International Journal of Community Medicine and Public Health

Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

http://www.ijcmph.com pISSN 2394-6032 | eISSN 2394-6040

DOI: https://dx.doi.org/10.18203/2394-6040.ijcmph20205407
Original Research Article

Outcomes of patients presenting with central nervous system

tuberculosis at a tertiary care center in India
Santhosh Rajendran1, Darshil Shah2*, Fatema Kapadia3, Ruchi Jani4, Jinal Pandya5,
Harpreet Singh6, Chinmay Jani6,7, Ami Parikh1

1
Department of Medicine, 1,4Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India
2
Department of Neurology, Hackensack University Medical Center, Hackensack, NJ, USA
3
Department of Psychiatry, Maimonides Medical Center, New York, USA
5
Department of Physiology, M.K. Shah Medical College, Ahmedabad, Gujarat, India
6
Department of Medicine, Mount Auburn Hospital, Beth-Israel Lahey Health, Cambridge, MA, USA
7
Harvard Medical School, Boston, MA, USA

Received: 29 October 2020

Revised: 23 November 2020
Accepted: 25 November 2020

*Correspondence:
Dr. Darshil Shah,
E-mail: shahdarshil550@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Tuberculosis (TB) is a major public health problem in India. Ten percent of all patients with TB have
CNS involvement. Delayed diagnosis of this disease is associated with increased mortality. This study assesses the
socio-demographic profile as well as outcomes in patients with various forms of CNS TB.
Methods: A prospective observational study conducted at V.S. Hospital, Ahmedabad, between December-2016 and
February-2018. Each patient was assessed from admission to 3- month follow up. The diagnosis of tuberculous
meningitis (TBM) and tuberculoma was done as per the Ahuja and Rajashekhar criteria, respectively. Neurological
status and functional outcome were graded based on modified Rankin score (mRS).
Results: Our study had 56 patients with a mean age of 35.01±11.46 years. We observed that increasing age was
associated with higher mRS (p=0.002). Fever was the most common symptom in patients with TBM (96. 15%),
unlike seizures (100%) in patients with tuberculomas with or without TBM. Patients with either isolated TBM or
tuberculoma had improvement in outcomes. On multivariate analysis, it was found that CN palsy (HR=0.38,
p=0.003), duration of illness (HR=0.35, p=0.005) and age (HR=0.33, p=0.008) were the most significant predictor of
worse outcomes.
Conclusions: Identification and evaluation of focal signs like seizures and focal neurological deficits along with
certain non-focal signs like headache and fever should raise high level of suspicion for TB in tropical regions at the
primary care levels for early diagnosis and treatment.

Keywords: CNS tuberculosis, Tubercular meningitis, Tuberculoma, Tuberculosis

INTRODUCTION of tuberculosis and 6% of extra pulmonary tuberculosis.1

The incidence of CNS Tb increases with increased
Tuberculosis (Tb) is a major public health problem not incidence of Tb infection. Ten percent of all patients with
only in India but the entire world. In immune competent tuberculosis are estimated to have CNS involvement.2
individuals, CNS tuberculosis constitutes 1% of all cases CNS TB usually results from hematogenous spread.

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 138
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

