The rapidly progressing and fatal outcome of rhombencephalitis by listeriosis in a 61-year-old male.

Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised individuals, pregnant women, and newborns. Listeriosis can manifest as meningitis, encephalitis, or sepsis, and its diagnosis requires a high index of suspicion. The case is reported of a rare presentation of rhombencephalitis by listeriosis in a 61-year-old male who initially suffered from subacute gastric disturbances and fever. Neurological consultation showed abnormal functions of cranial nerves and meningeal signs were observed. MRI revealed a poorly demarcated focus of approximately 45 × 16 × 15mm, indicating possible inflammatory processes, necessitating a lumbar puncture. Assessment of the CSF indicated infection with the bacterium- Listeria Monocytogenes, with the final diagnosis of Listeriosis encephalitis. Despite antibiotic therapy of Ceftazidine and Ampicillin, the patient's condition deteriorated, followed by death.

Integrating DNA/RNA microbe detection and host response for accurate diagnosis, treatment and prognosis of childhood infectious meningitis and encephalitis.

BACKGROUND: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. METHODS: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). RESULTS: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. CONCLUSIONS: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

Listeria monocytogenes: a rare cause of rhomboencephalitis in an immunocompetent patient.

We present an unusual case of Listeria monocytogenes rhomboencephalitis in a young, healthy patient. Although L. monocytogenes meningitis is usually associated with immunodeficiency, rhomboencephalitis is more commonly seen in immunocompetent patients. The wide differential for rhomboencephalitis can create a diagnostic challenge. Without prompt pathogen identification and appropriate antibiotic regimen, L. monocytogenes central nervous system infections can be fatal. Cerebro-Spinal Fluid (CSF) Polymerase Chain Reaction (PCR) aided a prompt diagnosis and adjustment of therapy to achieve a good patient outcome.

Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China.

BACKGROUND: Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited. METHODS: In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E). RESULTS: In total, 152 patients diagnosed with clinically suspected M/E at four tertiary hospitals were enrolled; ptNGS and mNGS were used in parallel for pathogen detection in CSF. Among the 89 patients who were diagnosed with definite infectious M/E, 57 and 39 patients had causal microbial detection via ptNGS and mNGS, respectively. The overall accuracy of ptNGS was 65.1%, with a positive percent agreement (PPA) of 64% and a negative percent agreement (NPA) of 66.7%; and the overall accuracy of mNGS was 47.4%, with a PPA of 43.8% and an NPA of 52.4% after discrepancy analysis. There was a significant difference in the detection efficiency between these two methods both for PPA (sensitivity) and overall accuracy for pathogen detection (P < 0.05). CONCLUSIONS: NGS tests have provided new information in addition to conventional microbiologic tests. ptNGS seems to have superior performance over mNGS for common causative pathogen detection in CSF for infectious M/E.

Japanese Spotted Fever Associated with Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion.

A 58-year-old woman had disseminated intravascular coagulation (DIC) and septic shock caused by Japanese spotted fever (JSF). Following treatment with minocycline, her general condition gradually improved; however, her disorientation persisted. Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) type II was diagnosed based on brain magnetic resonance imaging (MRI) showing a hyperintense area in the splenium of the corpus callosum and bilateral cerebral white matter on diffusion-weighted imaging. Thereafter, her consciousness gradually improved, but she continued to experience difficulty concentrating and attention deficits. MERS type II may take longer to improve than type I, and long-term follow-up is required.

Case Report: Severe Listeria Encephalitis With Complicated or Secondary Autoimmune Encephalitis and CNS Demyelinating Diseases.

Background: Listeria monocytogenes is an important food-borne bacterium. It rarely infects patients with complete immunity and causes meningocephalitis. Patients with severe Listeria encephalitis always experience a bad prognosis. Case Presentation: A 39-year-old male patient was admitted to our hospital due to fever for more than 10 days and disturbance of consciousness accompanied by convulsions for 2 days. Metagenomic next-generation sequencing (mNGS) results showed L. monocytogenes in both cerebrospinal fluid (CSF) and blood, indicating L. monocytogenes encephalitis. Autoimmune encephalitis and central nervous system (CNS) demyelinating autoantibodies in the CSF also showed positive results. The case was finally diagnosed as severe Listeria encephalitis with complicated or secondary autoimmune encephalitis and CNS demyelinating diseases. Conclusions: It is necessary to carry out infection and immunity screening in patients with severe encephalitis, especially for immunocompromised patients. mNGS plays a pivotal role in screening patients with severe and difficult neurological diseases.

Evaluation of the selection of cerebrospinal fluid testing in suspected meningitis and encephalitis.

