Objective CT criteria to determine the presence of abnormal basal enhancement in children with suspected tuberculous meningitis

Background There are no widely accepted objective criteria to determine the presence of basal enhancement on CT in children with suspected tuberculous meningitis (TBM).Objective To test nine recently described objective CT criteria for the presence of abnormal basal enhancement in children with suspected TBM against the definite diagnosis as determined by cerebrospinal fluid (CSF) culture.Materials and methods CT scans of patients with a clinical suspicion of TBM who had undergone lumbar puncture for CSF culture spanning a period of 4 years were reviewed for the presence of nine recently described criteria for the presence of abnormal basal enhancement. The radiologists were blinded to the final diagnosis based on CSF culture against which the criteria were tested. The criteria have been named: the ‘Y-sign’, ‘linear enhancement’, ‘double lines’, ‘infundibular recess of the third’, ‘ill-defined edge’, ‘nodular enhancement’, ‘join the dots’, ‘contrast filling the cisterns’, and ‘asymmetry’.Results A total of 65 patients were included in the study, 34 with culture-proven TBM and 31 with other diagnoses. Four individual criteria had a specificity of 100%, but the sensitivities of these criteria ranged from 15% to 53% only. Three other criteria had specificities of 97% and sensitivities ranging from 62% to 82%. The presence of more than one criterion in the same patient showed a specificity of 97% and sensitivity of 91%.Conclusions Very high specificity was demonstrated for all nine criteria, including 100% specificity for four individual criteria. Sensitivity was at best 82%, but improved to 91% when more than one criterion was present. These criteria need to be tested for inter- and intraobserver variability to prove their clinical usefulness.     

Definitive neuroradiological diagnostic features of tuberculous meningitis in children

Background: Although CT scanning is used widely for making the diagnosis and detecting the complications of tuberculous meningitis (TBM) in children, the radiological features are considered non-specific. CT is particularly suggestive of the diagnosis when there is a combination of basal enhancement, hydrocephalus and infarction, and even then the diagnosis may be in doubt. In this paper we introduce a new CT feature for making the diagnosis of TBM, namely, hyperdensity in the basal cisterns on non-contrast scans, and we assess which of the recognized CT features is most sensitive and specific. Objective: To determine the sensitivity and specificity of the presence of high-density exudates in the basal cisterns (on non-contrast CT) and basal enhancement (on contrast-enhanced CT) for the diagnosis of TBM in children, and to correlate these with the complications of infarction and hydrocephalus. Materials and methods: Retrospective review of CT scans with readers blinded to the diagnosis, which was based on a definitive culture of cerebrospinal fluid (CSF) for TBM or other bacteria. Computer-aided conversion of hard-copy film density to Hounsfield units was employed as well as a density threshold technique for determining abnormally high densities. Results: The most specific feature for TBM is hyperdensity in the basal cisterns prior to IV contrast medium administration (100%). The most sensitive feature of TBM is basal enhancement (89%). A combination of features (hydrocephalus, infarction and basal enhancement) is as specific as pre-contrast hyperdensity, but has a lower sensitivity (41%). There were statistically significant differences in the presence of hydrocephalus (p=0.0016), infarcts (P=0.0014), basal enhancement (P<0.0001) and pre-contrast density (P<0.0001) between the negative and positive TBM patient groups. The presence of granulomas was not statistically significant between the two groups (P=0.44). Conclusions: The presence of high density within the basal cisterns on non-contrast CT scans is a very specific sign for TBM in children. This will enhance diagnostic confidence, allow early institution of therapy and could reduce expenditure on contrast medium, scan time and radiation exposure. With the use of threshold techniques we believe that the pre-contrast hyperdensity may be detectable by a computer program that will facilitate diagnosis, and may also be modified to detect abnormal enhancement. Basal enhancement is a sensitive sign for the diagnosis of TBM and should be sought after contrast medium administration when no hyperdensity is seen in the basal cisterns or when this finding needs to be confirmed. The CT scan feature of hyperdense exudates on pre-contrast scans should be added to the inclusion criteria for the diagnosis of TBM in children.     

