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Successful Treatment of Granulomatous Amoebic Encephalitis with Combination Antimicrobial Therapy

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Successful Treatment of Granulomatous Amoebic Encephalitis with Combination Antimicrobial Therapy □ CASE REPORT □ Successful Treatment of Granulomatous Amoebic Encephalitis with Combination Antimicrobial Therapy Hideki Kato 1, Shigehisa Mitake 1, Hiroyuki Yuasa 1, Shigemasa Hayashi 2, Tatsuru Hara 3 and Noriyuki Matsukawa 4 Abstract Granulomatous amoebic encephalitis (GAE) is a rare but fatal infection. Due to its nonspecific symptoms and laboratory and neuroradiological findings, it is rarely diagnosed antemortem. We herein present the case of a 72-year-old Japanese woman who was diagnosed with GAE following the detection of a pathogen simi- lar to Balamuthia mandrillaris under a microscopic examination of cerebrospinal fluid sediment and who achieved remission with combination antimicrobial therapy. There are no previous reports of pathogens simi- lar to B. mandrillaris being detected in cerebrospinal fluid antemortem; therefore, this case may be used as a benchmark for further studies. Key words: granulomatous amoebic encephalitis (GAE), antimicrobial therapy, free-living amoebae, cerebrospinal fluid (CSF) (Intern Med 52: 1977-1981, 2013) (DOI: 10.2169/internalmedicine.52.0299) cases of survival. Because GAE is a rare disease with non- Introduction specific symptoms, making the diagnosis antemortem is dif- ficult. Additionally, there are no reports in which the Meningoencephalitis caused by free-living amoebae in- Balamuthia-like amoeba itself was found in cerebrospinal cludes two clinical entities: primary amoebic meningoen- fluid (CSF) (4). The present report describes a case of GAE cephalitis (PAM) and granulomatous amoebic encephalitis caused by amoebae with Balamuthia-like morphological (GAE). Both have a poor prognosis, usually resulting in characteristics detected in the CSF in which we administered death (1, 2). The pathogenic organism responsible for PAM antimicrobial therapy and were able to save the patient’s is Naegleria fowleri. Infection with this organism generally life. progresses rapidly following the development of symptoms and leads to death within ten days. GAE, in contrast, is Case Report caused by Acanthamoeba species and Balamuthia mandril- laris and progresses from subacute to chronic over several A 72-year-old right-handed Japanese woman presented to weeks to two years, followed by death. Since B. mandril- our emergency department complaining of disordered con- laris was first isolated from the brain of a pregnant mandrill sciousness and left-sided paralysis. She had a history of hy- baboon in 1986, it has been found to cause GAE in hu- pertension when she had traveled to Guam 20 years earlier. mans (3), with almost 200 cases having been reported Approximately six months prior to admission, she increas- worldwide. Balamuthia encephalitis can develop in children ingly complained of sleepiness and lethargy. Starting ap- and elderly individuals with normal immunity, while Acan- proximately two months prior to admission, her appetite had thamoeba species usually cause encephalitis in immunocom- also decreased, and she was diagnosed with depression and promised hosts. The prognosis of patients with GAE caused treated at a psychiatric clinic. Upon arrival to the emergency by B. mandrillaris is very poor, with only eight reported department, the patient exhibited slightly impaired con- １Department of Neurology, Tosei General Hospital, Japan, ２Department of Neurosurgery, Tosei General Hospital, Japan, ３Department of Parasi- tology, Kurume University School of Medicine, Japan and ４Department of Neurology, Nagoya City University, Japan Received for publication February 6, 2013; Accepted for publication April 19, 2013 Correspondence to Dr. Noriyuki Matsukawa, [email protected] 1977 Intern Med 52: 1977-1981, 2013 DOI: 10.2169/internalmedicine.52.0299 Figure 1. Magnetic resonance imaging (MRI) and MRA of the brain performed on admission (A- D) and day 9 posthospitalization (E, F). An axial T2-weighted image shows a high signal in the right insular cortex and left occipital lobe of the cerebrum (A). MRA shows occlusion of the right median cerebral artery (B). Diffusion-weighted MRI reveals a diffuse high signal in the right insular cortex and right parietal lobe (C, D). An axial T1-weighted image obtained following the administration of gadolinium shows nodular enhancement in the right insular cortex, meninges in the vicinity and left occipital lobe of the cerebrum (E, F). sciousness (Glasgow Coma Scale: E3V4M6). A physical ex- white and muddy. A CSF examination showed a cell count amination revealed a normal blood pressure (134/87 mmHg) of 1,153 cells/mm3 (46% neutrophils), a protein level of 134 with tachycardia (pulse: 101 beats per min) and a low-grade mg/dL, a sugar level of 40 mg/dL (the blood sugar level fever (37.6℃). She had no skin rashes, and her lymph was 119 mg/dL in blood collected simultaneously) and an glands were not enlarged. A neurological examination re- adenosine deaminase level of 5.5 IU/L. A microscopic ex- vealed a slight loss of muscle strength in the left arm and amination with