高通量测序技术诊断儿童结核性脑膜炎合并血管炎1例

Diagnosis of one child with tuberculous meningitis complicated with vasculitis confirmed by high-throughput sequencing technique

儿童结核性脑膜炎(TBM)致死率和致残率高,部分患儿早期临床症状不典型,而且缺乏有效的检测手段,早期诊断存在一定的困难.采用高通量宏基因组测序技术(mNGS),通过检测致病病原体基因,能明确临床感染性疾病的病原学诊断.华中科技大学同济医学院附属武汉儿童医院于2020年3月31日收治1例TBM合并血管炎患儿,该患儿发病时仅表现为头晕及呕吐,疑似颅内占位性疾病.之后患儿出现频繁抽搐、发热,意识障碍迅速加重,结合颅脑磁共振成像(MRI)及脑脊液常规和生化等辅助检查,考虑患儿为中枢神经系统感染,多次行结核分枝杆菌(MTB)芯片检测为阴性,结核菌素试验及初期T细胞斑点试验(T-SPOT.TB)检测均为阴性,无法确诊TBM.最终应用mNGS技术在脑脊液中检测出MTB基因序列,符合MTB感染,排除其他感染病原体,最终确诊为TBM,给予抗结核治疗后患儿病情好转.提示临床可采用mNGS技术对儿童不典型TBM进行早期诊断,精准治疗,从而改善患儿预后.

The mortality and disability rates of children with Tuberculous meningitis(TBM)are high.The early clinical symptoms of some children with this disease are not typical,and lack of effective detection means,thus doctors often meet certain difficulties in early diagnosis.Using high-throughput sequencing technology(mNGS)can identify the etiological diagnosis of clinical infectious diseases by detecting pathogenic genes.A child with TBM complicated with vasculitis was admitted to Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology on March 31,2020.The child presented only with dizziness and vomiting,so at first the diagnosis was suspected of intracranial space-occupying disease.Afterwards,frequent convulsion and fever occurred in the child symptoms and signs,and conscious disturbance developed and aggravated rapidly in severity.Combined with cranial magnetic resonance imaging(MRI),routine and biochemical examinations of cerebrospinal fluid,etc.auxiliary tests,the child was considered to be a central nervous system infection.The child underwent multiple Mycobacterium tuberculosis(MTB)chip tests,tuberculin test and initial T cell spot test of TB(T-SPOT.TB),because of negative results of all the above tests,a definite TBM diagnosis could not be made.Finally,the MTB gene sequence was positively detected by mNGS technique in cerebrospinal fluid,which was consistent with MTB infection,and in the mean time,other infectious pathogens were excluded.At last,the child was surely diagnosed with TBM.After anti-tuberculosis treatment,the child's condition was improved.It is suggested that mNGS can be used for early diagnosis and precise treatment of atypical TBM in children,so as to improve the prognosis of this disease.