Chronic meningitis

Background

• Infection or inflammation of the meninges and subarachnoid space lasting 4 or more weeks

Differential Diagnosis

Organism	Risk Factors	Clinical Features	Diagnosis	Treatment
Brucella	unpasteurized dairy or infected animals in endemic areas	undulating fever, CN palsies, behavioural changes	serology	doxycycline, ceftriaxone, or rifampin
Tropheryma whipplei	Whipple disease	cognitive impairment, ataxia, ophthalmoplegia, supranuclear gaze palsy, lymphadenopathy	CSF PCR	ceftriaxone followed by TMP-SMX
Cryptococcus	cell-mediated immunodeficiency	encephalitis with personality changes, memory loss, headache, may have skin lesions	CSF CrAg	amphotericin B and flucytosine
Coccidioides immitis	cell-mediated immunodeficiency, in endemic area	headache, altered mentation, nausea/vomiting, focal deficits, can has CSF eosinophilia	serum and CSF serology	fluconazole, intrathecal amphotericin B
Histoplasma capsulatum	cell-mediated immunodeficiency, in endemic area	constitutional symptoms	serum and urine antigen	amphotericin B followed by itraconazole
Angiostrongylus cantonensis	eating raw or undercooked shellfish, snails, or water plants in Asia and South Pacific	severe headache, pruritic rash, paresthesias, eosinophilia		self-limited (2 months)
Borrelia burgdorferi	exposure to Ixodes ticks	preceding erythema migrans	serology	ceftriaxone
Treponema pallidum pallidum	high-risk sexual contacts	concurrent sexually-transmitted infections	CSF VDRL	penicillin

• Fungal infections
  • Cryptococcus
  • Coccidioides
  • Histoplasma
  • Candida
  • Sporothrix (rare)
  • Blastomyces (rare)
  • Other rare molds: Scedosporium, Aspergillus, Cladophialophora, and other dematiaceous molds
• Bacterial infections
  • Mycobacterium tuberculosis
  • Treponema pallidum
  • Borrelia burgdorferi
  • Tropheryma whipplei
  • Actinomyces (parameningeal, rare)
  • Nocardia (with brain abscess)
  • Brucella (rare)
• Viral infections
  • Echovirus (meningoencephalitis)
• Parasitic infections
  • Acanthamoeba
  • Balamuthia
  • Taenia solium
  • Angiostrongylus cantonensis
• Other causes
  • Neurosurgical infection: ventricular shunt infection, infected prosthetic material
  • Tumours: diffuse gliomatosis, metastatic meningeal malignancies including lymphomatous meningitis
  • Others: sarcoidosis, Vogt-Koyanagi-Harada syndrome, Behçet syndrome, IgG4-related hypertrophic pachymeningitis

Investigations

• CSF tests:
  • Glucose, protein, cell count and differential (including eosinophils)
  • India ink on centrifuged sediment
  • Fungal culture of 3-5 mL of CSF
  • Cytopathology for malignant cells, including PCR or flow cytometry for monoclonal B cells
  • Periodic acid-Schiff stain for Whipple disease
  • VDRL test
  • Cryptococcal antigen
  • Histoplasma antigen
  • Aspergillus galactomannan antigen
  • Coccidioides antibody by complement fixation or immunodiffusion
  • PCR for tuberculosis, Whipple disease, enterovirus, and lymphoma
  • Culture for enterovirus and Acanthamoeba
• Blood tests
  • RPR or other routine syphilis screening
  • Serology for Coccidioides, Histoplasma, Toxoplasma, and Brucella antibodies
  • Serology for Histoplasma antigen (may be from blood or urine)
• Brain biopsy has low diagnostic yield in chronic meningitis