AIAN Review

Tuberculosis of the Spinal Cord

Divyani Garg, Divya M. Radhakrishnan1, Umang Agrawal2, Harshad Arvind Vanjare3, Edmond Jonathan Gandham4, Abi Manesh5
Department of Neurology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 1Department of Neurology, All India Institute of Medical Sciences,
New Delhi, 2Department of Infectious Diseases, PD Hinduja Hospital and MRC, Mumbai, Maharashtra, 3Departments of Radiodiagnosis, 4Neurological Sciences,
5
Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India
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Abstract
Tuberculosis involving the spinal cord is associated with high mortality and disabling long‑term sequelae. Although tuberculous radiculomyelitis
is the most frequent complication, pleomorphic clinical manifestations exist. Diagnosis can be challenging among patients with isolated spinal
cord tuberculosis due to diverse clinical and radiological presentations. The principles of management of tuberculosis of the spinal cord are
primarily derived from, and dependent upon, trials on tuberculous meningitis (TBM). Although facilitating mycobacterial killing and controlling
host inflammatory response within the nervous system remain the primary objectives, several unique features require attention. The paradoxical
worsening is more frequent, often with devastating outcomes. The role of anti‑inflammatory agents such as steroids in adhesive tuberculous
radiculomyelitis remains unclear. Surgical interventions may benefit a small proportion of patients with spinal cord tuberculosis. Currently,
the evidence base in the management of spinal cord tuberculosis is limited to uncontrolled small‑scale data. Despite the gargantuan burden of
tuberculosis, particularly in lower and middle‑income countries, large‑scale cohesive data are surprisingly sparse. In this review, we highlight
the varied clinical and radiological presentations, performance of various diagnostic modalities, summarize data on the efficacy of treatment
options, and propose a way forward to improve outcomes in these patients.

Keywords: Abscess, arachnoiditis, mycobacteria, myelopathy, syrinx, tuberculosis

Introduction variable benefits in small series of patients with adhesive

Spinal cord involvement in tuberculosis (TB) is a devastating
yet under‑recognized entity.[1] Nearly half of the patients with
tuberculous meningitis (TBM) may concomitantly harbor
spinal cord and spinal nerve root pathology.[2] Secondary
spinal cord involvement may also occur due to vertebral
TB.[3,4] Although the latter is often discussed in the literature,
there exists a paucity of information on primary spinal cord
TB (SCTB). Identification of spinal cord involvement in
TBM is imperative as it may lead to portentous complications
including adhesive radiculomyelitis, abscess, tuberculomas,
and syrinx formation.
Despite the widespread TB burden in low‑ and middle‑income
countries, large‑scale data on tuberculous spinal cord
involvement are lacking. Most descriptions of spinal TB are
focused on the osseous component and its complications,
and information on non‑osseous spinal TB emanates from
small single‑institution cohorts, case series, and case
reports. SCTB poses specific challenges toward clinical
recognition, diagnosis, and therapy. Diagnostic flow heavily
depends on radiological features. The optimum duration of
anti‑tubercular therapy (ATT) for meningeal TB or spinal TB
is variable in different guidelines, ranging from 9–12 up to
arachnoiditis.
In this review, we examine the pathophysiology, diagnostic
and therapeutic challenges, and outcomes in spinal tuberculous
meningitis, with the aim of synthesizing current pertinent
literature focused on non‑osseous manifestations and
overcoming specific gaps in the literature with respect to
diagnosis and treatment.
Search Methodology
We searched MEDLINE (PubMed) from 1953 to December
31, 2021. We identified studies on epidemiology, pathogenesis,
clinical features, diagnosis, treatment, and outcomes in
SCTB. The exact search terms used are provided in the
supplementary appendix. We mainly selected articles from
Address for correspondence: Dr. Abi Manesh,
Department of Infectious Diseases, Infectious Diseases Research and
Training Centre (IDTRC), Christian Medical College, Vellore ‑ 632 004,
Tamil Nadu, India.
E‑mail: abimanesh@gmail.com
Submitted: 03‑Jul‑2022 Revised: 21‑Aug‑2022 Accepted: 30‑Sep‑2022
Published: 17-Nov-2022

18 months.[5‑7] Even after ATT, radiculomyelitis, and syrinx

This is an open access journal, and articles are distributed under the terms of the Creative Commons
formation may complicate the post‑treatment course. Apart Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build
from ATT, adjunctive strategies such as immunomodulation upon the work non‑commercially, as long as appropriate credit is given and the new creations are
are routinely used in severe forms of TB, such as TB licensed under the identical terms.

meningitis. The impact of such interventions on SCTB is For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
unclear. Moreover, fibrinolysis has been employed with DOI: 10.4103/aian.aian_578_22

112 © 2022 Annals of Indian Academy of Neurology | Published by Wolters Kluwer - Medknow
 Garg, et al.: Spinal cord tuberculosis
the past 10 years but also referenced important older reports
and seminal descriptions. Articles in English were included.
We also cross‑searched reference lists of articles identified
by this search strategy. We included systematic reviews and
meta‑analyses, randomized trials, case series and case reports,
and animal research, wherever relevant.
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Pathogenesis and Pathophysiology
Tubercular radiculomyelopathy (TBRM) comprises all
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atypical forms of spinal tuberculosis such as tubercular
myelitis, intradural tuberculosis, and spinal cord
complications of tubercular meningitis.[8] Mycobacterium
tuberculosis (MTB) gains entry to the host through droplet
inhalation. Bacterial phagocytosis by macrophages triggers
a cascade of inflammation resulting in the primary complex.
During the short period of bacteremia, MTB can spread
hematogenously to the central nervous system (CNS) and
form granulomas on meninges, sub‑pial, and sub‑ependymal
surfaces known as “Rich foci,” which may later rupture or
grow.
The first description of spinal arachnoiditis leading to
subarachnoid obstruction and myelopathy was given by
Sir Victor Horsley. [9] In 1947, Ransome and Montiero
published four cases of tuberculous myelopathy in the
absence of Potts’s disease, contrary to the belief that TBRM
was always a complication of vertebral tuberculosis. [10]
Dastur reviewed 74 cases of tuberculous paraplegia without
evidence of Pott’s spine. [11] He observed extradural
granulomas and arachnoid lesions without dural involvement
in 64% and 20% of patients, respectively. Intramedullary
lesions and subdural extramedullary lesions were present
in 8% each.
Figure 1: Pathological changes associated with early and late tuberculous radiculomyelitis
Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
SCTB originates in one of three ways: 1) rupture or evolution
of hematogenously disseminated tubercular foci on the
spinal meninges or spinal cord, 2) downward extension of
intracranial exudates to subarachnoid space producing spinal
arachnoiditis, and 3) extension of adjacent vertebral disease
to spinal meninges.[1,12,13] The commonest mechanism is via
the hematogenous route.
Spinal leptomeningitis progresses over three phases: 1)
an initial radiculitis phase characterized by nerve root
inflammation, 2) the arachnoiditis phase defined by ongoing
fibroblast proliferation and collagen deposition causing
nerve root adhesions, and 3) the final adhesive arachnoiditis
phase identified by atrophied nerve roots encapsulated in
dense collagen.[14] The subarachnoid space in patients with
spinal TBM contains thick gelatinous exudates, encasing the
spinal cord and radicles partially or completely. There may
be hyperemia and edema of the cord and radicles because of
inflammation.[8,13,15] The exudates may cover several spinal
segments and are predominantly located posteriorly, possibly
due to the prolonged supine position of patients.
The pathogenesis of TBRM shares similarities with models
of experimental allergic encephalomyelitis (EAE).[16] The
characteristic features of TB myelitis include inflammatory cell
infiltration, perivascular demyelination, axonal damage, and
activation of glial tissue [Figure 1].[12,13] Inflammatory exudates
can damage the parenchyma by direct infiltration or cause
subarachnoid block due to elevated cerebrospinal fluid (CSF)
protein. Occasionally, extensive exudates compress the cord
without direct invasion. Demyelination of the entrapped nerve
roots and white matter damage leads to axonal loss. Occlusion
of the spinal vessels by necrotizing granuloma or vasculitis
can cause spinal cord infarction.[13,16]
113
 Garg, et al.: Spinal cord tuberculosis

