Diagnosis Of Lyme Neuroborreliosis Research Articles

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.

Cerebrovascular Events in Lyme Neuroborreliosis

Cerebrovascular events in neuroborreliosis are a rare condition described only in isolated or small case series. No specific clinical or radiological features have been identified, and diagnosis is based on very different criteria. We retrospectively describe cases diagnosed in the Stroke Unit of Nancy Hospital, located in the endemic area of the northeast of France. We also reviewed other cases found in the literature. We identified 5 cases in our center and 57 other reported cases. Mean age was 39 years (range 5 to 77). Possible previous contact with Borrelia burgdorferi (B burgdorferi) was found in about half of cases. Additional neurologic symptoms (headache, cognitive impairment, and/or gait disturbance) were found in 44% of cases. Cerebral imaging revealed both ischemic (87%) and hemorrhagic lesions (13%) with a multiterritorial aspect in 22% of strokes, and signs of vasculitis in 71%. Analysis of cerebrospinal fluid (CSF) revealed lymphocytic meningitis in 90% of cases and elevated protein level in 86%. CSF/serum anti-B burgdorferi antibody index (AI) was positive in 91% of cases. Outcome was favorable after appropriate antibiotic treatment. Our 5 patients presented a modified Rankin scale score 0-1, without any stroke recurrence, after a median follow-up of 2.8 years. The diagnosis of Lyme neuroborreliosis should be considered for patients with cerebrovascular events without obvious cause living in an endemic area, in the presence of repeat multiterritorial strokes at short intervals, other neurologic symptoms, a history of B burgdorferi infection, and radiological signs of vasculitis. Diagnosis can be confirmed by CSF analysis with AI but with an incomplete sensitivity.

The chemokine CXCL13 is elevated in the cerebrospinal fluid of patients with neurosyphilis.

BackgroundThe chemokine CXCL13 has been discussed as a diagnostic parameter with high specificity for Lyme neuroborreliosis (LNB) and as a marker of disease activity. Neurosyphilis and LNB share similar characteristics. We investigated retrospectively CXCL13 levels in the cerebrospinal fluid (CSF) of patients with neurosyphilis at initial diagnosis and during treatment.ResultsFive patients with neurosyphilis were identified retrospectively using an electronic database in a tertiary care hospital from 2005 to 2012. CXCL13 levels were measured using an ELISA. Five patients with definite LNB and 10 patients with multiple sclerosis (MS) served as controls. Median CXCL13 levels at baseline were 972 pg/mL for neurosyphilis patients, 8,000 pg/mL for LNB patients, and 7.8 pg/mL for MS patients. Patients with LNB and neurosyphilis showed significantly higher CXCL13 levels in their CSF compared to MS patients (p < 0.05, p < 0.001, respectively). CXCL13 levels in the CSF declined during treatment.ConclusionCXCL13 levels in the CSF of patients with neurosyphilis can be as high as in patients with LNB, exceeding the proposed threshold of 250 pg/mL for the diagnosis of LNB. Patients with encephalitic/myelitic syndromes appear to have especially high levels of CXCL13. Clinicians should be aware that high levels of CXCL13 are not found exclusively in LNB but also in other infectious diseases of the CNS.

Peripheral facial palsy as an initial symptom of Lyme neuroborreliosis in an Austrian endemic area.

The objective of this study was to analyze the percentage as well as clinical and laboratory characteristics of Lyme neuroborreliosis (LNB) in patients admitted with peripheral facial palsy. Additionally, we looked for diagnostic criteria to distinguish Bell's palsy from facial palsy due to LNB. Data collection was done retrospectively from 2007 until 2012. We identified 278 consecutive patients, who were admitted to the department of Neurology due to peripheral facial palsy. Patients were routinely investigated for LNB including clinical neurological examination and cerebral spinal fluid (CSF) analysis. Demographic and clinical data were analyzed according to a standardized protocol. In 19 (male (m)=14/female (f)=5) out of 278 patients (7%), a diagnosis of LNB was established. There were 8 patients (3%) identified with varicella zoster (VZV) (m=7/f=1) and 13 patients (5%) with facial palsy due to diabetic mononeuropathy (m=5/f=8). A total of 207 patients (75%) were diagnosed as Bell's palsy (m=110/f=97). Compared with CSF of patients with facial palsy due to VZV and diabetic mononeuropathy, patients with LNB showed higher cell count, protein and lactate levels, whereas patients with facial palsy due to diabetic mononeuropathy showed higher glucose level. With respect to seasonal clustering, an accumulation of 74% of the LNB cases was detected from June to October, whereas in the rest of the year there were only 26% of the LNB cases. Patients with Bell's palsy are more evenly distributed over the year. Regarding neurological signs and symptoms, radicular symptoms were only reported in the LNB group. Despite radicular symptoms for LNB, no specific signs or symptoms were found for facial palsy due to VZV, Bell's palsy, or diabetic mononeuropathy. According to the results of our study, we recommend CSF testing in any case for patients with facial palsy in an endemic area from June to October especially if additional radicular symptoms are present. To establish recommendations for a diagnostic workup in patients with facial palsy in areas endemic for Borrelia, the seasonal clustering of LNB as well as specific clinical features should also be confirmed in a future prospective trial.

