IgM In Cerebrospinal Fluid Research Articles

An Observational Study on Clinical Profile and Outcome of Japanese Encephalitis Patients Admitted in the Department of Medicine of a Tertiary Care Hospital of North Bank of Assam, India

Background: A significant public health issue in India is Japanese encephalitis (JE), which has a high fatality rate and causes residual neurological damage in survivors. The goal of the current study was to examine JE positive among patients who had been admitted with acute encephalitis syndrome (AES) and to analyse the differences in clinical profile, disease severity, neurological consequences, and mortality rate in Tezpur Medical College and Hospital. Methods: This study is a retrospective observational study in a patients who were diagnosed as Japanese encephalitis on the basis of JEV-specific IgM antibodies in blood and cerebrospinal fluid (CSF) samples. The study included 32 Japanese Encephalitis positive patients admitted in Tezpur Medical College and Hospital (who met the clinical case definition of AES) and thus, their clinical profile and outcome were analysed. Result: A total 32 JE cases were enrolled in the study diagnosed with CSF and Serum IgM ELISA antibody test. All of them were Serum IgM ELISA antibody positive, 9(28%) cases were both Serum and CSF IgM antibody positive. Most common age group affected was 12-20 years(31%). 59.37% cases recovered completely, 21.87% had neurological sequelae at the time of discharge and 18.75% died at ward. Conclusion: Japanese Encephalitis is one of the leading cause of AES in India. In our study it has been seen that GCS score on presentation and CSF cell counts has positive association with mortality and disease sequale. Adequate care and treatment should be provided in order to avoid subsequent complications/sequale. Proper vaccination and vector control can prevent or mitigate this disease.

Two-tiered serology in patients with Lyme neuroborreliosis

<p><strong>Introduction. </strong>Lyme borreliosis is a multisystem infectious disease caused by Borrelia burgdorferi sensu lato complex. It is transmitted by Ixodes ticks. Apart from erythema migrans, other manifestations require laboratory confirmation. The aim of our study was to analyze the results of Two-Tiered Testing in patients with possible Lyme neuroborreliosis (LNB).</p> <p><strong> Method.</strong> We conducted a prospective diagnostic study at the University Clinical Centre of Republic of Srpska from October 2017 to October 2021. The study included 51 patients exam ined and treated under suspicion of Lyme neuroborreliosis (LNB). We used Two-Tiered Testing through ELISA anti-Borrelia IgM/IgG and confirmatory Immunoblot anti-Borrelia test IgM/ IgG.</p> <p><strong> Results. </strong>ELISA anti-Borrelia IgM in serum was positive in 25.5% patients and IgG in 76.47%, while in cerebrospinal fluid (CSF) IgM was positive in 13.7% patients and IgG in 39.2%. Immuno blot test of anti-Borrelia IgM in serum was at the borderline in 7.84% patients, positive in 6.17% and no data for 35.29%, while IgG was positive in 54.9% of patients and no data for 37.25%. A strong correlation between results of ELISA anti-Borrelia IgM in serum and CSF was observed (ρ=0.802, p<0.001) and also between ELISA anti-Borrelia IgG and Immunoblot IgG in serum (ρ=0.787, p<0.001).</p> <p><strong>Conclusion.</strong> Two-Tiered Testing is very important in patients with possible LNB. False positive and false negative results are possible and test should be interpreted with caution and in correlation with the clinical manifestation and other avail able tests. More work needs to be done to develop new reli able diagnostic test for LNB, such as detection of CXCL13 in CSF, titrate the interleukin-6 (IL-6) in addition to the CXCL13 chemokine.</p>

NIPAH Virus Encephalitis: Unveiling the Epidemiology, Risk Factors, and Clinical Outcomes – A Systematic Review and Meta-Analysis