However, it can result from direct rupture or extension of Inclusion criteria

a subpial or subependymal focus (Rich focus).
Granulomatous inflammatory reaction in CNS may Inclusion criteria were all immuno-competent patients
involve the meninges, brain, spinal cord, and the bones diagnosed with CNS TB based on neuroimaging and
covering the brain and spinal cord. It may manifest in a laboratory findings; patients above 18 years of age;
variety of forms including parenchymal and patients who gave informed consent.
leptomeningeal tuberculomas, abscesses, cerebritis,
vasculitis, infarction, meningitis, and osteomyelitis.3 The Exclusion criteria
relative rarity and protean nature of its symptoms makes
tuberculosis of the CNS a formidable diagnostic Exclusion criteria were patients with potts spine and TB
challenge. myelitis; presence of secondary immunodeficiency states,
such as HIV infection and malignancy; pregnancy and
Inflammation of the meninges that surround the brain due lactation; patients lost to follow up.
to a mycobacterium tuberculosis infection is referred to as
TBM. It accounts for 70- 80 % of neurological Tb Patients presenting to the Emergency room that were
cases.4,5 The three pathologic features of tuberculous suspected to have CNS TB were admitted to the inpatient
meningitis are inflammatory meningeal exudates, ward. After taking an informed written consent, their
vasculitis of the arteries traversing this exudate (mainly socio-demographic and vital data were recorded.
small and medium-sized vessels) and disturbance of CSF Essential laboratory and radiological testing were done.
flow.6 The diagnosis of TBM was established as per
Ahuja et al criteria, which include the following Diagnostic criteria
diagnostic methods: (a) clinical (b) CSF examination (c)
radiological (d) evidence of extra-neural tuberculosis.7 We diagnosed Tb and TBM based on Rajashekhar and
Ahuja criteria respectively.7
Current WHO guidelines for treatment of TBM are based
on those developed to treat pulmonary TB and suggest Clinical evaluation and investigations
treatment with 2 months of rifampicin (RMP), isoniazid
(INH), pyrazinamide (PZE) and ethambutol (ETB) Demographic variables, co-morbidities, nutritional status,
followed by up to 10 months of RMP and INH for all and neurological status were recorded on admission and
patients.8 Adjunctive glucocorticoid therapy is beneficial thereafter at specified time; the neurological status was
in adults with tuberculous meningitis.9 Glucocorticoid evaluated on admission and categorized based on British
regimen followed is either dexamethasone or prednisone. MRC scale in patients with suspected TBM (Table 2). All
patients were evaluated based on haematological and
Aim and objectives standard biochemical profile, chest X Ray, ultrasound
abdomen, and neuroimaging. Lumbar puncture was only
Aim of this study was to assess the in-hospital outcome performed in patients with suspicion of TBM. The CSF
based on modified ranking scale (mRS) in patients with was examined for total cell count, lymphocyte count,
various forms of neurological TB who receive the daily typical cells, protein and sugar. CSF was then sent for
anti-tubercular treatment (ATT) as per WHO guidelines.8 AFB and gram staining. CSF CB NAAT was sent for all
patients. Repeat CSF examination was carried out when
Objectives were 1) to study the socio-demographic, clinically indicated; at the time of initial evaluation, plain
clinical, laboratory profile and radiological spectrum of CT of the brain was done in all patients with suspected
CNS tuberculosis 2) to study in-hospital outcome using neurological TB; plain and gadolinium enhanced MRI of
mRS of patients with CNS Tuberculosis and predictors of the brain were also done. All patients were neurologically
outcome 3) to assess the severity of CNS tuberculosis in assessed based on mRS (Table 1) on admission, at
patients using the mRS 4) to study 3-month treatment discharge and at 3-month follow up. Some patients with
outcomes in patients with various forms of CNS uncontrolled seizures, fever, and increasing CNS deficit
tuberculosis being treated with the daily ATT as per underwent repeat imaging and CSF examination.
WHO guidelines using the mRS.
Treatment and follow-up
METHODS
All patients were categorised into groups A, B and C
This was a prospective observational study conducted at based on diagnosis: TBM, TBM and Tuberculoma,
Sheth V.S. Hospital, a tertiary care hospital in Tuberculoma, respectively.
Ahmedabad, Gujarat between December 2015, and
February 2018. We collected data from 56 patients that Regular follow up was done up to 3 months after
were newly diagnosed with CNS TB. discharge. Neurological status and functional outcome
were recorded and graded based on mRS, on discharge
and follow up. Imaging and other appropriate
investigations were repeated when clinically indicated.

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 139
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

Follow up imaging was done for patients with isolated In patients with TBM, intravenous dexamethasone was
tuberculoma and TBM+tuberculoma at the 3rd month. administered followed by gradual tapering of oral
prednisolone (60 mg/day) for 2 to 3 weeks. Thereafter,
All patients with CNS TB were treated according to prednisolone was gradually tapered off over the next 2 to
WHO guidelines for a total duration of 2 months 3 weeks until stopped. In patients with intracranial
(intensive phase) and re-evaluated.8 On improvement they tuberculomas, oral prednisolone was administered for 3
were transitioned to two-drug regimen (continuation weeks.
phase).
Table 1: Modified rankin scoring.

Score Description
0 No symptoms at all
1 No significant disability despite symptoms; able to carry out all usual duties and activities
Slight disability:
2
unable to carry out all previous activities but able to look after own affairs without assistance
Moderate disability:
3
requiring some help, but able to walk without assistance
Moderately severe disability:
4
unable to walk without assistance and unable to attend to own bodily needs without assistance
Severe disability:
5
bedridden, incontinent and requiring constant nursing care and attention
6 Dead
This table describes the mRS, which was used to measure outcomes in all the three group, on admission, at discharge and at 3-month
follow up.
Table 2: Modified rankin scoring.

1. Stage 1 Fully conscious, no paresis

2. Stage 2 Decreased level of consciousness, no paresis
3. Stage 3 Deeply comatose with or without dense neurological deficit
This table describes the stages of BMRC scale. The stage was used to measure the prognosis and outcomes in patients of all the three
groups.

