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Fatal Granulomatous Amoebic Encephalitis Caused by Acanthamoeba in a Patient With Kidney Transplant: A Case

T. Entry criteria included renal lupus, neurologic lupus, or other organ systems with moderate-to-severe activity. Methods: We review the clinical charts of five youth meeting criteria for PANS in our PANS Clinic. general OCD, tic disorders, Sydenham chorea, general anxiety, etc. AIMS. Chest x-ray on presentation revealed atypical pneumonia, blood tests were positive for cold agglutinins, and at full autopsy, there was myocarditis, all in keeping with recent M pneumoniae infection. Likvorni nalaz može da bude neprome- njen, sa umerenom pleocitozom i umere­nom proteinorahijom, a ako je kombino- van sa meningitisom, sa nalazom koji odgovara za navedenu bolest.

On physical examination there were no clinical signs of SLE activity or infectious diseases. On DWI the central cystic component of metastasis is not as bright as abscess cavity containing pus. Speech was intact: language evaluation revealed expressive aphasia with impaired naming, intact repetition, and ability to follow simple commands. Cranial nerves and motor function were intact: deep tendon reflexes were 2+ and symmetric. She had downgoing toes bilaterally. Control brain MRI showed contrast enhancement on bilateral temporal lobes, with more intensivity in left, and encephalomalacia. Would you like to video or text chat with me?

Home transplant-related medications included tacrolimus, mycophenolate mofetil, prednisone, and valganciclovir for cytomegalovirus prophylaxis. Noncontrast CT head scan revealed hypodensity with mild mass effect in the left temporal lobe and insular cortex with the radiological differential diagnosis including encephalitis and acute stroke. The purulent exudates of acute meningitis are isointense with underlying brain that give rise to a “dirty” appearance on T1WI. This was associated with patchy cytotoxic edema and focal, subtle enhancement with a tiny single focus of necrosis. There were multiple microhemorrhages within and remote from this region. Appearances were of atypical infectious encephalitis with microhemorrhages secondary to either a necrotizing vasculitis or arising from a central embolic source (Figure A). There are multiple ill-defined areas of hyperintensity in the right cerebral white matter and central gray matter on this T2-weighted sequence.

On follow-up neurologic examinations, her mental status continued to fluctuate with speech impairment and hallucinations, which prompted electroencephalography that demonstrated diffuse slowing and a lumbar puncture with cerebrospinal fluid (CSF) analysis showing 12 white blood cells (80% lymphocytes, 14% monocytes, and 6% neutrophils), protein of 53 mg/dL, and glucose of 61 mg/dL. (Figure 1). These findings were more suggestive of cerebritis than an infarct. Minimal stimulation to the trigeminal sensory root seems to be sufficient to reactivate latent HSV in humans [40], while dexamethasone has been shown to induce HSV-1 reactivation in vitro in a dose-dependent manner [41]. The following day, she underwent stereotactic left craniotomy with left temporal lobe brain biopsy. With disease progression, the patient’s mental status progressively deteriorated: she became more lethargic and developed right arm weakness. Microscopy of the biopsy specimen showed necrotizing granulomas with acute inflammation, with microorganisms morphologically consistent with amoeba.

Photomicrographs were sent to the Centers for Disease Control and Prevention (CDC) for telediagnosis. The Centers for Disease Control and Prevention experts reviewed the images on day 13, and it was their opinion that the images showed free-living amoebae of the Acanthamoeba/Balamuthia type. (B) Chest x-ray on day 2 showed patchy congestion consistent with a right lower lobe pneumonia as well as pulmonary edema. A multidrug regimen was initiated that included miltefosine, pentamidine, sulfadiazine, flucytosine, fluconazole, and azithromycin. Methicillin-resistant Staphylococcus aureus was grown from brain tissue biopsy; therefore, treatment with parenteral vancomycin was initiated. Both tacrolimus and mycophenolate were discontinued, and prednisone was tapered off over several days. Acanthamoeba serology sent to the CDC laboratories to monitor response of therapy was negative.

The virus cycles between the Culex mosquito and hosts such as birds, horses, cats, bats, chipmunks, skunks, squirrels, and domestic rabbits. Cumulative clinical manifestations of disease and its treatment were compared between patients with and without Herpes Zoster to determine its risk factors. Unlike Balamuthia, Acanthamoeba has not been documented to be transmitted by solid organ transplant, and to exclude this possibility, further investigation and contact to transplant centers, including examination of donor samples, revealed that our patient’s infection was not a donor-derived infection and was most likely acquired by environmental exposure. The patient’s condition deteriorated despite being on combination antimicrobial therapy, and she eventually developed right-sided hemiplegia then coma. Repeat MRI of the showed further interval progression with worsening cerebritis, now involving most of the left cerebral hemisphere and left midbrain. Brain abscesses may result from hematogenous spread of a systemic infection, direct spread from an adjacent infection, progression of a focal region of cerebritis, or as the result of direct inoculation from trauma or surgery. Hospice care was initiated at the family’s request and the patient died 3 days later.