ABSTRACT Objective: This study assessed Nipah virus (NiV) encephalitis epidemiology, clinical outcomes, and risk variables to inform treatment and prevention. Methodology: In a PubMed systematic search, 929 citations were found. After screening and eligibility, 22 studies were included. This study obtained age, gender, geographic regions, diagnostic methods, data collection methods, and bias risk. The case fatality rate (CFR) and NiV infection risk variables were evaluated by meta-analysis. Results: Southeast Asia, especially Bangladesh and Malaysia, had the most NiV cases. The major diagnostic method was blood and cerebrospinal fluid IgM and IgG antibody tests, and males predominated. Proxy respondents and matched controls were utilized for risk factor analyses when patients could not answer. The pooled CFR for NiV encephalitis was 61.0%, indicating severity. Risk factors included pigs, nighttime bats near homes, tree climbing, and male gender. Conclusion: Southeast Asian public health is plagued by NiV encephalitis. The high CFR calls for better diagnosis, treatment, and prevention. NiV’s multiple risk factors must be understood for targeted therapy. Future research should fill knowledge gaps and improve NiV infection prevention.

Associations of the cerebrospinal fluid lymphocyte population with a clinical presentation of tick-borne encephalitis

In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To clarify their roles, we have evaluated cerebrospinal fluid (CSF) count of the main lymphocyte populations (considered as a proxy of the brain parenchyma lymphocytic infiltrate) in TBE patients and analyzed if they associate with clinical presentation, blood-brain barrier disruption and intrathecal antibody synthesis.We have studied CSF from 96 adults with TBE (50 with meningitis, 40 with meningoencephalitis, 6 with meningoencephalomyelitis), 17 children and adolescents with TBE and 27 adults with non-TBE lymphocytic meningitis. Th CD3+CD4+, Tc CD3+CD8+, double positive T CD3+CD4+CD8+, B CD19+ and NK CD16+/56+ cells were counted cytometrically with a commercial fluorochrome-stained monoclonal antibody set. The associations between the counts and fractions of these cells and clinical parameters were analyzed with non-parametric tests, p<0.05 considered significant.The TBE patients had lower pleocytosis with similar proportions of the lymphocyte populations compared to non-TBE meningitis. The different lymphocyte populations correlated positively with one another, as well as with CSF albumin, IgG and IgM quotients. The higher pleocytosis and expansion of Th, Tc and B cells associated with a more severe disease and neurologic involvement: Th with encephalopathy, myelitis and weakly with cerebellar syndrome, Tc with myelitis and weakly with encephalopathy, B with myelitis and with at least moderately severe encephalopathy. The double-positive T lymphocytes associated with myelitis, but not with other forms of CNS involvement. The fraction of double positive T cells decreased in encephalopathy and the fraction of NK in patients with neurologic deficits. In children with TBE, Tc and B counts were increased at the expense of Th lymphocytes in comparison with adults.The concerted intrathecal immune response, involving the main lymphocyte populations, increases with the clinical severity of TBE, with no evidently protective or pathogenic elements distinguishable. However, the particular populations including B, Th and Tc cells associate with different, though overlapping, spectra of CNS manifestations, suggesting they may be specifically related to TBE manifesting as myelitis, encephalopathy and cerebellitis. The double-positive T and NK cells do not expand evidently with severity and may be most closely associated with the protective anti-TBEV response.

