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Introduction: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders., Methods: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019., Results: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels., Conclusion: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We compared the clinical course of neonates with persistence of herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) after 21 days of treatment with high-dose acyclovir to that of neonates with clearance of the CSF after 21 days of therapy. Neonates with persistence of HSV DNA had a more severe clinical course with worse neurodevelopmental outcomes.

Objective: The study aimed to describe the prevalence of HSV DNA, VZV DNA, Enterovirus RNA, Parechovirus RNA, CMV DNA, EBV DNA, adenovirus DNA, HHV-6 DNA, HHV-7 DNA, HHV-8 DNA and Parvovirus B19DNA in children aged less 14 years with a suspected viral infection of the central nervous system in a clinical practice setting., Methods: Between January 2012 and May 2015, cerebrospinal fluids from 304 children were tested with an in-house real-time PCR method., Results: A positive PCR was detected in 64 subjects (21%): the mean number of tests performed in patients who showed a viral infection was 7.5, significantly higher (p = 0.001) with respect to that reported in negative samples (6.4). Enterovirus is the leading virus detected: 12 out of the 37 positive children reported were newborns (85.7% of all the newborns with a positive result). The second most frequently identified virus was HHV-7 (5 positive PCR out of 105 samples tested, 4.8%, if we excluded a child with a concomitant S. pneumoniae isolated), a prevalence significantly higher with respect to VZV (p = 0.02) and to CMV (p = 0.04). HHV-6 was the third most commonly identified aetiology (4.2%). All children were immunocompetent., Significance: Only a minority of children had a specific viral aetiology identified: the rate of HHV-7 positivity suggests a routine testing of these viruses within the diagnostic algorithm in immunocompetent paediatric patients. This approach could help to define the clinical role of this herpesvirus., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

A 74-year-old man presented with acute right-sided hemiparesis and epilepsia partialis continua in association with fever and confusion. Initial workup revealed possible cerebritis in the left medial frontal lobe without involvement of the temporal lobes. Cerebrospinal fluid (CSF) analysis revealed minimal lymphocytic pleocytosis but negative real-time herpes simplex virus (HSV) PCR. Acyclovir was discontinued on day 5 due to a negative infectious workup and clinical improvement. On day 9 his condition deteriorated and he was transferred to a higher level of acuity for advanced supportive care. Worsening encephalopathy and refractory status epilepticus ensued despite medical care. Repeat CSF analysis showed mild lymphocytic pleocytosis with negative real-time HSV PCR. Brain MRI revealed progression of cortical enhancement. Immunosuppressive therapy and plasma exchange were attempted without clinical response. On day 24, another lumbar puncture showed only mild lymphocytic pleocytosis. Brain MRI showed involvement of the right medial temporal lobe. Subsequently, acyclovir was resumed. The HSV-1 PCR result was positive on day 30. Unfortunately, the patient expired., (2015 BMJ Publishing Group Ltd.)

Genital herpes simplex virus (HSV) infections are very common worldwide. Approximately 22% of pregnant women are infected genitally with HSV, and most of them are unaware of this. The most devastating consequence of maternal genital herpes is HSV disease in the newborn. Although neonatal HSV infections remain uncommon, due to the significant morbidity and mortality associated with the infection, HSV infection in the newborn is often considered in the differential diagnosis of ill neonates. This review summarizes the epidemiology and management of neonatal HSV infections and discusses strategies to prevent HSV infection in the newborn., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Herpes simplex virus (HSV) remains an important cause of meningitis and encephalitis in adults, and polymerase chain reaction (PCR)-based tests are the "gold standard" for diagnosis. The objective of this study was to assess differences in semiquantitative PCR values, based on the crossing threshold (Ct) value for cases of HSV meningitis and encephalitis. A retrospective chart review was performed for 29 patients with a documented diagnosis of HSV meningitis or encephalitis during the course of 5 years from a large urban academic hospital. Demographic information, cerebrospinal fluid (CSF) laboratory findings, and PCR data were obtained for each patient. There was no statistically significant difference in the Ct values in patients with meningitis or encephalitis. In addition, no differences were found in CSF chemistry and hematology parameters. There is a broad range in relative concentrations of HSV DNA in the CSF in cases of meningitis and encephalitis.

Objective: The significance of detecting herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of infants with HSV encephalitis after receipt of prolonged therapy with high-dose (60 mg kg(-1) day(-1)) acyclovir is unknown. We report the clinical and laboratory characteristics, neuroimaging studies and outcomes of four neonates with HSV encephalitis who had persistence of CSF HSV DNA, by polymerase chain reaction (PCR) after 15 to 21 days of high-dose acyclovir therapy., Study Design: Retrospective chart review., Results: All four infants had abnormal neuroimaging studies and subsequently experienced severe developmental delay or death., Conclusion: A persistently positive CSF HSV PCR in neonates may be another risk factor for worse neurodevelopmental outcome. Prospective studies are needed to document how often HSV DNA persists in CSF, elucidate whether it represents an initially high CSF viral load, ongoing viral replication or viral resistance, and determine its possible association with neurodevelopmental impairment.

