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Lyme and the Brain or Lyme Neurology
Poliomyelitis-like syndrome with matching magnetic resonance features in a case of Lyme neuroborreliosis.
Charles V, Duprez TP, Kabamba B, Ivanoiu A, Sindic CJ.
Service de Neurologie, Cliniques Universitaires Saint-Luc, Universit Catholique de Louvain, Brussels, Belgium.
Publication Types:
PMID: 17878200 [PubMed - indexed for MEDLINE]
Comment in:
Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients.
Blanc F, Jaulhac B, Fleury M, de Seze J, de Martino SJ, Remy V, Blaison G, Hansmann Y, Christmann D, Tranchant C.
Department of Neurology, University Hospital of Strasbourg, Louis Pasteur University, Strasbourg, France. blanc.frdrc@free.fr
BACKGROUND: No consensual criteria exist to diagnose neuroborreliosis. The intrathecal anti-Borrelia antibody index (AI) is a necessary criterion to diagnose neuroborreliosis in Europe, but not in the United States. Previous studies to determine the diagnostic value of the AI found a sensitivity ranging from 55% to 80%. However, these studies included only typical clinical cases of meningitis or meningoradiculitis, and none had a control group with CSF anti-Borrelia antibodies. METHODS: We studied a sample of 123 consecutive patients with clinical signs of neurologic involvement and CSF anti-Borrelia antibodies. We determined the AI for all patients and a final diagnosis was made. Patients were then divided into three groups (neuroborreliosis, possible neuroborreliosis, control). RESULTS: Thirty of the 40 patients with neuroborreliosis had a positive AI (AI sensitivity = 75%). Two of the 74 patients with another neurologic diagnosis had a positive AI (AI specificity = 97%). CONCLUSION: The antibody index has a very good specificity but only moderate sensitivity. Given the lack of consensual criteria for neuroborreliosis and the absence of a "gold standard" diagnostic test, we propose pragmatic diagnostic criteria for neuroborreliosis, namely the presence of four of the following five items: no past history of neuroborreliosis, positive CSF ELISA serology, positive anti-Borrelia antibody index, favorable outcome after specific antibiotic treatment, and no differential diagnosis. These new criteria will need to be tested in a larger, prospective cohort.
PMID: 17785663 [PubMed - indexed for MEDLINE]
Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis.
Aalto A, Sjwall J, Davidsson L, Forsberg P, Smedby O.
Division of Radiology, Department of Medicine and Care, Faculty of Health Sciences, Linkping University, Linkping, Sweden. anne.aalto@imv.liu.se
BACKGROUND: Borrelia infections, especially chronic neuroborreliosis (NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. PURPOSE: To evaluate brain magnetic resonance imaging (MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. MATERIAL AND METHODS: Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- (with and without gadolinium), T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery (FLAIR) imaging were used. RESULTS: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls (no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients (rho = 0.83, P<0.01) and in controls (rho = 0.61, P<0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2-weighted imaging. CONCLUSION: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.
PMID: 17729007 [PubMed - indexed for MEDLINE]
[Clinical spectrum of neuroborreliosis]
[Article in Polish]
Owecki MK, Kozubski W.
Katedry i Kliniki Neurologii, Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu. michal.owecki@wp.pl
Lyme disease is a multisystem infectious disease with a wide variety of symptoms involving the skin as well as nervous, musculosceletal and cardiovascular systems. Lyme disease is caused by spirochaete Borrelia burgdorferi transmitted by Ixodes tics in endemic regions. The diverse manifestations of neuroborreliosis require it to be included in differential diagnosis of many neurological disorders. The paper reviews the spectrum of clinical symptoms of nervous system involvement in early and late Lyme disease.
Publication Types:
PMID: 17726871 [PubMed - indexed for MEDLINE]
Comment on:
Unexplained cerebral vasculitis and stroke: keep Lyme neuroborreliosis in mind.
Topakian R, Stieglbauer K, Aichner FT.
Publication Types:
PMID: 17706557 [PubMed - indexed for MEDLINE]
[Diagnostic difficulties in neuroborreliosis in children]
[Article in Polish]
Talarek E, Duszczyk E, Zarnowska H.
Klinika Chorb Zakaznych Wieku Dzieciecego AM w Warszawie.
OBJECTIVE: Analysis of clinical picture in children hospitalized because of suspicion of neuroborreliosis and evaluation of usefulness of testing serum and cerebrospinal fluid (CSF) for specific antibodies. MATERIAL AND METHODS: 23 children (age: 13 months - 15.5 years) were hospitalized: 11 children with facial palsy, 2 children with radiculopathy and 10 children with headache. In 21 children lumbar puncture and CSF examination was done. Serum of all children and CSF of 21 children were tested by ELISA for specific antibodies (IDEIA DakoCytomation). RESULTS: Meningeal signs in physical examination were found in 4 children and inflammatory CSF changes in 8 children. Specific antibodies in sera of 19 children and in CSF of 7 children. Neuroborreliosis was diagnosed in 12 children: in 9 facial palsy (in 6 with inflammatory CSF changes), in 2 Bannwarth's syndrome and in 1 aseptic meningitis. Diagnosis was confirmed by detection of specific antibodies in sera of 10 children and in CSF of 6 children. CONCLUSIONS: Meningitis in the course of neuroborreliosis is not always accompanied by meningeal signs. Positive serology is not an unequivocal confirmation of neuroborreliosis especially if symptoms are nonspecific (e.g. headache).
Publication Types:
PMID: 17702442 [PubMed - indexed for MEDLINE]
[Clinical forms of neuroborreliosis--the analysis of patients diagnosed in department of infectious diseases and neuroinfection medical academy in Bialystok between 2000-2005]
[Article in Polish]
Zajkowska J, Czupryna P, Kusmierczyk J, Ciemerych A, Ciemerych M, Kondrusik M, Pancewicz S, Grygorczuk S, Hermanowska-Szpakowicz T.
Klinika Chorb Zakaznvch i Neuroinfekcii AM w Bialvmstoku.
Increased morbidity of viral tick borne encephalitis since the 90's indicates growing risk of Rother tick borne diseases, including neuroborreliosis. Analysis of demographical, epidemiological and clinical data of patients hospitalised in Departament on Infectious Diseases and Neuroinfections in years 2000-2005 revealed that among patients with Lyme disease 13% were with neuroborreliosis with broad spectrum of neurologic symptoms as cranial nerves paresis (mainly n.VII), as well concentration and memory disturbances, and general symptoms. Some of patiets did not recall tick bite and did not present earlier borreliosis symptoms. Imaging only supports recognitio.
Publication Types:
PMID: 17702440 [PubMed - indexed for MEDLINE]
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Antibodies to recombinant decorin-binding proteins A and B in the cerebrospinal fluid of patients with Lyme neuroborreliosis.
Panelius J, Sillanp H, Seppl I, Sarvas H, Lahdenne P.
Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland. jaana.panelius@helsinki.fi
Cerebrospinal fluid (CSF) and serum samples from 34 patients with proven neuroborreliosis (NB) and 22 patients with suspected neuroborreliosis (SNB) from Finland were analysed for antibodies to decorin-binding proteins A (DbpA) and B (DbpB). Antibodies to recombinant protein antigens originating from Borrelia burgdorferi sensu stricto, B. afzelii, or B. garinii species were studied by enzyme-linked immunosorbent assay (ELISA). Of the 34 patients with NB, 100% of the CSF and 88% of the serum samples had IgG antibodies to 1 to 3 variants of DbpA and 79% of the CSF and 70% of the serum samples were positive for 1 to 3 DbpB variants. Antibodies to DbpB seemed to be associated with lymphocytic pleocytosis in the CSF and short duration of the disease, whereas antibodies to DbpA in the CSF were observed irrespective of the duration of the disease and lymphocytic pleocytosis. Among the variant antigens, CSF reactivity was mainly with the DbpB from B. garinii, whereas positivity with the DbpA from B. afzelii or B. garinii predominated. The results suggest that CSF antibodies to DbpB might be useful as a marker of active infection whereas antibodies to DbpA seem to persist a long time after acute phases of NB.
Publication Types:
PMID: 17701715 [PubMed - in process]
[Concentrations of pro-inflammatory cytokines IFN-gamma, IL-6, IL-12 and IL-15 in serum and cerebrospinal fluid in patients with neuroborreliosis undergoing antibiotic treatment]
[Article in Polish]
Pancewicz SA, Kondrusik M, Zajkowska J, Grygorczuk S.
Akademia Medyczna w Bialymstoku, Klinika Chorb Zakaznych i Neuroinfekcji. spancewicz@interia.pl
Pathogenesis of Lyme disease, including neuroborreliosis, remains unclear. However, pro-inflammatory cytokines seem to be involved and might be used to monitor the course of the disease. It has been also shown that B. burgdorferi protects itself from elimination by modulating function of the host's immune system. THE AIM OF THIS STUDY: The purpose of this study was to evaluate the serum and cerebrospinal fluid (CSF) concentrations of selected cytokines in patients with neuroborreliosis and their change during antibiotic treatment. MATERIAL AND METHODS: The group of 25 patients was examined, all undergoing antibiotic therapy due to meningitis caused by Borrelia burgdorferi infection. The group included 10 (40%) females and 15 (60%) males in the mean age x = 42,3 years. The control group for serum measurements consisted of 25 healthy individuals (mean age x =43, 1) while control group for CSF study included 10 patients (aged x = 53,5 years) from whom CSF with normal parameters was taken during diagnostic procedures neurosurgical. We examined serum and CSF before and after antibiotics for concentrations of interferon-gamma (INF-gamma), interleukin-6 (IL-6), interleukin-12 (IL-12) and interleukin-15 (IL-15). RESULTS: In the first examination the significant increase of IFN-gamma, IL-6, IL-2, IL-15 serum and CSF concentration was detected in comparison to control group. After 4-weeks antibiotic treatment the concentrations of studied cytokines decreased significantly in serum as well as in CSF but remained increased in comparison with controls. CONCLUSIONS: Although antibiotic treatment leads to withdrawal of clinical symptoms of neuroborreliosis and normalization of CSF general parameters, pro-inflammatory cytokines' concentrations in serum and CSF remain elevated. It may be explained by the persistence of inflammatory conditions, perhaps related to surviving of a fraction of Borrelia burgdorferi spirochetes within CNS tissue. This phenomenon might lead to development of chronic CNS lesions.
Publication Types:
PMID: 17684925 [PubMed - indexed for MEDLINE]
Clinical usefulness of intrathecal antibody testing in acute Lyme neuroborreliosis.
Lj¿stad U, Skarpaas T, Mygland A.
Department of Neurology, S¿rlandet Sykehus HF, Kristiansand, Norway. unn.ljostad@sshf.no
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.
Publication Types:
PMID: 17662007 [PubMed - indexed for MEDLINE]
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EEG with triphasic waves in Borrelia burgdorferi meningoencephalitis.
Eriksson B, Wictor L.
Division of Clinical Neurology, Lund University Hospital, Lund, Sweden. Bengt.B.Eriksson@skane.se
We describe a case of encephalopathy in which the clinical picture and triphasic waves in the EEG indicated a metabolic cause. However, the illness was caused by neuroborreliosis. The occurrence of triphasic waves in the EEG is a strong evidence of metabolic encephalopathy, but triphasic waves are not specific for metabolic encephalopathy. Triphasic waves have been described in a number of non-metabolic encephalopaties and structural brain lesions. To our knowledge, this is the first report of triphasic waves in Borrelia burgdorferi meningoencephalitis.
Publication Types:
PMID: 17661801 [PubMed - indexed for MEDLINE]
[Neuroborreliosis or borrelia hysteria. This case becomes a nightmare!]
[Article in German]
Aberer E.
Universittsklinik, fr Dermatologie, Medizinische Universitt Graz, Auenmbrugger Platz 8, A-8036 Graz, Osterreich.
Publication Types:
PMID: 17615738 [PubMed - indexed for MEDLINE]
Sensitivity and specificity of a commercial C6 peptide enzyme immuno assay in diagnosis of acute Lyme neuroborreliosis.
Skarpaas T, Lj¿stad U, S¿bye M, Mygland A.
Microbiology Unit, Division of Laboratory Medicine, S¿rlandet Hospital HF, Service Box 416, 4604, Kristiansand, Norway. tone.skarpaas@sshf.no
The purpose of this study was to evaluate the diagnostic sensitivity and specificity of a commercial C6 enzyme immuno assay, QuickC6, in acute Lyme neuroborreliosis (LNB) in endemic areas. Paired sera and cerebral spinal fluids (CSFs) from 60 patients with definite LNB, eight patients with possible LNB, 18 patients with conditions mimicking LNB and 42 persons with noninfectious neurological disease were examined. The case definition of LNB was based on strict criteria during a prospective 4-month follow-up. The sensitivity of QuickC6 was 98% both in sera and CSFs, and the diagnostic specificity was 61% in sera and 88% in CSFs. QuickC6 is a sensitive, simple and cost-effective screening test in serum and CSF in diagnosis of acute LNB. Specificity needs further evaluation.
Publication Types:
PMID: 17605055 [PubMed - indexed for MEDLINE]
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Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study.
Oksi J, Nikoskelainen J, Hiekkanen H, Lauhio A, Peltomaa M, Pitkranta A, Nyman D, Granlund H, Carlsson SA, Seppl I, Valtonen V, Viljanen M.
