Central nervous system tuberculosis | This topic last updated: Feb 01, 2017

Source: https://www.uptodate.com/contents/central-nervous-system-tuberculosis

INTRODUCTION — Central nervous system (CNS) tuberculosis (TB) includes three clinical categories:
tuberculous meningitis, intracranial tuberculoma, and spinal tuberculous arachnoiditis.

PATHOGENESIS — During the bacillemia that follows primary infection or late reactivation tuberculosis
(TB), scattered tuberculous foci (tubercles) are established in the brain, meninges, or adjacent bone.
Meningitis develops most commonly as a complication of postprimary infection in infants and young
children and from chronic reactivation bacillemia in older adults with immune deficiency caused by
aging, alcoholism, malnutrition, malignancy, human immunodeficiency virus (HIV) infection, or drugs
(eg, tumor necrosis factor [TNF]-alpha inhibitors).

FORMS OF CNS TUBERCULOSIS

Tuberculous meningitis — Empiric antituberculous therapy should be started immediately in any patient
with meningitis syndrome and cerebrospinal fluid (CSF) findings of low glucose concentration, elevated
protein, and lymphocytic pleocytosis if there is evidence of TB elsewhere, either clinically or historically,
or if prompt evaluation fails to establish an alternative diagnosis. Serial examination of the CSF by acid-
fast stain and culture is the best diagnostic approach. Smears and cultures will yield positive results even
days after treatment has been initiated. Nucleic acid amplification (NAA) testing also may be helpful.

Clinical manifestations — Patients with tuberculous meningitis progress through three phases:

•The prodromal phase, lasting two to three weeks, characterized by the insidious onset of malaise,
lassitude, headache, low-grade fever, and personality change.

•The meningitic phase with more pronounced neurologic features (eg, meningismus, protracted
headache, vomiting, lethargy, confusion, and varying degrees of cranial nerve and long-tract signs).

•The paralytic phase, in which the pace of illness accelerates rapidly; confusion gives way to stupor and
coma, seizures, and often hemiparesis.

For the majority of untreated patients, death ensues within five to eight weeks of the onset of illness.

Patients with tuberculous meningitis are categorized by stage on presentation, based upon mental
status and focal neurologic signs as follows:

•Stage I patients are lucid with no focal neurologic signs or evidence of hydrocephalus.

•Stage II patients exhibit lethargy, confusion; they may have mild focal signs, such as cranial nerve palsy
or hemiparesis.

•Stage III represents advanced illness with delirium, stupor, coma, seizures, multiple cranial nerve
palsies, and/or dense hemiplegia.

Diagnosis — Consist of cerebrospinal fluid (CSF) examination (including culture and nucleic acid testing)
and radiography. The demonstration of acid-fast bacilli (AFB) in the CSF remains the most rapid and
effective means of reaching an early diagnosis. We recommend that a minimum of three lumbar
punctures be performed at daily intervals, bearing in mind that empiric therapy need not be delayed
during this time.

Magnetic resonance imaging (MRI) is superior to computed tomography (CT) in defining lesions of the
basal ganglia, midbrain, and brainstem and for evaluating all forms of suspected spinal TB.

Treatment - We recommend initiation of antituberculous therapy on the basis of strong clinical

suspicion of CNS tuberculosis and should not be delayed until proof of infection has been obtained
(Grade 1B). Recommendations of the American and British Thoracic Societies, Infectious Disease Society
of America, and the United States Centers for Disease Control and Prevention, an initial two-month
period of intensive therapy, with four drugs (Grade 1B). The usual four-drug regimen includes daily
isoniazid, rifampin, pyrazinamide, and either moxifloxacin or levofloxacin or streptomycin for fully
sensitive isolates. Intensive therapy is followed by a prolonged continuation phase lasting 9 to 12
months, depending on clinical response and established drug sensitivity of the isolate. The usual
regimen in drug-sensitive disease is isoniazid and rifampin, given daily or three times a week.

Treatment of drug-resistant CNS TB must be individualized and should be guided by the drug
susceptibility pattern of the particular isolate. We suggest extending the duration of therapy to 18 to 24
months.

Adjunctive glucocorticoid therapy for all children and adults with convincing epidemiologic or clinical
evidence for tuberculous meningitis (Grade 1A).

For human immunodeficiency virus (HIV)-infected patients with TB involvement of the CNS who are not
already on antiretroviral therapy (ART), we recommend deferral of ART until eight weeks after starting
TB treatment, regardless of CD4 count (Grade 1B). Development of immune reconstitution inflammatory
syndrome in patients with CNS TB may cause severe or fatal neurological complications.