Predictors of mortality and poor outcome for patients with severe infectious encephalitis in the intensive care unit: a cross-sectional study.

BACKGROUND: There are few thorough studies assessing predictors of severe encephalitis, despite the poor prognosis and high mortality associated with severe encephalitis. The study aims to evaluate the clinical predictors of mortality and poor outcomes at hospital discharge in patients with severe infectious encephalitis in intensive care units. METHOD: In two Chinese hospitals, a retrospective cohort study comprising 209 patients in intensive care units suffering from severe infectious encephalitis was carried out. Univariate and multivariate logistic regression analyses were used to identify the factors predicting mortality in all patients and poor outcomes in all survivors with severe infectious encephalitis. RESULTS: In our cohort of 209 patients with severe encephalitis, 22 patients died, yielding a mortality rate of 10.5%. Cerebrospinal fluid pressure ≥ 400mmH2O (OR = 7.43), abnormal imaging (OR = 3.51), abnormal electroencephalogram (OR = 7.14), and number of rescues (OR = 1.12) were significantly associated with an increased risk of mortality in severe infectious encephalitis patients. Among the 187 survivors, 122 (65.2%) had favorable outcomes, defined as the modified Rankine Scale (mRS) score (0 ~ 3), and 65(34.8%) had poor outcomes (mRS scores 4 ~ 5). Age (OR = 1.02), number of rescues (OR = 1.43), and tubercular infection (OR = 10.77) were independent factors associated with poor outcomes at discharge in all survivors with severe infectious encephalitis. CONCLUSIONS: Multiple clinical, radiologic, and electrophysiological variables are independent predictive indicators for mortality and poor outcomes in patients with severe encephalitis in intensive care units. Identifying these outcome predictors early in patients with severe encephalitis may enable the implementation of appropriate medical treatment and help reduce mortality rates.

Isolation and habitat analysis of Balamuthia mandrillaris from soil.

Balamuthia mandrillaris is a free-living amoeba that causes meningoencephalitis in mammals. Over 200 cases of infection were reported worldwide, with a fatality rate of over 95%. A clear route of infection was unknown for a long time until a girl died of granulomatous amoebic encephalitis (GAE) in California, USA, in 2003 due to infection with B. mandrillaris detected in a potted plant. Since then, epidemiological studies were conducted worldwide to detect B. mandrillaris in soil and other environmental samples. We previously reported the isolation of B. mandrillaris from the soil in Japan; however, the existing B. mandrillaris culture method with BM3 medium and COS-7 cells was unsuccessful. Therefore, in this study, we aimed to conduct soil analysis to determine the growth conditions of B. mandrillaris. B. mandrillaris-positive soils were defined as soils from which B. mandrillaris was isolated and environmental DNA was PCR-positive. Soils inhabited by B. mandrillaris were alkaline, with high electrical conductivity and characteristics of nutrient-rich soils of loam and clay loam. The results of this study suggest a possible reason for the high prevalence of GAE caused by B. mandrillaris among individuals employed in agriculture-related occupations.

Immunogens in Balamuthia mandrillaris: a proteomic exploration.

Balamuthia mandrillaris is the causative agent of granulomatous amoebic encephalitis, a rare and often fatal infection affecting the central nervous system. The amoeba is isolated from diverse environmental sources and can cause severe infections in both immunocompromised and immunocompetent individuals. Given the limited understanding of B. mandrillaris, our research aimed to explore its protein profile, identifying potential immunogens crucial for early granulomatous amoebic encephalitis diagnosis. Cultures of B. mandrillaris and other amoebas were grown under axenic conditions, and total amoebic extracts were obtained. Proteomic analyses, including two-dimensional electrophoresis and mass spectrometry, were performed. A 50-kDa band showed a robust recognition of antibodies from immunized BALB/c mice; peptides contained in this band were matched with elongation factor-1 alpha, which emerged as a putative key immunogen. Besides, lectin blotting revealed the presence of glycoproteins in B. mandrillaris, and confocal microscopy demonstrated the focal distribution of the 50-kDa band throughout trophozoites. Cumulatively, these observations suggest the participation of the 50-kDa band in adhesion and recognition mechanisms. Thus, these collective findings demonstrate some protein characteristics of B. mandrillaris, opening avenues for understanding its pathogenicity and developing diagnostic and therapeutic strategies.