Department of Medicine, Turku University Central Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland. jarmo.oksi@utu.fi
Despite rather strict recommendations for antibiotic treatment of disseminated Lyme borreliosis (LB), evidence-based studies on the duration of antibiotic treatment are scarce. The aim of this multicenter study was to determine whether initial treatment with intravenous ceftriaxone (CRO) for 3 weeks should be extended with a period of adjunct oral antibiotic therapy. A total of 152 consecutive patients with LB were randomized in a double-blind fashion to receive either amoxicillin (AMOX) 1 g or placebo (PBO) twice daily for 100 days. Both groups received an initial treatment of intravenous CRO 2 g daily for 3 weeks, followed by the randomized drug or PBO. The outcome was evaluated using the visual analogue scale at the follow-up visits. The final analysis included 145 patients, of whom 73 received AMOX and 72 PBO. Diagnoses of LB were categorized as either definite or possible, on the basis of symptoms, signs, and laboratory results. The diagnosis was definite in 52 of the 73 (71.2%) AMOX-treated patients and in 54 of the 72 (75%) PBO patients. Of the patients with definite diagnoses, 62 had neuroborreliosis, 45 arthritis or other musculoskeletal manifestations, and 4 other manifestations of LB. As judged by the visual analogue scale and patient records, the outcome after a 1-year follow-up period was excellent or good in 114 (78.6%) patients, controversial in 14 (9.7%) patients, and poor in 17 (11.7%) patients. In patients with definite LB, the outcome was excellent or good in 49 (92.5%) AMOX-treated patients and 47 (87.0%) PBO patients and poor in 3 (5.7%) AMOX-treated patients and 6 (11.1%) PBO patients (difference nonsignificant, p = 0.49). Twelve months after the end of intravenous antibiotic therapy, the levels of antibodies against Borrelia burgdorferi were markedly decreased in 50% of the patients with definite LB in both groups. The results indicate that oral adjunct antibiotics are not justified in the treatment of patients with disseminated LB who initially receive intravenous CRO for 3 weeks. The clinical outcome cannot be evaluated at the completion of intravenous antibiotic treatment but rather 6-12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies do not seem to provide any useful information for further care of the patient.
Publication Types:
PMID: 17587070 [PubMed - indexed for MEDLINE]
[Lymphadenopathy and absences]
[Article in German]
Staub E, Strozzi S, Aebi C.
Medizinische Poliklinik, Universittskinderklinik, Inselspital Bern.
A 6-year-old boy presented with deterioration of general well-being during several weeks, headache and swelling of lymph nodes in the neck. In addition, the parents reported brief episodes resembling typical absence seizures. Serological tests and the examination of cerebrospinal fluid revealed neuroborreliosis. At the same time, electroencephalography showed characteristic patterns of absence epilepsy. The boy's condition improved rapidly during a 2-week course of intravenous ceftriaxone and after initiation of antiepileptic therapy. To our knowledge, absence epilepsy has not previously been reported in association with neuroborreliosis. We consider the two conditions to be coincidental.
Publication Types:
PMID: 17566418 [PubMed - indexed for MEDLINE]
Borrelia garinii induces CXCL13 production in human monocytes through Toll-like receptor 2.
Rupprecht TA, Kirschning CJ, Popp B, Kastenbauer S, Fingerle V, Pfister HW, Koedel U.
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, D-81377 Munich, Germany.
Recent studies have suggested an important role for the B-cell-attracting chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms, Borrelia garinii (the Borrelia species most frequently found in NB patients) and Treponema pallidum, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety N-palmitoyl-S-(bis[palmitoyloxy]propyl)cystein (Pam(3)C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam(3)C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with B. garinii, this suggests that TLR2 is a major mediator of Borrelia-induced secretion of CXCL13 from human monocytes.
Publication Types:
PMID: 17562761 [PubMed - indexed for MEDLINE]
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Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT Jr; Quality Standards Subcommittee of the American Academy of Neurology.
Department of Neurosciences, Overlook Hospital, NYU School of Medicine, Summit, NJ, USA.
OBJECTIVE: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed? METHODS: The authors analyzed published studies (1983-2003) using a structured review process to classify the evidence related to the questions posed. RESULTS: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis. CONCLUSIONS: There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (> or =8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A).
Publication Types:
PMID: 17522387 [PubMed - indexed for MEDLINE]
 
Pathogen specificity and autoimmunity are distinct features of antigen-driven immune responses in neuroborreliosis.
Kuenzle S, von Bdingen HC, Meier M, Harrer MD, Urich E, Becher B, Goebels N.
Clinical Neuroimmunology Unit, Department of Neurology, University Hospital Zrich, Frauenklinikstrasse 26, CH-8091 Zrich, Switzerland.
Neuroborreliosis (NB) is a chronic infectious disease of the central nervous system (CNS) caused by a tick-borne spirochete, Borrelia burgdorferi. In addition to direct effects of the causative infectious agent, additional immunity-mediated mechanisms are thought to play a role in the CNS pathology of NB. In order to further understand the involvement of humoral immune mechanisms in NB, we dissected the intrathecal antibody responses down to the single-plasma-cell level. Starting with single-cell reverse transcription-PCR of fluorescence-activated cell sorter-sorted cerebrospinal fluid plasma cells from an NB patient, we identified expanded clones and resurrected the antigen specificity of their secreted antibodies through recombinant expression of the correctly paired immunoglobulin heavy- and light-chain genes as monoclonal antibodies (MAbs). As expected, we found specificity for the causative infectious agent, B. burgdorferi, among the clonally expanded plasma cell (cePC)-derived MAbs. However, from an independent cePC of the same patient, we could derive MAbs specific for human CNS myelin, without detectable cross-reactivity with B. burgdorferi antigens. While reactivity against B. burgdorferi is a known feature of humoral immune responses in NB, we show (i) that immune responses specific for self antigens may be a distinct feature of CNS infections independent of pathogen reactivity and (ii) that humoral autoimmunity in NB (since found in cePC) is the result of a truly antigen-driven immune response. Our findings indicate that in NB mechanisms may be at play that induce distinct immune responses specific for pathogen and self antigens independent from "molecular mimicry."
Publication Types:
PMID: 17517881 [PubMed - indexed for MEDLINE]
[Role of biological assays in the diagnosis of Lyme borreliosis presentations. What are the techniques and which are currently available?]
[Article in French]
De Martino SJ.
Laboratoire associ au CNR Borrelia, laboratoire de bactriologie, hpitaux universitaires de Strasbourg, 3, rue Koeberl, 67000 Strasbourg, France. sylvie.demartino@medecine.u-strasbg.fr
The biological diagnosis of Borrelia burgdorferi sensu lato infection is usually made by antibody detection in patient sera. Thus, serological testing (Elisa, immunoblotting) is essential for a biological diagnosis. Specific antibody detection is usually done in serum and CSF of patients suspected of Lyme borreliosis. Laboratories must follow European recommendations to validate these assays in routine practice. Antibody detection lacks sensitivity in the early cutaneous phase of the infection. Therefore, serological testing is not recommended for the diagnosis of erythema migrans. The interpretation of serology must take into account the variability of Elisa sensitivity and specificity and the lack of standardization for Western-blotting in Europe. Besides these indirect diagnosis techniques, there is also direct detection of spirochetes by culture or by in vitro DNA amplification but these require adequate samples. These molecular tests must not be performed routinely, but only for specific clinical situations and in specialized laboratories only.
Publication Types:
PMID: 17512148 [PubMed - indexed for MEDLINE]
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Comment in:
Lyme neuroborreliosis: infection, immunity, and inflammation.
Pachner AR, Steiner I.
Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. pachner@umdnj.edu
Lyme neuroborreliosis (LNB), the neurological manifestation of systemic infection with the complex spirochaete Borrelia burgdorferi, can pose a challenge for practising neurologists. This Review is a summary of clinical presentation, diagnosis, and therapy, as well as of recent advances in our understanding of LNB. Many new insights have been gained through work in experimental models of the disease. An appreciation of the genetic heterogeneity of the causative pathogen has helped clinicians in their understanding of the diverse presentations of LNB.
Publication Types:
PMID: 17509489 [PubMed - indexed for MEDLINE]
Central nervous system involvement of previously undiagnosed chronic lymphocytic leukemia in a patient with neuroborreliosis.
Kalac M, Suvic-Krizanic V, Ostojic S, Kardum-Skelin I, Barsic B, Jaksica B.
Department of Medicine, Merkur University Hospital, Zagreb Medical School, Zagreb, Croatia. mkalac@mef.hr
Leukemic involvement of the central nervous system (CNS) in previously undiagnosed chronic lymphocytic leukemia (CLL) is very rare. We report the case of a 62-year-old man with neuroborreliosis in which cytologic, immunocytochemical, and flow cytometry analyses revealed the presence of clonal B-lymphocytes in the cerebrospinal fluid (CSF). After the patient received antimicrobial therapy, his meningeal symptoms cleared up, and the number of cells in the CSF decreased. Monoclonal lymphocytes were still detectable at the same percentage, however, despite systemic chlorambucil therapy. The application of intrathecal dexamethasone therapy led to the disappearance of B-cell CLL (B-CLL) cells in the CSF. We presumed that the neuroborreliosis enabled the transmigration of leukocytes, including B-CLL cells, across the blood-brain barrier via activation of matrix metalloproteinase 9, an enzyme known to open the blood-brain barrier.
Publication Types:
PMID: 17483076 [PubMed - indexed for MEDLINE]
Cerebrospinal-fluid profile in neuroborreliosis and its diagnostic significance.
Bednrova J.
Department of Clinical Microbiology, Faculty Hospital Brno, Czechia. bednarovaj@fnbrno.cz
Selected cerebrospinal-fluid (CSF) parameters (intrathecal synthesis of Borrelia-specific antibodies, oligoclonal IgG bands, CSF-to-serum quotient of albumin as a marker of blood-CSF barrier function and cytology) and typical CSF profile in neuroborreliosis were evaluated with the aim of elucidating possible clinical and laboratory similarities of neuroborreliosis (NB) and other neurological diseases (OND). From the cohort of 58 patients (38 diagnosed for NB, 20 with OND) NB patients had positive Borrelia-specific IgG antibodies in 97 % and positive Borrelia-specific IgM antibodies in 55 %; oligoclonal IgG bands were detected in 55%. The blood-CSF barrier was impaired in 89%, positive cytology was detected in 97% of the NB patients. Evaluation of specific intrathecal synthesis improves CSF diagnosis of NB, therefore, a combined CSF analysis has to be considered along with the clinical picture and medical history when formulating the diagnosis of NB.
PMID: 17455797 [PubMed - indexed for MEDLINE]
Comment in:
Case records of the Massachusetts General Hospital. Case 11-2007. A 59-year-old man with neck pain, weakness in the arms, and cranial-nerve palsies.
Greer DM, Schaefer PW, Plotkin SR, Hasserjian RP, Steere AC.
Department of Neurology, Massachusetts General Hospital, USA.
Publication Types:
PMID: 17429088 [PubMed - indexed for MEDLINE]
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Tick-borne encephalitis with polyradiculitis documented by MRI.
Pfefferkorn T, Feddersen B, Schulte-Altedorneburg G, Linn J, Pfister HW.
Department of Neurology, Klinikum Grosshadern, University of Munich, Munich, Germany. thomas.pfefferkorn@med.uni-muenchen.de
Publication Types:
PMID: 17420411 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis presenting as the syndrome of inappropriate antidiuretic hormone secretion.
Perkins MP, Shumway N, Jackson WL Jr.
Walter Reed Army Medical Center, Washington DC, USA. Michael.Perkins@NA.AMEDD.ARMY.MIL
We describe a case of a patient presenting with the syndrome of inappropriate hormone secretion (SIADH) caused by Lyme neuroborreliosis.
Publication Types:
PMID: 17406193 [PubMed - indexed for MEDLINE]
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Seronegative Lyme neuroborreliosis in a patient on treatment for chronic lymphatic leukemia.
Harrer T, Geissdrfer W, Schoerner C, Lang E, Helm G.
Dept. of Medicine III, University Hospital Erlangen, Krankenhausstr. 12, 91054, Erlangen, Germany. Thomas.Harrer@med3.imed.uni-erlangen.de
We report on a patient who developed seronegative Lyme neuroborreliosis complicating chemotherapy for chronic lymphatic leukemia. After the fifth cycle of chemotherapy (FCR: fludarabine, cyclophosphamide, rituximab and prednisone) the 63-year-old patient developed night sweat, arthralgia in elbows, wrists, proximal interphalangeal joints (PIPs) and strong neuropathic pain in both legs, followed by paresthesia and hypesthesia in the feet, arms and face. Laboratory analysis revealed an elevated C-reactive protein (CRP), a slight elevation of liver enzymes and decreased IgG levels. Cerebrospinal fluid (CSF) analysis showed a lymphomononuclear pleocytosis and an elevation of protein. A broad diagnostic work-up was negative including a negative Borrelia IgG and IgM ELISA. The patient did not remember recent tick bites, but after specific questioning he recollected a transient erythema on his leg developing just before the start of the last cycle of chemotherapy. As the combination of neuropathic pain and arthralgia, the transient erythema and the lymphomononuclear pleocytosis raised the suspicion of Lyme neuroborreliosis, the patient was treated for 3 weeks with ceftriaxone. On therapy all symptoms resolved and CRP normalized. Retrospective PCR analysis of a CSF sample confirmed the clinical diagnosis by detecting Borrelia garinii DNA. This case demonstrates that in immunosuppressed patients borrelial serology may be negative and that additional diagnostic approaches (including tests for direct Borrelia detection) may be needed to demonstrate borrelial infection.
Publication Types:
PMID: 17401717 [PubMed - indexed for MEDLINE]
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[Ocular manifestations of Lyme disease]
[Article in French]
Bodaghi B.
Service d'ophtalmologie, universit Paris-VI, CHU de la Piti-Salptrire, 47-83, boulevard de l'Hpital, 75651 Paris cedex 13, France. bahram.bodaghi@psl.ap-hop-paris.fr
Despite the wide spectrum of clinical entities, eye involvement remains a rare event in patients with Lyme borreliosis. Most of ocular manifestations occur during the late phase of the disease. The infection needs to be considered along with more conventional causes of ocular inflammation, particularly in regions where Lyme disease is common. The pathogenesis of this condition remains controversial. Direct ocular infection and a delayed hypersensitivity mechanism may be involved at different disease stages. Uveitis and optic neuritis are the most common ocular complications. Serological testing lacks sensitivity and specificity. In atypical cases, ocular fluids sampling and analysis may be proposed. PCR seems to be an interesting diagnostic tool, allowing genotypic analysis. In the majority of cases, therapeutic strategy should be based on the association of antibiotics and corticosteroids. A new course of antibiotics may be prescribed to patients with chronic or relapsing inflammation due to bacterial persistence in ocular tissues.
