Central nervous system tuberculosis: An

overview
Author: Ravindra Kumar Garg, MD, DM, FRCP
Section Editors: John Bernardo, MD, Morven S Edwards, MD
Deputy Editor: Elinor L Baron, MD, DTMH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Jun 2022. | This topic last updated: Jun 08, 2021.

INTRODUCTION

Forms of central nervous system (CNS) infection due to Mycobacterium

tuberculosis include meningitis, tuberculoma, and spinal arachnoiditis.

The epidemiology and pathogenesis of CNS tuberculosis (TB) are reviewed

here, as are clinical issues related to tuberculoma and spinal arachnoiditis.
Clinical issues related to tuberculous meningitis are discussed separately.
(See "Tuberculous meningitis: Clinical manifestations and diagnosis".)

Issues related to management of CNS TB are discussed separately. (See

"Central nervous system tuberculosis: Treatment and prognosis".)

Issues related to pulmonary TB and miliary TB are discussed separately.

(See "Clinical manifestations and complications of pulmonary tuberculosis"
and "Diagnosis of pulmonary tuberculosis in adults" and "Epidemiology
and pathology of miliary and extrapulmonary tuberculosis".)

Issues related to treatment of TB are discussed separately. (See "Treatment

of drug-susceptible pulmonary tuberculosis in HIV-uninfected nonpregnant
adults" and "Treatment of drug-resistant pulmonary tuberculosis in
adults".)
Issues related to treatment of TB in patients with HIV infection are
discussed separately. (See "Treatment of drug-susceptible pulmonary
tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy"
and "Treatment of pulmonary tuberculosis in adults with HIV infection:
Follow-up after initiation of therapy".)

EPIDEMIOLOGY

Among patients with TB, approximately 1 to 5 percent are complicated by

CNS TB [1-11]. Therefore, in regions where the prevalence of TB is high and
the prevalence of postprimary dissemination is common among children
and young adults, all three forms of CNS TB (tuberculous meningitis,
intracranial tuberculoma, and spinal tuberculous arachnoiditis) are
encountered relatively frequently [1-11].

In regions where the prevalence of TB is low, such as North America and

Western Europe, extrapulmonary manifestations of TB are observed
primarily in adults with reactivation disease, and the predominant form of
CNS disease is meningitis. In the United States in 2018, there were 1828
cases of extrapulmonary tuberculosis, of which 3.8 percent involved the
meninges [12].

HIV is an important risk factor for CNS TB [1,13-15]. Among patients with
TB, those with HIV infection have a five-fold increase in the likelihood of
having CNS involvement and disseminated TB compared with those
without HIV infection; this risk increases among patients with CD4 count
<100 cells/microL [1].

PATHOGENESIS

During the bacillemia that follows primary infection or late reactivation TB,
scattered tuberculous foci (tubercles) are established in the brain,
meninges, or adjacent cranial bone. (See "Tuberculosis: Natural history,
microbiology, and pathogenesis".)

The establishment of a cortical or meningeal tubercle (Rich focus), with

subsequent rupture into the subarachnoid space, is the critical event in the
development of TB meningitis [16]. The widespread and dense distribution
of foci seen in association with progressive miliary TB greatly increases the
chance that juxta-ependymal tubercles will be established. (See
"Epidemiology and pathology of miliary and extrapulmonary tuberculosis".)

The spillage of tubercular bacilli and tubercular protein into the

subarachnoid space produces an intense hypersensitivity reaction, giving
rise to inflammatory changes that are most marked at the base of the
brain. Three features dominate the pathology and explain the clinical
manifestations [16,17]:

● Thick gelatinous exudate, most marked at the basal part of the brain,
eventually produces a fibrous mass that encases adjacent cranial
nerves and vessels of Circle of Willis, leading to cranial nerve palsies
and periventricular infarcts, respectively.

