Fungal Infections of the Nervous System

Brain scan of a patient with meningitis


There’s something creepy about fungus. Maybe it’s because fungi are so unlike more familiar forms of life, such as plants or animals. Or maybe it’s the association between a fungus and things that are dead or dying. While no infection is welcome, something about fungal infections seems uniquely nasty. This is particularly the case when the fungus invades something as prized and private as our brains.

Fungal infections of the central nervous system are not particularly common, but when such infections occur, the results can be devastating. What follows is a rogue's gallery of familiar fungal infections in neurology, but unfortunately, the complete list of all possible invaders would be considerably longer.


Aspergillus species are very common in nature. Despite frequent exposure, human infection with Aspergillus is relatively uncommon, unless the immune system has been suppressed. Risk factors for a suppressed immune system include diabetes, steroid treatment, organ transplants, cancers, trauma, malnutrition, and AIDS, among others.

The organism enters the body after being breathed into the lungs, where it enters the bloodstream. Once in the blood, Aspergillus can infect many different organs, including the brain.

Aspergillus that invades the brain can cause seizures or focal deficits, like numbness or weakness. It can also cause meningitis. Symptoms of meningitis include a headache, fever, and a rigid neck.

On an MRI, an Aspergillus infection causes an abscess that looks like a cannonball in the brain. Treatment is with an antifungal agent such as voriconazole or amphotericin. Even with treatment, the mortality of this infection is relatively high.

Candida Albicans

Almost everyone is already harboring candida in the body; it’s part of the normal flora of the gastrointestinal and genitourinary tracts. Sometimes an event happens that causes candida to outgrow its normal boundaries, which usually causes yeast infections in women. Candida is also well known for causing thrush, a whitish coating of the mouth and throat.

In immuno-compromised patients, Candida species may enter the blood and spread to various areas in the body. Candida may cause meningitis, most often in premature neonates, or as a surgical complication. Diagnosis is made by gathering a large amount of cerebrospinal fluid (CSF) to grow in a lab culture.

Coccidioides Immitis

Coccidioides is found in the deserts of the southwestern United States and Central and South America. Infection with coccidiosis can cause numerous problems, ranging from the usually benign valley fever to lethal meningitis.

If not treated, approximately 95 percent of patients with coccidial meningitis will die within two years, according to the National Institutes of Health.

Approximately 150,000 Coccidioides infections occur every year, and fewer than 100 progress to meningitis. However, it may take months from the initial infection for meningitis to become obvious.

Symptoms include a severe headache, as well as other symptoms that may not be present until late in the course of the disease.

The diagnosis of coccidia meningitis is best done by examination of CSF, obtained by a lumbar puncture. Antibodies for the organism can be tested for using that CSF. On rare occasions, a biopsy of the tissues surrounding the brain (meninges) may be needed for an accurate diagnosis.

The preferred treatment for coccidiosis infections is oral fluconazole. Some doctors will add amphotericin B. If hydrocephalus is present, a shunt may be necessary as well. It may take weeks before there is any obvious improvement.

Cryptococcus Neoformans

Cryptococcus enters the body through the lungs after someone breathes in a fungal spore. From there, the fungus enters the bloodstream and spreads through the body, particularly to the brain. This is especially the case in people whose immune systems are suppressed, though occasionally healthy people also are infected by Cryptococcus.

Cryptococcus usually causes an aseptic meningoencephalitis (inflammation of the brain and surrounding tissues), with a headache, fever, and often a stiff neck and vomiting. The encephalitis component causes associated memory changes and other cognitive deficits.

Cryptococcal meningitis can be diagnosed by running appropriate tests on cerebrospinal fluid collected by a lumbar puncture. If the pressure of the CSF is measured, it can be very high in these infections.

An MRI frequently shows no changes, though sometimes a mass may be present. A blood test can also be done in patients for a cryptococcal antigen that can be useful in making this diagnosis.


Histoplasmosis is a fungus that may be found in normal, healthy people—but it also occasionally causes serious illness. In the United States, it’s usually found in the Ohio and Mississippi River valleys in the Midwestern states.

Most of the time, the fungus only causes problems in people whose immune systems are compromised by conditions like AIDS or certain medications. Histoplasma can cause fever, weight loss, and fatigue.

While histoplasmosis can cause problems throughout the body—especially the lungs—when it attacks the central nervous system, it can be detected by searching for antigens in cerebrospinal fluid. The organism does not seem to grow easily in a laboratory. Half of the time, cultures of CSF do not grow the organism, even if there is an infection. Sometimes, a brain or meningeal biopsy is the only way to make the diagnosis.

Histoplasmosis that enters the central nervous system can be very difficult to treat. About 60 to 80 percent of patients respond to treatment initially, according to the National Institutes of Health, but about half of these may relapse in later years.

In the case of relapse, some patients may require long-term—or even life-long—anti-fungal treatment.

Amphotericin B is the recommended treatment for those patients sick enough to be hospitalized. Those who are less severely ill may be better treated with itraconazole.


Mucormycosis is one of the most feared neurological infections. When this fungus invades the brain or important blood vessels around the brain, the mortality rate is very high. Only a few patients have ever been cured under these conditions.

The fungi that cause these infections are actually commonly found in nature and all humans are regularly exposed. Like many fungal infections, almost all human cases of invasion occur when the patient is immunocompromised.

A mucormycosis infection of the brain usually starts in the nasal sinuses, where the disease initially mimics sinusitis with a headache, congestion, and fever. The fungus kills invaded tissues quickly and can spread from the sinuses directly into the eyes and brain.

Rarely, the fungus can reach the brain through other routes, such as after being injected into the bloodstream with intravenous drugs.

As soon as the diagnosis of mucormycosis is made, a surgeon is required in order to cut away all dead tissue. This surgery can be disfiguring, as the nasal cartilage, the orbit of the eye, and the palate may all have to be removed. Early initiation of a strong anti-fungal agent such as amphotericin is also critical. Even with aggressive treatment, survival of such invasive cerebral mucormycosis is rare.

A Word From Verywell

Most cases of neurological fungal infections occur in people whose immune systems aren't working properly. While a fungus can attack healthy people, such infections are relatively rare. That said, these infections can be very serious, or even lethal, and need to be recognized and treated as soon as possible.

Was this page helpful?

Article Sources

  • Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347:408.
  • Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54 Suppl 1: managementS16.
  • Igel HJ, Bolande RP. Humoral defense mechanisms in cryptococcosis: substances in normal human serum, saliva, and cerebrospinal fluid affecting the growth of Cryptococcus neoformans. J Infect Dis 1966; 116:75.
  • Johnson RH, Einstein HE. Coccidioidal meningitis. Clin Infect Dis 2006; 42:103
  • Segal BH. Aspergillosis. N Engl J Med 2009; 360:1870.
  • Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore) 1990; 69:244.
  • Wheat LJ, Musial CE, Jenny-Avital E. Diagn Management of central nervous system histoplasmosis. Clin Infect Dis 2005; 40:844.