Diagnosis Of Lyme Neuroborreliosis Research Articles

Lyme Neuroborreliosis-Significant Local Variations in Incidence within a Highly Endemic Region in Sweden.

The aim of this study was to perform a detailed epidemiological overview of Lyme neuroborreliosis (LNB) 2008-2021 in a highly Lyme borreliosis-endemic area in Sweden using a geographic information system (GIS). Diagnosis of LNB was based on clinical symptoms and analysis of cerebrospinal fluid (CSF) according to European guidelines. From laboratory databases and medical records, we detected all patients with CSF pleocytosis and intrathecal anti-Borrelia antibody production and listed clinical features. The distribution of LNB cases within Kalmar County, Sweden was investigated using GIS. In total, 272 cases of definite LNB were confirmed with an average yearly incidence of 7.8/100,000. Significant differences in incidence were noted between children 0-17 years (16/100,000) and adults 18+ years (5.8/100,000) (p < 0.001), between rural (16/100,000) and urban areas (5.8/100,000) (p < 0.001) and between selected municipalities (p < 0.001). Distinct clinical differences in presentation of LNB were also noted between children and adults. Thus, the incidence of LNB varies significantly locally and in relation to age, and clinical presentation shows differences between children and adults. Surveillance of LNB and knowledge of local epidemiological conditions may facilitate preventive measures.

Značaj dijagnostike neuroborelioze u Republici Srbiji

Lyme neuroborreliosis (LNB) is the most common disseminated form of LB in Europe. It is a tick transmitted disease, caused by Borrelia burgdorferi sensu lato complex (Bb). There are numerous tests on the market for neuroborreliosis diagnostics, but none is reliable enough to confirm the diagnosis of LNB alone. Measuring antibody index (AI), although a gold standard test, is unable to distinguish current infection from a resolved one. Support can partially be found in CXCL-13 concentration follow up, which will decrease after successful therapy. Microbiology testing is just a support in establishing LNB diagnosis, and must be considered in conjunction with exposure history, clinical presentation, and other laboratory findings.

Socio-demographic Characteristics of Tick Bite and Erythema migrans not associated with the Diagnosis of Neuroboreliosis

Introduction Lyme neuroborreliosis (LNB) is a tick-borne infection caused by bacteria Borrelia burgdorferi sensu lato that accounts for 10-15% of all Lyme borreliosis cases in Europe. LNB can present with a variety of neurological manifestations. We aimed to describe the typical anamnestic, clinical and laboratory features of patients diagnosed with LNB and to describe the differences between paediatric and adult cases. Additionally, we assessed the factors associated with definite LNB. Methods We retrospectively evaluated data of patients with suspected LNB had undergone lumbar puncture and were admitted to the Infectious diseases department of University hospital Bratislava, Slovakia, between September 2019 and May 2022. Patients were divided into three categories according to the diagnostic criteria of European Federation of Neurological Societies: A) cases with definite LNB, B) cases with possible LNB, C) non-LNB controls. Results In total, 139 patients were included in the analysis. 32 individuals were classified as definite LNB, 23 as possible LNB and 84 as non-LNB controls. 55.5% were females and 35.3% were children aged&lt;18 years. 56.3% of patients with definite LNB reported a history of tick bite, and 21.9% a history of erythema migrans (EM). Peripheral facial nerve palsy (PFNP) was the most common clinical symptom in patients with definite LNB (65.6%), followed by headache (50.0%), fever (21.9%) and radicular pain (18.8%). In a univariate and multivariable analyses neither history of tick bite nor history of EM were significantly associated with definite LNB. Factors independently associated with definite LNB in multivariable analyses were (i) age &lt; 18 years (aOR 7.89, 95% CI 2.00-31.03, p &lt; 0,003), (ii) female gender (OR 6.34; 95% CI 1.66-24.17, p &lt; 0.007), and (iii) facial nerve palsy (OR 10.54; 95% CI 2.41-55.19, p &lt; 0.002). Conclusion We found that peripheral facial nerve palsy is the strongest predictor of definite LNB, and that the children&lt;18 years and females in our study were more likely to be diagnosed with LNB. Our study also suggests that anamnestic data on history of tick bite and EM contribute little to the diagnosis of LNB and that the examination of CSF is essential for the diagnosis of LNB.

