Tuberculosis Meningitis 10 April, 2009

Ⅰ overview TBM is the most serious type in children with tuberculosis TBM is an early primary complications in Primary tuberculosis the incidence is significantly decreased after BCG vaccination

Ⅱ Epidemiology Age of Onset：More common in 1 ~5 year-old 1180 TBM in Beijing Children's Hospital <3y 56.7%，<1y 48.5% (half the number) Onset in Season ： common in Winter or spring

Ⅲ Pathogenesis Hematogenous dissemination： blood-CSF path main Brain , meningeal tuberculosis rupture secondly Tuberculosis in nearly organize direct spread occasionally

Ⅳ Pathology Extensive lesions 病变以脑底部最明显 “脑底脑膜炎” Lesions in the bases of skull “basilar meningitis” (most obvious) 病变以脑底部最明显 “脑底脑膜炎” leptomeningeal hyperemia, edema, Inflammatory exudate The inflammatory exudate is accumulated in the subarachnoid（ cistern in pavimentum cerebri ） cranial nerve lesion cerebrovascular disorder。 Pyocephalus and Hydrocephalus。 Tuberculoma

Ⅴ Clinical manifestation Most typical cases ----slow onset nervous system symptom General symptom Tuberculosis toxic symptom meningeal irritation sign cranial nerve lesion irritative or destructive symptoms of encephalon intracranial hypertension spinal cord disorder symptom

ⅤClinical manifestation prodromal period （prophase） meningeal irritation period （metaphase） coma period （advanced stage） intracranial hypertension meningeal irritation sign cranial nerve lesion irritative or destructive symptoms of encephalon pyramid sign;pyramidal sign convulsion Tuberculosis toxic symptom Headache vomiting Personality change symptom increased go into coma spinal cord dysfunction

Ⅵ Diagnoses (Ⅰ)History： Age, Seasons, (Ⅱ)clinical feature： History of exposure and BCG vaccination, History of infectious diseases (Ⅱ)clinical feature：

(Ⅲ) CSF Examination ： 1、routine： 2、biochemistry： 3、film preparation： Appearance：Like ground-glass ， floccule or membrane High pressure Cell count（Lymphocytes）：50～500×106/L 2、biochemistry： Protein  、glucose and chloride  3、film preparation： precipitum acid-fast stain positive 30%

(Ⅲ) CSF Examination ： 3、Others 1）tubercle bacillus antigen detection 2）anti-tuberculosis antibody （one of the early diagnosis evidence） 3）adenosine deaminase （ADA）activity TBM：ADA  >9μ/L 4）immunoglobulin：IgG  5）detect DNA fragment 6）tubercle bacillus culture film preparation and cultivation --- may be have a clear diagnosis

(Ⅳ) X-ray examination (Ⅴ)CT or MRI early: normal (Ⅵ) PPD-Test Chest X-ray: About 85% have tuberculose focus (Ⅴ)CT or MRI early: normal progression：Shadow of the basal ganglia enhanced, cistern density  , fuzzy, calcification, ventricular dilatation, cerebral edema or infarct foci (Ⅵ) PPD-Test

枕区环形增强灶、侧脑室室管膜异常增强、侧脑室明显扩大 图2 ：同一病人的冠状面T1W 枕区环形强化灶 图1 T1W横断面：注射造影剂后显示 枕区环形增强灶、侧脑室室管膜异常增强、侧脑室明显扩大 图2 ：同一病人的冠状面T1W a. Transverse T1W image after contrast administration reveals ringlike enhancement in occipital region and abnormal enhancement of the ependymal of the ventricles b. coronal T1W image of same patient （同一病人的冠状面T1W）

Ⅶ Differential Diagnosis 1、purulent meningitis 2、Viral Encephalitis 3、Cryptococcus neoformans meningitis 4、cerebral abscess 鉴别诊断 1、化脑 2、病毒性脑炎 3、新型隐球菌脑膜炎 4、脑脓肿

