Pathology of Tuberculosis of the Central Nervous System in Children

Pathophysiology

  • Infected droplet inhalation: M. tuberculosis bacilli enter the host by droplet inhalation, the initial point of infection being the alveolar macrophages. Localized infection escalates in the lungs, with dissemination to the regional lymph nodes to produce the primary complex (Ghon’s focus). During this phase of transient bacteremia, tubercle bacilli can seed other organs in the body (7, 16-18).
  • Dissemination to the CNS hematogenous: This mode of dissemination is particularly the case with miliary TB. Infection may start as subpial or subependymal cortical foci of metastatic caseous lesions (Rich focus) (19).
  • TB meningitis due to rupture of Rich focus into subarachnoid space: The location of the expanding tubercle (i.e., Rich focus) (19) determines the type of CNS involvement. This occurs as a complication of postprimary infection in infants and young children and from reactivation in older adults and those with immunodeficiency.
  • Subarachnoid exudate infiltrates vessels: A thick gelatinous exudate infiltrates the cortical or meningeal blood vessels, producing inflammation, obstruction, or infarction. Basal meningitis accounts for the frequent dysfunction of cranial nerves III, VI, and VII, eventually leading to communicating or obstructive hydrocephalus from obstruction of basilar cisterns. Subsequent neurological pathology is produced by three general processes: adhesion formation, obliterative vasculitis, and encephalitis or myelitis (7, 17-19).
  • Tuberculomas/TB abscesses: These lesions result from the coalescence of caseating granulomas without rupture into subarachnoid space or as a paradoxical reaction despite adequate drug therapy.
  • Spinal TB arachnoiditis: This is a focal inflammatory disease at single/multiple levels that encases the spinal cord in a gelatinous/fibrous exudate.

Classification of neurotuberculosis

  • Meningovascular: This results in TB meningitis and meningoencephalitis, spinal arachnoiditis, and radiculomyelitis/myelitis.
  • Parenchymal: Present in this type are tuberculomas (tuberculous granuloma) and TB abscesses (20, 21).
  • Secondary involvement of nervous system: In this form spinal-cord disease or compression can occur due to vertebral osteomyelitis as well as diffuse brain involvement (miliary tuberculosis of brain) due to hematogenous dissemination (20, 21).

Histopathology

  • Microscopic appearance: The inflammation produced with TB infection is granulomatous, with epithelioid macrophages and Langhans’ giant cells along with lymphocytes, plasma cells, a few PMNs, fibroblasts with collagen, and characteristic caseous necrosis in the center. The inflammatory response is mediated by a type IV hypersensitivity reaction (18, 22, 23).
Histology of a tuberculous granuloma: Central caseation surrounded by epithelioid macrophages and Langhans’ giant cells along with lymphocytes and plasma cells is seen. The inflammatory response is mediated by a type IV hypersensitivity reaction.

Stains

  • Acid fast stain (Ziehl-Neelsen or Kinyoun’s): These stains show the organisms as slender red rods.
  • Auramine-rhodamine stain: This stain causes fluorescence of the organisms when viewed under the fluorescence microscope. Although nonspecific, it is used for screening as more organisms will be apparent.