Comprehensive analyses of transcriptomes induced by Lyme spirochete infection to CNS model system.

Lyme disease is a zoonotic disease caused by infection with Borrelia burgdorferi (Bb), the involvement of the nervous system in Lyme disease is usually referred to as Lyme neuroborreliosis (LNB). LNB has diverse clinical manifestations, most commonly including meningitis, Bell's palsy, and encephalitis. However, the molecular pathogenesis of neuroborreliosis is still poorly understood. Comprehensive transcriptomic analysis following Bb infection could provide new insights into the pathogenesis of LNB and may identify novel biomarkers or therapeutic targets for LNB diagnosis and treatment. In the present study, we pooled transcriptomic dataset of Macaca mulatta (rhesus) from our laboratory and the human astrocyte dataset GSE85143 from the Gene Expression Omnibus database to screen common differentially expressed genes (DEGs) in the Bb infection group and the control group. Functional and enrichment analyses were applied for the DEGs. Protein-Protein Interaction network, and hub genes were identified using the Search Tool for the Retrieval of Interaction Genes database and the CytoHubba plugin. Finally, mRNA expression of hub genes was validated in vitro and ex vivo from Bb infected models and normal controls by quantitative reverse transcription PCR (qRT-PCR). A total of 80 upregulated DEGs and 32 downregulated DEGs were identified. Among them, 11 hub genes were selected. The pathway enrichment analyses on 11 hub genes revealed that the PI3K-Akt signaling pathway was significantly enriched. The mRNA levels of ANGPT1, TLR6, SREBF1, LDLR, TNC, and ITGA2 in U251 cells and/or rhesus brain explants by exposure to Bb were validated by qRT-PCR. Our study suggested that TLR6, ANGPT1, LDLR, SREBF1, TNC, and ITGA may be candidate mammal biomarkers for LNB, and the TLR6/PI3K-Akt signaling pathway may play an important role in LNB pathogenesis.

Discriminating between Lyme neuroborreliosis and other central nervous system infections by use of biomarkers CXCL13 and IL-6

CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved by the addition of IL-6, a non-specific infection biomarker. The aim of this study was to measure the concentrations of CXCL13 and IL-6 in cerebrospinal fluid, in the attempt to evaluate the diagnostic performance of these two biomarkers, in the differentiation between definite and possible LNB, as well as between LNB and other neuroinfections. This study used a cross-sectional design to quantify the levels of CXCL13 and IL-6 in cerebrospinal fluid (CSF) specimens from consecutive patients examined for central nervous system (CNS) infections at Lillebaelt Hospital in the Region of Southern Denmark. CXCL13 and IL-6 were measured simultaneously using the Bio-Plex 200 multiplex Cytokine Immunoassay System (Bio-Rad). Based on clinical and paraclinical findings, we grouped patients into six separate groups: definite LNB, possible LNB, Viral CNS infection, non-Borrelia Bacterial CNS infection, Other CNS disease (with pleocytosis) and Negative (without pleocytosis). A combined interpretation of four variables (leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF) is presented using principal component cluster analysis. We included by chart review 390 patients discharged with definite LNB (n = 31), possible LNB (n = 10), confirmed Viral or non-Borrelia Bacterial CNS infection (n = 34), Other CNS disease (n = 58), and Negative (n = 257) for CXCL13 and IL-6 analysis. Principal component analysis (PCA) revealed three distinct clusters based on leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF from 380 included patients (10 possible LNB patients excluded). The clusters clearly differentiate the groups: definite LNB, non-Borrelia Bacterial CNS infection and Negative (without pleocytosis). A receiver operating characteristic (ROC) curve comparing LNB patients (n = 31) and all non-LNB conditions with CSF pleocytosis (n = 99) indicated an optimal CXCL13 cut-off value of 50.7 pg/mL, resulting in a sensitivity and a specificity of 93.6 and 91.1%, respectively. The ROC analysis comparing patients with confirmed non-LNB CNS infection (n = 34) and all others with CSF pleocytosis (n = 97) resulted in an optimal IL-6 cut-off value of 111.5 pg/mL, yielding a sensitivity and a specificity of 78.8% and 82.5% respectively. Of the ten possible LNB patients, three cases (with CXCL13 levels above cut-off) fall within the LNB cluster, and one case is just outside, providing some laboratory support for the diagnosis of LNB. The remaining six possible LNB patients (with CXCL13 levels below the 50.7 cut-off) had little support for the diagnosis of LNB in the PCA-plot. The results of this study confirm that CXCL13 is a valuable supplement for diagnosis of LNB, and that the combination of CXCL13 and IL-6 may be used to differentiate cases of LNB from other CNS infections. Furthermore, IL-6 can be of differential diagnostic value when evaluating patients with possible LNB.