Outcomes were defined based on mRS. The scores can be Clinical features
scaled as following- good: 0-4, bad: 5, death: 6
Fever was the most common presenting symptom in
Statistical analysis was carried out using the SPSS group A. Seizures were present in all patients with
software version 20. Descriptive analysis was performed tuberculomas (groups B and C). Focal neurological
using chi-square test. Pearson’s test was done to evaluate deficit in the form of hemiparesis or hemiplegia was seen
co-relation between two variables. Multivariate analysis in 53% from Group B compared to only 23% in Group A
was done using linear regression analysis. and 17.5 % in Group C. All patients of Group C had
seizures followed by headache, Fever, focal neurological
RESULTS deficits and choreoathethoid movements at an incidence
of 100%, 59%, 76.5%,17.5% and 5.9% respectively.
Out of total 56 patients, 26 patients had TBM, 13 had (Figure 1)
TBM with tuberculosis and 17 had Tuberculoma.
BMRC clinical staging of illness
Age and gender distribution
All patients from group A and B were staged based on
A total of 56 patients between the ages of 18 to 65 were BMRC scale. Most patients presented at stages 2 (33%)
enrolled in this study. The mean age was 35±11 years. and 3 (48%) (Figure 2).
We observed that increasing age was associated with
higher mRS. (Pearson’s correlation factor 0.398, We observed that most patients in group B presented at
p=0.002). There were 27 (48%) females in our study. advanced stages of the disease. Only 7.69% patients
(Table 3). presented in stage 1 compared to 26.9% patients in Group
A (Figure 2).

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 140
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

Table 3: Gender distribution of patients in the study.

Age group Male Female Total Rankin score

(in years) Number Percent Number Percentage Number Percent at admission
<30 11 37.9% 12 44.4% 23 41% 3.13
30-39 6 20.7% 7 25.9% 13 23.2% 3.14
≥40 12 41.4% 8 29.6% 20 35.7% 3.25
Total 29 52% 27 48% 56 100%
The mean age was 35 +/- 11 years. Increasing age was associated with higher mRS. (Pearson’s correlation factor 0.398, p=0.002).

120
100 Group A Group B
80
60
40
20
0
Altered Diminished Neurologic
Fever Headache Seizures CNS Palsy
Sensorium vision deficts
Group A 96.15 92.31 65.38 69.23 15.23 15.38 23.08
Group B 61.54 92.31 100 61.54 30.03 15.38 53.85
This figure illustrates the presenting symptoms in Group A and Group B: Headache being most common in Group A and Seizures being
most common presenting symptom in Group B.

Figure 1: Presenting symptoms in group A and group B (TBM with or without Tuberculoma).

Stage 1 Stage 2 Stage 3

61.53
70
46.1

60
50
30.76
26.9

26.9

40
30
7.69

20
10
0
GROUP A GROUP B

This figure illustrates the BMRC stages of patients in Groups: A, B and C at presentation.

Figure 2: Comparison of BMRC staging of groups A and B.

Duration of the symptoms severe elevation of proteins, of which 23.07% had mild
elevation (<100 mg/dl), 43% had moderate elevation
Out of 56 patients, 41 (73.21%) had a prolonged duration (101–500) and 25.6 % had severe elevation (500-1500).
of illness (2 weeks to 3 months) and were being treated 43% showed normal sugar levels and 57% of patients had
by a primary care physician. On multivariate analysis a <2/3rds serum sugar level.
long duration of illness was associated with poor
outcomes (HR of 0.35 and p=0.005). Out of 56 patients, only 16 patient’s CSF detected
mycobacterium tuberculosis on CSF TBNAAT and
CSF analysis Rifampicin resistance was not detected on either. CSF
ADA were done only in 12 patients out of which it was
CSF analysis was done in group A and B and the results sensitive among 8 patients. In none of the patients we
were compared and evaluated. 71% of patients who were able to document AFB in the CSF.
presented in stage 2 and stage 3 of illness had moderate to

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 141
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