1027. Cerebrospinal Fluid Findings of Solid Organ Transplant Recipients with West Nile Virus Infections

Abstract Background In the solid organ transplant (SOT) population, West Nile virus (WNV) neuroinvasive disease can have significant morbidity and mortality. We evaluated cerebrospinal fluid (CSF) findings in neuroinvasive WNv infections among SOT recipients. Methods We retrospectively reviewed medical records of all SOT recipients at our institution with WNv neuroinvasive disease (meningitis, encephalitis, meningo-encephalitis) from 2010 to 2018. Descriptive statistics were examined on key variables. Results Eight transplant patients with mean age 54.47 years (12.79) were included: 5 kidney transplants, 1 in each kidney-pancreas, liver and lung transplants. Median time from transplant to infection was 49.8 months (2.7-175.4) and mean time-to-diagnosis 2 days (1.31) . On admission, mean total CSF WBC count was 134.57 cells/mm3 (150.82), mean lymphocyte count 56.29 cells/mm3 (32.32), mean neutrophil count 27.14 cells/mm3 (34.34), and mean CSF protein 95.4 mg/dL (40.52mg/dL). West Nile virus CSF IgG at the time of diagnosis was negative in 7 patients, and not performed on 1 patient. WNv diagnosis is depicted below. Serum and CSF WNV Antibodies in Neuroinvasive Disease in SOT Recipients WNV CSF and serum IgG was negative at the time of diagnosis in 7/8 patients. Initial CSF IgM was positive in 3 out of 7 patients. Conclusion WNv infection produces a CSF pleocytosis with neutrophilic predominance, though we noted more lymphocytic predominance among SOT recipients. CSF IgM and IgG are important diagnostics in neuroinvasive WNv. Disclosures Diana F. Florescu, MD, AlloVir: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|NobelPharma: Grant/Research Support|Novavax: Grant/Research Support|Regeneron: Grant/Research Support|SymBio: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support.

Inflammatory Markers Differentiate Cerebral Venous Sinus Thrombosis from Mimics.

Imaging tests always misdiagnose anatomical variants of cerebral sinuses as cerebral venous sinus thrombosis (CVST). Anatomical variants of cerebral sinuses are called CVST mimics. This study aimed to identify the role of inflammatory markers in differentiating CVST from mimics. A total of 146 patients diagnosed as CVST and 93 patients with mimics were recruited in this study. Receiver operating characteristic (ROC) analysis was performed to demonstrate the sensitivity and specificity of inflammatory markers for diagnosing CVST. Rank logistic regression analysis was performed to identify the association of markers to CVST severity and prognosis. CVST presented higher inflammatory reactions compared with mimics, demonstrated by the neutrophil count (5.11 [3.97-6.80] vs. 3.06 [2.34-3.86]), interleukin (IL)-6 (7.42 [3.85-14.22] vs. 2.47 [1.50-4.00]), and neutrophil-to-lymphocyte ratio (NLR; 3.19 [2.18-4.62] vs. 1.66 [1.16-2.22]). ROC analysis showed markers with area under the curve (AUC) >0.8, including IL-6 (optimal cutoff: 3.790; kappa value: 0.499), neutrophil count (3.975; 0.522), and NLR (2.070; 0.476). After propensity score matching, only IL-6 had an AUC >0.8, with an optimal cutoff of 3.060 and a kappa value of 0.636. Ranked logistic regression showed that IL-6 (odds ratio, 95% confidence interval: 1.063, 1.026-1.101; 1.029, 1.009-1.050), cerebrospinal fluid (CSF) immunoglobulin (Ig) A (0.279, 0.110-0.706; 0.398, 0.162-0.974), CSF IgM (22.399, 3.004-167.001; 9.545, 1.382-65.928), and CSF IgG (1.287, 1.124-1.473; 1.232, 1.091-1.392) were independently correlated with the baseline and follow-up mRS. In conclusion, inflammatory markers in CVST were different from those in mimics. These markers, especially IL-6, could not only differentiate CVST from its mimics, but also evaluate CVST severity and prognosis.

Diagnostic performance of different specimens in detecting enterovirus A71 in children with hand, foot and mouth disease

Hand, foot and mouth disease (HFMD) is a major public health problem among children in the Asia-Pacific region. The optimal specimen for HFMD virological diagnosis remains unclear. Enterovirus A71 (EV-A71) neutralizing antibody titres detected in paired sera were considered the reference standard for calculating the sensitivity, specificity, positive and negative predictive value of throat swabs, rectal swabs, stool, blood samples and cerebrospinal fluid (CSF) by RT-PCR or ELISA assay. In this study, clinical samples from 276 HFMD patients were collected for analysing the sensitivity of different kind of specimens. Our results showed that stool had the highest sensitivity (88%, 95% CI: 74%–96%) and agreement with the reference standard (91%). The order of diagnostic yield for EV-A71 infection was stool sample ​≥ ​rectal swab ​> ​throat swab ​> ​blood sample ​> ​CSF sample, and using a combination of clinical samples improved sensitivity for enterovirus detection. The sensitivity of ELISA for IgM antibody detection in sterile-site specimens was significantly higher than that of RT-PCR (serum/plasma: 62% vs. 2%, CSF: 47% vs. 0%) (P ​< ​0.002). In conclusion, our results suggest that stool has the highest diagnostic yield for EV-A71-infected HFMD. If stool is unavailable, rectal swabs can be collected to achieve a similar diagnostic yield. Otherwise, throat swabs may be useful in detecting positive samples. Although IgM in blood or CSF is diagnostically accurate, it lacks sensitivity, missing 40%–50% of cases. The higher proportion of severe cases and shorter interval between onset and sampling contributed to the increase in congruency between clinical testing and the serological reference standard.

