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 »  Introduction
 »  Material and Methods
 »  Results
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Year : 2004  |  Volume : 52  |  Issue : 2  |  Page : 194-196

Tuberculous meningitis with pulmonary miliary tuberculosis: A clinicoradiological study

Department of Neurology, Sanjay Gandhi PGIMS, Lucknow, India

Correspondence Address:
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow - 226014, India
[email protected]

 » Abstract 

BACKGROUND AND AIMS: This study aims at evaluating the clinical and radiological outcome of tuberculous meningitis (TBM) patients with pulmonary miliary tuberculosis. MATERIAL AND METHODS: Diagnosis of TBM was based on clinical, CT scan or MRI and CSF criteria, and that of miliary tuberculosis on chest radiograph. Detailed clinical evaluation was done in all. Severity of meningitis was graded into Grades I, II and III. Complete hemogram, serum chemistry and Montaux tests were performed. The recovery was defined on the basis of 6 months Barthel index score as poor, partial or complete. RESULTS: 20 out of 165 patients with TBM had pulmonary miliary tuberculosis. Their mean age was 30 years; there was one child and 13 patients were females. The mean duration of symptoms was 6.3 months. Montoux test was negative in 9 patients. Six patients were in stage I, 3 in stage II, and 11 in stage III meningitis. Hemoglobin was below 12 gm% in 13 and liver dysfunction and hypocalcaemia was present in 8 and 18 patients respectively. CT scan was abnormal in 16 patients and revealed hydrocephalus (10), granuloma (7), exudates (3) and infarction (1). MRI was abnormal in 7 out of 8 patients and 3 of these patients had normal CT scan. MRI revealed multiple granuloma in 7 patients and exudates in 2. At 6 months, 2 patients died, 10 had complete, 2 had partial and 4 had poor recovery. CONCLUSION: TBM with pulmonary miliary tuberculosis was commoner amongst females who were anemic and hypocalcaemic. MRI revealed multiple granuloma and the majority of the patients improved.

How to cite this article:
Kalita J, Misra U K. Tuberculous meningitis with pulmonary miliary tuberculosis: A clinicoradiological study. Neurol India 2004;52:194-6

How to cite this URL:
Kalita J, Misra U K. Tuberculous meningitis with pulmonary miliary tuberculosis: A clinicoradiological study. Neurol India [serial online] 2004 [cited 2021 Sep 27];52:194-6. Available from:

 » Introduction Top

Miliary tuberculosis in immunocompetent adults is rare even in endemic areas. Data from CDC reported 1.3% cases of tuberculosis as miliary.[1] Central nervous system involvement in the form of meningitis or tuberculoma is recognized clinically in 16-30% patients with miliary tuberculosis[2],[3],[4] although meningeal involvement can be found in the postmortem in 29-54% patients.[2],[3] Most of the earlier studies on TBM with pulmonary miliary tuberculosis were conducted before the advent of modern chemotherapeutic agents and imaging.[5] Silent intracranial tuberculoma in miliary tuberculosis has been reported on gadolinium enhanced MRI.[6],[7] There is a paucity of comprehensive reports analyzing the clinical, radiological and prognosis of TBM patients with miliary pulmonary tuberculosis in the modern era. This study aims at evaluating the clinical, and CT and MRI changes in TBM patients with miliary pulmonary tuberculosis and their 6-month outcome.

 » Material and Methods Top

This is a retrospective analysis of 20 out of 165 TBM patients who had miliary tuberculosis of lung and who were managed in the last 8 years. They were subjected to detailed clinical evaluation. Glasgow coma scale was used for assessment of consciousness. Montaux test, hematology, serum chemistry and radiograph of chest were carried out. Contrast enhanced cranial CT scan was done using a third generation CT scanner and 10 mm axial sections were obtained. Cranial MRI was carried out on a 2T scanner operating at 1.5 T and T1, T2, PD and gadolinium enhanced T1 sequences were obtained. The presence of hydrocephalus, exudate, infarction and tuberculoma was noted. The diagnosis of TBM was based on clinical, CSF and radiological criteria. The essential criteria included presence of meningitic syndrome comprising headache, vomiting and fever for 2 weeks or more in whom malaria, septic and fungal meningitis were excluded. The supportive criteria included predominant lymphocytic pleocytosis with raised protein; radiological evidence of tuberculosis on CT or MRI scan which included exudate, hydrocephalus, tuberculoma and infarction singly or in combination, evidence of extra CNS tuberculosis and response to antitubercular therapy. The presence of essential and at least 3 out of 4 supportive criteria was considered suggestive of TBM. The presence of AFB in CSF, positive PCR, positive IgM ELISA or AFB in CSF culture was considered as definite evidence of TBM.[8] The severity of meningitis was graded into: stage I (meningitis only) stage II (meningitis with focal neurological deficit) and stage III (meningitis with altered sensorium). Patients were prescribed 4-drug antitubercular therapy (RHZE). Routine CT scan or ultrasound of abdomen, and bone marrow examination were not performed for documenting the dissemination. The outcome was defined on the basis of 6 months Barthel index (BI) score as complete (BI 20), partial (BI 12-19) or poor (BI<12).[9]