Ⅷ treatment bed rest （Ⅰ）General treatment Nutrition Nursing Care Coma Patients：nasogastric feeding、 pressure sore prevention attention Water-Electrolyte Balance （Ⅰ）一般治疗 卧床休息 加强营养 护理、空气 昏迷病人鼻饲、翻身拍背、防褥疮 注意水电解质平衡

Ⅷ treatment （Ⅱ）Anti-tuberculosis therapy Principle：Early , Complete Intensification treatment INH+RFP（早、中期） INH+RFP+SM INH+RFP+SM+PZA 3~4M (Ⅱ)抗结核治疗 原则：早期、彻底治疗 强化治疗: INH+RFP（早、中期） INH+RFP+SM 3~4个月 INH+RFP+SM+PZA INH 15~25mg/kg.d RFP 10~20mg/kg.d SM 15~20mg/kg.d PZA 20~30mg/kg.d INH 15~25mg/kg.d RFP 10~20mg/kg.d SM 15~20mg/kg.d PZA 20~30mg/kg.d

（Ⅱ）Anti-tuberculosis therapy Consolidation treatment INH+RFP 巩固治疗INH+RFP 总疗程不<12月 或CSF正常后继续治疗6月 course of treatment≥12M or when CSF normal, continue treatment 6M

Ⅷ treatment CSF secretion：lateral ventricles choroid（占70%） （Ⅲ）decrease intracranial hypertension CSF secretion：lateral ventricles choroid（占70%） Ependyma、encephalon ----TBM， Inflammatory stimulation, secretion absorption：arachnoid granulations ---- TBM， absorb disturbance circulation： ---- TBM, inflammatory in base of skull, pathway blocked ↑ （ Ⅲ ）降低颅高压 CSF分泌：侧脑室脉络膜丛（占70%） 室管膜和脑实质----TBM时，炎症刺激，分泌 吸收：蛛网膜颗粒---- TBM时，回收障碍 循环： ---- TBM时，颅底炎症，通路受阻

1、dehydrant （Ⅲ）decrease intracranial hypertension 20%mannitol：0.5~1.0(2.0)g/kg.次 iv q4h~q6h 2、adrenocortical hormone Dx 0.2~0.4mg/kg.d 3、lateral ventricular puncture 4、lumbar puncture decompression, intrathecal injections： INH、Dx 5、Surgery： Ventriculoperitoneal shunt or external drainage 1、脱水剂 20%甘露醇：0.5~1.0(2.0)g/kg.次 iv q4h~q6h 2、肾上腺皮质激素 Dx 0.2~0.4mg/kg.d 3、侧脑室穿刺引流 4、腰穿减压、鞘注 INH、Dx 5、外科手术 脑室腹腔分流术或外引流术

1、Control convulsions、Antipyretic （Ⅳ）adrenocortical hormone therapy Dx 0.2~0.4mg/kg.d Prednison 1~2mg/kg.d （ 4 weeks after decreasing，course：8~12 weeks ） （Ⅴ）others 1、Control convulsions、Antipyretic 2、Water-Electrolyte Balance disturbances Hyponatremia（dilutional, Cerebral ） Hypokalemia （Ⅵ）follow observation at least 3～5years （四）肾上 腺皮质激素治疗 Dx 0.2~0.4mg/kg.d Prednison 1~2mg/kg.d（ 四周后渐减量，疗程8~12周） （五）对症处理 1、抗惊厥、退热 2、水、电解质紊乱的处理 低钠血症（稀释性、脑性） 低钾血症 （六）随访观察 至少3～5年

criterion of cure Symptoms disappeared CSF normal No recurrence (2 years After the end of Treatment) 治愈标准 症状消失 脑脊液正常 疗程结束后2年无复发

Ⅸ Prognosis (Relevant factors) age Time of therapy--- early or late The degree of brain damage Therapeutic method--- correct？ Tubercle bacillus--- resistance？ 九、预后（相关因素） 1、年龄 2、治疗时间早晚 3、脑实质损害程度 4、治疗方法正确与否 5、结核杆菌是否耐药