The Early Diagnosis And Pathogenesis Of Tuberculous Meningitis

Objective:Tuberculous meningitis(TBM),a chronic central nervous system infection disease caused by Mycobacterium tuberculosis, has high rates of case fatality and mutilation. The key point of prognostic resides in the early diagnosis and antituberculosis treatment promptly. Early diagnosis of tuberculous meningitis has been troubled clinicians. It reported the diagnosis rate was only 10% in early stage (within one week). Seeking the early method which is rapid is called the problem urgent to be solved at present. In this study, upon the foundation of CSF routine examination, CSF Cytology,mycobacterial antigen in monocytes (macrophages) and IFN-gamma levels in cerebrospinal are detected.To evaluate the clinical value of the methods in the early diagnosis and the pathogenesis of tuberculous meningitis.Methods:CSF samples were collected from 206 patients with definite diagnosis. All these patients were from the Second Hospital of Hebei Medical University during the period of 2004 October~2007 September. These patients were divided into two groups.⑴TBM group(Case group): Totally 102 patients. Among them 75 patients were pure TBM,5 patients have a history of exposure to tuberculosis,16 patients combined Pulmonary tuberculosis,2 patients combined Tuberculous peritonitis,3 patients combined Tuberculous pleurisy and 1 patient combined TB pyelonephritis. (2)Other diseases(Control group): Of the 124 patients,18 had pyogenic meningitis,46 had meningoencephalitis of viral,11 had cryptococcal meningitis, 9 had brain cysticercosis,8 had blood disease,6 had Guillain-Barre syndrome (GBS),3 had myelitis,4 had Multiple Sclerosis,5 had subarachnoid hemorrhage(SAH),5 had cerebral thrombosis,5 had meningeal carcinomatosis and 4 had Cerebral venous sinus thrombosis.CSF was collected by lumbar puncture in all patients, and analyzed within 12 hours~48 hours, biochemical, cytology (MGG dye, Indian ink and aricine blue staining), demonstration of mycobacterial antigen in monocytes (macrophages) are carried out at the same time.Some of the CSF was detected by ABC-ELISA method in order to evaluate the value of IFN-gamma.Results:1 CSF routine test: The case group was 102 of abnormal, and the rate of abnormality was 100%; the control group was 105 of abnormal and the rate of abnormality was 84.7%.2 CSF Cytology: A total of 112 cases in TBM group show a mixed-cell response in CSF(72.5%);but Control group, lack of specificity of change,33 cases show a mixed -cell response in CSF(26.6%).If take a mixed-cell response in CSF as the diagnostic criteria, the sensitivity was 72.5%, and specificity was 73.4%. At the dynamic observation, patients in TBM group show polymorphonuclear dominant mixed-cell response before anti-tuberculosis treatment, while neutrophil gradually reduced after 2~3weeks treatment. The monocyte and lymphoid cells increased at the same time,but a mixed-cell response would last a long time .3 The demostration of antigens in monocytes: The sensitivity was 83.3%, and specificity was 93.5%.Compared the positive rate of≤14 days(87.8%),15～30days(88.8%),>30days(68%), it didn't have significant difference.So the demostration of antigens in monocytes is suitable for the early diagnosis.4 The levels of IFN-gamma:Compare the IFN-γlevels in cerebrospinal fluid in case group (223.4±141.2 pg/ml) and control group(31.40±21.5 pg/ml),there was a statistical significance. Take 100 pg/ml as the diagnostic criteria, the sensitivity and the specificity was 71.4% and 96.9%. Compare the IFN-γlevels of≤14 days,15～30days,>30days, there was a statistical significance. At the dynamic observation, the IFN-γlevel gradually delined with the condition improves in case group, but the levels didn't increase with the aggravation of disease.And the control group didn't change too much around the treatment.5 Compare the clinical value of CSF Cytology,mycobacterial antigen in monocytes (macrophages) and IFN-gamma levels in cerebrospinal, it didn't have significant difference. If joint the three methods the sensitivity may reach 96.3%Conclusions:1 The sensitivity of antigens demonstration is the highest,while the specificity of determination of IFN-gamma is the highdest.2 Determination of IFN-gamma has the highest sensitivity and specificity at the early stage of disease(less than a month).3 Joint the three method will be helpful to elevate the diagnosis rate.