Cerebrospinal fluid markers of inflammation and brain injury in Lyme neuroborreliosis- a prospective follow-up study.

The purpose of this study was to evaluate levels and kinetics of cerebrospinal fluid (CSF) markers of inflammation and brain injury in patients with Lyme neuroborreliosis (LNB). Adult patients with clinically suspected LNB were enrolled, in a prospective clinical study in the South East of Sweden. Patients were classified according to the European Federation of Neurological Societies' guidelines. Definite cases of LNB were re-examined one month later including a repeat CSF investigation. Routine laboratory parameters were investigated along with CSF levels of neurodegenerative markers glial fibrillary acidic protein (GFAp), total tau (t-tau) and neurofilament light protein (NFL), as well as neuroinflammatory markers soluble triggering receptor expressed on myeloid cells 2 (sTREM2), YKL-40 and CXCL13. Non-LNB served as controls. An additional comparison group consisted of spinal anesthesia subjects (SAS) without known central nervous system conditions. CSF levels of sTREM2 and CXCL13 were elevated in definite LNB patients at diagnosis compared with non-LNB patients (p<0.001) and SAS (p≤0.01). In addition, CSF levels of sTREM2, YKL-40 and CXCL13 rapidly declined in at follow-up after antibiotic treatment. In contrast, CSF levels of GFAp and t-tau did not differ across LNB groups, and did not change after treatment. Although in a limited number of LNB patients, the results indicate a predominance of microglial and neuroinflammatory involvement rather than parenchymal CNS injury in CSF at diagnosis of LNB with a prompt decline after antibiotic treatment. The findings provide pathogenetic insights and may be of value in differential diagnosis of CSF findings.

Retrospective Evaluation of Various Serological Assays and Multiple Parameters for Optimal Diagnosis of Lyme Neuroborreliosis in a Routine Clinical Setting.

ABSTRACTLaboratory diagnosis of Lyme neuroborreliosis (LNB) is challenging, and validated diagnostic algorithms are lacking. Therefore, this retrospective cross-sectional study aimed to compare the diagnostic performance of seven commercial antibody assays for LNB diagnosis. Random forest (RF) modeling was conducted to investigate whether the diagnostic performance using the antibody assays could be improved by including several routine cerebrospinal fluid (CSF) parameters (i.e., leukocyte count, total protein, blood-CSF barrier functionality, and intrathecal total antibody synthesis), two-tier serology on serum, the CSF level of the B-cell chemokine (C-X-C motif) ligand 13 (CXCL13), and a Borrelia species PCR on CSF. In total, 156 patients were included who were classified as definite LNB (n = 10), possible LNB (n = 7), or non-LNB patient (n = 139) according to the criteria of the European Federation of Neurological Societies using a consensus strategy for intrathecal Borrelia-specific antibody synthesis. The seven antibody assays showed sensitivities ranging from 47.1% to 100% and specificities ranging from 95.7% to 100%. RF modeling demonstrated that the sensitivities of most antibody assays could be improved by including other parameters to the diagnostic repertoire for diagnosing LNB (range: 94.1% to 100%), although with slightly lower specificities (range: 92.8% to 96.4%). The most important parameters for LNB diagnosis are the detection of intrathecally produced Borrelia-specific antibodies, two-tier serology on serum, CSF-CXCL13, Reibergram classification, and pleocytosis. In conclusion, this study shows that LNB diagnosis is best supported using multiparameter analysis. Furthermore, a collaborative prospective study is proposed to investigate if a standardized diagnostic algorithm can be developed for improved LNB diagnosis.IMPORTANCE The diagnosis of LNB is established by clinical symptoms, pleocytosis, and proof of intrathecal synthesis of Borrelia-specific antibodies. Laboratory diagnosis of LNB is challenging, and validated diagnostic algorithms are lacking. Therefore, this retrospective cross-sectional study aimed to compare the diagnostic performance of seven commercial antibody assays for LNB diagnosis. Multiparameter analysis was conducted to investigate whether the diagnostic performance using the antibody assays could be improved by including several routine (CSF) parameters. The results of this study show that LNB diagnosis is best supported using the detection of intrathecally produced Borrelia-specific antibodies, two-tier serology on serum, CSF-CXCL13, Reibergram classification, and pleocytosis. Furthermore, we propose a collaborative prospective study to investigate the potential role of constructing a diagnostic algorithm using multiparameter analysis for improved LNB diagnosis.

