|Year : 2018 | Volume
| Issue : 1 | Page : 12-15
Clinical profile of pediatric neurotuberculosis patients at a tertiary care center of Western India
Ranvijay Singh1, Nishitha Shetty2, Maryam Naveed3, Mridula Preetham Talari4, Deepak Verma5, Varsha Kulkarni6
1 Department of Medicine, RCSM Government Medical College, CPR Hospital, Kolhapur, India
2 Department of Medical Oncology, Father Muller Medical College, Mangalore, Karnataka, India
3 Department of Medicine, CMH Lahore Medical College, Lahore, Pakistan
4 Department of Medicine, Gandhi Medical College, Secunderabad, India
5 Department of Medicine, Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
6 Department of Medicine, SVS Medical College, Mahbubnagar, Telangana, India
|Date of Web Publication||24-Jan-2018|
Dr. Ranvijay Singh
Department of Medicine, RCSM Government Medical College, CPR Hospital, Near Dasara Chowk, Kolhapur - 416 002, Maharashtra
Source of Support: None, Conflict of Interest: None
Aim: The aim of this study is to determine the clinical profile of neurotuberculosis in the age group of 6 months to 10 years and its association with biochemical analysis of cerebrospinal fluid (CSF) and neuroradiological findings. Methods: Retrospective assessment of the medical records of confirmed cases of neurotuberculosis from January 2010 to June 2014 was carried out. Results: Of the 46 cases studied, mean age at presentation was 3.4 years. Male-to-female ratio was 1.55:1. Fever, vomiting, headache, seizures, and focal neurological deficits were the most common presenting clinical symptoms. Protein–energy malnutrition (PEM) was detected in 39 cases. On systemic examination, the order of involvement of cranial nerves was VII, II, III, IV, VI, and V. Positive Mantoux test was present in only 11 cases. CSF findings showed lymphocytic predominance, raised protein levels with a decreased to normal glucose levels. Neuroimaging by computed tomography scan/magnetic resonance imaging of the brain gave a definite diagnosis in thirty cases of which hydrocephalus, basal exudates, tuberculoma, and infarctions were the most common findings. The primary focus of tuberculosis was found in the lungs on chest roentgenogram in 12 cases. Conclusions: Neurotuberculosis occurs with increased frequency in the age group of 1–5 years. Fever may be of short duration at presentation in contradiction to current medical literature. PEM is a predisposing factor for the development of the disease. A tuberculin sensitivity test may be negative in cases of neurotuberculosis. CSF analysis and neuroimaging are pivotal in the establishment of a diagnosis.
Keywords: Neurotuberculosis, pediatric, protein-energy malnutrition
|How to cite this article:|
Singh R, Shetty N, Naveed M, Talari MP, Verma D, Kulkarni V. Clinical profile of pediatric neurotuberculosis patients at a tertiary care center of Western India. Muller J Med Sci Res 2018;9:12-5
|How to cite this URL:|
Singh R, Shetty N, Naveed M, Talari MP, Verma D, Kulkarni V. Clinical profile of pediatric neurotuberculosis patients at a tertiary care center of Western India. Muller J Med Sci Res [serial online] 2018 [cited 2018 Feb 20];9:12-5. Available from: http://www.mjmsr.net/text.asp?2018/9/1/12/223908
| Introduction|| |
Tuberculosis is one of the oldest and widespread infectious diseases with a high prevalence, particularly in India. According to the WHO Global Tuberculosis Report 2016, 10.4 million cases were reported worldwide out of which 5.9 million (56%) were seen in males, 3.5 million (34%) were seen in females, and 1 million (10%) in children. HIV cases account 1.2 million (11%) of all new incident TB cases worldwide. As per the WHO Global Tuberculosis Report 2016, an estimated 2.840 million new incident cases are from India with 995,000 cases seen in females and 1.850 million cases in males. In the pediatric population, an estimated 255,000 new incident cases are being seen in children <14 years of age. A total of 1740,435 cases were notified in India with mortality rate being 38.8 per 100,000 population. It is estimated that neurotuberculosis is responsible for 5%–10% of extrapulmonary cases and accounts for 1% of overall tuberculosis cases.