Wild-type Yellow fever virus in cerebrospinal fluid from fatal cases in Brazil, 2018.

Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a hemorrhagic and viscerotropic acute disease. Severe YF has been described in approximately 15-25% of YF patients, with 20-50% of severe YF cases being fatal. Here we analyzed cerebrospinal fluid (CSF) samples collected during the YF outbreak in Brazil in 2018, aiming to investigate CNS neuroinvasion in fatal YFV cases. YFV RNA was screened by RT-qPCR targeting the 3'UTR region of the YFV genome in CSF. CSF samples were tested for the presence of anti-YFV IgM and neutralizing antibodies, coupled with routine laboratory examinations. Among the 13 patients studied, we detected anti-YFV IgM in CSF from eight patients and YFV RNA in CSF from five patients. YFV RNA genomic load in CSF samples ranged from 1.75×103 to 5.42×103 RNA copies/mL. We genotyped YFV from three CSF samples that grouped with other YFV samples from the 2018 outbreak in Brazil within the South-American I genotype. Even though descriptions of neurologic manifestations due to wild type YFV (WT-YFV) infection are rare, since the last YF outbreak in Brazil in 2017-2018, a few studies have demonstrated WT-YFV RNA in CSF samples from YF fatal cases. Serological tests indicated the presence of IgM and neutralizing antibodies against YFV in CSF samples from two patients. Although the presence of viral RNA, IgM and neutralizing antibodies in CSF samples could indicate neuroinvasiveness, further studies are needed to better elucidate the role of YFV neuroinvasion and possible impacts in disease pathogenesis.

Neurological Disease Associated with Chikungunya in Indonesia.

Chikungunya virus (CHIKV) is recognized but rarely considered as a cause of central nervous system infection in endemic areas. A total of 244 patients with acute meningoencephalitis in Indonesia were retrospectively tested to identify whether any CHIKV infection was associated with neurological manifestations, especially in provinces known for CHIKV endemicity. Cerebrospinal fluid (CSF) and blood specimens were tested using CHIKV-specific real-time reverse transcription polymerase chain reaction and IgM ELISA, alongside a panel of neurotropic viruses. We report four cases of suspected or confirmed CHIKV-associated neurological disease, including CHIKV RNA detection in CSF of one patient and in acute serum of another, and CHIKV IgM in CSF of three patients and in serum of a fourth. In conclusion, CHIKV should be considered as a cause of neurologic disease in endemic areas and especially during outbreaks, in addition to the more common arboviral diseases such as dengue and Japanese encephalitis viruses.

P1112: TREATING BING-NEEL SYNDROME USING A TAILORED APPROACH: EXPERIENCE OF A SPECIALIST NEUROHAEMATOLOGY CLINIC

Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse; the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17; 49%) had previously received therapy for LPL; median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26; 54%) had ≤10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28; 80%), leptomeningeal tissue biopsy (n=3; 9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4; 11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28; 96%), MYD88L265P mutation (18/28; 64%) and immunoglobulin gene rearrangement (12/28; 43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) ± thiotepa/idarubicin; n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1); one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had ≥4 cycles followed by BCNU/thiotepa autologous stem cell transplant; 10 proceeded to ‘consolidation’ (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached; 2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy; 7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image:Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib; however, there are treatment-related toxicities emphasising the need for a tailored approach.