Tuberculin reactivity in tuberculous meningitis

Objective: To study tuberculin reactivity in childhood tuberculous meningitis both in clinical and histopathological (HP) context.Methodology: Children with tuberculous meningitis (TBM) were given tuberculin test by Mantoux technique, which was read at the end of 72 hours after the placement of skin test. Histopathological examination of the punch biopsy specimen of the tuberculin test site was performed and histopathological grading of the tuberculin reaction was compared with clinical reaction and clinical parameters.Results: Of the 50 children studied, 68% of them were malnourished and 42% had BCG scar. Tuberculin test was positive in 22 (44%) cases. Spearman analysis showed negative correlation between stage of TBM and the size of tuberculin reaction. BCG status did not affect the size of tuberculin reaction. Histopathological grade of the tuberculin reaction was found to be directly proportional to the size of the tuberculin reaction and it was not affected by the stage of TBM.Conclusion: Tuberculin positivity is low in TBM irrespective of the nutritional status. At least some degree of inflammatory reaction can be seen at the site of tuberculin administration. In tuberculin negative cases, varying grades of cellular response in the absence of clinical induration can be seen in histopathology.     

Value of early follow-up CT in paediatric tuberculous meningitis

Background: The value of CT in the diagnosis of tuberculous meningitis (TBM) in children is well reported. Follow-up CT scanning for these patients is, however, not well described and, in particular, the value of early follow-up CT has not been addressed for children with TBM. Objective: To assess the value of early follow-up CT in children with TBM in identifying diagnostic, prognostic and therapeutically relevant features of TBM. Materials and methods: A retrospective 4-year review of CT scans performed within 1 week and 1 month of initial CT in children with proven (CSF culture-positive) and probable TBM (CSF profile-positive but culture-negative) and comparison with initial CT for the diagnostic, prognostic and therapeutic CT features of TBM. Results: The CT scans of 50 children were included (19 definite TBM; 31 probable TBM). Of these, 30 had CT scans performed within 1 week of the initial CT. On initial CT, 44 patients had basal enhancement. Only 24 patients had contrast medium-enhanced follow-up scans. Important findings include: 8 of 29 patients (who were not shunted) developed new hydrocephalus. New infarcts developed in 24 patients; 45% of those who did not have infarction initially developed new infarcts. Three of the six patients who did not show basal enhancement on initial scans developed this on the follow-up scans, while in seven patients with pre-existing basal enhancement this became more pronounced. Two patients developed hyperdensity in the cisterns on non-contrast medium scans. Eight patients developed a diagnostic triad of features. Three patients developed CT features of TBM where there was none on the initial scans. Conclusions: Early follow-up CT is useful in making a diagnosis of TBM by demonstrating features that were not present initially and by demonstrating more sensitive, obvious or additional features of TBM. In addition, follow-up CT is valuable as a prognostic indicator as it demonstrates additional infarcts which may have developed or become more visible since the initial study. Lastly, follow-up CT has therapeutic value in demonstrating hydrocephalus, which may develop over time and may require drainage. We advise routine follow-up CT in patients with suspected TBM within the first week of initial CT and optionally at 1 month.     

小儿结核性脑膜炎临床特征分析

目的总结小儿结核性脑膜炎(简称结脑)的临床特征,探讨早期诊断的有效方法。方法回顾性分析2001-01—2004-12重庆医科大学附属儿童医院103例临床诊断结核性脑膜炎的住院患儿病例资料。结果(1)全组病例中,<3岁的婴幼儿49例(47.6%);(2)全组患儿主要临床表现为:发热、颅内压增高、抽搐、意识障碍;(3)38例有明确结核接触史,共占36.9%;(4)全组88例行头颅CT检查,77例异常,阳性率为87.5%,其中51例伴随脑积水改变(66.2%)。最早于病程第4天即有CT异常。结论(1)发热伴颅内压增高、脑神经损害是小儿结核性脑膜炎常见的表现。(2)诊断小儿结核性脑膜炎应重视对结核接触史询问,加强密切接触亲属结核感染的检查,年龄越小,价值越大。(3)头颅CT是结核性脑膜炎早期诊断和判断预后比较有效的方法,对疑诊病人应及时进行头颅CT检查及动态随访CT变化。(4)提高病原学检查对确诊结脑及筛查有效药物治疗均有重要意义。     