In the latter stages of the disease, the tenacious exudates get

organized, leading to the clumping of fibrin‑glazed roots. There
may be atrophy of nerve roots as well, together known as
chronic adhesive arachnoiditis. Arachnoid adhesions obstruct
CSF flow with the formation of loculations.[8,11] Irregular
subarachnoid space can cause occlusion of vessels leading to
damage to the cord and radicles; cord atrophy is seen in the
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final stages.
Syrinx develops as a late complication of TBM, though
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the precise mechanism of syrinx formation is unclear. One

proposed mechanism is obliterative endarteritis causing
ischemic injury and softening of the spinal cord, resulting in
cavitation. Another hypothesis is that of obstruction of CSF
flow due to local scarring, forcing the CSF into the central canal
through Virchow–Robin (VR) spaces; the dilated VR spaces
coalesce to form a syrinx.[17,18] Savoiardo proposed an alternate
hypothesis of syrinx formation. Neck movement‑induced
elongation of the spinal cord (fixed by adhesions) results in the
squeezing of the necrotic pulp or cystic spaces in the cord.[19]
The disruption of the spinal cord at areas of least resistance
causes upward extension of the syrinx; on rare occasions, the
syrinx can communicate with the subarachnoid space.[20]
Similar to TBM, TBRM might be a delayed hypersensitivity
reaction to tubercle bacilli protein. TBRM commonly develops
during the treatment of TBM. The likely explanation for
this paradox is the recovery of the delayed hypersensitivity
response with treatment. Enhanced immune reaction to
tubercular antigen, released during ATT due to mycobacterial
death, is a putative mechanism.[21]
To summarize, TB affects the spinal cord by four mechanisms:
1) obstruction of venous drainage associated with meningitis,
causing edema of the border zone, 2) vasculitis‑related or
thrombotic occlusion leading to ischemic myelomalacia, 3)
development of intramedullary tuberculomas with caseation
necrosis, and 4) rarely, vascular occlusion resulting in cord
infarction.
Clinical Presentation
Tuberculous involvement of the spinal cord is highly variable
in presentation, ranging from exclusively lower motor
neuron (LMN) or upper motor neuron (UMN) to mixed
UMN/LMN type of neurological involvement [Figure 2].
In a case series from northern India amongst 71 patients
with TBM, 33 (46.4%) had clinical features of the spinal
cord and nerve root involvement. Paraparesis was variably
of UMN (6 patients; 8.4%), LMN (10; 14%), and mixed
(6; 8.4%) type.[2]
In a retrospective study from South Africa, 274 patients with
spinal tuberculosis without bony involvement were assessed
amongst both HIV‑infected and HIV‑uninfected individuals.
The majority (76%) of patients were HIV‑infected.[22] Spinal
cord involvement frequently followed TBM as a paradoxical
reaction. Paradoxical reaction presenting as spinal involvement
Figure 2: Clinical phenotypes in spinal cord tuberculosis
was seen in 24% of HIV and 14% of HIV‑uninfected patients.
Radiculomyelitis was observed in 210 (77%) patients. Other
common manifestations included spondylitis (39%), subdural
abscess (15%), and intramedullary tuberculoma (12%).
Radiculomyelitis
TBRM is the most frequent manifestation of tuberculous spinal
cord involvement. TBRM is a broad term that is variably
employed to include tubercular myelitis, arachnoiditis, spinal
cord tuberculoma, spinal cord edema, or infarction.[21] It is this
variation in descriptive case reports that lends challenges to
estimates of its exact incidence. Inflammation of the arachnoid
membrane, called arachnoiditis, leads to the involvement of
nerve radicles encased by the arachnoid membrane as they
traverse out of the spinal canal. Clinically, arachnoiditis
presents as an LMN syndrome affecting the lower limbs
typically, with hypotonia, areflexia, radicular pain, paresthesia,
and in long‑standing situations, muscle atrophy. Bladder
and bowel involvement in the LMN pattern may also occur.
Lumbosacral radicles are most commonly involved, giving
rise to cauda equina syndrome. Frequently, conus syndrome
may also occur. This is clinically characterized by prominent
sphincter disturbances, perianal or saddle anesthesia,
and extensor plantar response with absent ankle reflexes,
representing an admixture of UMN and LMN features. TBRM
may appear at variable periods, even in patients who are
adequately treated.[21,23] It has also been described to develop
as a paradoxical response during therapy.[24] Multifocal
loculations and adhesive arachnoiditis are contributors to
syrinx development, treatment non‑response, and poor
outcome.[25]
Tubercular spinal abscess
Intramedullary spinal cord abscess is an exceedingly rare
presentation.[26‑28] Typical presentation is myelopathy, with
paraparesis of acute or subacute onset, sensory deficits, and
bowel/bladder involvement. The thoracic spinal cord is the
most affected, followed by the cervical and lumbar regions.
This predilection is determined by differential blood flow to

