potentially improve the prognosis for patients.
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  • 文章类型: Journal Article
    目的小儿中枢神经系统(CNS)感染后内分泌后遗症的发生率尚不清楚。我们进行了这项范围审查,以评估儿科年龄的既往中枢神经系统感染患者内分泌改变的发生率。方法我们的筛选过程包括随机和非随机对照试验。所有类型的观察性研究,前瞻性和回顾性,已被包括在内。结果10项研究纳入我们的综述。所有研究中的累积患者人数为211,人群研究的平均年龄为4.9(±5岁)。纳入的论文描述了以下急性中枢神经系统感染:脑膜炎(9项研究报告了85例)和脑炎(3项研究描述了65例)。两例病例报告和一项回顾性研究报告了结核分枝杆菌CNS感染导致的垂体功能低下。在五项研究中,患者在感染时出现了内分泌合并症。另一项研究分析了49名以前患有结核性脑膜炎的年轻人,平均年龄为5.9±5.0岁:7名患者患有生长激素缺乏症,其中四人也有促性腺激素缺乏症;其他三人有促性腺激素缺乏症,促肾上腺皮质激素缺乏,和轻度高催乳素血症.结论对既往中枢神经系统感染患者进行规范化的多学科随访和研究至关重要。虽然垂体储备筛查在这些患者中并不常见,临床和研究中心应建立内分泌学评估,监测营养参数,以早期发现垂体功能减退症的体征和症状,并对既往有中枢神经系统感染的儿童进行适当的护理.
    Purpose The incidence of endocrine sequelae following central nervous system (CNS) infections in pediatric age is not known. We conducted this scoping review to assess the incidence of endocrinological alterations in patients with prior CNS infections in pediatric age. Methods Our screening process included both randomized and non-randomized controlled trials. All types of observational studies, prospective and retrospective, have been included. Results Ten studies were included in our review. The cumulative number of patients in all of the studies was 211, the mean age of the population study was 4.9 (±5 years). The included papers described the following acute CNS infections: meningitis (nine studies reported eighty-five cases) and encephalitis (three studies described sixty-five cases). Two case reports and one retrospective study reported hypopituitarism as a consequence of Mycobacterium tuberculosis CNS infection. In five studies the patients developed endocrine comorbidities at the time of infection. Another study analyzed 49 young adults who previously had tuberculous meningitis at a mean age of 5.9 ± 5.0 years: seven patients had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia. Conclusion Standardized multidisciplinary follow-up and research of patients with prior CNS infection is crucial. Although pituitary reserve screening is not commonly performed in these patients, clinical and research centers should set up an endocrinological evaluation with monitoring of auxological parameters to detect the signs and symptoms of hypopituitarism early and to initiate the appropriate care in children with previous CNS infections.
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  • 文章类型: Journal Article
    背景:麻醉师在急性疟疾感染期间的分娩和分娩管理中起着重要作用。此类病例的围产期麻醉考虑因素仍不清楚。
    结果:重要的围产期考虑因素包括血小板减少症和凝血病的严重程度,血液动力学状态和心脏病,以及中枢神经系统(CNS)受累的可能性。几种抗疟药可能与围手术期药物相互作用,导致低血糖,高铁血红蛋白血症,或QT延长。通常不应该引产。患者容量状态应在诱导前进行优化,但考虑到脑水肿的风险,应谨慎使用液体。在中枢神经系统受累的情况下,应保持颅内压。病例报告描述了神经轴麻醉的成功使用,但这种方法需要进一步确认安全性。尽管在怀孕期间伴随着气道管理的风险,在某些情况下,由于中枢神经系统感染和疾病并发症的机会,首选全身麻醉。无论分娩方式如何,都需要对神经系统和出血状态进行严格的术后评估。
    结论:尽管疟疾流行,妊娠合并急性疟疾患者的围手术期风险和首选麻醉模式仍未得到充分研究,结局数据有限.
    BACKGROUND: Anesthesiologists play an important role in the management of labor and delivery during acute malaria infection. The peripartum anesthesia considerations for such cases remain unclear.
