Abstract
Background:
Neurotuberculosis is among the most severe type of tuberculosis with high mortality and morbidity in all age groups. Various sociodemographic and disease-/treatment-related factors have emerged over the years that can affect clinical and radiologic features of neurotuberculosis.
Objective:
To investigate various clinical and neuroradiologic presentations of neurotuberculosis.
Methodology:
This cross-sectional study was done in a tertiary care center of northern India. The patients between the ages of 3 months and 18 years with newly diagnosed neurotuberculosis were enrolled after taking informed consent.
Results:
A total of 78 patients (37% males) were enrolled. Fifty-six patients (72%) had tubercular meningitis (TBM) and 22 (28%) isolated tuberculomas. Very high percentage of patients in both the groups was BCG vaccinated. In the tubercular meningitis group, fever (68%), headache (59%), and vomiting (54%) were the most common complaints whereas in the tuberculoma group, seizures (95.5%) were the main complaint and systemic symptoms were rare. In tubercular meningitis patients, cerebrospinal fluid–based studies showed cartridge-based nucleic acid amplification test (Xpert MTB/RIF) positivity for Mycobacterium tuberculosis in 17.6% cases, whereas on gastric aspirate and sputum examination, acid-fast bacilli were seen in 30.7% and cartridge-based nucleic acid amplification test was positive in 19% patients. On neuroimaging, hydrocephalus was seen in 44.6% of tubercular meningitis patients, infarcts in 32%, and basal exudates in 12% patients only; coexistent tuberculomas were seen in 53%.
Conclusion:
Compared with the available literature, the present study showed a smaller percentage of children <5 years of age, stage III tubercular meningitis cases, and typical neuroradiologic findings like hydrocephalus and basal exudates and more tuberculomas associated with tubercular meningitis.
Neurotuberculosis is the most dangerous form of tuberculosis, because of its high mortality and possible risk of serious neurologic sequelae. Around 2% to 5% of all TB patients develop neurotuberculosis. 1 Tubercular meningitis (TBM) accounts for 25% of all extrapulmonary tuberculosis. 2 Tubercular meningitis is the commonest type of neurologic tuberculosis encountered in childhood. Other intracranial forms include tuberculoma, tubercular brain abscess, tubercular encephalitis, tubercular vasculitic infarcts, and tubercular brain abscess, whereas Pott spine, Pott paraplegia, nonosseous spinal tuberculoma, spinal arachnoiditis, and spinal meningitis constitute the extracranial or spinal forms. 3
Tuberculosis is an ancient disease and has seen several changes over time. Several factors might affect the presentation of neurotuberculosis. Public health care and social preventive measures like immunization and hygiene have seen marked improvement in almost all countries of the world. Literature shows that Bacillus Calmette-Guerin (BCG) vaccination significantly lowers the severity of neurotuberculosis. 4 Inadvertent use of antibiotics with antitubercular effect (eg, amoxy clavulanic acid, levofloxacin, and amikacin) has become rampant, which may alter the course and presentation of the disease. The incidence of multidrug-resistant and extensively drug resistant strains of tuberculosis are increasing. Coinfection with human immunodeficiency virus is also commonly seen, making patients more vulnerable to complications and drug resistance. All these factors may cause a change in the clinical and radiologic features of neurotuberculosis. This study was therefore conducted with the primary aim of studying clinical and radiologic spectrum of central nervous system tuberculosis in children and correlating it with nutritional, BCG vaccination and socioeconomic status.
Methodology
Study Design and Population
This prospective, single-center, cross-sectional study was undertaken at the Government Medical College and Hospital, a tertiary care hospital situated in the city of Chandigarh in northern India. The patients were enrolled after taking written informed consent and assent (whenever applicable) from parents, patients, caretakers before recruiting for the study. The study was conducted over a period of 20 months.
Inclusion/Exclusion Criteria
All eligible pediatric patients between the ages of 3 months and 18 years with newly diagnosed neurotuberculosis attending Government Medical College and Hospital, Chandigarh, from December 2017 to July 2019 were invited to participate in the study.
