脑室-腹腔分流术治疗结核性脑膜炎并发脑积水

目的探讨脑室-腹腔分流术(VPS)治疗结核性脑膜炎(TBM)合并脑积水的效果。方法回顾性分析2004年1月至2010年7月行VPS治疗的15例TBM合并脑积水患者的临床资料。结果 15例患者全部行VPS,术后意识均好转、症状减轻,未发生结核性腹莫炎。术前抗结核治疗1月以上者10例,均无分流管堵塞发生;而另外5例抗结核治疗不足1月者,分流管堵塞者2例。脑脊液蛋白含量在0.5g/L以上者6例中2例堵管;脑脊液蛋白在0.5g/L以下的9例中,无堵管者。结论 VPS是治疗TBM并发脑积水的有效方法,术前最好能抗结核治疗1月以上。     

Use of urokinase in the treatment of tuberculous meningitis hydrocephalus

We present a patient with hydrocephalus after tuberculous meningitis successfully treated with urokinase. She presented with multiple episodes of headache, fever, and vomiting. She underwent external ventricular drainage and was treated with urokinase in addition to dexamethasone, acetazolamide, and 4 antituberculous drugs. She was evaluated clinically, radiologically, and by laboratory work-up. On short-term clinical follow-up (3 months), she was asymptomatic after the treatment with urokinase. She was radiologically evaluated 3 weeks after the treatment. An MRI of the brain showed a decrease in ventricular size. Urokinase can be considered as a safe and promising adjunctive treatment for tuberculous meningitis hydrocephalus.     

新型隐球菌性脑膜炎与结核性脑膜炎的鉴别

目的探讨新型隐球菌性脑膜炎(CNM)和结核性脑膜炎(TBM)在临床、脑脊液方面的区别,以期早期诊断、治疗,改善病人的预后。方法回顾性比较10例CNM和86例TBM患者的临床特点、脑脊液改变的异同。结果两种脑膜炎均以亚急性或慢性形式起病,CNM组患者视盘水肿和呕吐症状明显多于TBM组;CNM组患者脑脊液开放压力和细胞数增加更明显,但头痛、发热、抽搐、精神症状、消瘦、盗汗、大小便障碍、意识障碍、脑膜刺激征、病理征阳性、脑神经损伤、肢体瘫痪、感觉障碍以及脑脊液蛋白质、葡萄糖、氯化物改变等均无显著差异。结论综合分析临床资料和脑脊液资料有助于鉴别两种脑膜炎。     

Use of intrathecal hyaluronidase in the management of tuberculous meningitis with hydrocephalus

A preliminary study to evaluate the efficacy of intrathecal hyaluronidase was carried out in nine children suffering from tuberculous meningitis with communicating hydrocephalus. This was followed by a randomized trial in which five cases were treated with intrathecal hyaluronidase, while six cases were treated by the insertion of a ventriculoperitoneal shunt. No untoward reaction of any significance was noted. The results were judged in terms of improvement in the sensorium and mentation, in specific neurological deficit (e.g., visual impairment and hemiparesis), and in overall functional performance. Although most of the patients receiving hyaluronidase showed some improvement in the sensorium, only one of the nine preliminary cases and one of the five cases in the randomized trial showed a total recovery of function. Two of the six shunted patients, however, showed complete recovery. Shunt insertion led to further improvement in two of the nine preliminary cases who had failed to respond to treatment with hyaluronidase. This preliminary study shows that intrathecal hyaluronidase does, in most cases, lead to an improvement in the sensorium but does not offer any particular advantage over shunt insertion in terms of regression of specific neurological deficit or overall functional improvement.     

Clinical early diagnosis of tuberculous meningitis]

We examined 37 tuberculous meningitis, 30 active pulmonary tuberculosis, and 31 nontuberculous disease patient's CSF and serum antitubercular antibody IgG with polymerized OT as an antigen by the method of ELISA, respectively. It is shown that there is of a specificity to the diagnosis of tuberculous meningitis. We also reexamined the serum antitubercular antibody daily, as well as CSF antitubercular antibody, and CSF routine and biochemical indexes weekly for 16 tuberculous meningitis inpatients ill no more than five days. It was found that CSF antitubercular antibody became positive five days earlier than self serum antitubercular antibody, seven days earlier than typical tuberculous meningitis CSF. It is shown that the positive of the CSF antitubercular antibody may be used as the basis of the early diagnosis of tuberculous meningitis. Through antitubercular therapy and monthly re-examinations of the above indexes, it was found that CSF and serum antitubercular antibody became negative earlier than the recovery of CSF routine and biochemical indexes, and so the examination of CSF and serum antitubercular antibody has some reference value to determine curative effects and prognosis.     