Publication Types:
PMID: 17376626 [PubMed - indexed for MEDLINE]
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[Clinical manifestations and epidemiological aspects leading to a diagnosis of Lyme borreliosis: neurological and psychiatric manifestations in the course of Lyme borreliosis]
[Article in French]
Crange A.
Service de neurologie, centre hospitalier universitaire Henri-Mondor, APHP, universit Paris-XII, 94000 Crteil, France. alain.creange@hmn.ap-hop-paris.fr
Lyme disease is associated with various systemic and neurological manifestations. The neurological and psychiatric manifestations of Lyme disease are more frequently observed during its secondary phase (stage 2) than during its late tertiary phase (stage 3). In stage 2, cerebrospinal fluid and bacterial tests are consistent with the ongoing infection. Painful meningoradiculitis, encephalomyelitis and encephalitis, and symptoms of depression are the most characteristic at this stage. The diagnosis should be based on the association of clinical, epidemiological, and biological features. Adequate treatment usually leads to recovery. In stage 3 of the disease, the link between neurological manifestations and initial infection is uncertain. Distal axonal polyneuropathy and chronic encephalopathy are the most frequently reported presentations.
Publication Types:
PMID: 17368785 [PubMed - indexed for MEDLINE]
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[Treatment of Lyme borreliosis secondary and tertiary stages]
[Article in French]
Hansmann Y.
Service des maladies infectieuses et tropicales, hpitaux universitaires de Strasbourg, 1, place de l'Hpital, BP 426, 67091 Strasbourg cedex, France. yves.hansmann@chru-strasbourg.fr
The treatment of secondary and tertiary Lyme borreliosis is difficult because of antibiotic lack of efficacy. This fact may be explained by several factors: the specific pathophysiology, involving not only the presence of bacteria, but also immunological reactions. There is no specific method of diagnosis resulting in difficulties for good indication of treatment and to evaluate treatment efficacy. The literature review shows that ceftriaxone and doxycycline are the two most efficient antibiotics in this indication. Even if the methodology of the published studies is not always convincing, these two antibiotics proved their efficacy in articular as well as in neurological forms of the disease. In the late stage of borreliosis, antibiotics are less efficient. Various treatment modalities with different dosage or duration of treatment cannot let us conclude on a convincing regimen.
Publication Types:
PMID: 17367972 [PubMed - indexed for MEDLINE]
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Myasthenia and neuroborreliosis with excessively high acetylcholine-receptor antibodies.
Finsterer J.
Krankenanstalt Rudolfstiftung, Vienna, Austria. duarte@aonmail.at
In a 29-y-old male with neuroborreliosis, partially responsive to ceftriaxone, myasthenia gravis with acetylcholine-receptor antibodies elevated almost 1000 times the upper reference limit was diagnosed. Pyridostigmine resolved all remaining neurological deficits. During a 1-y follow-up the patient remained symptom free, despite persistently high acetylcholine-receptor antibodies. They were attributed to epitope homology of the acetylcholine receptors and Borrelia surface antigens.
Publication Types:
PMID: 17366045 [PubMed - indexed for MEDLINE]
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Complete recovery from an unusual cause of coma.
Rovers JM, Louwerse ES, de Jager CP.
Department of Neurology, St. Elisabeth Hospital, Hilvarenbeekseweg 60, Postbus 90151, 5000 LC, Tilburg, The Netherlands. jmprovers@hotmail.com
Publication Types:
PMID: 17325838 [PubMed - indexed for MEDLINE]
Comment on:
Predictive model for Lyme meningitis: a reply.
Avery RA, Frank G, Eppes SC.
Publication Types:
PMID: 17200294 [PubMed - indexed for MEDLINE]
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Lyme borreliosis and multiple sclerosis are associated with primary effusion lymphoma.
Batinac T, Petranovic D, Zamolo G, Petranovic D, Ruzic A.
Department of Dermatovenerology, Rijeka University Hospital, Kresimirova 42, 51000 Rijeka, Croatia.
Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by chronic inflammation and demyelination. Studies suggested that the viral, especially Epstein-Barr virus infection, and bacterial infections, especially Borrelia burgdorferi infection, play a role in etiology of MS. MS prevalence parallels the distribution of the Lyme disease pathogen B. burgdorferi. Criteria used for diagnosis of MS can also be fulfilled in other conditions such as Lyme disease, a multisystem disorder resulting from infection by the tick-borne spirochete, B. burgdorferi. In the late period of Lyme disease demyelinating involvement of central nervous system can develop and MS can be erroneously diagnosed. A Lyme borreliosis can mimick central nervous system lymphoma. Also, B. burgdorferi has been implicated not only in etiology of MS, but also in etiology of lymphoma. Studies suggested that there is an increased risk of non-Hodgkin lymphoma in patients, who had a history of autoimmune diseases such as MS and that both non-Hodgkin's lymphomas and Hodgkin's disease were associated with Epstein-Barr virus infection. A small group of lymphomas called primary effusion lymphomas (PEL) is a recently individualized form of non-Hodgkin's lymphoma (WHO classification) that exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. These lymphomas have also been linked to Epstein-Barr virus and human herpes virus type 8 infections but virus negative cases have been described. Therefore, we propose that MS and neuroborreliosis are linked to central nervous system primary effusion lymphomas. As a first step in confirming or refuting our hypotheses, we suggest a thorough study of CSF in the patients suspected for the diagnosis of MS and Lyme borreliosis.
PMID: 17197115 [PubMed - indexed for MEDLINE]
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Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals.
Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, Ekerfelt C.
Division of Clinical Immunology, Faculty of Health Sciences, University of Linkping, Sweden. sara.jarefors@imk.liu.se
Lyme borreliosis (LB) can, despite adequate antibiotic treatment, develop into a chronic condition with persisting symptoms such as musculoskeletal pain, subjective alteration of cognition and fatigue. The mechanism behind this is unclear, but it has been postulated that an aberrant immunological response might be the cause. In this study we investigated the expression of the T helper 1 (Th1) marker interleukin (IL)-12Rbeta2, the marker for T regulatory cells, forkhead box P3 (FoxP3) and the cytokine profile in patients with a history of chronic LB, subacute LB, previously Borrelia-exposed asymptomatic individuals and healthy controls. Fifty-four individuals (12 chronic LB, 14 subacute LB, 14 asymptomatic individuals and 14 healthy controls) were included in the study and provided a blood sample. Mononuclear cells were separated from the blood and stimulated with antigens. The IL-12Rbeta2 and FoxP3 mRNA expression was analysed with real-time reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of IL-12Rbeta2 on CD3(+), CD4(+), CD8(+) and CD56(+) cells was assessed by flow cytometry. Furthermore, the secretion of interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL-12p70 and IL-13 was analysed by enzyme-linked immunospot (ELISPOT) and/or enzyme-linked immunosorbent assay (ELISA). Chronic LB patients displayed a lower expression of Borrelia-specific IL-12Rbeta2 on CD8(+) cells and also a lower number of Borrelia-specific IFN-gamma-secreting cells compared to asymptomatic individuals. Furthermore, chronic LB patients had higher amounts of Borrelia-specific FoxP3 mRNA than healthy controls. We speculate that this may indicate that a strong Th1 response is of importance for a positive outcome of a Borrelia infection. In addition, regulatory T cells might also play a role, by immunosuppression, in the development of chronic LB.
Publication Types:
PMID: 17177959 [PubMed - indexed for MEDLINE]
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Comparison of immunofluorescence assay (IFA) and LIAISON in patients with different clinical manifestations of Lyme borreliosis.
Cerar T, Ruzic-Sabljic E, Cimperman J, Strle F.
Institute of Microbiology and Immunology, Medical Faculty Ljubljana, University of Ljubljana, Slovenia. tjasa.cerar@mf.uni-lj.si
Serological tests for detection of borrelial antibodies are frequently used in laboratory diagnostics of Lyme borreliosis. Unfortunately these tests are not standardized and the results obtained with different assays may not be concordant. The aim of the present study was to compare two different serological tests, IFA and LIAISON, for detection of Borrelia burgdorferi sensu lato IgM and IgG antibody. We analyzed the serological immune response in 383 patients with different clinical manifestations of Lyme borreliosis and in 49 healthy blood donors. LIAISON detected IgM and IgG antibodies more often than IFA in all groups of patients except those with chronic Lyme borreliosis. The differences were significant for IgM and IgG antibodies in patients with solitary erythema migrans and in those with early disseminated Lyme borreliosis. There was no significant difference in the specificity of the two tests.
Publication Types:
PMID: 17160608 [PubMed - indexed for MEDLINE]
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What we have learned about Lyme borreliosis from studies in children.
Sood SK.
Pediatric Infectious Diseases, Schneider Children's Hospital at North Shore, Albert Einstein College of Medicine, Manhasset, NY 11030, USA. sood@lij.edu
Although pediatric Lyme borreliosis (LB) need not be a separate nosological entity, there are clinically important differences in presentation, antibiotic regimens and outcomes in children, which provide lessons that can be extrapolated to the disease as it affects adults. A large proportion of the worldwide data is obtained from children. The aim of this presentation is not to present an exhaustive review of the pediatric literature, but to review a selection of pediatric studies that have made a significant contribution to our body of knowledge in Lyme borreliosis.
Publication Types:
PMID: 17160601 [PubMed - indexed for MEDLINE]
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Complement activation in Lyme neuroborreliosis--increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS.
Henningsson AJ, Ernerudh J, Sandholm K, Carlsson SA, Granlund H, Jansson C, Nyman D, Forsberg P, Nilsson Ekdahl K.
Department of Infectious Diseases, Ryhov County Hospital, 551 85, Jnkping, and Division of Clinical Immunology, Department of Molecular and Clinical Medicine, Linkping University, Sweden. Anna.Henningsson.Jonsson@lj.se
A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.
Publication Types:
PMID: 17157926 [PubMed - indexed for MEDLINE]
[Trigeminal neuralgia, neuroborreliosis, and herpes: finding the intruder]
[Article in French]
Abetel G, Danthe C, Hungerbhler P, Lavanchy JD, Nicollier A, Russ D.
Publication Types:
PMID: 17073180 [PubMed - indexed for MEDLINE]
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Cerebrospinal fluid-infiltrating CD4+ T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early lyme encephalitis.
Lnemann JD, Gelderblom H, Sospedra M, Quandt JA, Pinilla C, Marques A, Martin R.
Neuroimmunology Branch, Cellular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Neurological manifestations of Lyme disease are usually accompanied by inflammatory changes in the cerebrospinal fluid (CSF) and the recruitment of activated T cells into the CSF compartment. In order to characterize the phenotype and identify target antigens of CSF-infiltrating T cells in early neuroborreliosis with central nervous system (CNS) involvement, we combined T-cell cloning, functional testing of T-cell responses with positional scanning synthetic combinatorial peptide libraries, and biometric data analysis. We demonstrate that CD4+ gamma interferon-producing T cells specifically responding to Borrelia burgdorferi lysate were present in the CSF of a patient with acute Lyme encephalitis. Some T-cell clones recognized previously uncharacterized B. burgdorferi epitopes which show a specific enrichment for lysine, such as the heat shock-induced chaperone HSP90. Degenerate T-cell recognition that included T-cell responses to borrelia-specific and CNS-specific autoantigens derived from the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) could be demonstrated for one representative clone. Our results show that spirochetal antigen-specific and Th1-polarized CD4+ lymphocytes infiltrate the CSF during monophasic CNS symptoms of Lyme disease and demonstrate that cross-recognition of CNS antigens by B. burgdorferi-specific T cells is not restricted to chronic and treatment-resistant manifestations.
Publication Types:
PMID: 17060473 [PubMed - indexed for MEDLINE]
Reinfection with Lyme borreliosis presenting as a painful polyradiculopathy: Bannwarth's, Beevor's and Borrelia.
Miller RF, O'Connell S, Manji H.
Publication Types:
PMID: 17043300 [PubMed - indexed for MEDLINE]
Central nervous system borreliosis mimicking a pontine tumour.
Latsch K, Tappe D, Warmuth-Metz M, Hebestreit H.
Children's Hospital, and Institute of Hygiene and Microbiology, University of Wrzburg, D-97080 Wrzburg, Germany. Latsch_K@kinderklinik.uni-wuerzburg.de
In childhood, facial nerve palsy and headache are typical symptoms of second and third stage neuroborreliosis. While focal demyelination is occasionally observed on MRI scans, the appearance of a tumorous lesion is extremely rare. The case of a 10-year-old girl with neuroborreliosis mimicking a space-occupying lesion in the brainstem, without any previously recognized manifestations of borreliosis, is reported.
Publication Types:
PMID: 17030923 [PubMed - indexed for MEDLINE]
Motion-onset and pattern-reversal visual evoked potentials in diagnostics of neuroborreliosis.
Kubov Z, Szanyi J, Langrov J, Kremlcek J, Kuba M, Honegr K.
Department of Pathophysiology, Charles University in Prague, Faculty of Medicine in Hradec Krlov, Czech Republic. kubova@lfhk.cuni.cz
Neuroborreliosis is a form of borreliosis that affects the central and/or peripheral nervous system. Although it can mimic neurologic and ophthalmologic disorders such as multiple sclerosis and optic neuritis, visual evoked potential (VEP) examination is usually not used in neuroborreliosis diagnostics. Combined VEP testing (pattern-reversal VEPs and VEPs produced in response to linear and radial motion) was performed in 81 patients with neuroborreliosis verified by laboratory results (positive polymerase chain reaction or intrathecal antibodies production). Thirty-four patients reported diplopia or blurred vision related to borreliosis. In 33 (40%) patients the VEPs were delayed: motion-onset VEPs were pathologic in 22 (27%) patients, reversal VEPs in 5 (6%) patients, and both VEP types in 6 (7%) patients. The findings suggest that VEP testing (especially the motion-onset VEP testing) can confirm CNS involvement. Much higher sensitivity of motion-onset VEPs in comparison with reversal VEPs can result from rather selective (earlier) involvement of the magnocellular system or the dorsal stream of the visual pathway.