Diagnostic stewardship interventions can decrease unnecessary antimicrobial therapy and microbiology laboratory resources and costs. This retrospective cross-sectional study evaluated factors associated with inappropriate initial cerebrospinal fluid (CSF) testing in patients with suspected community-acquired meningitis or encephalitis. In 250 patients, 202 (80.8%) and 48 (19.2%) were suspected meningitis and encephalitis, respectively. 207 (82.8%) patients had inappropriate and 43 (17.2%) appropriate testing. Any inappropriate CSF test was greatest in the immunocompromised (IC) group (n = 54, 91.5%), followed by non-IC (n = 109, 80.1%) and HIV (n = 44, 80%). Ordering performed on the general ward was associated with inappropriate CSF test orders (adjOR 2.81, 95% CI [1.08-7.34]). Laboratory fee costs associated with excessive testing was close to $300,000 per year. A stepwise algorithm defining empiric and add on tests according to CSF parameters and patient characteristics could improve CSF test ordering in patients with suspected meningitis or encephalitis.

Impact of the FilmArray meningitis/encephalitis panel on antimicrobial duration among patients with suspected central nervous system infection.

Ten controlled studies evaluated antimicrobial use following implementation of the FilmArray meningitis and encephalitis panel versus usual care. Only one-half of studies identified significant reductions in antibiotic duration, with 8/10 reporting modest reductions for acyclovir. Coupling the FilmArray meningitis and encephalitis panel with interventions by antimicrobial stewardship programs may help enhance its clinical impact.

MYCOTIC PNEUMONIA AND ENCEPHALITIS IN SOUTHERN PUDU (PUDU PUDA).

This case series describes six confirmed cases of mycotic encephalitis and/or mycotic pneumonia in southern pudu (Pudu puda). One case involved a 10.5-yr-old intact female that presented with an inability to stand, eventually progressing to grand mal seizures. Magnetic resonance imaging showed a lesion within the cerebellar vermis with edema causing cerebellar herniation. The animal was euthanized based on a grave prognosis. Gross and histologic examination revealed primary central nervous system phaeohyphomycosis. Curvularia spicifera was sequenced from the cerebellar tissue. This is the first time this fungus has been reported as a primary central nervous system infection in an artiodactyl species. The remaining five cases occurred in neonates between 17 and 67 days old. Clinical signs varied widely, including facial swelling, weakness, posterior paresis, and sudden death. Antifungal therapy was initiated in three neonatal animals but was unsuccessful in each case. All neonates had active mycotic pneumonia caused by Aspergillus fumigatus or Mucor spp. at time of death; four of these animals also had disseminated disease that caused mycotic encephalitis. This case series indicates that fungal disease should be included in the differential diagnosis list of any pudu presenting for neurologic or respiratory clinical signs.

Follow-up of a Rickettsia felis encephalitis: Some new insights into clinical and imaging features.

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.

Encephalitis and meningitis in Western Africa: a scoping review of pathogens.

OBJECTIVE: To give an overview of the recently reported literature on the aetiologies of meningitis and encephalitis in western sub-Saharan Africa. METHODS: We conducted a scoping review following PRISMA guidance on published meningitis and encephalitis cases in the 16 countries of the United Nations-defined western sub-Saharan African region as identified in cohort studies, case series, and case reports, published 01/01/2000-08/01/2020, and available in four databases in August 2020 with an abstract in English, French or Italian. RESULTS: There were 38 distinct pathogens identified from 91 cohort studies' data and 48 case reports or case series' data. In cohort-level data, the majority of cases were caused by Neisseria meningitidis (71.5%), Streptococcus pneumoniae (17.6%) and Haemophilus influenzae (7.3%). In case report- and case series-level data, 40.5% of patients were <18 years old, 28.6% were female, and 28.6% were known to be immunocompromised. The case fatality rate was 39.3%. The most commonly reported pathogens among immunocompetent patients were Salmonella species (13 cases) and Ebola virus (9 cases), and the most commonly reported pathogen among immunocompromised patients was Cryptococcus neoformans (18 cases). Most cohort cases (52.3%) derived from Niger followed by Burkina Faso (28.6%). Most cases from single reports or series were reported from Nigeria (21.4%), Mali (20.2%) and Burkina Faso (19.0%). CONCLUSIONS: Given the small number of pathogens reported, our findings underscore the need to better screen, diagnose and monitor populations in western sub-Saharan Africa for additional CNS pathogens, including those posing significant outbreak risks.

Antimicrobial therapy and the potential mechanisms in Alzheimer's disease.