Tuberculous meningitis and HIV

Objective : To identify factors associated with HIV-infected status in children admitted with tuberculous meningitis (TBM), and to find out whether HIV co-infection affects in-hospital outcome.Methods : This prospective hospital-based study was conducted from May 2000 to August 2003. All consecutive children, aged 1 month to 12 years of age, admitted with a diagnosis of TBM were enrolled. Relationship between 35 featuresviz., two demographic factors, nine clinical features, 13 neurological features, five laboratory (including cerebrospinal fluid) parameters, six radiological (including computed tomography scan brain) features, and the two outcomes (disabled survivor or death); with HIV-infected status was assessed.Results : Of a total 123 TBM cases enrolled, eight (6.5%) were HIV-infected. There was no significant difference between the two groups, except that more children in the HIV-infected group had Hb< 8 gm/dl: both on bivariate analysis, (OR, 12.0; 95% CI, 2.6–55.9; P = 0.001) and on multivariate analysis (OR, 12.30; 95% CI, 1.9–79.6; P = 0.008). Outcome was similar in both the groups.Conclusion: Only presence of Hb< 8 gm/dl was associated with HIV-infected status. HIV co-infection did not affect the outcome.     

Radiological and clinical features of basal ganglia infarction in tuberculous meningitis

Abstract A patient with choreoathetosis and dystonia who had computerized tomography evidence of basal ganglia damage resulting from tuberculous meningitis is presented. It is important to distinguish these extrapyramidal movements from fits, and the observation of such movements in a clinical setting of meningitis should alert physicians to the diagnosis of tuberculous meningitis.     

Radiological and clinical features of basal ganglia infarction in tuberculous meningitis

A patient with choreoathetosis and dystonia who had computerized tomography evidence of basal ganglia damage resulting from tuberculous meningitis is presented. It is important to distinguish these extrapyramidal movements from fits, and the observation of such movements in a clinical setting of meningitis should alert physicians to the diagnosis of tuberculous meningitis.     

Oesophageal perforation as a complication of primary pulmonary tuberculous lymphadenopathy in children

Background Involvement of the oesophagus by tuberculosis is rare, and erosion and perforation of the oesophagus by tuberculous lymphadenopathy is an unusual complication of primary pulmonary tuberculosis. There are very few reports describing both CT and contrast swallow appearances of these lesions. Objective To describe the CT and contrast swallow appearances of oesophageal erosion and perforation by lymphadenopathy as a complication of primary pulmonary tuberculosis in children. Materials and methods Imaging of three children with confirmed pulmonary tuberculosis and oesophageal perforation was retrospectively reviewed. Results Tuberculosis was confirmed by culture in all three patients. Contrast swallow demonstrated a contained leak in two patients and a tracheo-oesophageal fistula in one. Two patients had mediastinal air and one patient had a mediastinal collection on CT. All patients had features diagnostic of pulmonary tuberculosis on CT. Conclusion The imaging features comprise leakage of contrast medium with or without fistula formation on contrast swallow, large low-density lymph nodes on CT, and mediastinal air. The use of retrievable stents is a promising idea in this condition.     

Comparing three-dimensional volume-rendered CT images with fibreoptic tracheobronchoscopy in the evaluation of airway compression caused by tuberculous lymphadenopathy in children

Background  Lymphobronchial tuberculosis (TB) causes airway compression in 38% of patients. The airway obstruction is conventionally assessed with fibreoptic tracheobronchoscopy (FTB). Multidetector-row spiral computed tomography (MDCT) with three-dimensional volume rendering (3-D VR) has significantly improved the imaging of the airways. No previous studies have assessed the accuracy of 3-D VR in determining the degree of airway compression in children due to TB lymphadenopathy. Objective  To compare 3-D VR CT to FTB for the assessment of airway compression due to TB lymphadenopathy in children. Materials and methods  Included in the study were 26 children presenting with symptoms of airway compression caused by pulmonary TB. MDCT of the chest and FTB were performed in all patients. Retrospective 3-D VR reconstruction of the major airways was performed from the original CT raw data and used to evaluate the tracheobronchial tree for site and degree of airway compression and then compared to the FTB findings. FTB was used as the reference standard Results  By FTB 87 sites of airway compression were identified. Using the 3-D VR technique, 138 sites of airway compression were identified, of which 78 (90%) matched with the sites identified by FTB. The sensitivity and specificity of 3-D VR when compared with that of FTB was 92% and 85%, respectively. In four patients (15%), severe narrowing of the bronchus intermedius made FTB evaluation of the right middle and right lower lobe bronchi impossible. VR demonstrated significant distal obstruction in three of these four patients Conclusion  3-D VR demonstrates a very good correlation with FTB in determining airway compression caused by TB lymphadenopathy in children. In combination with FTB, 3-D VR adds confidence to the bronchoscopy findings and complements FTB by adding additional information on the status of the airway distal to severe obstructions unreachable by FTB.     