Antibodies to decorin-binding protein B (DbpB) in the diagnosis of Lyme neuroborreliosis in children

Laboratory support is needed to confirm the clinical diagnosis of Lyme neuroborreliosis (LNB). Antibodies to Borrelia-specific proteins have been used to improve serological diagnostics. The aims of this study were to assess the occurrence of antibodies to decorin-binding protein B (DbpB) in serum and cerebrospinal fluid (CSF) in children with LNB and to evaluate the performance of DbpB variants in the diagnosis of LNB in children. Serum and CSF sample pairs were available from 57 children evaluated for LNB. Based on the presence of anti-flagella antibodies and pleocytosis in the CSF, patients were divided into three different groups: confirmed LNB (n=24), possible LNB (n=16), and non LNB (n=17). Recombinant DbpBs from three Borrelia burgdorferi sensu lato species - Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii - were used in an ELISA to detect IgG antibodies. The sensitivity of variant recombinant DbpBs in serum and CSF samples varied between 0% and 46% and between 0% and 42%, respectively. In CSF, the most sensitive antigen was the DbpB variant from B. garinii. Serum or CSF antibodies to DbpB do not appear to be beneficial in the laboratory diagnosis of LNB in children.

The degree of damage in the peripheral facial nerve palsy in children depending on the cause: The role of Lyme neuroborreliosis

Symptoms of peripheral facial nerve paralysis occur in patients of all age groups. Etiology of this disease is very diverse. The aim of this work is to estimate facial nerve damage in relation to presumable cause, including cases in which Lyme neuroborreliosis has been confirmed by laboratory testing. Thirty-three patients with symptoms of facial nerve paralysis were examined from January to September 2012 in the Department of Pediatric Neurology of the Provincial Specialist Children's Hospital in Olsztyn. Facial nerve function was classified on a three-stage scale created by the authors of this work. Full neurological examination was performed in all patients. Laboratory tests for Lyme-specific antibodies IgG and IgM by enzyme-linked immunosorbent assay has also been performed. In the study group, diagnosis of Lyme neuroborreliosis was confirmed in nine patients. Analysis shows that the stage of facial nerve damage in the group with Lyme disease was significantly heavier and that percentage of mild paralysis was significantly higher in the group of patients in whom Lyme disease has not been confirmed. The role of neuroborreliosis among the infectious factors ought to be emphasized. It seems significant that in patients with confirmed Lyme disease the stage of facial nerve damage was considerably deeper and the recovery was slower.

CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation.

BackgroundLaboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based on the detection of intrathecal Borrelia burgdorferi–specific antibody production (increased antibody index (AI)). However, AI can be negative in patients with early LNB and, conversely, can remain elevated for months after antibiotic treatment. Recent studies suggested that the chemokine CXCL13 in the cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin-level determination has been used to assess the degree of neuroinflammation in a wide variety of diseases.MethodsCXCL13 concentrations were analyzed in CSF samples of 366 retrospectively identified individuals. The samples represented pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection, and untreated neurosyphilis. The panel included also samples from patients with multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients, 24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin concentrations were determined in a subset of these samples.ResultsThe CXCL13 concentrations in CSF samples of untreated LNB patients were significantly higher (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8 pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml). The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of 99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations declined significantly from 16,770 pg/ml before to 109 pg/ml after the treatment.CSF neopterin concentration was significantly higher among the untreated LNB patients than in the non-LNB group. The use of neopterin concentration 10.6 nM as the cut-off led to a sensitivity of 88.6% and a specificity of 65.0% for the diagnosis of LNB. The CSF neopterin concentrations decreased statistically significantly with the treatment.ConclusionsThese results clearly indicate that highly elevated CSF CXCL13 levels are strongly associated with untreated LNB. CXCL13 outperformed neopterin and appears to be an excellent biomarker in differentiating LNB from viral CNS infections and from other neuroinflammatory conditions.