    RESULTS: Important peripartum considerations include the severity of thrombocytopenia and coagulopathy, hemodynamic status and cardiac disease, and the likelihood of central nervous system (CNS) involvement. Several antimalarial drugs may interact with perioperative medications, causing hypoglycemia, methemoglobinemia, or QT prolongation. Labor should usually not be induced. Patient volume status should be optimized pre-induction, but fluids should be administered with caution given the risk of cerebral edema. In case of CNS involvement intracranial pressure should be maintained. Case reports describe the successful use of neuraxial anesthesia but this approach requires further confirmation of safety. Despite the risks accompanying airway management in pregnancy, in some cases, general anesthesia was preferred due to the chance of CNS infection and disease complications. Tight postoperative assessments of neurological and bleeding status are indicated regardless of the mode of delivery.
    CONCLUSIONS: Despite the prevalence of malaria, the perioperative risk and preferred mode of anesthesia for pregnant patients with acute malaria remain under-researched and outcome data are limited.
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  • 文章类型: Journal Article
    如果不能准确诊断和治疗,中枢神经系统(CNS)的感染会导致严重的后果。涉及CNS感染的广谱病原体可能使诊断具有挑战性。基于聚合酶链反应(PCR)的多重分子诊断面板可以快速,同时检测脑脊液(CSF)中的多种神经病原体。本研究旨在评估生物快速脑膜炎/脑炎RT-PCRMX-17面板(Bioeksen,伊斯坦布尔,Türkiye),一种新的多重PCR测试,诊断中枢神经系统感染。该小组可以检测到一系列病原体,包括大肠杆菌K1流感嗜血杆菌,单核细胞增生李斯特菌,脑膜炎奈瑟菌,肺炎链球菌,无乳链球菌,肠道病毒(EV),单纯疱疹病毒(HSV)1和2,HHV-6,HHV-7,HHV-8,人副病毒(HPeV),水痘带状疱疹病毒(VZV),脑脊液样本中的巨细胞病毒(CMV)和隐球菌/新生球菌。这项回顾性研究包括2022年6月至2023年7月期间送往布尔萨乌卢达大学健康应用和研究中心微生物学实验室的128名患者的128份CSF样本,以寻找中枢神经系统感染因子。患者临床,放射学和实验室数据从医院信息记录系统(HIRS)收集.通过培养鉴定细菌病原体,而使用快速跟踪诊断(FTD)多重RT-PCR面板(FastTrackDiagnosticsLtd.,卢森堡)对于HSV-1、HSV-2、VZV,EV,腮腺炎病毒和HPeV.然后使用BioSpeedy面板测试储存的CSF样品,并将结果与培养物和FTD面板的结果进行比较。根据传染病和儿科传染病专家,如果检测到的病原体与患者的症状和CSF特征一致,则认为是阳性的。检测到但患者症状和脑脊液特征不支持的病原体被归类为不确定临床相关性(UCR)。在128名中枢神经系统感染因子检测患者中,44例(34.4%)被诊断为中枢神经系统感染。所有方法的病原体总检出率为43.2%(19/44)。Bio-Speedy小组在29.5%(13/44)的患者中发现了病原体,其次是FTD面板(20.5%,9/44)和文化(9.1%,4/44)。通过培养鉴定了四种细菌,其中三个也被Bio-Speedy小组检测到。此外,六种细菌被Bio-Speedy小组鉴定,没有被文化识别的。FTD小组确定了九种病毒,其中四个也被Bio-Speedy确定。总的来说,Bio-Speedy小组检测到19种阳性病原体中的13种(9种细菌和4种病毒:[S.肺炎(n=3),VZV(n=3),脑膜炎奈瑟球菌(n=2),流感嗜血杆菌(n=2),单核细胞增生性乳杆菌(n=1),大肠杆菌(n=1)veEV(n=1)]。然而,Bio-Speedy小组确定了15种病原体[S.肺炎(n=1),大肠杆菌(n=1),C.gatti/新生动物(n=1),CMV(n=8),HHV-6(n=3)veHHV-7(n=1)]被认为是UCR。Bio-Speedy在确诊中枢神经系统感染的患者中确定了最高百分比(29.5%)的病原体。然而,应根据患者特征解释检测结果,以确保对患者进行适当的管理.使用多种方法和多重测试可以提高中枢神经系统感染的诊断准确性。
    Infections of the central nervous system (CNS) can lead to severe outcomes if not accurately diagnosed and treated. The broad spectrum of pathogens involved in CNS infections can make diagnosis challenging. Polymerase chain reaction (PCR) -based multiplex molecular diagnostic panels can rapidly and simultaneously detect multiple neuropathogens in cerebrospinal fluid (CSF). This study was aimed to assess the Bio-Speedy Meningitis/Encephalitis RT-PCR MX-17 panel (Bioeksen, İstanbul, Türkiye), a novel multiplex PCR test, in diagnosing CNS infections. The panel can detect a range of pathogens, including Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, enterovirus (EV), herpes simplex virus (HSV) 1 and 2, HHV-6, HHV-7, HHV-8, human parechovirus (HPeV), varicella zoster virus (VZV), cytomegalovirus (CMV) and Cryptococcus gatti/neoformans in CSF samples. This retrospective study included 128 CSF samples from 