Etiology Of Encephalitis Research Articles

Herpes Simplex Virus Encephalitis in Patients With Autoimmune Conditions or Exposure to Immunomodulatory Medications.

Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is most common, accounting for ∼15%-40% of adult encephalitis diagnoses. We aim to investigate the association between immune status and HSV encephalitis (HSVE). Using a US Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. We used the US Medicaid Analytic eXtract data between 2007 and 2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age and sex-matched adult cases of HSVE with a sufficient enrollment period (12 months before HSVE diagnosis) to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson Comorbidity Index, and non-autoimmune comorbidities. Incidence of HSVE was ∼3.01 per 105 person-years among adults. A total of 951 HSVE cases and 95,100 age and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong (adjusted odds ratio (OR) 2.6; 95% CI 2.2-3.2). The association of HSVE and immunomodulating medications had an OR of 2.2 (CI 1.9-2.6), also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: OR 2.3 (CI 1.9-2.7) for autoimmune disease and 2.0 (CI 1.7-2.3) for immunosuppressive and immunomodulatory medications. In a large, national population, HSVE is strongly associated with preexisting autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date.

Clinical epidemiology, determinants, and outcomes of viral encephalitis in Ghana; a cross-sectional study.

Viral encephalitis is a rare, yet severe neurological disorder. It poses a significant public health threat due to its high morbidity and mortality. Despite the disproportionate burden of the disease in impoverished African countries, the true extent of the problem remains elusive due to the scarcity of accurate diagnostic methods. The absence of timely and effective diagnostic tools, particularly Real-time Polymerase Chain Reaction, has led to misguided treatment, and an underestimation of the disease burden in Ghana. We conducted a prospective cross-sectional study to determine the viral aetiologies of encephalitis among patients presenting to a major referral hospital in Ghana from May 2019 and August 2022. The study aimed at providing a comprehensive information on the clinical epidemiology, and outcomes of viral encephalitis in Ghana. Clinical samples were collected from patients presenting with signs and symptoms of encephalitis and tested for viral agents using real-time polymerase chain reaction. We assessed the clinical epidemiology, risk factors and outcome of individuals using descriptive and logistic regression analysis. Seventy-seven (77) patients were enrolled unto the study. The participants frequently presented with fever (85.7%), seizures (80.5%), lethargy (64.9%) and headache (50.6%). Viruses were detected in 40.3% of the study participants in either cerebrospinal fluid, rectal or oral swab samples. The most frequently detected viruses were cytomegalovirus (48.4%), enteroviruses (38.7%) and HSV (29.0%). Twenty-one (27.3%) of the patients died while on hospital admission. Gender (OR = 5.70 (1.536-1.172), p = 0.01), and negative polymerase chain reaction test results were identified as significant factors associated with death. Antiviral treatment increased the chance of survival of viral encephalitis patients by 21.8%. Our results validate the crucial role of molecular tools as essential for the rapid diagnosis of viral encephalitis, enabling effective treatment and improved patient outcomes. This study contributes valuable epidemiological and clinical insight into viral encephalitis in Ghana.

Negative HIV encephalitis and meningoencephalitis management algorithm Decision-making