Metagenomic next-generation sequencing for diagnosis of fatal Balamuthia amoebic encephalitis.

INTRODUCTION: Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging. CASE DESCRIPTION: A 52-year-old male patient, who had no previous history of skin lesions, presented to the emergency department with an acute headache, walking difficulties, and disturbance of consciousness. The patient underwent a series of examinations, including regular cerebrospinal fluid (CSF) studies and magnetic resonance imaging, and tuberculous meningoencephalitis was suspected. Despite being treated with anti-TB drugs, no clinical improvement was observed in the patient. Following corticosteroid therapy, the patient developed a rapid deterioration in consciousness with dilated pupils. Metagenomic next-generation sequencing (mNGS) revealed an unexpected central nervous system (CNS) amoebic infection, and the patient died soon after the confirmed diagnosis. CONCLUSION: This study highlights the application of mNGS for the diagnosis of patients with suspected encephalitis or meningitis, especially those caused by rare opportunistic infections.

Encephalitis in HIV-negative immunodeficient patients: a prospective multicentre study, France, 2016 to 2019.

BackgroundData on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.AimWe aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.MethodsPatients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson's chi-squared test and Student's t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.ResultsID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70-6.85).ConclusionsVaricella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.

A multicenter evaluation of the QIAstat-Dx meningitis-encephalitis syndromic test kit as compared to the conventional diagnostic microbiology workflow.

PURPOSE: Rapid diagnosis and treatment of infectious meningitis and encephalitis (ME) is critical to minimize morbidity and mortality. Recently, Qiagen introduced the CE-IVD QIAstat-Dx ME panel (QS-ME) for syndromic diagnostic testing of meningitis and encephalitis. Some data on the performance of the QS-ME in comparison to the BioFire FilmArray ME panel are available. In this study, the performance of the QS-ME is compared to the current diagnostic workflow in two academic medical centers in the Netherlands. METHODS: A total of 110 cerebrospinal fluid samples were retrospectively tested with the QS-ME. The results obtained were compared to the results of laboratory-developed real-time PCR assays (LDTs), IS-pro, bacterial culture, and cryptococcal antigen (CrAg) testing. In addition, the accuracy of the QS-ME was also investigated using an external quality assessment (EQA) panel consisting of ten samples. RESULTS: Four of the 110 samples tested failed to produce a valid QS-ME result. In the remaining 106 samples, the QS-ME detected 53/53 viral targets, 38/40 bacterial targets, and 7/13 Cryptococcus neoformans targets. The discrepant bacterial results consisted of two samples that were previously tested positive for Listeria monocytogenes (CT 35.8) and Streptococcus pneumoniae (CT 40), respectively. The QS-ME detected one additional result, consisting of a varicella-zoster virus signal (CT 35.9), in a sample in which both techniques detected Streptococcus pyogenes. Finally, 100% concordance was achieved in testing a blinded bacterial ME EQA panel. CONCLUSION: The QS-ME is a relevant addition to the syndromic testing landscape to assist in diagnosing infectious ME.

Balamuthia mandrillaris amoebic encephalitis mimicking tuberculous meningitis.

A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients.

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

Mental health outcomes of encephalitis: An international web-based study.

