Tuberculoma complicating tuberculous meningitis: description of one paediatric case

Intracranial tuberculoma is a possible complication of meningeal, miliary or pulmonary tuberculosis. In developing countries it represents 30% of space-occupying intracranial lesions, in industrialised countries only 0.1-0.2%. One recently recognised phenomenon is the development ex novo or the enlargement of the tuberculoma during antitubercular chemo-antibiotic therapy. Here we report the clinical case of an immunocompetent Italian baby girl who presented an intracranial tuberculoma during tuberculous meningitis. We underline how such an event is possible, the need for early neuroradiological evaluation and its favourable course, maintaining adequate antitubercular therapy associated with steroid therapy.     

Paradoxical response to chemotherapy in neurotuberculosis

OBJECTIVE: Our objective was to investigate the paradoxical response and the factors responsible for such an uncommon (but known) response to chemotherapy in neurotuberculosis. MATERIAL AND METHODS: Ten children with intracranial tuberculomas/neurotuberculosis were retrospectively studied, who were on regular antituberculous chemotherapy. Any deterioration of the neurological condition, increase in the size of the lesion or appearance of new lesions was studied clinically and radiologically during the follow-up period. RESULTS: An atypical response to chemotherapy was observed from 3 weeks to 1 year of chemotherapy. Four of the 10 children, who were receiving chemotherapy for either post-tubercular meningitis (TBM), hydrocephalus (2) or TBM (2), developed multiple granulomas in 3 and hydrocephalus in 1 case. The remaining 6 children who were diagnosed to have granulomas at their presentation deteriorated at the follow-up despite regular chemotherapy. CT scans were repeated in 7 of 10 cases at the time of neurological deterioration, out of which 5 children showed appearance of new granulomas or abscess(es) and 2 showed an increase in the size of their preexisting granulomas. One patient with faintly enhancing granulomas in the posterior fossa responded to an additional use of steroids. The remaining 9 patients required surgical intervention on account of their neurological deterioration. CONCLUSIONS: (1) Paradoxical responses to intracranial tuberculoma/neurotuberculosis can occur at any time even up to 1 year during chemotherapy despite a regular standard antitubercular treatment. (2) New granuloma(s) or abscess(es) may appear in children receiving chemotherapy for TBM during the follow-up. (3) Hydrocephalus may also appear despite a regular chemotherapy in treated TBM cases. (4) Immature faintly enhancing tuberculomas have a more likely chance of resolution with antituberculous chemotherapy and glucocorticoids, while a well-formed and probably large-sized (>3 cm) granuloma may have a risk of paradoxical enlargement.     

Localized basal meningeal enhancement in tuberculous meningitis

Background Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). Objective To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. Materials and methods CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. Results The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Conclusion Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic.     

Tuberculous meningitis in native Dutch children: A report of four cases

Although it is believed that in the western countries tuberculosis is a disease confined to high-risk groups such as immigrants, we describe four cases of tuberculous meningitis (TBM) in native Dutch children. The inverse relation between the delay in starting therapy and the clinical outcome makes early diagnosis of TBM essential. The often non-specific presenting symptoms and laboratory results, the time-consuming character of cultures and the unfamiliarity of western medical staff with the disease all may contribute to a delay in diagnosis of TBM. We believe that especially gadolinium-enhanced MRI or contrast-enhanced CT can be very helpful in the early diagnosis. Although not specific, hydrocephalus and basal meningeal enhancement on MRI or CT, together with the clinical suspicion can suggest the diagnosis to such an extent that there is enough reason to start antituberculous treatment.     

Imaging intracranial tuberculosis in childhood

A morphologically based imaging review of intracranial tuberculosis in childhood is presented. The computed tomography and magnetic resonance features of parenchymal tuberculoma, tuberculous meningitis and meningeal/meniningocerebral tuberculoma are illustrated. Recent insight into the nature of tuberculoma necrosis and its magnetic resonance correlation is reviewed. Pathogenesis, relevant clinical background and the role of modern imaging is discussed.     