Children were included if they fulfilled the Uniform TBM Resource Case Definition criteria for tubercular meningitis 2,5 or radiologic features were suggestive of tuberculomas or tubercular brain abscess.
Study Procedure and Data Collection
All newly diagnosed cases of neurotuberculosis within defined age group were screened for potential eligibility. The patients were enrolled from pediatric and general medicine emergency, wards, pediatric, and adult neurology clinics. Baseline evaluation on enrolment was undertaken by a physician/study investigator, and all information was recorded on a structured case record form. Baseline evaluation included sociodemographic characteristics, age, gender, height, weight, and nutritional status assessed by direct parent/patient interview and examination of the patient. BCG vaccination status and history of close contact with tuberculosis case was recorded. Socioeconomic status was assessed by a modified version of the Kuppuswamy scale. 6 It is an important tool for assessing socio-economic status in hospital and community-based studies in India which takes account of education, occupation of the head of the family and total family income. After obtaining scores for all 3 parameters, a person can be classified into one of 5 socioeconomic classes: upper, upper middle, lower middle, upper lower, and lower. Patients were examined thoroughly at first contact; findings of general physical and systemic examination were noted. Assessment for malnutrition was done as per WHO weight for age charts in children younger than 5 years and according to body mass index in older children. Detailed neurologic examination was done. Level of consciousness was assessed by the Glasgow Coma Scale and in younger children a modified Glasgow Coma Scale was used.
Tubercular Meningitis: Definition and Staging
The diagnosis of tubercular meningitis was made according to the Uniform TBM Resource Case Definition criteria. 5 As per these criteria, there is a clinical entry criterion that comprises of symptoms and signs of meningitis, including 1 or more of the following: headache, irritability, vomiting, fever, neck stiffness, convulsions, focal neurologic deficits, altered consciousness, or lethargy. Patients are further assigned into definite, probable, and possible tubercular meningitis categories on the basis of microbiological evidence of brain or spinal tuberculosis or a diagnostic score. The diagnostic score comprises clinical criteria, cerebrospinal fluid criteria, cerebral imaging criteria, and evidence of tuberculosis elsewhere with a maximum score of 20. If alternative diagnoses are established, then the case is classified as no tuberculous meningitis.
The determination of the clinic stages of tubercular meningitis was done according to the criteria of the British Medical Research Council, which is as follows: stage I: no focal neurologic findings and a Glasgow Coma Scale score of 15; stage II: a Glasgow Coma Scale score of 15 and presenting with focal neurologic deficit or a Glasgow Coma Scale score between 10 and 14 regardless of the presence of focal neurologic deficit; stage III: all patients with a Glasgow Coma Scale score <10. 7
Tuberculoma
The intracranial lesions were considered tuberculomas if there was (1) radiologic/microbiological evidence of tuberculosis elsewhere in body, (2) history of contact for tuberculosis, (3) on neuroimaging: diagnosis was made as per the features described in literature. 8 -10
Tubercular brain abscess
Because it is difficult to differentiate large caseating tuberculomas with liquefaction from tubercular abscess, it was decided that as per literature, on magnetic resonance imaging (MRI), lesions which were >3 cm in size with a thin smooth wall, with or without multiloculation and presence of restricted diffusion on diffusion-weighted imaging sequence with low apparent diffusion coefficient value would be considered as brain abscess. 8
Investigations
Baseline investigations were done in all the inpatients. Assessment for anemia was done per WHO recommendations of anemia. 11 Serum Sodium levels <135 mg/dL were considered as hyponatremia and >150 mg/dL as hypernatremia. The supportive investigations for tuberculosis included chest radiograph, gastric aspirate or sputum for acid-fast bacilli / cartridge-based nucleic acid amplification test (Xpert MTB/RIF) / acid-fast bacilli culture, Mantoux skin test and family screen for tuberculosis. Cartridge-based nucleic acid amplification test (Xpert MTB/RIF) is a fully automated, cartridge-based nucleic acid amplification technology that simultaneously detects Mycobacterium tuberculosis bacilli and rifampicin resistance. 12 Its use has been recommended in extrapulmonary tuberculosis by the World Health Organization (WHO) since 2013. 13 Mantoux skin test was considered positive in patients with endurance diameter >10 mm. HIV testing was done in all cases, in children less than 1.5 years, maternal HIV was done by enzyme-linked immunosorbent assay technique. All patients with suspected tubercular meningitis underwent lumbar puncture except for the ones with absolute contraindications like severe raised intracranial pressure or shock. Cerebrospinal fluid was sent for routine biochemistry (sugar, protein), cytology, culture, adenosine deaminase levels, acid-fast bacilli, LJ medium culture and cartridge-based nucleic acid amplification test. Cerebrospinal fluid sugar <45 mg/dL, proteins >60 mg/dL, adenosine deaminase >20 U/dL were considered significant.