● Tuberculous vasculitis with resultant inflammatory vascular changes

leads to spasm, constriction, thrombosis, and occlusion of
intracerebral vessels. Occlusion of cerebral arteries results in infarction
of the brain parenchyma. Infarcts in tuberculous meningitis are
typically small, multiple, bilateral, and frequently located in the
periventricular regions. The most involved structures are the basal
ganglia, thalamus, and internal capsule. Periventricular infarcts are
ascribed to arteritis of deep penetrating vessels of Circle of Willis,
particularly the lenticulostriate arteries [18,19]. Multiple lesions are
common and a variety of stroke syndromes may result; the basal
ganglia, cerebral cortex, pons, and/or cerebellum may be involved [20].
 Intracranial vasculitis is a common feature in autopsy studies, and a
major determinant of residual neurologic deficits. In one autopsy study
including 27 patients, for example, phlebitis and varying degrees of
arteritis were demonstrated in 22 cases, including 8 patients with
associated hemorrhagic cerebral infarction [21].

● Hydrocephalus eventually develops in the majority of patients with

tuberculous meningitis. Communicating hydrocephalus results from
extension of the inflammatory process to the basilar cisterns and
impedance of cerebrospinal fluid circulation and resorption.
Noncommunicating or obstructive hydrocephalus caused by
obstruction of the aqueduct develops less frequently, from contraction
of exudate surrounding the brainstem or because of a brainstem
tuberculoma that blocks drainage.

FORMS OF DISEASE

Forms of CNS TB include tuberculous meningitis, tuberculoma, and spinal

arachnoiditis.

Tuberculous meningitis — Issues related to tuberculous meningitis are

discussed separately. (See "Tuberculous meningitis: Clinical manifestations
and diagnosis" and "Central nervous system tuberculosis: Treatment and
prognosis".)

Tuberculoma — A tuberculoma is a conglomerate granulomatous focus

that develops from coalescing tubercles acquired during disseminated
bacillemia. Tuberculomas occur most commonly in the brain; they may also
occur in the spinal cord.

Clinical manifestations — Tuberculomas are often clinically silent and

may reach considerable size in the absence of meningeal inflammation
[22,23]. In the setting of TB meningitis, subclinical tuberculomas (single or
multiple) may be observed on radiographic imaging. (See 'Tuberculous
meningitis' above.)

Alternatively, tuberculoma may present as a clinically evident mass lesion

of the brain in the absence of TB meningitis. This presentation occurs most
commonly in endemic areas and typically consists of a child or young adult
with headache, seizure, progressive hemiplegia, and/or signs of elevated
intracranial pressure [24,25].

Tuberculomas may develop during adequate antituberculous therapy; this

may be a result of the immune response against dying M. tuberculosis
organisms.

Radiographic findings — Radiographically, tuberculomas are discrete,

ring-enhancing lesions of the brain surrounded by perilesional edema; they
may be single or multiple.

On contrast computed tomography imaging, radiographic findings of early-

stage tuberculoma consist of low density or isodense lesions, often with
edema out of proportion to mass effect and with little encapsulation (
image 1) [24-26]. Later-stage tuberculomas are well encapsulated, isodense
or hyperdense, and have peripheral ring enhancement.

On magnetic resonance imagining (MRI), tuberculomas appear

hypointense on T1-weighted images and hyperintense on T2-weighted
images (image 1). With contrast enhancement, there is either ring-shaped
or homogeneous disc-shaped enhancement.

In one meta-analysis including 404 patients with CNS TB, intracranial

tuberculomas were observed on initial neuroimaging in 49 percent of
cases; of these, multiple tuberculomas were observed in 78 percent of
cases [18]. Innumerable small tuberculomas may be observed in patients
with tuberculous meningitis associated with miliary TB (image 2).
Diagnosis — The diagnosis of tuberculoma should be suspected in
patients with mass lesion of the brain and relevant epidemiologic factors
(eg, history of prior TB infection or disease, known or possible TB exposure,
and/or past or present residence in or travel to an area where TB is
endemic).

