Epstein-Barr Virus DNA In Cerebrospinal Fluid Research Articles

Presence of Epstein-Barr virus in cerebrospinal fluid is associated with increased mortality in HIV-negative cryptococcal meningitis.

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P=0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P=0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.

Lessons from Epstein-Barr virus DNA detection in cerebrospinal fluid as a diagnostic tool for EBV-induced central nervous system dysfunction among HIV-positive patients.

Polymerase chain reaction (PCR) analysis of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) remains vital for evaluating active EBV infection involving the central nervous system (CNS). CSF EBV DNA was often found in conjunction with other microbial infection affecting the CNS among patients infected with human immunodeficiency virus (HIV). Sometimes CSF EBV DNA is detectable in patients without neurological symptoms. This review focused on the clinical and laboratory features of CNS EBV infection among patients with HIV, and discussed various types of EBV-associated CNS infections, and predominant neoplasms involving CNS such as primary central nervous system lymphoma (PCNSL), CNS-non-Hodgkin's lymphoma, smooth muscle tumors and leiomyosarcomas, EBV encephalitis or myelitis, EBV meningitis and EBV coinfection with other causative agents were also included. Furthermore, the metagenomic next-generation sequencing technique with high sensitivity for the detection of pathogenic coinfection in the CSF were also reviewed. We concluded that CSF EBV-DNA detection with high sensitivity and specificity could be a useful diagnostic tool for CNS lymphoma among HIV patients; however, it is still unknown for other CNS diseases. We further summarized and conclude that positive CSF EBV-DNA detection combined with specific brain focal lesions could be a minimally invasive method to diagnose PCNSL. The occurrence of positive CSF EBV-DNA was influenced by PCR detection limit, PCR methods, immunocompromised status, the possible influence of anti-herpetic therapy and anti-HIV therapy, and the size and location of a tumor mass. Uniform PCR methods as vital diagnostic tools and optimal EBV-DNA load threshold need to be established.

Clinical significance of Epstein-Barr virus polymerase chain reaction in cerebrospinal fluid.

Epstein-Barr virus (EBV) is implicated in various neurological conditions. However, the relationship between EBV DNA in cerebrospinal fluid (CSF) and central nervous system (CNS) infection is unclear. We evaluated the clinical manifestation of patients with EBV DNA detected in CSF. We reviewed the medical records of patients admitted to Seoul National University Hospital from January 2000 to March 2021 who underwent EBV polymerase chain reaction (PCR) tests in CSF. The subjects were divided into positive and negative groups depending on the presence of EBV DNA, and further clinical information was obtained from positive patients. CSF EBV PCR tests were performed in 807 patients, and 57 (7.1%) tested positive. Pleocytosis was common (81.1%) in CSF samples with EBV DNA detected, and the proportion was significantly higher than that in samples that were EBV PCR negative (44.5%, p < 0.0001). Among 57 patients with EBV DNA detected in CSF, 51 (89.5%) were diagnosed with CNS infection or inflammatory disorders. Of the 51 patients, 31 (60.8%) had possible etiologies other than EBV. Follow-up evaluation was conducted in 19 of 20 patients, and 63.2% showed a favorable outcome. Positive EBV PCR in CSF is mostly nonspecific and should be interpreted with caution. A comprehensive workup is needed to identify other etiologies before considering EBV as the sole culprit.

Presence of Epstein-Barr virus DNA in cerebrospinal fluid is associated with greater HIV RNA and inflammation.

The current study aimed to investigate whether cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA was associated with viral, inflammatory and neuronal damage biomarkers in people living with HIV (PLWH). A cross-sectional diagnostic study on CSF fluid samples in patients undergoing lumbar punctures for clinical reasons, to better understand the role of EBV and CMV in the CNS on HIV RNA replication, blood-brain-barrier (BBB) damage and biomarkers of neuronal damage/inflammation. EBV, CMV DNA and HIV RNA were measured on CSF, through real time (RT)-PCR, from PLWHs undergoing lumbar punctures for clinical reasons (excluding oncho-haematological comorbidities). Immune-enzymatic assays evaluated blood-brain barrier inflammation and damage. Patients were stratified according to plasma HIV RNA levels in viremic (≥50 copies/ml) and aviremic (<50 copies/ml). We included 297 participants. Among 167 viremic patients CSF EBV and CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic individuals CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis (P < 0.001), higher CSF HIV RNA (P < 0.001) and neopterin levels (P = 0.002). In aviremic participants detectable EBV DNA was associated with pleocytosis (P = 0.056), higher neopterin (P = 0.027) and immune globulins (P = 0.016) in the CSF; CSF escape was more common in those with detectable EBV DNA (50 vs. 21.2%, P = 0.036). EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was associated with higher biomarkers levels of neuronal damage/inflammation. The role of EBV reactivation in HIV-associated central nervous system disorders warrants further studies.