Neuroradiology
Computed tomography (CT) and MRI (1.5 tesla) of brain were initially planned in all the patients. However, because of financial constraints and the critical condition of some patients, MRI and magnetic resonance spectroscopy (MRS) could not be done in all the patients. The neuroimages were reported by a trained radiologist. All CTs and MRIs were carefully assessed for evidence of meningeal enhancement, basal exudates, hydrocephalus, tuberculomas, tubercular brain abscess, and infarcts. For tuberculomas, specific features noted were their location, number, size, shape, caseation, and conglomeration. In MRS, lipid peak was assessed.
As per the clinical and radiologic features, it was planned to classify patients into the following types: tubercular meningitis, isolated tuberculoma (single or multiple), and tubercular brain abscess.
Outcome Measures
The primary outcome measures were proportion of various clinical presentations of neurotuberculosis among all enrolled cases and their relation with nutritional, BCG vaccination, and socioeconomic status and comparison of clinical and radiologic features of various presentations of neurotuberculosis.
Statistical Analysis
Data were appropriately entered into Microsoft Excel and exported to SPSS version 22 for final analysis. Descriptive statistics was used to define demographic and baseline variables. Continuous data were presented as mean ± SD or median (interquartile range) and dichotomous data as percentage. The distribution of the data was tested by Kolmogorov-Smirnov test. The continuous data was compared by using Student t test for normally distributed data and Mann-Whitney test for skewed data. The dichotomous data were compared using chi-square test or Fisher exact test wherever applicable. To find independent predictor variables associated with outcomes, multivariable logistic regression analysis was used. Statistical analysis was done using SPSS window software, version 22.
Results
Patients’ Sociodemographic Characteristics
A total of 78 patients were enrolled, 29 (37%) were males. Most of the patients (69/78; 88%) were inpatients. Among 78 patients, 56 (72%) were tubercular meningitis and 22 (28%) isolated tuberculomas. Mean age of the total patients was 127 ± 61 months (M±SD). Most of the tubercular meningitis cases (25/56 [44.6%]) were seen in age group >12 years whereas children <5 years constituted only 21.4% (Table 1). In tuberculoma group, 14/22 (63.6%) were 6-12 years, whereas none of the patients were <5 years of age (P value .016). The females constituted 37/56 (66%) in tubercular meningitis as compared to 12/22 (54%) in tuberculoma group. In the tubercular meningitis group, 39 patients (70%) were immunized as compared to 100% in tuberculoma group (P value .014).
Demographic Details (N = 78).
As per the Modified Kuppuswamy Scale, none of the patients in both the groups belonged to an upper socioeconomic class. The children in the tubercular meningitis group with body mass index <3rd centile constituted most of the cases, 29/56 (51.8%), indicating increased susceptibility for tubercular meningitis in malnourished children, whereas only 2/22 patients (9.1%) in tuberculomas group had a body mass index <3rd centile (P value .007).
Clinical Features
The most common presentation in the tubercular meningitis group was fever (68%), headache (59%), and vomiting (54%) (Table 2). Seizures were reported in 21/56 patients (37.5%), altered sensorium in 18/56 cases (32%), and focal deficits in 11/56 (19.6%). Excessive irritability was noted in only 3/56 cases (5.4%). Among respiratory symptoms, cough was present in 13/56 cases (23.2%). Seizures were the most common presenting complaint in patients with tuberculoma (21/22 [95.5%]), followed by headache in 5/22 (22.7%) and focal deficits in 3/22 (13.6%). Fever was noted in only 5/22 cases (22.7%) and cough in 1/22 (4.5%). Thus, systemic symptoms in the tuberculoma-only group were uncommon compared with the tubercular meningitis group (Table 2).