Aptamer-Based Screen of Neuropsychiatric Lupus Cerebrospinal Fluid Reveals Potential Biomarkers That Overlap With the Choroid Plexus Transcriptome.

As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform. CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases. Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, α2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins. Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential.

Novel Synthetic Peptide-based Enzyme Linked Immunosorbent Assay for Antibody Detection in Viral Infections of the Central Nervous System

Introduction: Viral infections of Central Nervous System (CNS) are associated with severe neurological sequelae and can lead to significant morbidity if not adequately diagnosed and treated. An immunological assay detecting antibodies in the Cerebrospinal Fluid (CSF) of the patients is widely used for diagnosis of viral infections of the CNS. In the present study, diagnostic efficacy of in-house designed synthetic peptide based Enzyme Linked Immunosorbent Assay (ELISA) was evaluated for detection of antibodies against neurotropic viruses panel such as Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella Zoster Virus (VZV), Japanese Encephalitis Virus (JEV), Dengue (DENV), West Nile Virus (WNV) and Chandipura Virus (CHPV) in CSF of suspected cases. Aim: To determine the diagnostic efficacy of in-house developed synthetic peptide-based ELISA in viral infections of the CNS. Materials and Methods: A retrospective study was conducted in Central India Institute of Medical Science, Nagpur, Maharashtra, India. The suspected case of CNS viral infections of the patients were enrolled in this study from January 2013 to December 2015. Total 150 suspected cases of viral CNS infections and 135 control cases were recruited. Total 32 synthetic peptides of highly immunogenic proteins of respective seven neurotropic viruses were designed and synthesised. The designed peptides were evaluated in CSF samples of both the viral CNS infections and control cases for detection of Imunoglobulin G (IgG) and IgM antibodies using in-house developed antibody detection method. The developed tests were further compared with commercially available antibody detection ELISA kit. The sensitivity and specificity of peptide-ELISA were determined by Receiver Operating Curve (ROC) analysis and p-value was calculated by comparison of means by t-test. Results: Out of total 150 cases of CNS viral infections, a total of 31 CSF samples including 15 for CMV and 16 of JEV were positive by in-house peptide ELISA. The synthetic peptides STGDVVDISP, KQKSLVEL, RTLEVFKE, RSSNVED of CMV and ITYECPK, RRSVSVQT, GESSLVN of JEV showed a significant difference in mean absorbance value for IgM and IgG antibodies in CSF of suspected cases of viral CNS infection. Conclusion: The results demonstrated that the synthetic peptide-based ELISA is rapid, cost-effective, simple and efficient immunodiagnostic assay for initial screening of viral CNS infection.

Utility of autoantibody against an UCH-L1 epitope as a serum diagnostic marker for neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most serious complications of systemic lupus erythematosus (SLE), lacking efficient diagnostic biomarkers. Previous studies have shown that anti-ubiquitin carboxyl hydrolase L1(UCH-L1) autoantibody is a promising cerebrospinal fluid (CSF) biomarker for NPSLE diagnosis. The purpose of this study is to explore the serum autoantibodies against different UCH-L1 epitopes and investigate the potential diagnostic value of serum autoantibodies against different UCH-L1 epitopes in NPSLE. The epitopes of UCH-L1 protein were predicted in DNAStar software. The serum levels of different UCH-L1 epitope autoantibodies in 40 NPSLE patients, 32 SLE patients without neuropsychiatric symptoms and 21 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Data were analysed using Pearson correlation analysis, ROC curve analysis, nonparametric Mann-Whitney test, t-test and χ2 test. We screened three candidate epitopes of UCH-L1 protein. The autoantibody against amino acid 58 to 69 of UCH-L1 (UCH58-69) showed highest diagnostic power in distinguishing NPSLE patients from SLE patients without neuro-psychiatric symptoms (p=0.0038). The ROC analysis showed that the specificity and sensitivity of anti-UCH58-69 were 92.3% and 37.5%, respectively. In addition, increased serum anti-UCH58-69 levels were associated with increased SLEDAI, CSF microprotein, CSF leukocyte count, ESR, AnuA, anti-dsDNA, IgG and IgM but with decrease of C3 in SLE patients. The serum levels of anti-UCH58-69 significantly increased in NPSLE patients compared with SLE patients without neuropsychiatric symptoms and were correlated with disease severity. Anti-UCH58-69 autoantibody may become a novel serum biomarker for NPSLE non-invasive diagnosis, which might be applicable for NPSLE early screening and diagnosis.