CT features of tuberculous intracranial abscesses in children

Background Intracranial tuberculous (TB) abscesses still cause a diagnostic dilemma on both CT and MRI as they may mimic neoplasms. Recognition of TB abscesses may prompt further imaging and appropriate trial of therapy, and may reduce the need for biopsy. Objective To report the CT features of eight intracranial TB lesions in children initially diagnosed as neoplasms and eventually treated as TB abscesses. Materials and methods We undertook a 3-year retrospective review of children with an initial CT diagnosis of intracranial neoplasm who were subsequently diagnosed as having TB abscesses. Results Eight patients out of 60 with an initial diagnosis of a neoplasm on CT were misdiagnosed and were ultimately determined to have TB abscesses after biopsy or a trial of anti-TB therapy. The most consistent constellation of findings for the lesions were low density (n = 5), ring enhancement (n = 8), cerebral hemisphere location (n = 7), mass effect (n = 6), surrounding oedema (n = 5) and absence of a soft-tissue-density mass (n = 8). Conclusion In endemic regions, intracranial lesions with these appearances on CT should undergo further imaging and possibly a trial of anti-TB therapy before considering biopsy.     

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目的改良脑脊液样本处理方法和优化PCR检测系统,提高结核性脑膜炎诊断阳性率。方法建立微波碱性非离子型表面活性剂氯仿法,并用二甲基亚砜(DMSO)优化结核杆菌插入序列IS6110PCR检测系统;分别用微波碱性非离子型表面活性剂氯仿法和简易氯仿法处理1998年7月至2004年11月间华中科技大学同济医学院同济医院收集的108份脑脊液样本,经5%DMSO优化的PCR诊断系统扩增,将结果进行比较。结果微波碱性非离子型表面活性剂氯仿法处理脑脊液模板PCR诊断结核性脑膜炎阳性率为88%,简易氯仿法为71%,假阳性率均为0。结论微波碱性非离子型表面活性剂氯仿法和5%DMSO优化的IS6110PCR检测系统可有效提高结核性脑膜炎诊断的阳性率。     

ELISA-its evaluation in diagnosis of tuberculosis meningitis

Diagnostic utility of an enzyme linked immunosorbent assay (ELISA) in hospitalised patients with clinical symptoms suggestive of tuberculous meningitis (94 cases) was studied. CSF Anti-tubercular IgG antibody levels were estimated by ELISA in 44 cases of proven tuberculous meningitis, 24 proven pyogenic meningitis and in 48 non-tuberculous cases. The cut off dilution was established at a CSF dilution of 1 :1 (undiluted) with positive and negative controls. The ELISA test had a sensitivity of 97.72% and a specificity of 95.35% using MSE antigen. When compared with conventional smear examination and culture isolation from specimens, the ELISA test proved statistically superior in the detection rate or diagnosis of clinically suspected tuberculous meningitis cases (P < 0.05).     

脑室腹膜分流术治疗小儿结核性脑膜炎脑积水

目的总结小儿结核性脑膜炎后脑积水（TBMH）行脑室腹膜分流术（VPS）的效果，分析其影响因素，探讨VPS的适应证和时机。方法总结我院经VPS治疗小儿TBMH病例56例，部分病例VPS手术前行脑室外引流（EVD）。结果手术后GOS分级，效果较好（恢复良好和中度致残）33例，占58．9％；效果较差（重度致残、植物生存和死亡）23例，占41．1％。手术后COS与手术前GCS分级、TBM分级、手术前抗结核治疗时间等有关，而与患儿的年龄、手术前是否有癫痫发作、脑积水的类型和程度、手术前CSF细胞计数和蛋白含量等无关。发生非感染性堵管4例，分流管感染2例，腹部伤口感染1例，腹部CSF囊肿1例。结论VPS治疗TBMH可以取得较好的效果，手术前GCS和TBM分级是影响TBMH患儿行VPS治疗预后最重要的因素。     