Meningoencephalitis is a serious, relatively frequent infection, with a worldwide incidence of 3.5 to 7.4 per 100,000 inhabitants per year and a high mortality rate (10 to 12%). The objective of our work was to determine the etiologies of encephalitis and meningoencephalitis using the most modern microbiological diagnostics and to propose a management algorithm diagnosis. Materials and methods: This is a prospective descriptive study of 141 patients aged over 28 days with symptoms suggestive of HIV-negative encephalitis and meningoencephalitis during the period from April 1, 2012 to August 31, 2015. Several types of analyzes of the various samples (LCS, serum, nasopharyngeal samples) were carried out, including 2671 by PCR, 404 direct examinations and bacterial culture, 219 viral cultures and 380 serologies. The number of pathogens screened for the patients included in this study varied from 1 to 31 pathogens. Results: In Batna, a wide range of pathogens cause acute encephalitis. Of the 141 patients, 111 (78.7%) had at least one etiological diagnosis (63 certain, 80 probable and 32 possible). Diagnosis was confirmed for 58 (41.2%) patients, probable for 41 (29.1%), and possible for 12 (8.5%). The overall incidence of encephalitis in our region is 2.15 / 100,000 inhabitants with an average age of 30.8 years (standard deviation = 21.5 years). The most frequently identified etiological pathogen was KB 30 (21.3%), followed by EBV 20 (14.2%), HSV 14 (9.9%), CMV 11 (7.8%), Coronavirus 18 (12.5), and Adenovirus 6 (4.3%).The search for patients with a confirmed and/or probable monomicrobial agent, numbering 53 (37.6%), was essential to come out with a decision-making algorithm regarding the diagnostic approach. Coinfections were identified for 48 patients (34%), of whom 12 (8.5%) had more than 2 pathogens found. 21.3% of cases remained of undetermined cause. Evolution was unfavorable for 67 or 47.2%. There were 43 cases of death (30.5%), with 20 cases of after-effects. Conclusion: This study made it possible to highlight for the first time the etiologies of encephalitis and meningoencephalitis with their clinical and para-clinical particularities, in the region of eastern Algeria (Batna), which allowed the development of a decision-making algorithm for the diagnostic approach allowing rapid and appropriate care for our patients.

Virus discovery in dogs with non-suppurative encephalitis reveals a high incidence of tick-borne encephalitis virus infections in Switzerland.

Viral infections are a frequent cause of disseminated non-suppurative encephalitis in dogs. However, using routine diagnostic methods, the specific virus may remain unknown due to extensive or complete viral clearance or because the virus is unexpected or new. A metatranscriptomics-based approach of combining high-throughput sequencing (HTS) and bioinformatics analysis was used to investigate the viral etiology in archival cases of dogs with non-suppurative encephalitis. In formalin-fixed paraffin embedded (FFPE) brain material from the years 1976 to 2021 a high incidence of tick-borne encephalitis virus (TBEV) was detected. Moreover, canine distemper virus (CDV) was identified without typical demyelinating lesions and canine vesivirus (CaVV) was detected as an unexpected virus associated with non-suppurative encephalitis. We demonstrated the viral presence in brain tissues at the sites of inflammation by immunohistochemistry (IHC) and in situ hybridization (ISH). These results highlight the value of emerging sequencing technologies in veterinary diagnostics and expand our knowledge on the etiologies of encephalitis in dogs.

Immunocompromise and herpes simplex virus type 1 encephalitis (HSVE): a nationwide cohort and case-control study (S25.009)

<h3>Objective:</h3> We aim to determine whether a relationship exists between immunocompromise as defined by autoimmune disease or immunosuppressive and immunomodulatory medications in patients and incident HSVE. <h3>Background:</h3> Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is commonest. The association between immune status and HSVE is unclear. Using a U.S. Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. <h3>Design/Methods:</h3> We used the U.S. Medicaid Analytic eXtract Database between the years of 2007–2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age- and sex-matched adult cases of HSVE with a sufficient enrolment period to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson comorbidity index, and non-autoimmune comorbidities. <h3>Results:</h3> Incidence of HSVE was ~3.01 per 10⁵ person-years among adults. A total of 951 HSVE cases and 95,100 age- and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong, adjusted OR 2.6 (95% CI [2.2, 3.2]). The association of HSVE and immunomodulating medications had an OR of 2.2 [1.9, 2.6], also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: 2.3 [1.9, 2.7] for autoimmune disease and 2.0 [1.7, 2.3] for immunosuppressive and immunomodulatory medications. <h3>Conclusions:</h3> In a large, national population, HSVE is strongly associated with pre-existing autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date. <b>Disclosure:</b> Dr. Tang has received personal compensation for serving as an employee of Third Rock Ventures. Dr. Bhattacharyya has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Bhattacharyya has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Continuum. The institution of Dr. Bhattacharyya has received research support from Alexion Pharmaceuticals. The institution of Dr. Bhattacharyya has received research support from National Institute of Health. The institution of Dr. Bhattacharyya has received research support from UCB. Dr. Bhattacharyya has received publishing royalties from a publication relating to health care. Dr. Bhattacharyya has received publishing royalties from a publication relating to health care. Dr. Bhattacharyya has received publishing royalties from a publication relating to health care. Dr. Miyawaki has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Family Health, Inc.. Dr. Miyawaki has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Morrison and Mahoney. Dr. Miyawaki has stock in Cincinnati Bengals. Dr. Miyawaki has received publishing royalties from a publication relating to health care. Dr. Miyawaki has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with US Department of Health and Human Services. Dr. Yoshida has received personal compensation for serving as an employee of OM1, Inc. Dr. Yoshida has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for OM1, Inc. Dr. Wilcox has nothing to disclose. Karen Costenbader has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Karen Costenbader has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Karen Costenbader has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Glaxo Smith Kline. Karen Costenbader has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca Pharmaceuticals LP. Karen Costenbader has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Arthritis and Rheumatology. Karen Costenbader has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Uptodate. Karen Costenbader has stock in Neutrolis. The institution of Karen Costenbader has received research support from Gilead. The institution of Karen Costenbader has received research support from Exagen. The institution of Karen Costenbader has received research support from Merck. Karen Costenbader has received personal compensation in the range of $0-$499 for serving as a grant reviewer with NIH. Prof. Solomon has nothing to disclose. Mr. Guan has nothing to disclose. Miss Lahey has nothing to disclose.