Neurosyphilis and Lyme neuroborreliosis.

Neurosyphilis (NS) and Lyme neuroborreliosis (LNB) are spirochetal diseases with distinct clinical manifestations. The diagnosis of NS remains challenging due to imperfect diagnostic criteria and testing modalities. With LNB, misconceptions about diagnosis and treatment lead to considerable morbidity and drug related adverse effects. Although studies continue investigating alternate approaches and new diagnostic tests for NS, few data exist to change current approaches to diagnosis, management or follow up. In the diagnosis of LNB, the chemokine CXCL13 shows promising diagnostic accuracy. A systematic review discourages the use of cell-based assays when investigating Lyme disease. Clinical studies show no benefit from extended antibiotic treatment for patients with unspecific symptoms labelled as having Lyme disease. The diagnosis of NS may be delayed due to a lack of specificity of findings, low suspicion for syphilis, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis is required provide timely diagnosis and management of NS. Fortunately, penicillin remains the treatment of choice. Overdiagnosis and overtreatment in patients labelled as having Lyme disease can be avoided by an evidence-based approach towards diagnosis and treatment.

Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark

The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate. To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort. This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020. Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi. The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort. Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort. In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.

Comparative Analysis of the Euroimmun CXCL13 Enzyme-Linked Immunosorbent Assay and the ReaScan Lateral Flow Immunoassay for Diagnosis of Lyme Neuroborreliosis.

Diagnosis of Lyme neuroborreliosis (LNB) is challenging, as long as Borrelia-specific intrathecal antibodies are not yet detectable. The chemokine CXCL13 is elevated in the cerebrospinal fluid (CSF) of LNB patients. Here, we compared the performances of the Euroimmun CXCL13 enzyme-linked immunosorbent assay (CXCL13 ELISA) and the ReaScan CXCL13 lateral flow immunoassay (CXCL13 LFA), a rapid point-of-care test, to support the diagnosis of LNB. In a dual-center case-control study, CSF samples from 90 patients (34 with definite LNB, 10 with possible LNB, and 46 with other central nervous system [CNS] diseases [non-LNB group]) were analyzed with the CXCL13 ELISA and the CXCL13 LFA. Classification of patients followed the European Federation of Neurological Societies (EFNS) guidelines on LNB. The CXCL13 ELISA detected elevated CXCL13 levels in all patients with definite LNB (median, 1,409 pg/ml) compared to the non-LNB controls (median, 20.7 pg/ml; P < 0.0001), with a sensitivity of 100% and a specificity of 84.8% (cutoff value, 78.6 pg/ml; area under the receiver operating characteristic [ROC] curve, 0.93). Similarly, the CXCL13 LFA yielded elevated CXCL13 levels in 31 patients with definite LNB (median arbitrary value, 223.5) compared to the non-LNB control patients (median arbitrary value, 0; P < 0.0001) and had a sensitivity and specificity of 91.2% and 93.5%, respectively (cutoff arbitrary value, 22.5; area under the ROC curve, 0.94). The correlation between the CXCL13 levels obtained by ELISA and LFA was strong (Spearman correlation coefficient r = 0.89; P < 0.0001). The CXCL13 ELISA and the CXCL13 LFA are comparable diagnostic tools for the detection of CXCL13 in the CSF of patients with definite LNB. The advantage of the CXCL13 LFA is the shorter time to result.