114 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023

 Garg, et al.: Spinal cord tuberculosis
the spinal cord, with thoracic regions receiving nearly 45%
of total cord blood flow. Diagnosis may be challenging as,
unlike the brain, ring enhancement on MRI may be minimal
to absent in the spinal cord.[29] Epidural and spinal subdural
tubercular abscesses may also occur, rarely without osseous
involvement.[30,31]
Syrinx formation
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Syringomyelia is an uncommon late complication of TBM
although both early and paradoxical development on ATT
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has been reported.[32] The development of syrinx following
TBM may be delayed by several years of symptom‑free
intervals. Early syrinx formation was first reported by Daif
et al. in two cases, developing after 11 days and 6 weeks
of the onset of tubercular meningitis.[33] In a series of
10 HIV‑infected patients with post‑tubercular syrinx formation,
syringomyelia developed after a median of 21 months after
initial diagnosis.[34] In contrast, in the same report, the authors
identified (via literature review) that the duration among
46% of HIV‑uninfected patients for post‑tubercular syrinx
development was longer (>4 years), compared to 8% of
HIV‑infected individuals.
Spinal cord infarction
Obliterative endarteritis or infective thrombosis of the spinal
vessels is a potential complication. However, spinal cord strokes
have been infrequently described. In one patient, paraparesis
developed after ATT for TBM, which was attributed to spinal
infarction, demonstrated on diffusion‑weighted imaging.[35]
Reports of spinal cord infarction in the setting of tubercular
meningitis are scarce. This is surprising, considering the
frequent occurrence of infarcts in the brain. Up to 41% of
patients with CNSTB display infarcts on imaging.[36] Whether
this discrepancy is due to the under‑recognition of spinal
infarcts, or whether spinal vessels are less susceptible to
obliterative endarteritis, is unclear.
Tuberculomas
Spinal tuberculomas, which may occur in the intramedullary,
extramedullary intradural, or extradural location are rare. It
is estimated that intramedullary spinal tuberculomas occur
in 2/100,000 cases of TB and 2/1,000 cases of CNS TB.[37]
There are above 100 individual case reports and a few small
case series indexed in PubMed that report intramedullary
spinal tuberculoma. The usual location is the thoracic
spinal cord; however, these have been reported from other
regions, including the cervical cord and conus. Literature on
extramedullary intradural tuberculomas is even scarcer. These
may mimic en plaque meningioma.[38] TBM may concur with
spinal cord tuberculoma, but more commonly, the latter follows
the former.[39] Tuberculomas of the spinal cord have been
shown to respond well to ATT, with or without concomitant
steroids.
Isolated myelitis
Tuberculosis is a rare cause of transverse myelitis (TM). Both
short‑segment and rarely, longitudinally extensive transverse
Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
myelitis (LETM) have been reported in the literature and
should enter the differential diagnosis for TM in countries in
which tuberculosis is endemic. In a review of 10 patients with
tuberculous LETM, extensive myelitis extending up to the
conus was described.[40] Most of these patients presented with
acute or subacute onset paraplegia with bladder involvement,
in association with fever, headache, or altered sensorium. The
duration from symptom onset to presentation ranged from
1 day to up to 2 months. Of six patients tested for aquaporin‑4
antibodies, all were negative.
Cervicodorsal involvement is the most frequent.[41] Several
case reports have described LETM in tuberculosis and
reported an association with neuromyelitis optica spectrum
disorders (NMOSD).[42,43] However, the current evidence is
tenuous and needs to be corroborated in larger case‑control
studies. The underlying pathogenesis is likely to be
immune‑mediated. Most patients demonstrate excellent clinical
and radiological responses to a combination of steroids and
ATT.
Vertebral tuberculosis with cord involvement
Osseous vertebral involvement may lead secondarily to
spinal cord involvement. The dorsal vertebral region has
increased predilection for this complication, considering
the narrow width of the spinal canal in this region, in
combination with the physiological kyphosis at the thoracic
column, which physically may push the tuberculous tissue
toward the cord.
Paraplegia in spinal osseous tuberculosis may be
early‑onset (paraplegia of active disease) or late‑onset (paraplegia
of healed disease), as per Hodgson’s classification.[44] Various
mechanisms underlying early‑onset paraplegia include
mechanical factors (compression via granulation tissue/
abscess, vertebral collapse/instability, gibbus formation),
apart from arachnoiditis, spinal cord infarction, myelitis, and
tuberculomas described above. Paraplegia of healed disease
may be due to bony factors such as severe kyphosis and
pachymeningitis.
Impact of HIV on presentation
Southeast Asia and Africa are endemic for TB‑HIV co‑infection.
Although the effects of this co‑infection are well studied in
pulmonary TB, there is a paucity of data regarding the clinical
manifestations and outcomes for extra‑pulmonary TB, and
lesser for spinal cord involvement. In non‑HIV patients, TBM
with concomitant spinal meningitis occurs in around 10%
of the patients.[45] This association is, however, stronger in
patients with HIV, with one report documenting this figure to be
around 48%.[22] TB‑HIV immune reconstitution inflammatory
syndrome (IRIS) in the spinal cord predominantly presents
as radiculomyelitis[46,47] though epidural abscess and spinal
tuberculomas have been documented as well.[1]
Modi et al. found that of 97 patients presenting with
non‑traumatic myelopathy in South Africa, 50% had HIV,
of whom 50% had concomitant tuberculosis.[48] Bhigjee
115
 Garg, et al.: Spinal cord tuberculosis
et al. similarly found tuberculosis to be the most common
cause of myelopathy among people living with HIV.[49] In
another similar large series from South Africa comprising
216 patients, acute‑onset myelopathy/cauda equina syndrome
in HIV‑positive patients was largely attributable to tuberculosis,
with non‑spondylitis forms being more common than
spondylitis at a lower CD4 count.[50] Marais et al. observed
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that syringomyelia was a relatively early manifestation (within
4 years) in HIV patients with neurological TB compared to
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non‑HIV patients, with relatively high mortality and poor
outcomes.[22] In another large case series from South Africa
involving 274 patients with spinal TB disease without
bony involvement on plain X‑ray, 76% of the patients were
co‑infected with HIV. The clinical presentation and outcomes
were similar in both HIV and non‑HIV cohorts. However,
compared to non‑HIV patients, patients with HIV more
commonly presented with radiculomyelitis had a significantly
higher incidence of paradoxical spinal cord disease, lower
rates of vertebral destruction in patients with concomitant
spondylitis, higher incidence of TBM, and a lower CSF
glucose.[22]
Paradoxical worsening in spinal cord tuberculosis
Paradoxical worsening, characterized by the worsening
of preexisting lesions or the development of new lesions,
complicates almost a third of patients with SCTB. The
paradoxical worsening is important as it may confuse
the clinicians and elicit doubts regarding the diagnosis and
possible drug resistance. Younger age, HIV infection, a
large burden of disease, mycobacterial smear positivity, and
elevated proteins are risk factors for paradoxical worsening.
Many unique features are associated with SCTB. Although
most paradoxical worsening in TBM is not of significant
long‑term clinical consequence, residual sequelae are
common among patients with SCTB. Large vessel infarcts
characterizing TBM are uncommonly recorded in autopsy
and radiological studies of SCTB. Imaging and CSF findings
may not correlate with clinical worsening in the spinal
cord.[51]
Three patterns of paradoxical worsening occur in patients with
spinal TB: 1. new onset spinal cord involvement in patients
with TB elsewhere, 2. worsening of existing spinal cord lesions,
and 3. remote worsening, for example, development of syrinx.
Patients with a large burden of diseases, such as military TB,
often present with new onset brain or spinal cord involvement.
The release of mycobacterial antigens on antimycobacterial
therapy is the putative mechanism. Almost 50% of patients with
SCTB worsen while on treatment. Preliminary data suggests
early worsening (less than 4 weeks of antimycobacterial
therapy) may be associated with younger age, female sex,
and associated with CSF changes. Late worsening, while on
therapy, is usually secondary to worsening tuberculomas within
or on the surface of the cord. Remote events such as syrinx
formation rarely complicate SCTB even after the completion
of antimycobacterial therapy.
116 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
Evaluation
History
SCTB generally occurs secondary to the spondylitic form
of tuberculosis, after rupturing of granuloma into the spinal
cord, or due to secondary seeding from TBM. The patient
may present with constitutional symptoms such as fever, night
sweats, weight loss, and loss of appetite. The patient may
complain of symptoms of radiculomyelitis, spinal meningitis,
bowel/bladder involvement, transverse myelitis, tuberculous
abscess, and syrinx formation. Headache, fever, vomiting, and
altered sensorium may suggest concurrent CNS involvement,
which warrants urgent attention. Other possible clues may
include hemoptysis, cough, breathlessness, lymphadenopathy,
and recurrent urinary tract infections. History of earlier TB
infection, known or possible TB exposure, and residence in
endemic regions must be elicited to further consolidate this
diagnosis.
CSF findings
CSF findings in patients with spinal cord disease are similar
to those seen in patients with TBM, with predominantly
lymphocytic leukocytosis (10–100 cells/µL), high protein,
and low CSF glucose [Table 1]. Patients with concomitant
HIV infection and those with early meningeal disease may
have predominant neutrophilic leukocytosis.[52] In patients
with subarachnoid block, CSF protein concentration may
be as high as 2 g/dL. CSF smear for AFB, TB cultures, and
newer molecular tests may help clinch the diagnosis. Isolated
forms of spinal tuberculosis such as arachnoiditis in the
absence of meningitis, may be more difficult to diagnose.
A targeted biopsy followed by microbiological, molecular, and
histopathological analyses may help in these cases.
Molecular Tests
Xpert MTB/Rif
Xpert MTB/Rif is a semi‑nested cartridge‑based polymerase
chain reaction (PCR), which provides information regarding
the presence of TB and rifampicin resistance within 2 h of the
sample being processed using the wild‑type mycobacterial
DNA through five partially overlapping fluorescent probes.
Limited diagnostic sensitivity (55–80%), difficult interpretation
of rifampicin resistance in cases of “very low load,” and the
availability of Xpert Ultra preclude its use in the diagnosis of
TBM and SCTB.[53]
Xpert Ultra
Xpert MTB/Rif Ultra, a cartridge‑based nested PCR test, is
now endorsed by the World Health Organization (WHO) for
the diagnosis of TBM.[54] Recently, two large prospective
studies carried out in the African cohorts found that the
sensitivity of CSF Xpert Ultra was significantly higher than
Xpert MTB/Rif and TBMGIT in the diagnosis of TBM in the
HIV population.[55,56] A Vietnamese study,[57] however, failed to
find a significant difference between CSF Xpert Ultra and CSF
Xpert MTB/Rif to diagnose TBM, which may be explained by
 Garg, et al.: Spinal cord tuberculosis
the fact that only 15% of the patients in the Vietnamese cohort
were HIV positive, who are expected to have higher bacillary
loads in the CSF.
Pyrosequencing
Pyrosequencing (PSQ) is real‑time PCR providing information
on extremely drug‑resistant (XDR)‑defining mutations within
6 h in the MTB genome. A small pilot study comprising
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13 patients with suspected TBM found that pyrosequencing,
when performed directly on the CSF samples, established the
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diagnosis in 84.6% of the patients compared to Xpert MTB/
Rif (15%) and TBMGIT (30.7%).[58] It detected six patients
with drug‑resistant TB, who were not detected by TBMGIT
culture. A further larger study conducted on 100 patients
with suspected TBM found that the diagnostic accuracy of
pyrosequencing was significantly higher compared to Xpert
MTB/Rif and TBMGIT (98% vs. 43% vs. 45%) in the diagnosis
of TBM.[58] Despite the limitations of the small sample size,
the retrospective nature of the study, lack of information about
HIV status, and the inherent limitations of the test (expensive,
requirement of molecular expertise), the ability of this test to
provide information on XDR‑defining mutations within 6 h
when performed directly on the CSF sample with excellent
diagnostic performance may have significant implications
on clinical outcomes, especially in regions endemic for
drug‑resistant TB.
Next‑generation sequencing
Newer molecular techniques such as targeted next‑generation
sequencing and whole‑genome sequencing are presently
being evaluated in the diagnosis of tuberculosis. Although
pyrosequencing provides information on resistance to isoniazid,
rifampicin, fluoroquinolones, and aminoglycosides, whereas
targeted next‑generation sequencing provides additional
information on resistance to pyrazinamide, ethambutol,
linezolid, bedaquiline, capreomycin, and clofazimine. A recent
study on 40 uncultured sputum samples found that tNGS
provided results for 39/40 samples with a significantly faster
time than phenotypic MGIT (3 vs. 21 days, P: 0.0068).[59]
The utility of these molecular techniques in TBM and spinal
cord involvement remains uncertain and may offer an exciting
avenue for research.
Imaging
Magnetic resonance imaging (MRI) is the most sensitive
tool for the anatomical assessment of the spinal cord and
surrounding nerve roots [Table 2]. In the setting of tuberculous
infection, MRI provides an accurate estimate of the extent
Table 1: Cerebrospinal fluid findings in various forms of spinal cord tuberculosis[22]
CSF findings Isolated
myelitis (n=19)
Neutrophil cell count [median (IQR) ×106/L] 0 (0‑0)
Lymphocyte cell count [median (IQR) ×106/L] 0 (0‑2)
Proteins (g/L) median (IQR) 0.8 (0.6‑1)
Glucose (mmol/L) median (IQR) 2.75 (2.5‑3.25)
Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
of the involved structures and associated complications.
Imaging abnormalities may present as enhancement along
the surface of the cord and thickening and enhancement
of the nerve roots, the presence of nodular enhancement
along the surface of the cord, edema within the cord, and
ring‑enhancing lesions within the substance of the cord.[2,60,61]
MRI is also a useful tool to assess epidural collection secondary
to adjacent tuberculous spondylodiscitis causing cord/nerve
compression [Figures 3 and 4]. Meningitis and arachnoiditis
are considered the two most common imaging findings, seen in
more than 50% of cases in patients with TBRM.[2,61] The most
important imaging differential for nodular enhancement along
the surface of the cord/nerve roots would be drop metastases
from an intracranial primary, whereas for intramedullary
tuberculoma, it would be focal metastasis. Table 3 enlists the
imaging differences between tuberculous and non‑tuberculous
myelitis, supported by Figures 5a and b.
Predictors of asymptomatic spinal cord involvement in
patients with TBM
Patients with TBM, especially with concomitant HIV
infection, are at a higher risk of developing cord involvement.
A gadolinium‑enhanced MR imaging of the spine in these
cases may help in detecting occult nodules/granulomas,
if present.[23] A pilot study performed by Srivastava et al.
found that 3/16 patients with TBM with no symptoms
suggestive of spinal cord involvement had evidence of spinal
arachnoiditis on MRI when performed within 1 month of
diagnosis of TBM. These patients had higher CSF protein
(520 ± 48.5 mg/dL vs. 300 ± 43.7 mg/dL) compared to those
without radiculomyelitis.[62] Wadia et al. noted patients with
TBM with no symptoms suggestive of spinal cord involvement
and showed the presence of exudates around the spinal cord and
nerve roots.[8] Gupta et al., in a prospective study comprising
71 consecutive patients of newly diagnosed TBM, found
that 11% had evidence of spinal meningitis on MRI despite
being asymptomatic.[2] Univariate analysis showed that high
CSF protein and a baseline‑modified Barthel index < 12 were
significant predictors of spinal cord involvement in patients
with TBM, though multivariate analysis did not find these
factors to be statistically significant.
Patients with osseous forms of spinal tuberculosis comprise yet
another important population, which may be at a higher risk
of cord involvement. Sae‑Jung et al., in a retrospective study
comprising 125 patients with spinal tuberculosis, found that
cord signal changes and notable Cobbs angle were significant
predictors of neurological deterioration.[63] A similar study
Epidural Subdural Meningitis/radiculitis without
abscess (n=12) abscess (n=20) epidural/subdural abscess (n=84)
0 [0‑0] 38 (4‑202) 2 (0‑16)
0 (0‑12) 32 (6‑320) 28 (5‑70)
3.9 (1‑6) 5.1 (4‑20) 2.2 (1‑4.4)
2.75 (2‑3.75) 3 (1.25‑4)
117
 Garg, et al.: Spinal cord tuberculosis
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a c d e

