Viral Infections Of Central Nervous System Research Articles

Emergence of Parechovirus A4 Central Nervous System Infections among Infants in Kansas City, Missouri, USA.

Among known parechovirus (PeV) types infecting humans, PeV-A3 (formerly HPeV3) and PeV-A1 (formerly HPeV1) are associated with pediatric central nervous system (CNS) infections. The prevalence of PeV-A3 among hospitalized infants with sepsis-like illness and viral CNS infection is well described; however, the contribution of PeV-A4 to infant CNS infection is relatively unexplored. We report the first 11 U.S. cases of PeV-A4 CNS infections occurring in Kansas City infants during 2010 to 2016 and compare the clinical presentation with that of PeV-A3. PeV-positive cerebrospinal fluid (CSF) specimens from 2010 to 2016 underwent sequencing for genotyping. Among all PeV-CSF positives, PeV-A4 was detected in 11 CSF samples from 2010 to 2016. PeV-A4 was first detected in 2010 (n = 1/4), followed by detections in 2014 (n = 1/39), 2015 (n = 6/9), and 2016 (n = 3/33). The median age of PeV-A4-infected infants in weeks (median, 4; range, 1 to 8) was similar to that of infants infected with PeV-A3 (median, 4; range, 0.25 to 8). Clinical characteristics of PeV-A4 (n = 11) were compared with those of select PeV-A3-infected children (n = 34) with CNS infections and found to be mostly similar, although maximum temperature was higher (P = 0.017) and fever duration was shorter (P = 0.03) for PeV-A4 than for PeV-A3. Laboratory test results were also similar between genotypes, although they showed significantly lower peripheral white blood cell (P = 0.014) and absolute lymphocyte (P = 0.04) counts for PeV-A4 infants. Like PeV-A3, PeV-A4 caused summer-fall seasonal clusters of CNS infections in infants, with mostly similar presentations. Further surveillance is necessary to confirm potential differences in laboratory findings and in fever intensity/duration.

Intrathecal complement activation by the classical pathway in tick-borne encephalitis

Tick-borne encephalitis (TBE) is one of the most prevalent viral central nervous system (CNS) infections in Eurasia and neurological sequelae are common. The immune responses are considered crucial for the pathogenesis. The aim of this study was to explore the activation of the complement system in TBE. The complement system is a part of the innate immune response in the CNS, which previously has been reported to be activated in other flavivirus infections. We analyzed complement factors in 44 paired cerebrospinal fluid (CSF) and serum samples from 20 cases of TBE in the acute and later stages, as well as in serum and CSF from 32 healthy controls. The concentrations of complement factors C1q, C3a, C3b, and C5a were determined with commercially available ELISA kits. Clinical data to categorize the severity of disease and outcome was retrieved from the medical records of the TBE patients. We found significantly higher concentrations of all of the analyzed complement factors in the CSF from TBE patients compared to the healthy controls. In particular, the marked increment of C1q concentrations in the CSF (p < 0,001 as compared to controls) indicated an intrathecal activation by the classical pathway. There was no correlation between complement factor concentrations in the CSF and severity of the disease in the acute phase or with sequelae at 6 months follow-up. We have found an intrathecal complement activation in TBE, and the marked increase of complement factor C1q indicated an activation by the classical pathway.

Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study

Background: There are sparse and limited studies on small sample size reporting the application of next-generation sequencing (NGS) in the detection of central nervous system (CNS) viral infections. We assessed the diagnostic performance of NGS of cerebrospinal fluid (CSF) for predicting viral infections of the CNS caused by the neurotropic herpes viruses in a pilot population. Materials and Methods: We prospectively collected CSF samples from 24 patients with CNS viral infection from April 2017 to October 2018. Of the 24 patients, 19 patients were infected with herpes simplex virus 1 (HSV-1), 1 patient with HSV-2, and 4 patients with varicella-zoster virus (VZV). All CSF samples were screened for viral DNA using NGS technologies to detect viral CNS infections. Results: Of the 24 patients with confirmed viral CNS infection caused by the neurotropic herpes viruses, 10 (10/24, 41.67%) patients exhibited positive NGS results. With the help of NGS, HSV-1 DNA was detected in the CSF of 6 patients (6/19; 31.58%). HSV-2 DNA was detected in 1 patient (1/1; 100%) and VZV DNA was detected in 3 patients (3/4; 75%). The positive rate of virus detected by NGS decreased with time. The positive rates of NGS of CSF in the first, second, and third weeks were 54.5% (6/11), 44.4% (4/9), and 0% (0/4), respectively. Conclusions: NGS method is a promising pathogen detection tool for identifying viral CNS infections. It should be recommended to sequence viral DNA of CSF in the early stage of CNS viral infections.

Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains.

Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood–brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes.

Kynurenine Is a Cerebrospinal Fluid Biomarker for Bacterial and Viral Central Nervous System Infections.

The tryptophan-kynurenine-nicotinamide adenine dinucleotide (oxidized; NAD+) pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in central nervous system (CNS) infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers. We measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 221 cerebrospinal fluid samples from patients with bacterial and viral (due to herpes simplex, varicella zoster, and enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (due to anti-N-methyl-D-aspartate receptor [NMDA] encephalitis and multiple sclerosis), and noninflamed controls (ie, individuals with Bell palsy, normal pressure hydrocephalus, or Tourette syndrome). Kyn concentrations correlated strongly with CSF markers of neuroinflammation (ie, leukocyte count, lactate concentration, and blood-CSF-barrier dysfunction), were highly increased in bacterial and viral CNS infections, but were low or undetectable in NMDA encephalitis, multiple sclerosis, and controls. Trp concentrations were decreased mostly in viral CNS infections and neuroborreliosis. Multiple logistic regression analysis revealed that combinations of Kyn concentration, Trp concentration, and Kyn/Trp concentration ratio with leukocyte count or lactate concentration were accurate classifiers for the clinically important differentiation between neuroborreliosis, viral CNS infections, and autoimmune neuroinflammation. The Trp-Kyn-NAD+ pathway is activated in CNS infections and provides highly accurate CSF biomarkers, particularly when combined with standard CSF indices of neuroinflammation.

Importance of cerebrospinal fluid investigation during dengue infection in Brazilian Amazonia Region.

BACKGROUND Amazon, the largest tropical forest of the world, has suffered from dengue outbreaks since 1998. Cerebrospinal fluid (CSF) of patients, from Amazonas state, suspected of central nervous system (CNS) viral infection was studied using molecular and immunological methods. OBJECTIVE To evaluate the importance of CSF investigation in patients with acute dengue virus (DENV) infection of CNS. METHODS CSF samples of 700 patients were analysed by reverse transcription polymerase chain reaction (RT-PCR) to detect the presence of dengue virus (DENV) RNA and by enzyme-linked immunosorbent assay (ELISA) to detect presence of DENV specific IgM. FINDINGS DENV infection was detected in 4.3% of the CSF samples; 85.7% (24/28) by DENV IgM and 14.3% (4/28) by viral RNA. DENV detected by viral RNA were to be found serotypes DENV-2 (three patients) and DENV-1 (one patient). The neurological diagnosis in patients CNS infection of DENV included encephalitis (10), meningoencephalitis (10), meningitis (6), acute myelitis (1), and encephalomyelitis (1). The majority (89.3%) had intrathecal inflammation: pleocytosis, hyperproteinorrachia and DENV IgM antibodies. Hypoglycorrhachia and/or high levels of lactate in CSF were found in 36% of the patients. Co-infection (CMV, HIV, EBV, and/or Mycobacterium tuberculosis) was observed in eight (28.6%) cases. CONCLUSIONS We found intense inflammatory CSF that is unusual in CNS disorders caused by dengue infection. It may be due co-infections or the immunogenetic background of the local Amerindian Brazilian population. CSF examination is an important diagnostic support tool for neurological dengue diagnosis.

T3 level may be a helpful marker to predict disease prognosis of acute central nervous system viral infections

Aim of the study: Acute central nervous system viral infections are progressive and inflammatory diseases with inflammatory cells infiltrating into the central nervous system (CNS), and thyroid hormone (TH) level is associated with the oxidative and antioxidant status. Variations in oxidative stress and antioxidant status are related to the pathogenesis of inflammatory diseases. Our study aimed to investigate the possible correlation between viral infections in CNS and TH levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3).Materials and methods: We measured serum concentrations of TSH, fT4, and fT3 in 206 individuals, including 59 viral meningitis (VM) patients, 60 viral encephalitis (VE) patients, and 87 healthy controls.Results: Our findings showed that VE and VM patients had lower levels of fT3 and higher levels of fT4 compared with healthy controls, whether male or female. Moreover, levels of TSH and fT3 in patients with viral infections in CNS were inversely correlated with disease prognosis measured by the Glasgow Outcome Scale.Conclusions: Variations in TH level may represent the oxidative status and are surrogate biomarkers for disease prognosis of acute central nervous system viral infections.

