Specific fungi associated with CNS infections

Increased use of immunosuppressive drugs, increasingly potent broad-spectrum antibiotics, and the spread of AIDS have made fungal infections of the CNS much less rare than they once were. They may even be predicted from the clinical context.141

Most patients with a fungal infection of the central nervous system (CNS) have some predisposing flaw in their immune response that allows invasion by relatively nonvirulent fungi:

Immune risk/deficit	Representative fungi
Prematurity	Candida albicans
Inherited immune defects (e.g., chronic granulomatous disease, severe combined immunodeficiency)	Candida, Cryptococcus, Aspergillus
Acquired immune defects
Steroids	Cryptococcus, Candida
Cytotoxic agents	Aspergillus, Candida
HIV infection	Cryptococcus, Histoplasma
Alcoholism	Sporothrix
Iron chelator therapy	Zygomycetes
Intravenous drug abuse	Candida, Zygomycetes
Ketoacidosis	Zygomycetes
Trauma, foreign body	Candida

Different clinical syndromes are more commonly associated with various specific fungi:

Species	Relative incidence	Clinical syndrome
		Meningitis	Abscess	Infarct
Cryptococcus	Common	Common	Infrequent	Infrequent
Coccidioides	Common	Common	Infrequent	Infrequent
Candida	Common	Occasional	Occasional	Rare
Molds (e.g., Aspergillus)	Occasional	Infrequent	Occasional	Common
Zygomycetes	Occasional	Infrequent	Occasional	Common
Histoplasma	Occasional	Infrequent	Infrequent	Infrequent
Blastomyces	Occasional	Infrequent	Infrequent	Rare
Sporothrix	Occasional	Infrequent	Rare	Rare

Information on the epidemiology, diagnosis, and treatment of CNS fungal infections that can be complicated by seizures is listed in Table: Epidemiologic, diagnostic, and therapeutic aspects of CNS fungal infections

Fungal meningitis

Clinical manifestations of fungal meningitis are less stereotyped than the manifestations of bacterial meningitis. Patients often present with a chronic meningitis syndrome (defined as meningitis that persists for at least 1 month). In fact, fungal meningitis is always a consideration in the differential diagnosis of any patient with a chronic meningitis syndrome.

CSF cultures are frequently negative. Because fungal meningitis often involves the base of the brain more prominently than the spinal cord, cisternal CSF may yield organisms when lumbar CSF is negative. Repeated examinations of lumbar CSF or aspirates of cisternal or ventricular fluid may be needed before a diagnosis is made.139,140 Cryptococcal meningitis is the easiest fungal CNS infection to diagnose via CSF analysis.

Seizures with CNS fungal infections

The full range of seizure symptomatology can occur secondary to CNS fungal infections. There are many reports of patients presenting with new-onset seizures who deteriorated or died before a fungal cause was diagnosed,142 underscoring the importance of liberal inclusion of fungal infection in the differential diagnosis of new-onset seizure, especially when any predisposing clinical context exists.143

Anticonvulsant therapy follows routine guidelines. The clinician must be aware of frequent antifungal-anticonvulsant interactions. Maintenance anticonvulsant therapy is usually required, even after definitive antifungal treatment.

Immune Response Table adapted from JR Perfect, DT Durack. Fungal Meningitis. In WM Scheld, RJ Whitley, DT Durack (eds), Infections of the Central Nervous System. Philadelphia: Lippincott–Raven, 1997;721–739.
Different clinical syndromes Table adapted from JR Perfect, DT Durack. Fungal Meningitis. In WM Scheld, RJ Whitley, DT Durack (eds), Infections of the Central Nervous System. Philadelphia: Lippincott–Raven, 1997;721–739.
Adapted from: Goldstein MA and Harden CL. Infectious states. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;83-133.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised March 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

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