(A–C) T2 brain magnetic resonance imaging of the patient with granulomatous amoebic encephalitis caused by Acanthamoeba. Brain imaging demonstrates progressive changes of cerebritis visible as T2 hyperintensity with mass effect that initially … Magnetic resonance angiography (MRA) was normal, the serologic test results of enterovirus, herpes simplex virus (type 1 and type 2), cytomegalovirus, hepatitis virus (A, B, C, D and E), HIV, Epstein-Barr virus, Mycoplasma pneumoniae and Chlamydia pneumoniae were all negative. (B) Higher magnification of (A) showing … (A,B) Sagittal section of rat hippocampus incubated with the patient’s cerebrospinal fluid (CSF; diluted 1:20). It has been isolated from soil, dust, sand, nasal swab samples, feces, vegetables, fish, reptiles, birds, mammals, and various water samples including fresh water, seawater, tap water, bottled mineral water, indoor/outdoor swimming pools, aquariums, and sewage [1]. The differential diagnosis based on clinical and radiological findings included necrotizing vasculitis, an infectious process with secondary hemorrhage and thrombosis (such as toxoplasmosis, neurocysticercosis, and herpes encephalitis), cerebritis, primary and metastatic neoplastic processes, and cerebral venous thrombosis.

Treatment with steroids was instituted to decrease the mass effect and treat the most likely diagnosis, which was CNS vasculitis. The clinical syndromes associated with Acanthamoeba infections remain rare. Aside from the well known Acanthamoeba keratitis associated with the use of contaminated contact lenses in the presence of microabrasions of the cornea, granulomatous amoebic encephalitis (GAE) is being recognized more frequently, especially with the growing population of immune-compromised hosts [3]. As such, GAE is now being diagnosed at the time of acute illness presentation, rather than at post mortem examination [4, 5]. Again, the neurologic SLE subset did the best (regardless of cyclophosphamide treatment group). Metabolic/genetic evaluation was also negative for detectable abnormalities, and included normal results for lactate, pyruvate, ammonia, fatty acid profile, acylcarnitine profiles, serum/urine/cerebral spinal fluid (CSF) amino acid profiles, mucopolysaccharide and oligopolysaccharide profiles, cytogenetic fluorescence in situ hybridization (FISH), Fragile X, array comparative genomic hybridization, and mercury. Imaging findings in the early stages of infection are often nonspecific.

Lesions are either multifocal, with discrete focal lesions at the grey/white matter junction, or present as a larger solitary mass-like lesion. A Monoclonal mouse anti-human CD5 antibody was used at 1:200 (Dako). Acanthamoeba is traditionally described as affecting the posterior structures of the brain [7]. The author for correspondence is in possession of this document. With worsening infection, eventually the signs of raised intracranial pressure develop invariably leading to coma and death. Diagnosis is usually only confirmed with brain biopsy. This can delay the diagnosis and commencement of treatment and may contribute to the subsequent fatal outcome, particularly in the immune-compromised patients [2, 4, 6].

There are no reported cases of donor-derived infections with Acanthamoeba unlike Balamuthia mandrillaris, another free-living amoeba that has been reported to result from donor-derived infections in organ recipients. Our patient’s donor had negative tissue examination for Acanthamoeba [10]. Cerebrospinal fluid analysis in GAE demonstrates lymphocytic pleocytosis, low glucose, and high protein. Careful examination of CSF cytology may rarely reveal the trophozoites [8]. Acanthamoeba serology can potentially be used to follow disease activity [11, 12]. Histologic examination of tissue specimens such as skin or brain biopsies with the regular (H&E) staining can be diagnostic. Antigen detection of Acanthamoeba using indirect immunofluorescence testing in tissue specimens and molecular diagnostics with PCR are available in some laboratories, including US CDC laboratories [4].

As our patient’s clinical condition deteriorated, all the cerebral lesions enlarged with the appearance of multiple new microhemorrhages. The volume of affected brain tissue and necrosis increased in size. The enhancement pattern of the largest lesion evolved over time: initially focal and asymmetric eventually becoming a peripheral thin rim. This would confirm an inflammatory zone that has been previously shown histologically to correlate with an inflammatory response secondary to amoebic trophozoite infiltration of the pial vessels and a border zone encephalitis [9]. Multiple antimicrobials have been used in the treatment of GAE in various combinations that include, but are not limited to, trimethoprim/sulfamethoxazole, pentamidine, sulfadiazine, pyrimethamine, azithromycin, rifampin, flucytosine, albendazole, miltefosine, metronidazole, ketoconazole, fluconazole, voriconazole, and amphotericin B. Polymicrobial therapy is potentially more effective if combined with resection of the lesions to better control the infection. Among all the solid organ transplant recipients, there was only 1 case report in the English literature of a survivor with liver transplant who was on cyclosporine monotherapy as an immunosuppressant at the time of diagnosis.

He underwent resection of the brain lesion followed by trimethoprim/sulfamethoxazole and rifampin treatment [13]. Minimal immunosuppression can also provide a favorable outcome if coupled with effective surveillance and increased awareness of such infections. Although rare, Acanthameoba infection is associated with several clinical presentations such as keratitis, skin infections, sinusitis, and pneumonitis. Disseminated infections are being reported more frequently, especially in the immune-suppressed hosts that include GAE. Disseminated infections used to be a post mortem diagnosis, but with the increased index of suspicion of such infections and the newer methods of diagnosis, earlier detection and treatment can be achieved. A Monoclonal mouse anti-human CD5 antibody was used at 1:200 (Dako). The few survivors of GAE received combination antimicrobial therapy.

Regimens that include miltefosine have shown efficacy to treat both Balamuthia and Acanthamoeba infections, but that is based only on case reports, given the rarity of these infections [11].