128 patients sent to Bursa Uludağ University Health Application and Research Center Microbiology Laboratory between June 2022 and July 2023 to search for CNS infectious agents. Patient clinical, radiological and laboratory data were collected from the Hospital Information Record System (HIRS). Bacterial pathogens were identified through culture, while viral pathogens were detected in CSF samples using the Fast Track Diagnostics (FTD) multiplex RT-PCR panel (Fast Track Diagnostics Ltd., Luxembourg) for HSV-1, HSV-2, VZV, EV, mumps virus and HPeV. The stored CSF samples were then tested using the BioSpeedy panel and the results were compared with those of the culture and the FTD panel. Pathogens that were detected were considered positive if they were consistent with the patient\'s symptoms and CSF characteristics according to infectious disease and pediatric infectious disease specialists. Pathogens detected but not supported by the patient\'s symptoms and CSF characteristics were classified as uncertain clinical relevance (UCR). Out of the 128 patients tested for CNS infectious agents, 44 (34.4%) were diagnosed with a CNS infection. The overall pathogen detection rate with all methods was 43.2% (19/44). The Bio-Speedy panel identified pathogens in 29.5% (13/44) of the patients, followed by the FTD panel (20.5%, 9/44) and culture (9.1%, 4/44). Four bacteria were identified with culture, three of which were also detected by the Bio-Speedy panel. Additionally, six bacteria were identified with Bio-Speedy panel, that were not identified by culture. The FTD panel identified nine viruses, four of which were also identified by Bio-Speedy. In total, the Bio-Speedy panel detected 13 of the 19 positive pathogens (nine bacteria and four viruses: [S.pneumoniae (n= 3), VZV (n= 3), N.meningitidis (n= 2), H.influenzae (n= 2), L.monocytogenes (n= 1), E.coli (n= 1) ve EV (n= 1)]. However, the Bio-Speedy panel identified 15 pathogens [S.pneumoniae (n= 1), E.coli (n= 1), C.gatti/neoformans (n= 1), CMV (n= 8), HHV-6 (n= 3) ve HHV-7 (n= 1)] considered as UCR. The Bio-Speedy identified the causative pathogens in the highest percentage (29.5%) of patients with confirmed CNS infections. Nevertheless, test results should be interpreted based on patient characteristics to ensure appropriate patient management. Using multiple methods and multiplex tests may improve diagnostic accuracy for CNS infections.
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  • 文章类型: Journal Article
    中枢神经系统感染(CNSI)是一种以复杂病原体为特征的疾病,快速的疾病进展,高死亡率和高致残率。这里,我们评估了宏基因组下一代测序(mNGS)在中枢神经系统感染诊断中的临床价值,并探讨了影响mNGS结果的因素。我们进行了一项回顾性研究,将mNGS与包括培养在内的常规方法进行比较,涂片等.111名疑似中枢神经系统感染患者被纳入本研究,并记录临床资料。采用卡方检验评估独立二项变量,以p<0.05为有统计学意义的阈值。在111例登记案件中,57.7%(64/111)被诊断为中枢神经系统感染。从这些案例中,mNGS发现39.6%(44/111)的真阳性病例,7.2%(8/111)假阳性病例,35.1%(39/111)真阴性病例,18.0%(20/111)假阴性。mNGS的敏感性和特异性分别为68.7%(44/64)和82.9%(39/47),分别。与文化相比,mNGS在CNSI患者中提供了更高的病原体检出率(68.7%(44/64)与26.5%(17/64),p<0.0001)。与传统方法相比,正百分比同意和负百分比同意分别为84.60%(44/52)和66.1%(39/59)。在物种特异性读数(SSRN)≥2时,mNGS在诊断明确的病毒性脑炎和/或脑膜炎中的表现最佳(曲线下面积[AUC]0.758,95%置信区间[CI]0.663-0.854)。在具有显著CSF异常(CSFWBC>300*106/L)的细菌性CNSI患者中,脑脊液mNGS阳性率较高。总而言之,常规微生物检测不足以检测所有神经侵入性病原体,和mNGS在CNSI中表现出令人满意的诊断性能,总体检出率高于培养(p<0.0001)。
