Central Nervous System

Tuberculosis
Barry Harris and Tara Morris

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 risk of or who have contracted TB.As is well known,TB
ABSTRACT can affect multiple organ systems, the most common being
Although the incidence of tuberculosis (TB) has pulmonary. However, research shows that as many as 10% of
decreased in the United States, this infection is a persons with pulmonary TB develop central nervous system
formidable force worldwide.TB can have an (CNS) TB, which can manifest as meningitis or lesions of
insidious presentation, affecting multiple organ the brain or spine.3-5 In addition, extrapulmonary TB,
systems, including the central nervous system including miliary (disseminated) disease, is on the rise sec-
(CNS). Although this may be a rare complication ondary to its increased prevalence in HIV-infected persons,
of TB, it can be a devastating omission for the medically underdeveloped populations, and alcohol and
patient.Therefore, it is imperative for health care intravenous drug abusers.1,6 For these reasons, it is imperative
providers to keep CNS TB in the differential to maintain a high degree of suspicion when patients with
when evaluating neurologic issues.The goal of TB risk factors present with neurologic complaints.
this article is to enlighten the midlevel provider
about the possible presentations of CNS TB, CASE STUDIES
review diagnostic and laboratory studies, and TB meningitis can present in several ways. Let us review
explain treatment options. a few case studies.
Keywords: brain, central nervous system, CNS,
meningitis,TB, tuberculoma, tuberculosis, spine Case Study 1
Patient: 44-year-old man
Past medical history (PMH): HIV, CD4 count of 53,
miliary TB of the chest
Why should we care about tuberculosis (TB)? Recent Presentation: headache, vertigo, nausea, vomiting
reports have estimated that the incidence of TB has Magnetic resonance imaging (MRI): multiple ring-enhancing
declined in the United States. lesions (Figures 1 and 3) and cerebral edema (Figure 2)
Worldwide, it is estimated by the World Health Differential diagnoses: lymphoma, CNS/neuro tuberculoma
Organization that each year, there are more than eight mil- Surgery: right temporal open brain biopsy
lion new cases of TB, and three million people each year Specimen: positive for acid-fast bacillus (AFB)
die of TB.1 Overall, it is estimated that 19% to 43% of the Rx: ethambutol (EMB), isoniazid (INH), pyrazinamide
world’s population has TB, including 15 to 30 million (PZA), rifabutin
Americans.According to the Centers for Disease Control
(CDC), 14,517 new cases of TB were reported in the Case Study 2
United States during 2004, with foreign-born persons con- Patient: 66-year-old man
stituting 54%.The top five countries of origin of foreign- PMH: rheumatoid arthritis
born persons with TB were Mexico, the Philippines, Presentation: 4 weeks of headache and fatigue
Vietnam, India, and China.Additionally, US-born blacks MRI: enhancing right temporal lesion with vasogenic
represented 45% of TB cases in the United States and more edema (Figures 4-6)
than 20% of all cases. Of note,Texas, California, and New Differential diagnoses: suspected glioma, lymphoma,
York accounted for 42% of the overall cases reported in CNS/neuro tuberculoma
2004.2 Surgery: frontal-temporal craniotomy, excisional biopsy,
Although the overall incidence of TB has declined in and temporal lobectomy
the United States in recent years,2 it is a formidable disease Specimen: frozen: hypercellular, suspected malignancy;
because of its highly infectious nature, insidious presenta- final: AFB
tion, and propensity for latency. Health care workers in the Rx: patient referred to and transferred to the infectious
United States need to be able to identify persons who are at disease team

320 The Journal for Nurse Practitioners - JNP May 2007

 Figure 1. Axial MRI showing typical ring Figure 2. Axial MRI (Flare sequence) Figure 3. Coronal MRI showing typical
enhancing lesions of CNS TB. showing cerebral edema. ring enhancing lesions of CNS TB.

Figure 4. Coronal MRI with multiple ring Figure 5. MRI showing typical Figure 6. Coronal MRI with ring enhancing
enhancing lesions. vasongenic edema. mass and associated edema.

Figure 7. Axial MRI with an abnormally shaped Figure 8. Sagital MRI showing ring enhancing Figure 9. Coronal MRI showing ring enhancing
ring enhancing lesions typical of CNS TB. lesion (seen in coronal view on Figure 9). lesion (seen in sagital view on Figure 8).