India ink staining, bacterial and tuberculosis leg with left spatial neglect. Blood tests showed a white bacillus cultures and cerebrospinal cytological diagnoses blood cell count of 10,610/mm3, a red blood cell count of were all negative. Axial T1-weighted imaging with gadolin- 355×103/mm3, an Hb level of 9.9 g/dL, a hematocrit level of ium of repeated head MRI revealed nodular pathological 29.7%, a platelet count of 35.5×104/mm3 and a C-reactive changes in the right insular cortex, meninges in the vicinity protein level of 2.86 mg/dL. T2-weighted magnetic reso- and left occipital lobe of the cerebrum (Fig. 1E, F). Because nance imaging (MRI) demonstrated a high signal in the bacterial and/or fungal meningitis was suspected, ceftriaxone right insular cortex and left occipital lobe of the cerebrum at a dose of 2 g/day and fluconazole at a dose of 200 mg/ (Fig. 1A). High signals were observed in the right insular day were intravenously administered. Markers for several cortex and right parietal lobe on diffusion-weighted imaging, kinds of fungal antigens, viral antibodies and syphilis were while occlusion of the right middle cerebral artery (MCA) all negative in both the serum and CSF. There were no ab- branch was observed on MR angiography (Fig. 1B, C, D). normal findings on a random skin biopsy, and no malignant Transthoracic echocardiography did not show left ventricle tumors were found in various tests. Anti-HIV antibodies enlargement or thrombus formation. Based on this informa- were also negative. On day 32, a skull-opening brain biopsy tion, the patient was diagnosed with a cerebral infarction was performed. A pure white, cheese-like, homogenous sub- (atherothrombotic infarction) and treated accordingly. Star- stance filled the right Sylvian fissure and adhered to the tis- ing on day 3 of hospitalization, she complained of a head- sue so that the M1-M2 portion of the right MCA was cov- ache and loss of appetite. On day 9 of hospitalization, a ered. Although the external shape of the MCA was main- lumbar puncture was performed because she developed tained, black discoloration characterized the middle of the vomiting, a fever of 38℃ and nuchal rigidity. The initial M2 portion. The biopsied brain tissue manifested slight glio- pressure was 22 cmH2O, and the CSF appeared yellowish sis; however, there was no blood vessel inflammation or 1978 Intern Med 52: 1977-1981, 2013 DOI: 10.2169/internalmedicine.52.0299 sulting in remission. PCR analyses of the CSF and IIF staining of biopsy sec- tions are usually used to diagnose GAE (4, 5). Recently, high-sensitivity real-time PCR targeting the RNase P gene has been developed (6). In the current case, however, the PCR test was negative for amoebae, including B. mandril- laris, N. fowleri and Acanthamoeba species. One possible reason for the negative PCR results is an insufficient number of amoebic cells in the CSF sample. A report by the Califor- nia Encephalitis Project demonstrated that the rate of posi- tive findings on PCR tests using CSF samples obtained from patients with presumptive Balamuthia amoebic encephalitis Figure 2. Amoebae observed on microscopy. The cerebro- was only 25% (7). In the current case, IIF staining was also spinal fluid was centrifuged, and the sediment was observed negative. This may have been due to the fact that the tissue with an optical microscope. Pseudopods branching off, which biopsy specimen was almost necrotic and did not include appear to be Balamuthia mandrillaris trophozoites, are visible. the inflammatory site or blood vessels. However, we visual- Scale bar: 100 μm. ized a number of living amoebae with extending, branched, pseudopodia on a direct microscopic examination of the granuloma or tumor formation. We therefore considered a centrifuged CSF antemortem. Based on the available infor- diagnosis of amoebic meningoencephalitis, and on day 40, mation, including the specific morphological characteristics we observed a number of living amoebae on a direct micro- and the patient’s chronic clinical course, we considered the scopic examination of the centrifuged CSF. The amoebae GAE to be due to B. mandrillaris rather than Acanthamoeba had extended, branched pseudopodia, a specific characteris- species or N. fowleri, although we were unable to determine tic of B. mandrillaris amongst trophozoites of known patho- the species using PCR tests of the CSF or IIF staining of bi- genic amoebae (Fig. 2). To determine the species of opsy specimens. amoeba, we performed a polymerase chain reaction (PCR) There have been four reports of meningoencephalitis test of the CSF and indirect immunofluorescence (IIF) stain- caused by B. mandrillaris in Japan. Although brain biopsies ing of the biopsy specimens for B. mandrillaris, N. fowleri were performed antemortem in these cases, the biopsy find- and Acanthamoeba species; however, all tests were negative. ings did not lead to a diagnosis (8-10). Unlike N. fowl- Although we were unable to identify the type of amoeba, eri (11), Acanthamoeba species and B. mandrillaris are usu- we diagnosed the patient with GAE based on the morphol- ally not visible in the CSF on microscopic examinations an- ogy and initiated treatment with fluconazole (400 mg/day temortem.
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