Publication Types:
PMID: 17016151 [PubMed - indexed for MEDLINE]
[Laboratory diagnosis of infection caused by Borrelia burgdorferi]
[Article in Danish]
Dessau RB, Bangsborg JM, Jensen TP, Hansen K, Lebech AM, Andersen C¯.
Dansk Selskab for Klinisk Mikrobiologi, Dansk Selskab for Infektionsmedicin. ram.dessau@dadlnet.dk
The laboratory diagnosis of Lyme disease in Denmark is reviewed with recommendations for serological testing. In Denmark the laboratory testing is performed with an ELISA technique. Most laboratories use an assay based on purified flagella antigen. The two-tier approach with Western Blot as confirmatory testing is not recommended since the contribution to the diagnostic specificity is only marginal. Predictive values of Lyme serology are presented, based on the estimated prevalence of the different stages of Lyme disease in Denmark.
Publication Types:
PMID: 16942701 [PubMed - indexed for MEDLINE]
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Interaction of a neurotropic strain of Borrelia turicatae with the cerebral microcirculation system.
Sethi N, Sondey M, Bai Y, Kim KS, Cadavid D.
Department of Neurology and Neuroscience, Center for the Study of Emerging Pathogens, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, MSB H506, Newark, NJ 07103, USA.
Relapsing fever (RF) is a spirochetal infection characterized by relapses of a febrile illness and spirochetemia due to the sequential appearance and disappearance of isogenic serotypes in the blood. The only difference between isogenic serotypes is the variable major outer membrane lipoprotein. In the absence of specific antibody, established serotypes cause persistent infection. Studies in our laboratory indicate that another consequence of serotype switching in RF is a change in neuroinvasiveness. As the next step to elucidate this phenomenon, we studied the interaction of the neurotropic Oz1 strain of the RF agent Borrelia turicatae with the cerebral microcirculation. During persistent infection of antibody-deficient mice, we found that serotype 1 entered the brain in larger numbers and caused more severe cerebral microgliosis than isogenic serotype 2. Microscopic examination revealed binding of B. turicatae to brain microvascular endothelial cells in vivo. In vitro we found that B. turicatae associated with brain microvascular endothelial cells (BMEC) significantly more than with fibroblasts or arachnoidal cells. The binding was completely eliminated by pretreatment of BMEC with proteinase K. Using transwell chambers with BMEC barriers, we found that serotype 1 crossed into the lower compartment significantly better than serotype 2. Heat killing significantly reduced BMEC crossing but not binding. We concluded that the interaction of B. turicatae with the cerebral microcirculation involves both binding and crossing brain microvascular endothelial cells, with significant differences among isogenic serotypes.
Publication Types:
PMID: 16940140 [PubMed - indexed for MEDLINE]
Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid.
Strle F, Ruzic-Sabljic E, Cimperman J, Lotric-Furlan S, Maraspin V.
Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. franc.strle@kclj.si
BACKGROUND: The most common cause of Lyme neuroborreliosis in Europe is Borrelia garinii, followed by Borrelia afzelii. However, no series describing patients with culture-confirmed cases of Lyme neuroborreliosis have been published, and no comparison of findings for patients with B. garinii and B. afzelii isolated from cerebrospinal fluid (CSF) has been reported. METHODS: All adult patients identified at a single medical center during a 10-year period who had borreliae isolated from CSF and typed as B. garinii or B. afzelii (using large DNA fragment patterns obtained with the MluI restriction endonuclease and separated with pulsed-field gel electrophoresis) were included. RESULTS: A comparison of 23 patients who had B. garinii isolated from CSF with 10 patients who had B. afzelii isolated from CSF revealed that a reliable clinical diagnosis of Lyme neuroborreliosis (before obtaining a CSF culture and intrathecal borrelial antibody production result) was established more frequently in the B. garinii group than in the B. afzelii group (19 of 23 patients vs. 1 of 10 patients). Patients in the B. garinii group reported radicular pains and expressed meningeal signs more often, but reported dizziness less often (occurrences of several other symptoms and/or signs were comparable). Lymphocytic pleocytosis, as well as several other CSF abnormalities, were frequent among patients with B. garinii isolated from CSF but were rare among patients in the B. afzelii group. CONCLUSIONS: Patients with B. garinii isolated from their CSF have a distinct clinical presentation, compared with patients with B. afzelii. B. garinii causes what, in Europe, is appreciated as typical early Lyme neuroborreliosis (Bannwarth syndrome), whereas the clinical features associated with B. afzelii are much less specific and more difficult to diagnose.
Publication Types:
PMID: 16912943 [PubMed - indexed for MEDLINE]
[Western-blot with VLSE protein and "in vivo" antigens in Lyme borreliosis diagnosis]
[Article in Polish]
Zajkowska J, Kondrusik M, Pancewicz S, Grygorczuk S, Swierzbinska R, Hermanowska-Szpakowicz T, Czeczuga A, Sienkiewicz I.
Klinika Chorb Zakainych i Neuroinfekcji AM w Bialymstoku.
The aim of the study was the evaluation of the efficiency of Western blot (EcoLine) test detecting simoultanous presence of IgM and IgG antibodies against B. burgdorferi in diagnosis of early and late stage of Lyme borreliosis. The comparison of results achieved by performing test Western-blot, ELISA (based on recombinant antigens of three genospecies of Borrelia) and EIA (based on antigens of one B. burgdorferi genospecies). The tests Western blot: EcoLine (Virotech) with antygens "in vivo", ELISA Borrelia IgM, IgG recombinant (Biomedica), EIA: B. b. ss. IgG, EIA B. garinii IgG, EIA B. afzelii IgG (TestLine) were used. Results showed efficacy of detecting IgM, IgG antibodies against VlsE simultanously and IgG antibodies against "in vivo" antigens in diagnosis of early stages of Lyme disease when atypical picture skin lessions arise diagnostic doubts and in discerning early and late stage of disease. The EIA tests based on one B. burgdoreferi genospecies seem less effective in comparison to ELISA tests based on 3 genospecies antigens.
Publication Types:
PMID: 16909799 [PubMed - indexed for MEDLINE]
[New aspects of pathogenesis of Lyme borreliosis]
[Article in Polish]
Zajkowska J, Grygorczuk S, Kondrusik M, Pancewicz S, Hermanowska-Szpakowicz T.
Klinika Chorb Zakaznych i Neuroinfekcji AM w Bialymstoku.
B. burgdorferi can evade the destructive effects of the immune system by binding host's complement regulators, which leads to inhibition of the complement activation cascade. Complement activity is blocked by CRASPs--complement regulator acquiring surface proteins. Complement resistance might therefore represent one major pathogenic factor favoring spirochete transmission to the vertebrate host, as well as determine host reservoirs of Borrelia burgdorferi genospecies. The cause of neuro-psychiatric disorders developing in some patients with Lyme borreliosis is still unknown. One of the hypotheses links them to neuro-hormonal disturbances induced by B. burgdorferi infection.
Publication Types:
PMID: 16909797 [PubMed - indexed for MEDLINE]
[Intercellular adhesion molecules sICAM-1, sICAM-2, sICAM-3 and IFNgamma in neuroborreliosis and tick-borne encephalitis]
[Article in Polish]
Pietruczuk M, Pietruczuk A, Pancewicz S, Zajkowska J, Swierzbinska R, Hermanowska-Szpakowicz T.
Oddzial Internistyczno-Kardiologiczny SP ZOZ w Soklce.
OBJECTIVE: The aim of this study was to evaluate the serum and CSF concentration of soluble intercellular adhesion molecules sICAM-1, sICAM-2, sICAM-3 and proinflammatory cytokine IFNgamma in patients with tick-borne encephalitis (TBE) and neuroborreliosis. METHODS: The study group consisted of 40: 20 with TBE meningitis and 20 with Lyme meningitis. The serum and CSF levels of adhesion molecules and IFNgamma were determined by ELISA assay twice: before and after treatment. RESULTS: Before treatment the concentrations of adhesion molecules and IFNgamma in serum as well as in CSF were significantly higher in both studied groups than in control group (with the exception of the serum level of sICAM-2 in TBE group). After the treatment, the serum parameters in TBE group decreased to the control level. CSF levels were also reduced, but still remained higher than in the control group. In patients with neuroborreliosis serum concentration of sICAM-1 and sICAM-2 did not change as compared with its level before treatment but other studied parameters in serum and CSF decreased significantly. CONCLUSIONS: The results of our study confirm the participation of intercellular adhesion molecules in the pathogenesis of viral (TBE) and bacterial (neuroborreliosis) neuroinfections.
Publication Types:
PMID: 16909787 [PubMed - indexed for MEDLINE]
[Multifocal central nervous system lesions --multiple sclerosis or neuroborreliosis?]
[Article in Polish]
Drozdowski W.
Klinika Neurologii AM w Bialymstoku.
Multiple sclerosis is the most frequent multifocal disease of the central nervous system, but in a diagnosis of atypical cases about 100 other diseases should be considered. Neuroborreliosis plays a particular role among them, especially in endemic regions. Difficulties result from similarities of clinical symptoms and lack of specific diagnostic investigations. Diagnostic procedures in neuroborreliosis are mostly based on laboratory analyses and serologic examinations of serum and cerebrospinal fluid, in connection with a clinical picture and an epidemiological state. Since the year 2001, multiple sclerosis neurological diagnostic is based on the diagnostic criteria established under the auspices of The US National Multiple Sclerosis Society and International Federation of Multiple Sclerosis Societies. Those recommendations regarding relapsing-remitting MS and primary progressing MS are discussed in this paper. Current knowledge of those diseases warrants cautiousness in the diagnostic of atypical cases.
Publication Types:
PMID: 16909774 [PubMed - indexed for MEDLINE]
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Evaluation of an internally controlled real-time PCR targeting the ospA gene for detection of Borrelia burgdorferi sensu lato DNA in cerebrospinal fluid.
Gooskens J, Templeton KE, Claas EC, van Dam AP.
Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
This study reports the development and evaluation of an internally controlled real-time PCR targeting the ospA gene for detection of Borrelia burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii and Borrelia valaisiana. DNA was extracted using QIAamp DNA Blood Mini kit columns. DNA from 33 B. burgdorferi sensu lato strains reacted in the assay, whereas no reactivity was observed with DNA from four relapsing fever Borrelia spp., 11 unrelated spirochaetes, and 31 unrelated microorganisms. The quantitative sensitivity of the assay was 1-10 fg of Borrelia DNA and one to five cultured Borrelia spirochaetes. Cerebrospinal fluid (CSF) specimens from 70 patients sent for routine testing for neuroborreliosis, and three CSF specimens containing B. garinii were also tested. Positive PCR results were obtained with all three culture-confirmed neuroborreliosis specimens, five of ten neuroborreliosis specimens with specific antibodies in CSF and pleocytosis, none of nine specimens from possible cases of early neuroborreliosis (antibodies in serum, CSF pleocytosis, no antibodies in CSF), one of 15 specimens from patients with active or past Lyme disease with neurological signs (antibodies in serum, no pleocytosis or antibodies in CSF), and none of 36 specimens from patients without Lyme borreliosis (no antibodies in serum or CSF). Overall, the real-time PCR assay enabled sensitive and specific detection of all B. burgdorferi sensu lato species tested. The PCR had a sensitivity of 50% in patients with neuroborreliosis. The main diagnostic role of the assay could be to confirm neuroborreliosis in patients for whom the diagnosis is doubtful.
Publication Types:
PMID: 16882295 [PubMed - indexed for MEDLINE]
Nonparalytic poliomyelitis in Lyme borreliosis.
van Baalen A, Muhle H, Straube T, Jansen O, Stephani U.
University Medical Center Schleswig-Holstein, Christian-Albrechts-Universitt zu Kiel, Germany. van.baalen@pedneuro.uni-kiel.de
Publication Types:
PMID: 16861483 [PubMed - indexed for MEDLINE]
[Stage-oriented treatment of Lyme borreliosis]
[Article in German]
Fingerle V, Wilske B.
Nationales Referenzzentrum fr Borrelien, Max v. Pettenkofer Institut, LMU Mnchen. nrz-borrelien@mvp.uni-muenchen.de
Every manifestation of Lyme borreliosis needs to be treated with antibiotics. The type of antibiotic applied and duration of treatment will depend on the stage and severity of the disease. Erythema migrans, Borrelia lymphocytoma, Lyme arthritis and acrodermatitis chronica atrophicans are primarily treated orally. If neurological symptoms, severe Lyme carditis or eye manifestations are present, intravenous treatment is initially recommended. For oral therapy, doxycycline, amoxicillin, cefuroxime and, if intolerance is shown, azithromycin, are available. For intravenous treatment ceftriaxone, cefotaxime or penicillin G is employed. The overall prognosis for treated Lyme borreliosis is good. However, in particular when manifestations with substantial organic injury have persisted, incomplete healing must be expected. With the exception of erythema migrans, every manifestation should be subjected to a careful diagnostic work-up prior to the start of treatment, because premature antibiotic administration is not only associated with an elevated risk for the patient, but can also mask important diagnostic signs.
Publication Types:
PMID: 16859159 [PubMed - indexed for MEDLINE]
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Symptoms of post-Lyme syndrome in long-term outcome of patients with neuroborreliosis.
Pcha D, Moravcova L, Lasikova S, Holeckova D, Maresova V.
Publication Types:
PMID: 16857637 [PubMed - indexed for MEDLINE]
Comment in:
Comment on:
Predictive model for Lyme meningitis.
Porwancher R.
Publication Types:
PMID: 16818599 [PubMed - indexed for MEDLINE]
Is neuroborreliosis a medical emergency?
Halperin JJ.
NYU School of Medicine, Great Neck, NY, USA. Halperin@LINeuro.com
Although Lyme disease affects the nervous system in many ways (collectively known as neuroborreliosis), only rarely does it present as a medical emergency. In extreme cases, it may cause (1) encephalitis, (2) a rapidly progressive peripheral neuropathy, or (3) a painful truncal radiculopathy that may be confused with a severe visceral process. Knowing when to consider this spirochetosis in the differential diagnosis requires an understanding of its true clinical spectrum, and of an appropriate diagnostic and therapeutic approach.