Case Study 3 INCIDENCE

Patient: 22-year-old Mexican man (recently moved from The incidence of TB is increasing worldwide.6 Some
Mexico to the United States) reports keep TB as the “leading cause of death due to a
PMH: None single infectious agent” and the seventh leading cause of
Presentation: 3 months of headache death and disability worldwide.3,7 Many factors predis-
Computed tomography (CT) scan: posterior fossa mass, mild pose a person to TB. Bayindir et al8 state that 95% of
obstructive hydrocephalus their patients had low social, economic, and nutritional
MRI: 3-cm ring-enhancing mass in the superior vermis conditions.There are approximately 300 to 400 cases of
(Figures 7-9) TB meningitis in the United States each year.9 CNS
Differential diagnoses: lymphoma, CNS/neuro TB tuberculomas are seen in 0.55% to 15% of systemic TB
Surgery: suboccipital craniotomy, mass resection, dural cases, depending on the study reviewed.3,8,10 Intracranial
patch, right occipital intraventricular catheter tuberculomas are seen in about 1% of all patients with
Specimen: frozen: granulomatous mass; final: AFB TB,6 whereas intradural spinal tuberculomas are reported
Rx: EMB, INH, PZA, rifabutin to be 2% to 5% of CNS tuberculomas.11

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PATHOGENESIS Table 1. Risk Factors
TB is an infectious disease caused by the obligate aerobic • Immunosuppression, HIV, AIDS
bacillus, Mycobacterium tuberculosis.12 It is transmitted • Alcoholism
through inhalation of as few as 1 to 10 aerosolized
• Immigration
droplets containing the bacteria. As the bacteria multiply
• Diabetes
in the alveoli and macrophages of the lung, the complex
cell-mediated immune response generates a granuloma- • Underlying malignancies

tous reaction, resulting in a tubercle and caseating necrosis • Chronic renal failure
(a small rounded lesion with a necrosing center).9 Its • Immunosuppressive drugs
outer waxy capsule makes it more resistant to destruction. • Intravenous drug abuse
As a result, this bacterium can persist in old necrotic and • Contact with people known to have TB
calcified lesions and is capable of reinitiating growth. If
• Poor ventilation
the bacteria are not contained, the infection can be
• Homelessness
hematogenously spread to other sites.9
• Crowding (ie, incarceration, group home, etc)
The location of TB spread to the CNS is directly
related to the pattern of blood flow and usually spreads
to the cerebral hemispheres and basal ganglia in adults
and to the cerebellum in children.The ratio of PRESENTING SIGNS AND SYMPTOMS
intramedullary to intracranial lesions are found to relate CNS TB presents in many different ways. A patient may
to spinal cord versus brain weight, about 1:42.10 Spinal be asymptomatic, have pulmonary symptoms, or have
lesions are most often found in the thoracic spine and neurologic deficits alone. As one can see from the case
often present as subacute cord compression.12 studies, all of the patients had headaches, but one had
A tubercle that ruptures in the subarachnoid space vertigo and another fatigue. CNS TB usually has signs
results in TB meningitis, whereas deep lesions cause and symptoms of increased intracranial pressure or space-
tuberculomas or abscesses.The tuberculoma capsule is occupying lesions in the brain or spine.15 Common com-
composed of fibroblasts, lymphocytes, epithelioid cells, plaints may include headache, stiff neck, fever, weight
and Langhans giant cells, and its core is a necrotic loss, blurry vision, confusion, lethargy, nausea, vomiting,
caseous center.13,14 When this core liquefies, the lesion and, for spinal cord lesions, lower extremity weakness or
becomes a tuberculous abscess, packed with AFB.Vascular bowel or bladder symptoms. Signs of meningitis may
inflammation, vasculitis, and edema, which can occur include altered mental status, fever, seizure, cranial nerve
around the lesions, are products of the immune response deficits, papilledema, or meningismus. Patients with
and can cause additional clinical complications.TB tuberculomas will have a physical examination that is
meningitis is a result of an intense hypersensitivity consistent with the location in the brain of the space-
reaction that gives rise to inflammatory changes involv- occupying lesion, which may include cranial nerve
ing cranial nerves.The inflammation can also affect deficits, altered mental status, visual changes, hemiparesis,
blood vessels, resulting in vasculitis and subsequent or seizures. Patients with spinal cord lesions will have a
thrombosis or infarction, causing strokelike syndromes. physical examination consistent with the location of the
Communicating hydrocephalus can also occur secondary lesion in the spinal cord.8,15
to impedance of cerebrospinal fluid (CSF) circulation
and reabsorption.1 (The arachnoid layer is the primary DIAGNOSTIC TESTING
layer where CSF is reabsorbed.) Imaging
A CT scan of the brain should be done if there is suspi-
RISK FACTORS cion for intracranial or intramedullary TB.The CT scan
Risk factors associated with acquiring TB are listed should be done with and without contrast. Immature
in Table 1. Only patients with pulmonary TB are infec- lesions are hypodense and nonenhancing. Mature lesions
tious1; however, the risk factors for developing pul- are isodense to hyperdense with solid, ring, or mixed
monary and extrapulmonary TB are comparable. enhancement.There is a typical target sign suggestive of