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。     

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。     

Intracranial tuberculoma. Evaluation and treatment

We used computerized tomography (CT) to screen 83 patients with partial seizures who had 1) increased intracranial pressure; 2) evidence of systemic tuberculosis; or 3) focal neurological deficit. We found intracranial tuberculoma in 20 (24%). In addition, of 55 patients with tuberculous meningitis, 12 had associated tuberculoma. The image morphology on CT scans showed ring lesions (14), discs (10), and irregular coalescing masses (8). Perilesional edema frequently was present. After appropriate antitubercular therapy, clinical outcome for seizures, neurological deficit, and increased intracranial pressure was satisfactory. CT lesions regressed within 12 weeks of inauguration of medical therapy in most patients. Medical management of tuberculoma is advocated, with surgery limited to those in whom such treatment is ineffective.     

Paradoxical intracranial tuberculoma requiring surgical treatment

Paradoxical enlargement of intracranial tuberculomas or development of new ones during adequate antituberculous chemotherapy is an uncommon event. Treatment of such cases is controversial. Steroid therapy is usually advocated without change in the antituberculous drug program. However, in some patients whose lesions fail medical treatment, or who have superficially located large lesions, surgical therapy may be required. A 15-year-old girl with pulmonary miliary tuberculosis, tuberculous meningitis and multiple intracranial tuberculomas is presented. While her pulmonary lesions and intracranial tuberculomas except one were healed with chemotherapy, one tuberculoma increased in size 1 month after starting chemotherapy. She was followed with dexamethasone treatment in addition to antituberculous therapy for 2 months. Then, the lesion was removed because it had increased in size in spite of appropriate chemotherapy.     

Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

Background Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. Objective To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Materials and methods Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Results Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. Conclusion The association of a focal lesion in the basal ganglia of children with progressive hemiparesis, neuropsychiatric symptoms and ipsilateral cerebral and/or brain stem hemiatrophy should prompt the diagnosis of ectopic germinoma, avoiding delay in the diagnosis and further irreversible clinical deterioration, in a malignancy with an otherwise favorable prognosis. In these patients, hemiatrophy preceding or accompanying the imaging depiction of a basal ganglia mass lesion is thought to be caused by a paraneoplastic process.     

Diagnostic and prognostic value of CT brain scan in term neonates with moderate and severe birth asphyxia

Twenty term neonates with moderate (stage II) and 5 with severe (stage III) hypoxic ischemic encephalopathy (HIE) were prospectively studied to determine diagnostic and prognostic value of CT brain scan. Three neonates expired, 4 were lost to follow up while 18 were followed up to 18 months of age. Cerebral hypodensities were noted in 20 and intracranial hemorrhage (ICH) in 8, of which 6 had both ICH and hypodensity. Twelve of 14 infants with hypodensities and 5 of 6 with ICH who were followed up were handicapped at 18 months. Thirteen of 18 babies followed up were subjected to repeat CT scans between 9 and 18 months of age for assessing extent and severity of brain damage. Major abnormality noted on repeat CT scans was cerebral atrophy. All 6 infants whose follow-up scans were abnormal had neurological sequelae, while of 7 infants who had normal repeat CT scans, 5 had neurological sequelae. We do not recommend repeat CT scans in patients with HIE as a parameter to predict neurologic outcome.     

CT features of lymphobronchial tuberculosis in children, including complications and associated abnormalities

Background

Lymphobronchial tuberculosis (TB) is tuberculous lymphadenopathy involving the airways, which is particularly common in children.

Objective

To describe CT findings of lymphobronchial TB in children, the parenchymal complications and associated abnormalities.

Materials and methods

CT scans of children with lymphobronchial TB were reviewed retrospectively. Lymphadenopathy, bronchial narrowing, parenchymal complications and associations were documented.