The risk of developing neurotuberculosis is reported to be higher in untreated primary tuberculosis cases in children than in adults. The diversity in tuberculosis symptoms, the prolonged asymptomatic course of the disease, delay in diagnosis, decreased efficacy of Anti-TB treatment in advanced cases, high occurrence of false-negative chest radiographs, and tuberculin tests pose a challenge in the early diagnosis of neurotuberculosis., Subsequent to infection by mycobacterium tuberculosis or reactivation of old tuberculosis, there occurs primary bacillemia, which leads to tuberculous foci being established in various tissues such as the meninges, vertebral column, brain, etc. In children, this results commonly due to primary infection.
The prerequisite for causation of neurotuberculosis is the occurrence of a Subependymal tubercle which progresses and ruptures into the subarachnoid space. This leads to spillage of tubercular protein into the subarachnoid space leading to a hypersensitivity reaction. This typically results in the formation of gelatinous basal exudates. The exudate infiltrates the cortico-meningeal vessels producing vasculitis which leads to border zone encephalitis. Further involvement of large vessels such as the middle meningeal artery due to arteritis or secondary to entrapment by cerebral edema results in infarction. The basal exudates block the basal subarachnoid cisterns interfering with the normal drainage of cerebrospinal fluid (CSF) out of the ventricular system resulting in communicating hydrocephalus.,
The stage at presentation and age of onset are the decisive factors in the clinical outcome, morbidity, and mortality of patients with neurotuberculosis. Moreover, the survivors manifest a wide variety of neurological sequelae., This study was conducted to assess the clinical presentation of neurotuberculosis in the age group of 6 months to 10 years and its association with neuroimaging and biochemical analysis of CSF.
| Methods|| |
A retrospective study of hospital medical records was done at a tertiary health-care center in Mumbai from January 2010 to June 2014. A total of 102 cases presenting with febrile encephalopathy in the age group of 6 months to 10 years were included out of which 46 cases of neurotuberculosis were selected on the basis of CSF analysis confirming neurotuberculosis and pathognomonic radiological (computed tomography [CT] scan or magnetic resonance imaging [MRI] brain) features. Patients with coexisting central nervous system abnormalities such as anatomical malformations, epilepsy, and other isolated or coexisting infections (pyogenic meningitis, viral meningoencephalitis) were excluded from the study. The records of age, presenting symptoms, clinical symptoms, signs, disease manifestations, and anthropometry were noted. Investigations such as X-ray chest, CSF analysis, Mantoux test, and neuroimaging (CT scan and/or MRI brain) were noted. The statistical method applied was the Pearson's Chi-Square test.
| Results|| |
Out of the total 102 cases of febrile encephalopathy, 46 cases of isolated neurotuberculosis were found in the study. The cases showed a male preponderance (male:female-1.55:1). The mean age of presentation was 3.4 years with a maximum number of cases 33 (71.74%) in the age group of 1–5 years, followed by 7 (21.74%) cases between 6 and 10 years, and 6 (13.04%) cases in <1-year age group [Figure 1]. Fever of <15 days was found in 25 cases (54.35%) and >15 days in 21 cases (45.65%), seizures in 27 cases (58.70%), altered sensorium in 25 cases (52.17%), vomiting in 20 cases (45.65%), and focal deficits in 12 cases (26.09%).
Focal neurological deficits were present in 12 cases (26.02%) which included hemiplegia in 9 cases (19.57%), monoplegia in 2 (4.35%), and diplegia in 1 case (2.17%). Irregular respiration was found in 12 cases (26.09%), papilledema in 3 cases (64.08%), and blood pressure exceeding the 95th percentile was found in 21 cases (45.65%), all of which were suggestive of raised intracranial pressure. Significant cervical lymphadenopathy was present in five cases (10.87%). Involvement of cranial nerves was of the following order, VII in nine cases (19.57%), II in five cases (13.04%), III in two cases (6.52%), IV in two cases (6.52%), and V and VI in one case (2.17%). Strabismus was present in five cases (10.87%), nystagmus in three (6.52%), and complete blindness due to optic atrophy in one case (2.17%).