f g h j
Figure 3: Imaging findings in spinal tuberculosis. Sagittal and axial imaging of the spine (T2‑weighted images a, b, e, f, g, i, j and post‑contrast
T1‑weighted c, d, h) showing thickening and nodularity along the cauda equina nerve roots (a and b) associated with post‑contrast enhancement
(c and d) suggestive of radiculitis. A well‑defined oval, partially cystic lesion (e) is seen involving the thoracic cord with edema out of proportion to the
lesion suggestive of an evolving abscess. Image (f) demonstrates a long‑segment cord hyperintensity and expansion suggestive of myelitis associated
with the syrinx. Multiple T2W hypointense lesions involving the cord with mild surrounding edema (g) suggest the presence of multiple intramedullary
tuberculomas, whereas nodular and ring‑like enhancement along the surface of the cord suggest meningeal inflammation and tuberculomas (h).
Image (i) demonstrates long‑segment myelitis, whereas cord compression secondary to tuberculous spondylodiscitis‑associated extradural abscess
is seen in image (j)

118 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023

 Garg, et al.: Spinal cord tuberculosis
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a b c d
Figure 4: Sagittal imaging of the cervicothoracic spine (b) (T2‑weighted images a and c and post‑contrast T1‑weighted images b and d) demonstrate
inflammatory exudates along the dorsal aspect of the thoracic cord (a) causing anterior displacement of the cord with cord hyperintensity (a) and
post‑contrast enhancement (b). Image (c) demonstrates scalloping of the thoracic cord with resultant cord edema secondary to chronic arachnoiditis.
No obvious post‑contrast surface enhancement is seen (d); however, there is an enhancing parenchymal granuloma involving the cervical cord

from India found that kyphosis >30 degrees, cord edema, and
canal encroachment (>50%) were significant predictors of
neurological deficit.[64] Wang et al. found that elderly patients
with cervical and lumbar vertebral involvement were more at
risk of developing neurological disturbances.[65]
To summarize, in patients with TBM, high CSF protein is
an important predictive marker of asymptomatic spinal cord
disease. Concurrent spine screening by gadolinium‑enhanced
MRI may be helpful in these cases. In those with osseous spinal
cord involvement, old age, kyphosis of more than 30 degrees,
and cord edema were important predictors of neurological
deterioration.
Treatment of Spinal Cord TB
What do guidelines say?
The established guidelines for the management of CNS
TB largely focus on TBM.[5,6,66‑68] There are no specific
recommendations to treat SCTB. Management principles
for TBRM are derived from the treatment guidelines for
CNS TB.
The WHO guidelines for the treatment of drug‑susceptible CNS
TB recommend the administration of ATT in two phases.[66]
The initial 2 months of the intensive phase are followed by
a continuation phase of 7 or 10 months. In the intensive
phase, the patient receives a combination of four first‑line
drugs (isoniazid, rifampicin, pyrazinamide, and streptomycin).
In the continuation phase, 2‑drug (isoniazid and rifampicin)
ATT is given. The British Infection Society (BIS) and National
Institute for Health and Care Excellence (NICE) guidelines
also recommend at least 12 months of ATT for all forms of
CNS TB; isoniazid, rifampicin, pyrazinamide, and ethambutol
for initial 2 months followed by isoniazid and rifampicin
for 10 months.[68] The NICE guidelines advocate managing
tuberculous involvement of the spinal cord as CNS TB. The
American Thoracic Society (ATS) recommends 9–12 months
of ATT for meningeal involvement; isoniazid, rifampicin,
pyrazinamide, and ethambutol for the initial 2 months followed
by isoniazid and rifampicin for 7–10 months.[6] Similarly,
the Index‑TB guidelines in India recommend 2 months of
isoniazid, rifampicin, pyrazinamide, and ethambutol followed
by isoniazid, rifampicin, and ethambutol for 7 months for the

Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023 119

 Garg, et al.: Spinal cord tuberculosis

Table 2: Imaging findings in various forms of spinal tuberculosis

Categories T2W T1W Post‑contrast T1W Diffusion‑weighted
imaging
Radiculitis Thickening and clumped nerves Thickening and clumped nerves Diffuse nerve enhancement in the ‑
acute phase usually accompanied
by leptomeningeal enhancement
(the most common finding)
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Myelitis Long‑segment cord hyperintensity Long segment cord iso/hypointensity Patchy areas of cord enhancement ‑
with expansion in the acute phase with expansion in the acute phase in the acute phase
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Syringomyelia Long‑segment central Long‑segment central hypointensity Rare ‑

hyperintensity with CSF signal
intensity
Parenchymal/ Well‑defined oval to rounded Well‑defined lesions iso/hypointense Nodular enhancement in smaller ‑
surface lesions, central hyperintensity to cord parenchyma lesions, ring enhancement in larger
tuberculomas in the acute phase, central lesions
hypointensity in the chronic phase
Parenchymal Well‑defined lesions with central Iso to hypointense to cord Ring enhancement Central diffusion
Abscess hyperintensity and extensive parenchyma restriction present
surrounding cord edema and
expansion
Vertebral TB Cord compression secondary to an Cord compression secondary to an The compressed cord may show ‑
with secondary epidural abscess, cord may show epidural abscess, cord may show enhancement in the acute phase
cord involvement hyperintensity hypointensity
Spinal cord Segmental cord hyperintensity in The involved area may be iso/ Enhancement is seen in the Involved areas show
infarction arterial territory distribution hypointense to the cord parenchyma subacute phase diffusion restriction

Table 3: Imaging differences between tuberculous vs. non‑tuberculous myelitis

MRI
Long segment cord
hyperintensity on T2W
sagittal sequence
Cord hyperintensity on
T2W axial sequence
Granulomas along the
surface of the cord
Granulomas involving
the substance of the cord
Enhancement pattern of
cauda equina nerve roots
Tuberculous myelitis
Common, often associated with surface
enhancement
Commonly involves the entire cross‑section of
the cord
Common
Larger granulomas may show diffusion restriction
Common and often multiple
Nerves can show both smooth or nodular
enhancement depending on the disease burden
Non‑tuberculous myelitis
Common, surface enhancement is less common (examples
include viral myelitis, arachnoiditis, dural arteriovenous fistula,
neuromyelitis optica spectrum disorder, cord infarction)
Commonly consists of a portion of the cross‑section (example
includes anterior spinal artery infarct, which affects anterior
two‑thirds of the cord, small eccentric hyperintensities are seen in
multiple sclerosis, posterior column involvement with subacute
combined degeneration of cord and tabes dorsalis)
Less common involvement of the entire cross‑section of the cord
(examples include myelitis related to infections such as melioidosis)
Uncommon (intracranial drop metastasis may mimic granulomas)
Diffusion restriction is not common
Uncommon and often solitary (examples metastasis and
cysticercosis)
Smooth enhancement is more common (for example, acute
inflammatory demyelinating polyneuropathy)
Nodular enhancement is rare (for example, drop metastasis)

treatment of CNS TB.[5] Whether patients with extensive spinal
arachnoiditis will benefit from prolonged ATT is unclear.
Role of ATT in spinal cord TB
TB myelitis
Neurological insufficiency in TB myelitis is secondary to
inflammatory activity.[1] Previous reports suggest an excellent
response of TB myelitis to a combination of ATT (isoniazid,
rifampicin, pyrazinamide, ethambutol/streptomycin) and
adjuvant steroids.[24,69,70] Early initiation of ATT is important.
In two different series, involving four cases of longitudinally
extensive transverse myelitis (LETM) because of TB, medical
therapy alone resulted in a favorable outcome.[71,72] In a recent
review of 10 reported cases of tubercular LETM, treatment
with ATT and steroids resulted in clinical and radiological
improvement.[40] Patients with damaged anterior horn cells
have poor recovery with ATT.[73] The patient should receive a
combination ATT for at least 9–12 months. Further extension
of therapy in some cases is dictated by an amalgamation of
clinical, radiological, and other supportive evaluations that
suggest active disease, although guidelines remain unclear
on this issue.
Corticosteroids and hyaluronidase may be an adjuvant therapy
to ATT. Steroids are often used as a pulse therapy in patients
with severe concerns, such as LETM or severe arachnoiditis,