Results

Infants comprised 51% of patients. The commonest site of lymphadenopathy was the subcarinal mediastinum (97% of patients). Bronchial compression was seen in all children (259 bronchi, of these 28% the bronchus intermedius) with severe or complete stenosis in 23% of affected bronchi. Parenchymal complications were present in 94% of patients, including consolidation (88%), breakdown (42%), air trapping (38%), expansile pneumonia (28%), collapse (17%) and bronchiectasis (9%), all predominantly on the right side (63%). Associated abnormalities included ovoid lesions, miliary nodules, pleural disease and intracavitary bodies.

Conclusion

Airway compression was more severe in infants and most commonly involved the bronchus intermedius. Numerous parenchymal complications were documented, all showing right-side predominance.     

Pure methotrexate encephalopathy presenting with seizures: CT and MRI features

With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures. Received: 23 June 1997 Accepted: 8 September 1997     

Miliary tuberculosis in children. Clinical and laboratory manifestation in 19 patients.

The clinical course of 19 children with miliary tuberculosis was studied. Complaints were nonspecific and included fever, anorexia, weight loss, and night sweats. Although all but one child had a miliary infiltrate visible on the chest roentgenogram, only 13 had a positive reaction to the purified protein derivative of the tuberculin test at admission to the hospital. Outcome was excellent unless the child also had tuberculous meningitis or was in a far advanced state of the disease. Miliary tuberculosis continues to be a rare but important cause of illness in the pediatric population. Seriously ill children with undiagnosed conditions of febrile disease deserve an aggressive evaluation for miliary tuberculosis, including an epidemiological survey, serial chest roentgenograms, and extensive, repeated culturing.     

Intracranial tuberculosis in the Netherlands: Four paediatric cases

Abstract Since 1987 a resurgence of tuberculosis is occurring in the Netherlands in analogy to the situation in other industrialised countries. So far this has not been associated with an increased incidence of tuberculous meningitis, which is still a rare complication of the disease. Four cases of intracranial tuberculosis were recently diagnosed in our hospital. All children were from middle-class Dutch families with no identified risk for tuberculosis. An extensive contact identification search could identify a contact in two patients. Two children were in an advanced stage of disease before diagnosis. Skin tests were repeatedly negative in all cases which delayed treatment in two cases for almost 2 weeks. One patient developing a cerebral tuberculous focus during therapy responded well to a second course of corticosteroids. Three children developed severe neurological sequelae.Conclusion This report illustrates that suspicion of intracranial tuberculosis is warranted in the case of an ill-defined inflammatory neurological syndrome.     

Clinical manifestations of tuberculosis in children

The natural history and clinical manifestations of tuberculosis in children differ significantly from those of the disease seen in adults. The two main factors determining the risk of progression to disease are patient age and immune status. Neonates have the highest risk of progression to disease, and in infancy miliary and meningeal involvement is common. Children from 5 to 10 years of age are less likely to develop disease than other age groups, and adolescent patients can present with progressive primary tuberculosis or cavitary disease. Immunocompromised patients are more likely both to progress to tuberculous disease and to have extrapulmonary manifestations; diagnostic tests are also of lower yield in this population. The most common sites of disease in children are intrathoracic disease and superficial lymphadenopathy. Clinical manifestations are often due to a profound inflammatory response to a relatively low burden of organisms. This is reflected in the low yield of diagnostic tests; consequently, the diagnosis of tuberculosis is often based upon a positive skin test, epidemiological information, and compatible clinical and radiographic presentation.     

Congenital tuberculosis localised to the ear.

We report two infants who had localised congenital tuberculous otitis. In both cases the infants presented with an ear discharge and both mothers had been diagnosed as having miliary tuberculosis. Infection is thought to have occurred in utero or during birth.     

Miliary tuberculosis with acute respiratory failure and histiocytic hemophagocytosis. Successful treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213

A 14-year-old girl with high fever, dyspnea and bilateral miliary nodules on chest X-ray, developed a rapidly progressive respiratory failure associated with histiocytic hemophagocytosis. Histologic examination of bone marrow biopsy revealed tuberculous granulomas with caseating necrosis. We report a pediatric case in which treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213 was successful.     

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.