A Retrospective Review on Encephalitis in the University of Colorado Health Care System and a Proposed Diagnostic Approach (P8-10.005)

<h3>Objective:</h3> To define current diagnostic testing and resource utilization patterns for patients hospitalized with encephalitis. <h3>Background:</h3> In the US, encephalitis results in &gt;20,000 hospitalizations, over 1,000 deaths, and more than $2 billion in hospital charges yearly (Vora et al, 2014). Correctly and rapidly distinguishing between infectious and non-infectious causes of encephalitis is critical for early initiation of therapeutic interventions. A systematic, electronic medical record (EMR)-based diagnostic pathway may improve the accuracy and cost-effectiveness of diagnostic investigations in encephalitis. Here we present demographic, clinical and resource utilization data from patients hospitalized with encephalitis within a single, large hospital system over a twelve-month period. A proposed diagnostic pathway and prospective intervention study are additionally outlined. <h3>Design/Methods:</h3> This is a retrospective study identifying cases of encephalitis using ICD-10 codes from University of Colorado Hospital (UCH) system EMR for chart review. Cases identified within a 12-month period (01 June 2021 to 31 May 2022), are under review for analysis of key clinical and outcome measures. <h3>Results:</h3> A diagnosis of encephalitis was identified in 140 patients hospitalized during a twelve-month period preceding diagnostic pathway implementation. Patient ages ranged from 20 to 90 years (mean 57). There was equal division between sexes. 78% of patients were white, 14% were Black or African American, and 14% the race was unknown. All patients had a lumbar puncture performed. Magnetic resonance imaging of the brain was obtained for 43% of patients. Additional clinical and resource utilization data will be extracted and analyzed. <h3>Conclusions:</h3> The UCH system has a high volume of encephalitis cases accompanied by a high utilization of diagnostic testing. Analysis of clinical, outcome and resource utilization metrics may identify areas for improvement, allowing for rational design, implementation, and subsequent prospective study of an EMR-based diagnostic pathway to facilitate the rapid and cost-effective determination of encephalitis etiologies. <b>Disclosure:</b> Dr. Garza has nothing to disclose. Dr. Matthews has nothing to disclose. Dr. Sauer has nothing to disclose. Mr. Engebretson has nothing to disclose. Ms. Valdez has a non-compensated relationship as a Valdez with The Rocky Mountain MS Center non-profit partner that is relevant to AAN interests or activities. The institution of Stefan Sillau has received research support from Alzheimer’s Association. The institution of Stefan Sillau has received research support from Hewitt Family Foundation; State of Colorado. The institution of Stefan Sillau has received research support from PCORI. The institution of Stefan Sillau has received research support from NINR. The institution of Stefan Sillau has received research support from Michael J. Fox Foundation. The institution of Stefan Sillau has received research support from Department of Defense. The institution of Stefan Sillau has received research support from Colorado Department of Public Health and Environment. The institution of Stefan Sillau has received research support from Benign Essential Blepharospasm Research Foundation. Stefan Sillau has a non-compensated relationship as a Statistician with Novartis that is relevant to AAN interests or activities. Stefan Sillau has a non-compensated relationship as a Statistician with Biogen that is relevant to AAN interests or activities. Dr. Carlson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Carlson has received research support from Horizon Therapeutics. Dr. Carlson has a non-compensated relationship as a Health Service Subcommittee Member with American Academy of Neurology that is relevant to AAN interests or activities. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Novartis. The institution of Dr. Piquet has received research support from Abbvie. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP.