 » Results Top

Twenty patients with TBM had pulmonary miliary tuberculosis. Their mean age was 30 (range 10-70) years; they included one child and 13 females. The duration of symptoms ranged between 2 and 24 (mean 5.3) months. All had meningeal symptoms and signs, except fever, headache and vomiting were absent in 1, 4 and 6 patients respectively. Anorexia and weight loss were present in all except 2 patients. History of tubercular contact, alcohol addiction and recurrent skin infection was present in one each. BCG vaccination was received only by a 10-year-old child. The sensorium was altered in 11 patients and GCS score ranged between 4 and 15 (mean 13.5). Seizures were present in 7 and focal weakness in 9 (2 paraparesis, 4 hemiparesis and 3 quadriparesis). Tendon reflexes were exaggerated in 6 patients. Sensations were abnormal in the lower limbs in 2 patients who had paraplegia and 1 hemiplegic patient had hemisensory loss. Papilledema and optic atrophy were present in 3 patients each. Six patients had sixth and 4 had facial nerve palsy. Six patients were in stage I, 3 in stage II and 11 in stage III meningitis. Leucocytosis was present in 3, raised ESR in 17 and hemoglobin was below 12 gm/dl in 13 patients. Serum bilirubin was raised in 6 and transaminases were raised in 8 patients. Serum calcium ranged between 8.4 and 10.8 (mean 8.8) mg/dl and in 18 patients it was below 9 mg/dl. Serum phosphorous was normal in all but serum alkaline phosphatase was raised in 13 patients. Ionized calcium was low in all the patients (range 1.96-3.22, mean 2.60 mg/dl) [Figure - 1]. Serum protein was low in 6 patients (below 6 gm/dl) and hypoalbuminemia was present in 15 patients (below 3.5 gm/dl). Montaux test was negative in 9 patients. CSF was abnormal in all and revealed raised protein 75-400 (mean 130) mg/dl, sugar 20-60 (mean 30.2) mg/dl, and lymphocytic pleocytosis (10-300/mm3, mean 93/mm3). CSF was positive for AFB in 6, for PCR in 3 and for IgM ELISA in 1 patient. CD4+ count done in 1 patient was 145/mm3 and HIV serology was negative in all. Cranial CT scan was abnormal in 16 patients, and revealed hydrocephalus in 10 (communicating 8 and obstructive 2), periventricular cap in 3 and tuberculoma in 7 patients (single 2 and multiple 4). Meningeal enhancement was present in 3 and subcortical infarctions in 1 patient [Figure - 2]. Cranial MRI in 8 patients revealed abnormality in 7 which included multiple tuberculoma in 7 [Figure:3] and meningeal enhancement in 2. In 3 of these patients CT scans were normal. Spinal MRI was carried out in 3 patients and revealed intramedullary cervical tuberculoma in 1, T2 hyperintensity in cervical spinal cord, and collapse of L5 vertebra in 1 each. Two patients died in the hospital. At 6-month follow-up 10 patients had complete, 2 had partial and 4 had poor recovery. One patient initially recovered completely, but developed quadriplegia at 6 months due to Pott's spine and two were lost to follow-up.

