CSF protein level – A predictor of optic atrophy in tubercular meningoencephalitis (TBM) in paediatric age group
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RAJENDRA KUMAR BUNDELA*, SARAN KUMAR SATSANGI**, LUXMI SINGH***, PRADYUMN SINGH****, BISHAN B LAL**,KAMAL N MISHRA*****
*Assistant Professor, Department of Ophthalmology, **Professor & Head, Department of Ophthalmology, ***Associate Professor, Department of
Ophthalmology, ****Associate Professor, Department of Pathology, *****Associate Professor, Department of Paediatric, Era’s Lucknow Medical
College And Hospital, Lucknow (UP) India And S N Medical College, Agra** (UP) India
To evaluate the correlation of CSF protein level with occurrence of optic atrophy in Tubercular
Meningoencephalitis (TBM) in pediatric age group.
Design: Retrospective longitudinal study. Method: 82 diagnosed
cases of TBM were included in the study. Routine ophthalmoscopic examination was done in all the cases and
fundus findings with special reference to characteristic optic disc changes were recorded, the fundus examination
was done initially at the time of diagnosis of TBM and repeated after 6 month of starting ATT. During routine CSF
examination micro protein analysis was done by standard commercial kit and using manufacturer guide line. The
two observations i.e. Disc changes and CSF protein level are correlated.
Result: Out of total 82 diagnosed children
with TBM, 28 developed optic nerve involvement in form of papilloedema, temporal pallor and optic atrophy, out of
these 28 patients of optic nerve involvement, 26 patients (92.85%) had initial CSF protein level >101 mg%. Despite
6 months of continuous ATT, out of 28 patients 7(25%) developed papilloedema, 9(32.14%) had temopral pallor
& 12(42.9%) had Optic atrophy. In the12 patients who developed optic atrophy the initial CSF protein level was
106 mg % in 1(6.7%), between 151-200mg% in 2(18.9%) and between 200-300mg% in 9(32.1%) patients. These
findings were statistically significant (p < 0.01).
Conclusion: Children with TBM having high protein content of
CSF at the time of diagnosis are more likely to develop optic atrophy. More so higher the initial protein level, more
are the chances of child developing optic atrophy.
Tuberculosis in children is one of the major health hazard
and it is estimated that 11% (1million) of the annual TB cases
occur in children less than 15 years of age.
1 The incidence of
CNS TB (Neurotuberculosis) especially TBM is related to the
prevalence of TB in community and it is still the most common
type of chronic CNS infection in developing countries.
of the clinical presentation and sequelae of TBM are the result
of an immunologically direct inflammatory reaction to the
Tubercular Bacilli implanted to meninges results in formation
of small lesion (Rich foci), the location of expanding rich
focus determines the type of involvement. The tubercles (foci)
rupturing into the subarachnoid space cause meningitis and if
more deeper in parenchyma it cause abscesses or tuberculoma.
In case of tubercular arachnoiditis, inflammatory exudates
surround both optic nerve, but do not infiltrate. Such dense
inflammatory exudates surrounding both optic nerve can
produce optic neuritis per se. Periarteritis and occlusion of
small vessels is frequently seen due to direct compression as
well as ischemia causing neural damage.
The common lesions in order of frequency are papillitis, optic
atrophy and papilloedema.
5 In addition TBM may result in
arachnoiditis and infarction.
In children, papilloedema may progress to primary optic
atrophy and blindness resulting from involvement of optic
nerves and chiasma by basal exudates (i.e., Optochiasmatic
Eighty two diagnosed cases of TBM between the age group
of 6 months to 15 years were included in this retrospective
longitudinal study conducted in department of ophthalmology
in collaboration with department of paediatrics at SN
Medical College, Agra and Era’s Lucknow Medical College
and Hospital, Lucknow. India, during the period, January
2005 to December 2008. The diagnosis to TBM as per WHO
1 Clinical presentation included fever, convulsions,
vomiting, altered sensorium and recurrent infection, cough,
neurologic deficits in the form of quadriparesis, hemiplegia,
or monoplegia, Positive family history of tuberculosis,
Cerebrospinal Fluid (CSF) showing pleocytosis and protein
level more then 40mg%, Montoux test, X-ray chest picture
suggestive of tuberculosis.
Ocular fundus examination using direct ophthalmoscope
(Heine beta 200 S. Germany), and fundus camera (Zeiss
visucam NMFA digital camera, Germany), was done on initial
diagnosis of TBM and after 6 months of receiving ATT. Optic
disc changes were assessed and diagnosis of optic atrophy
was made on the basis of altered disc color (varies from pale
to white), disc margin pattern , appearance of optic disc cup
shape, reduction in numbers of small blood vessels on disc
surface ( Kesten Baum Index).