Objective: To determine the clinical presentations, laboratory and imaging findings of patients with HSE and positive CSF PCR then compare these with information from other viral encephalitis patients in order to find clinical clues that might help clinicians in early diagnosis and treatment of HSE while awaiting for the CSF PCR result., Material and Method: A patient group with both HSE and positive CSF PCR and a control group of patients with other viral encephalitis were identified from Siriraj Hospital database within the period of 1997-2006. Medical notes of these patients were reviewed and relevant information, including clinical, laboratory and imaging study, were extracted. Then, descriptive statistics, unpaired t-test and Fisher's exact test were performed with the purpose to determine any clinical or laboratory clues that are significantly different between these two groups, which might help clinicians in making an early diagnosis of HSE., Results: Seven HSE cases and 22 cases in control group were included. Fever, headache, alteration of consciousness, behavioral change, neck stiffness are the most commonly found clinical presentations in HSE patients with CSF PCR positive. CSF examination show CSF leukocytosis with lymphocyte predominate, decreased CSF:blood glucose ratio and elevated CSF protein in all cases. However, no single clinical or laboratory finding helps in differentiating HSE with positive CSF PCR from other viral encephalitides, except radiological abnormalities of temporal lobe, which yields a positive predictive value of 0.5 and a negative predictive value of 0.93., Conclusion: Our study showed that HSE shares common clinical and laboratory findings with other viral encephalitides, except for temporal lobe involvement. Early diagnosis is important and empirical acyclovir should be commenced early in patients with viral encephalitis, especially for those with radiological abnormalities on the temporal lobe.

Herpes simplex virus infection of the central nervous system is still a significant cause of morbidity and often mortality. Early diagnosis is critical because treatment with the antiviral drug acyclovir dramatically decreases morbidity and mortality in children. The use of polymerase chain reaction techniques is a diagnostic procedure in herpes simplex virus infection, but negative polymerase chain reaction test results of cerebrospinal fluid herpes simplex virus can occur within the first 72 hours of illness, with subsequent test results becoming positive as in this case. Therefore, diffusion-weighted magnetic resonance may play a major role as a first and early diagnostic step.

In this report, characteristics of two cases of Herpes simplex virus (HSV) encephalitis with normal cerebrospinal fluid (CSF) findings at the time of admission have been discussed and the current literature has been reviewed. The diagnosis of the cases (one was 23 years old male, and the other was 75 years old female patient) was made on the magnetic resonance imaging (MRI) findings concordant with HSV encephalitis, together with HSV-1 DNA positivity by polymerase chain reaction (PCR). Both of the patients were treated with acyclovir (3 x 750 mg/day) lasting for 15 days and 21 days, respectively. The first male patient recovered with mild neurological defects, whereas the second female patient died because of nosocomial pneumonia and septicemia. In conclusion, even the CSF findings are normal, in cases considered to be HSV encephalitis, MRI should be the first radiological diagnostic step and the diagnosis should be confirmed by the detection of HSV DNA in CSF by PCR.

Objective: To assess the performance of a polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF) for the diagnosis of nervous system infections caused by herpesvirus, and to estimate the incidence of encephalitis due to herpes simplex virus type 1 in the adult population of the island of Gran Canaria., Methods: We studied 330 CSF specimens from 312 patients (281 HIV-negative and 31 HIV-positive) remitted to investigate clinically suspected encephalitis or meningitis, or to study neuropathy or demyelinating disease. A multiplex PCR technique was used to detect herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (CMV), Epstein-Barr virus and human herpesvirus type 6. The patients' clinical records were reviewed to establish the definite diagnosis., Results: Nine samples from eight patients (2.6%) showed positive results (9.7% of patients with pathological CSF and none with normal CSF). The eight patients had clinical and analytic findings of herpesvirus nervous system infection: HSV-1 DNA in four patients with encephalitis, HSV-2 DNA in one patient with meningitis, VZV DNA in two patients with meningitis and CMV DNA in one HIV-positive patient with encephalitis. Herpesvirus was the cause of 50% of encephalitis cases and 10% of meningitis cases. The incidence of HSV-1 encephalitis was five cases per million inhabitants per year., Conclusions: Diagnosis of herpesvirus nervous system infections by PCR in CSF is not appropriate when CSF parameters are normal. We found a higher incidence of herpesvirus encephalitis than has been reported in other studies.

Objective: To evaluate the usefulness of a rapid and simple PCR method in the diagnosis of herpetic meningoencephalitis in a pediatric population., Patients and Methods: One hundred twenty-three cerebrospinal fluid samples from 114 pediatric patients attending the Hospital Sant Joan de Déu in Barcelona for clinical suspicion of viral meningoencephalitis or to rule out a possible herpetic etiology were evaluated. In addition to classical methods, the diagnostic technique used was PCR amplification of a highly preserved region of the DNA polymerase gene common to herpes virus 1 and 2. All patients were administered acyclovir on admission and until the results of PCR were known. If the result was negative, withdrawal of acyclovir was considered after clinical reexamination. If the result was positive, the therapy was continued for 20 days., Results: Herpes simplex DNA was detected in four patients. In all patients, clinical outcome confirmed the results of PCR, whether positive or negative. PCR results were available within 6.30 and 72 hours (mean: 18 hours)., Conclusion: This simple and rapid PCR technique can be applied in the daily routine of the microbiology laboratory. It allows early diagnosis of herpetic meningocephalitis or, when lacking, exclusion of Herpes simplex etiology.