BACKGROUND AND PURPOSE: Acute encephalitis is associated with psychiatric symptoms. Despite this, the extent of mental health problems following encephalitis has not been systematically reported. METHODS: We recruited adults who had been diagnosed with encephalitis of any aetiology to complete a web-based questionnaire. RESULTS: In total, 445 respondents from 31 countries (55.1% UK, 23.1% USA) responded. Infectious encephalitis constituted 65.4% of cases, autoimmune 29.7%. Mean age was 50.1 years, 65.8% were female, and median time since encephalitis diagnosis was 7 years. The most common self-reported psychiatric symptoms were anxiety (75.2%), sleep problems (64.4%), mood problems (62.2%), and unexpected crying (35.2%). Self-reported psychiatric diagnoses were common: anxiety (44.0%), depression (38.6%), panic disorder (15.7%), and posttraumatic stress disorder (PTSD; 21.3%). Severe mental illnesses such as psychosis (3.3%) and bipolar affective disorder (3.1%) were reported. Self-reported diagnosis rates were broadly consistent with results from the Psychiatric Diagnostic Screening Questionnaire. Many respondents also reported they had symptoms of anxiety (37.5%), depression (28.1%), PTSD (26.8%), or panic disorder (20.9%) that had not been diagnosed. Rates of psychiatric symptoms did not differ between autoimmune and infectious encephalitis. In total, 37.5% respondents had thought about suicide, and 4.4% had attempted suicide, since their encephalitis diagnosis. More than half of respondents (53.5%) reported they had no, or substandard, access to appropriate mental health care. High rates of sensory hypersensitivities (>75%) suggest a previously unreported association. CONCLUSIONS: This large international survey indicates that psychiatric symptoms following encephalitis are common and that mental health care provision may be inadequate. We highlight a need for proactive psychiatric input.

Unexpected trends of amoebic encephalitis in Pakistan.

Annual reported cases of Naegleria fowleri (NF), popularly known as brain eating amoeba, are becoming a huge challenge for Pakistani health authorities. Karachi has seen cases regularly up till the present but Lahore has not. The spread of this amoeba in non-chlorinated water is a major concern for the authorities. NF is an amoeba commonly found in warm freshwater environments such as lakes, hot springs and poorly chlorinated swimming pools. It poses a significant risk during hot weather when water-related recreational activities are popular. Where there is a non-chlorinated water supply, its spread is aggravated.

The Patient Perspective in Encephalitis Research.

Research on autoimmune and infectious encephalitis has made substantial progress in recent years in revealing the pathophysiology of these diseases, establishing robust diagnostic criteria, and developing promising treatment options, with a range of clinical trials currently underway. Outcome measures in studies on autoimmune and infectious encephalitis mainly relied on established and widely used tools such as the modified Rankin Scale (mRS). However, the mRS was developed to assess stroke outcome and has a strong focus on motor symptoms and the degree of dependence in daily activities. For example, approximately 80% of patients with anti-NMDA receptor encephalitis (i.e., the most common autoimmune encephalitis variant) achieve a good outcome 2 years after disease onset when evaluated using the mRS.1 In contrast to these findings, recent studies show that a majority of patients with anti-NMDA receptor encephalitis suffer from relevant and persistent cognitive impairment, despite mRS scores indicating good or very good recovery.2,3 This shows that the mRS fails to detect clinically relevant long-term symptoms in these patients. Indeed, persisting cognitive deficits with their detrimental effect on quality of life are specifically important in the frequently very young patients with encephalitis. More recently, encephalitis-specific scores have been developed, e.g., the CASE score for the clinical assessment of patients with autoimmune encephalitis.4 While this score is tailored to symptoms in autoimmune encephalitis, it has a strong focus on acute disease symptoms and is less well suited to capture long-term sequalae.

Latent human herpesvirus 6 is reactivated in CAR T cells.

Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6)1. Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4+ T cells. Using single-cell sequencing, we identify a rare population of HHV-6 'super-expressors' (about 1 in 300-10,000 cells) that possess high viral transcriptional activity, among research-grade allogeneic chimeric antigen receptor (CAR) T cells. By analysing single-cell sequencing data from patients receiving cell therapy products that are approved by the US Food and Drug Administration2 or are in clinical studies3-5, we identify the presence of HHV-6-super-expressor CAR T cells in patients in vivo. Together, the findings of our study demonstrate the utility of comprehensive genomics analyses in implicating cell therapy products as a potential source contributing to the lytic HHV-6 infection that has been reported in clinical trials1,6-8 and may influence the design and production of autologous and allogeneic cell therapies.

Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia / Experience with the Biofire FilmArray® for infectious meningitis/encephalitis in a high complexity institution in Bogotá, Colombia

Introducción: La meningoencefalitis infecciosa (MEI) es una emergencia neurológica con importante morbimortalidad. El panel Biofire FilmArray? para meningitis/encefalitis (FAME) en el líquido cefalorraquídeo (LCR) ha demostrado ser una valiosa herramienta para el diagnóstico etiológico de la MEI, facilitando una terapia antimicrobiana dirigida. El objetivo es determinar el impacto del panel FAME en las decisiones terapéuticas antimicrobianas en pacientes con sospecha de MEI en las primeras 24 horas de la valoración clínica. Pacientes y métodos: Estudio observacional descriptivo que comenta las manifestaciones cínicas, los resultados de neuroimágenes y paraclínicos, y la antibioticoterapia de pacientes con sospecha de MEI. Se realizó un análisis del impacto que tiene el FAME en la terapia antimicrobiana en las primeras 24 horas de la valoración clínica de los pacientes. Resultados: Se incluyó a 44 pacientes. El tiempo promedio para obtener el resultado del panel FAME en el LCR fue de nueve horas, con un 20,4% (9/44) de pruebas positivas. En las primeras 24 horas de la valoración clínica, su resultado tuvo impacto en las decisiones terapéuticas antimicrobianas en el 75% (33/44) de los casos. En pacientes con alta sospecha clínica de MEI, el resultado del FAME permitió cambiar la terapia empírica inicial a una dirigida en el 15% (3/20) y suspender la terapia empírica inicial en el 35% (7/20) de los sujetos. En pacientes con baja sospecha clínica de MEI, su resultado permitió que al 25% (6/24) se le confirmara la sospecha y se le iniciara antibioticoterapia dirigida; y que al 70,8% (17/24) se le descartara el diagnóstico y no se le iniciara tratamiento. Conclusiones: El resultado del panel FAME en el LCR tiene alto impacto en la toma de decisiones terapéuticas antimicrobianas en las primeras 24 horas de la valoración clínica. Sin embargo, su interpretación debe hacerse con el contexto clínico, la epidemiología local y otros estudios diagnósticos.(AU)

Introduction: Infectious meningoencephalitis (IME) is a neurological emergency with a significant rate of morbidity and mortality. The Biofire FilmArray® meningitis/encephalitis (FAME) panel for testing in cerebrospinal fluid (CSF) has proven to be a valuable tool for the aetiological diagnosis of IME, facilitating targeted antimicrobial therapy. The aim is to determine the impact of the FAME panel on antimicrobial therapeutic decisions in patients with suspected IME in the first 24 hours of clinical assessment. Patients and methods: This is a descriptive observational study that comments on the clinical manifestations, the neuroimaging and paraclinical findings, and the antibiotic therapy of patients with suspected IME. An analysis was performed to determine the impact of FAME on antimicrobial therapy in the first 24 hours of the clinical assessment of patients. Results: Altogether 44 patients were included. The average time required to obtain the result of the FAME panel for testing in CSF was nine hours, with 20.4% (9/44) of tests yielding positive results. Within 24 hours of clinical assessment, their outcome had an impact on antimicrobial treatment decisions in 75% (33/44) of cases. In patients with a high clinical suspicion of IME, the result of FAME made it possible to change the initial empirical therapy to a targeted therapy in 15% (3/20) of cases and to discontinue the initial empirical therapy in 35% (7/20) of the subjects. In patients with low clinical suspicion of IME, their result allowed 25% (6/24) to have their suspicion confirmed and they were started on targeted antibiotic therapy; in contrast, 70.8% (17/24) had their diagnosis ruled out and were not started on treatment. Conclusions: The result of the FAME panel for testing in CSF has a high impact on antimicrobial therapeutic decisions within 24 hours of clinical assessment. However, it must be interpreted with the clinical context, local epidemiology and other diagnostic studies.(AU)

