宏基因组二代测序技术在结核性脑膜炎诊断中的应用并文献复习

Application of Metagenomic Next-Generation Sequencing in TBM Diagnosis and Literature Review

摘要: 目的：探讨宏基因组二代测序技术(metagenomics next-generation sequencing, mNGS)在结核性脑膜炎(tubercular meningitis, TBM)诊断中的应用价值。方法：回顾性分析2022年3月20日济宁医学院附属医院神经内科收治的一例TBM患者的临床资料以及2024年8月3日济宁医学院附属医院消化内科收治的一例TBM患者的临床资料，总结mNGS在TBM诊断中的应用并进行文献复习。结果：病例1：患者女性，57岁，因“头疼5天”入院。最初症状为全头部胀痛，尤其是双眼眶部，伴有发热。在初步检查中，发现患者的C反应蛋白、甘油三酯、葡萄糖、钾、钠和氯等指标异常。患者入院后，头痛持续，伴有恶心、呕吐，饮食和睡眠受到影响。脑脊液生化及常规显示脑脊液蛋白质增多，糖及氯化物降低，以及单核细胞比例升高，提示中枢神经系统感染的可能，结合患者弟弟有肺结核病史的信息，医生考虑结核性脑膜炎的可能。最终，脑脊液mNGS结果证实了结核分枝杆菌复合群的存在，该患者确诊为TBM。病例2：患者女性，66岁，因“发热、纳差、恶心半月余”入院。最初表现为发热、纳差、恶心等症状，随后被诊断为中枢神经系统感染，疑似病毒性脑膜炎。治疗过程中，患者接受了多种药物治疗，包括抗病毒、改善脑代谢、补钠、保肝和抑酸护胃的药物。然而，患者的症状并未完全缓解，头痛、恶心持续存在，且在治疗过程中出现了低钠、低钾等电解质紊乱。最终，通过脑脊液行mNGS，确诊为TBM。结论：mNGS对TBM的诊断具有良好的特异性，敏感性有待进一步提升。在协助临床医生诊断具有挑战性的TBM时，mNGS有着巨大的潜力，但其高成本仍然是主要限制因素。

Abstract: Objective: To investigate the diagnostic utility of metagenomics next-generation sequencing (mNGS) in tubercular meningitis (TBM). Methods: A retrospective analysis was conducted on the clinical data of a TBM case admitted to the Department of Neurology at the Affiliated Hospital of Jining Medical University on March 20, 2022, and another TBM case admitted to the Department of Gastroenterology at the same institution on August 3, 2024. This analysis aimed to evaluate the application of mNGS in diagnosing TBM and included a comprehensive review of the relevant literature. Case 1 involves a 57-year-old female patient presenting with a “5-day history of headache”. The initial clinical manifestations included generalized head swelling and pain, with a particular emphasis on the orbital regions of both eyes, accompanied by fever. Upon initial evaluation, laboratory tests revealed abnormalities in C-reactive protein, triglycerides, glucose, potassium, sodium, and chloride levels. Following hospital admission, the patient continued to experience persistent headaches, along with nausea and vomiting, which adversely affected her dietary intake and sleep patterns. Cerebrospinal fluid biochemistry and routine examination showed increased cerebrospinal fluid proteins, decreased sugar and chloride, and increased monocyte ratio, suggesting the possibility of a central nervous system infection. Combined with the information that the patient’s younger brother had a history of tuberculosis, the physician considered the possibility of tuberculous meningitis. Ultimately, CSF mNGS results confirmed the presence of Mycobacterium tuberculosis complex, and the patient was diagnosed with TBM. Case 2: The patient was a 66-year-old woman who was admitted to the hospital with “fever, loss of appetite, and nausea for more than half a month”. She initially presented with fever, anorexia, and nausea, and was subsequently diagnosed with a central nervous system infection suspected to be viral meningitis. In the course of treatment, the patient received a variety of medications, including antivirals, cerebral metabolic enhancers, sodium supplementation, hepatoprotectants, and gastric acid suppressants. However, the patient’s symptoms did not completely resolve, with persistent headaches and nausea, and electrolyte disturbances such as low sodium and potassium developed over the course of treatment. Finally, the diagnosis of TBM was confirmed by cerebrospinal fluid mNGS. Conclusions: mNGS has good specificity for the diagnosis of TBM, with sensitivity to be further improved. The mNGS has great potential to assist clinicians in the diagnosis of challenging TBM, but its high cost remains a major limiting factor.