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TB. CT findings are similar to that of many other CNS tant tests to order. Scans that reveal lesions should imme-
lesions, including fungal infections, neurosarcoidosis, bac- diately be referred to a neurosurgery team for further
terial infections, and some metastatic disease.16 workup and diagnosis. Once the diagnosis is finalized, it
An MRI scan is more specific and sensitive than a is important to use a multidisciplinary approach to
CT scan and should be done with and without contrast. patient care.
T1-weighted images show central isointensity.T2-
weighted images show an isotense to hypertense core DIFFERENTIAL DIAGNOSIS
and a hyperintense rim, ring, or conglomerate of rings Possible differential diagnoses include necrotic tumors,
with enhancement.3 MRI findings may also mimic sev- pyogenic abscess, toxoplasmosis, meningitis,
eral of the aforementioned lesions. lymphoma, and neoplasm.

Laboratory Tests TREATMENT

Laboratory results are not discussed much in the liter- Surgical intervention for intracranial tuberculomas is
ature. Diagnosis is often made on history and physical, generally not recommended because prolonged pharma-
suspicion, and diagnostic imaging. cologic therapy combined with corti-
Some laboratory findings are listed costeroids is usually effective in treat-
here. ing these lesions. However, surgery
Cerebrospinal fluid. Lumbar punc-
Always get an may be warranted if immediate
tures that remove 10 to 15 mL provide AFB smear when decompression is necessary or if biopsy
the best information. CSF studies may testing CSF. is required for definitive diagnosis.3
show normal findings17 or have elevated CDC guidelines recommend a 9-
protein, decreased glucose, or pleocytosis. to 12-month pharmacologic treatment
Results of CSF polymerase chain reaction tests may be regimen for CNS TB and offer four regimens for adminis-
diagnostic. Most patients will have an elevated opening
15,16
tering treatment.The initial phase of treatment in the first
pressure as well.18 2 months should include INH, rifampin (RIF), PZA, and
Always get an AFB smear when testing CSF. EMB.The medications can be given daily throughout the
Although there are a fair amount of false negatives, with first phase, daily for 2 weeks, and then twice weekly for 6
serial AFB smears (up to 4) the diagnostic yield is 87%.9 weeks, or three times weekly throughout.With differing
Mantoux tests. Mantoux tests may be positive or administration schedules come differing doses of the
negative. drugs. If the organism’s drug susceptibilities are known,
Other blood work. Sedimentation rate, C-reactive and it is fully susceptible, EMB need not be included in
protein, and white blood cell count may also be elevated. the initial phase. PZA should be avoided in severe liver
Biopsy of the lesion should be done if the diagnosis disease, gout, and, perhaps, pregnancy.The continuation
is unclear and the lesion is in an accessible area or if neu- phase should consist of INH and RIF for 7 to 10 months,
rologic compromise is present. Histopathology may show and this timeline should be prolonged if the patient was
a central necrosis, lymphocytes, Langerhans giant cells, or initially slow to respond to treatment.15,19,20 When patients
epithelioid cells.8,11 Bacilli may or may not be present. with intracranial tuberculomas experience increased
intracranial pressure or neurologic symptoms, corticos-
DIAGNOSTIC PATHWAY teroids can be added to the regimen, although their value
No definitive diagnostic pathway is available for CNS is still under investigation.6,15,17
TB. Many times the diagnosis is discovered on biopsy. Several cases of paradoxical enlargement of intracra-
Often, the clinical diagnosis is neoplasm; therefore, it is nial tuberculomas or development of new ones during
appropriate to work up the lesion as a neoplasm. treatment have been observed.3,6,15,17 Initiation of steroids
When a patient has a history that is consistent with in these patients was helpful in many cases, often helping
risk factors for TB, a Mantoux test is an appropriate to prevent surgical intervention.3 The development of
place to start. If there are any signs of headache or neu- intracranial TB lesions while on anti-TB therapy should
rologic deficit, CT scan, MRI scan, or both are impor- not be considered a failure of treatment. Rather, treat-