Clinical Characteristics and Treatment Outcome of Eosinophilic Meningoencephalitis in South Indian Children: Experience From a Prospective Registry.

BACKGROUND: To describe the clinical features and therapeutic outcomes of a prospective cohort of children with eosinophilic meningoencephalitis. METHODS: Children admitted with clinical features suggestive of meningitis along with cerebrospinal fluid (CSF) eosinophilia during the period of 14 years (2008 to 2021) were included. Their baseline characteristics, epidemiologic associations, and treatment outcomes were analyzed and compared with the previous studies. RESULTS: We identified 25 children (13 males) satisfying the inclusion criteria. The median age at presentation was 3.9 years (range 0.8 to 17 years); 68% were aged less than two years. Fourteen (56%) children had a history of exposure to snails. Most of them presented with fever, headache, irritability, lateral rectus palsy, and early papilledema. Symptoms started three to 42 days (median duration: 14 days) before admission to our center. All children had peripheral eosinophilia, which ranged from 9% to 41%. The mean CSF white blood cell count was 416/mm3 (range 50 to 1245 cells/mm3) with CSF eosinophilia ranging from 11% to 80%. Brain magnetic resonance imaging was done in 24 children and was normal in 15 (62.5%). Leptomeningeal enhancement was seen in two (8.3%) children, and other nonspecific changes were noted in seven (29.1%) children. All children recovered without any neurological deficits with a standard treatment regimen of albendazole and oral steroids. All were asymptomatic at the last follow-up. None of them had any recurrence during the follow-up period. CONCLUSION: We report one of the largest clinical series of children with eosinophilic meningoencephalitis from an endemic area of South India.

Assessment of pathogenic potential of Acanthamoeba isolates by in vitro and in vivo tests.

Acanthamoeba are free-living protozoa present ubiquitously in numerous environmental reservoirs that exist as an actively feeding trophozoite or a dormant cyst stage. The pathogenic Acanthamoeba are known to cause Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). Despite their omnipresence, the number of infections is quite low. The reason behind this low frequency of Acanthamoeba infections could be the existence of many non-pathogenic strains or a successful host immune response to these infections. Studies in the past have proposed a few physiological parameters for the differentiation of pathogenic and non-pathogenic strains. Additionally, in vivo experiments are known to play an essential role in understanding the virulence of parasites, immunological aspects, and disease pathogenesis. The thermotolerance (30 °C, 37 °C, and 40 °C) and osmotolerance (0.5 M, 1 M, and 1.5 M) tests were performed on 43 Acanthamoeba isolates from patients with keratitis (n = 22), encephalitis (n = 5), and water samples (n = 16). In addition, the genotype of 10 Acanthamoeba isolates (keratitis (n = 2), encephalitis (n = 2), water (n = 6)) was determined and were then evaluated for pathogenicity on mouse model by inducing Acanthamoeba keratitis and amoebic encephalitis. The results of the thermotolerance and osmotolerance assays categorized 29/43 (67.4%) isolates as pathogenic, 8 as low pathogenic (18.6%), and the remaining 6 (13.9%) as non-pathogenic. The 10 Acanthamoeba isolates were categorized as T11 (5 isolates), T5 (2 isolates), T4 (2 isolates), and T10 (1 isolate) genotypes. Out of 10 Acanthamoeba isolates, 9 were successful in establishing AK, amoebic encephalitis, or both in the mice model, and a single isolate was found non-pathogenic. Two isolates from water samples were non-pathogenic in the physiological tests but successfully established Acanthamoeba infection in the mice model. The results of the physiological assays and in vivo experiments were analogous for 7 isolates while 1 isolate from the water was low pathogenic in the physiological assays but failed to produce pathogenicity during in vivo experiments. The physiological parameters are not very dependable to test the pathogenic potential of Acanthamoeba isolates, and thus results must always be validated by in vivo experiments. There is no infallible approach for determining the potential pathogenicity of environmental isolates of Acanthamoeba because several parameters regulate the pathogenic potential.