    Central nervous system Infections (CNSIs) is a disease characterized by complex pathogens, rapid disease progression, high mortality rate and high disability rate. Here, we evaluated the clinical value of metagenomic next generation sequencing (mNGS) in the diagnosis of central nervous system infections and explored the factors affecting the results of mNGS. We conducted a retrospective study to compare mNGS with conventional methods including culture, smear and etc. 111 suspected CNS infectious patients were enrolled in this study, and clinical data were recorded. Chi-square test were used to evaluate independent binomial variables, taking p < 0.05 as statistically significant threshold. Of the 111 enrolled cases, 57.7% (64/111) were diagnosed with central nervous system infections. From these cases, mNGS identified 39.6% (44/111) true-positive cases, 7.2% (8/111) false-positive case, 35.1% (39/111) true-negative cases, and 18.0% (20/111) false-negative cases. The sensitivity and specificity of mNGS were 68.7% (44/64) and 82.9% (39/47), respectively. Compared with culture, mNGS provided a higher pathogen detection rate in CNSIs patients (68.7% (44/64) vs. 26.5% (17/64), p < 0.0001). Compared to conventional methods, positive percent agreement and negative percent agreement was 84.60% (44/52) and 66.1% (39/59) separately. At a species-specific read number (SSRN) ≥ 2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] 0.758, 95% confidence interval [CI] 0.663-0.854). In bacterial CNSIs patients with significant CSF abnormalities (CSF WBC > 300*106/L), the positive rate of CSF mNGS is higher. To sum up, conventional microbiologic testing is insufficient to detect all neuroinvasive pathogens, and mNGS exhibited satisfactory diagnostic performance in CNSIs and with an overall detection rate higher than culture (p < 0.0001).
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  • 文章类型: Journal Article
    宏基因组下一代测序(mNGS)在脑脊液(CSF)病原体检测中的应用受到限制,微生物,和生物信息没有很好的联系。我们分析了428名入选患者的临床特征,脑脊液中mNGS的病原体诊断效率,CSF中的微生物群落结构和组成,以及CSF中微生物和临床生物标志物的相关性。一般特征没有特异性,但有助于制定鉴别诊断。CSFmNGS的检出率(34.6%)高于传统方法(5.4%)。从发病到CSF采集时间≤20天时,mNGS检出率较高,脑脊液白细胞计数>200×106/L,脑脊液蛋白浓度>1.3g/L,或非术后细菌性中枢神经系统感染(CNSi)的脑脊液葡萄糖浓度≤2.5mmol/L。脑脊液不是严格的无菌环境,潜在的病原体可能导致CSF微生物群的生态失调。此外,临床生物标志物与CNS病原体显著相关.临床数据有助于选择适当的机会来获得mNGS的准确结果,并可以推测mNGS结果是否正确。我们的研究是探索不同CNSI中CSF微生物组的开创性研究。
    The application of metagenomic next-generation sequencing (mNGS) in pathogens detection of cerebrospinal fluid (CSF) is limited because clinical, microbiological, and biological information are not well connected. We analyzed the 428 enrolled patients\' clinical features, pathogens diagnostic efficiency of mNGS in CSF, microbial community structure and composition in CSF, and correlation of microbial and clinical biomarkers in CSF. General characteristics were unspecific but helpful in formulating a differential diagnosis. CSF mNGS has a higher detection rate (34.6%) compared to traditional methods (5.4%). mNGS detection rate was higher when the time from onset to CSF collection was ≤20 days, the CSF leukocytes count was >200 × 106/L, the CSF protein concentration was >1.3 g/L, or CSF glucose concentration was ≤2.5 mmol/L in non-postoperative bacterial CNS infections (CNSi). CSF was not strictly a sterile environment, and the potential pathogens may contribute to the dysbiosis of CSF microbiome. Furthermore, clinical biomarkers were significantly relevant to CNS pathogens. Clinical data are helpful in choosing a proper opportunity to obtain an accurate result of mNGS, and can speculate whether the mNGS results are correct or not. Our study is a pioneering study exploring the CSF microbiome in different CNSIs.
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