Pseudotumor Cerebri in Lyme Disease: A Case Report and Literature Review
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Keywords:
Pseudotumor cerebri
Papilledema
Neuroborreliosis
Pleocytosis
LYME
CSF pleocytosis
Lyme Neuroborreliosis
To evaluate the frequency of clinical forms as well as laboratory and neuroimaging results of patients with diagnosed neuroborreliosis in the years 2000-2005 due to neuroborreliosis.The records of 125 patients at the age of 21-83 (mean 49 years) treated in the years 2000-2005 in the Department of Infectious Diseases and Neuroinfections, Medical University, Bialystok were subject to retrospective analysis. Diagnosis was based on case history along with a clinical picture and presence of antibodies against Borrelia burgdorferi, using ELISA test (Borrelia IgM and Borrelia IgG recombinant Biomedica). The subject of the detailed analysis was demographic data, clinical symptoms as well as subjective complaints, results of neurological examinations, the results of cerebrospinal fluid (CSF) parameters and results of serologic tests.The most frequent clinical symptoms observed were: headaches 71%, vertigo 44%, meningeal symptoms 22% and neurological paresis 27% (including facial palsy--23%). Inflammatory changes in CSF in the form of increased proteins concentration and pleocytosis were present among 34% of patients. In all cases the antibodies against B. burgdorferi were present in CSF in diagnostically significant titer. Serum presence of antibodies antiborrelia IgM was found with 55% of patients and anibodies antiborrelia IgG with 76% of patients. 17% of patients suffering from neuroborreliosis were also coinfected with tick-borne encephalitis virus. Along with the neurological symptoms, which were crucial to diagnosis, general symptoms coexisted, such as: weakness 35%, arthralgia 54% and nausea 17%. In the analyzed period of time neuroborreliosis was diagnosed in a 13% of hospitalized patient suffering from borreliosis.Absence of erythema migrans does not exclude existence of neuroborreliosis. Symptoms that may suggest presence of neuroborreliosis are not only neurological symptoms such as facial palsy, but also memory and concentration disorders and general symptoms.
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Due to the wide spectrum of clinical manifestations of Lyme neuroborreliosis laboratory investigations are necessary to confirm the diagnosis. Serum and CSF antibodies against Borrelia burgdorferi (Bb) as well as mononuclear CSF pleocytosis are usually present in patients with suspected neuroborreliosis. In some cases, however, the results may be conflicting, causing difficulty for the clinician in making a therapeutic decision. We therefore analysed the value of clinical symptoms, the presence of intrathecal antibody production against Bb with a modified IFA and a capture ELISA test, and the presence of Bb in the CSF with PCR testing in eleven children with suspected neuroborreliosis. In six of eight children with probable neuroborreliosis we could demonstrate intrathecal antibody production against Bb. In only one of these cases could Bb be detected in the CSF with the PCR assay. In two children the clinical manifestations consisting of erythema chronicum migrans and facial palsy, the presence of mononuclear CSF pleocytosis, and the presence of Bb specific antibodies in serum supported the diagnosis of neuroborreliosis, despite the absence of intrathecal specific antibodies. Three additional children with possible neuroborreliosis based on the occurrence of nonspecific clinical symptoms along with high serum antibody titers to Bb were included in the study. Intrathecal antibodies against Bb could not be detected and the PCR result was negative; therefore the diagnosis of neuroborreliosis was not substantiated in these three patients. We conclude that in addition to clinical symptoms, serological evidence and CSF findings suggestive of neuroborreliosis, the demonstration of intrathecal specific antibody synthesis against Bb may be helpful in establishing a definitive diagnosis of neuroborreliosis. The absence of CSF antibodies, however, does not necessarily indicate a lack of CNS involvement, especially if the examination is performed early in the course of disease. PCR testing in CSF is not suitable for routine application in the diagnosis of Lyme neuroborreliosis.