Brainstem auditory evoked response in tuberculous meningitis

Brainstem auditory evoked response (BAER) abnormalities in tuberculous meningitis (TBM) were determined in 50 cases of tuberculous meningitis (36 male and 14 female) and 50 normal healthy children. Fifty six per cent cases had abnormal BAER findings. The commonest BAER abnormality observed in 32% was a combination of prolonged latency and prolonged interval while unilateral and bilateral absent response was observed in 4% cases. Prolonged latency was observed in 16% patients. Seizure activities, modified glasgow coma scale (GCS), raised intracranial pressure (ICP) and TBM stage III were significantly correlated with abnormal BAER, while age, sex, duration of illness, depressed sensorium, neurological deficit and CSF findings did not have a significant correlation with abnormal BAER. Follow up could be done in ten patients only. All the three patients with only prolonged latency had a normal BAER on follow up, two out of four patients with prolonged latency and prolonged interval had normalization of BAER while in three patients, initial as well as follow up BAER was normal. The present study shows that BAER abnormalities are observed in more than fifty per cent of the patients of tuberculous meningitis.     

Circulatory System in Children with Localized Scleroderma

The circulatory system was studied in 43 children (ages 3–18 years, mean 10.6 years; 32 girls, 11 boys) suffering from localized cutaneous forms of scleroderma. The following studies were undertaken: general pediatric examination, cardiologic examination including routine electrocardiogram (ECG), 24-h Holter ECG monitoring, echocardiography plus Doppler study, and a treadmill exercise test. Three children found to have congenital heart malformations were excluded from the study. Children with localized scleroderma were often lighter and shorter than their appropriate controls. The most common ECG abnormality was incomplete right bundle branch block, but other ECG and Holter abnormalities were found as well. Abnormal echocardiographic results were obtained in 16 cases. The abnormalities concerned valvar function (in all heart valves but predominantly in the mitral valve). It was found that the children suffering from scleroderma had different indices than controls for left ventricular mass index, mitral valve function and left ventricular filling. During the exercise test (conducted according to Bruce's protocol) we found no difference between patients and controls.     

儿童结核性脑膜炎近期预后的影响因素

目的：探讨影响儿童结核性脑膜炎（TBM）近期预后的因素。方法：采用回顾性病例分析的方法,收集2007年1月至2011年2月137 例住院治疗的TBM患儿的临床资料,对30个可能影响近期预后的因素进行了单因素及多因素logistic回归分析。结果：137例TBM患儿中,临床分期为早、中、晚期病例分别为21例（15.3%）、67例（48.9%）、49例（35.8%）。单因素分析显示TBM的临床分期为晚期、昏迷、Babinski征阳性、颅神经损害、肢体瘫痪、抽搐、头颅CT或MRI明显异常、脑脊液蛋白量升高等因素与近期预后不良有关;而糖皮质激素的使用、PPD皮试反应阳性、住院时间延长与预后良好有关。多因素分析显示：临床分期为晚期（OR=11.168,95%CI 3.521~35.426）和脑膜刺激征阳性（OR=4.275, 95%CI 1.043~17.521）是影响TBM近期预后的危险因素,而住院时间延长（OR=0.893, 95%CI 0.825~0.968）是影响近期预后的保护因素。结论：TBM患儿出现脑膜刺激征及临床分期越晚提示预后不良,适当的延长住院时间有利于改善近期预后。     

Detection of antigen and antibody in childhood tuberculous meningitis

Objective Mycobacterium tuberculosis excretory secretory 31 kDa, a serine protease antigen (M. tb ES-31), prepared fromMycobacterium tuberculosis H₃₇Ra culture medium has been shown to have potential in detecting tuberculosis. Precise diagnosis and management of tuberculous meningitis, in children in particular, is essential to curtail mortality and morbidity. Methods In this study, M. tb ES-31 antigen, was used in Indirect ELISA to detect tuberculous IgG antibody, in sera and CSF samples while affinity purified anti ES-31 goat antibody was used in sandwich ELISA for detection of tuberculous antigen. In sixty-five samples each of CSF and sera from cases with neurotuberculosis and control with non-tuberculous diseases were collected from Kasturba Hospital, Sevagram. Results Among the 20 patients suffering from neurotuberculosis the IgG antibody was detected in 17(85%) of CSF and 16(80%) of sera samples, while antigen was detected in 18 (90%) in CSF and 16 (80%) in sera. Overall specificity of the assay for both IgG antibody and antigen detection in CSF was 96% while in sera it was 94% for IgG antibody and 96% for antigen detection. Conclusion This study showed the usefulness of mycobacterial serine protease antigen and its antibody in detecting neurotuberculosis.