Neurosurgery notes/Infection/Cranial infection/Fungal infections/Cryptococcosis

Cryptococcosis

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Fungal infections

Numbers

  • The second most freqeunt CNS fungal infection
  • Diagnosed more frequently in living patients than any other fungal disease.
  • Most frequent fungal meningitis
    • There are rarely cryptococcomas in the parenchyma.

C. neoformans

  • Bird faeces
  • Single budding yeast with a thick capsule. The capsule disappears during the tissue preparation to form the characteristic halo.
  • Enters the body through the respiratory tract.
    • Dehydrated yeast cells or basidiospores (<5 to 10 µm) are sufficiently small for inhalation and alveolar deposition.
  • Macrophage is generally considered the central effector cell against C. Neoformans
    • Ingests and kills the yeast and releases proinflammatory cytokines (e.g., interleukin-12)
  • T-cells are believed to contribute to host defence by providing cytokines (e.g., interferon) that activate macrophage fungicidal activity and promote the transformation of alveolar macrophages into giant cells capable of ingesting large encapsulated yeast cells
  • Once established in the lungs, C. neoformans may spread to intrathoracic lymph nodes and then hematogenously disseminate to seed the meninges,
  • Meningoencephalitis is more appropriate than meningitis because the brain parenchyma is almost always involved.

Two forms

Cryptococcal meningitis

  • Number
    • Occurs in 4–6% of patients with AIDS.
  • Presentation
    • Fever
    • Malaise
    • H/A
    • Meningeal signs
      • Nuchal rigidity, photophobia
      • Occur in only ≈ 25%.
    • Encephalopathic symptoms
      • Lethargy, altered mentation
      • Due to increased ICP
        • (With or without hydrocephalus on CT/MRI)
      • Occur in a minority
  • Can also occur without AIDS
    • Cryptococcus gattii can infect the brain of immunocompetent hosts
  • Radiological
    • Dilation of Virchow-Robbins spaces
    • MRI the signal is similar to CSF on T1WI & T2WI, but will be higher on FLAIR
  • Late deterioration in the absence of documented infection may respond to
    • Dexamethasone 4mg q 6 hrs transitioned to prednisone 25mg PO q d

Cryptococcoma (mucinous pseudocyst)

  • A parenchymal collection which occurs almost exclusively in AIDS patients.
  • Much less common than cryptococcal meningitis.
  • Radiological
    • No enhancement of the lesion or the meninges.
    • Usually 3–10mm in diameter and are frequently located in the basal ganglia
      • Due to spread by small perforating vessels

Occurs in both

  • Healthy
  • Immunocompromised
    • In HIV, Cryptococcus neoformans is the typical agent

Evaluation

  • LP
    • Raised OP (75%)
  • Test
    • Cryptococcus antigen is positive (90%),
      • Serum cryptococcal antigen: almost always elevated with CNS involvement
      • CSF cryptococcal antigen raised
    • CSF cultures are positive (75%),
    • India ink stain is positive (50%)

Treatment

  • Amphotericin B (0.7 mg/kg IV split in QDS) + fluconazole (100mg/kg PO split in QDS)
    • ≥ 2 weeks if renal function is normal
    • Most immunocompetent patients will be successfully treated with 6 weeks of therapy
    • After 2 weeks of treatment, repeat the LP
      • Look for clearance of the organism from the CSF.
      • Positive CSF cultures after 2 weeks of treatment are predictive of future relapse and are associated with worse outcome
  • Treatment failures
    • Defined as
      • Lack of clinical improvement after 2 weeks of appropriate therapy, including
        • Management of ICHT, or
        • Relapse after an initial response (defined as either a positive CSF culture and/or rising CSF cryptococcal Ag titer with a compatible clinical picture).
    • Management
      • Optimal management has not been defined
      • Trial with alternative antifungals (e.g. flucytosine) or higher doses of fluconazole
  • Management of raised ICP OP≥25cm H₂O
    • Not effective with corticosteroids, acetazolamide, and mannitol
    • Daily LPs
      • Drain enough CSF to reduce ICP by 50% (typically 20–30 ml)70
      • May be suspended when pressures are normal for several consecutive days
    • Lumbar drain
      • Occasionally needed for extremely high OPs (> 40cm H₂O)
      • When frequent LPs are required to or fail to control symptoms69
    • CSF shunt
      • Considered when daily LPs are no longer tolerated or when signs and symptoms of ICHT are not being relieved
      • Neither dissemination of infection through the distal shunt nor creation of a nidus of infection refractory to medical therapy has been described
      • Options
        • Lumboperitoneal shunt
        • VP or VA shunt
  • Maintenance therapy (secondary prophylaxis)
    • HIV patients who have completed 10 weeks of treatment should be maintained on fluconazole 200mg q d until immune reconstitution occurs, otherwise lifetime treatment is indicated
    • Some experts perform an LP to document negative CSF culture and antigen before stopping maintenance
  • Risk of recurrence is low for patients who remain asymptomatic after a complete course of therapy and have sustained increase (> 6 months) of CD4+ counts to ≥ 200cells/mcl.
  • Cerebral cryptococcosis
    • The presence of multifocal gelatinous cysts within the bilateral basal ganglia is a classic pattern of CNS involvement by Cryptococcus in the immunocompromised host.
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