In group A and B proteins ranged from 79-1500 mg/dl which 23.07% had mild elevation (<100 mg/dl), 43% had
and the mean proteins was 287mg/dl in group A and moderate elevation (101–500) and 25.6 % had severe
393.6 mg/dl in group B. In group A and B, total cell count elevation (500-1500).
ranged from 6–145/cu.mm with mean total cell count of
56.12/cu.mm in group A and 75.32/cu.mm in group B, Table 4: CSF findings in Group A and Group B.
lymphocyte count ranged from 5-118/cu.mm with mean
lymphocyte count of 44.8/cu.mm in group A and Group A Group B
62.07/cu.mm in group B (Table 4). CSF parameters (n=26) (n=13)
N (%) N (%)
Imaging Proteins
79-100 10 (38.4) 2 (15)
On imaging the most common finding was meningeal 100-500 9 (35) 8 (61)
enhancement, 65% in Group A and 61% in group B. All 500-1500 7 (26.6) 3 (24)
the patients in group B and C showed granulomas. Lymphocytes cell count
Infarcts were mostly seen in group B patients (46%)
5-50 18 (69) 4 (30)
(χ2=3.692, p=0.05). Solitary lesion (63%) appears to be
more common than multiple lesions (39%) in our study. 50-100 8 (31) 7 (53)
Most patients with tuberculoma with or without TBM 100-118 - 2(17)
(group B and C) (n=30) had supratentorial (97%) location Total cell count
of lesion in with parietal lobe (56%) being the most 6-50 11 (42) 2 (15)
common site seen in 17 patients (Table 5, 6). 50-100 14 (54) 8 (61)
100-145 1 (4) 3 (24)
71% of patients who presented in stage 2 and stage 3 of
illness had moderate to severe elevation of proteins, of

Table 5: Imaging findings in group A and group B.

S. no. Imaging Meningeal enhancement Basal exudates Infarcts Hydrocephalus

1. Group A 65% 34% 19% 58%
2. Group B 61% 38% 46% 38%
On imaging the most common finding was meningeal enhancement, 65% in Group A and 61% in Group B.

Table 6: Lesions in group B and C.

S. no. Imaging findings Group B (%) Group C (%) Total (%)

1. Solitary lesion 5 (38.4) 14 (82.3) 19 (63.3)
2. Multiple lesion 8 (61.6) 3 (17.7) 11 (36.6)
Solitary lesion (63%) appears to be more common than multiple lesions (39%) in our study.

Concurrence of pulmonary tuberculosis Month follow up: The highest mean was maintained by
Group B on 3-month follow up (3.33±1.92) (Table 7).
Out of 56 patients 14 had active pulmonary tuberculosis
infection based on Chest X-ray results. Amongst all Improvement scale for groups A, B and C from
groups, group C had higher incidence of co-infection admission to 3 months follow up
(29%). Pulmonary TB was associated with poor outcome
(p=0.009). We compared the mRS of group A patients from
admission to discharge. The mean difference was found
Outcomes to be 0.85±0.88 and p<0.001 indicating significant
improvement. There was also a significant improvement
On admission: Out of 56 patients most had a mRS of 4 between modified Rankin score at discharge and follow-
(29%). Group B had the highest mean of modified Rankin up, with a mean difference of 0.81±0.80 and p=0.001
score (4.23±0.72). The lowest mean for mRS was (Table 8).
observed in Group C (1.29±1.3) (Table 7).
On comparing mRS between admission to discharge in
In hospital: Even during in-hospital group B displayed Group B, the mean difference was found to be 0.70±1.26
the highest mean score (3.69±1.62) and group C and p=0.069. There was no significant difference
displayed the lowest (0.81±1.04). There were 3 deaths in (p=0.982) between mRS at discharge and follow-up. We
group B and 2 deaths in group A (Table 7). can attribute this to higher mortality in this group (23%)

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 142
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

as compared to other groups and the severity of disease We can see that there is significant functional
(Table 8). improvement in patients belonging to groups A and C,
both at the end of hospital stay and at 3-month follow up
On comparing mRS from admission to discharge in but not in group B (Table 8). Patients diagnosed with
Group C, the mean difference was found to be 0.59±0.62, isolated tuberculoma had a better outcome (100%) than
p<0.001 denoting a significant improvement. There was a groups A (84%) and B (54.9%). Highest mortality was
significant improvement between mRS at discharge and seen in group B (Table 9).
follow-up as well. The mean difference was found to be
0.53±0.80 p=0.015 (Table 8).

Table 7: Modified Rankin score (mRS) in different groups.

On admission In-hospital 3-month follow up

mRS Groups
A B C A B C A B C
0-1 2 - 12 8 1 13 11 3 14
2-3 6 2 3 5 6 4 8 2 1
4 8 5 2 9 2 0 3 2 -
5 10 6 - 2 1 0 1 2 -
6 - - - 2 3 0 2 3 -
Mean 3.85±1.25 4.23±0.72 1.29±1.31 2.84±1.89 3.69±1.62 0.812±1.04 1.95±1.82 3.33±1.92 0.4±0.63
This table shows the modified Rankin Scale of all the groups (Group A, Group B, Group C) on admission, at discharge and after a 3-
month Follow up. The mean mRS was 4. Group B had the highest mean mRS at all the three instances.

Table 8: Comparison of improvement in outcomes of groups A, B and C patients from admission to follow up.