120 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023

 Garg, et al.: Spinal cord tuberculosis

a
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Figure 5: (a) Imaging findings in non‑tuberculous myelitis. Long‑segment T2W hyperintensity on sagittal imaging of the cord. Image a demonstrates
heterogeneous cord hyperintensity associated with swelling seen with melioidosis of the cord. Image b1 shows long‑segment cord hyperintensity
extending up to the conus. Digital subtraction angiography (image b2) demonstrates an abnormal tortuous vessel along the surface of the cord
confirming the diagnosis of a dural arteriovenous fistula. Image c1 shows a long‑segment cord hyperintensity in a patient with hyperacute paraplegia
raising suspicion for cord infarct. Diffusion restriction is seen on diffusion imaging (c2) confirming the diagnosis. (b) Image a1 shows localized T2W
cord hyperintensity with the scalloping of the cord suggestive of arachnoiditis. During surgery, the thecal sac was found to contain multiple cysticercal
cysts. Image a2 shows central cord signal changes in the same patient secondary to cysticercal arachnoiditis. Image b demonstrated short‑segment
cord T2W cord hyperintensity in a patient with disseminated CMV infection. Images c1 and c2 show a solidary cysticercus granuloma with a ring‑like
post‑contrast enhancement. The lesion showed significant regression with steroids. Image d demonstrates smooth enhancement of the cauda equina
nerve roots in a patient with acute inflammatory demyelinating polyneuropathy; whereas nodular enhancement is seen (image e) in a patient with
leptomeningeal carcinomatosis

or large tuberculomas with significant edema, causing Intradural extramedullary tuberculomas

paraparesis, as per the literature. Regimens are variable, with
steroid durations ranging from 8 weeks to 6 months.
TB spinal arachnoiditis
Treatment of TB spinal arachnoiditis may be medical
or surgical. Medical therapy remains the mainstay of
management.[24,69] As arachnoiditis is diffuse, surgery may be
of limited role. If there is a resistant strain, drugs are modified
according to the sensitivity pattern.
Evidence shows that medical therapy alone will be insufficient
for the management of spinal intradural extramedullary
tuberculoma. ATT combined with surgical excision yields
excellent results.[24,69,74,75]
Intramedullary tuberculoma and abscess
Before the MRI era, surgical excision of the intramedullary
lesion was the technique of choice for both diagnosis and
treatment. Currently, ATT is the preferred treatment for

Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023 121

 Garg, et al.: Spinal cord tuberculosis
intramedullary tuberculoma and abscess.[2,21,24,28] Adjunctive
corticosteroid therapy results in a favorable outcome. With
early diagnosis and treatment, one can avoid complications
and unnecessary surgical intervention. Surgery is indicated
in the management of spinal intramedullary tuberculoma for
1) a large lesion with rapid progression of neurological deficits,
2) deterioration of neurological status despite medical therapy,
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3) inconclusive neuroimaging findings, and 4) paradoxical
increase in the size of the lesion after ATT.[75‑77]
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Therapy for spinal cord paradoxical worsening
Corticosteroids are the main immunomodulatory therapy in
CNS TB. The evidence is largely derived from patients with
TBM without HIV infection. Importantly, corticosteroid
therapy decreases mortality without impact on disability in
TBM. Corticosteroids probably beneficially impact SCTB as
well, as close to a third of TBM patients have concomitant
spinal cord involvement. However, no randomized trials
have evaluated the role of steroids in spinal TB so far.
The percentage of paradoxical worsening in SCTB is
higher than in TBM. Often paradoxical worsening happens
despite receiving adequate steroids. The role of adjunctive
immunomodulatory therapy in these individuals is unclear.
Adjunctive thalidomide therapy at low doses (3–5 mg/kg/day)
produced a favorable response in two children with tuberculous
mass lesions involving the spinal cord.[78] The duration of
thalidomide therapy used in these patients was 8 weeks
although some advocate shortened regimens of less than a
month. However, longer durations have been used in children
with optic neuritis (median 2, interquartile range [IQR]
1.3–7.3 months).[78] Painful paresthesia may develop with
longer regimens due to the development of sensory axonal
neuropathy. Infliximab, a tumor necrosis factor‑alpha inhibitor
has been successfully used in three patients with paradoxical
worsening involving the brain and spinal cord.[79] Larger studies
Table 4: Studies on the use of fibrinolysis for tuberculous arachnoiditis
Study Study design No. of Patients
Gourie‑Devi Case series 14 patients with spinal
et al., 1980[80] TBA
Sodhani et al., Prospective 25 patients with spinal
1986[82] controlled study TBA
Gourie‑Devi and Non‑randomized 66 patients; 39 were
Satishchandra, clinical trial given ITHA (group A)
1991[81] and 27 were not given
ITHA (group B). Both
groups received standard
ATT and steroid therapy.
Samal et al., Retrospective 19 patients with spinal
2020[83] TBA; 11°CA; 5 had both
ATT=Anti‑tubercular therapy, ITHA=intrathecal hyaluronidase, OCA=optico‑chiasmatic arachnoiditis, TBA=tuberculous arachnoiditis
122 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
evaluating the benefits of steroid therapy and other alternative
agents are needed.
Evidence for other interventions
Fibrinolysis
The use of hyaluronidase as an adjuvant in the treatment of
tuberculous arachnoiditis has been described in non‑randomized
studies in the 1980s and 90s [Table 4].[80‑82] In a recent
retrospective description of the use of intrathecal hyaluronidase
among patients with spinal tubercular arachnoiditis or
optico‑chiasmatic arachnoiditis, weekly hyaluronidase for
10 weeks was administered, besides ATT and steroids. Of
19 patients with spinal arachnoiditis, 10 were independent
at the completion of therapy.[83] The benefits of fibrinolysis
reported from observational literature need augmentation by
further evaluation in a randomized trial setting.
Surgical management
Intramedullary tuberculomas, intra‑conal abscess
Patients with intramedullary TB can present with a mass‑like
presentation mimicking intramedullary tumor, sometimes
like an intramedullary abscess. The aim of surgery is to
perform safe surgical excision of the lesion without causing
new neurological deficits. The surgical procedure involves
laminectomy done at the level of the lesion. The dura is opened,
and CSF is let out to allow the pulsations of the cord. A midline
myelotomy is performed after identifying the lesion. After
identifying the lesion, a plane is developed to safely excise the
lesion. Intraoperative neuromonitoring helps in safe surgical
excision. The pia mater is closed by welding technique and
the dura is closed primarily.
Syringomyelia
The best management for post‑TB syringomyelia is
unclear. Often patients are treated by placing a
Fibrinolysis used Outcomes
THA 500‑3000 IU every Near normalcy in 5 patients, good recovery in
week to fortnight over 6, fair recoveries in 3 during follow‑up over 5
3-16 weeks to 30 months based on ‘functional deficit scale.’
ITHA 1500 IU weekly No difference between groups clinically, in
for 10 weeks compared CSF parameters and myelogram
with prednisolone therapy
(40‑60 mg for 6 weeks) in
sex‑matched patients
ITHA 1500 IU every 10‑14 Significant decrease in final CSF protein level
days based on CSF protein in group A compared to group B. Significant
levels: average of 5.9 decrease in mean disability and functional
injections (range 2‑14) deficit in group A compared to group B.
Initial treatment of Of 19 patients with spinal TBA, 10 were
arachnoiditis with IV independent at end of therapy; patients in
methylprednisolone. In case whom ITHA was initiated within 12 weeks of
of ‘non‑response,’ ITHA the onset of symptoms had better outcomes
was given weekly (1500 IU
per dose) for 10 weeks
 Garg, et al.: Spinal cord tuberculosis

syringe‑subarachnoid shunt with mixed results.[24] A focal meningitis, 29 (14.6%) had spinal tubercular meningitis, and
laminectomy is performed. The dura and the arachnoid are among those who completed therapy, 84% were dependent for
opened. A small myelotomy is done in the center of the syrinx their activities of daily living.[71]
to open it. One of the shunt tubes is gently guided cranially or
Unique anatomical location within a restricted space, complex
caudally into the syrinx. The other end of the tube is placed
vascularity, and close proximity of neural tracts predispose to
in the subarachnoid cavity beneath the dentate ligament. This
poor outcomes. There may be several further reasons for poor
helps to keep the shunt in place. The dura is then closed. Spinal
outcomes, mainly engendered by the underlying pathology.
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cord function, specifically motor evoked potential (MEP),