Establishing a diagnosis of tuberculoma can be challenging. A presumptive

diagnosis may be made in the setting of relevant clinical and epidemiologic
factors and typical radiographic findings (see 'Radiographic findings'
above), particularly if a definitive diagnosis of TB has been established from
an extraneural site of disease (such as lung, gastric fluid, lymph nodes,
bone marrow, or liver). (See "Diagnosis of pulmonary tuberculosis in
adults" and "Tuberculosis disease in children".)

A definitive diagnosis of tuberculoma is established via needle biopsy of

the CNS lesion for histopathology and acid-fast bacilli (AFB) stain and
culture; however, surgical intervention should be avoided as it may
precipitate meningitis. In addition, lumbar puncture is usually avoided
because of concern for elevated intracranial pressure and risk of brainstem
herniation. For cases in which cerebrospinal fluid (CSF) is examined,
findings may demonstrate elevated protein concentration, normal glucose
concentration, and pleocytosis (10 to 100 cells/microL, typically lymphocyte
predominant) [6].

Patients with suspected CNS TB should undergo chest radiography; in the

setting of relevant signs or symptoms, diagnostic evaluation for pulmonary
TB should be pursued. In addition, for patients with signs and symptoms of
suggestive of TB at other sites, diagnostic evaluation should be pursued
accordingly (such as lymph node biopsy, bone marrow biopsy); such
interventions may be safer and more accessible than CNS-based diagnosis
[6]. (See "Diagnosis of pulmonary tuberculosis in adults", section on
'Radiographic imaging' and "Tuberculous lymphadenitis" and "Clinical
manifestations, diagnosis, and treatment of miliary tuberculosis".)
For patients with HIV and low epidemiologic risk and low clinical suspicion
for TB, a trial of empiric treatment for toxoplasmosis (prior to proceeding
with brain biopsy) may be useful in some circumstances. (See "Approach to
the patient with HIV and central nervous system lesions".)

Differential diagnosis — The differential diagnosis of tuberculoma

includes:

● Neurocysticercosis – Neurocysticercosis (NCC) and tuberculoma share

similar epidemiologic, clinical, and radiographic features. Distinction
between these two entities requires careful attention to radiographic
features (identification of a scolex within a cystic lesion is a
pathognomonic radiographic finding for NCC) and thorough evaluation
for evidence of extraneural TB. (See "Cysticercosis: Clinical
manifestations and diagnosis".)

● Cryptococcoma – Cryptococcoma and tuberculoma share similar

clinical and radiographic features. Cryptococcus gattii is more likely
than Cryptococcus neoformans to cause cryptococcoma (of the lungs
and/or brain); however, given that C. gattii is concentrated in the
northwestern United States and southwestern Canada, this species has
less epidemiologic overlap with TB than C. neoformans. In the absence
of contraindication to lumbar puncture, CSF should be examined;
routine studies should be performed, in addition to cryptococcal
antigen, India ink staining, and fungal culture. Alternatively, brain
biopsy may be warranted. (See "Cryptococcus gattii infection: Clinical
features and diagnosis" and "Epidemiology, clinical manifestations,
and diagnosis of Cryptococcus neoformans meningoencephalitis in
patients with HIV" and "Clinical manifestations and diagnosis of
Cryptococcus neoformans meningoencephalitis in HIV-seronegative
patients".)

● CNS toxoplasmosis – Toxoplasmosis is the most common CNS infection

in HIV-infected patients with CD4 count <100 cells/microL who are not
 receiving appropriate prophylaxis. Patients typically present with
headache, fever, and altered mental status; focal neurologic deficits or
seizures are also common. A definitive diagnosis requires a compatible
clinical syndrome, identification of ≥1 mass lesions on brain imaging,
and detection of the organism in a biopsy specimen; for most patients
a presumptive diagnosis is made to avoid a brain biopsy. (See
"Toxoplasmosis in patients with HIV" and "Approach to the patient with
HIV and central nervous system lesions".)