[Experience with the Biofire FilmArray® for infectious meningitis/encephalitis in a high complexity institution in Bogota, Colombia]. / Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia.

INTRODUCTION: Infectious meningoencephalitis (IME) is a neurological emergency with a significant rate of morbidity and mortality. The Biofire FilmArray® meningitis/encephalitis (FAME) panel for testing in cerebrospinal fluid (CSF) has proven to be a valuable tool for the aetiological diagnosis of IME, facilitating targeted antimicrobial therapy. The aim is to determine the impact of the FAME panel on antimicrobial therapeutic decisions in patients with suspected IME in the first 24 hours of clinical assessment. PATIENTS AND METHODS: This is a descriptive observational study that comments on the clinical manifestations, the neuroimaging and paraclinical findings, and the antibiotic therapy of patients with suspected IME. An analysis was performed to determine the impact of FAME on antimicrobial therapy in the first 24 hours of the clinical assessment of patients. RESULTS: Altogether 44 patients were included. The average time required to obtain the result of the FAME panel for testing in CSF was nine hours, with 20.4% (9/44) of tests yielding positive results. Within 24 hours of clinical assessment, their outcome had an impact on antimicrobial treatment decisions in 75% (33/44) of cases. In patients with a high clinical suspicion of IME, the result of FAME made it possible to change the initial empirical therapy to a targeted therapy in 15% (3/20) of cases and to discontinue the initial empirical therapy in 35% (7/20) of the subjects. In patients with low clinical suspicion of IME, their result allowed 25% (6/24) to have their suspicion confirmed and they were started on targeted antibiotic therapy; in contrast, 70.8% (17/24) had their diagnosis ruled out and were not started on treatment. CONCLUSIONS: The result of the FAME panel for testing in CSF has a high impact on antimicrobial therapeutic decisions within 24 hours of clinical assessment. However, it must be interpreted with the clinical context, local epidemiology and other diagnostic studies.

TITLE: Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia.Introducción. La meningoencefalitis infecciosa (MEI) es una emergencia neurológica con importante morbimortalidad. El panel Biofire FilmArray? para meningitis/encefalitis (FAME) en el líquido cefalorraquídeo (LCR) ha demostrado ser una valiosa herramienta para el diagnóstico etiológico de la MEI, facilitando una terapia antimicrobiana dirigida. El objetivo es determinar el impacto del panel FAME en las decisiones terapéuticas antimicrobianas en pacientes con sospecha de MEI en las primeras 24 horas de la valoración clínica. Pacientes y métodos. Estudio observacional descriptivo que comenta las manifestaciones cínicas, los resultados de neuroimágenes y paraclínicos, y la antibioticoterapia de pacientes con sospecha de MEI. Se realizó un análisis del impacto que tiene el FAME en la terapia antimicrobiana en las primeras 24 horas de la valoración clínica de los pacientes. Resultados. Se incluyó a 44 pacientes. El tiempo promedio para obtener el resultado del panel FAME en el LCR fue de nueve horas, con un 20,4% (9/44) de pruebas positivas. En las primeras 24 horas de la valoración clínica, su resultado tuvo impacto en las decisiones terapéuticas antimicrobianas en el 75% (33/44) de los casos. En pacientes con alta sospecha clínica de MEI, el resultado del FAME permitió cambiar la terapia empírica inicial a una dirigida en el 15% (3/20) y suspender la terapia empírica inicial en el 35% (7/20) de los sujetos. En pacientes con baja sospecha clínica de MEI, su resultado permitió que al 25% (6/24) se le confirmara la sospecha y se le iniciara antibioticoterapia dirigida; y que al 70,8% (17/24) se le descartara el diagnóstico y no se le iniciara tratamiento. Conclusiones. El resultado del panel FAME en el LCR tiene alto impacto en la toma de decisiones terapéuticas antimicrobianas en las primeras 24 horas de la valoración clínica. Sin embargo, su interpretación debe hacerse con el contexto clínico, la epidemiología local y otros estudios diagnósticos.