Publication Types:
PMID: 16757836 [PubMed - indexed for MEDLINE]
Comment on:
[Penicillin V is the first choice in the treatment of erythema migrans]
[Article in Swedish]
Bennet L, Stiernstedt S, Berglund J, Hagberg L, Karlsson M, Olsson I, Ornstein K.
Publication Types:
PMID: 16729462 [PubMed - indexed for MEDLINE]
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Subarachnoid hemorrhage due to Borrelia burgdorferi-associated vasculitis.
Jacobi C, Schwark C, Kress B, Hug A, Storch-Hagenlocher B, Schwaninger M.
Department of Neurology, Ruprecht-Karl University, Heidelberg, Germany. christian_jacobi@med.uni-heidelberg.de
We report the case history of a patient who suffered a subarachnoid hemorrhage (SAH) in association with early Lyme neuroborreliosis. After a tick bite, this patient developed erythema chronicum migrans and complained of stinging radicular pain in both legs. A computed tomography (CT) scan was performed because of acute headache and nuchal rigidity, which revealed an occipital SAH. Cerebrospinal fluid analysis provided further evidence of acute neuroborreliosis. Digital substraction angiography showed irregularities in the right posterior cerebral artery, which might be due to vasculitis, but no aneurysms.
Publication Types:
PMID: 16722982 [PubMed - indexed for MEDLINE]
MR imaging assessment of brain and cervical cord damage in patients with neuroborreliosis.
Agosta F, Rocca MA, Benedetti B, Capra R, Cordioli C, Filippi M.
Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
BACKGROUND AND PURPOSE: Neuroborreliosis is frequently indistinguishable from multiple sclerosis (MS) on both clinical and radiologic grounds. By using MR imaging, we assessed "occult" brain white matter (WM), brain gray matter (GM), and cervical cord damage in patients with neuroborreliosis in an attempt to achieve a more accurate picture of tissue damage in these patients, which might contribute to the diagnostic work-up. METHODS: We studied 20 patients with neuroborreliosis and 11 sex- and age-matched control subjects. In all subjects, we acquired dual echo, T1-weighted, diffusion tensor (DT) and magnetization transfer (MT) MR imaging scans of the brain and fast short-tau inversion recovery and MT MR imaging scans of the cervical cord. T2-visible lesion load was measured by using a local thresholding segmentation technique. Mean diffusivity and fractional anisotropy histograms of the brain and cervical cord MT ratio histograms were produced. Normalized brain volumes (NBV) were measured by using SIENAx. RESULTS: Brain T2-visible lesions were detected in 12 patients, whereas no occult damage in the normal-appearing WM and GM was disclosed by using MT and DT MR imaging. No macroscopic lesions were found in the cervical cord, which was also spared by occult pathology. NBV did not differ between patients with neuroborreliosis and control subjects. CONCLUSION: This study shows that, contrary to what happens in MS, occult brain tissue damage and cervical cord pathology are not frequent findings in patients with neuroborreliosis. These observations might be useful in the diagnostic work-up of patients with neuroborreliosis and T2 brain lesions undistinguishable from those of MS.
PMID: 16611786 [PubMed - indexed for MEDLINE]
[Clinical polymorphism of neuroborreliosis at a late stage of the disease]
[Article in Russian]
Vel'gin SO, Protas II, Ponomarev VV, Drakina SA, Shcherba VV.
Publication Types:
PMID: 16608111 [PubMed - indexed for MEDLINE]
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Adhesion of Borrelia garinii to neuronal cells is mediated by the interaction of OspA with proteoglycans.
Rupprecht TA, Koedel U, Heimerl C, Fingerle V, Paul R, Wilske B, Pfister HW.
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, D-81377 Munich, Germany.
To study pathogenic mechanisms of Lyme meningoradiculitis, dorsal root ganglia (DRG) cells and two neuronal cell lines (B50, SH-SY5Y) were incubated with Borrelia garinii, the Borrelia species most frequently isolated from CSF of Lyme neuroborreliosis patients in Europe. We demonstrated that (I) OspA-positive B. garinii adhere to neuronal cells, (II) Borrelia adhesion can be blocked by a monoclonal antibody against OspA, (III) preincubation with proteoglycans interferes with the adhesion process and (IV) rOspA directly binds to the proteoglycans. This indicates that both OspA and the cell bound proteoglycans are involved in the attachment of B. garinii to neuronal cells.
Publication Types:
PMID: 16603253 [PubMed - indexed for MEDLINE]
Comment in:
[Penicillin V treatment in erythema migrans can give a false security]
[Article in Swedish]
Wahlberg P, Nyman D.
Publication Types:
PMID: 16583549 [PubMed - indexed for MEDLINE]
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Comment on:
Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis.
Scheid R.
Publication Types:
PMID: 16568298 [PubMed - indexed for MEDLINE]
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Immunophenotypic patterns of T-cell activation in neuroinflammatory diseases.
Heinrich A, Ahrens N, Schmidt S, Khaw AV.
Department of Neurology, University of Greifswald, Greifswald, Germany. alexander.heinrich@bkh-guenzburg.de
OBJECTIVES: We aimed to gain insights into the pathogen-specific differences in early adaptive immune responses following central nervous system infections with Borrelia burgdorferi and viral pathogens by studying the immunophenotypic patterns of T-cell activation. Moreover, we wished to determine whether the expression of T-cell activation markers reflects disease activity in multiple sclerosis (MS). METHODS: Proportions of cerebrospinal fluid T-cells expressing the markers HLA-DR, CD25 and CD38 were determined in patients with MS (n = 40), acute viral meningomyeloradiculoneuritis (VID, n = 26), early neuroborreliosis (NB, n = 23) and non-inflammatory neurologic diseases (n = 51) by using flow cytometry. In relapsing-remitting MS, disease activity was assessed by clinical examination and magnetic resonance imaging. RESULTS: For each of the surface markers that were examined, significant differences in T cell proportions were found between patient groups. The proportion of HLA-DR+ T cells was higher and that of CD25+ T cells lower in NB compared with VID. These differences were attributable only to the early phase of the disease (< or = 6 days after symptom onset). Among MS patients, there was a trend for higher proportions of T cells expressing activation markers in patients with gadolinium-enhancing lesions. CONCLUSIONS: The decreased CD25 expression in NB may reflect immunomodulatory effects of B. burgdorferi facilitating persistent infection. Larger prospective studies of T-cell activation markers for ascertaining the association between cellular markers and clinical surrogates of disease activity in MS are warranted.
PMID: 16542164 [PubMed - indexed for MEDLINE]
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Clinical aspects of neuroborreliosis and post-Lyme disease syndrome in adult patients.
Pfister HW, Rupprecht TA.
Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany. hans-walter.pfister@med.uni-muenchen.de
The diagnostic criteria of active neuroborreliosis include inflammatory changes of the cerebrospinal fluid (CSF) and an elevated specific Borrelia CSF-to-serum antibody index, indicating intrathecal Borrelia antibody production. Patients with neuroborreliosis are usually treated with intravenous ceftriaxone for 2-3 weeks. In case of allergy, doxycycline may be used. Treatment efficacy is detected by the improvement of the neurological symptoms and the normalization of the CSF pleocytosis. The measurement of serum and CSF antibodies is not suitable for follow-up, because they frequently persist. Post-Lyme disease (PLD) syndrome is characterized by persistent complaints and symptoms after previous treatment for Lyme borreliosis, e.g., musculoskeletal or radicular pain, dysaesthesia, and neurocognitive symptoms that are often associated with fatigue. There is no formal definition of the PLD syndrome, and its pathogenesis is unclear. Recent controlled studies do not support the use of additional antibiotics in these patients, but recommend primarily symptomatic strategies.
Publication Types:
PMID: 16524775 [PubMed - indexed for MEDLINE]
[All physicians must be capable to diagnose Borrelia infection. A case report, or how to be a patient]
[Article in Swedish]
Norrby E.
Kungl Vetenskapsakademien, Centrum fr vetenskapshistoria, Stockholm. erling@kva.se
Publication Types:
PMID: 16491554 [PubMed - indexed for MEDLINE]
[Soluble CD40 and soluble CD40L concentrations in the serum and the cerebrospinal fluid of patients with tick borne encephalitis and neuroborreliosis]
[Article in Polish]
Zajkowska JM, Kondrusik M, Pancewicz S, Swierzbinska R, Grygorczuk S, Hermanowska-Szpakowicz T.
Klinika Chorb Zakanych i Neuroinfekcji, Akademia Medyczna w Bialymstoku, Bialystok. zajkowsk@kki.pl
BACKGROUND AND PURPOSE: The interaction between CD40 and CD40L is essential in generating of an immunological response also intrathecally. The aim of the study was estimation of a concentration soluble form of CD40, CD40L (CD154) in the bacterial and viral inflammation of the central nervous system in two compartments - blood circulation and intrathecally, before and after the treatment. MATERIAL AND METHODS: sCD40 and sCD40L were tested twice before and after treatment in pairs serum and CSF of 40 patients treated in the Dept. of Infectious Diseases and Neuroinfections. Patients were divided in two groups: (n=20) patients with tick borne encephalitis (TBE) (group I, n=20) and patients with neuroborreliosis in the form of lymphocytic meningitis (group II, n=20). ELISA assays were performed. RESULTS: Significantly increased concentrations of sCD40, sCD40L in CSF (higher in neuroborreliosis) were measured. We found also an increased concentration of sCD40L in inflammatory CSF in both tested groups (in neuroboreliosis lasting also after 4 weeks of treatment), compared with the control group (below the detection limit in normal CSF). CONCLUSIONS: Results of estimation of the sCD40 and sCD40L concentrations indicate their role in the intrathecal inflammation process of bacterial and viral etiology. The increased serum concentration of sCD40L in TBE and CD40 in neuroborreliosis indicate that peripheral activation of the immunological system persists after cessation of treatment and after the clinical recovery. The defense mechanisms are more pronounced in neuroborreliosis than in tick borne encephalitis.
Publication Types:
PMID: 16463218 [PubMed - indexed for MEDLINE]
Co-existance of toxoplasmosis and neuroborreliosis - a case report.
Gustaw K, Beltowska K, Dlugosz E.
Department of Neurodegenerative Diseases, Institute of Agricultural Medicine, Jaczewskiego 2, 20-090 Lublin, Poland. kasiagu@yahoo.ca
The 53-year-old woman was initially diagnosed with multiple sclerosis, despite the fact that she did not really meet the clinical criteria. Her only symptoms were clumsiness and weakness of the right extremities. Being a veterinary research worker she had been exposed to infectious material. In 1995, she was diagnosed with ELISA as having toxoplasmosis and treated as such. In 2002, after the infectious, flu-like disease, she revealed arthritis and drowsiness, also with memory and language impairment. The patient continued to have symptoms consistent with previously examined clumsiness. She was diagnosed with Lyme via ELISA and PCR, and treated. She made a full recovery from acute symptoms. After a few months, neurological and neuropsychological examinations were performed. On the background of mild cognitive decline apraxia and difficulties of attention were noted as the main problems. A apraxia of the right hand complicated the patient's life and depreciated her quality of life. The patient underwent MRI examination. FSE, FAST and FLAIR sequences were made. The MRI demonstrated the appearance of several small hyperintense lesions in the white matter of the left and right frontal and left parietal lobe. These lesions were typical of the post-inflammatory leucoencephalopathy. Additionally, a ring-shaped, low-intensity lesion in the posterior part of the left parietal lobe was noticed. The lesion was 8 mm in diameter and described to be an old toxoplasmosis lesion. The patient had been treated and the symptoms consistent with Lyme disease resolved. Patient continues to have symptoms consistent with focal destruction of the parietal lobe. Over the past six months, she has not progressed and relapsed in a manner that is consistent with MS.
Publication Types:
PMID: 16457490 [PubMed - indexed for MEDLINE]
Autoantibodies to human manganese superoxide dismutase (MnSOD) in children with facial palsy due to neuroborreliosis.
Eiffert H, Karsten A, Ritter K, Ohlenbusch A, Schlott T, Laskawi R, Christen HJ.
Department of Medical Microbiology, University Hospital, Gttingen, Germany.
AIM: Acute peripheral facial palsy due to neuroborreliosis is associated with a distal neuritis. In patients with Lyme disease the activity of antioxidant enzymes is decreased. With respect to the pathogenesis of neuroborreliosis, sera of children with acute peripheral facial palsy were investigated for autoantibodies against human manganese superoxide dismutase (MnSOD), which were suspected of raising the oxidative injury of infected tissues. METHODS: Sera of 20 children with acute peripheral palsy with neuroborreliosis, sera of 20 children with facial palsy without reference to Lyme disease and sera of 14 blood donors were tested for antibodies against human MnSOD using an ELISA. RESULTS: The concentrations of IgM autoantibodies to MnSOD of the children with neuroborreliosis were significantly increased, compared with the two control groups. CONCLUSIONS: We propose that the antibodies detected block the protective effects of MnSOD resulting in an increased oxidative inflammation.
Publication Types:
PMID: 16429379 [PubMed - indexed for MEDLINE]
[Onset of Leber's hereditary optic neuropathy in association with borreliosis]
[Article in French]
Macarez R, Bazin S, Lagauche D, Soulli B, Giordano P, May F, Guigon B.
Service d'Ophtalmologie, HIA Clermont Tonnerre, BP 41, 29240 Brest-Armes.
INTRODUCTION: The diagnosis of Lyme disease in the presence of an acute optical neuritis always raises a difficult diagnostic problem. We present a case of Lyme-associated Leber's hereditary optic neuropathy (LHON). OBSERVATION: A 17-year-old Eurasian young man presented with left-eye visual impairment for 1 month. This loss of vision acuity in the left eye is related to an optic neuropathy. Mitochondrial DNA testing showed a G to A substitution at position 11778 confirming a diagnosis of LHON. The family history disclosed a case of LHON in a maternal cousin. The mother's family is Asian. Besides, serum examination of anti-Borrelia antibodies was performed and was positive against Borrelia burgdorferi garinii. The patient history indicated that he had been possessing a dog and was living in an endemic area of Lyme disease. But he did not recall receiving a tick bite nor having any erythema chronicum migrans. Initial examination showed bilateral green-red axis colour vision defects which made us fear bilateralisation of the optic neuropathy, which occurred 2 months later (that is 3 months after the onset of symptoms on the left eye). An antibiotic treatment by ceftriaxone was administered for 4 weeks all in all; and a long term ubidecarenone therapy was established. At present, after a 1-year follow up, the eyes' conditions remains unchanged. CONCLUSION: To our knowledge, this would be the first case reporting such an association, in which we can discuss the fortuitous character or the role of the infectious factor in the developing of the mitochondrial pathology. This observation also raises the problem of the positive diagnosis of Lyme disease when tick bite and erythema are absent or underestimated.