Seventeen children (36.96%) had hypertonia while nine children (19.57%) showed hypotonia and twenty children (9.2%) presented with a normal tone. The power was reduced in 33 patients (71.74%), 1 case (2.17%) with Grade I power, 1 case with Grade II (2.17%) power, 20 cases (43.48%) with Grade III power, and 11 cases (23.91%) with Grade IV power while 1 patient could not be assessed due to a poor general condition. Decorticate posture was present in four cases (8.70%) and decerebrate posture in five cases (10.87%). Nine cases (19.57%) had positive Kernig's sign, and in 23 cases (50%) nuchal rigidity was seen. Dystonia was present in four cases (8.70%), choreoathetoid movements in five cases (10.87%), and hemiballismus in one case (2.17%). 1 patient had both choreoathetosis and dystonia. Deep tendon reflexes were normal in 22 cases (47.83%), absent in 4 cases (8.70%) and exaggerated in 20 cases (43.48%). Plantar reflex was normal in 25 cases (54.35%) and extensor in 21 cases (45.65%).
Bacillus Calmette–Guérin (BCG) scar was seen in only twenty cases (43.48%). Tuberculin sensitivity test (Mantoux test) gave a positive reaction (induration >10 mm) in 11 cases (27%,) and a negative reaction in 35 cases (73%). CSF analysis was done in 37 cases out of 46. The lumbar puncture was contraindicated in remaining 9 patients due to raised intracranial pressure associated with decorticate posturing. CSF protein was elevated in 30 cases (65.22%), normal in 6 cases (13.04%) while 1 case (2.17%) showed decreased protein levels. CSF glucose was decreased in 19 cases (41.30%), normal in 13 cases (28.26%) while an elevated level was seen in 5 cases (10.87%). Lymphocytic predominance in CSF was seen in 29 cases (65.22%) while neutrophilic predominance was seen in 2 cases (4.35%) and in 6 cases no cellularity was observed.
CSF smear microscopy and culture for acid-fast bacilli were negative in all the cases. The neuroimaging findings were as depicted in [Figure 2]. Hydrocephalus was seen in a maximum number of cases with neurotuberculosis (47.83%), followed by basal exudates (26.09%), tuberculoma (23.91%), and vasculitic infarcts (15.22%). Chest X-ray was abnormal only in 12 cases (26.09%) out of 46 cases. Patchy infiltrates in both lung fields were present in four cases, lobar consolidation in three cases, miliary shadows in two cases, cavitary lesion in two cases, collapsed lobe, and perihilar lymphadenopathy in one case.
| Discussion|| |
Neurotuberculosis is a serious burden on the health-care system in India., The disease has been known to occur in different age groups but has maximum incidence in the first 5 years of life according to the current medical literature.,, In this study, the mean age at presentation of the disease was found to be 3.4 years, and the maximum number of cases (thirty cases [65.22%]) were seen in the age group of 1–5 years.
In our study, the majority had fever of < 15 days which is in contrast to the study of Farinha et al. and Bhargava et al. which points to a typical presentation of fever for >15 days at hospitalization., Most of the other symptoms noted were due to raised intracranial tension. It has been noted that focal deficits and seizures occur as a result of the involvement of the brain parenchyma as these signs are not seen in patients with isolated meningeal involvement.