Multiplex PCR for rapid diagnosis of tuberculous meningitis

Rapid and specific diagnosis of tubercular meningitis is of paramount importance to decrease morbidity and mortality. The aim of the study was to evaluate multiplex PCR using protein b, MPB 64, and IS6110 primers directed against M. tuberculosis complex for the diagnosis of tuberculous meningitis (TBM). Multiplex PCR was performed on 18 TBM confirmed cases (culture was positive), 92 clinically suspected TBM cases and 100 non-TBM (control group) patients. Multiplex PCR had a sensitivity of 94.4% for confirmed cases and specificity of 100% for confirmed TBM cases. In 92 clinically diagnosed but unconfirmed TBM cases, multiplex PCR was positive in 84.78% cases. The overall sensitivity of microscopy, culture and multiplex cases were 1.81, 16.73, and 86.63% and specificity was 100, 100, and 100% respectively. Multiplex PCR using protein b, MPB 64, and IS6110 primers has a high sensitivity and specificity in diagnosis of tubercular meningitis.     

Rapid diagnosis of tuberculous meningitis by a dot-immunobinding assay

In this study, a dot-immunobinding assay (Dot-Iba) was standardized to measure circulating antimycobacterial antibodies in the cerebrospinal fluid (CSF) specimens for the rapid laboratory diagnosis of tuberculous meningitis (TBM). Specific CSF-IgG antibody to Mycobacterium tuberculosis from a culture proven patient with TBM was isolated and coupled with activated Cynogen bromide-Sepharose 4B. Using an immunoabsorbent affinity chromatography, 14 kDa antigen present in the culture filtrates of M. tuberculosis was isolated and this antigen was used in the Dot-Iba, to quantitate specific antimycobacterial antibodies in CSF specimens. The Dot-Iba gave positive results in all the 5 culture proven patients with TBM and gave no false positive results in CSFs from patients with partially treated pyogenic meningitis. Dot-Iba developed in our laboratory is a simple, rapid and specific method and more importantly suited for the routine application in laboratories with limited resources.     

Multidrug-resistant tuberculous meningitis

Multidrug-resistant tuberculous meningitis is now appearing worldwide, including in the United States, and is difficult to diagnose and treat. We discuss methods to diagnose tuberculous meningitis, review current and experimental assays for determining drug resistance, and consider approaches to management of the patient. We review the epidemiology of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis in both pulmonary and meningeal infections, discuss promising molecular methods for determining drug resistance, and review current approaches toward treatment of patients. The incidence of multidrug-resistant tuberculous meningitis is increasing, and diagnosing and treating these patients will be a major challenge. There is a need to improve rapid methods of isolating the organism from cerebrospinal fluid, to advance molecular methods to rapidly test the isolate for antibiotic sensitivity, and to develop new antituberculosis drugs, especially ones that cross the blood-cerebrospinal fluid barrier.     

Endoscopy for tuberculous hydrocephalus

Introduction The role of endoscopy in hydrocephalus due to infectious aetiology is unclear. Tuberculous hydrocephalus is a useful model to study because it presents particular challenges and the pathophysiology of the cerebrospinal fluid disturbance is well known.Materials and methods We present the results of 24 endoscopic operations in tuberculous meningitis.Result Endoscopic third ventriculostomy (ETV) was attempted in 17 patients: seven were successful, five failed, and five were not completed due to abnormal anatomy. There were five fenestration procedures, three of which were successful. Endoscopic biopsy of two tuberculomas failed to yield a bacteriological result. These operations were more difficult to perform than for hydrocephalus due to other aetiologies.Conclusion Although ETV is technically possible in this situation, it is imperative that the patients are adequately selected for the procedure to ensure optimal treatment and that the surgeon has experience with difficult cases.     