Publication Types:
PMID: 16395203 [PubMed - indexed for MEDLINE]
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Neuroborreliosis with progression from pseudotumor cerebri to aseptic meningitis.
Steenhoff AP, Smith MJ, Shah SS, Coffin SE.
Division of Infectious Diseases, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Steenhoff@email.chop.edu
We report a patient with an initial diagnosis of Lyme-associated pseudotumor cerebri who developed cerebrospinal fluid pleocytosis consistent with Lyme meningitis. The case illustrates the importance of considering neuroborreliosis in the differential diagnosis of pseudotumor cerebri and describes the evolution of cerebrospinal fluid findings in this condition.
Publication Types:
PMID: 16395117 [PubMed - indexed for MEDLINE]
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Intrathecal antibody production in a mouse model of Lyme neuroborreliosis.
Li L, Narayan K, Pak E, Pachner AR.
Department of Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 S. Orange Ave., Newark, NJ 07103, USA.
Intrathecal antibody (ITAb) production is a common feature of neurological diseases, yet very little is known about its mechanisms. Because ITAb is prominent in human Lyme neuroborreliosis (LNB), in the present study we established a mouse model of LNB to study ITAb production. We injected different strains of Borrelia burgdorferi into a variety of mouse strains by the intracerebral (i.c.) route to develop the model. Spirochetal infection and ITAb production were identified by complementary methods. This study demonstrates that the mouse model of LNB can be utilized to test hypotheses related to the mechanisms of ITAb production.
Publication Types:
PMID: 16387369 [PubMed - indexed for MEDLINE]
Concentration of interferon-inducible T cell chemoattractant and monocyte chemotactic protein-1 in serum and cerebrospinal fluid of patients with Lyme borreliosis.
Grygorczuk S, Zajkowska J, Swierzbinska R, Pancewicz S, Kondrusik M, Hermanowska-Szpakowicz T.
Department of Infectious Diseases and Neuroinfections, Medical University of Bialystok, Poland. neuroin@amb.edu.pl
PURPOSE: Chronic inflammation in Lyme borreliosis may be sustained by aberrant inflammatory response, characterized by Th1 lymphocyte predominance, which in turn may be determined by chemokines synthesized in inflammatory focus. The aim of the study was to evaluate synthesis of chemokines: interferon-induced T cell chemoattractant (I-TAC--chemoattractant for Th1 lymphocytes), and monocyte chemotactic protein (MCP-1) in Lyme borreliosis. MATERIAL AND METHODS: Study group consisted of 13 patients with erythema migrans, 10 with Lyme arthritis and 6 with neuroborreliosis. Serum, as well as cerebrospinal fluid (CSF) in neuroborreliosis, was obtained before (examination 1) and during (examination 2) antibiotic treatment. Control serum was obtained from 8 healthy volunteers and control csf from 8 patients in whom meningitis and neuroborreliosis was excluded after diagnostic lumbar puncture. The samples were assayed for MCP-1 and I-TAC by ELISA. RESULTS: Serum mean I-TAC concentration in examination 1 was 73.0 pg/ml in erythema migrans, 78.9 pg/ml in Lyme arthritis and 87.3 pg/ml in neuroborreliosis (29.9 pg/ml in controls, difference significant for neuroborreliosis) and did not change significantly in examination 2. MCP-1 serum concentration was significantly increased to 497.5 pg/ml in neuroborreliosis in examination 2. I-TAC concentration in csf remained low, while MCP-1 concentration in examination 1 was increased to 589.1 pg/ml, significantly higher than simultaneously in serum. CONCLUSIONS: I-TAC synthesis is increased in Lyme borreliosis and may be a factor favoring predominance of Th1 lymphocyte subset. MCP-1 creates chemotactic gradient towards central nervous system and may contribute to csf pleocytosis in neuroborreliosis.
PMID: 16358960 [PubMed - indexed for MEDLINE]
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[Neuroborreliosis and diphasic meningoencephalitis -- common features and differences]
[Article in German]
Kaiser R.
Neurologische Klinik, Klinikum Pforzheim GmbH, Pforzheim. rkaiser@klinikum-pforzheim.de
Publication Types:
PMID: 16355317 [PubMed - indexed for MEDLINE]
[Late manifestations of Lyme borreliosis]
[Article in German]
Rossi M.
Abteilung Infektiologie, Kantonsspital Luzern, Luzern. marco.rossi@ksl.ch
Month to years after an early local or an early disseminated infection some patients develop late manifestations of lyme borreliosis. Most frequently involved organs are the skin (acrodermatitis chronica atrophicans), joints (Lyme arthritis) and the nervous system. A history of exposure and the clinical picture may suggest Lyme borreliosis, however, confirmation by serological and other tests is needed. Antibiotic treatment during early stages normally prevents development of late manifestations. Late stages persist if not treated. By adequate antimicrobial therapy they are treatable and usually show a good prognosis. Recovery may be delayed, some patients suffer from residual difficulties. Currently there is no accepted case definition for a "post lyme syndrome". The term "chronic Lyme disease" suggests (a never proven) persistent infection by viable bacteria. Repeated and prolonged antibiotic treatments are not indicated.
Publication Types:
PMID: 16350537 [PubMed - indexed for MEDLINE]
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Junctional rhythm in association with neuroborreliosis.
Kaltman JR, Tanel RE, Vetter VL, Shah MJ, Rhodes LA.
The Cardiac Center of The Children's Hospital of Philadelphia and Division of Pediatric Cardiology, Department of Pediatrics, University of Pennsylvania School of Medicine, 19104, USA. kaltman@email.chop.edu
Publication Types:
PMID: 16340763 [PubMed - indexed for MEDLINE]
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Tick prevention in a population living in a highly endemic area.
Stjernberg L, Berglund J.
Department of Community Medicine, Lund University, Malm, Sweden. louise.stjernberg@bth.se
AIMS: To describe environmental and personal tick-preventive measures and their predictors, taken by a population living in a highly tick-endemic area. METHODS: Owing to the recent confirmation of human tick-borne encephalitis cases, vaccination against tick-borne encephalitis was offered to the population living in the endemic area through the use of leaflets and media campaigns. At the time of the initial dose, information and enrollment to this cohort study was carried out. Participants' characteristics, frequency of tick-bites and preventive measures were included in questionnaires. Logistic analysis was used to determine behavioural differences in activities taken in order to prevent tick bites. CONCLUSION: In total, 70% of the permanent residents had themselves vaccinated before the next tick season. Of the studied participants 356/517 (69%) regularly took preventive measures in their environment and/or personally. Women in particular, and those previously treated for a tick-borne disease, took significantly more preventive measures. When analysing all variables together, spending less time in a tick-endemic area and being tick-bitten during the latest tick season significantly increased the probability of taking preventive measures. After being tick-bitten, men were more inclined to start taking preventive measures than women. Awareness of the risks caused by living in a high tick-endemic area influenced the participant's daily life through preventive activities. Public health action should be considered, thus encouraging out-of-door activities for the population without anxiety as to the risks of contracting tick-borne disease after being tick-bitten.
Publication Types:
PMID: 16332608 [PubMed - indexed for MEDLINE]
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[Cytokine CXCL13--a possible early CSF marker for neuroborreliosis]
[Article in German]
Rupprecht TA, Koedel U, Angele B, Fingerle V, Pfister HW.
Neurologische Klinik der LMU Mnchen-Grosshadern.
The definitive diagnosis of acute neuroborreliosis (NB) is based upon the presence of lymphomonocytic CSF pleocytosis and intrathecal Borrelia burgdorferi (B.b.)-specific antibody production (expressed by an antibody index of >2). However, the latter might be absent in early stages of the disease. Now a recently discovered additional CSF marker-the cytokine CXCL13-was found to be positive in every initial CSF sample from patients with NB and therefore could be a valuable tool for early diagnosis and initiation of antibiotic therapy. We report an unusual case of NB in a patient with a history of metastatic carcinoma of the prostate and unilateral polyradiculitis. While no intrathecal B.b.-specific antibody production could be demonstrated initially, the CSF CXCL13 level was high (>500 ng/g vs <1.7 ng/g in healthy controls). During the course of the disease, the antibody index turned positive (4.8) and the patient responded to antibiotic therapy, thus confirming the diagnosis. In this case, measuring CXCL13 in the CSF would have led to earlier diagnosis and treatment of NB.
Publication Types:
PMID: 16308679 [PubMed - indexed for MEDLINE]
Different B-cell populations are responsible for the peripheral and intrathecal antibody production in neuroborreliosis.
Lakos A, Ferenczi E, Komoly S, Granstrm M.
Center for Tick-borne Diseases, Visegrdi 14, H-1132 Budapest, Hungary. alakos@axelero.hu
The diagnosis of neuroborreliosis (NB)--a serious complication of Lyme disease--relies on demonstration of intrathecal borrelia antibody production. We hypothesized that if a qualitative difference between the cerebrospinal fluid and the serum immunoblot-banding patterns was observed, then the borrelia antibodies found in the CSF could not be the result of leakage of serum antibodies to the CSF due to blood-brain barrier damage, but rather had to be produced intrathecally. CSF/serum pairs from 69 NB patients and from 85 control patients with other neurological disorders were investigated. All samples were tested blindly by immunoblot and a commercial capture ELISA kit for NB. The concordance between the two methods was 85.7%. When using the other method as reference, the accuracy of the two assays in the two patient materials was similar: 80% for sensitivity and 95% for specificity. Four types of comparative immunoblot-banding patterns that reflected intrathecal borrelia antibody synthesis were distinguished. The study showed that a simple comparison between the immunoblot pattern of serum and CSF samples allows for a reliable diagnosis of NB by demonstration of intrathecal antibody production. This is the first study to show that a qualitative difference of the antibody response between the immune response of serum and CSF is a rule. The findings also imply that partly different B-cell populations are responsible for the antibody production in the blood and in the central nervous system. In addition, our observation provides possible implications for other infectious diseases with CNS involvement.
Publication Types:
PMID: 16303786 [PubMed - indexed for MEDLINE]
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Chronic lymphocytic meningitis in an adolescent.
Banarer M, Cost K, Rychwalski P, Bryant KA.
Department of Pediatrics , University of Louisville, Louisville, KY 40202, USA.
Publication Types:
PMID: 16291364 [PubMed - indexed for MEDLINE]
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Lyme meningoradiculitis and myositis after allogeneic hematopoietic stem cell transplantation.
Rodrguez M, Chou S, Fisher DC, De Girolami U, Amato AA, Marty FM.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
We describe a patient with a history of allogeneic hematopoietic stem cell transplantation complicated by chronic graft-versus-host disease who developed painful meningoradiculitis and myositis due to Lyme borreliosis. To our knowledge, this is the first report of such an infection occurring after allogeneic hematopoietic stem cell transplantation in the United States.
Publication Types:
PMID: 16288389 [PubMed - indexed for MEDLINE]
Central nervous system Lyme disease.
Halperin JJ.
Department of Neurology, North Shore University Hospital, Manhasset, NY 11030, USA. halperin@nshs.edu
Nervous system infection with Borrelia burgdorferi frequently causes meningitis and rarely causes encephalomyelitis. Altered cognitive function also can occur in the absence of central nervous system infection. Recently developed serodiagnostic tools, such as the C6 assay, and appropriate use of Western blotting promise to improve diagnostic accuracy. Treatment trials have demonstrated the efficacy of relatively brief courses of oral antimicrobial agents, even in peripheral nervous system infection and meningitis. Several well-performed studies have clearly shown that prolonged antimicrobial treatment of "post-Lyme disease" is ineffective. Diagnosis and treatment of Lyme disease continue to improve.
Publication Types:
PMID: 16263055 [PubMed - indexed for MEDLINE]
[Serum and cerebrospinal concentrations of sICAM-1 sICAM-2, sICAM-3 in neuroborrellosis and tick borne encephalitis--preliminary report]
[Article in Polish]
Zajkowska JM, Izycka A, Jablonska E, Hermanowska-Szpakowicz T, Kondrusik M, Pancewicz S, Grygorczuk S, Swierzbinska R.
Klinika Chorb Zakanych i Neuroinfekcji Akademii Medycznej, Bialymstoku. zajkowsk@kki.pl
OBJECTIVE: The aim was to evaluate the concentrations of the soluble forms of ICAM-1, ICAM-2, ICAM-3 in the serum and cerebrospinal fluid (CSF) of patients with neuroborreliosis and thick borne encephalitis before and after therapy in comparison with the control group. MATERIAL AND METHODS: We examined 30 patients, 10 in each group: neuroborreliosis-group I (NB), tick borne encephalitis--group II (TBE) and in the control group (group K). The diagnosis of neuroborreliosis and TBE based on the clinical features was confirmed by ELISA assays: FSME Virus/TBE Virus test (VIRION, Germany) for TBE and Borrelia IgM and IgG Recombinant (Biomedica Austria) for NB. The assays of sICAM-1, sICAM-2, sICAM-3 (ELISA, Bender Med System, USA) were performed twice in group I and II: before and after 3-4 weeks long treatment and once in control group. RESULTS AND CONCLUSIONS: Increased concentration of soluble forms of ICAM-1, ICAM-2, ICAM-3 in CSF suggest their important role in inflammatory process of viral and bacterial origin. In NB group, the serum concentrations of sICAM-1, sICAM-2 were significantly increased before and after treatment in comparison with control as well as with the analogous test results in TBE group. It may suggest NB as the part of systemic inflammation. The CSF concentration of sICAM-2 decreases after treatment in NB group in comparison with the analogous test results of TBE group. The increased CSF concentration of sICAM-2 in TBE group when compared to the CSF concentration in NB group suggest slow recovery and still persisting immunological activation in this group, even when the neurological symptoms disappeared. Increased concentrations in CSF in both diseases indicate intrameningeal activity of lymphocytes and may be a useful marker of inflammation.