● Brain abscess – Clinical manifestations of brain abscess may be

subacute and nonspecific. Lumbar puncture is contraindicated in
patients with papilledema or focal symptoms or signs; if it is feasible to
obtain CSF, findings may demonstrate elevated protein concentration,
low glucose concentration, and pleocytosis. A microbiologic diagnosis
may be established culture of material obtained via stereotactic-guided
aspiration or surgery. (See "Pathogenesis, clinical manifestations, and
diagnosis of brain abscess".)

● CNS lymphoma – CNS lymphoma is an important cause of CNS lesion

in HIV-infected patients. Clinical presentation is typically acute to
subacute, with symptoms such as confusion, lethargy, memory loss,
hemiparesis, aphasia, and/or seizures progressing over days to weeks.
The diagnosis is established via brain biopsy. (See "HIV-related
lymphomas: Primary central nervous system lymphoma" and
"Approach to the patient with HIV and central nervous system lesions".)

● Brain tumor (primary or metastatic brain) – Clinical manifestations of

brain tumor include headache, seizures, focal deficits, cognitive
dysfunction, and increased intracranial pressure. The diagnosis is
suspected based on radiographic findings and confirmed via biopsy.
(See "Overview of the clinical features and diagnosis of brain tumors in
adults".)
Management — Issues related to management of tuberculoma are
discussed separately. (See "Central nervous system tuberculosis: Treatment
and prognosis", section on 'Tuberculoma'.)

Spinal arachnoiditis

Pathogenesis and epidemiology — Spinal tuberculous arachnoiditis

develops in the context of breakdown of granulomatous foci within the
spinal cord or meninges; in such cases, the spinal cord and spinal nerve
roots are encased in tuberculous exudates. This can occur at any level of
the spinal cord or by extension from an adjacent area of spondylitis [27,28].
(See "Bone and joint tuberculosis", section on 'Spondylitis (Pott disease)'.)

The resulting inflammatory reaction is usually confined locally and

progresses gradually over weeks to months, producing a partial or
complete encasement of the cord by a gelatinous or fibrous mass. A
characteristic feature of tuberculous arachnoiditis, which differentiates it
from other types of arachnoiditis, is its propensity to affect spinal cord,
meninges, and nerve roots together in varying combinations [28].

Spinal tuberculous arachnoiditis occurs with variable frequency in patients

with TB meningitis. In one series including 71 patients with TB meningitis,
46 percent had concomitant symptoms/signs of spinal cord and spinal
nerve root involvement [28]. The most common site was the lumbosacral
region (32 percent), followed by thoracolumbar (10 percent), thoracic (8.5
percent), and cervical (4 percent) regions. Risk factors for development of
spinal cord involvement included long mean duration of illness prior to
diagnosis and delay in initiation of antituberculous therapy.

Clinical manifestations — Clinical manifestations of tuberculous spinal

arachnoiditis are protean. The most common presentation is an ascending
or transverse radiculomyelopathy of variable pace, at single or multiple
levels [27]. Tuberculous radiculomyelopathy may precede, coincide with, or
follow (by months or years) an initial episode of TB meningitis.
Patients with spinal tuberculous arachnoiditis usually present with
subacute onset of nerve root and cord compression signs. Symptoms
include spinal or radicular pain, hyperesthesia or paresthesia in the
distribution of the nerve root, upper or lower motor neuron paralysis, and
bladder or rectal sphincter incontinence. Vasculitis may result in
thrombosis of the anterior spinal artery and infarction of the spinal cord.

Some patients with unrecognized chronic, indolent spinal tuberculous

arachnoiditis progress to frank TB meningitis as a late complication of
disease. (See 'Tuberculous meningitis' above.)