Free Immunoglobulin Light Chains in Patients with Tick-Borne Encephalitis: Before and after Treatment.

Background: Tick-borne encephalitis (TBE) is inflammation of the central nervous system (CNS) caused by a viral infection which may be associated with increased synthesis of immunoglobulins. It can lead to inter alia, breakdown of the blood-brain barrier (BBB), or even death and, unfortunately, treatment is only symptomatic. Therefore, the aim of the present study was assessment of the concentrations of free light chains (FLC) kappa (κ) and lambda (λ in the cerebrospinal fluid (CSF) and serum of patients with TBE. Methods: A total of 58 cerebrospinal fluid and serum sample pairs were analyzed. Samples were collected from patients with TBE before and after treatment. FLC were measured using the turbidimetric method. The values of κIgG-index, λIgG-index, κFLC-index and λFLC-index were calculated using relevant formulas. Results: Pre-treatment serum λFLC concentrations were higher in comparison to post-treatment levels. Moreover, it was observed that CSF λFLC, TBEV IgM, TBEV IgG, and serum TBEV IgG, as well as the values of λFLC-index, κFLC-index, and λIgG-index were elevated after treatment. In the total study group, the concentrations of CSF κFLC and λFLC, and values of four indexes: κFLC-index, λFLC-index, κIgG-index, and λIgG-index correlated with each other and with CSF TBEV IgM and IgG antibodies. The CSF level of TBEV IgG was also associated with serum IgG TBEV and CSF IgM TBEV antibodies. Additionally, serum κFLC correlated with serum and CSF λFLC. Conclusion: This is the first study that demonstrates statistically significant differences in serum and CSF λFLC, as well as in the calculated values of three algorithms: λIgG-index, κFLC-index, and λIgG-index prior to and following treatment of TBE. Our findings may indicate that these differences reflect the intrathecal synthesis of immunoglobulins and increased permeability of BBB in patients with TBE. Moreover, it could provide the basis for developing new therapeutic strategies.

An Unusual Case of Meningitis in an Adolescent.

An Unusual Case of Meningitis in an Adolescent.

Outcome of Japanese Encephalitis Virus (JEV) Infection in Pediatric and Adult Patients at Mahosot Hospital, Vientiane, Lao PDR.

.Although Japanese encephalitis virus (JEV) infection is an important cause of acute febrile illness in Lao PDR (Laos), patient outcome has not been evaluated. We prospectively followed up 123 JEV-infected patients (70 children < 15 years and 53 adults ≥ 15 years) admitted at Mahosot Hospital, Vientiane, from 2003 to 2013. Japanese encephalitis virus infection was diagnosed by the detection of anti-JEV IgM in cerebrospinal fluid and/or IgM seroconversion. Neurological sequelae were assessed using the Liverpool Outcome Score (LOS), total (maximum score = 75), and final (maximum score = 5). The median (interquartile range [IQR]) age of the patients was 12.0 (7.5–18.8) years, and 57% were male. The median (IQR) duration of patients’ follow-up was 4.5 (3.2–7.3) years. Of all patients, 10/123 (8.1%) died during hospitalization, and 13/123 (10.6%) died at home after discharge, giving a mortality of 18.7% (23/123) (33 [26.8%] patients were lost to follow-up). The frequency of neurological sequelae at the last follow-up was 61.2% (48.4% in adults and 69.4% in children, P = 0.135). The proportion of patients with severe and moderate functional impairment at the last follow-up was significantly higher in children (25%) than in adults (6.5%), P = 0.042. Half of the patients who were still alive at the last follow-up (67) and for whom LOS data were available (22) had improvements in their total and final LOS between discharge and the last follow-up. The total and final LOS at discharge were not significantly different between children and adults, but total LOS at the last follow-up was significantly higher in adults than in children (median [IQR]: 74.5 [73–75] versus 73.0 [73–75], P = 0.019).