Human herpesvirus 7 encephalitis in an immunocompetent adult and a literature review

BackgroundHuman herpesvirus 7 (HHV-7) is a common virus that infects children early and is accompanied by lifelong latency in cells, which is easy to reactivate in immunodeficient adults, but the underlying pathological mechanism is uncertain in immunocompetent adults without peculiar past medical history. Even though the clinical manifestation of the encephalitis caused by HHV-7 is uncommon in immunocompetent adults, the HHV-7 infection should not be neglected for encephalitis for unknown reasons.Case presentationWe reported here a case of HHV-7 encephalitis with epileptic seizures. While the brain computer tomography was standard, electroencephalography displayed slow waves in the temporal and bilateral frontal areas, then HHV-7 DNA was detected in the metagenomic next-generation sequencing of cerebrospinal fluid. Fortunately, the patient recovered after treatment and was discharged 2 months later. We also collected the related cases and explored a better way to illuminate the underlying mechanism.ConclusionThe case indicates clinicians should memorize HHV-7 as an unusual etiology of encephalitis to make an early diagnosis and therapy.

Endemic Viral Disease - Expert Group Opinion for Solid Organ Transplant Recipients in South Asia – Dengue, Chikungunya, Zika, Rabies, Japanese Encephalitis, and Nipah Virus

South Asia is endemic to many virus infections such as arboviruses such as dengue virus, chikungunya virus, Zika virus, Japanese encephalitis (JE) virus, and rabies virus. Arbovirus infections present as fever, rash, arthralgia, myalgia, etc., Although transmission of these viruses has rarely been reported in organ transplants, in the endemic season, there is a possibility as the donor might be in an incubation period. Donor deferral for at least 30 days is advised in any donor with confirmed or suspected cases of arboviral infection. Rabies and JE can cause encephalitis and remain undiagnosed many times, so donors with unknown etiology of encephalitis should be excluded from donation. Nipah virus is an emerging virus, which is reported mainly from Bangladesh, Siliguri, and Kerala in India, however, no case of donor-derived infection has been reported yet.

Mitochondrial Disease Masquerading as Recurrent Encephalopathy

A young male who was a diabetic presented with gradually progressive hearing loss, recurrent episodic behavioral abnormality, easy fatigability, proximal weakness, and seizures. The patient was evaluated in detail to find out the etiology of encephalitis. The serum autoimmune encephalitis panel was negative. On magnetic resonance imaging of the Brain, there was temporoparietal T2 and fluid-attenuated inversion recovery hyperintensity. In the magnetic resonance spectroscopy study, a lactate peak was found. So, the patient was evaluated for mitochondrial illness mitochondrial encephalopathy lactic acidosis with stroke-like symptoms) and it was confirmed by a genetic study. This case illustrates that though it is a rare disease, always a strong clinical index of suspicion is required for the diagnosis of mitochondrial disorders in case of multisystem involvement so that diagnosis would not be missed.