GeneXpert MTB/RIF对结核性脑膜炎诊断价值的 Meta分析

目的 系统评价 GeneXpert MTB/RIF 在结核性脑膜炎诊断中的应用价值。方法 通过计 算机检索 PubMed、Ovid、Embase、Scopus、Web of Science、Cochrane Library 及中国知网、维普数据库、万 方数据库等国内外数据库,收集建库至 2021 年 11 月发表的与 GeneXpert MTB/RIF 诊断结核性脑膜炎相 关的中英文文献。应用 RevMan 5.3 和 Meta-Disc 1.4 软件进行文献质量评价和 Meta 分析,计算汇总敏感 度、特异度、阳性似然比（PLR）、阴性似然比（NLR）、诊断比值比（DOR）,绘制汇总受试者工作特征（SROC） 曲线并计算曲线下面积（AUC）。结果 共纳入 28 篇文献,共包含 5 137 例临床标本。Meta 分析显示, GeneXpert MTB/RIF 用于诊断结核性脑膜炎的汇总敏感度为 0.412（95%CI：0.392～0.431）,特异度为 0.967 （95%CI：0.961～0.973）。以临床综合诊断标准为诊断标准,GeneXpert MTB/RIF 用于诊断结核性脑膜炎 的汇总敏感度和特异度分别为 0.362（95%CI：0.340～0.384）、0.973（95%CI：0.964～0.980）;以结核分枝 杆菌培养为标准,GeneXpert MTB/RIF 诊断结核性脑膜炎的汇总敏感度和特异度分别为 0.589（95%CI： 0.547～0.630）和 0.961（95%CI：0.950～0.970）。脑脊液离心处理后,GeneXpert MTB/RIF 诊断结核性脑膜 炎的汇总敏感度和特异度分别为 0.431（95%CI：0.405～0.456）、0.966（95%CI：0.957～0.973）。HIV 感染情 况下,GeneXpert MTB/RIF诊断结核性脑膜炎的汇总敏感度为0.405（95%CI：0.375～0.434）,特异度为0.967 （95%CI：0.956～0.976）。结论 脑脊液经离心处理后,GeneXpert MTB/RIF 检测对结核性脑膜炎有较高 的诊断价值,可作为快速诊断结核性脑膜炎的有效方法。     

Effects of the implantation of Ommaya reservoir in children with tuberculous meningitis hydrocephalus: a preliminary study

Objective

The role of Ommaya reservoir implantation in children with tuberculous meningitis hydrocephalus (TBMH) has been seldomly reported. Therefore, we performed this study to determine the role of the Ommaya reservoir in the treatment of children with TBMH.

Methods

We retrospectively analyzed the effects of Ommaya reservoir implantation in 12 children with TBMH. Intracapsular puncture of the reservoir was performed for draining the cerebrospinal fluid and the TBM was treated by intraventricular injection of isoniazid.

Results

The ideal treatment outcome was observed in nine (75?%) of the 12 children; two (16.7?%) children developed serious disabilities and one of them (8.3?%) eventually died. The treatment method was effective for all six (100?%) children with Palur grade II TBM but showed no effect in three (50?%) children with grade III and IV TBM. The number of leukocytes in the cerebrospinal fluid decreased to 20?×?10⁶/L (75?%) within 2?weeks after implantation of the reservoirs. Finally, the Ommaya reservoirs in eight children were removed but were retained in four children. Four children had to undergo ventriculoperitoneal shunt.

Conclusion

Ommaya reservoir implantation has been shown to be effective in treating children with TBMH. This method may be largely suitable for children with early grade II TBM or partly in children with grade III TBM who have mild or moderate hydrocephalus that can alleviate after short-term treatment. Thus, a good proportion of children who undergo Ommaya reservoir implantation can avoid ventriculoperitoneal shunt surgery.     