Intercellular Communication Is Key for Protective IFNα/β Signaling During Viral Central Nervous System Infection.

A variety of viruses can induce central nervous system (CNS) infections and neurological diseases, although the incidence is rare. Similar to peripheral infections, IFNα/β induction and signaling constitutes a first line of defense to limit virus dissemination. However, CNS-resident cells differ widely in their repertoire and magnitude of both basal and inducible components in the IFNα/β pathway. While microglia as resident myeloid cells have been implicated as prominent sentinels of CNS invading pathogens or insults, astrocytes are emerging as key responders to many neurotropic RNA virus infections. Focusing on RNA viruses, this review discusses the role of astrocytes as IFNα/β inducers and responders and touches on the role of IFNα/β receptor signaling in regulating myeloid cell activation and IFNγ responsiveness. A summary picture emerges implicating IFNα/β not only as key in establishing the classical "antiviral" state, but also orchestrating cell mobility and IFNγ-mediated effector functions.

Epidemiology and clinical outcomes of viral central nervous system infections

BackgroundCentral nervous system (CNS) viral infections are an important cause of morbidity and mortality. No data are available regarding their epidemiology in Qatar. DesignWe retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at Hamad Medical Corporation. Those with abnormal CSF finding were included in our study. We excluded those with missing medical records, no clinical evidence of viral CNS infection, or proven bacterial, fungal or tuberculosis CNS infection. CNS clinical findings were classified as meningitis, encephalitis or myelitis. ResultsAmong 7690 patients with available CSF results, 550 cases met the inclusion criteria (meningitis 74.7%; encephalitis 25%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16–60 years old. Viral etiology was confirmed in 38% (enterovirus, 44.3%; Epstein-Barr virus, 31%; varicella zoster virus, 12.4%). The estimated incidence was 6.4 per 100,000 population. Two persons died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3±5.2 days), 38% received vancomycin (mean duration 2.7±5.4 days) and 38% received at least one other antibiotic. Intravenous acyclovir was continued for more than 48h in patients with confirmed negative viral etiology (mean duration 5±5.6 days). ConclusionViral etiology is not uncommon among those evaluated for CNS infection in Qatar. Clinical outcomes are excellent in this group of patients. Antibiotics and acyclovir are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of viral CNS infections.

Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections

BackgroundA variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells (hiPSCs) offer an extraordinary window for modeling pathogen-CNS interactions, and other cellular interactions, in three-dimensional (3D) neuronal cultures that can recapitulate several aspects of in vivo brain tissue.MethodsHerein, we describe a prototype of scaffold-free hiPSC-based adherent 3D (A-3D) human neuronal cultures in 96-well plates. To test their suitability for drug screening, A-3D neuronal cultures were infected with herpes simplex virus type 1 (HSV-1) with or without acyclovir.ResultsThe half maximal inhibitory concentration (IC50) of acyclovir was 3.14 μM and 3.12 μM determined using flow cytometry and the CX7 High Content Screening platform, respectively.ConclusionsOur A-3D neuronal cultures provide an unprecedented opportunity for high-content drug screening programs to treat human CNS infections.

Infecciones víricas endémicas: dengue,fiebre del Nilo y otras viriasis

We highlight the endemic viral infections caused by Arbovirus, whose clinical manifestations can be categorised into three large syndromes: fever-arthralgia-rash; viral haemorrhagic fever and central nervous system infections (CNS). In this chapter and based on overall worldwide incidence, the likelihood of imported cases and of local transmission, we shall focus on the following viruses: chikungunya, dengue and zika (all of them may present with similar symptoms and arthritis, and they share the same geographic distribution). We would also focus on viruses causing haemorrhagic fevers, of which we will focus on Crimea Congo virus (local cases having recently been described in our country); yellow fever and Ebola virus (the latest due to the growing interest after the recent epidemic that posed a threat to world health), and viruses affecting the CNS (Japanese encephalitis, Central European encephalitis and West Nile fever).

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with Streptococcus sanguinis sepsis.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) develops in association with systemic as well as central nervous system (CNS) viral or bacterial infections. AESD is most often noted with influenza or human herpesvirus 6 infection in previously healthy infants. However, AESD has also been reported in an infant with developmental retardation and in a mentally and motor-disabled adolescent. Here, we report the case of a 4- year-old female with significant development delay due to spinal muscular atrophy, who developed AESD during Streptococcus sanguinis sepsis with no apparent CNS infection. Although the patient had extremely high serum procalcitonin (45.84 ng/mL, reference; <0.4) on admission indicating a poor prognosis, she was successfully managed for sepsis and AESD.