Clinico-Epidemiologic Features and Outcome of Infectious and Immune-mediated Pediatric Encephalitis

Introduction: The etiology of encephalitis involves an enormous range and can be classified as infectious or immune-mediated. There are several factors influencing its prognosis and has been associated with significant morbidity and mortality. This study aims to evaluate the clinico-epidemiologic characteristics and outcomes of infectious and immune-mediated encephalitis among pediatric patients. Methodology: Retrospective descriptive cross-sectional study that included patients aged 6 months to 17 years old with encephalitis in a tertiary hospital between January 2010 to December 2020. Results: A total of 23 cases were reviewed and 60.87% were infectious while that of immune-mediated was 39.13%. Among those with identified infectious cause, Mycoplasma pneumonia was the most common (28.57%). Infectious encephalitis was more common among younger males (35.71%) while immune-mediated affected female adolescents more (55.56%). The most common neurologic manifestation was altered mental status and/or behavioral changes. Treatment such as antibiotics (78.26%), anticonvulsant therapy (78.26%), and steroids (43.48%) were given. All immune-mediated cases received steroids. More than half of patients had complete recovery (56.52%). Conclusion: Pediatric encephalitis should be considered among patients with neurologic dysfunction with or without systemic involvement. Behavioral changes in an apparently well child should prompt clinicians to consider anti-NMDAR encephalitis, especially if viral studies are negative and with no other known cause. Viruses remain to be the most common etiology, but other possible causes should be highly considered such as anti-NMDAR and Mycoplasma. A normal CSF analysis, imaging and/or encephalography (EEG) may not totally exclude encephalitis. Prognosis is relatively good hence an early diagnosis and initiation of appropriate management is important.

Study of Demographic Profile, Etiology, and Clinical Outcome in Patients Admitted With Acute Encephalitis Syndrome From the Western Part of India.

BackgroundDetermining the etiology of encephalitis always remains a challenge to clinicians, and also, variables that predict outcome in acute phase settings are not known precisely. The autoimmune causes of acute encephalitis are increasing due to the availability of newer diagnostic markers, whereas earlier studies were primarily focused on infectious causes. We conducted a prospective study to determine the demographic profile, etiological aspect, and in-hospital outcome of patients admitted with acute encephalitis syndrome (AES) in our tertiary care center.Materials and methodThis observational prospective study was carried out at a tertiary care hospital between November 2016 and October 2018. With a sample size of 72, appropriate statistical analysis was done.ResultsThe incidence of AES usually escalates during the rainy season, with arboviral etiologies being predominant. The majority of the patients with AES with a likely infectious etiology could not be diagnosed with presently available viral marker studies. Among various clinical variables, a low Glasgow Coma Scale (GCS) score on admission, a high CSF protein value, and diffusion restriction on brain MRI was associated with poor outcome.ConclusionAcute encephalitis and encephalitis-related mortality impose a considerable burden on current medical practice. The reported demographics of hospitalized patients with encephalitis may be changing, which are important factors to consider for etiological workup.

Effectiveness of a single dose of Japanese encephalitis vaccine among adults, Assam, India, 2012–2018

BackgroundJapanese encephalitis virus (JEV) remains the major etiology of encephalitis throughout Asia. In India, the state of Assam alone contributes more than one-third of the national burden of JE. Between 2011 and 2014, a single dose of JE vaccine SA 14-14-2 (LAJEV) was administered among adults aged 15–65 years residing in Sivasagar and Dibrugarh districts of Assam, India. We monitored the trend of JE incidence between 2009 and 2018 using JE surveillance data, estimated the long-term effectiveness of the single dose of LAJEV and estimated the coverage of JE vaccine in two districts. MethodsWe compared the JE vaccination status of laboratory-confirmed hospitalized JE patients (case) and age, sex and locality matched healthy individuals (controls) to estimate the effectiveness of single dose of JE vaccine. We used surveillance data for 2009–2018 to calculate the incidence of JE among adults. We conducted a community-based survey to estimate the coverage of JE vaccine in the two districts. ResultsA total of 452 laboratory-confirmed JE case-patients and 904 matched healthy controls were enrolled in the study between 2012 and 2018. The effectiveness of a single dose of JE vaccine over the 7-year period was 77.0 (95% CI: 67.0–83.0). Vaccine effectiveness decreased from 91% (95% CI: 73.0–97.0) in first year of vaccination to 71% (95% CI: 21.0–90.0) at six years post-vaccination. The incidence of adults JE cases declined from 10.5 per 100,000 in the pre-vaccination period to 5.7 per 100,000 in the years following vaccination. The coverage of vaccine among adults in two districts was 40.1% (36.8–43.5). ConclusionsA single dose of JE vaccine offered adequate protection for at least six years. Conducting mass vaccination campaigns periodically would further reduce the incidence of JE in endemic districts in Assam.