Clinical Details.
Abbreviations: CN, cranial verve; GCS, Glasgow Coma Scale.
The history of viral exanthematous illness in recent past was reported in 13/56 tubercular meningitis patients (23%), compared with 2/22 patients with tuberculoma (9.1%), thus suggesting increased predisposition to severe neurotuberculosis after viral exanthematous illness. Thirty-two percent (18/56) of tubercular meningitis patients had history of tuberculosis contact, compared to only 2/22 patients (9.1%) with tuberculoma (Table 2).
On logistic regression analysis, it was seen that patients with a history of tuberculosis contact had a 7 times increased risk of tubercular meningitis. Also, patients with a body mass index <3rd centile had a 32 times higher chance of acquiring tubercular meningitis.
At admission, 48% (27/56) patients with tubercular meningitis had a Glasgow Coma Scale score of 15, 15/56 (25%) had a score between 11 and 14, and 15/56 (26.8%) had scores <10. Only 24/56 patients (43%) had meningismus. Around 30% patients had tone abnormalities in the form of increased/decreased tone. The features of raised intracranial tension like hypertension and papilledema were noted in 9/56 (16%) each and abnormal posturing in 4/56 (7%). Cranial nerve involvement was seen in 13/56 tubercular meningitis patients (23%), out of which the 6th cranial nerve was the most common (8/56 [14.3%]) in cranial nerve palsy (Table 2). In the tuberculoma group, none of the patients had altered sensorium; only 1 patient had pupillary abnormality associated with papilledema and 6th cranial nerve palsy. Around 34% patients of tubercular meningitis presented in stage I, 39% in stage II, and 27% in stage III.
Investigations
As per WHO classification of anemia, 39/56 patients (69.6%) with tubercular meningitis had anemia, 25/39 (64%) had moderate anemia, 33% mild and 2.5% severe, whereas in the tuberculoma group, 12/22 patients (55%) had anemia, which was mild in 10/12 (83.3%) and moderate in 2/12 (16.6%). Hyponatremia was seen in 23/56 (41.1%) with tubercular meningitis, whereas only 5/22 (22%) tuberculoma patients had hyponatremia. Enzyme-linked immunosorbent assay for HIV was negative in all patients. Lumbar puncture could be performed in 51/56 (91%) of tubercular meningitis patients only; the rest had contraindications for lumbar puncture (Table 3). In the cerebrospinal fluid, lymphocytic pleocytosis was seen in 23/51 patients (45%), increased cerebrospinal fluid proteins in 60% and hypoglycorrhachia in 68%. Cerebrospinal fluid adenosine deaminase could be done in 22 patients only, among them only 4/22 (18%) had increased adenosine deaminase levels. Only 1 patient showed acid-fast bacilli in the cerebrospinal fluid, whereas the cerebrospinal fluid cartridge-based nucleic acid amplification test was positive for Mycobacterium tuberculosis in 9/51 patients (17.6%), and all were rifampicin sensitive. Lumbar puncture was performed in only 4 patients with tuberculoma, and no abnormality was detected in cerebrospinal fluid of any of the patients.
Cerebrospinal Fluid Findings (N = 78).
Abbreviations: ADA, adenosine deaminase; CBNAAT, cartridge-based nucleic acid amplification test.
Neuroimaging
Either contrast-enhanced CT (CECT) or MRI with magnetic resonance spectroscopy (MRS) was performed in all patients. CT could be done in 38 patients, whereas MRI was done in 51 patients.