Epidemiology, clinical and imaging features of rhombencephalitis caused by L. monocytogenes. A retrospective observational study. / Epidemiología, clínica y resultados de imagen de rombencefalitis causada por L. monocytogenes. Un estudio observacional.

INTRODUCTION: To date, few studies have explored the specific risk factors of patients with listeriosis who develop rhombencephalitis, and there is insufficient information regarding imaging findings and clinical symptoms in patients with this disease. This work aimed to analyze the imaging findings associated with L. monocytogenes rhombencephalitis in a cohort of patients with listeriosis. MATERIALS AND METHODS: We conducted a retrospective observational study of all declared cases of listeriosis in a tertiary hospital from Granada, Spain, from 2008 to 2021. Risk factors, comorbidities, and clinical outcomes were collected for all patients. In addition, clinical symptoms and magnetic resonance imaging (MRI) findings were included for those patients who developed rhombencephalitis. Descriptive and bivariate analyses were performed using SPSS statistical software (IBM SPSS, version 21). RESULTS: Our cohort comprised 120 patients with listeriosis (41.7% women, mean age: 58.6 ± 23.8 years), of which 10 (8.3%) had rhombencephalitis. The most frequent MRI findings in patients with confirmed rhombencephalitis were T2-FLAIR hyperintensity (100%), T1 hypointensity (80%), scattered parenchymal enhancement (80%), and cranial nerve enhancement (70%), while the most frequent anatomical involvement were pons, medulla oblongata, and cerebellum. Complications occurred in 6 patients (abscess in 4, hemorrhage in 2, hydrocephalus in 1). CONCLUSIONS: Rhombencephalitis is associated with an increased in-hospital mortality in patients with listeriosis. The anatomical distribution and imaging characteristics of neurolisteriosis could be useful to suggest the diagnosis. Future studies with greater sample size should explore the association between anatomical location, imaging patterns, and associated complications (e.g., hydrocephalus, hemorrhage), and clinical outcomes.

TITLE: Epidemiología, clínica y resultados de imagen de rombencefalitis causada por L. monocytogenes. Un estudio observacional.Introducción. Hasta la fecha, pocos estudios han explorado los factores de riesgo específicos de los pacientes con listeriosis que desarrollan rombencefalitis, y no hay suficiente información sobre los hallazgos de imagen y los síntomas clínicos en pacientes con esta enfermedad. El objetivo de este trabajo fue analizar los hallazgos de imagen asociados a la rombencefalitis por L. monocytogenes en una cohorte de pacientes con listeriosis. Materiales y métodos. Se realizó un estudio observacional retrospectivo de todos los casos declarados de listeriosis en un hospital terciario de Granada, España, desde 2008 hasta 2021. Se recogieron los factores de riesgo, las comorbilidades y los resultados clínicos de todos los pacientes. Además, se incluyeron los síntomas clínicos y los hallazgos de resonancia magnética (RM) de los pacientes que desarrollaron rombencefalitis. Se realizaron análisis descriptivos y bivariados utilizando el software estadístico SPSS (IBM SPSS, versión 21). Resultados. Nuestra cohorte incluyó a 120 pacientes con listeriosis (41,7%, mujeres; edad media: 58,6 ± 23,8 años), de los cuales 10 (8,3%) tenían rombencefalitis. Los hallazgos más frecuentes en la RM de los pacientes con rombencefalitis confirmada fueron hiperintensidad en T2-FLAIR (100%), hipointensidad en T1 (80%), realce parenquimatoso disperso (80%) y realce de los nervios craneales (70%), mientras que la afectación anatómica más frecuente fue en la protuberancia, la médula oblongada y el cerebelo. Se produjeron complicaciones en seis pacientes (absceso en cuatro, hemorragia en dos e hidrocefalia en uno). Conclusiones. La rombencefalitis se asocia a un aumento de la mortalidad intrahospitalaria en pacientes con listeriosis. La distribución anatómica y las características de imagen de la neurolisteriosis podrían ser útiles para sugerir el diagnóstico. Futuros estudios con mayor tamaño muestral deberían explorar la asociación entre la localización anatómica, los patrones de imagen y las complicaciones asociadas (por ejemplo, hidrocefalia y hemorragia), y los resultados clínicos.