Mean
Groups S. no. Comparisons Mean P value
improvement
Modified Rankin score on admission 3.77
1 0.85±0.88 <0.001
Modified Rankin score- hospital outcome on discharge 2.92
A
Modified Rankin score-hospital outcome 2.92
2 0.81±0.80 <0.001
Modified Rankin score on 3-month follow up 2.12
Modified Rankin score on admission 4.31
3 0.70±1.26 0.069
Modified Rankin score- hospital outcome on discharge 3.62
B
Modified Rankin score-on discharge 3.62
4 0.02±1.08 0.982
Modified Rankin score on 3-month follow up 3.60
Modified Rankin score on admission 1.35
5 0.59±0.62 <0.001
Modified Rankin score- hospital outcome on discharge 0.76
C
Modified Rankin score-on discharge 0.76
6 0.53±0.80 0.015
Modified Rankin score on 3-month follow up 0.24
This table determines the improvement of mean mRS in all the three groups A, B and C by comparing the mean mRS at admission with
mean mRS at discharge and mean mRS at discharge with mean mRS at 3-month follow up within each group.

Multivariate analysis the 3 groups. Certain variables like diminished vision

(HR=0.57, p<0.001), limb weakness (HR=0.42, p=0.001),
We carried out multivariate analysis to find out the pulmonary TB (HR=0.28, p=0.009) and hydrocephalus
association of different factors with general outcome of (HR=0.26, p=0.038) were observed to have statistical
patients. We included following variables: age, fever, significance in linear regression analysis in groups A and
headache, altered sensorium, seizures, limb weakness, B. In our study the sixth cranial nerve was the most
meningeal signs, pulmonary TB, duration of illness and affected cranial nerve.
cranial nerve palsy in linear regression model. Above
mentioned variables explained 34.1% (R square value) of Table 9: Comparison of improvement outcomes in all
variance occurring in general outcomes. groups from admission to follow up.

Also, it was found that CN palsy (HR=0.38, p=0.003), Group A (%) Group B (%) Group C (%)
duration of illness (HR=0.35, p=0.005) and age Good 23 (84) 7 (54.9) 17 (100)
(HR=0.33, p=0.008) were the most significant predictor Bad 1 (4) 2(14.4) -
of worse outcomes as per linear regression analysis in all Death 2(8) 3(23) -

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 143
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

This table indicates that the outcomes in Group B (TBM + nerve was most affected. We checked cranial nerve palsy
tuberculoma) is worse as compared to isolated TBM or isolated as a predictor of poor outcome by multivariate analysis
tuberculoma. and the factor was found to be significant (p=0.003).