Tubercular meningitis
Twenty-six patients 26/56 (46%) had meningeal enhancement, 25/56 patients (44.6%) had hydrocephalus, and 18/56 (32%) had infarcts (Table 4). Basal exudates, which are considered to be a characteristic feature of tubercular meningitis, were seen in 7/56 patients (12%) only (Figure 1). Coexistent tuberculomas were seen in 30 patients (53%); among them, 15 (50%) had multiple tuberculomas scattered throughout the encephalon followed by the frontal in 6 (20%), 4 (13%) had tuberculoma in cerebellum, and 2 (6.6%) had tuberculoma in thalamus. Fifty percent tuberculomas were <1 cm and 11/30 (36%) were 1 to 2 cm; only 4/30 (13%) were >2 cm. The conglomeration was seen in 19/30 tuberculomas (63%). MRI could be performed in only 24 tubercular meningitis patients with coexistent tuberculoma; 18/24 (75%) tuberculomas were noncaseating in appearance (Figure 2). Thus, most of the tuberculomas were small in size, conglomerated, and noncaseating. MRS could be done in only 13 tubercular meningitis patients with coexistent tuberculoma, among which 12/13 (93%) had elevated lipid lactate peaks.
Neuroimaging Findings.
Note: Bold faces denotes characteristics of Tuberculoma.
Tubercular meningitis.
Tuberculoma.
Isolated tuberculoma group
The most common affected site was frontal in 10/22 (45.5%), followed by parietal 5/22 (22.7%) and temporal 18.2% (4/22) (Table 4). In contrast to the tubercular meningitis group, multiple scattered tuberculomas were seen in only 3/22 patients (13.6%). No tuberculomas were seen in the occipital, cerebellar, and thalamic areas. In 50% cases (11/22) tuberculomas were <1 cm, in 45.5% they were 1 to 2 cm (10/22), and in only 1 patient, the tuberculoma was >2 cm in size. The conglomeration was seen in 20 patients (91%). MRI with MRS could be performed in only 18 patients, of which, 17 had noncaseating tuberculoma (94.4%). The elevated lipid lactate peak was seen in 17 patients (94.4%).
To summarize, tuberculomas associated with tubercular meningitis were mostly multiple and scattered compared with the single and frontal location in the tuberculoma-only group. The posterior parts of the brain (occipital lobe and cerebellum) and thalamus were spared in isolated tuberculoma group whereas in tubercular meningitis these areas were also affected. Caseation was sparingly seen in both the groups.
None of the patients had tubercular brain abscess.
Supportive Investigations
Among tubercular meningitis patients, 25/56 (44.6%) had a positive Mantoux reaction, compared with only 1 patient with tuberculoma, thus proving its utility in diagnosing a severe type of neurotuberculosis. The chest radiograph was abnormal in 23/56 patients (42%), the commonest abnormality was miliary pattern in 12/55 (21.8%), followed by patch in 7/55 (12.7%) and pleural effusion in 4/55 (7.3%). In the tuberculoma group, only 1 patient had an abnormal chest radiograph in the form of pleural effusion (1/15; 7.7%). Gastric aspirate /sputum examination could be done in only 52 tubercular meningitis patients; acid-fast bacilli were seen in 16/52 patients (30.7%). In 10 patients (19.2%), the cartridge-based nucleic acid amplification test was positive for Mycobacterium tuberculosis, and all of them were rifampicin sensitive. In the tuberculoma group, sputum cartridge-based nucleic acid amplification test was done in 11 patients only, of which 2/11 (18%) were positive for rifampicin-sensitive Mycobacterium tuberculosis.
Management
In the tubercular meningitis group, 20/56 patients (35.7%) required management for raised intracranial pressure. Mannitol was given to all 20 patients, with acetazolamide in 16 (28.6%) and glycerol in 13 (23.2%). Twelve of 56 patients (21.4%) underwent ventriculoperitoneal shunting. Mechanical ventilation was required in 8/56 (14.3%), and 7/56 (12.5%) needed inotropic support. None of these maneuvers were required in patients with isolated tuberculomas.
As per the Lancet case definition, 10/56 cases of tubercular meningitis (17.9%) were classified in the definitive tubercular meningitis group; most of the cases, 40/56 (71.4%), were probable tubercular meningitis and 6/56 (10.7%) were classified in the possible tubercular meningitis group.