Alzheimer's disease treatments have been a heavily investigated research area, however, new drugs have failed one after another. Some scientists have begun to reposition drugs, including antimicrobial agents. Here, the treatment effects of nine antimicrobial agents on Alzheimer's disease and their possible therapeutic mechanisms are described to clarify their efficacy. In vivo and in vitro studies are quite encouraging and tend to demonstrate that antimicrobial therapy is effective in Alzheimer's disease. Nevertheless, unsatisfactory clinical efficacy, side effects, and insufficient knowledge have yet to be overcome. Further laboratory and clinical studies are required to recommend antimicrobial treatment regimens.

Epidemiology, Etiology and Clinical Aspects of Childhood Acute Encephalitis in a Tertiary Pediatric Hospital in Costa Rica.

BACKGROUND: Limited data are available on childhood encephalitis in Latin America. Our study aimed to increase insight on clinical presentation, etiology and outcome of children with acute encephalitis in Costa Rica. METHODS: We conducted a prospective, observational study during an 8-month period at the Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera" in Costa Rica. Case definition was according to "International Encephalitis Consortium" in children <13 years. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. RESULTS: Forty patients were identified. Mean age was 5 years and 57.5% were male. Most frequently neurologic symptoms were altered mental status (100.0%), headache (57.5%) and seizures (52.5%). Etiology was determined in 52.5% of cases. Probable or confirmed viral etiology was identified in 6 cases (15.0%) and bacterial etiology in also 6 cases (15.0%). A possible etiology was identified in 7 cases (17.5%). Autoimmune encephalitis was diagnosed in 2 patients (5.0%). Enterovirus and Streptococcus pneumoniae were the most common confirmed agents. No cases of herpes simplex virus were found. Etiology of 19 cases (47.5%) remained unknown. Sequelae were reported in 45.0% of patients. Mortality rate was 15.0% (6 cases), 3 caused by virus (adenovirus, human herpesvirus 6, enterovirus), 2 by bacteria (S. pneumoniae, Haemophilus influenzae type b) and 1 of unknown etiology. Diffuse cerebral edema was the most important mortality predictor (P < 0.001). CONCLUSIONS: Acute encephalitis in our study was associated with significant morbidity and mortality. Early and aggressive antiviral, antibiotic and anticerebral edema treatment is necessary when acute encephalitis is suspected.

The Microbiota-Gut-Brain Axis and Alzheimer's Disease: Neuroinflammation Is to Blame?

For years, it has been reported that Alzheimer's disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota-gut-brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood-brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota-host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD.

Toxoplasmic Encephalitis Followed by Primary EBV-Associated Post-Transplant Lymphoproliferative Disorder of the Central Nervous System in a Patient Undergoing Allogeneic Hematopoietic Stem Cell Transplant: A Case Report.

Toxoplasmic encephalitis (TE) and post-transplant lymphoproliferative disorder of the central nervous system (CNS-PTLD) are major complications after allogeneic hematopoietic stem cell transplant (allo-SCT); both are fatal without timely diagnosis and disease-specific treatment. Differential diagnosis of TE and CNS-PTLD can be challenging because brain biopsy, a gold standard for diagnosis, is sometimes not possible, owing to poor patient condition after allo-SCT. Here, we describe a case of isolated CNS-PTLD arising during the therapeutic course of TE. A 51-year-old man was admitted with mental abnormalities and fever on Day 106 after allo-SCT to treat myelodysplastic syndrome. Magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhanced lesions in the brain, and the result of polymerase chain reaction (PCR) for Toxoplasma gondii in cerebrospinal fluid was positive; therefore, he was diagnosed with TE. Anti-Toxoplasma therapy led to clinical improvement, and the result of subsequent PCR was negative. However, he developed left-sided hemiplegia on Day 306. Head MRI revealed a new lesion and a growing lesion, presenting as ring-enhanced nodules. Brain biopsy was performed, and a pathologic diagnosis of Epstein-Barr virus-associated CNS-PTLD was made. There was no evidence of TE. He was treated successfully by reducing immunosuppressants, followed by rituximab administration and a donor lymphocyte infusion, resulting in complete remission. While T.gondii-specific PCR has great value for diagnosis of TE, CNS-PTLD can be diagnosed only by brain biopsy; hence, brain biopsy may be warranted in cases of suspected PTLD.

[Pneumonia and benign acute myositis of childhood due to Mycoplasma pneu-moniae associated with encephalitis: A case report]. / Neumonía y miositis aguda benigna de la infancia por Mycoplasma pneumoniae asociado a encefalitis: reporte de caso.