The present study was conducted to assess the usefulness of adding the multiplex nested-polymerase chain reaction assay of cerebrospinal fluid samples to routine diagnostic testing for herpesvirus encephalitis and to monitor the efficacy of therapy. Cerebrospinal fluid samples from 45 patients with presumed herpesvirus encephalitis were tested for herpes simplex virus, varicella-zoster virus, cytomegalovirus, human herpesvirus 6, and Epstein-Barr virus. Ten of the 45 patients were positive for a virus using the polymerase chain reaction assay: herpes simplex virus (n=5), Epstein-Barr virus (n=3), and herpes simplex virus plus the Epstein-Barr virus (n=2). Cerebrospinal fluid from two patients who had undergone acyclovir therapy gave negative results. Analysis of cerebrospinal fluid by multiplex polymerase chain reaction can be useful for establishing an accurate diagnosis and as a marker of the efficacy of therapy.

Brain biopsy has been considered the gold-standard test for the diagnosis of herpetic encephalitis. However, because of its cruence, other non invasive methods have been developed for its diagnosis. In recent years polymerase chain reaction (PCR) in cerebrospinal fluid has been employed for the diagnosis of herpetic encephalitis (HE). We report two cases of clinically suspected HE in which DNA of herpes simplex virus was amplified by PCR from cerebrospinal fluid, and review the role of this method for the diagnosis of HE. Two patients were admitted to the emergency room presenting clinical pictures and cerebrospinal fluid samples suggestive of lymphocytic meningoencephalitis. Both were admitted in the intensive care unit because of altered level of consciousness, beginning empiric treatment with intravenous acyclovir as HE was suspected. Clinical outcomes were favourable in both cases, being confirmed the presence of herpes simplex DNA in cerebrospinal fluid by PCR in the two patients. We have reviewed in the literature the value of PCR for the diagnosis of HE in comparison with other ancillary tests as brain biopsy and serology. PCR could reach according with some authors a sensibility of 98% and a specificity of 94%.

Background: Herpes simplex virus (HSV) is the most common cause of acute sporadic encephalitis in the United States. PCR of DNA extracted from cerebrospinal fluid (CSF) allows for reliable diagnosis of herpes simplex encephalitis (HSE). A faster turnaround time for HSE testing would improve patient management and lead to better outcomes. The aims of this study, therefore, were to develop a microchip-based electrophoretic method for rapid detection of HSV PCR products, and to compare the performance characteristics of liquid hybridization/gel retardation as an established clinical PCR product detection method with the new microchip-based method., Methods: The study examined archival DNA from 33 selected CSF specimens submitted for HSV PCR testing to the clinical laboratory. One aliquot of the HSV PCR product was analyzed by liquid hybridization/gel retardation analysis, and a second PCR aliquot was analyzed directly with a microchip capillary electrophoresis system using an instrument built in-house. PCR samples were introduced directly into the microchip without a desalting step by use of a novel fluidic interface. Channel surfaces on the glass microchip were silanized, followed by derivatization with polyvinylpyrrolidone., Results: Of the 33 CSF specimens tested by liquid hybridization analysis of HSV PCR products, 10 tested positive for HSV DNA, 2 gave a weakly positive result, and 21 tested negative. Total analysis time for detection of HSV DNA by gel retardation assay was 18 h. Microchip electrophoresis provided identical results in <110 s/sample, achieving 100% sensitivity and specificity compared with the established method., Conclusions: Microchip-based electrophoresis can rapidly and accurately separate HSV PCR products, giving results identical to those obtained by liquid hybridization but with substantially decreased turnaround time. Clinical implementation of the new method will help to improve patient management and outcomes.

Aim: To investigate the diagnostic potential of herpes simplex virus (HSV) DNA in cerebrospinal fluid and serum; to correlate the findings with outcome in the child and with type of maternal infection., Methods: Cerebrospinal fluid and serum specimens from 36 children with verified neonatal HSV infections, diagnosed between 1973 and 1996, were examined using the polymerase chain reaction technique (PCR)., Results: In 21 children for whom both cerebrospinal fluid and sera were available, HSV DNA was found in one or both specimens in 19 (90%). Overall, HSV DNA was found in the cerebrospinal fluid of 74% of 27 children, and in the sera of 20 out of 30 children (67%). In two children HSV DNA was not demonstrable in either serum or cerebrospinal fluid. In sequential specimens from four children, the persistence of HSV DNA after the end of intravenous treatment was associated with a poor prognosis., Conclusions: These findings indicate that HSV DNA detection in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace the detection of virus in other locations using virus isolation and antigen detection.