Etiological structure of neuroinfections

The aim of the study was to study the etiological structure and epidemiological features of infectious diseases that occur with central nervous system damage in hospitalized patients.Material and methods. A retrospective study of the medical histories of 376 patients with meningitis and encephalitis was conducted.Results and discussion. At the pre-hospital stage, only 198 (52.6 %) patients were diagnosed with «meningitis, encephalitis», which indicates that primary care physicians are not sufficiently alert to diseases of the central nervous system (CNS). When studying the epidemiological history, contact with infectious patients was noted in 69 (18.3 %) patients. The structure of neuroinfections in hospitalized patients was dominated by meningitis (334 cases - 88.8 %), encephalitis was found in 42 (11.2 %) patients. Among meningitis, purulent processes (205 people - 61.4 %) prevailed over serous ones (127 patients - 38.0 %); 2 patients were diagnosed with mycotic meningitis. In adults, the etiology of the disease was clarified in 58 (44.6 %) of 130 patients with bacterial meningitis and in 22 (27.8 %) of 79 with serous meningitis; among children - in 60 (80 %) of 75 patients with purulent meningitis and in 23 (47.9 %) of 48 with serous processes. Encephalitis and meningoencephalitis were detected in 30 adult patients and 12 children. The etiology of encephalitis was established in 13 (43.35) adults and 4 (25 %) children.

Etiological and Clinical Profile of Acute Nonbacterial Encephalitis in Children: A Single-Center Prospective Study.

Encephalitis is a serious neurological syndrome caused by inflammation of the brain. The diagnosis can be challenging and etiology remains unidentified in about half of the pediatric cases. We aimed to investigate demographic, clinical, laboratory, electroencephalographic and neuroimaging findings, and outcome of acute encephalitis of nonbacterial etiology. This prospective study included children hospitalized with the diagnosis of acute encephalitis between 2017 and 2019. Microbiological investigations of the cerebrospinal fluid (CSF) were recorded. All CSF specimens were tested for anti-N methyl D-aspartate receptor (NMDAR) antibodies. In total, 31 children aged 10 months to 17 years (median = 6 years) were included. Pathogens were confirmed in CSF in three patients (9.7%): varicella zoster virus, herpes simplex virus type 1 (HSV-1), and both HSV-1 and NMDAR antibodies. Presenting features included encephalopathy (100%), fever (80.6%), seizure (45.2%), focal neurological signs (29%), and ataxia (19.4%). On clinical follow-up of median 9 (6-24) months, six patients showed neurological deficits: together with two patients who died in hospital, total eight (25.8%) patients were considered to have unfavorable outcome. Need for intubation, receiving immunomodulatory treatment, prolonged hospitalization, and high erythrocyte sedimentation rate at admission were associated with unfavorable outcome. The etiology of encephalitis remains unexplained in the majority of children. HSV-1 is the most frequently detected virus, consistent with the literature. The fact that anti-NMDAR encephalitis was detected in one child suggests autoimmune encephalitis not being rare in our center. The outcome is favorable in the majority while about one-fifth of cases suffer from sequelae.

Neuro-Ophthalmic Features of Autoimmune Encephalitides.

Over the past decade, there has been a remarkable advancement in the understanding of autoimmune etiologies of encephalitis. The first identified generation of paraneoplastic encephalitis tends to occur in older populations, responds poorly to immunotherapy, and is mediated by T-cell damage with antibodies directed toward intracellular antigens. A new generation of autoimmune encephalitides has been described, which are mediated by antibodies to cell-surface proteins, tend to occur in younger individuals, are less frequently associated with malignancy, and often respond better to treatment compared to their intracellular antigen-related paraneoplastic counterparts. This review will focus on several specific antibody-mediated autoimmune encephalitides with neuro-ophthalmic pertinence. Literature review and personal clinical experience. Several of the antibody-mediated encephalitides, specifically N-methyl-D-aspartate receptor, dipeptidyl-peptidase-like protein 6, glial fibrillary acidic protein, metabotropic glutamate receptor 1 (mGluR1), gamma-aminobutyric acid receptor, glutamic acid decarboxylase 65 (GAD65), collapsing response mediator protein 5 (CRMP5), and kelch-like protein 11 (KLHL11), contain features of neuro-ophthalmic interest. The novel cell-surface protein-directed autoimmune encephalitis group can present with a wide range of afferent and efferent neuro-ophthalmic manifestations. Neuro-ophthalmologists should be familiar with these antibody-associated syndromes, which are treatable and often require a high index of suspicion for diagnosis.

