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Case Report

Management of Paradoxical Response in Pediatric

Tubercular Meningitis with Methylprednisolone
Nitin Nema, Abha Verma, Kuldeep Singh1, Virendra Mehar1

ABSTRACT Access this article online

Website:
Paradoxical response to anti‑tubercular drugs remains a diagnostic dilemma. In India where www.meajo.org
tuberculosis is quite prevalent, paradoxical response to anti‑tubercular treatment (ATT) is DOI:
either misdiagnosed or under‑diagnosed. We report two cases of optochiasmatic arachnoiditis 10.4103/0974-9233.129775
due to paradoxical response in children suffering from tuberculous meningitis. Visual acuity
Quick Response Code:
was recorded as no light perception in all eyes of both patients while they were taking 4‑drug
ATT (isoniazid, rifampicin, pyrazinamide and ethambutol). However their systemic conditions
did not worsen. They were treated with intravenous methylprednisolone for five days followed
by systemic corticosteroids on a tapering dose for four weeks along with ATT. This case report
highlights the importance of early recognition of this sight‑threatening complication and
timely, effective treatment to prevent permanent blindness.

Key words: Anti‑Tubercular Treatment, Intravenous Methylprednisolone, Optochiasmatic

Arachnoiditis, Paradoxical Response, Tubercular Meningitis

INTRODUCTION due to a paradoxical response to ATT and the successful

management of these cases.

T he incidence of tuberculosis is quite high in India. 1

Tuberculous meningitis (TBM) is the most devastating form
of extrapulmonary tuberculosis in children,2,3 especially males.4,5
CASE REPORTS

Therefore, TBM is an important cause of optochiasmatic Case 1

arachnoiditis (OCA) in the Indian subcontinent.6
OCA is an inflammation around the optic chiasm and optic
nerves. This inflammatory involvement of anterior visual
pathway results in marked exudation in the leptomeninges6
seen on magnetic resonance imaging (MRI) as basal exudates,
which are most prominent around the optic chiasm.7,8 It
may occur during the course of neurotuberculosis or as a
paradoxical response to anti‑tubercular treatment (ATT).6,9
OCA leads to profound visual impairment and, without timely
diagnosis and effective treatment, it may cause irreversible
blindness.6,10
Reports of OCA are rare in the literature particularly in pediatric
patients. We report two cases of OCA who developed blindness
A six‑year‑old male, who was fully immunized and his
vaccinations were current, was treated for stage II TBM for one
month, with good response, developed profound diminution
of vision. He was on oral 4‑drug ATT, that comprised
of isoniazid (5 mg/kg/day), rifampicin (10 mg/kg/day),
pyrazinamide (25 mg/kg/day) and ethambutol (15 mg/kg/day),
and systemic steroids (1 mg/kg/day) on a tapering dose.
The visual acuity was no light perception in both eyes. The
anterior segment examination was unremarkable except
for semi‑dilated pupils, which were not reactive to light.
The fundus examination showed slight disc hyperemia with
well‑defined margins bilaterally. Brain magnetic resonance
imaging (MRI) showed extensive enhancing basal exudates
along with dilatation of lateral and third ventricles and
obstruction at the aqueductal level [Figure 1]. A diagnosis of

Departments of Ophthalmology, 1Pediatrics, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India
Corresponding Author: Dr. Nitin Nema, Department of Ophthalmology, SAIMS, 55 Shri Nagar Main, Indore ‑ 452 018, Madhya Pradesh, India.
E‑mail: nemanitin@yahoo.com