An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid

BackgroundTick-borne encephalitis (TBE) is an infectious disease endemic to large parts of Europe and Asia. Diagnosing TBE often relies on the detection of TBEV-specific antibodies in serum and cerebrospinal fluid (CSF) as viral genome is mostly not detectable once neurological symptoms occur. ObjectivesWe evaluated the performance of TBEV IgM and IgG ELISAs in both serum and CSF of confirmed TBEV patients and discuss the role of (CSF) serology in TBEV diagnostics. Study designFor the assay evaluation we collected specimen from confirmed TBEV patients. Assay specificity was assessed using sera from patients with a related flavivirus infection or other acute infection. A selected ELISA assay was used to analyze TBEV-specific antibodies in CSF and to evaluate the use in confirming TBE diagnosis. ResultsIn this study the overall sensitivity of the IgM TBEV ELISAs was acceptable (94 -100 %). Four out of five IgM ELISA’s demonstrated an excellent overall specificity from 94 -100% whereas a low overall specificity was observed for the IgG TBEV ELISAs (30-71%). Intrathecal antibody production against TBEV was demonstrated in a subset of TBE patients. ConclusionsIn four out of five ELISAs, IgM testing in serum and CSF of TBE patients is specific and confirmative. The lack of IgG specificity in all ELISAs emphasizes the need of confirmatory testing by virus neutralisation, depending on the patient’s background and the geographic location of exposure to TBEV. A CSF-serum IgG antibody index can support the diagnosis specifically in chronic disease or once IgM has disappeared.

Clinical analysis of 8 cases with anti-GQ1b antibody syndrome

Objective: To investigate the clinical characterization, treatment and prognosis of anti-GQ1b antibody syndrome. Methods: The clinical data of 8 patients with positive serum anti-GQ1b antibody from the Department of Neurology of Nanjing Brain Hospital between June 2016 and July 2018 were analyzed retrospectively. Their serums were tested by immunoblotting. Relevant literatures were reviewed to investigate possible pathogenesis. Results: Of the 8 cases, 4 cases were male, 4 cases were female; their age ranged from 16 to 76 (47±21) years old. Seven of them were with acute onset, the time course of the disease ranged from 2 to 15 (7±4) days. Six cases had a history of influenza prior to the onset of the presenting symptoms. In terms of the clinical manifestations of the eight patients, two were affected with Guillain-Barre syndrome (GBS), two with Cavernous sinus syndrome, one with Miller Fisher syndrome, one with both GBS and spinal cord demyelination, one with Bulbar paralysis, and one with chronic inflammatory demyelinating polyneuropathy (CIDP). The anti-GQ1b antibody IgG in serum was positive in 6 patients, two of whom were combined with positive IgG of anti-GD1b antibody in serum. The anti-GQ1b antibody IgM in serum was positive in 1 patient, and the anti-GQ1b antibody IgM and anti-GT1b antibody IgM in cerebrospinal fluid (CSF) were both positive in the other patient. In terms of the treatment, 3 patients (3/8) received vitamin B treatment only, 2 patients (2/8) received steroid plus vitamin B treatment, 2 patients (2/8) received intravenous immunoglobulin (IVIG) plus vitamin B treatment, and 1 patient (1/8) received steroid plus IVIG treatment. During the 8-33 months' follow-up after discharge, 6 patients were significantly improved in their symptoms, one with mild diplopia, one with limbs weakness, numbness and difficulty in walking. The symptoms of one patient (case 3) fluctuated twice and recovered again after treatment. Conclusions: The disease spectrum of anti-GQ1b antibodies syndrome is broad, and main symptom is ophtalmoplegia. Immunotherapy with IVIG and steroid would be beneficial to prognosis.