The development of syrinx/cavitation and myelomalacia
somatosensory evoked potential (SSEP), and D waves are
leads to permanent sequelae.[41] Additionally, in patients with
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monitored throughout the procedure to minimize the risk of

postoperative neurological deficit.
Outcomes in spinal cord tuberculosis
Outcomes among patients with spinal cord involvement in TB
are variable and predictors of outcomes are unclear.
Large studies reporting outcomes of various types of spinal cord
involvement are rare. Most available studies are single‑center
experiences, retrospective in nature, and document outcomes
with radiculomyelitis, the commonest presentation. In the
available studies [Table 5], poor outcomes were reported
in up to 35–85% of the study population despite standard
mycobacterial therapy and steroids. This is markedly higher
compared to any other form of tuberculosis, including TBM.
In one study of 71 patients with TBM, 33 (46.4%) had
spinal cord and/or nerve root involvement clinically.
MRI demonstrated meningeal enhancement (40; 56.3%),
myelitis (16; 22.5%), tuberculoma (4; 5.6%), CSF loculation
(4; 5.6%), myelomalacia (3; 4.2%), and syrinx (2; 2.8%).
Radiculomyelitis was determined to be associated with
high CSF protein (>250 mg/dL) and was associated with
unfavorable outcomes (modified Barthel index <12 or death)
at 6 months.[2] In a recent series of 198 patients with tubercular
tuberculous myelitis, involvement of the anterior horn cells
may portend a poor prognosis in terms of motor recovery.[73]
LETM, which frequently spans nearly the entire spinal cord
length, is associated with poorer recovery. In addition, we
hypothesize that some of these patients are developing spinal
cord ischemia, which remains under‑recognized, and may
portend a poor prognosis.
Future directions
There are many avenues for focused research in spinal cord
TB. A discrepancy between what the guidelines enunciate
and what neurologists practice at the ground level in India is
reflective of the multiple lacunae that exist.[85]
The most striking concern with SCTB is poor long‑term
outcomes. At least a third of patients remain severely
disabled while the proportion is less than 15% in TBM.[86]
A long‑sighted, multi‑pronged approach is needed to reduce
this disability in SCTB [Figure 6]. Firstly, there is an acute
need for the documentation of long‑term outcomes with
antimycobacterial therapy and steroids in large multicentric
cohorts of patients. The pleomorphic presentations and
varied anatomical involvements mandate such large studies.
Secondly, the mechanism of long‑term sequelae in SCTB is

Table 5: Outcomes of spinal cord tuberculosis (reporting studies with at least 20 patients; studies chiefly reporting on
tuberculous spondylodiscitis were excluded
Study Number of Types of HIV infection Paradoxical Adjunctive Follow‑up
patients involvement worsening therapy
Gupta, 2015, 71 patients Spinal cord and Unknown Eleven (26.82%) All received Good outcome at 6 months
Single‑center spinal nerve root 8 weeks of defined as modified
prospective study, involvement steroids Barthel’s Index of ≥12 in
India[2] 27 (66%) patients
Marais, 2018, 274 patients, The majority had 209/274 69 patients had Details not Among the 89 patients
Retrospective 89 followed up spinal disease patients (76%) paradoxical available who followed up at 9
single‑center, South at the end of 9 without bony worsening (62 in months, 38 (44%) were
Africa[22] months involvement HIV infected and 7 able to walk
among uninfected)
Liu, 2018, 52 patients All patients have All HIV 26 patients All patients The overall outcome
retrospective prominent spinal uninfected (52%); median received steroids was unclear; none of the
single‑center, cord involvement duration 30 days patients died; outcomes
China[51] (isolated after initiation of were similar regardless
spondylitis was therapy of whether patients
excluded) developed paradoxical
worsening or not
Goyal et al., 2019, A total of 244 All patients had None Not known 93.4% of the Poor outcome defined by
Ambispective patients with arachnoiditis total cohort modified Rankin scale ≥3
single‑center cohort CNS TB; 25 had received steroids in 21 patients (84%).
study, India[84] arachnoiditis

Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023 123

 Garg, et al.: Spinal cord tuberculosis
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Figure 6: Future direction in spinal cord tuberculosis
unclear. Although the thick characteristic gelatinous exudative
inflammation is responsible for adhesive complications such
as arachnoiditis, the molecular mechanisms responsible are
not elucidated.
Large vessel infarctions are uncommon in TB of the spinal
cord. Transmural inflammation of the vessels with cellular
infiltration, intimal thickening, and subintimal proliferation
with or without granulomas are central to pathogenesis for
TBM.[12] Whether similar mechanisms are operational in
SCTB needs to be evaluated. Vascular endothelial growth
factor (VEGF) and matrix metalloproteinase‑9 play a major
role in the pathogenesis of TBM.[87‑89] Role of the above
mediators in SCTB needs to be studied. Only a proportion of
patients with disseminated TB develop adhesive arachnoiditis.
Variations encoding a promoter region in the leukotriene
A4 hydrolase (LTA4H) gene, a critical link in balancing the
pro and anti‑inflammatory eicosanoids appear to predict
hyper‑inflammatory and hypo‑inflammatory phenotypes and
the subgroup of patients who benefit the most from steroid
therapy in TBM.[90‑92] Whether this finding can be extended to
SCTB is not clear. The degree of reduction of CSF tryptophan
appears to predict survival in TBM. Both mycobacterial factors
and host genome single nucleotide polymorphisms appear
to play a strong role. Whether tryptophan metabolism plays
such a critical role in SCTB is undetermined.[93,94] Finally,
whether adjunctive agents such as tumor necrosis factor
alpha‑blockers such as infliximab and thalidomide and other
immunomodulatory strategies can further improve outcomes
of patients who worsen despite antimycobacterial therapy
and steroids needs to be studied. The role of aspirin and
antifibrinolytics in the management of TBRM also should be
studied in randomized trials.
Conclusions
Diagnosis and management of patients with spinal cord
tuberculosis are difficult. Clinical presentations can be
diverse and paradoxical worsening frequently occurs. Often,
microbiological confirmation and drug sensitivity are lacking,
making the diagnosis of resistant TB challenging. Drug
124 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
resistance may be presumed in a patient who shows suboptimal
response or worsening to the first‑line regimen, in the absence
of drug sensitivity testing. The subsequent regimens should be
as per national guidelines for resistant TB.
Currently, the management of SCTB is not different from
TBM. Studies evaluating the underlying pathophysiology and
efficacy of strategies for augmented mycobacterial killing and
controlling host inflammation in SCTB are urgently needed.
Acknowledgments
We would like to thank our institutes for their support.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Garg RK, Malhotra HS, Gupta R. Spinal cord involvement in tuberculous
meningitis. Spinal Cord 2015;53:649‑57.
2. Gupta R, Garg RK, Jain A, Malhotra HS, Verma R, Sharma PK. Spinal
cord and spinal nerve root involvement (myeloradiculopathy) in
tuberculous meningitis. Medicine (Baltimore) 2015;94:e404.
3. Rajasekaran S, Soundararajan DCR, Shetty AP, Kanna RM. Spinal
tuberculosis: Current concepts. Global Spine J 2018;8:96S‑108S.
4. Garg D, Goyal V. Spinal tuberculosis treatment: An enduring bone of
contention. Ann Indian AcadNeurol 2020;23:441‑8.
5. Sharma SK, Ryan H, Khaparde S, Sachdeva KS, Singh AD, Mohan A,
et al. Index‑TB guidelines: Guidelines on extrapulmonary tuberculosis
for India. Indian J Med Res 2017;145:448‑63.
6. Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A,
et al. Official American thoracic society/centers for disease control
and prevention/infectious diseases society of america clinical practice
guidelines: Treatment of drug‑susceptible tuberculosis. Clin Infect Dis
2016;63:e147‑95.
7. WHO | Guidelines for treatment of tuberculosis. WHO.Available from:
https://www.who.int/tb/publications/2010/9789241547833/en/.
8. Wadia NH, Dastur DK. Spinal meningitides with radiculo‑myelopathy:
Part 1. Clinical and radiological features. J Neurol Sci 1969;8:239‑60.
9. Horsley V. A Clinical lecture on chronic spinal meningitis: Its differential
diagnosis and surgical treatment. Br Med J 1909;1:513‑7.
10. Ransome GA, Montiero ES. A rare form of tuberculous meningitis. Br
Med J 1947;1:413.
11. Dastur HM. Diagnosis and neurosurgical treatment of tuberculous
disease of the CNS. Neurosurg Rev 1983;6:111‑7.
12. Dastur DK, Manghani DK, Udani PM. Pathology and pathogenetic
mechanisms in neurotuberculosis. Radiol Clin North Am 1995;33:733‑52.
13. Dastur D, Wadia NH. Spinal meningitides with radiculo‑myelopathy. 2.
Pathology and pathogenesis. J Neurol Sci 1969;8:261‑97.
14. Vidyasagar C, Murthy HK. Spinal tuberculosis with neurological
deficits. Natl Med J India 1996;9:25‑7.
15. Dastur HM. A tuberculoma review with some personal experiences. I.
brain. Neurol India 1972;20:11126.
16. Dastur DK. The pathology and pathogenesis of tuberculous
encephalopathy and myeloradiculopathy: A comparison with allergic
encephalomyelitis. Childs Nerv Syst 1986;2:13‑9.
17. Caplan LR, Norohna AB, Amico LL. Syringomyelia and arachnoiditis.
J Neurol Neurosurg Psychiatry 1990;53:106‑13.
18. Fehlings MG, Bernstein M. Syringomyelia as a complication of
tuberculous meningitis. Can J Neurol Sci 1992;19:84‑7.
19. Savoiardo M. Syringomyelia associated with postmeningitic spinal
arachnoiditis. Filling of the syrinx through a communication with the
subarachnoid space. Neurology 1976;26:551‑4.
20. Giménez‑Roldán S, Esteban A Benito C. Communicating syringomyelia
 Garg, et al.: Spinal cord tuberculosis
following cured tuberculous meningitis. J Neurol Sci 1974;23:185‑97.
21. Hernández‑Albújar S, Arribas JR, Royo A, González‑García JJ,
Peña JM, Vázquez JJ. Tuberculousradiculomyelitis complicating
tuberculous meningitis: Case report and review. Clin Infect Dis
2000;30:915‑21.
22. Marais S, Roos I, Mitha A, Mabusha SJ, Patel V, Bhigjee AI. Spinal
tuberculosis: Clinicoradiologicalfindings in 274 patients. Clin Infect Dis
2018;67:89‑98.
23. Chang KH, Han MH, Choi YW, Kim IO, Han MC, Kim CW.
Downloaded from http://journals.lww.com/annalsofian by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hC
Tuberculousarachnoiditis of the spine: Findings on myelography, CT,
and MR imaging. AJNR Am J Neuroradiol 1989;10:1255‑62.
24. Freilich D, Swash M. Diagnosis and management of tuberculous
ywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 06/30/2023
paraplegia with special reference to tuberculousradiculomyelitis.
J Neurol Neurosurg Psychiatry 1979;42:12‑8.
25. Kaynar MY, Koçer N, Gençosmanoğlu BE, Hanci M. Syringomyelia‑‑as
a late complication of tuberculous meningitis. ActaNeurochir (Wien)
2000;142:935‑8.
26. Tacconi L, Arulampalam T, Johnston FG, Thomas DGT. Intramedullary
spinal cord abscess: Case report. Neurosurgery 1995;37:817‑9.
27. Liu J, Zhang H, He B, Wang B, Niu X, Hao D. Intramedullary
tuberculoma combined with abscess: Case report and literature review.
World Neurosurg 2016;89:726.e1‑4.
28. BIndira D. Spinal intramedullary tuberculoma and abscess : A rare
cause of paraparesis. Neurol India 2002;50:494.
29. Chittem L, Bommanakanti K, Alugolu R. ‘Precipitation sign’: A new
radiological sign for spinal intramedullary tubercular abscess. Spinal
Cord 2014;52(Suppl 1) S1‑2.
30. Arora S, Kumar, R. Tubercular spinal epidural abscess involving the
dorsal‑lumbar‑sacral region without osseous involvement. J Infect Dev
Ctries 2011;5:544‑9.
31. Ozates M, Ozkan U, Kemaloglu S, Hosoglu S, Sari I. Spinal subdural
tuberculous abscess. Spinal Cord 2000;38:56‑8.
32. Pandey S, Nayak R, Mehndiratta MM. Early syringomyelia in tubercular
meningitis: Arare occurrence. J Neurol Res 2013;3:46‑8.
33. Daif AK, Rajeh S, Ogunniyi A, Boukai A, Tahan A. Syringomyelia
developing as an acute complication of tuberculous meningitis. Can J
Neurol Sci 1997;24:73‑6.
34. Marais S, Roos I, Mitha A, Patel V, Bhigjee AI.
Posttubercularsyringomyelia in HIV‑infected patients: A report of
10 cases and literature review. J Neurol Sci 2018;395:54‑61.
35. Koplay M, Erdogan H, Sivri M, Nayman A, Paksoy Y. Unusual reason
of spinal cord infarction: Tuberculousmeningitis. Acta Neurol Belg
2016;116:87‑9.
36. Salvador GLO, Basso ACN, Barbieri PP, Leitao CA, Teixeira BCA,
Neto AC. Central nervous system and spinal cord tuberculosis:
Revisiting an important disease. Clin Imaging 2021;69:158‑68.
37. Sardana V, Shringi P. Intramedullary tuberculoma of the spinal cord,
clinical features & imaging: Possibility of early diagnosis with imaging?
Indian J Tuberc 2020;67:346‑8.
38. Ozek E, Iplkcioglu AC, Erdal M. Intraduralextramedullarytuberculoma
mimicking en plaque meningioma. Neurol India 2009;57:211.
39. Jeong D‑K, Kwon Y‑M. Intraduralextramedullarytuberculoma of
the spinal cord following tuberculous meningitis. Korean J Spine
2015;12:107‑10.
40. Md Noh MSF, Bahari N, Abdul Rashid AM. Tuberculousmyelopathy
associated with longitudinally extensive lesion: Aclinicoradiological
review of reported cases. J Clin Neurol 2020;16:369‑75.
41. Wasay M, Arif H, Khealani B, Ahsan, H. Neuroimaging of tuberculous
myelitis: Analysis of ten cases and review of literature. J Neuroimaging
2006;16:197‑205.
42. Zatjirua V, Butler J, Carr J, Henning F. Neuromyelitisoptica and
pulmonary tuberculosis: A case‑control study. Int J Tuberc Lung Dis
2011;15:1675‑80.
43. Li R, Zhong X, Qiu W, Wu A, Dai Y, Lu Z, et al. Association between
neuromyelitisoptica and tuberculosis in a Chinese population. BMC