Diagnostic challenges in patients with suspected Lyme neuroborreliosis

Lyme neuroborreliosis is a tick–borne spirochetal infection, which may affect the peripheral or central nervous system at the early or late stages of the disease. The purpose of the work is to analyze modern scientific literature on the issues of clinical manifestations, diagnostics of early and late Lyme neuroborreliosis. Analysis of the scientific literature related to the diagnosis of Lyme neuroborreliosis was carried out. According to the authors of the researches, it was found that clinical presentation varies with disease stage, and Lyme neuroborreliosis is reported in up to 25 % of patients with Lyme disease. The clinical manifestations of this not uncommon disorder nowadays depend on the neurological structures which are primarily involved. The full clinical picture of Lyme neuroborreliosis may mimic other diseases, so atypical symptoms can result in diagnostic delay or misdiagnosis. Conclusions. The incidence of Lyme neuroborreliosis seems to be much higher than previously assumed. Cerebrospinal fluid examination (detection of Borrelia burgdorferi IgM and IgG specific antibodies) is essential for the diagnosis of early and late Lyme neuroborreliosis, as successful treatment of early Lyme neuroborreliosis can prevent the expensive and devastating consequences of late Lyme neuroborreliosis.

Lyme Neuroborreliosis in a Patient with Breast Cancer: MRI and PET/CT Findings.

We present a case demonstrating the performance of different radiographical and nuclear medicine imaging modalities in the diagnostic work-up of a patient with Lyme neuroborreliosis. The patient presented in late summer 2019 with radicular pains followed by a foot drop and peripheral facial palsy, both right-sided. Due to a history of breast cancer, disseminated malignant disease was initially suspected. Bone metastasis was ruled out by skeletal scintigraphy. Magnetic resonance imaging (MRI) of the neuroaxis and a whole body 18F-FDG PET-CT was performed within 48 hours. The MRI revealed a strong contrast enhancement of the conus medullaris and fibers of the cauda equina, while the 18F-FDG PET/CT was without pathological findings. Examination of cerebrospinal fluid led to the definitive diagnosis of Lyme neuroborreliosis with monocytic pleocytosis and a positive intrathecal test for Borrelia burgdorferi. The patient became pain-free after 10 days of ceftriaxone, and the paralysis slowly regressed the following month. This case highlights the difficulty of the diagnosis of Lyme neuroborreliosis and discusses the relevant imaging findings.

Lyme Neuroborreliosis in a Critically Ill Patient

Lyme neuroborreliosis (LNB) is a nervous system infection caused by the species of the spirochete Borrelia. A woman, with a history of right facial palsy, was admitted to the physical and rehabilitation medicine (PRM) unit for the rehabilitation of presumed sequalae of aneurism rupture and neuromuscular weakness related to critical illness. She presented in the PRM unit with flaccid quadriparesis, right facial nerve paresis, bulbar paresis, aphonia, dysphagia, and hypoactive deep-tendon reflexes. Electromyography (EMG) revealed multifocal neuropathy and serologic tests revealed positive for Borrelia (IgG). The patient was treated with 2 weeks of intravenous ceftriaxone with a marked improvement in the following days. LNB diagnosis was made due to the clinical presentation, positive Borrelia serology, and great improvement with targeted therapy. Neuromuscular weakness related to critical illness was the main differential diagnosis; however, weakness in bulbar and facial musculature and the EMG findings were not consistent with this diagnosis.

A Neurologist's View of Lyme Disease and Other Tick-Borne Infections.