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The aim of this study was to evaluate the usefulness of borrelia serology (Quick ELISA C6 Borrelia assay kit) as a diagnostic tool in cases of suspected neuroborreliosis. A retrospective patient material consisting of 124 paired serum and cerebrospinal fluid samples with a positive anti-borrelia antibody index (AI) using the IDEIA Lyme Neuroborreliosis test was compared with 124 AI-negative matched control subjects. The patients were divided into four groups based on presence of pleocytosis and age above or below 12 years. The presence of positive C6 serology in AI-positive patients with pleocytosis was 89% (83/93), significantly different (p<0.01) from in patients without pleocytosis (58%, 18/31). In AI-positive patients aged > or =12 years with pleocytosis, 94% (51/54) had a positive C6 serology. Of AI-positive patients with a symptom duration of more than 30 days, 93% (27/29) were positive by the C6 test. We conclude that the C6 serum test, together with clinical evaluation, is a powerful diagnostic tool in adult (> or =12 years) European patients with suspected neuroborreliosis with a symptom duration of more than 30 days. Patients with suspected neuroborreliosis and positive C6 results should be further investigated by lumbar puncture for definite diagnosis.
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Our objective was to obtain data on patients with erythema migrans (EM) who have symptoms/signs suggesting nervous system involvement and to compare epidemiologic, clinical, and microbiologic findings in patients with and without cerebrospinal fluid (CSF) pleocytosis.Adult patients with EM and suspected early Lyme neuroborreliosis were included in this study.Of 161 patients, 31 (19%) had elevated and 130 (81%) had normal CSF cell counts. In contrast to patients with normal CSF cell counts, those with pleocytosis (1) more often reported radicular pain and more often presented with meningeal signs but less frequently complained of malaise; (2) had larger EM skin lesions despite similar duration; (3) more commonly had Borrelia garinii isolated from EM skin lesions (odds ratio for pleocytosis was 31 times higher in patients with established B. garinii skin infection compared to patients with other Borrelia species isolated from their EM skin lesion) and from CSF; and (4) more frequently fulfilled microbiologic criteria for established borrelial infection of the central nervous system. The positive predictive value of pleocytosis for microbiologically proven borrelial infection of the central nervous system (defined by isolation of Borrelia from CSF and/or demonstration of intrathecal synthesis of borrelial antibodies) was 67.9%, whereas normal CSF white cell counts ruled out Lyme neuroborreliosis with a predictive value of 91.9%.Comparison of European patients with EM who had symptoms/signs suggesting early Lyme neuroborreliosis revealed several differences in the clinical presentation and in microbiologic test results according to CSF findings.
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Lyme borreliosis has in a few years turned out to be a health problem not only in the United States, but also in many European countries. When it affects the nervous system, Lyme borreliosis acts as the great disease imitator. Because of this characteristic it is often difficult to diagnose on clinical grounds. Patients with neuroborreliosis might appear within all medical disciplines. Clinical markers, such as preceding tick bite and/or ECM, are important clues to the diagnosis. Mononuclear pleocytosis and elevated CSF protein are present in most patients with neuroborreliosis. Final evidence for the diagnosis is the demonstration of specific antibodies in serum and/or CSF. Measurement of antibody titers should be carried out in both serum and CSF, since these methods are complementary when trying to obtain a serological diagnosis of neuroborreliosis.
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Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery.Children being evaluated for NB (n = 177) in southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but no Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid. Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174).Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified.Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.
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Laboratory 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.
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We evaluated the diagnostic performance of two assays, one bead‐based assay and one enzyme‐linked immunosorbent assay (ELISA), for the determination of CXCL13 levels in cerebrospinal fluid (CSF) from patients with suspected Lyme neuroborreliosis (LNB). Patients investigated for LNB were retrospectively included (n = 132): 35 with definite LNB, 8 with possible LNB with CSF pleocytosis but normal antibody index (AI), 6 with possible LNB with elevated AI but no CSF pleocytosis and 83 non‐ LNB patients. CSF samples had been drawn before antibiotic treatment and were analysed for CXCL 13 by Quantikine ELISA (R&D Systems) and recomBead (Mikrogen). Receiver operating characteristic analyses based on the definite LNB and non‐ LNB groups revealed a best performance cut‐off of 56 pg/mL for Quantikine and 158 pg/mL for recomBead (sensitivity and specificity 100% for both assays). When applying these cut‐off levels on the study groups, the two assays performed equally well regarding sensitivity and specificity. In the group of patients with pleocytosis but negative AI , the majority of whom were children with short symptom duration, the CXCL 13 analysis supported the LNB diagnosis in half of the cases. We consider CSF ‐ CXCL 13 analysis a useful diagnostic tool, in addition to Borrelia ‐specific AI , in laboratory diagnostics of LNB.
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