Thwaites Guy, Fisher Martin, Hemingway Cheryl, Scott Geoff, Solomon Tom, Innes John
Centre for Molecular Microbiology and Infection, Imperial College, Exhibition Road, South Kensington, London, UK.
J Infect. 2009 Sep;59(3):167-87. doi: 10.1016/j.jinf.2009.06.011. Epub 2009 Jul 4.
The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).
本指南旨在描述一种实用且基于证据的儿童和成人中枢神经系统结核病的诊断与治疗方法。我们针对结核性脑膜炎(TBM)、无脑膜炎的脑内结核瘤以及影响脊髓的结核病提供了指导。我们的关键建议如下:1. TBM是一种医疗急症。治疗延迟与死亡密切相关,对于所有疑似TBM的患者应立即开始经验性抗结核治疗。不要等待微生物学或分子诊断确认。2. TBM的诊断最好通过腰椎穿刺和脑脊液(CSF)检查来进行。如果CSF白细胞增多(主要为淋巴细胞)、CSF蛋白升高且CSF:血浆葡萄糖<50%,则怀疑为TBM。结核分枝杆菌CSF显微镜检查和培养的诊断阳性率随送检CSF量的增加而提高;如果诊断仍不确定,应重复腰椎穿刺。3. 影像学对于脑结核瘤和累及脊髓的结核病的诊断至关重要,尽管放射学表现不能确诊。应尽可能尝试进行组织诊断(通过组织病理学和分枝杆菌培养),可通过病变本身的活检,或通过从肺、胃液、淋巴结、肝脏、骨髓等神经外疾病部位进行诊断性采样。4. 所有形式的中枢神经系统结核病的治疗应包括4种药物(异烟肼、利福平、吡嗪酰胺、乙胺丁醇)治疗2个月,然后2种药物(异烟肼、利福平)治疗至少10个月。所有TBM患者均应给予辅助性皮质类固醇(地塞米松或泼尼松龙),无论疾病严重程度如何。5. 患有中枢神经系统结核病的儿童理想情况下应由熟悉并擅长儿童结核病的儿科医生管理,否则应由儿科传染病科提供支持。英国和爱尔兰儿童HIV协会(CHIVA)提供了关于HIV感染儿童管理的进一步指导(www.chiva.org.uk)。6. 所有疑似或确诊结核病的患者均应接受HIV感染检测。HIV感染和未感染个体的中枢神经系统结核病诊断和治疗原则相同,尽管HIV感染会扩大鉴别诊断范围,且抗逆转录病毒治疗会使管理变得复杂。HIV感染患者的结核病应在专科单位由同时精通HIV和结核病的医生管理,或由HIV和结核病专家联合管理。抗逆转录病毒药物和抗结核药物的联合使用应遵循英国HIV协会发布的指南(www.bhiva.org)。