Treatment of tuberculous meningitis

INTRODUCTION: Tuberculous meningitis and brain tuberculomas are currently rare in the western world but remain serious. Improved outcome requires early recognition and treatment of these conditions. STATE OF ART: Treatment is usually begun before diagnostic confirmation. Therapeutic principles are now better defined thanks to recent recommendations and studies. Antituberculous therapy begins with two months of a combination of four drugs: isoniazid, rifampicin, ethambutol and pyrazinamid. Then follows a longer phase of bitherapy with isoniazid and rifampicin, lasting at least four months but usually extended to seven or ten months as a precaution. Patients at risk of toxic neuropathy should receive pyridoxine supplementation. Corticosteroids must be systematically added during the first eight weeks of treatment, beginning with high dose before progressive tapering. Hyponatremia is common, often induced by emesis and cerebral salt wasting syndrome. Therefore saline supply rather than water restriction is required. Non-obstructive hydrocephaly can usually be managed with diuretic therapy including acetazolamid, sometimes complemented by serial lumbar punctures. Neurosurgical interventions are rarely needed. Monitoring of treatment tolerance and efficacy is mainly clinical. Central nervous system imaging and cerebro-spinal fluid analysis are only required to explain clinical deterioration. CONCLUSION: With adequate and prompt anti-tuberculous, anti-inflammatory and supportive treatment, the prognosis of central nervous system tuberculosis can be greatly improved.     

可溶性DLL1检测在结核性脑膜炎早期诊断中的价值探讨

目的 探讨脑脊液(CSF)及血清中可溶性Delta-Like-Ligand 1 (DLL1)的检测对结核性脑膜炎(结脑)早期诊断的临床意义. 方法 选取郑州大学第一附属医院神经内科自2008年12月至2011年3月收治的CNS感染性疾病患者110例,其中结脑患者50例、病毒性脑(膜)炎(病脑)患者30例、化脓性脑膜炎(化脑)20例、隐球菌脑膜炎(隐脑)10例,另正常对照组30例.ELISA法测定各组受试者入院后CSF、血清中可溶性DLL1的含量,动态观察结脑组患者治疗后不同时间CSF中DLL1的含量并分析DLL1含量与CSF蛋白、细胞数的相关性. 结果 与病脑组、化脑组、隐脑组、正常对照组比较,结脑组患者CSF、血清中DLL1的含量增高,差异有统计学意义(P＜0.05),而病脑组、化脑组、隐脑组与正常对照组之间相比差异无统计学意义(P＞0.05).治疗好转的14例结脑患者CSF中DLL1含量在第2、4、6周逐渐降低,而治疗加重的4例患者CSF中可溶性DLL1含量第1、2(4)、6周逐渐升高,差异均有统计学意义(P＜0.05).结脑患者CSF中DLL1的含量与CSF蛋白、细胞数均无明显相关关系. 结论 CNS感染时结脑患者的CSF和血清中可溶性DLL1的含量显著增高,对于结脑的早期鉴别诊断具有重要参考意义.     

Stroke in tuberculous meningitis

Stroke in tuberculous meningitis (TBM) occurs in 15-57% of patients especially in advance stage and severe illness. The majority of strokes may be asymptomatic because of being in a silent area, deep coma or associated pathology such as spinal arachnoiditis or tuberculoma. Methods of evaluation also influence the frequency of stroke. MRI is more sensitive in detecting acute (DWI) and chronic (T2, FLAIR) stroke. Most of the strokes in TBM are multiple, bilateral and located in the basal ganglia especially the 'tubercular zone' which comprises of the caudate, anterior thalamus, anterior limb and genu of the internal capsule. These are attributed to the involvement of medial striate, thalamotuberal and thalamostriate arteries which are embedded in exudates and likely to be stretched by a coexistent hydrocephalus. Cortical stroke can also occur due to the involvement of proximal portion of the middle, anterior and posterior cerebral arteries as well as the supraclinoid portion of the internal carotid and basilar arteries which are documented in MRI, angiography and autopsy studies. Arteritis is more common than infarction in autopsy study. The role of cytokines especially tumor necrosis factor (TNFα), vascular endothelial growth factor (VEGF) and matrix metaloproteineases (MMPs) in damaging the blood brain barrier, attracting leucocytes and release of vasoactive autocoids have been suggested. The prothrombotic state may also contribute to stroke in TBM. Corticosteroids with antitubercular therapy were thought to reduce mortality and morbidity but their role in reducing strokes has not been proven. Aspirin also reduces mortality and its role in reducing stroke in TBM needs further studies.     

Chronic untreated tuberculous meningitis

Summary We describe a 34-year-old man who suffered from tuberculous meningitis for 2 years without receiving antituberculous medication. Our case is compared with other forms of indolent or benign variants of the disease.