DISCUSSION The spectrum of vision impairment ranged from legal

blindness to functional impairment of vision. In our study
Fifty-six patients with newly diagnosed CNS tuberculosis we found that vision impairment was a significant
were registered and followed up. They ranged between 18 predictor of poor outcome Sinha et al reported that 27%
to 65 years of age, with the majority lying in the 20 to 29 of TBM patients had decreased vision due to
group. Increasing age was associated with a poor outcome optochiasmaticarachanoiditis (OCA).21 Aaron et al
(p=0.006). Similar to WHO reports, we had almost equal reported 14% patients with OCA.22 Choreoathetoid
distribution among both sexes.9 In our study 67 % of movements were a presenting symptom of tuberculoma in
patients had TBM (with or without associated 5% patients. Alarcon et al have also documented
tuberculoma). choreoathetoid movement to be the presenting
manifestation of tuberculoma.23
All our patients diagnosed as highly probable cases of
TBM had fever and headache as their initial presenting Total 71% of patients who presented in stage 2 and stage
symptoms. Study by Thwaites et al also observed similar 3 of illness had moderate to severe elevation of proteins.
trends in which these patients only had very mild and few This shows that those who presented in advanced stages
symptoms on earlier presentation.10 Most patients with had higher levels of CSF proteins which was similar to
early TBM suffered from only headache without any earlier studies.24,25 There was no correlation between the
localized symptoms. Therefore, increased surveillance of severity of the illness and the CSF sugar levels in our
suspicious cases in endemic areas is crucial. There is lack study. In contrary Hosoglo showed a correlation between
of awareness regarding CNS TB in the primary care rural severity of the illness and CSF sugar levels.24 The CSF
centres.11 In a study of 48 adults with TBM in France, a analysis in our study resulted in an average of total count
delay of 3 days between presentation and initiation of :<200/cu.mm, lymphocytes counts>80% total white cells
anti-tuberculous therapy was associated with increased and CSF protein>80 mg/dl, while these values ranged
risk of death.12 It is found that one of the most important from<750–1000/cu.mm, 10% to>70% of total white cells
determinants of outcome and prognosis in these cases is and 80 mg/dl to 100 mg/dl for CSF protein, respectively
the neurological stage of the disease at which treatment in other studies.26-28 Seventy six percent of the patients
has been started. Mortality and morbidity remain low if showed tuberculous range of lymphocytic pleocytosis and
ATT and corticosteroids are initiated before the patient elevated total counts in group A and B. In our study we
progresses beyond stage I, while in stage III the mortality were not able to document the microorganism in the
is almost 50% and those who recover may have some biological fluid.
form of neurological deficit.13,14
Definitive diagnosis of tuberculous meningitis depends
In our study all patients that were diagnosed with a upon the detection of the tubercle bacilli in the CSF,
tuberculoma had seizures as one of the presenting either by smear examination or by bacterial culture. It has
complaints. Various studies have shown similar findings. been claimed that if large volumes of CSF are carefully
Maduranth et al and Arseni et al have reported seizures to examined the organism can be found in over 90% of
be the predominant manifestation in around 90% and centrifuged CSF specimens.5 CSF CB-NAAT was sent in
85% of their patients with tuberculoma respectively. In a all patients and it was sensitive in 41% in our study
study of MRI findings on childhood epilepsy, Gulati et al compared to 38%, 53%, 66% in Armand et al, Moure et
reported tuberculoma as the the most common finding.15- al and, Vadwai et al respectively. Rifampicin resistance
17
was not seen in any patients.29-31 CSF adenosine
deaminase (ADA) was sent in 12 patients and was
Hemiparesis and hemiplegia were seen in 23% patients sensitive in 8 patients. Standardized cut-offs of ADA
from group A and in 53% from group B in our study. 15- values for the diagnosis of TBM have not been
57% of TBM patients were found to have cerebral established, and the values used in various studies ranged
infarcts, mainly during stage three of the illness.18,19 from>5.0 to>15 IU/liter. High CSF ADA activity has
According to a study published by Hsieh and colleagues, been reported from patients with lymphomas, malaria,
75% of the infarcts in the “TB zone” were supplied by brucellosis, pyogenic meningitis, cryptococcal meningitis,
the medial lenticulostriate and thalamo-perforating and cerebral lymphomas.32,33 CSF ADA activity is not
arteries, whereas infarcts in the “ischaemic zone” recommended as a routine diagnostic test for CNS
supplied by the lateral lenticulostriate, anterior choroidal tuberculosis.34
and thalamo-geniculate arteries were seen only in 11% of
the patients.20 TB vasculitis is seen in severe TBM (stage A study done by Goyal et al observed that meningeal
II to III). We checked limb weakness as a predictor of enhancement was seen in approximately 60% of patients
poor outcome by multivariate analysis and the factor was with TBM.25 We also saw similar finding in our study,
found significant (p=0.001). In our study the sixth cranial with 65% TBM patients showing meningeal

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 144
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