One of the leading causes of pneumonia in children between 5 to 15 years is Mycoplasma pneumoniae, a bacterium that causes atypical clinical manifestations such as myositis and encephalitis. We report a 5-year-old girl who presented functional limitations of the lower extremities preceded by an upper respiratory infection. Later on, she developed pneumonia and encephalitis. Antibiotics and antivirals were administered due to the clinical deterioration of the patient. IgM serology for Mycoplasma pneumoniae was positive, while the other viral studies were negative. The clinical course was favorable with a progressive decrease in respiratory distress, sensorial disorder, and improvement in the functional limitations of the lower limbs after 15 days of treatment.

Una de las principales causas de neumonía en niños entre 5 y 15 años es el Mycoplasma pneumoniae, una bacteria que causa manifestaciones clínicas atípicas como la miositis y encefalitis. Reportamos un caso de una niña de cinco años que presentó limitación funcional en extremidades inferiores precedida por una infección respiratoria superior. Posteriormente, se complicó con neumonía y encefalitis. Se administraron antibióticos y antivirales debido al deterioro clínico del paciente. La serología de inmunoglobulinas para Mycoplasma pneumoniae fue positiva; mientras que los demás estudios virales fueron negativos. El curso clínico fue favorable con disminución progresiva de la dificultad respiratoria, trastorno del sensorio y mejoría en la limitación funcional en las extremidades inferiores a los 15 días de tratamiento.

Predictors of infectious meningitis or encephalitis: the yield of cerebrospinal fluid in a cross-sectional study.

BACKGROUND: Cerebrospinal fluid (CSF) analyses are recommended in patients with meningitis and/or encephalitis, but evidence regarding its diagnostic yield is low. We aimed to determine predictors of infectious pathogens in the CSF of adult patients presenting with meningitis, and/or encephalitis. METHODS: Consecutive patients with meningitis and/or encephalitis form 2011-17 at a Swiss academic medical care center were included in this cross-sectional study. Clinical, neuroradiologic, and laboratory data were collected as exposure variables. Infectious meningitis and/or encephalitis were defined as the composite outcome. For diagnosis of bacterial meningitis the recommendations of the European Society of Clinical Microbiology and Infectious Diseases were followed. Viral meningitis was diagnosed by detection of viral ribonucleic or deoxyribonucleic acid in the CSF. Infectious encephalitis was defined according to the International Encephalitis Consortium (IEC). Meningoencephalitis was diagnosed if the criteria for meningitis and encephalitis were fulfilled. Multinomial logistic regression was performed to identify predictors of the composite outcome. To quantify discriminative power, the c statistic analogous the area under the receiver-operating curve (AUROC) was calculated. An AUROC between 0.7-0.8 was defined as "good", 08-0.9 as "excellent", and > 0.9 as "outstanding". Calibration was defined as "good" if the goodness of fit tests revealed insignificant p-values. RESULTS: Among 372 patients, infections were diagnosed in 42.7% presenting as meningitis (51%), encephalitis (32%), and meningoencephalitis (17%). Most frequent infectious pathogens were Streptococcus pneumoniae, Varicella zoster, and Herpes simplex 1&2. While in multivariable analysis lactate concentrations and decreased glucose ratios were the only independent predictors of bacterial infection (AUROCs 0.780, 0.870, and 0.834 respectively), increased CSF mononuclear cells were the only predictors of viral infections (AUROC 0.669). All predictors revealed good calibration. CONCLUSIONS: Prior to microbiologic workup, CSF data may guide clinicians when infection is suspected while other laboratory and neuroradiologic characteristics seem less useful. While increased CSF lactate and decreased glucose ratio are is the most reliable predictors of bacterial infections in patients with meningitis and/or encephalitis, only mononuclear cell counts predicted viral infections. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03856528. Registered on February 26th 2019.

Etiology and prognosis of encephalitis in French Guianese children: a retrospective record-based study.

Acute encephalitis is an important cause of mortality and morbidity in children. We retrospectively identified children (≤15 years of age) admitted with suspected encephalitis at the Intensive Care Unit of the Pediatric Department of Cayenne Hospital between January 2007 and December 2018. A total of 30 children with acute encephalitis were identified. The incidence rate varied from 0 to 10.40 cases/100000 children under 15 years. Proven encephalitis was diagnosed in 73% of patients. Nine cases of acute disseminated encephalomyelitis were diagnosed. The causes of infection (44%) were Haemophilus influenzae, followed by Cryptococcus spp and Varicella Zoster Virus. Four children (13%) died: one case of Streptococcus pneumoniae, one of Haemophilus influenzae, one of Mycobacterium tuberculosis and one with no identified cause. Seventeen percent of children had moderate to severe neurological sequelae. The only factor associated with poor outcome was young age at the time of hospitalization (p = 0.03). Conclusion: This study highlights both vaccine-preventable pathogens and acute disseminated encephalomyelitis as the leading causes of childhood encephalitis in French Guiana.