Laboratory Diagnosis of Pediatric Herpesvirus Infections of the Central Nervous System by a Multiplex Polymerase Chain Reaction Assay and Intrathecal Antibodies

Abstract Introduction Central nervous system (CNS) viral infections are a serious problem requiring accurate diagnosis and treatment. Human herpesviruses (HHVs) are an important cause of these infections. Recent research has focused on new diagnostic methods allowing accurate and rapid identification of viral infections because there are still diagnostic difficulties for these infections. This study was done to determine the etiologic role of human herpes viruses and to obtain information that will contribute to the diagnostic algorithm in suspected cases of viral encephalitis or aseptic meningitis. Materials and Methods In our study, herpes simplex virus (HSV)-1, HSV-2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and HHV-6 DNA was detected in the cerebrospinal fluid (CSF) by multiplex polymerase chain reaction (PCR) and virus-specific immunoglobulin G (IgG) antibodies in CSF and serum by EIA in pediatric encephalitis/meningitis cases. Results HSV-1 and VZV were detected in 5 and 3.3% of aseptic meningitis cases, respectively, but no encephalitis cases. Other viruses were not identified as etiologic agents. The seroprevalences were determined as 72.4, 34.3, 81.9, 93.3, 88.6, and 80.9%, respectively for HSV-1, HSV-2, VZV, CMV, EBV, and HHV-6. The performance of specific IgG CSF/serum antibody index (AI) was not satisfactory. Conclusion Our study indicates that the multiplex PCR method is the most suitable for the diagnosis of CNS infections caused by HHVs. However, due to the high cost of the PCR method, the positive results of the specific AI may be significant, but the negative results are unreliable, especially in limited health care facilities.

Viral infections of the central nervous system in Qatar: epidemiology, pathogenesis and clinical outcomes.

Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. They are common causes of morbidities and mortality. There are no previous epidiomologic studies about viral CNS infections done in Qatar or in the Gulf region. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcome of viral central nerveous system infection in patients across a larger national healthcare system. We retrospectively evaluated all cerebrospinal fluid findings from January 2011 - March 2015 at any of the 7 hospitals in the Hamad Medical Corporation healthcare system. We included those with an abnormal CSF finding in our study. We excluded those with missing medical records, those with no clinical evidence of CNS infection or proven bacterial CNS infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, persons with abnormal CSF and CNS clinical findings were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology. Among 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. Persons from Southeast Asia (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) accounted for 39.6 of all infections. A definitive virologic etiologic agent was found in 38%, among whom enterovirus was the most common (44.3%) followed by Epstein-Barr virus (31%) and varicella zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest discharged to home. Ninety-eight per cent were admitted to medical ward (mean stay 7.8±6.4 days) and 2 % to an intensive care unit. (mean stay 2.7±5.4 days). Among those with confirmed viral etiology, 83.8% received ceftriaxone, 38% received vancomycin and 38% received at least one other antibiotic. Viral etiology is not uncommon among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections.

Paediatric Virology and its interaction between basic science and clinical practice (Review).

The 3rd Workshop on Paediatric Virology, which took place on October 7th, 2017 in Athens, Greece, highlighted the role of breast feeding in the prevention of viral infections during the first years of life. Moreover, it focused on the long-term outcomes of respiratory syncytial virus and rhinovirus infections in prematurely born infants and emphasised the necessity for the development of relevant preventative strategies. Other topics that were covered included the vaccination policy in relation to the migration crisis, mother-to-child transmission of hepatitis B and C viruses, vaccination against human papilloma viruses in boys and advances on intranasal live-attenuated vaccination against influenza. Emphasis was also given to the role of probiotics in the management of viral infections in childhood, the potential association between viral infections and the pathogenesis of asthma, fetal and neonatal brain imaging and the paediatric intensive care of children with central nervous system viral infections. Moreover, an interesting overview of the viral causes of perinatal mortality in ancient Greece was given, where recent archaeological findings from the Athenian Agora’s bone well were presented. Finally, different continuing medical educational options in Paediatric Virology were analysed and evaluated. The present review provides an update of the key topics discussed during the workshop.

