Changyu Liu,1,* Yihan Cai,2,* Kaixuan Yuan,1 Mengdi Lu,1 Yangxi Deng,1 Xiaoli Chen,1 Long Ye,1 Shanzhao Cui,1 Jingwen Lyu,1,3 Yong Ling1 

1Department of Clinical Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Xiaolan People’s Hospital of Zhongshan (The Fifth People’s Hospital of Zhongshan), Zhongshan, Guangdong, 528415, People’s Republic of China; 3State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, 200433, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jingwen Lyu, Email lvjingwen66@163.com Yong Ling, Email lingyong@gdph.org.cn

Background: Tuberculous meningitis (TBM) remains a significant clinical challenge due to limitations in traditional diagnostic methods, such as cerebrospinal fluid (CSF) analysis and tuberculosis culture, which often have long turnaround times and low sensitivity and specificity. This case report highlights the pivotal role of metagenomic next-generation sequencing (mNGS) in enhancing clinical knowledge for the diagnosis and management of TBM, supplementing insights into its clinical presentation and treatment.
Case Presentation: A 56-year-old male patient was admitted to the hospital with a chief complaint of “unconsciousness for 4 days”. Following five days of antimicrobial therapy, the patient showed significant improvement with no fever or headache, but exhibited a suspicious left-sided Babinski sign (+). MRI revealed evidence of cerebral infarction, while spiral CT imaging showed hydrocephalus accompanied by interstitial cerebral edema. A lumbar puncture revealed elevated intracranial pressure, increased protein levels in CSF, reduced glucose and chloride concentrations, and negative results for CSF smear, CSF culture, and blood culture. T-SPOT testing was positive, and mNGS of CSF detected Mycobacterium tuberculosis (M. tuberculosis) Based on clinical and etiological findings, a diagnosis of tuberculous meningitis was confirmed. The patient was treated with quadruple anti-tuberculosis therapy combined with linezolid, resulting in clinical improvement. He was subsequently transferred to a specialized chest hospital for further management.
Conclusion: The patient’s condition improved after 5 days of treatment. TBM is notoriously challenging to diagnose and treat. Traditional diagnostic methods, such as smear microscopy and tuberculosis culture, often yield low positive rates, delaying timely diagnosis and intervention. Early detection, accurate diagnosis, and prompt treatment are crucial for improving patient outcomes. mNGS of CSF has proven to be a powerful tool in TBM diagnosis, enabling early and precise identification of the pathogen, thereby facilitating timely treatment and reducing TBM-related mortality.

Keywords: tuberculous meningitis, metagenomic next-generation sequencing, diagnosis