Neurol 2014;14:33.
44. Hodgson AR, Yau A. Pott’s paraplegia: A classification based upon the
living pathology. Spinal Cord 1967;5:1‑16.
45. Seddon JA, Hesseling AC, Marais BJ, Jordaan A, Victor T, Schaaf HS.
The evolving epidemic of drug‑resistant tuberculosis among children in
Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
Cape Town, South Africa. Int J Tuberc Lung Dis 2012;16:928‑33.
46. Asselman V, Thienemann F, Pepper DJ, Boulle A, Wilkinson RJ,
Meintjes G, et al. Central nervous system disorders after starting
antiretroviral therapy in South Africa. AIDS 2010;24:2871‑6.
47. Pepper DJ, Schomaker M, Wilkinson RJ, de Azevedo V, Maartens G.
Independent predictors of tuberculosis mortality in a high HIV
prevalence setting: A retrospective cohort study. AIDS Res Ther
2015;12:35.
48. Modi G, Ranchhod J, Hari K, Mochan A, Modi M. Non‑traumatic
myelopathy at the Chris Hani Baragwanath Hospital, South Africa‑‑the
influence of HIV. QJM 2011;104:697‑703.
49. Bhigjee AI, Madurai S, Bill PL, Patel V, Corr P, Naidoo MN, et al.
Spectrum of myelopathies in HIV seropositive South African patients.
Neurology 2001;57:348‑51.
50. Candy S, Chang G, Andronikou S. Acute myelopathy or caudaequina
syndrome in HIV‑positive adults in a tuberculosis endemic setting:
MRI, clinical, and pathologic findings. AJNR Am J Neuroradiol
2014;35:1634‑41.
51. Liu Y, Wang Z, Yao G, Lu Y, Hu Z, Yao H, et al. Paradoxical reaction in
HIV‑negative tuberculous meningitis patients with spinal involvement.
Int J Infect Dis 2019;79:104‑8.
52. Vinnard C, Macgregor RR. Tuberculousmeningitis in HIV‑infected
individuals. Curr HIV/AIDS Rep 2009;6:139‑45.
53. Ajbani K, Kazi M, Tornheim J, Naik S, Soman R, Shetty A, et al.
Pyrosequencing to resolve discrepant Xpert MTB/RIF and mycobacterial
growth indicator tube 960. Lung India 2018;35:168‑70.
54. Khonga M, Nicol MP. Xpert MTB/RIF Ultra: Agamechanger for
tuberculous meningitis? Lancet Infect Dis 2018;18:6‑8.
55. Cresswell FV, Tugume L, Bahr NC, Kwizera R, Bangdiwala AS,
Musubire AK, et al. Xpert MTB/RIF Ultra for the diagnosis of
HIV‑associated tuberculous meningitis: Aprospective validation study.
Lancet Infect Dis 2020;20:308‑17.
56. Bahr NC, Nuwagira E, Evans EE, Cresswell FV, Bystrom PV,
Byamukama A, et al. Diagnostic accuracy of Xpert MTB/RIF ultra for
tuberculous meningitis in HIV‑infected adults: A prospective cohort
study. Lancet Infect Dis 2018;18:68‑75.
57. Donovan J, Thu DDA, Phu NH, Dung VTM, Quang TP, Nghia HDT,
et al. Xpert MTB/RIF ultra versusXpert MTB/RIF for the diagnosis of
tuberculous meningitis: A prospective, randomised, diagnostic accuracy
study. Lancet Infect Dis 2020;20:299‑307.
58. Ajbani K, Kazi M, Agrawal U, Jatale R, Soman R, Sunavala A, et al.
Evaluation of CSF pyrosequencing to diagnose tuberculous meningitis:
A retrospective diagnostic accuracy study. Tuberculosis (Edinb)
2021;126:102048.
59. Kambli P, Ajbani K, Kazi M, Sadani M, Naik S, Shetty A, et al. Targeted
next generation sequencing directly from sputum for comprehensive
genetic information on drug resistant mycobacterium tuberculosis.
Tuberculosis (Edinb) 2021;127:102051.
60. Sharma A, Goyal M, Mishra NK, Gupta V, Gaikwad SB. MR imaging of
tubercular spinal arachnoiditis. AJR Am J Roentgenol 1997;168:807‑12.
61. Saxena D, Pinto DS, Tandon AS, Hoisala R. MRI findings in tubercular
radiculomyelitis. e Neurological Sci 2021;22:100316.
62. Srivastava T, Kochar DK. Asymptomatic spinal arachnoiditis in patients
with tuberculous meningitis. Neuroradiology 2003;45:727‑9.
63. Sae‑Jung S, Wongba N, Leurmprasert K. Predictive factors for
neurological deficit in patients with spinal tuberculosis. J Orthop
Surg (Hong Kong) 2019;27:2309499019868813.
64. Mittal S, Yadav G, Ahuja K, Ifthekar S, Sarkar B, Kandwal P, et al.
Predicting neurological deficit in patients with spinal tuberculosis – A
single‑center retrospective case‑control study. SICOT‑J 2021;7:7.
65. Wang H, Yang X, Shi Y, Zhou Y, Li C, Chen Y, et al. Early predictive
factors for lower‑extremity motor or sensory deficits and surgical
results of patients with spinal tuberculosis: A retrospective study of
329 patients. Medicine 2016;95:e4523.
66. Treatment of Tuberculosis: Guidelines. World Health Organization;
2010.
67. Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J,
et al. British infection society guidelines for the diagnosis and treatment
of tuberculosis of the central nervous system in adults and children.
J Infect 2009;59:167‑87.
125
 Garg, et al.: Spinal cord tuberculosis
68. Overview | Tuberculosis | Guidance | NICE. Available from: https://
www.nice.org.uk/guidance/ng33.
69. Hristea A, Constantinescu RVM, Exergian F, Arama V, Besleaga M,
Tanasescu R.Paraplegia due to non‑osseous spinal tuberculosis: Report
of three cases and review of the literature. Int J Infect Dis 2008;12:425‑9.
70. Zhang Y, Zhu M, Wang L, Shi M, Deng H. Longitudinally extensive
transverse myelitis with pulmonary tuberculosis: Two case reports.
Medicine (Baltimore) 2018;97:e9676.
71. Jain RS, Kumar S, Mathur T, Tejwani S. Longitudinally extensive
Downloaded from http://journals.lww.com/annalsofian by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hC
transverse myelitis: A retrospective analysis of sixty‑four patients
at tertiary care center of North‑West India. Clin Neurol Neurosurg
2016;148:5‑12.
ywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 06/30/2023
72. Sahu SK, Giri S, Gupta N. Longitudinal extensive transverse myelitis
due to tuberculosis: A report of four cases. J Postgrad Med 2014;60:409.
73. Goyal MK, Lal M. Tubercular longitudinally extensive transverse
myelitis with lower motor neuron paralysis. Trop Doct 2021;51:117‑9.
74. Luo L, Pino J. An intraduralextramedullarytuberculoma of the spinal
cord in a non‑HIV‑infected patient: Case report and review of the
literature. Lung 2006;184:187‑93.
75. Nomura S, Akimura T, Kitahara T, Nogami K, Suzuki M. Surgery for
expansion of spinal tuberculoma during antituberculous chemotherapy:
A case report. Pediatr Neurosurg 2001;35:153‑7.
76. Ramdurg SR, Gupta DK, Suri A, Sharma BS, Mahapatra AK. Spinal
intramedullary tuberculosis: A series of 15 cases. Clin Neurol Neurosurg
2009;111:115‑8.
77. Muthukumar N, Venkatesh G, Senthilbabu S, Rajbaskar R. Surgery for
intramedullary tuberculoma of the spinal cord: Report of 2 cases. Surg
Neurol 2006;66:69‑74.
78. vanToorn R, Solomons RS, Seddon JA, Schoeman JF. Thalidomide
use for complicated central nervous system tuberculosis in children:
Insights from an observational cohort. Clin Infect Dis 2021;72:e136‑45.
79. Marais BJ, Cheong E, Fernando S, Daniel S, Watts MR, Berglund LJ,
Barry SE, et al. Use of infliximab to treat paradoxical tuberculous
meningitis reactions. Open Forum Infect Dis 2021;8:ofaa604.
80. Gourie‑Devi M, Padmini R, Satish P. Use of intrathecalhyaluronidase in
spinal arachnoiditis complicating tuberculous meningitis. Indian J Med
Res 1980;71:581‑93.
81. Gourie‑Devi M, Satishchandra P. Hyaluronidase as an adjuvant in
the management of tuberculous spinal arachnoiditis. J Neurol Sci
1991;102:105‑11.
82. Sodhani P, Singh NK, Thacker AK, Katiyar BC, Misra S.
Intrathecalhyaluronidase therapy in tuberculous spinal arachnoiditis.
126 Annals of Indian Academy of Neurology ¦ Volume 26 ¦ Issue 2 ¦ March-April 2023
J Assoc Physicians India 1986;34:636‑8.
83. Samal P, Elavarasi A, Kumar A, Prabhakar A, Vishnu VY, Singh MB,
et al. Intrathecal Hyaluronidase in Tubercular Arachnoiditis. Infect Dis
Clin Pract 2020;28:230‑3.
84. Goyal V, Elavarasi A, Abhishek, Shukla G, Behari M. Practice trends in
treating central nervous system tuberculosis and outcomes at a tertiary
care hospital: A cohort study of 244 cases. Ann Indian Acad Neurol
2019;22:37‑46.
85. Khadilkar SV, Kadam ND, Kulkarni RV, Meshram CM, Meshram AR,
Patel BA, et al. Guidelines versus ground lines: Tuberculosis of the
central nervous system. Neurol India 2019;67:787‑91.
86. Török ME, Nguyen DB, Tran THC, Nguyen TBY, Thwaites GE,
Hoang TQ, et al. Dexamethasone and long‑term outcome of
tuberculous meningitis in Vietnamese adults and adolescents. PLoS One
2011;6:e27821.
87. Misra UK, Kalita J, Singh AP, Prasad S. Vascular endothelial growth
factor in tuberculous meningitis. Int J Neurosci 2013;123:128‑32.
88. Husain N, Awasthi S, Haris M, Gupta RK, Husain M. Vascular endothelial
growth factor as a marker of disease activity in neurotuberculosis.
J Infect 2008;56:114‑9.
89. Green JA, Tran CTH, Farrar JJ, Nguyen MTH, Nguyen PH, Dinh SX,
et al. Dexamethasone, cerebrospinal fluid matrix metalloproteinase
concentrations and clinical outcomes in tuberculous meningitis. PLoS
One 2009;4:e7277.
90. Fava VM, Schurr E. Evaluating the impact of LTA4H genotype and
immune status on survival from tuberculous meningitis. J Infect Dis
2017;215:1011‑3.
91. Whitworth L, Coxon J, van Laarhoven A, Thuong NTT, Dian S,
Alisjahbana B, et al. A bayesiananalysis of the association between
leukotriene A4 Hydrolase genotype and survival in tuberculous
meningitis. Elife 2021;10:e61722.
92. vanLaarhoven A, Dian S, Ruesen C, Hayati E, Damen MSMA, Annisa J,
et al. Clinical parameters, routine inflammatory markers, and LTA4H
genotype as predictors of mortality among 608 patients with tuberculous
meningitis in Indonesia. J Infect Dis 2017;215:1029‑39.
93. vanLaarhove, A, Dian S, Aguirre‑Gamboa R, Avila‑Pacheco J,
Ricaño‑Ponce I, Ruesen C, et al. Cerebral tryptophan metabolism and
outcome of tuberculous meningitis: An observational cohort study.
Lancet Infect Dis 2018;18:526‑35.
94. vanCrevel R, ULTIMATE consortium. Improving host‑directed therapy
for tuberculous meningitis by linking clinical and multi‑omics data.
Tuberculosis (Edinb) 2021;128:102085.