Diagnosis of viral central nervous system infections using antipeptide antibody against viral antigen by ELISA

Viral infections of the central nervous system (CNS) occur sporadically and have been extensively studied because of the potential for permanent neurological damage or death. The neurotropic viruses have been reported to lead to various CNS infections. The objective of the present study is to develop an antigen detection ELISA protocol for detection and quantification of viral antigen in CNS infections by assessing the usefulness of antipeptide antibodies against potential peptides of cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), Japanese encephalitis virus (JEV), dengue (DENV), West Nile virus (WNV) and Chandipura virus (CHPV). Atotal of 182 cerebrospinal fluid (CSF) samples from confirmed, suspected and non-viral infections of the CNS were evaluated using panels of antipeptide antibodies against synthetic peptides of viral proteins. The cases of confirmed and suspected viral infections of the CNS showed 77% and 11% positivity, respectively, for the detection of viral antigen using antipeptide against synthetic peptides of CMV, EBV, VZV and JEV. The concentration of viral antigen was also obtained by using antipeptide of respective viruses in CSF from both the groups. The viral antigen concentration was also correlated with viral load in confirmed cases of viral infection of the CNS. This study demonstrates the use of antipeptide against synthetic peptide derived from CMV, EBV, VZV and JEV in diagnostics of viral infections of the CNS using patients' CSF samples. Keywords: viral infection of the CNS; synthetic peptide; antipeptide antibody; viral load; antigen concentration.

Acute viral infections of the central nervous system, 2014‐2016, Greece

In order to investigate the viral etiology of acute infections of central nervous system (CNS), multiplex and single PCRs combined with serology for arboviruses were applied on samples from 132 hospitalized patients in Greece during May 2014-December 2016. A viral pathogen was detected in 52 of 132 (39.4%) cases with acute CNS infection. Enteroviruses predominated (15/52, 28.8%), followed by West Nile virus (9/52, 17.3%). Phleboviruses, varicella-zoster virus, and Epstein-Barr virus accounted for 15.4%, 13.5%, and 11.5% of the cases, respectively. The study gives an insight into the etiology of viral CNS infections in a Mediterranean country, where arboviruses should be included in the differential diagnosis of acute CNS infections.

Low serum uric acid levels in patients with acute central nervous system viral infections.

Most acute central nervous system (CNS) viral infections lead to either encephalitis or meningitis. Many neurotropic viruses may cause CNS dysfunctions through various mechanisms including oxidative stress. Serum uric acid (SUA) levels, which are associated with oxidative stress and antioxidant status, are reduced in patients with various neurological disorders, including multiple sclerosis. We investigated the possible correlation between SUA levels and clinical disease status in patients with acute CNS viral infections. We measured SUA concentrations in 336 individuals, including 179 healthy individuals and 157 patients with acute CNS viral infections. We found that the patients had lower SUA levels than the healthy individuals did irrespective of sex. Effective therapy significantly increased SUA levels. The patients’ SUA levels were correlated inversely with outcomes as measured with the Glasgow Outcome Scale. SUA levels may be a biomarker for predicting treatment outcomes and prognoses for patients with acute CNS viral infections with inflammatory components.

Viral Infections of the Central Nervous System in Qatar: Epidemiology, Pathogenesis and Clinical Outcomes

BackgroundViral central nervous system (CNS) infections are common causes of morbidity and mortality globally. There are no existing data about viral CNS infections in Gulf Cooperation Council countries. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcomes of viral central nerveous system infection in patients in Qatar.MethodsWe retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at any of the 7 hospitals in the Hamad Medical Corporation. We included those with an abnormal CSF findings and excluded those with missing medical records, no clinical evidence of CNS infection and those with proven bacterial infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, patients were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology.ResultsAmong 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. The most common presenting signs and symptoms are listed in the table. Persons of Southeast Asian origin accounted for 39.6% of all infections. A definitive virologic etiologic agent was found in 38%, with enterovirus being the most common (44.3%) followed by Epstein–Barr virus (31%) and varicella-zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3 ± 5.2 days), 38% received vancomycin (mean duration 2.7 ± 5.4 days) and 38% received at least one other antibiotic.ConclusionViral etiology is common among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections.Disclosures A. Butt, Merck: Investigator, Grant recipient

Treatment of Theiler's virus-induced demyelinating disease with teriflunomide.

Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS. We assessed the effects of the treatment on central nervous system (CNS) viral load, intrathecal immune response, and progressive neurological disability in mice intracranially infected with TMEV. In the TMEV-IDD model, we showed that teriflunomide has both anti-inflammatory and antiviral properties, but there seemed to be no impact on disability progression and intrathecal antibody production. Notably, benefits in TMEV-IDD were mostly mediated by effects on various cytokines produced in the CNS. Perhaps the most interesting result of the study has been teriflunomide's antiviral activity in the CNS, indicating it may have a role as an antiviral prophylactic and therapeutic compound for CNS viral infections.