Publication Types:
PMID: 16245421 [PubMed - indexed for MEDLINE]
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Sequential analyses of neurobiochemical markers of cerebral damage in cerebrospinal fluid and serum in CNS infections.
Lins H, Wallesch CW, Wunderlich MT.
Department of Neurology, Otto-von-Guericke-University Magdeburg, Germany.
OBJECTIVE: To elucidate the relation between release patterns and cerebrospinal fluid/serum concentrations of neurobiochemical markers of cerebral damage and their potential value as monitoring parameters in central nervous system infections. METHODS: We investigated protein S-100B and neuron-specific enolase (NSE) in 102 sequential cerebrospinal fluid (CSF)-serum-pairs in patients with bacterial (n = 11) or viral (n = 13) meningitis/meningoencephalitis and neuroborreliosis (n = 8) in comparison with controls (n = 13). RESULTS: Highest S-100B values in CSF and serum were found on admission and showed a significant decrease afterwards. Comparison between disease groups revealed significant differences between bacterial and viral meningitis and neuroborreliosis for S-100B and also when compared with controls. NSE was not significantly elevated. CONCLUSIONS: S-100B is altered in CNS infection but does not provide additional benefit in the differential diagnosis when compared with standard CSF parameters. Nevertheless, S-100B values might be used as an additional monitoring parameter especially when sequential lumbar punctures are contraindicated.
Publication Types:
PMID: 16218912 [PubMed - indexed for MEDLINE]
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PCR in lyme neuroborreliosis: a prospective study.
Pcha D, Moravcov L, Zdrskù E, Maresov V, Hulnskù V.
First Clinic for Infectious Diseases, Second Medical Faculty of Charles University, Faculty Hospital Bulovka, Czech Republic.
OBJECTIVES: DNA proof is the only widely available direct diagnostic tool in Lyme borreliosis. Sensitive PCR detecting of spirochetal DNA was prepared and a prospective study in neuroborreliosis was performed. MATERIALS AND METHODS: 57 hospitalised patients with active neuroborreliosis and proved CSF antibodies synthesis were examined. Nested-PCR (utilizing three targets) was used for the detection of specific DNA in plasma, CSF and urine. RESULTS: Before treatment 36 positive patients (63.1%) were found in all tested specimens in parallel, 28 patients (49.1%) were positive in urine, 20 in CSF (35.0%) and 16 in plasma 28.0%). Later only urine was tested and the following results were obtained: 17 positive patients (30.0%) immediately after treatment, 8 (14.0%) after 3 months and one patient persisted positivity after 6 months. CONCLUSIONS: The highest sensitivity of PCR was achieved in the acute period of neuroborreliosis - 63.1% in three body fluids comparing with CSF antibody synthesis.
Publication Types:
PMID: 16218909 [PubMed - indexed for MEDLINE]
Expression of complement factor H binding immunoevasion proteins in Borrelia garinii isolated from patients with neuroborreliosis.
Alitalo A, Meri T, Comstedt P, Jeffery L, Tornberg J, Strandin T, Lankinen H, Bergstrm S, Cinco M, Vuppala SR, Akins DR, Meri S.
Department of Bacteriology and Immunology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
The Lyme disease-pathogen Borrelia burgdorferi binds the complement inhibitor factor H (FH) to its outer surface protein E- (OspE) and BbA68-families of lipoproteins. In earlier studies, only serum-resistant strains of the genospecies B. burgdorferi sensu stricto or B. afzelii, but not serum-sensitive B. garinii strains, have been shown to bind FH. Since B. garinii often causes neuroborreliosis in man, we have readdressed the interactions of B. garinii with FH. B. garinii 50/97 strain did not express FH-binding proteins. By transforming the B. garinii 50/97 strain with an OspE-encoding gene from complement-resistant B. burgdorferi (ospE-297), its resistance to serum killing could be increased. OspE genes were detected and cloned from the B. garinii BITS, Pistoia and 40/97 strains by PCR and sequencing. The deduced amino acid sequences differed in an N-terminal lysine-rich FH-binding region from OspE sequences of resistant strains. Recombinant B. garinii BITS OspE protein was found to have a considerably lower FH-binding activity than the B. burgdorferi sensu stricto 297 OspE protein P21 (P21-297). Unlike bacteria that had been kept in culture for a long time, neurovirulent B. garinii strains from neuroborreliosis patients were found to express approximately 27-kDa FH-binding proteins. These were not recognized by polyclonal anti-OspE or anti-BbA68 antibodies. We conclude that B. garinii strains carry ospE genes but have a decreased expression of OspE proteins and a reduced ability to bind FH, especially when grown for prolonged periods in vitro. Recently isolated neuroinvasive B. garinii strains, however, can express FH-binding proteins, which may contribute to the virulence of neuroborreliosis-causing B. garinii strains.
Publication Types:
PMID: 16208765 [PubMed - indexed for MEDLINE]
Paralytic strabismus as a manifestation of lyme borreliosis.
Zrinsak O, Masnec-Paskvalin S, Corak M, Baani B, Mandi Z.
University Department of Ophthalmology, Clinical Hospital, Systers of Mercy, Zagreb, Croatia. ozrinscak@yahoo.co.uk
Lyme disease is a multi-system organ disorder caused by Borrelia burgdorferi. Although ocular manifestations have been reported, these remain a rare feature of the disease. This report shows a 49-years old patient that has been bitten by a tick and as consequence of which developed symptoms of the Lyme disease. In 1998 the patient was hospitalized in our Eye Clinic due to operating treatment of the paralytic strabismus (abductal nerve paralysis), as a rare feature of the Lyme disease. Postoperative squint angle was significantly reduced, but without any temporal movement. Diplopia was still present, though slightly reduced with the use of prism eyeglasses. The improvement of the quality of life was achieved, as well as the patient's satisfaction.
Publication Types:
PMID: 16193697 [PubMed - indexed for MEDLINE]
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Up-regulation of Borrelia-specific IL-4- and IFN-gamma-secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis.
Widhe M, Skogman BH, Jarefors S, Eknefelt M, Enestrm G, Nordwall M, Ekerfelt C, Croner S, Bergstrm S, Forsberg P, Ernerudh J.
Division of Clinical Immunology, University of Linkping, Sweden. mona.widhe@cmm.ki.se
The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-gamma, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of 'confirmed NB' (n = 34), 'possible NB' (n = 30) and 'non-NB' (n = 10). The number of Borrelia-specific IL-4- and IFN-gamma-secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN-gamma was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN-gamma responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.
PMID: 16176932 [PubMed - in process]
Erratum in:- Ned Tijdschr Geneeskd. 2005 Sep 24;149(39):2200.
[Clinical reasoning and decision-making in practice. An older man with prostate carcinoma and a painless paraparesis of the legs]
[Article in Dutch]
Ruitenberg A, Vecht ChJ, van den Bent MJ, Taal W.
Erasmus MC, afd. Neurologie, Rotterdam.
A 78-year-old man with metastasised prostate carcinoma presented with a painless paraparesis. His cerebrospinal fluid showed elevated protein and a mononuclear pleiocytosis, but cytology investigations of 5 separate samples revealed no malignant cells in the cerebrospinal fluid. Extensive viral and bacterial tests (including ELISA for Borrelia burgdorferi) of serum and cerebrospinal fluid were negative. On the day radiation therapy for presumed leptomeningeal metastases was due to start the IgG and IgM Western blot for Borrelia were found to be positive, indicating neuroborreliosis. Soon after the start of antibiotic therapy the paraparesis began to improve and after four weeks the patient had made a complete recovery. In patients with a progressive paraparesis, neuroborreliosis should be considered even in the absence of pain.
Publication Types:
PMID: 16121663 [PubMed - indexed for MEDLINE]
Bilateral facial nerve palsy in the course of neuroborreliosis in children-dynamics, laboratory tests and treatment.
Mlodzikowska-Albrecht J, Zarowski M, Steinborn B, Winczewska-Wiktor A, Gurda B, Wigowska-Sowinska J.
Chair and Department of Developmental Neurology Poznan University of Medical Sciences, Poland. albrecht@amp.edu.pl
PURPOSE: Presentation of four patients with bilateral peripheral facial nerve palsy as a clinical manifestation of neuroborreliosis in children--diagnostic, treatment and prognosis. MATERIAL AND METHODS: In 2002-2004 in The Chair and Department of Developmental Neurology, 24 children from the Wielkopolska region were admitted with diagnosis of borreliosis. Among all the children with borreliosis, confirmed by serologic examination, 4 (16.7%) demonstrated bilateral peripheral facial palsy (PFP). We investigated the presence of IgM class and IgG class specific antibodies in the sera and cerebrospinal fluid (CSF) of 4 patients with bilateral PFP. (Detected by immunoenzymatic methods--ELISA.) RESULTS: Before the occurrence of PFP all the children manifested unspecified systemic symptoms such as headaches, muscle and articulation pains, weakness and in two cases a mood depression. At first all patients demonstrated elevated IgM antibodies and proper levels of IgG antibodies. Control tests administered within 2-14 months later reduction of antibodies was indicated. Two patients demonstrated significant pleocytosis in CSF test, (without the meningeal symptoms). All children were treated with physiotherapeutic procedures and were administered antibiotic intravenously. CONCLUSIONS: PFP is one of the most frequent neurological symptoms of borreliosis in children. In case of acute PFP and especially the bilateral form of PFP, neuroborreliosis is the most probable diagnosis. All children reported PFP at one side first and after several weeks the paresis of the facial nerve on the opposite side usually appeared. The clinical state of children started to improve after the introduction of physiotherapy and this process usually lasted several months.
PMID: 16119630 [PubMed - indexed for MEDLINE]
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Diaphragmatic paralysis and respiratory failure as a complication of Lyme disease.
Abbott RA, Hammans S, Margarson M, Aji BM.
Publication Types:
PMID: 16107377 [PubMed - indexed for MEDLINE]
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New antigens for serologic diagnosis of neuroborreliosis in children.
Heikkil T, Saxen H, Seppl I, Lnnqvist T, Sillanp H, Lahdenne P.
Hospital for Children and Adolescents, University of Helsinki, Finland.
OBJECTIVE: To evaluate serology with novel Borrelia-specific protein or peptide antigens in the laboratory diagnosis of neuroborreliosis (NB) in children. METHODS: The performance of enzyme-linked immunosorbent assays with several recombinant borrelial protein antigens and invariable region 6 synthetic peptide antigen and of a commercial enzyme-linked immunosorbent assay with the flagella antigen were evaluated in the serodiagnosis and follow-up of children with clinical suspicion of NB. Serum samples were obtained from 20 children with neurologic symptoms indicative of NB. The patients were retrospectively divided into 2 groups based on the laboratory tests at presentation indicating definite (n = 7) or probable (n = 13) NB. RESULTS: In addition to cerebrospinal fluid (CSF) lymphocytic pleocytosis and CSF antiflagella antibodies, all 7 patients with definite NB had serum IgG antibodies to at least 2 of the 3 novel antigens at presentation. The 13 patients with probable NB had variable laboratory findings: CSF pleocytosis (n = 7), CSF antiflagella IgM antibodies (n = 4), serum antiflagella IgM and/or IgG antibodies (n = 10). Of these 13 patients, 7 had serum IgG antibodies to 2 of the 3 novel antigens at presentation. During long term follow-up, serum anti-invariable region 6 antibodies disappeared. CONCLUSIONS: The present study suggests that assessment of serum antibodies to a panel of Borrelia-specific antigens could improve the laboratory diagnosis of NB at presentation.
Publication Types:
PMID: 16094226 [PubMed - indexed for MEDLINE]
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Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain reaction in children with Lyme meningitis.
Avery RA, Frank G, Eppes SC.
Department of Pediatrics, Alfred I. duPont Hospital for Children and Nemours Children's Clinic Wilmington, DE 19899, USA.
BACKGROUND: Cerebrospinal fluid (CSF) laboratory tests are frequently collected to help differentiate Lyme meningitis from other causes of aseptic meningitis. Previous studies using Lyme CSF polymerase chain reaction (PCR) have yielded varied results (sensitivity between 10 and 90%). No studies have specifically examined the diagnostic utility of Lyme CSF-PCR in North American children with Lyme meningitis. METHODS: Retrospective chart review of children presenting to a children's hospital in a Lyme-endemic region between October 1999 and September 2004. Patients were included if they had both Lyme serology and Lyme CSF-PCR performed during the same hospital encounter and had documented meningitis. Patients were considered to have Lyme meningitis if they had meningitis and met CDC criteria for Lyme disease. The Lyme CSF-PCR assay amplified a Borrelia burgdorferi DNA flagellin gene sequence. RESULTS: Of 108 patients with meningitis who qualified for the study, 20 patients met criteria for Lyme meningitis and 88 were classified as aseptic meningitis. Positive Lyme CSF-PCR was found in 1 patient (1 of 20, 5%) with Lyme meningitis and one patient classified as aseptic meningitis (1 of 88, 1%). Lyme CSF-PCR had a sensitivity of 5% and a specificity of 99%. The only Lyme meningitis patient with positive Lyme CSF-PCR had the highest CSF white blood cell count and CSF protein values compared with the other Lyme meningitis patients. CONCLUSIONS: This is the first study to evaluate Lyme CSF-PCR exclusively in North American children. This commercially available laboratory test is not generally helpful for identifying Lyme meningitis because of its low sensitivity.
Publication Types:
PMID: 16094225 [PubMed - indexed for MEDLINE]
Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients with late-stage lyme borreliosis: a pilot study.
Weissenbacher S, Ring J, Hofmann H.
Department of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany.
