Granulomatous Amebic Encephalitis

A malnourished 8-year-old girl with history of facial trauma 3 months prior, presented with somnolence, vomit and non-specific headache; a head CT was obtained (not shown), reporting a left frontal tumour. Lumbar puncture was performed and CSF analysis showed no abnormalities.

A brain MRI was performed for further characterization, which showed an intra-axial left frontal, heterogeneous lesion with extensive vasogenic oedema and mild mass effect; diffusion restriction and avid enhancement of the edges were present (Figure 1). Spectroscopic analysis suggested a necrotic centre with hypercellular edges (Figure 2). It was concluded that this was a high-grade glial tumour with central necrosis. The study also noticed left facial soft tissue swelling with avid enhancement and a small abscess on the nose (Figure 3).

The patient was taken to neurosurgery where the surgical team found a tumour-like lesion with macroscopic necrotic/hemorrhagic aspect. Trans-operatory histopathological evaluation reported a granulomatous inflammatory process with no neoplastic cells.

Over the next few days, her neurological status worsened; the patient also developed fever and facial swelling increased importantly. A second MRI was performed, showing increase in soft tissue inflammation that extended to the nasal fossa and even the left maxillary sinus as well as periorbital cellulitis. The surgical site now showed a heterogeneous lesion with central high diffusion restriction and peripheral thin enhancement resembling an abscess (Figures 4 and 5).

She rapidly deteriorated and died 5 days after the surgery was performed. Histopathological results from the lesion excision arrived after the patient’s dead revealing granulomatous amebic encephalitis (Figure 6).

Free-living amoebas are ubiquitous protozoan parasites in the environment. Their transmission occurs with no intermediate host. They are found in water, airborne dust and soil. Amoebas causing CNS infections in humans include Naegleria fowleri, Acanthamoeba sp., Balmuthia mandrillaris, and Sappinia pedata. All of these species cause central nervous system (CNS) infections [1].

Two types of amebic CNS infections have been identified. Primary amebic meningoencephalitis is an amebic CNS infection caused by Naegleria fowleri, which is caught from inhalation infected water sources. Direct dissemination to the brain causes a severe infection with mortality rates reported as high as 99% [2]. Granulomatous amebic encephalitis is a rare subacute-chronic CNS infection that can be caused by Acanthamoeba species, B. mandrillaris, and S. pedata.

Acanthamoeba can be found in soil, air and water rich in biofilms. Inhalation or direct contact are the main forms of transmission; then, hematogenous spread carries it to the brain. It mainly affects immunocompromised hosts, causing a disease with prolonged clinical course characterized by headache, low-grade fever, behavioural anomalies and focal neurological deficits.

Balamuthia mandrillaris is commonly isolated from soil. It affects more commonly males than females (2.5:1) and about half of the patients are younger than 15 years old, occurring in both, immunocompromised and immunocompetent patients [3]. It may start as a skin infection that causes a non-ulcerated asymptomatic plaque which may or may not have satellite lesions; the most common location is the face, over the nose. Hematogenous spread carries it to the brain, where thrombotic angiitis causes the symptoms, leading to hemorrhage, infarction and necrosis. The course of the disease may be subacute (2-12 weeks), with headache and vomiting being the main symptoms, evolving ultimately to stupor and coma [4].

On MR imaging, two patterns have been identified; multifocal lesions and a pseudotumoral pattern. Multifocal lesion show T2 hyperintensity and a heterogeneous or ringlike enhancement in post-gadolinium imaging. These affect the diencephalon, thalamus, brain stem, and posterior fossa structures. Intralesional hemorrhage occurs often which is explained by necrotizing angiitis. Multifocal lesions in GAE are thought to represent focal areas of cerebritis or microabscesses. The pseudotumoral pattern often shows a mass-like lesion with heterogeneous signal intensity, and often linear and superficial gyriform enhancement after gadolinium administration. This pattern is probably explained by inflammatory response with border zone encephalitis and microabscess formation [5, 6].

Histopathologic evaluation shows a diffuse granulomatous reaction, surrounding infiltrate with lymphocytes and plasma cells, and abundant multinucleated giant cells inside and outside granulomas. Definitive diagnosis requires visualization of a trophozoite; visualization of the nucleus and nucleolus of the amoeba may be a distinguishing clue [7]

Treatment includes wide resection of the CNS and skin lesions when possible [8]. Optimal antibiotic therapy is still uncertain, with patients receiving a number of different antibiotic combinations, mostly with poor response; the combination of pentamidine, sulfadiazine, fucytosine, fuconazole, azithromycin or clarithromycin, and miltefosine is recommended for treatment of Balamuthia infection [9].

Conclusion

Amoebic brain infections are rare but highly lethal. It is important to consider that there are two imaging patterns for granulomatous amebic encephalitis, including multifocal and pseudotumoral. Skin lesions (when present), added to clinical course and imaging findings must prompt histopathological evaluation to initiate appropriate management, which can be life-saving.

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