Diagnosis — The diagnosis of spinal arachnoiditis should be suspected in

patients with relevant clinical manifestations (subacute onset nerve root
and cord compression signs) and relevant epidemiologic factors (history of
prior TB infection or disease, known or possible TB exposure, and/or past
or present residence in or travel to an area where TB is endemic).

A presumptive diagnosis of spinal arachnoiditis may be made in the setting

of typical radiographic findings (spinal MRI with nodular arachnoiditis) and
CSF examination (unusually high CSF protein levels, with or without
pleocytosis), particularly if a definitive diagnosis of TB has been established
from an extraneural site of disease (such as lung, gastric fluid, lymph
nodes, bone marrow, or liver). (See "Diagnosis of pulmonary tuberculosis in
adults" and "Tuberculosis disease in children".)

Radiographically, spinal cord and spinal nerve root involvement manifests

with diffuse enhancement of meninges overlying spinal cord and nerve
roots. In tuberculous myelitis, there is T2/fluid-attenuated inversion
recovery hyperintensity spreading over multiple segments [27-29].

In patients who present with signs and symptoms of meningitis as well as

spinal cord involvement, CSF diagnostic studies (positive smear, positive
nucleic acid amplification tests) may suffice for diagnosis. In patients with
subarachnoid block, the CSF protein concentration may be as high as 2
g/dL; other CSF findings may include elevated protein concentration,
normal glucose concentration, and pleocytosis (10 to 100 cells/microL,
typically lymphocyte predominant). There are no data to establish the
reliability of CSF examination for the diagnosis of isolated forms of spinal
TB; in the absence of meningitis, a definitive diagnosis of spinal
arachnoiditis is established via needle biopsy of the CNS lesion for
histopathology and AFB stain and culture.

Patients with suspected TB should undergo chest radiography; in the

setting of relevant signs or symptoms, diagnostic evaluation for pulmonary
TB should be pursued. In addition, for patients with signs and symptoms of
suggestive of TB at other sites, diagnostic evaluation should be pursued
accordingly (such as lymph node biopsy, bone marrow biopsy); such
interventions may be safer and more accessible than CNS-based diagnosis
[6]. (See "Diagnosis of pulmonary tuberculosis in adults", section on
'Radiographic imaging' and "Tuberculous lymphadenitis" and "Clinical
manifestations, diagnosis, and treatment of miliary tuberculosis".)

Differential diagnosis — Other presenting forms of spinal cord and nerve

root involvement in the setting of tuberculosis include [27]:

● Spinal tuberculoma – A spinal tuberculoma is a granulomatous focus in

the spinal cord that develops from coalescing tubercles acquired
during disseminated bacillemia (image 3). Clinically, it presents with
features suggestive of subacute transverse myelopathy, characterized
by progressive limb weakness, sensory deficits, and bowel and bladder
dysfunction. (See 'Tuberculoma' above.)

● Tuberculous spondylitis and vertebral osteomyelitis (Pott disease) –

Tuberculous spondylitis and vertebral osteomyelitis represent a
disease continuum; involvement may include the intervertebral joints,
one or more vertebral bodies, and one or more intervertebral disc
spaces. (See "Bone and joint tuberculosis".)
Other infectious causes of spinal cord and nerve root involvement include:

● Cytomegalovirus infection (CMV) – In HIV-infected patients, the most

common cause of lumbosacral polyradiculopathy is CMV infection. The
diagnosis is established via CSF evaluation, including assessment of
CSF viral load. (See "AIDS-related cytomegalovirus neurologic disease".)

● Syphilis – Uncommonly, syphilitic meningitis may affect the spinal cord

and cause meningomyelitis or hyperplastic pachymeningitis with
polyradiculopathy. Diagnostic testing includes serum treponemal and
nontreponemal tests and spinal fluid examination to assess for
presence of pleocytosis, elevated protein concentration, and CSF
Venereal Disease Research Laboratory tests. (See "Neurosyphilis".)