Middle East African Journal of Ophthalmology, Volume 21, Number 2, April - June 2014 189
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Nema, et al.: Management of Paradoxical Response with Methylprednisolone
paradoxical tuberculous OCA was made on the basis of MRI
findings, cerebrospinal fluid (CSF) analysis (cells 910/cu mm,
protein 230 mg/dL, glucose 30 mg/dL, Pandy test positive),
and clinical findings. Under cover of ATT, intravenous
methylprednisolone (IVMP), 30 mg/kg body weight/day, was
administered. After three doses the visual acuity increased
to light perception in both eyes. IVMP was continued for
two more days and then the medication was changed to oral
prednisolone tablets (2 mg/kg body weight/day in single
dose) on a tapering schedule for a month. The vision slowly
improved over a period of 12 weeks. Seven months after
the visual loss, brain MRI showed decreased inflammation
of the meningeal sheaths around the optic nerves and mild
hydrocephalus [Figure 2]. ATT was stopped after 12 months.
At the 18 months follow‑up visit, the best corrected vision
was 6/18 in right eye and 6/12 in the left. The pupils in both
eyes were approximately 4 mm in diameter round and briskly
reactive to torch light. Fundus examination showed optic disc
pallor bilaterally [Figure 3].
Case 2
A four‑year‑old male child, fully immunized and his vaccinations
were current, had stage I TBM with hydrocephalus, was
on oral ATT for three weeks. He underwent surgery for
ventriculoperitoneal shunt (VP shunt) under general
anesthesia after his systemic condition stabilized. Preoperative
Figure 1: Contrast‑enhanced MRI brain showing enhancing basal exudates in the
perichiasmal region (arrow) with moderate dilatation of lateral and third ventricles
and aqueductal obstruction
a b
Figure 3: a and b. Diffuse bilateral optic disc pallor
190 Middle East African Journal of Ophthalmology, Volume 21, Number 2, April - June 2014
ophthalmoscopic examination showed a normal fundus.
Six days postoperatively, the child was referred back to us by
the pediatric surgeon with complaints of bilateral loss of vision.
The child was on 4‑drug ATT (isoniazid 5 mg/kg/day, rifampicin
10 mg/kg/day, pyrazinamide 25 mg/kg/day and ethambutol
15 mg/kg/day) but not on systemic steroids. The visual acuity
at this visit was no fixation or following of light. There was no
light perception in both eyes with absence of pupillary reaction
to light. Fundus examination by indirect ophthalmoscope
and 78 D slit‑lamp ophthalmoscopy showed normal fundi
bilaterally. Brain MRI showed enhancing lesions at the level
of optic chiasm involving both the optic nerves. A diagnosis
of paradoxical OCA was made on the basis of the clinical
picture, CSF analysis (cells 120/cu mm, 90% lymphocytes,
protein 20 mg/dL) and neuroimaging findings. The child was
started on 30 mg/kg body weight IVMP for five days and then
placed on systemic prednisolone (2 mg/kg body weight/day)
on tapering dose along with systemic ATT. Two weeks after
starting systemic corticosteroids, the child started to perceive
light on vision testing. ATT was stopped after a year and the
best corrected visual acuity at that time was 6/18 in both eyes.
The pupils were round, semi‑dilated with brisk reaction to light.
Fundus examination showed prominent temporal pallor of the
optic nerve head in both eyes [Figure 4]. Magnetic resonance
imaging of the brain showed VP shunt in situ with no evidence
of exudate in the optochiasmatic region.
Figure 2: Contrast‑enhanced MRI brain seven months after initiation of treatment
showing decreased exudates around the optochiasmatic region (arrow)
a b
Figure 4: Optic discs of right (a) and left (b) eyes showing pallor
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Nema, et al.: Management of Paradoxical Response with Methylprednisolone
DISCUSSION
Tuberculosis is a common cause of morbidity and mortality in
developing countries such as India. TBM is the most serious
form of TB in children below five years of age.2,3 There is
preponderance of the disease in male children.4,5
OCA refers to inflammatory changes with exudates in the
leptomeninges around the optic chiasm and the optic nerve.6
Tuberculosis is endemic in India, hence, OCA can occur during
the course of treatment for TBM or following withdrawal
of systemic steroids.6,9 OCA is the leading cause of visual
impairment in TBM.6,10 Early recognition of this condition and
appropriate treatment can prevent further visual loss and, at
least, salvage some functional vision.6
A reliable method of establishing the diagnosis of OCA includes
visual complaints, abnormal pupillary reactions to light, dilated
fundus examination with special attention on the examination of
optic nerve head and contrast‑enhanced MRI. Dense plaque‑like
basal exudates especially around the optic chiasm are seen on
MRI that show enhancement and hypertrophy of the chiasm
and proximal optic nerves.11 These features may be associated
with hydrocephalus.6
Paradoxical reaction is defined as appearance of fresh symptoms,
physical and radiological signs in a patient who had shown
improvement with ATT.9 It may present while the patient is on
ATT and steroids.6 It can occur as early as 2 weeks and as late
as 18 months after the initiation of ATT.12 Paradoxical response
must be differentiated from drug‑resistant tuberculosis where
there is a worsening of the patient symptoms. In the absence of
specific CSF findings and negative culture report, the diagnosis
of paradoxical deterioration depends mainly on close clinical
monitoring.12
The paradoxical response to ATT is an exaggerated host-organism
interaction resulting in massive inflammation.12,13 Effective
treatment with ATT leads to revival of the host’s immune system.
Additionally, the death of M. tuberculosis causes activation and
accumulation of lymphocytes and macrophages at the site of
bacterial deposition or toxin production.12 This is predominantly
seen in the basal region of the brain implicating the optic chiasm
and optic nerves.
The management of OCA remains a challenge and prognosis in
most of the cases remains poor.14 Systemic oral corticosteroids,
IVMP, 6 intrathecal hyaluronidase, 15 thalidomide 16 and
microsurgical scraping of exudates have been used to treat
OCA with variable results.
The treatment of OCA due to paradoxical reaction includes
high‑dose systemic corticosteroids along with continuation of
Middle East African Journal of Ophthalmology, Volume 21, Number 2, April - June 2014 191
ATT. The rationale behind the use of adjuvant steroids lies in
reducing the harmful effects of inflammation as anti‑tubercular
drugs kill the organisms.9 Treatment with corticosteroids
decreases the basal exudates and stabilizes vision, and in some
cases improves vision.6
In this case report, the two children were responding well to
ATT when they noticed profound vision loss. The first child was
receiving systemic steroid on a tapering dose while the second
child was on ATT only. Both cases were small male children with
high protein content and cell count in the CSF who developed
paradoxical OCA. They responded well to intensive high‑dose
intravenous methylprednisolone and systemic corticosteroids
with reasonably good final visual acuity.
CONCLUSION
Ophthalmologists and pediatricians should be aware of the
paradoxical response to ATT. One must predict OCA in children
suffering from TBM who present with severe visual loss without
systemic deterioration and with high CSF protein and pleocytosis
and perichiasmal exudates on MRI. Prompt treatment with
IVMP followed by oral steroid may salvage vision in these
children.
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Cite this article as: Nema N, Verma A, Singh K, Mehar V. Management of
paradoxical response in pediatric tubercular meningitis with methylprednisolone.
Middle East Afr J Ophthalmol 2014;21:189-92.
Source of Support: Nil, Conflict of Interest: None declared.

192 Middle East African Journal of Ophthalmology, Volume 21, Number 2, April - June 2014