Univariate comparisons between treatment groups and the
association were made using the Gaussian test, Chi square test
and Fisher exact test by using statistical software SPSSv16.
The findings and results of the present study were based on
observations made on 82 diagnosed patients of TBM, between
the age group of 6 month to 15 years (Table 2) of whom 48
(58.5%) were male and 34 (41.5%) were female (Table 1),
Out of these patients, 42 (51.2%) were more than or equal to
5 years of age and 25 (30.5%) between ages of 1 year to less
than 3 years.
At the time of initial presentation 28 (34.2%) patients had CSF
protein level in the range of 40-100 mg% while remaining 54
(65.9%) had CSF protein level in the range of 101-300 mg%
(Table 3). All the patients received four anti tubercular drug i.e.,
Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and fourth one
either Ethambutol (E) or Streptomycin (S). After six months
of continuous ATT, amongst 42(51.2%) patients who were on
RHZ+E regimen and had initial CSF protein level between
40-150 mg%, no patient developed optic atrophy; however
only single patient (16.7%) out of 11 patients who were in
151-200mg% CSF protein level group and had temporal pallor
of optic disc at the time of first presentation, developed in
optic atrophy. While out of 28 patients in initial higher CSF
protein level group 201-300mg%, 4(26.7%) patients developed
with optic atrophy. In patients who received RHZ+S regimen,
optic atrophy developed in 3(23.1%) patients with CSF level
101-200 mg% and in 4(38.6%) patients with CSF level201-
300 mg% (Table 4). The result shows that incidence of optic
atrophy is independent of ATT regime. Over all incidence
of ultimate optic atrophy increase with initial higher CSF
protein level. In present study it was nil with 40-100mg% CSF
protein level and 32.14% with 201-300mg% level. This was
statistically significant (p < 0.01).
Observations showed that in patients having optic nerve
involvement with initial lower CSF level, it cleared off in due
course of treatment but in patients having higher CSF protein
levels and initial optic nerve involvement, it either did not clear
off or landed up in optic atrophic changes as partial (temporal
pallor) or frank optic atrophy (Table 5 ).
Overall mortality of TBM is 15-75% as reported by various
5 There has been slight decrease in mortality due to
TBM in last 10 years,
1 but the morbidity due to TBM continues
to be the same over the last two decades. This is because of
expansion of tuberculoma or development of multiple new
brain lesions during treatment of TBM, and though uncommon,
has been reported in literature as “Paradoxical response” .
is possibly due to type IV hypersensitivity reaction developing
with in the initial lesion and resulting in cerebral vasculitis,
infarction and oedema.
The large majority of TBM cases (75-85%) are below the
age of 5 years. The peak incidence is in 3-5 years age group.
The neurological damage was maximum in children less
than or equal to 3 years of age and optic atrophy occurred in
a large majority of cases. There is preponderance of boys.
Our findings are akin with those as reported in literature. The
neurological damage is significantly enhanced in children
whose duration of disease is more than one month.
5 The stage
of TBM at which treatment is started constitutes the singularly
important prognostic factor for probability of optic nerve
involvement and children developing optic atrophy.
5 Kalita and
associates in their study of 65 patients of TBM with follow up
for 1 year have reported the, optic atrophy incidence as high as
15 In our study the incidence of optic atrophy is 42.14%.
The further higher incidence of optic atrophy in TBM in our
study is probably because of late start of ATT in majority cases
for some practical reasons.
Optic atrophy may some time be the only primary manifestation
of TBM and in some case it is reversible, if adequate ATT is
given in the early stage of disease.
Our study shows that as the initial protein level go higher
the ultimate incidence of optic atrophy goes higher. There is
general consensus that fixed dose combinations can be used
safely in children.
1 Our study also shows that incidence of
optic atrophy is independent of ATT regime. BCG Vaccination
in new born confers valuable protection and prevents.
hematogenous dissemination and development of TBM to
extent of 60-80%.
A combination of patient’s awareness, early start of treatment
and regular follow up may be of avail in prevention of optic
atrophy in children suffering with TBM. Further follow up
studies with still higher number series of cases are required.
Since in the present study group most of the children were
brought to hospital much late and they could not get ATT in the
initial phase. Majority of them were from poor socioeconomic
status and malnourished which in itself are the contributing
factors to high mortality and neurological damage.