Fatal granulomatous amebic encephalitis initially presenting with a cutaneous lesion.

We present a case of a 66-year-old man with a cutaneous Balamuthia mandrillaris lesion that progressed to fatal granulomatous amoebic encephalitis. We provide a summary of Australian cases and describe the clinical features and approach to diagnosing this rare but devastating condition, including the importance of PCR for diagnosis.

Characteristics, management, and outcomes of patients with infectious encephalitis requiring intensive care: A prospective multicentre observational study.

PURPOSE: Infectious encephalitis (IE) is a severe disease which requires intensive care unit (ICU) admission in up to 50% of cases. We aimed to describe characteristics, management and outcomes of IE patients who required ICU admission. MATERIALS AND METHODS: Ancillary study focusing on patients with ICU admission within the ENCEIF cohort, a French prospective observational multicentre study. The primary criteria for outcome was the functional status at hospital discharge, categorized using the Glasgow outcome scale (GOS). Logistic regression model was used to identify risk factors for poor outcome, defined as a GOS ≤ 3. RESULTS: We enrolled 198 ICU patients with IE. HSV was the primary cause (n = 72, 36% of all IE, 53% of IE with microbiological documentation). Fifty-two patients (26%) had poor outcome at hospital discharge, including 22 deaths (11%). Immunodeficiency, supratentorial focal signs on admission, lower cerebrospinal fluid (CSF) white cells count (<75/mm3), abnormal brain imaging, and time from symptoms onset to acyclovir start >2 days were independent predictors of poor outcome. CONCLUSION: HSV is the primary cause of IE requiring ICU admission. IE patients admitted in ICU have a poor prognosis with 11% of in-hospital mortality and 15% of severe disabilities in survivors at discharge.

Diagnosing Balamuthia mandrillaris amebic meningoencephalitis in a 64-year-old woman from the Southwest of China.

Balamuthia mandrillaris amebic encephalitis (BAE) can cause a fatal condition if diagnosis is delayed or effective treatment is lacking. Patients with BAE have been previously reported in 12 provinces of China, with skin lesions being the primary symptom and encephalitis developing after several years. However, a significantly lower number of cases has been reported in Southwest China. Here we report an aggressive BAE case of a 64-year-old woman farmer with a history of skin lesions on her left hand. She was admitted to our hospital due to symptoms of dizziness, headache, cough, vomiting, and gait instability. She was initially diagnosed with syphilitic meningoencephalitis and received a variety of empirical treatment that failed to improve her symptoms. Finally, she was diagnosed with BAE combined with amebic pneumonia using next-generation sequencing (NGS), qRT-PCR, sequence analysis, and imaging studies. She died approximately 3 weeks after the onset. This case highlights that the rapid development of encephalitis can be a prominent clinical manifestation of Balamuthia mandrillaris infection.