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ment should be continued for a prolonged course, and Social issues that must be considered in successful TB
high-dose corticosteroids added to the regimen. Repeat treatment are language barriers, socioeconomic differ-
MRI scans should be done every few months to track ences, access to resources (transportation, clinic, etc),
the lesion or lesions.3,21 insurance issues, child care, and housing.19 As is common-
In addition, many special circumstances are consid- ly known, having an effective social support system is
ered when initiating treatment. Drug resistance or his- essential for successful treatment of most ailments.
tory of previous therapy may change the pharmacologic
constituents and duration of treatment. In another PROGNOSIS
example, the regimen for children is much the same as Prognosis varies depending on the studies that are exam-
the regimen for adults; however, EMB is not frequently ined. Bayindir et al8 and Wang et al4 believe that the out-
used because of its serious side effects of blurred vision, come depends on the age and clinical stage of the
sudden changes in vision, and inability to see the colors patient. Both studies also suggest that prognosis is worse
red and green. In patients who are HIV positive, the when there is a rapid deterioration in the patient’s neu-
once weekly dosing regimen for the continuation phase rologic status. However, Muthukumar et al11 suggest that
is not an option because of the development of resist- medical and surgical outcomes have had good results.
ance to RIF, and those with a CD4 count of less than Some researchers speculate that a treatment regimen
100 should receive daily or three times weekly dosing. involving surgery (depending on the superficiality of the
Furthermore, anti-TB medications interact with anti- lesion) and a regimen that is purely pharmacologic will
retroviral agents; therefore, it is recommended that both result in resolution of symptoms. However, it is
treatment of these patients be deferred to an HIV-relat- possible that patients treated with drugs alone are more
ed TB specialist. For patients with renal insufficiency or likely to return to baseline.15
end-stage renal disease, special dosing considerations
must be addressed. In the face of liver disease, prudent SUMMARY
use of anti-TB drugs is recommended. INH, RIF, and Although CNS TB is a rare complication of TB, it is a seri-
PZA can cause hepatitis or worsen liver disease. ous disease, and early recognition and treatment are imper-
However, because of the effectiveness of these drugs, ative. Early diagnosis can prevent further deterioration and
their use is still recommended, depending on results of result in better prognosis.When a patient with known TB
liver enzyme tests. has neurologic complaints, immediate action must be taken
If serum aspartate transaminase is more than three to evaluate for CNS TB. In addition, this diagnosis should
times the normal level before initiation of treatment, the be on the differential for any patient seeking treatment
CDC offers several alternative regimens. In women who with neurologic symptoms, whether or not the patient has
are pregnant or breastfeeding, streptomycin is the only been diagnosed with pulmonary TB. CSF studies, CT and
drug that is documented to be harmful to the fetus, MRI scans, the Mantoux test, and brain biopsy, if necessary,
causing deafness. (Streptomycin is not commonly used in can aid in establishing a diagnosis of CNS TB.Although
treatment because of high rates of resistance.) Women there are varying opinions as to duration of treatment, the
who are taking first-line anti-TB drugs can continue addition of corticosteroids, and the role of surgery in treat-
breastfeeding because the small concentrations of the ment, it is generally agreed that the pharmacologic regi-
drugs in the breast milk do not cause toxicity in the men is the mainstay of treatment.
newborn.19 Dosing and regimen specifics can be found at
the CDC website, www.cdc.gov. References
The CDC also recommends directly observed thera- 1. Leonard, MK. (2002, 10/01/2002). Tuberculosis: forms of tuberculosis. 2002
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5. Skendros P, Kamaria F, Kontopoulos V, Tsitouridis I, Sidiropoulos L.
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tuberculoma requiring surgical treatment. Pediatr Neurosurg.
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tuberculomas due to miliary tuberculosis. South Med J. 2005;98(1):111-113.
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nervous system tuberculomas. Eur J Neurol. 2005;12(10):797-804. on the lives of patients and families everyday.
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Barry Harris, RN, BSN, MSN, CRNP-BC, and Tara Health
Morris, MHR, MHS, PA-C, work in the Department of Dental
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