Tick-borne infections-including tick-borne encephalitis viruses, represented in the United States by rare infections with Powassan and deer tick viruses, and more often Lyme disease-are of increasing importance to neurologists. Lyme neuroborreliosis (LNB) causes all or part of a triad including meningitis, radiculoneuritis, and cranial neuritis. Rarely, parenchymal brain and spinal cord involvement occur, with focal findings on examination and magnetic resonance imaging (MRI). LNB diagnosis requires plausible exposure, objective evidence of nervous system involvement, and, generally, positive two-tier serology. Central nervous system (CNS) LNB is almost always accompanied by abnormal cerebrospinal fluid (CSF) (cells, protein), often with intrathecal antibody production, which is determined by concentration-adjusted comparison of serum and CSF antibody. Measuring CSF antibody in isolation and nucleic acid-based testing of CSF are not useful in LNB and should be avoided. LNB treatment is highly effective with a 2- to 3-week course of antibiotics. Increasing evidence suggests that LNB not involving the CNS parenchyma can be treated successfully with oral doxycycline.

Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis - a pilot study.

Background The aim of this study was to evaluate the diagnostic performance of cerebrospinal fluid (CSF) free light chains (FLCs) in the diagnosis of Lyme neuroborreliosis (LNB). Methods Serum and CSF levels of κ- and λ-FLC, albumin and total concentration of immunoglobulin M (IgM) were determined together with CSF chemokine CXCL13 in 23 patients with definite LNB, 35 inflammatory neurological disease control (INDC) and 18 non-inflammatory control (NIC) patients. Indices and intrathecal fractions (IFs) of FLC and IgM were calculated. Results Significant differences in FLC indices and IFs were found between the LNB group and both control groups, p ≤ 0.007. Sensitivity of intrathecal κ- and λ-FLC synthesis reached 78%-87% in LNB patients with a specificity of 94%-100% in NIC patients, whereas specificity in INDC patients was 69%. The corresponding frequencies of positive results for IF and index of IgM and CSF CXCL13 in these three diagnostic groups were 74%-96% in LNB patients, 0% in NIC patients and 3%-6% in INDC patients at the chosen cut-off levels. Conclusions The findings of this study show a moderate to high sensitivity of CSF κ- and λ-FLC in LNB patients with a high specificity in NIC patients. However, overlap in CSF κ- and λ-FLC levels between LNB and INDC patients calls for caution in the interpretation and limits the diagnostic usefulness in the LNB diagnosis. CSF CXCL13 appears to be the most valuable additional biomarker of LNB aside from routine parameters such as CSF pleocytosis and anti-Borrelia antibody index.

Opsoclonus in a child with neuroborreliosis: Case report and review of the literature

Opsoclonus consists of massive erratic rapid eye jerks. They may occur in isolation or in association with myoclonus and ataxia, i.e., opsoclonus-myoclonus syndrome (OMS). We report the case of a 9-year-old girl who suffered from headaches for several days and was shown to have opsoclonus and left peripheral facial palsy. Work-up excluded the diagnosis of neuroblastoma, but CSF analysis showed aseptic meningitis, and serology for Borrelia burgdorferi (Lyme) was positive. The outcome was favorable with complete regression of symptoms after treatment with ceftriaxone 2g/day for 3 weeks. Although rare, the diagnosis of Lyme neuroborreliosis must be raised in the presence of isolated opsoclonus, particularly if the clinical picture is incomplete and if other features, such as peripheral facial palsy and pleocytosis in the CSF, are present.

CXCL13 concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other neurological disorders determined by Luminex and ELISA

