Granulomatous amoebic encephalitis (GAE) is a rare, usually fatal, subacute-to-chronic

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

disease caused by certain species of free-living

amoeba An amoeba (; less commonly spelled ameba or amœba; plural ''am(o)ebas'' or ''am(o)ebae'' ), often called an amoeboid, is a type of cell or unicellular organism with the ability to alter its shape, primarily by extending and retracting pseudop ...

e of the genera ''

Acanthamoeba ''Acanthamoeba'' is a genus of amoebae that are commonly recovered from soil, fresh water, and other habitats. ''Acanthamoeba'' has two evolutive forms, the metabolically active trophozoite and a dormant, stress-resistant cyst. Trophozoites are ...

'', ''

Balamuthia ''Balamuthia mandrillaris'' is a free-living amoeba that causes the rare but deadly neurological condition granulomatous amoebic encephalitis (GAE). ''B. mandrillaris'' is a soil-dwelling amoeba and was first discovered in 1986 in the brain of ...

'' and '' Sappinia''. The term is most commonly used with ''Acanthamoeba''. In more modern references, the term "balamuthia amoebic encephalitis" (BAE) is commonly used when ''Balamuthia mandrillaris'' is the cause.

Symptoms and signs

GAE starts slowly, with symptoms like headache, nausea, dizziness, irritability and a low-grade fever. The CNS symptoms depend on the part of the brain that is infected. Changes in behavior are an important sign. Other CNS signs may include

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

focal neurologic signs Focal neurologic signs also known as focal neurological deficits or focal CNS signs are impairments of nerve, spinal cord, or brain function that affects a specific region of the body, e.g. weakness in the left arm, the right leg, paresis, or pleg ...

diplopia Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...

(double vision),

cranial nerve palsies Cranial nerve disease is an impaired functioning of one of the twelve cranial nerves. Although it could theoretically be considered a mononeuropathy, it is not considered as such under MeSH. It is possible for a disorder of more than one crani ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, confusion, and personality changes. Some of the symptoms may mimic

glioma A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms ...

(especially

brainstem glioma A brainstem glioma is a cancerous glioma tumor in the brainstem. Around 75% are diagnosed in children and young adults under the age of twenty, but have been known to affect older adults as well. Brainstem gliomas start in the brain or spinal c ...

), or other brain diseases, which may hamper timely diagnosis. The symptoms are caused by inflammatory

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...

of brain tissue brought on by compounds released from the organisms.

Diagnosis

The condition can be difficult for doctors to diagnose, because it is a rare disease. A

brain biopsy Brain biopsy is the removal of a small piece of brain tissue for the diagnosis of abnormalities of the brain. It is used to diagnose tumors, infection, inflammation, and other brain disorders. By examining the tissue sample under a microscope, the ...

will reveal the presence of infection by pathogenic amoebas. In GAE, these present as general inflammation and sparse granules. On microscopic examination, infiltrates of amoebic

cysts A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...

and/or

trophozoites A trophozoite (G. ''trope'', nourishment + ''zoon'', animal) is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing '' Plasmodium falciparum'' and those of the '' Giardia'' group. (The complement of the tropho ...

will be visible.

Treatment

''Acanthamoeba''

Antifungal drugs including

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...

, miconazole,

5-flucytosine Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...

and

pentamidine Pentamidine is an antimicrobial medication used to treat African trypanosomiasis, leishmaniasis, '' Balamuthia'' infections, babesiosis, and to prevent and treat pneumocystis pneumonia (PCP) in people with poor immune function. In African tryp ...

have been shown to be effective against ''Acanthamoeba'' ''in vitro''.Final Diagnosis - Case 156
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''Balamuthia''

Like with ''Acanthamoeba'', infection of the brain with this organism rapidly turns fatal in most cases. However some survivors have been reported: Two patients survived after being successfully treated with a therapy consisting of

flucytosine Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious ''Candida'' infections and cryptococcosis. It may be used by itself or with other antifungals for ...

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...

, sulfadiazine, and azithromycin.

Thioridazine Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwid ...

trifluoperazine Trifluoperazine, marketed under the brand name Stelazine among others, is a typical antipsychotic primarily used to treat schizophrenia. It may also be used short term in those with generalized anxiety disorder but is less preferred to benzodiaze ...

was also given. Successful treatment in these cases was credited to "awareness of ''Balamuthia'' as the causative agent of encephalitis and early initiation of antimicrobial therapy." In one case,

cloxacillin Cloxacillin is an antibiotic useful for the treatment of a number of bacterial infections. This includes impetigo, cellulitis, pneumonia, septic arthritis, and otitis externa. It is not effective for methicillin-resistant ''Staphylococcus aureus ...

ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and join ...

, and

amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis ...

were tried, but this treatment protocol did not prove effective.

Prognosis

Even with treatment, CNS infection with ''Acanthamoeba'' is often fatal, and there are very few recorded survivors, almost all of whom had permanent neurocognitive deficits. The prognosis is largely influenced by the time of diagnosis, how virulent and sensitive the ''Acanthamoeba'' strain is, and, most crucially, the immune status of the affected person. Due to it commonly being an

opportunistic infection An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immun ...

, the prognosis is generally poor, with a mortality rate approaching 90%. ''Sappinia pedata'' can cause GAE, however only one case of GAE due to ''S. pedata'' infection has ever been reported, and the patient survived without any long-term consequences.

References

External links

{{DEFAULTSORT:Granulomatous Amoebic Encephalitis Waterborne diseases Encephalitis Rare infectious diseases