CSF protein level-A predictor of optic atrophy in tubercular meningoencephalitis

by admin on January 28, 2014


CSF protein level – A predictor of optic atrophy in tubercular meningoencephalitis (TBM) in paediatric age group

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*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.

2 Many

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).

Statistical analysis

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” .

10-13 It

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.



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