There was significant correlation between the neuroradiologic features and tubercular meningitis staging. As the stage of tubercular meningitis advanced, more patients had hydrocephalus (P = .001) and infarcts (P = .013). Tuberculomas were more common in stage 1.
Outcome
Of the 56 tubercular meningitis patients, 4 died during hospital stay. Three patients were between 5 and 10 years of age and 1 patient was 18 years old, all of them died as a result of raised intracranial pressure. One patient expired after 4 months on antitubercular therapy (on telephonic follow-up), cause of death was not known. None of the tuberculoma patients expired during hospital stay. Rest of the patients are in follow-up.
Discussion
In the present study, 56 patients (72%) were of tubercular meningitis and 22 (28%) had isolated tuberculomas. Female patients (63%) were more commonly affected. More than half of the tubercular meningitis patients had malnutrition. A very high number of patients were immunized with BCG (70% in the tubercular meningitis group and 100% in the tuberculoma group). Twenty-seven percent patients presented with stage II tubercular meningitis. Among radiologic features, 45% tubercular meningitis patients had hydrocephalus, 32% infarcts, 53% tuberculomas, and only 12% had basal exudates.
This study is unique because most of the earlier studies had enrolled tubercular meningitis patients only. In the 1950s and 1960s, Udani et al 14 and Dastur et al 15 have described tubercular encephalitis/encephalopathy presenting acutely and mimicking viral encephalitis. In the recent literature, only tubercular meningitis has been mentioned as neurotuberculosis. In the present study, tubercular meningitis was more common than tuberculoma. Isolated tuberculomas were not seen in <5 years of age, indicating predisposition for severe type of neurotuberculosis in younger age group.
As per literature, males are more commonly affected by tubercular meningitis, whereas in our study, females outnumbered males (1.5 times) which could be due to pure chance or shifting demographic features. 2,16,17 It was commoner in children older than 6 years; only 21% with tubercular meningitis were younger than 5 years. This is in contrast to the literature, where tubercular meningitis cases are more common in younger age groups and tuberculoma are more common in older age groups. 2,17 -19 Almost half of tubercular meningitis patients had severe malnutrition, whereas only 9% tuberculoma patients had malnutrition, this finding supports the fact that malnutrition predisposes to severe form of neurotuberculosis. Most of the studies have shown similar findings. 2,20,21 Earlier studies have shown lower BCG coverage in tubercular meningitis patients, thereby suggesting more chances of severe neurotuberculosis without BCG vaccination. 2,17,20 -23 The present study shows a 69% positive BCG vaccination status in tubercular meningitis patients, thus questioning the role of BCG in preventing more serious disease. Mantoux positivity was seen in 45% cases of tubercular meningitis and only 4.5% patients with tuberculoma. Other studies show a lower Mantoux positivity rate. 2,17,20,23,24 We conclude that Mantoux is still a reasonably reliable investigation to support the diagnosis of disseminated tuberculosis. The history of tubercular contact was found in 32% cases only; thus, one should suspect tubercular meningitis even if no known contact for tuberculosis is found.
Fever was the most common presenting complaint in tubercular meningitis patients, followed by headache and vomiting, whereas seizures, altered sensorium, and meningismus were seen in a lower percentage of patients. Earlier studies have shown 50% to 90% of cases presenting with altered sensorium, which might be because of selection bias; few studies have enrolled febrile encephalopathy patients only, thus automatically enrolling advanced stages of tubercular meningitis. 2,14,17,20,24 -26 Over the years, the percentage of patients presenting with altered sensorium has decreased markedly; an explanation could be increased awareness about the disease leading to an early diagnosis or fewer patients progressing to its severe form because of partial treatment with antibiotics with antitubercular effect prior to presentation. 19,21,27 Loss of appetite and weight loss, which are classical features of tuberculosis, were seen in very few patients. Isolated tuberculomas patients had seizures as the most common presenting complaint; other studies have also reported headache, vomiting, and fever with varying frequency. 26,28,29 Only 27% tubercular meningitis patients presented in stage 3. This is in contrast to the studies done previously, where 40% to 86% patients presented in stage 3. 2,23 -25,30 In another recent study from the Indian subcontinent, only 22% patients presented in stage III. 27
The abnormality in chest radiograph was seen in 42% tubercular meningitis patients, earlier studies have reported abnormalities in chest radiographs in up to 70% to 80% cases. 23,24 This emphasizes the utility of chest radiograph in all suspected neurotuberculosis cases.
