Use of FDG‐PET in Balamuthia mandrillaris Amebic Encephalitis

An 81-year-old man presented with 2 weeks of feeling "not present." He endorsed mild confusion and fatigue. A brain magnetic resonance imaging (MRI) showed a peripherally enhancing, right parieto-occipital lesion measuring 4 × 3.5 cm with hemosiderin staining, mildly reduced diffusion, and substantial vasogenic edema (see Figure 1). The HIV antigen/antibody was negative. The blood sedimentation rate and C-reactive protein were normal. Cerebrospinal fluid (CSF) demonstrated 82 white blood cells/ul (66% lymphocytes, 17% monocytes, and 17% atypical mononuclear cells) and elevated protein of 97 mg/dl. Gram stain and bacterial culture were negative. A meningitis/encephalitis polymerase chain reaction (PCR) test (Biofire FilmArray, BioMérieux Diagnostics) from the CSF was negative. Biopsy of the parieto-occipital lesion demonstrated organisms with morphological appearance of amoebas, and Balamuthia mandrillaris was detected by PCR (through the University of Washington Department of Laboratory Medicine and Pathology1) from the CSF. The patient was started on combination therapy with miltefosine 50 mg 3 times daily, azithromycin 500 mg daily, fluconazole 1,000 mg daily, flucytosine 3,000 mg every 6 hours, sulfadiazine 1,500 mg every 6 hours, and albendazole 400 mg twice daily. His course was complicated by drug-related toxicities, including nausea/vomiting and acute kidney and liver injury, leading to discontinuation of albendazole (after 3 weeks), flucytosine (after 4 weeks), and sulfadiazine (after 3 months). He improved on a regimen of miltefosine, azithromycin, and renally dose-adjusted fluconazole. Serial MRIs demonstrated interval decrease in the size of the lesion. Repeat CSF evaluation after 18 months on treatment was normal with negative B. mandrillaris PCR and metagenomic next generation sequencing. Although the parieto-occipital lesion had reduced in size, the rim-enhancing lesion still measured 2.7 × 2.2 cm after 2 years on treatment, with markedly reduced diffusion of internal contents (see Figure 1). The 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) with concurrent MRI (FDG-PET/MRI) showed no appreciable radiotracer uptake (see Figure 1). Together with clinical recovery, reduction in lesion size, and normal CSF parameters, the FDG-PET provided additional data to support successful treatment of the infection. All antimicrobial therapy was stopped. Surveillance FDG-PET/MRI, most recently about 1 year since stopping therapy, has been stable. B. mandrillaris, a free-living amoeba found in soil, is an emerging pathogen that infects the central nervous system (CNS) and skin. The classic neurologic syndrome caused by B. mandrillaris is an encephalitis with solitary or multifocal enhancing mass lesions with surrounding edema, typically with mild heterogeneous reduced diffusion and small volume hemorrhage.2 Diagnosis often requires sampling of brain tissue for histopathology, indirect immunofluorescent staining, or molecular testing (eg, PCR). The reported case fatality rate for Balamuthia encephalitis is high, although this may reflect delays in diagnosis and treatment. Because of the high risk of morbidity and mortality, recommended treatment is a minimum of 1 year.3 In the absence of evidence-based data or expert opinion to guide clinical practice, the decision to end antimicrobial therapy for rare CNS infections like Balamuthia is challenging. This case demonstrates the utility of FDG-PET as an adjunct to assess therapeutic response to antimicrobials. Although FDG-PET has been used to diagnose and evaluate patients with Balamuthia encephalitis and for treatment monitoring of bacterial brain abscesses, it has not been used to confirm cure of amoebic infections.4, 5 Given the rarity of Balamuthia encephalitis, high mortality, and lack of biomarkers to track therapeutic response, FDG-PET is a novel tool that can verify treatment success and guide duration of therapy for Balamuthia encephalitis. The authors are grateful to the patient and his family, along with the large clinical team across institutions who contributed to the patient's care. Kristoffer E. Leon: Writing – original draft; writing – review and editing; investigation. Andreas M. Rauschecker: Writing – original draft; writing – review and editing; investigation; visualization; supervision. Felicia C. Chow: Conceptualization; writing – original draft; writing – review and editing; supervision; investigation; methodology. The authors have no potential conflicts of interest to disclose. Institutional review board approval was not required for this report.