 » Discussion Top

In this study on 20 TBM patients with miliary tuberculosis, 19 were adults, all belonged to a tubercular endemic area and three had a history of tuberculosis. Therefore, miliary tuberculosis in these patients was most likely of the reactivation type. None of our patients presented with pulmonary or hepatic symptomatology, although 6 patients had raised bilirubin and 8 had raised transaminases suggesting associated hepatic dysfunction. The determinants of successful dissemination include the state of specific or non-specific host cellular immunity, mycobacterial virulence and bacterial load. Our patients neither had HIV infection nor an apparent cause of immunosuppression but detailed immunological studies were not done. Negative Montaux test in 9 and low CD4 in 1 patient suggest impaired cellular immunity. Another patient was alcoholic and 1 had recurrent skin infection which may be consistent with underlying immunodeficiency.
Thirteen females had hemoglobin below 12 gm/dl, and 18 patients had hypocalcaemia suggesting underlying nutritional deficiency. Tuberculosis is common in undernutrition but exactly how malnutrition favors the development of this disease is not known. Most probably multiple factors are responsible.[10] Osteomalacia is still common in India, especially in females who are under purdah, who have repeated childbirth with prolonged lactation and poor intake because of economic and sociocultural reasons.[11] Reports from northern India revealed low serum 25 (OH) vitamin D in healthy individuals and attributed it to low calcium intake and poor sun exposure, especially in females.[12] In humans, hydroxy vitamin D3 enhances macrophage microbial activity in vitro. It has been suggested that lack of sunlight and adequate diet, with resultant deficiency of the synthesis of vitamin D3 predisposes to diseases and perhaps dissemination of tuberculosis. High occurrence of tuberculosis has been reported in Gujarati Asians in west London who were deficient in 25 hydroxycholecalciferol.[13] This may explain the high frequency of miliary TB in females in our study, however, it requires further investigations.
The relationship between pulmonary and cranial miliary lesions is controversial. In a study, all 7 patients with pulmonary miliary tuberculosis without CNS symptoms and signs revealed miliary shadows in cranial MRI.[14] In contrast, only two-thirds patients out of 16 patients with miliary TB had cerebral involvement and 50% of these patients had symptoms of meningitis.[15] All our patients had meningitis; and on MRI 7 had miliary tuberculoma including the 3 patients who had normal CT suggesting a higher yield of MRI in detecting miliary granuloma.
The prognosis of miliary tuberculosis is linked to age, immune status and multi-organ involvement but CNS involvement has been reported as an independent predictor of mortality in the post-isoniazide era. About 50% miliary tuberculosis cases with associated meningitis die and death is related to the depth of coma.[15] Lower mortality (18%) in our study may be due to 4-drug antitubercular therapy, absence of HIV or immunosuppression, lack of routine use of corticosteroid therapy and treatment in a tertiary care center.
In this study most of the patients were females who were anemic and hypocalcaemic. MRI revealed multiple granuloma and the majority of the patients improved following antitubercular therapy. For evaluation of risk factors further studies are needed to evaluate TBM with and without pulmonary miliary tuberculosis. 

 » References Top

1.Rieder HL, Kelly GD, Bloch AB, Cauthen GM, Snider DE Jr. Tuberculosis diagnosed at death in the United states. Chest 1991;100:678-81.  Back to cited text no. 1  [PUBMED]  
2.Slavin RE, Walsh TJ, Pollack AD. Late generalised tuberculosis: A clinical pathologic analysis and comparison of 100 cases in the preantibiotic and antibiotic eras. Medicine 1980;59:352-66.  Back to cited text no. 2  [PUBMED]  
3.Munt PW. Miliary tuberculosis in the chemotherapy era: with a clinical review in 69 American adults. Medicine 1972;51:139-55.  Back to cited text no. 3  [PUBMED]  
4.Maartens G, Wilcox PA, Benatar SR. Miliary tuberculosis: Rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med 1990;89:291-6.  Back to cited text no. 4    
5.Lorber J. Current results in treatment of tuberculous meningitis and miliary tuberculosis. Br Med J 1956;4974:1009-11.  Back to cited text no. 5  [PUBMED]  
6.Eide FF, Gean AD, So YT. Clinical and radiographic findings in disseminated tuberculosis of the brain. Neurology 1993;43:1427-9.  Back to cited text no. 6  [PUBMED]  
7.Gee GT, Bazan C 3rd, Jinkins JR. Miliary tuberculosis involving the brain: MR findings. AJR Am J Roentgenol 1992;73:589-93.  Back to cited text no. 7    
8.Misra UK, Kalita J, Roy AK, Mandal SK, Srivastav M. Role of clinical radiological and neurophysiological changes in predicting the outcome of tuberculous meningitis: An multivariable analysis. J Neurol Neurosurg Psychiat 2000;68:300-3.  Back to cited text no. 8    
9.Misra UK, Kalita J, Srivastava M, Mandal SK. Prognosis of tuberculosis meningitis; a multivariate analysis. J Neurol Sci 1996;137:57-61.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Enarson DA, Murray JF. Global Epidemiology of tuberculosis. In: Rom WN, Garay S (Ed). Tuberculosis. Boston: Little brown; 1996:57-75.   Back to cited text no. 10    
11.Vaishnava HP. Vitamin D deficiency in osteomalacia in northern India. J Assoc Phys India 1975;23:477-84.   Back to cited text no. 11    
12.Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N. Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr 2000;72:472-5.   Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in West London: A case control study. Lancet 2000;355:618-21.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Gupta RK, Kohli A, Gaur V, Lal JH, Kishore J. MRI of the brain in patients with miliary pulmonary tuberculosis without signs and symptoms of central nervous system involvement 1997;39:699-704.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Sasaki Y, Yamagishi F, Yagi T, Yamatani H, Kuroda F, Shoda H. The complication with tuberculosis of the central nervous system in patients with miliary tuberculosis. Kekkaku 2000;75:423-7.  Back to cited text no. 15  [PUBMED]  


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