Intrathecally produced IgG and IgM antibodies to recombinant VlsE, VlsE peptide, recombinant OspC and whole cell extracts in the diagnosis of Lyme neuroborreliosis

Detection of intrathecally produced specific antibodies (AI) is essential in the diagnosis of Lyme neuroborreliosis (LNB); however, the performance of various newer AI detection methods has not been systematically assessed. Here we assessed and compared advanced test systems for detecting borrelia IgG-AI and IgM-AI. Serum and cerebrospinal fluid (CSF) samples from well-defined LNB and tick-borne encephalitis (TBE) patients, 25 each, were tested with three antibody detection systems, one based on chemiluminescence (CLA) and two based on enzyme-linked immunosorbent assays (ELISA), employing different antigens for detection of IgG and IgM antibodies. In samples from patients with LNB, IgG-AI was detected in 20 samples by CLA, 19 by ELISA1, and 22 by ELISA2, and IgM-AI was detected in 16 samples by CLA, six by ELISA1, and 11 by ELISA2. In samples from TBE patients, IgG-AI was positive in one case by CLA and ELISA2, and in 7 cases by ELISA1, whereas IgM-AI was positive in one case by CLA and in none by ELISA. IgG-AI and IgM-AI were not detected within the first week of disease. Duration of disease correlated with IgG-AI while IgM-AI results were heterogeneous for each test assay. Moreover, the levels of IgG-AI, but not IgM-AI, correlated with protein concentration in CSF. IgG is the relevant immunoglobulin isotype for detecting intrathecal synthesis of borrelia antibodies. The highest sensitivity and specificity were achieved by the antibody detection assay using VlsE IR6 peptide. Detection of IgM-AI yielded heterogenous results and did not support the laboratory diagnosis of LNB.

Laboratory diagnosis of Lyme neuroborreliosis: a comparison of three CSF anti-Borrelia antibody assays

The diagnosis of Lyme neuroborreliosis (LNB) requires the detection of intrathecal synthesis of Borrelia-specific antibodies, but in very early disease, the sensitivity may be low. We compared the performance of the second-generation IDEIA Lyme Neuroborreliosis test (Oxoid), based on purified native flagellum antigen, with two newly developed tests based on several recombinant antigens for the diagnosis of LNB. Patients investigated for LNB during 2003 through 2007 were included (n = 175); 52 with definite LNB, four with possible LNB and 119 non-LNB patients. Serum and cerebrospinal fluid (CSF) were analysed with the IDEIA Lyme Neuroborreliosis (Oxoid), VIDAS Lyme IgG (bioMérieux) and recomBead Borrelia IgM and IgG (Mikrogen) assays. Intrathecal antibody indices (AIs) were calculated according to the manufacturers’ protocols. The IDEIA test performed with an overall sensitivity (IgM and IgG AIs taken together) of 88 % and a specificity of 99 %. The VIDAS test showed a sensitivity of 86 % and a specificity of 97 %. An overall sensitivity of 100 % and a specificity of 97 % were achieved by the recomBead test. We conclude that the three assays performed equally well regarding specificity, but our data suggest an improved diagnostic sensitivity with the recomBead Borrelia test.