Low intrathecal immune response of anti–EBNA-1 antibodies and EBV DNA from multiple sclerosis patients

Numerous studies have been carried out to determine whether an Epstein–Barr virus (EBV) infection can be considered a risk factor for multiple sclerosis (MS), following the evidence of an increase in IgG response to nuclear antigen-1 (EBNA-1) in both serum and cerebrospinal fluid (CSF) from MS patients. However, the possible interaction between EBV and MS has still not been well characterized, and the possible pathogenic role is yet to be determined. A case-control study (76 cases and 75 controls) was conducted to investigate anti-EBV antibodies synthesis in serum and CSF through intrathecal specific IgG synthesis to EBNA-1, as well as the presence of EBV DNA in plasma, peripheral blood mononuclear cells, and CSF from MS patients. Intrathecal EBNA-1 specific IgG synthesis was detected in 6.6% MS patients and in 17.3% controls. No EBV DNA was found in plasma or CSF, and our findings showed no evidence of high intrathecal EBNA-1 specific IgG synthesis or of significant EBV DNA in CSF in MS patients.

The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons

Background The presence of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) is used as a marker of HIV-associated primary central nervous system lymphoma (PCNSL). In our setting, EBV DNA is frequently detected in the CSF of HIV-infected patients with miscellaneous neurological diseases and thus its presence is a poor predictor of PCNSL. Objectives To determine whether quantification of EBV DNA in CSF improves its diagnostic specificity for PCNSL. Study design EBV viral loads were determined on CSF samples from 55 HIV-infected patients with CNS disease. Results Twenty of the 55 patients had detectable EBV DNA in their CSF (median viral load 6120 copies/ml, range 336–1,034,000 copies/ml). PCNSL was confirmed in 2 patients. Their CSF EBV loads were 1,034,000 and 15,460 copies/ml, respectively. Using a cut-off of 10,000 copies/ml improved the specificity and positive predictive value (PPV) compared to a qualitative result for the diagnosis of PCNSL (96% vs. 66% and 50% vs. 10%, respectively). Conclusion EBV DNA is commonly detected in CSF of HIV-infected patients. Quantitative PCR improves the diagnostic specificity, however, the PPV remains too low for it to be used as an isolated marker for PCNSL.

Quantitative CSF PCR in Epstein-Barr virus infections of the central nervous system.

Acute Epstein-Barr virus (EBV) infection of the central nervous system (CNS) is associated with meningoencephalitis and other neurological syndromes and with CNS lymphomas (CNSLs). Diagnosis is based on serological studies and more recently on detection of EBV DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR). We measured EBV DNA by quantitative PCR and EBV mRNA by RT-PCR in the CSF in patients with EBV-associated neurological disorders. EBV was identified as the cause of CNS infection in 28 patients: 14 with CNSL, 10 with encephalitis, and 4 with postinfectious neurological complications. CSF analysis showed that patients with CNSL had high EBV load (mean +/- standard error of 4.8 +/- 0.2 log(10) DNA copies/ml) and low leukocyte counts (22 +/- 7 cells/microl); encephalitis was characterized by high EBV load (4.2 +/- 0.3 log(10) DNA copies/ml) and high leukocyte counts (143 +/- 62 cells/microl); and patients with postinfectious complications showed low EBV load (3.0 +/- 0.2 log(10) DNA copies/ml) with high leukocyte counts (88 +/- 57 cells/microl). Lytic cycle EBV mRNA, a marker of viral replication, was identified in 10 CSF samples from patients with CNSL and encephalitis. These studies demonstrate the utility of quantitative CSF PCR and establish the presence of lytic cycle EBV mRNA in CSF of patients with EBV-associated neurological disease.

Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system

Epstein-Barr virus (EBV) is constantly associated with AIDS-related primary lymphomas of the central nervous system (CNS). To assess whether EBV DNA in cerebrospinal fluid (CSF) could be used as a tumour marker, CSF samples that had been taken within 180 days before death from 85 patients with HIV infection and neurological disorders at necropsy were examined retrospectively by nested polymerase chain reaction (PCR) for EBV. Histologically evident primary CNS lymphomas were found in 17 patients, and EBV was shown in tissue by in-situ hybridisation in 16 of the 16 cases examined. All 17 patients with primary CNS lymphoma had EBV DNA in CSF. EBV DNA was found in CSF from 1 of 68 HIV-infected patients without histologically detectable lymphoma at necropsy. PCR for EBV DNA in CSFwas 100% sensitive and 98·5% specific for AIDS-associated primary CNS lymphoma, and may be useful as a diagnostic tumour marker.