Protein–energy malnutrition (PEM) was present in 84.78% with maximum cases having Grade II and Grade III PEM. Hence, it can be noted that PEM is a predisposing factor for extrapulmonary tuberculosis., BCG scar was seen in only 43.48%. As described by Awasthi and van Den Bos, the BCG immunization is more effective in preventing neurological sequelae in central nervous system tuberculosis patients than preventing the disease itself.,,,
VII, II, III, IV, and VI cranial nerve palsy in that order are most commonly seen in Neurotuberculosis.,, Even in our study, a similar pattern was seen. Involvement of basal ganglia in neurotuberculosis accounts for the presence of involuntary movements with a significant proportion of patients in our study had the same. A negative tuberculin test (Mantoux test) was seen in 35 cases (76.08%). This is expected since neurotuberculosis commonly occurs with immunosuppression reflecting the absence of immune-mediated hypersensitivity reaction to tuberculin. On CSF analysis, proteins were found to be elevated with low glucose levels as mentioned in the literature., Lymphocytic predominance was seen commonly which is justified considering that neurotuberculosis is a chronic inflammatory disease. According to the existing literature, neutrophil predominance is considered atypical in comparison to lymphocyte predominance.,
On neuroimaging, hydrocephalus was seen in 47.83% and basal exudates in 26.09%. These findings contradict the study done by Lee et al. where basal exudates were found in 100% cases while hydrocephalus in 78% of cases. Neuroimaging is highly effective in establishing the diagnosis of neurotuberculosis and should be carried out on admission in any patient with clinical suspicion of the disease.,,, Twenty-six percent had a primary focus of infection in the lung on chest X-Ray which is in accordance with the current literature.,,,
| Conclusions|| |
Neurotuberculosis occurs with increased frequency in the age group of 1–5 years. Fever of <15 days duration should not be considered atypical while suspecting neurotuberculosis in a child with febrile encephalopathy, especially in the presence of other features suggesting the same. PEM is a contributory factor for the development of the disease. A negative tuberculin test is common due to immune suppression in patients with neurotuberculosis. CSF findings of elevated proteins, depressed to normal glucose levels, and a lymphocytic predominance is strong grounds in favor of neurotuberculosis. CT/MRI brain is pivotal in establishing the diagnosis of neurotuberculosis.
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| References|| |
Cherian A, Thomas SV. Central nervous system tuberculosis. Afr Health Sci 2011;11:116-27.
Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central nervous system tuberculosis: Pathogenesis and clinical aspects. Clin Microbiol Rev 2008;21:243-61.
Garcia-Monco JC. Central nervous system tuberculosis. Neurol Clin 1999;17:737-59.
Thwaites GE, Tran TH. Tuberculous meningitis: Many questions, too few answers. Lancet Neurol 2005;4:160-70.
Pavlinac PB, Naulikha JM, John-Stewart GC, Onchiri FM, Okumu AO, Sitati RR, et al. Mycobacterium tuberculosis
bacteremia among acutely febrile children in Western Kenya. Am J Trop Med Hyg 2015;93:1087-91.
Chatterjee S. Brain tuberculomas, tubercular meningitis, and post-tubercular hydrocephalus in children. J Pediatr Neurosci 2011;6:S96-100.
Chan KH, Cheung RT, Lee R, Mak W, Ho SL. Cerebral infarcts complicating tuberculous meningitis. Cerebrovasc Dis 2005;19:391-5.
N.K Venkataramana. Hydrocephalus Indian Scenario- A review. J Pediatr Neurosci. 2011;611-22.
Vadivelu S, Effendi S, Starke JR, Luerssen TG, Jea A. A review of the neurological and neurosurgical implications of tuberculosis in children. Clin Pediatr (Phila) 2013;52:1135-43.
Chang KH, Han MH, Roh JK, Kim IO, Han MC, Kim CW, et al.
Gd-DTPA-enhanced MR imaging of the brain in patients with meningitis: Comparison with CT. AJNR Am J Neuroradiol 1990;11:69-76.
Molavi A, LeFrock JL. Tuberculous meningitis. Med Clin North Am 1985;69:315-31.
Bhargava S, Gupta AK, Tandon PN. Tuberculous meningitis – A CT study. Br J Radiol 1982;55:189-96.
Farinha NJ, Razali KA, Holzel H, Morgan G, Novelli VM. Tuberculosis of the central nervous system in children: A 20-year survey. J Infect 2000;41:61-8.
van den Bos F, Terken M, Ypma L, Kimpen JL, Nel ED, Schaaf HS, et al.
Tuberculous meningitis and miliary tuberculosis in young children. Trop Med Int Health 2004;9:309-13.
Mittal SK, Aggarwal V, Rastogi A, Saini N. Does B.C.G. Vaccination prevent or postpone the occurrence of tuberculous meningitis? Indian J Pediatr 1996;63:659-64.
Idriss ZH, Sinno AA, Kronfol NM. Tuberculous meningitis in childhood. Forty-three cases. Am J Dis Child 1976;130:364-7.
Awasthi S, Moin S. Effectiveness of BCG vaccination against tuberculous meningitis. Indian Pediatr 1999;36:455-60.
Lee LV. Neurotuberculosis among Filipino children: An 11 years experience at the Philippine children's medical center. Brain Dev 2000;22:469-74.
[Figure 1], [Figure 2]