Cerebrospinal fluid chemokine CXCL13 in the diagnosis of neuroborreliosis in children

The diagnosis of Lyme neuroborreliosis (LNB) requires laboratory confirmation because neurological symptoms indicative of LNB are not specific. Recent studies have suggested that a chemokine, CXCL13, could have an important role in the diagnosis of LNB. The aim of this study was to assess CXCL13 levels in the cerebrospinal fluid (CSF) of children with LNB. CSF samples were available for 57 children with symptoms indicative of LNB. Based on the presence of anti-flagella antibodies and pleocytosis in CSF, patients were divided into 3 different groups: confirmed LNB (n = 24), possible LNB (n = 16), and non-LNB (n = 17). CXCL13 levels were determined with a commercial kit (Quantikine). All 24 patients with confirmed LNB had elevated CXCL13 levels in CSF. Elevated CXCL13 was also observed in the majority of patients without anti-flagella antibodies in the CSF (possible LNB). Of the 17 non-LNB and 50 control samples, 1 was positive. In LNB, the production of CXCL13 in CSF seems to precede antibody production. Assessment of CSF CXCL13 may improve the diagnostics for children with possible LNB.

Can ELISPOT Be Applied to A Clinical Setting as A Diagnostic Utility for Neuroborreliosis?

The aim of this prospective study was to investigate the diagnostic performance of Borrelia (Bb)-induced interferon (IFN)-γ secretion detected by ELISPOT modified to be feasible for clinical laboratories as a supplementary test to the laboratory diagnosis of Lyme neuroborreliosis (LNB) in an endemic setting. Between 2002 and 2004, patients with symptoms of suspected clinical LNB were included in a study conducted on the Åland islands in the Finnish archipelago, which is a hyper-endemic area for Lyme borreliosis (LB). Fourteen patients with confirmed LNB and 103 patients with non-LNB were included, and the numbers of spontaneous and Bb-induced IFN-γ-secreting cells were assayed by the ELISPOT test. The ELISPOT assay showed a weak diagnostic performance with a sensitivity of 36% and a specificity of 82%. The findings in this study show that this ELISPOT-assay modified to be feasible in clinical routine laboratories is not useful as a supplementary diagnostic tool in the laboratory diagnosis of patients with clinically suspected LNB.

High sensitivity and specificity of the C6-peptide ELISA on cerebrospinal fluid in Lyme neuroborreliosis patients

Lyme neuroborreliosis (LNB) is a serious but treatable disease. The diagnosis of LNB poses a challenge to clinicians, and improved tests are needed. The C6-peptide ELISA is frequently used on serum but not on cerebrospinal fluid (CSF). Data on the sensitivity of the C6-peptide ELISA in CSF in patients suffering from LNB have been conflicting. Serum–CSF pairs from 59 LNB patients, 36 Lyme non-neuroborreliosis cases, 69 infectious meningitis/encephalitis controls and 74 neurological controls were tested in a C6-peptide ELISA. With the optimal cut-off of 1.1, the sensitivity of the C6-peptide ELISA for LNB patients in CSF was 95%, and the specificity was 83% in the Lyme non-neuroborreliosis patients, 96% in the infectious controls, and 97% in the neurological controls. These results suggest that the C6-peptide ELISA has a high sensitivity and good specificity for the diagnosis of LNB patients in CSF. The C6-peptide ELISA can be used on CSF in a clinical setting to screen for LNB.

Are high CSF levels of CXCL13 helpful for diagnosis of Lyme neuroborreliosis?

Neuroborreliosis (NB) is a serious complication of infection with the spirochete Borrelia burgdorferi that presents with a variety of clinical manifestations. Identification of Lyme NB and the decision to treat with IV or oral antibiotics are common challenges.1,2 For persons in endemic areas who present with classic manifestations of Lyme NB and evidence of systemic infection with B burgdorferi , the diagnosis is straightforward. However, for cases with atypical manifestations or ambiguous serology, diagnostic confirmation of Lyme NB can be difficult. The current method of choice for diagnosis of Lyme NB is the demonstration of CSF abnormalities (i.e., increased leukocyte count or elevated albumin CSF/serum ratio, indicating blood–CSF barrier dysfunction) plus the demonstration of intrathecal synthesis of Borrelia -specific antibodies.2,3 These tests suffer from important limitations. 1) Elevated CSF leukocytes or protein are not specific, and are found in other infectious and noninfectious inflammatory CNS diseases.3,4 2) Intrathecal production of Borrelia antibodies may be absent at the time of diagnostic lumbar puncture.4 3) Even the demonstration of intrathecal Borrelia -specific antibodies does not necessarily discriminate between active and past infection; specific antibody production persists for years in spite of successful treatment.5 In fact, an important problem is the difficulty determining whether …

Discriminating Lyme Neuroborreliosis from Other Neuroinflammatory Diseases by Levels of CXCL13 in Cerebrospinal Fluid

CXCL13 in cerebrospinal fluid (CSF) could be an important component for diagnosing Lyme neuroborreliosis (LNB). Levels of intrathecal CXCL13 were determined for 58 LNB patients and 210 controls; sensitivity was 88% and specificity was 89% (cutoff, 250 pg of CXCL13/ml of CSF). Elevated levels of CXCL13 can aid in the diagnosis of LNB, but levels should be interpreted with care.