enhancement. Few studies have shown that neurological deficits were more commonly seen in
Hydrocephalus is the most common CT findings.24 Study patients with tuberculomas. Headache and seizures were
by Swash et al revealed that hydrocephalus was the single common non-focal presenting symptoms. Patients having
most common abnormality in 52% to 80% of patients both TBM and tuberculomas at admission had a worse
with tuberculous meningitis.12 In our study hydrocephalus prognosis compared to others. Identification and
was the second most common finding (51%). Cerebral evaluation of focal signs like seizures and focal
infarction occurs in 15–57% of tuberculous meningitis neurological deficits along with certain non-focal signs
patients, mainly during stage III of the illness. like headache and fever should raise high level of
suspicion for TB. We need to increase awareness of CNS
On measuring outcomes, we observed that patients with TB in at the primary care rural centers in tropical regions
isolated TBM (84%) or tuberculomas (100%) mostly had of the world. This will help in early diagnosis and
better outcomes. Patients with both TBM and treatment.
tuberculoma on the other hand had a higher percentage of
patients with poor outcome (14.4%) and the highest ACKNOWLEDGEMENTS
mortality (23%). There are conflicting reports in literature
with some suggesting prognosis to be similar in TBM All the faculty and administrative staff of Smt. NHL
with and without tuberculoma while others showing Municipal Medical College and Sheth V. S. Hospital,
poorer outcome in patients with tuberculoma.25,35 In our Ahmedabad, India.
study patients with tuberculoma had much better outcome
than patients with TBM with or without tuberculoma. It is Funding: No funding sources
also found in one of the study that prognostic factors Conflict of interest: None declared
correlating with poor performance to ATT are age, raised Ethical approval: The study was approved by the
intracranial pressure, hydrocephalus, infection with multi- Institutional Ethics Committee
resistant mycobacterial strains, infection with HIV
whereas in our study cranial nerve palsy, higher age and REFERENCES
higher duration of illness showed poor outcomes.14 The
mortality rate in our study (18.6%) which showed 1. CDC, reported tuberculosis in the United States,
similarity to previous studies who had used the daily ATT 2004. Atlanta, GA. US Department of Health and
regimen(17 to 43%).36-38 Human Services, CDC. 2005. Available at:
https://www.cdc.gov/mmwr/preview/mmwrhtml/m
Limitations m5410a2.htm. Accessed on 20 July 2020.
2. Wood M, Anderson, M. Chronic meningitis.
Our study is an observational study with patients having Neurological infections; major problems in
Tb only. We did not have control subjects in our study for Neurology. Philadelphia: WB Saunders,
comparison of our outcomes. As our hospital caters to 1988;16:169-248.
lower socio-economic background population of western 3. Ahluwalia VV, Sagar GD, Singh TP, Arora N,
part of India, findings might be different in other socio- Narayan S, Singh MM. MRI spectrum of CNS
demographic background of the country. Due to the tuberculosis. J Ind Acad Clin Med. 2013;14(1):83-
economic background as well as lack of electronic 90.
medical record system, we did not have full accurate past 4. Tandon PN. Tuberculous meningitis. Hand book
medical as well as family history of all patients and Clinic Neurol. 1988;52:195-226.
therefore effects of other co-morbidities were not 5. Donald PR. The epidemiology of tuberculosis in
evaluated for outcomes. Also, we did not have accurate South Africa. Novartis Found Symp. 1998;217:24-
information about past vaccination in these patients. 35
Pulmonary Tb was diagnosed based on chest x-ray. Even 6. Sheller JR, Deg Prez RM. CNS Tuberculosis.
though CT scan test has higher accuracy in diagnosing Neurol Clin. 1986;4(1):143-58.
pulmonary Tb. Due to socio-economic profile of our 7. Ahuja GK, Mohan KK, Prasad K, Behari M.
patients as well as no change in management of CNS Tb, Diagnostic criteria for tuberculous meningitis and
CT Chest was not done in all of our patients. Despite the their validation. Tuber Lung Dis. 1994;75(2):149-
limitations as mentioned above, this study gives us 52.
detailed information of a unique population of CNS 8. In: th, editor. Treatment of Tuberculosis:
Tuberculosis patients in the western part of India. It will Guidelines. WHO Guidelines Approved by the
serve as a base-line for further studies with higher sample Guidelines Review Committee. Geneva 2010.
size, and matched case-control study design. 9. Kumarvelu S, Prasad K, Khosla A, Behari M, Ahuja
GK. Randomized controlled trial of dexamethasone
CONCLUSION in tuberculous meningitis. Tuber Lung Dis.
1994;75(3):203-7.
CNS Tuberculosis has varied presentations. In our study, 10. Thwaites GE, Hien TT. Tuberculous meningitis:
higher age, duration of illness, and cranial nerve palsy many questions, too few answers. Lancet Neurol.
were associated with worse outcome. Seizures and focal 2005;4(3):160-70.

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 145
 Rajendran S et al. Int J Community Med Public Health. 2021 Jan;8(1):138-146