Aetiology of encephalitis and meningitis in children aged 1-59 months admitted to the Children's Hospital, Lusaka, Zambia

Background: Meningitis and encephalitis are important causes of admissions and mortality in Zambia. Apart from bacterial causes, no data is available on viral agents that cause disease at the Children's Hospital, Lusaka, Zambia. We conducted a prospective descriptive study to determine the viral and bacterial causes of encephalitis and meningitis in children aged 1-59 months.&#x0D; Methods: From November 2016 to February 2018, we collected cerebrospinal fluid (CSF) samples and clinical details from children admitted to the inpatient wards with encephalitis and meningitis. Macroscopic examination, microscopy, bacterialculture and real-time (Multiplex) PCR were performed on the CSF samples.&#x0D; Results: A total of 106 patients were enrolled. The median age was 10 months and 81 (76.4%) had meningitis while 25 (23.6%) had encephalitis. One (0.9%) participant had Haemophilus influenzae detected by both culture and PCR. Two (1.9%) had Neisseria meningitidis while 5 (4.7%) had Streptococcus pneumoniae detected only by PCR. Viruses were detected in 26.4% (28/106) and 64% had meningitis. The viral agents detected were: EBV (10%); Parvovirus B19, Human herpes virus type 6, Human herpes virus type 7 and CMV at 2.8% each. A raised CSF WBC was associated with the case definition (P=0.01) of meningitis. Patients with meningitis were more likely to be alive at discharge than those with encephalitis (OR = 3.6, CI = 1.96 – 6.68, P-value &lt;0.001).&#x0D; Conclusions: Viral infections of the central nervous system (CNS) are the commonest causes of both encephalitis and meningitis at the Children's Hospital, Lusaka, Zambia.

Rapid detection of human herpes virus by next-generation sequencing in a patient with encephalitis

BackgroundThe inflammatory or non-inflammatory changes caused by the virus entering the nervous system and related tissues are central nervous system virus infections. Viral infection is a common infectious disease of the central nervous system, of which herpes simplex virus encephalitis is the most common. However, conventional laboratory techniques to detect an infectious agent are difficult to achieve etiological diagnosis.Case presentationHere we present a patient with severe and progressive encephalitis, requiring diagnosis of the specific pathogen to guide clinical treatments.ConclusionsApplication of next-generation sequencing provided a quick and definite diagnosis of the etiology of encephalitis and enabled our patient to be treated appropriately.

Aetiology of Encephalitis and Meningitis in Children Aged 1-59 Months Admitted to the Children's Hospital, Lusaka, Zambia

Background: Meningitis and encephalitis are important causes of admissions and mortality in Zambia. Apart from bacterial causes, no data is available on viral agents that cause disease at the Children's Hospital, Lusaka, Zambia. We conducted a prospective descriptive study to determine the viral and bacterial causes of encephalitis andmeningitis in children aged 1-59 months.&#x0D; Methods: From November 2016 to February 2018, we collected cerebrospinal fluid (CSF) samples and clinical details from children admitted to the inpatient wards with encephalitis and meningitis. Macroscopic examination, microscopy, bacterial culture and real-time (Multiplex) PCR were performed on the CSF samples.&#x0D; Results: A total of 106 patients were enrolled. The median age was 10 months and 81 (76.4%) had meningitis while 25 (23.6%) had encephalitis. One (0.9%) participant had Haemophilus influenzae detected by both culture and PCR. Two (1.9%) had Neisseria meningitidis while 5 (4.7%) had Streptococcus pneumoniae detected only by PCR. Viruses were detected in 26.4% (28/106) and 64% had meningitis. The viral agents detected were: EBV (10%); Parvovirus B19, Human herpes virus type 6, Human herpes virus type 7 and CMV at 2.8% each. A raised CSF WBC was associated with the case definition (P=0.01) of meningitis. Patients with meningitis were more likely to be alive at discharge than those with encephalitis (OR = 3.6, CI = 1.96 – 6.68, P-value &lt;0.001).&#x0D; Conclusions: Viral infections of the central nervous system (CNS) are the commonest causes of both encephalitis and meningitis at the Children's Hospital, Lusaka, Zambia.&#x0D; Disclosure: The authors declare no conflict of interest.