Viral RNA Degradation Makes Urine a Challenging Specimen for Detection of Japanese Encephalitis Virus in Patients With Suspected CNS Infection.

BackgroundJapanese encephalitis virus (JEV) is a leading cause of central nervous system (CNS) infections in Asia and results in significant morbidity and mortality. JEV RNA is rarely detected in serum or cerebrospinal fluid (CSF), and diagnosis of JEV infection is usually based on serological tests that are frequently difficult to interpret. Unlike serum or CSF, urine is relatively easy to obtain, but, to date, there has been minimal work on the feasibility of testing urine for JEV RNA.MethodsWe investigated the use of lysis buffer and a Microsep device to optimize urine storage for detection of JEV RNA by reverse transcription real-time polymerase chain reaction (RT-qPCR). The best of the studied methods was then evaluated in consecutive patients admitted to the hospital with suspected CNS infections in Laos.ResultsWe demonstrated degradation of JEV RNA in urine after even short storage periods at 4°C or –80°C. Although there was no advantage in using a Microsep concentration device alone, immediate addition of lysis buffer to fresh urine improved the detection of JEV RNA at the limit of detection.ConclusionsIn 2 studies of 41 patients with acute encephalitis syndrome, 11 (27%) were positive for JEV IgM in CSF and/or serum, and 2 (4.9%) were JEV RT-qPCR positive from throat swabs. JEV RNA was not detected in any of these patients’ urine samples. However, lysis buffer was only used during a prospective study, that is, for only 17/41 (41%) patient urine samples. Our findings suggest a need for larger studies testing urine for JEV RNA, with urine collected at different times from symptom onset, and using lysis buffer, which stabilizes RNA, for storage.

349. Retrospective Descriptive Analysis of West Nile Neuroinvasive Disease in Northwest Louisiana

BackgroundWest Nile virus (WNV) infection has become endemic in the continental United States. Eighty percent of the West Nile virus infections are asymptomatic. One in 150 individuals with West Nile virus infection develops West Nile neuroinvasive disease (WNND). The neurological manifestations include encephalitis, meningoencephalitis, meningitis, and acute flaccid paralysis.MethodsWe performed a retrospective descriptive study in our tertiary care hospital in Louisiana to describe the clinical features, Cerebrospinal fluid (CSF) findings and clinical outcomes. Patients aged >18 years admitted in our hospital between January 1, 2012 and December 31, 2017 were included. Hospital Electronic Health records were screened for diagnosis of WNND by ICD codes and positive WNV antibody testing in CSF.ResultsThere were a total of 23 patients identified with positive WNV IgM or IgG in CSF. Fifteen patients were males and eight were female. The median age was 48.8 years. Six patients were diagnosed with meningitis, 12 with encephalitis, and five with meningoencephalitis. Most Common presenting symptoms were altered mental status and fever in 15 patients. Only two patients gave history of mosquito bite. Incidence was peak in the month of August, July, and September.WNV IgG and IgM antibodies were positive in CSF in 13 patients. Four patients had only positive WNV IgM and six patients had only positive WNV IgG. The average number of days from the admission to diagnosis of infection ranged from 3 to 16 days with average of 8.9 days. CSF protein was >45 mg/dL in 12 patients and elevated white cell count (>5 mm3) in 20 patients. CSF protein >100 mg/dL was seen in nine patients. Lymphocytosis was present in 10 patients. The average length of stay was 13.3 days and nine patients required ICU stay. Only one patient was not given any antibiotics. The average duration of antibiotics was 6.4 days. On 1 year follow-up, eight patients had no residual deficits, four patients had residual deficits, two patients were deceased, and nine patients were lost to follow-up.ConclusionWNV infection has become endemic in Southern United States especially in summer months. Identifying the infection early in its clinical course would help to avoid unnecessary antibiotics when patients present with fever and meningeal symptoms. Including WNV antibodies in CSF studies is critical in making a diagnosis.Disclosures All authors: No reported disclosures.