11. DeAngelis LM. Intracranial tuberculoma: Case 28. Thwaites GE, Chau TT, Stepniewska K, Phu NH,
report and review of the literature. Neurology. Chuong LV, Sinh DX, et al. Diagnosis of adult
1981;31(9):1133. tuberculous meningitis by use of clinical and
12. Swash M, Oxbury J. Clinical Neurology. Churchill laboratory features. The Lancet.
Livingstone. 1991. 2002;360(9342):1287-92.
13. Garg RK, Malhotra HS, Kumar N. Paradoxical 29. Armand S, Vanhuls P, Delcroix G, Courcol R,
reaction in HIV negative tuberculous meningitis. J Lemaître N. Comparison of the Xpert MTB/RIF test
Neurol Sci. 2014;340(1-2):26-36. with an IS6110-TaqMan real-time PCR assay for
14. 1Katti MK. Pathogenesis, diagnosis, treatment, and direct detection of Mycobacterium tuberculosis in
outcome aspects of cerebral tuberculosis. Med Sci respiratory and nonrespiratory specimens. J Clin
Monit. 2004;10(9):RA215-29. Microbiol. 2011;49(5):1772-6.
15. Radhakrishnan K, Kishore A, Mathuranath PS. 30. Moure R, Muñoz L, Torres M, Santin M, Martín R,
Neurological tuberculosis. In: Sharma SK. ed. Alcaide F. Rapid detection of Mycobacterium
Tuberculosis. 1st edn Jaypee Publications, tuberculosis complex and rifampin resistance in
2001:209-28. smear-negative clinical samples by use of an
16. Arseni C. Two hundred and one cases of intracranial integrated real-time PCR method. J Clin Microbiol.
tuberculoma treated surgically. J Neurol, Neurosurg 2011;49(3):1137-9.
Psychiat. 1958;21(4):308. 31. Vadwai V, Boehme C, Nabeta P, Shetty A, Alland
17. Gulati P, Jena A, Tripathi RP, Gupta AK. Magnetic D, Rodrigues C. Xpert MTB/RIF: a new pillar in
resonance imaging in childhood epilepsy. Indian diagnosis of extrapulmonary tuberculosis? J Clin
Pediatr. 1991;28(7):761-65. Microbiol. 2011;49(7):2540-5.
18. Chan KH, Cheung RTF, Lee R, Mak W, Ho SL. 32. Corral I, Quereda C, Navas E, Martin-Davila P,
Cerebral Infarcts Complicating Tuberculous Pérez-Elías MJ, Casado JL, et al. Adenosine
Meningitis. Cerebrovasc Dis. 2005;19(6):391-5. deaminase activity in cerebrospinal fluid of HIV-
19. Tai M-LS, Viswanathan S, Rahmat K, et al. infected patients: limited value for diagnosis of
Cerebral infarction pattern in tuberculous tuberculous meningitis. Europ J Clinic Microbiol
meningitis. Sci Rep. 2016;6(1):38802. Infect Diseas. 2004;23(6):471-6.
20. Hsieh F-Y, Chia L-G, Shen W-C. Locations of 33. Schutte CM, Ungerer JP, du Plessis H, van der
cerebral infarctions in tuberculous meningitis. Meyden CH. Significance of cerebrospinal fluid
Neuroradiology. 1992;34(3):197-9. adenosine deaminase isoenzymes in tuberculous
21. Sinha MK, Garg RK, Anuradha HK, Agarwal A, (TB) meningitis. J Clin Lab Anal. 2001;15(5):236-8.
Singh MK, Verma R, et al. Vision impairment in 34. Thwaites G, Fisher M, Hemingway C, Scott G,
tuberculous meningitis: predictors and prognosis. Solomon T, Innes J. British Infection Society.
Journal of the neurological sciences. 2010;290(1- British Infection Society guidelines for the diagnosis
2):27-32. and treatment of tuberculosis of the central nervous
22. Aaron S, Mathew V, Anupriya A, Sunithi M, Maya system in adults and children. J Infect.
T, Goel M, et al. Tuberculous optochiasmatic 2009;59(3):167-87.
arachnoiditis. Neurol Ind. 2010;58(5):732. 35. Dastur DK, Manghani DK, Udani PM. Pathology
23. Alarcón F, Dueñas G, Cevallos N, Lees AJ. and pathogenetic mechanisms in neurotuberculosis.
Movement disorders in 30 patients with tuberculous Radiol Clin North Am. 1995;33(4):733-52.
meningitis. Mov Disord. 2000;15(3):561-9. 36. Dubé MP, Holtom PD, Larsen RA. Tuberculous
24. Hosoğlu S, Ayaz C, Geyik MF, Kökoğlu OF, Ceviz meningitis in patients with and without human
A. Tuberculous meningitis in adults: an eleven-year immunodeficiency virus infection. Am J Med.
review. Int J Tuberc Lung Dis. 1998;2(7):553-7. 1992;93(5):520-4.
25. Goyal M, Sharma A, Mishra NK, Gaikwad SB, 37. Traub M, Colchester AC, Kingsley DP, Swash M.
Sharma MC. Imaging appearance of Tuberculosis of the central nervous system. Q J
pachymeningeal tuberculosis. AJR Am J Med. 1984;53(209):81-100.
Roentgenol. 1997;169(5):1421-4. Kox LF, Kuijper S, Kolk AH. Early diagnosis of
26. Youssef FG, Afifi SA, Azab AM, Wasfy MM, tuberculous meningitis by polymerase chain
Abdel-Aziz KM, Parker TM, et al. Differentiation of reaction. Neurology. 1995;45(12):2228-32.
tuberculous meningitis from acute bacterial
meningitis using simple clinical and laboratory Cite this article as: Rajendran S, Shah D, Kapadia F,
parameters. Diagnost Microbiol Infect Disea. Jani R, Pandya J, Singh H, Jani C, Parikh A.
2006;55(4):275-8. Outcomes of patients presenting with central nervous
27. Moghtaderi A, Alavi-Naini R, Izadi S, Cuevas L. system tuberculosis at a tertiary care center in India.
Diagnostic risk factors to differentiate tuberculous Int J Community Med Public Health 2021;8:138-46.
and acute bacterial meningitis. Scand J Infect Dis.
2009;41(3):188-94.

International Journal of Community Medicine and Public Health | January 2021 | Vol 8 | Issue 1 Page 146