To what extent can clinical characteristics be used to distinguish encephalitis from encephalopathy of other causes? Results from a prospective observational study

BackgroundRecognizing patients with encephalitis may be challenging. The cardinal symptom, encephalopathy, has a wide array of differential diagnoses. In this prospective study we aimed to explore the etiology of encephalitis and to assess the diagnostic accuracy of symptoms and clinical findings in patients with encephalitis in an encephalopathic population.MethodsPatients with acute onset of encephalopathy (n = 136) were prospectively enrolled from January 2014–December 2015 at Oslo University Hospital, Ullevaal. Clinical and biochemical characteristics of patients who met the case definition of encephalitis were compared to patients with encephalopathy of other causes.ResultsAmong 136 patients with encephalopathy, 19 (14%) met the case-definition of encephalitis. For 117 patients other causes of encephalopathy were found, infection outside the CNS was the most common differential diagnosis. Etiology of encephalitis was confirmed in 53% (4 bacterial, 4 viral, 1 parasitic, and 1 autoimmune). Personality change, nausea, fever, focal neurology, recent travel history, and low inflammation markers were significantly more abundant in patients with encephalitis, but the diagnostic accuracy for individual parameters were low (area under the curve (AUC) < 0.7). The combination of fever (OR = 6.6, 95% CI, 1.6–28), nausea (OR = 8.9, 95% CI, 1.7–46) and a normal level of ESR (erythrocyte sedimentation rate < 17 mm/hr, OR = 6.9, 95% CI, 1.5–33) was significant in multivariate analysis with an AUC (area under the curve) of 0.85 (95% CI, 0.76–0.94). Moderately increased pleocytosis in CSF (5-100 × 106/L) further increased the diagnostic accuracy of this combination, AUC 0.90 (95% CI, 0.81–0.98).ConclusionsThere is a wide diversity in differential diagnoses in patients with encephalopathy, and no single symptom or finding can be used to predict encephalitis with high accuracy in this group. The combination of fever, nausea and a low ESR in an encephalopathic population, increased the diagnostic accuracy of encephalitis compared to solitary parameters. The triad could be a useful clinical tool for early diagnosis of encephalitis, and these patients should be considered for further diagnostics such as lumbar puncture (LP).

Computational prediction of miRNAs in Nipah virus genome reveals possible interaction with human genes involved in encephalitis.

Current re-emergence of Nipah virus (NiV) in India caused 11 deaths so far and many patients were kept in quarantine. A thorough study of previous outbreaks occurred in Malaysia, Bangladesh and India represents cases with high rate of fatality due to acute encephalitis. Our work involves genome analysis of NiV for prediction of miRNAs and their targeted genes in human in order to understand encephalitis origin. Ab-intio program-VMir was used for initial screening of genome, obtained nine pre-miRNAs was analyzed by ViralMir to check for any pseudo pre-miRNAs. Eighteen functional mature miRNAs were extracted from pre-miRNAs by using Mature-Bayes tool, which targets 669 genes in human genome as retrieved by miRDB. Gene ontology terms by PANTHER provide important pathways in which target genes were involved like Axon guidance, T cell activation, and nicotinic acetylcholine receptor signaling. Significant outcome was obtained after NCBI Gene and OMIM database mining and literature search for predicted target genes. TLR3, TJP1, NOTCH2, FHL1, and GRIA3 target genes obtained showed their involvement in host defense, blood brain barrier, neurogenesis, mental retardation and encephalitis. To conclude, we predicted significant genes in human that can be inhibited by miRNAs of NiV and results in etiology of encephalitis.