In one-third patients, sputum/gastric aspirate sample either revealed acid-fast bacilli or cartridge-based nucleic acid amplification test came positive (all rifampicin sensitive). Fewer patients in present study showed elevated proteins (60%) or pleocytosis (45%) in the cerebrospinal fluid compared with prior studies, which could be due to fewer cases of advanced disease. Thus, one should think twice before discarding the diagnosis of tubercular meningitis in the absence of typical cerebrospinal fluid findings. Acid-fast bacilli in the cerebrospinal fluid could be visualized in only 1 case, whereas cerebrospinal fluid cartridge-based nucleic acid amplification test was positive (rifampicin sensitive) in 17.6% cases showing its usefulness over conventional isolation techniques. In earlier studies, positive acid-fast bacilli smear/culture of cerebrospinal fluid was seen in 30% to 100% cases, whereas recent studies have reported only 0% to 12% positivity. 2,14,20,21,26 Genotypic tests (polymerase chain reaction, cartridge-based nucleic acid amplification test [Xpert MTB/RIF], Xpert MTB/RIF Ultra), line probe assays, loop-mediated isothermal amplification assay, metagenomic next-generation sequencing, pyrosequencing, etc) are new methods of diagnosing tuberculosis. 12,31 In pediatric tubercular meningitis, they are mentioned in recent studies only. Gunes et al 17 has reported detection of Mycobacterium tuberculosis by polymerase chain reaction in around 5% cases. As acid-fast bacilli detection is difficult because of the paucibacillary nature of tuberculosis in children and a lower amount of cerebrospinal fluid sample, the cartridge-based nucleic acid amplification test could be a very useful technique in making the diagnosis.
Among radiologic findings, the present study had fewer cases with hydrocephalus because compared with the available literature, in most previous studies, 60% to 90% cases had hydrocephalus, which could be due to a lower percentage of cases in advanced stages. 2,14,17,23 -26,30 Likewise, basal exudates were found in 75% to 100% cases in earlier studies, making detection of tubercular meningitis easier, but in our study only 12% had this important marker. 14,21,26,28,30 The percentage of associated tuberculomas in previous studies is 2% to 39%, whereas in our study it is 53%. 2,3,17,21,23,26,30 This higher incidence of tuberculomas could be due to better imaging techniques or a changing pattern of tubercular meningitis. Fatima et al 27 has also showed tuberculoma in 50% cases. In the present study, tubercular meningitis associated tuberculomas were either solitary or multiple, involving the posterior parts of the brain, basal ganglia, and thalamus. Isolated tuberculomas were usually conglomerate and anteriorly located; this is consistent with previous studies. 32 Bayinder et al 33 reported a series of 23 tuberculoma cases, most of whom were intracerebral (82%) and frontal in location. In another study, only a few patients had tuberculomas in the brain stem or cerebellum. 34
None of the patients in present study was HIV positive; thus, its results cannot be extrapolated to areas with high HIV prevalence.
Conclusion
Although our study might not be directly comparable to previous studies because of advancement in diagnosing techniques (better neurodiagnostics, genotype-based tests for tuberculosis, etc), we found a change in the clinical and radiologic pattern of neurotuberculosis in children. Perhaps there is a shift in the presentation of neurotuberculosis, which can only be assessed by multicentre studies.
Footnotes
Acknowledgment
We are thankful to Prof Ram Singh for his contribution to this study.
Author Contributions
SB, CA, RG, and NS performed the literature search. SB, CA, RG, and JC collected the data. All authors contributed to study conceptualization and manuscript writing.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval
Ethical clearance was taken from the institutional ethics committee of the Government Medical College and Hospital, Chandigarh, India (Ethics/2017/0044).