The aims of the study were to determine and compare the concentration of CXCL13 in cerebrospinal fluid (CSF) of patients with Lyme neuroborreliosis (LNB) and various other neurological disorders applying a Luminex based assay and ELISA, and to find factors associated with CXCL13 concentration. CSF samples obtained from four clinically well-defined groups of patients (proven LNB, suspected LNB, tick-borne encephalitis (TBE), and aseptic meningitis/meningoencephalitis other than TBE) – 25 samples per group – were analyzed. The performance of the Luminex recomBead CXCL13 assay (Microgen, Neuried, Germany) and ELISA (Euroimmun, Lübeck, Germany) was assessed by receiver operating characteristics. CXCL13 cut-off values were presented as functions of CSF lymphocyte/monocyte counts. Demographic variables, CSF findings, and history of erythema migrans were assessed as possible predictors for CXCL13 CSF concentrations by a general linear model. The calculated cut-off values determined by the maximum of the Youden index were >131 pg/mL for recomBead and >259 pg/mL for the ELISA. RecomBead showed a sensitivity of 88% (68.8–97.5%) and a specificity of 94% (83.5–98.7%). For the ELISA the corresponding values were 84% (63.9–95.5%) and 98% (89.4–99.9%). The CXCL13 concentration positively correlated with CSF lymphocyte/monocyte count and Borrelia-specific intrathecal antibody index (p < 0.05). High CXCL13 concentrations were only found in the group with proven LNB. CXCL13 levels above cut-off value were established in some patients with viral meningitis/meningoencephalitis but were not detected in patients with suspected LNB without pleocytosis. Applying a linearized cut-off of the CXCL13 concentration in the CSF which is dependent on the CSF cell count is a novel approach in the laboratory diagnosis of LNB.

Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis?

Background: Tests for direct detection of Borrelia burgdorferi sensu lato (Bb) in Lyme neuroborreliosis (LNB) are needed. Detection of Bb DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples.Methods: Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls.Results: Bb DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were Bb antibody negative. No Bb DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases.Conclusion: We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without Bb antibodies due to short duration of symptoms.

Chemokine CXC Ligand 13 in Cerebrospinal Fluid Can Be Used as an Early Diagnostic Biomarker for Lyme Neuroborreliosis: A Meta-Analysis.

Lyme neuroborreliosis (LNB), which is the most common neurological manifestation of Lyme disease (LD), seriously impairs both the central and peripheral nervous systems. Current LNB diagnostic methods and criteria are not very effective. Recently, several studies have indicated that a high concentration of the chemokine CXC ligand 13 (CXCL13) in cerebrospinal fluid (CSF) could be used as a new biomarker for the diagnosis of LNB. Thus, we carried out a meta-analysis to systematically analyze the data from these studies to evaluate the value of CXCL13 as an LNB biomarker. After searching for articles in several databases, including PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI), we included 7 articles in the meta-analysis with a total of 1299 patients with LNB or other neuroinflammatory diseases. From these 1299 patients, 343 patients with LNB served as the experimental group and 956 patients with other neuroinflammatory diseases or healthy individuals served as the control group. The analyses were performed using Meta-Disc1.4 statistical software. Based on the pooled specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve, we found that CXCL13 indeed has a high sensitivity and specificity for diagnosing LNB, which means that it can be used as a new diagnostic biomarker for the diagnosis of LNB.

The recomBead Borrelia antibody index, CXCL13 and total IgM index for laboratory diagnosis of Lyme neuroborreliosis in children

For laboratory diagnostics of Lyme neuroborreliosis (LNB), the recomBead Borrelia antibody index (AI) assay has shown promising results in a mixed age population, but has not previously been evaluated with specific focus on paediatric patients. The aim of the study was to evaluate the recomBead Borrelia AI assay in cerebrospinal fluid (CSF) for the laboratory diagnosis of LNB in children. We also wanted to explore whether early markers, such as CXCL13 in CSF and/or total IgM index could be useful as complementary diagnostic tools. Children being evaluated for LNB in a Swedish Lyme endemic area were included in the study (n = 146). Serum and CSF were collected on admission. Patients with other specific diagnoses were controls (n = 15). The recomBead Borrelia AI assay and the recomBead CXCL13 assay (Mikrogen) were applied together with total IgM index. The overall sensitivity for recomBead Borrelia AI (IgM and IgG together) was 74% and the specificity was 97%. However, the highest sensitivity (91%) at an acceptable level of specificity (90%) was obtained by recomBead Borrelia AI together with CXCL13 and total IgM index, showing a positive predictive value of 84% and a negative predictive value of 95%. Thus, the recomBead Borrelia AI assay performs with moderate sensitivity and high specificity in paediatric LNB patients. The major advantage seems to be increased sensitivity in the possible LNB group compared to the IDEIA assay. The diagnostic sensitivity may be further increased by using a combination of early markers, such as CXCL13 in CSF and total IgM index.