Noninfectious causes of spinal cord disorders and polyradiculopathy are

discussed further separately. (See "Disorders affecting the spinal cord" and
"Polyradiculopathy: Spinal stenosis, infectious, carcinomatous, and
inflammatory nerve root syndromes" and "HIV-related lymphomas: Primary
central nervous system lymphoma".)

Management — Issues related to management of spinal arachnoiditis are

discussed separately. (See "Central nervous system tuberculosis: Treatment
and prognosis", section on 'Spinal arachnoiditis'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected

countries and regions around the world are provided separately. (See
"Society guideline links: Diagnosis and treatment of tuberculosis".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in
plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient education
pieces are longer, more sophisticated, and more detailed. These articles are
written at the 10th to 12th grade reading level and are best for patients who
want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can
also locate patient education articles on a variety of subjects by searching
on "patient info" and the keyword(s) of interest.)

● Beyond the Basics topic (see "Patient education: Tuberculosis (Beyond

the Basics)")

SUMMARY
● Forms of central nervous system (CNS) tuberculosis (TB) include
tuberculous meningitis, tuberculoma, and spinal arachnoiditis. In
regions where the prevalence of TB is high and the prevalence of post-
primary dissemination is common among children and young adults,
all three forms of CNS TB (tuberculous meningitis, intracranial
tuberculoma, and spinal tuberculous arachnoiditis) are encountered
relatively frequently. In regions where the prevalence of TB is low,
extrapulmonary manifestations of TB are observed primarily in adults
with reactivation disease, and the predominant form of CNS disease is
meningitis. (See 'Epidemiology' above.)

● Issues related to tuberculous meningitis are discussed separately. (See

"Tuberculous meningitis: Clinical manifestations and diagnosis".)

● A tuberculoma is a conglomerate granulomatous focus that develop

from coalescing tubercles acquired during disseminated bacillemia.
 Tuberculomas occur most commonly in the brain; they may also occur
in the spinal cord. They may occur with or without overt manifestations
(headache, seizure, progressive hemiplegia, and/or signs of elevated
intracranial pressure), and with or without concomitant meningitis.
(See 'Clinical manifestations' above.)

● A presumptive diagnosis of tuberculoma may be made in the setting of

relevant clinical and epidemiologic factors and typical radiographic
findings (image 1) particularly if a definitive diagnosis of TB has been
established from an extraneural site of disease. A definitive diagnosis is
established via needle biopsy of the CNS lesion for histopathology and
acid-fast bacilli (AFB) stain and culture; however, surgical intervention
should be avoided as it may precipitate meningitis. In addition, lumbar
puncture is usually avoided because of concern for elevated
intracranial pressure and risk of brainstem herniation. (See 'Diagnosis'
above.)

● Spinal arachnoiditis develops in the context of breakdown of

granulomatous foci within the spinal cord or meninges; in such cases,
the spinal cord and nerve roots are encased in tuberculous exudates.
This can occur at any level of the spinal cord, or by extension from an
adjacent area of spondylitis. Patients with spinal tuberculous
arachnoiditis usually present with subacute onset of nerve root and
cord compression signs; these manifestations may precede, coincide
with, or follow (by months or years) an initial episode of tuberculous
meningitis. (See 'Clinical manifestations' above.)

● A presumptive diagnosis of spinal arachnoiditis may be made in the

setting of typical radiographic findings (spinal magnetic resonance
imaging with nodular arachnoiditis) and cerebrospinal fluid (CSF)
examination (unusually high CSF protein levels, with or without
pleocytosis), particularly if a definitive diagnosis of TB has been
established from an extraneural site of disease. In the absence of
 meningitis, a definitive diagnosis of spinal arachnoiditis is established
via needle biopsy of the CNS lesion for histopathology and AFB stain
and culture. (See 'Diagnosis' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate acknowledge John M Leonard, MD, who

contributed to an earlier version of this topic review.

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