CXCL13 chemokine in pediatric and adult neuroborreliosis

Diagnosis of Lyme neuroborreliosis (NB) depends on the proof of intrathecal antibody production against Borrelia burgdorferi. CXCL13 has been seen to be elevated early in NB, before antibody production has started. In this study, we determined the diagnostic role of the CXCL13 chemokine in cerebrospinal fluid (CSF) and serum for the first time in pediatric NB patients as well as in adults, compared to controls and blood donors (BD). CXCL13 levels were measured in CSF and serum of 33 children and 42 adult patients. Serum CXCL13 was measured in 300 BD. CSF CXCL13 levels were significantly elevated in definite and probable acute NB in children and adults compared to seropositive and seronegative neurological controls (P < 0.001). Serum CXCL13 levels showed great fluctuations and were not significantly elevated in NB patients. Our study suggests that CSF CXCL13 can be used as a diagnostic marker for NB in children as well. In contrast, CXCL13 serum levels show great variance even in the healthy population and are not indicative of active NB.

Borrelia Antibodies in Children Evaluated for Lyme Neuroborreliosis

We wanted to elucidate the value of Borrelia antibodies in serum and cerebrospinal fluid (CSF) for the diagnosis of Lyme neuroborreliosis (LNB). We analyzed the serological findings, by anti-flagellin assay, in 267 patients with neurological symptoms from the Stockholm area, where Lyme borreliosis is endemic. In the 70 children with LNB, intrathecal Borrelia antibody production was diagnostic and found in 50 (71%). Sixteen (23%) showed an elevated antibody titer in serum only, and 4 (7%) had no serologic findings. Borrelia IgG in serum, with or without concomitant IgM, was a specific (98%), but insensitive (43%) marker of infection. Isolated, false-positive serum IgM titers were common and found in 10 of 67 children (15%) with viral meningitis, as well as in 28 of 111 (25%) with various neurological symptoms and normal CSF. The specificity of an isolated Borrelia IgM titer in serum was 81%, and the positive predictive value for Borrelia infection only 50% in our material. On the other hand, absence of antibodies in blood had a negative predictive value of 94%, which increased to 97% if also CSF findings were included. Intrathecal antibody production is strongly supportive of an LNB diagnosis. Conversely, isolated, elevated levels of Borrelia IgM in serum occur in up to one-fourth of children with various neurological complaints, and should be interpreted with caution, especially in nonendemic areas.

Clinical usefulness of intrathecal antibody testing in acute Lyme neuroborreliosis

The aim of the study was to examine diagnostic sensitivity and temporal course of intrathecal Borrelia burgdorferi (Bb) antibody production in acute Lyme neuroborreliosis (LNB). We recruited consecutive adult patients with LNB diagnosis based on strict selection criteria. Serum and cerebrospinal fluid (CSFs) were obtained, and clinical examination was performed pre-treatment, and 13 days and 4 months post-treatment. Pre-treatment positive Bb antibody index (AI) was detected in 34 of 43 (79%). All nine pre-treatment Bb AI negative patients, and 26 of 34 pre-treatment Bb AI positive patients reported symptom duration <6 weeks. Eight patients, all Bb AI positive, reported symptom duration of 6 weeks or longer. Consequently, pre-treatment diagnostic sensitivity of Bb AI was 74% when symptom duration was <6 weeks, and 100% when 6 weeks or longer. Three patients converted from negative to positive Bb AI status post-treatment. The six patients who were persistently Bb AI negative had lower CSF cell count and protein at presentation, when compared with the patients with positive Bb AI. In conclusion, the diagnostic sensitivity of Bb AI is suboptimal in acute early LNB. Repeated post-treatment Bb AI testing, to confirm or reject LNB diagnosis, is unreliable, as the majority of initial Bb AI negative patients remained negative at follow-up.