BACKGROUND: Chronic neuropathic pain occurs in 10-15% of patients with neuroborreliosis and is difficult to treat. OBJECTIVE: We evaluated the effect of gabapentin monotherapy on residual pain in patients with neuroborreliosis after intravenous ceftriaxone treatment. METHODS: Ten patients with neuroborreliosis and a long-lasting history of neurologic symptoms were treated with gabapentin, starting with 300 mg/day. Doses were raised over a period of 4-12 weeks to the individually effective and tolerated maximum dose (500-1,200 mg). Treatment was maintained until pain disappeared and then gradually reduced in dose over weeks. If symptoms recurred, the doses were raised again. Therapy was maintained over an average of 1-2 years. RESULTS: Pain quality and pain quantity were evaluated using the McGill pain questionnaire and a visual analogue scale. There was an improvement of 'crawling' and 'burning' pain sensations, neck and radiating lumbar pain in 9/10 (90%) patients as well as a positive effect on mood, general feeling of health and quality of sleep in 5/10 (50%) patients. The average dose leading to a clear-cut pain reduction was 700 mg. CONCLUSIONS: In an open pilot study (10 patients), gabapentin monotherapy which has to our knowledge not been published as treatment of chronic neuropathic pain in patients with late Lyme borreliosis is efficacious in treating pain associated with neuroborreliosis and can thus improve quality of life in these patients. (c) 2005 S. Karger AG, Basel
Publication Types:
PMID: 16088158 [PubMed - indexed for MEDLINE]
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Gabapentin in dermatology.
Misery L.
Publication Types:
PMID: 16088149 [PubMed - indexed for MEDLINE]
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Comment in:
The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis.
Rupprecht TA, Pfister HW, Angele B, Kastenbauer S, Wilske B, Koedel U.
Department of Neurology, Ludwig-Maximilians University, Munich, Germany.
Using protein expression profiling, the authors identified an upregulation of the chemokine B lymphocyte chemoattractant (BLC) in the CSF of patients with neuroborreliosis but not in patients with noninflammatory and various other inflammatory neurologic diseases. This upregulation was confirmed by ELISA, showing increased BLC levels in every neuroborreliosis patient while being undetectable in patients with noninflammatory neurologic diseases. These results point to BLC as a putative additional diagnostic marker for neuroborreliosis.
PMID: 16087912 [PubMed - indexed for MEDLINE]
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Comment on:
Sublime diagnosis of Lyme neuroborreliosis.
Segal BM, Logigian EL.
Publication Types:
PMID: 16087895 [PubMed - indexed for MEDLINE]
Lyme borreliosis in Portugal caused by Borrelia lusitaniae? Clinical report on the first patient with a positive skin isolate.
da Franca I, Santos L, Mesquita T, Collares-Pereira M, Baptista S, Vieira L, Viana I, Vale E, Prates C.
Outpatients Clinic of Dermatology at the Tropical Diseases Unity of the Institute of Hygiene and Tropical Medicine, University Nova de Lisboa, Lisboa, Portugal. ifranca@netcabo.pt
BACKGROUND: Borrelia lusitaniae was isolated from an Ixodes ricinus tick in Portugal in 1993 for the first time. Further, this borrelia genospecies has been found in ixodid ticks collected around the coasts of southern Portugal and North Africa. Its reservoir has not been defined yet. B. lusitaniae was isolated once until now from a patient with a long standing and expanding skin disorder. PATIENT AND METHODS: A 46-year-old Portuguese woman presented with a skin lesion on the left thigh which had evolved slowly over ten years. The patient reported limb paraesthesias, cramps, chronic headaches, and cardiac rhythm disturbances. History of tick bites was negative nor had the patient ever noticed a skin lesion comparable with erythema chronicum migrans. Skin biopsies were taken for histological evaluation, culture and DNA detection. Antibodies to borrelia were searched by indirect immunofluorescence assay and Western-blot. RESULTS: A bilateral carpal tunnel syndrome and local synovitis was diagnosed. Dermato-histology was normal, serology was negative. Spirochaetal organisms were cultured from a skin biopsy and identified as B. lusitaniae. The patient improved after a 2-week course of intravenous ceftriaxone; the skin lesions did not expand further. CONCLUSIONS: This culture confirmed skin infection by B. lusitaniae in a patient from Portugal suggests an additional human pathogen out of the B. burgdorferi sensu lato complex in Europe, particularly in Portugal.
Publication Types:
PMID: 16053200 [PubMed - indexed for MEDLINE]
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Long-term outcome of facial palsy in neuroborreliosis.
Bagger-Sjbck D, Remahl S, Ericsson M.
Departments of Otolaryngology, Karolinska University Hospital, Stockholm, Sweden. dan.bagger-sjoback@ks.se
OBJECTIVES: The objectives of this study were to examine children with previous manifest neuroborreliosis and concommitant facial palsy to see whether there were any persisting symptoms and/or signs of persistent residual facial palsy. STUDY DESIGN: Open, controlled prospective study. SETTING: Tertiary referral center (University Hospital). PATIENTS: The study was conducted on twenty-four patients with clinically manifest neuroborreliosis and facial palsy 3 to 5 years prior to the investigation. MAIN OUTCOME MEASURES: Results of the clinical examination using the House-Brackmann scale were compared to results from two neuro-physiological examinations (qEMG and ENoG). RESULTS: Approximately one-half of the patients with reported subjective symptoms of residual facial palsy had signs of slight dysfunction in the clinical examination using the House-Brackmann scale. There was no correlation between the subjective feeling of facial dysfunction and presence of clinical signs. Likewise, about one-half of the subjective facial dysfunction group, as well as the control group, were found to demonstrate pathological values in their neurophysiological examinations using qEMG and ENoG. CONCLUSIONS: This study shows that the assumption is not true that all children who had neuroborreliosis with facial palsy will heal 100%. A small proportion of the children claim that several years after the infection, they have subjective symptoms of slight facial weakness on the affected side. Our study shows that some of these children, as well as some children without subjective symptoms of facial palsy, demonstrate a slight facial weakness when examined clinically. Likewise, signs of slight-to-moderate facial motor dysfunction were revealed in about half of the children with the two neurophysiological methods utilized in this study. It is interesting to note that there was no clear correlation between the presence of subjective symptoms, objective signs, and neurophysiological results.
PMID: 16015186 [PubMed - indexed for MEDLINE]
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Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis.
Borg R, Dotevall L, Hagberg L, Maraspin V, Lotric-Furlan S, Cimperman J, Strle F.
Department of Infectious Diseases, Sahlgrenska University Hospital, Gteborg, Sweden. rebecca.borg@infect.gu.se
This prospective, open-label, non-randomized trial at the University Departments of Infectious Diseases in Ljubljana, Slovenia, and Gteborg, Sweden, was conducted to compare the kinetics of the cerebrospinal fluid (CSF) mononuclear cell count after 10-14 d of ceftriaxone or doxycycline for treatment of Lyme neuroborreliosis. 29 patients were treated with intravenous ceftriaxone 2 g daily in Ljubljana and 36 patients with oral doxycycline 400 mg daily in Gteborg. The study protocol included lumbar puncture before and 6-8 weeks after treatment initiation. There was a marked decrease (1.2 log10 x 10(6)/l) of the median CSF mononuclear cell count following treatment. With the assumption of a linear regression of the logarithmic mononuclear cell counts between the 2 lumbar punctures, no significant difference between the 2 antibiotic treatments could be found. All patients were clinically much improved after treatment. At 6 months follow-up 23 (79%) of the ceftriaxone- and 26 (72%) of the doxycycline-treated patients were completely recovered. Intravenous ceftriaxone or oral doxycycline was found to be effective, safe, and convenient for treatment of Lyme neuroborreliosis.
Publication Types:
PMID: 16012005 [PubMed - indexed for MEDLINE]
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Relevance of immunological variables in neuroborreliosis and multiple sclerosis.
Bednrov J, Stourac P, Adam P.
Department of Clinical Microbiology, Faculty Hospital, Masaryk University, Brno, Czech Republic.
OBJECTIVES: The aims were to investigate the frequency of intrathecal synthesis of specific antibodies against measles (M), rubella (R) and varicella zoster (Z) viruses (MRZ reaction) as a diagnostic marker between multiple sclerosis (MS) and neuroborreliosis (NB) groups and to postulate the most typical cerebrospinal fluid (CSF) variables profile of these entities. METHODS: Three cohorts of patients were investigated: MS (n = 42), NB (n = 27) and other neurological diseases (OND) (n = 15). Measles, rubella, varicella zoster and borrelia-specific IgG antibodies were measured by ELISA, Q(alb) (CSF/serum albumin ratio) as a marker of blood-CSF barrier function and specific antibody indices (AI) were calculated according to relevant formulae. IgG oligoclonal bands (OB) were detected by isoelectric focusing and immunoenzymatic staining. RESULTS: Eighty-eight percent of MS patients had positive MRZ reaction and 26.2% had positive anti-borrelia AI. Eighty-nine percent of NB patients had positive anti-borrelia AI and two patients had individually anti-measles and rubella positive AI. MS-CSF variables profile included the presence of IgG OB in 81%, elevated Q(alb) in 31% and normal cell count in 66.7%. Of NB patients IgG OB were positive in 74%, elevated Q(alb) in 81.5% and normal cell count in 7.4%. CONCLUSION: MRZ reaction was proved as statistically significant marker in differential diagnosis between MS and NB. Typical CSF variables profile of these two entities is highly supportive, especially when MRZ is included.
PMID: 16008535 [PubMed - indexed for MEDLINE]
[Chronic borreliosis? No, psychosomatic illness! (interview by Dr. med. Brigitte Moreano)]
[Article in German]
Egle UT.
Publication Types:
PMID: 15966166 [PubMed - indexed for MEDLINE]
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Innate immune responses in Lyme borreliosis: enhanced tumour necrosis factor-alpha and interleukin-12 in asymptomatic individuals in response to live spirochetes.
Sjwall J, Carlsson A, Vaarala O, Bergstrm S, Ernerudh J, Forsberg P, Ekerfelt C.
Divisions of Infectious Diseases, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University Hospital, Linkping, Sweden. Johanna.Sjowall@imk.liu.se
Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in DCs and IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease.
Publication Types:
PMID: 15958074 [PubMed - indexed for MEDLINE]
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Painful hallucinations and somatic delusions in a patient with the possible diagnosis of neuroborreliosis.
Br KJ, Jochum T, Hger F, Meissner W, Sauer H.
Department of Psychiatry, Friedrich-Schiller-University of Jena, Jena, Germany. karl-juergen.baer@med.uni-jena.de
Neuroborreliosis has become the most frequently recognized tick-borne infection of the nervous system in Europe and the United States. In addition to dermatological, cardiac, articular, and neurologic manifestations, psychiatric disorders such as depression, panic attacks, and schizophrenia-like psychosis can also arise. We report on a 61-year-old woman who developed a severe pain syndrome following several tick bites. She was diagnosed with neuroborreliosis; she received various courses of antibiotics over several years, but without any clinical improvement in her condition. Her eventual admission to a psychiatric ward due to mental symptoms and neuroleptic treatment led to a dramatic improvement of her pain symptoms. However, increasing delusions disclosed a psychotic episode, which ceased over time. We discuss therapeutic difficulties and psychiatric complications in the absence of a clear-cut diagnosis of neuroborreliosis. Although this patient might have suffered from late-onset schizophrenia with painful hallucinations right from the start of her disease, the case highlights psychiatric complications that might be associated with neuroborreliosis.
Publication Types:
PMID: 15951656 [PubMed - indexed for MEDLINE]
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Early differentiation of Lyme from enteroviral meningitis.
Shah SS, Zaoutis TE, Turnquist J, Hodinka RL, Coffin SE.
Divisions of Infectious Diseases, The Children's Hospital of Philadelphia, PA, USA.
BACKGROUND: Differentiating Lyme meningitis from enteroviral meningitis remains difficult because both occur mostly in the summer and early fall. This distinction is clinically important because pathogen-specific diagnostic test results are not available immediately and only patients with Lyme meningitis require parenteral antibiotic therapy. OBJECTIVES: The objective of this study was to identify clinical and laboratory features that might help clinicians distinguish patients with Lyme meningitis from those with enteroviral meningitis. METHODS: This cross-sectional study compared patients diagnosed with Lyme or enteroviral meningitis evaluated at a large children's hospital between January 1, 1999 and September 20, 2002. RESULTS: Twenty-four patients with Lyme meningitis and 151 patients with enteroviral meningitis had median ages of 10.5 and 5.5 years, respectively (P < 0.0001). There was an equal proportion of boys with Lyme (63%) and enteroviral meningitis (62%; P = 1.0). The duration of symptoms before evaluation was longer for patients with Lyme meningitis (12 days) than with enteroviral meningitis (1 day; P < 0.0001). Cranial neuropathy was a presenting feature in 71% of children with Lyme meningitis. Cranial neuropathy, erythema migrans rash or papilledema occurred in 88% of patients with Lyme meningitis; no patients with enteroviral meningitis exhibited any of these findings (P < 0.0001). Lyme meningitis was unlikely when cerebrospinal fluid neutrophils exceeded 10% (negative predictive value, 99%). CONCLUSIONS: We identified several clinical and laboratory features that may permit early differentiation of Lyme from enteroviral meningitis. These results may assist clinicians with decisions regarding additional testing and empiric antibiotic therapy.
PMID: 15933566 [PubMed - indexed for MEDLINE]
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The nervous system as ectopic germinal center: CXCL13 and IgG in lyme neuroborreliosis.
Narayan K, Dail D, Li L, Cadavid D, Amrute S, Fitzgerald-Bocarsly P, Pachner AR.
University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Lyme neuroborreliosis (LNB) is a chronic infection in which B-cell activation, plasma cell infiltration, and enhanced Ig production in infected tissue are prominent feature. However, little is known about how B cells and plasma cells invade and persist in target organs. To assess this issue, we developed real-time PCR measurements of IgG and CXCL13 production. We used these RNA assays and specific enzyme-linked immunosorbent assays for protein and demonstrated that human peripheral blood mononuclear cells (PBMCs), stimulated by Borrelia burgdorferi sonicate, produced CXCL13 and IgG. Magnetic separation of PBMC populations and flow cytometry showed that CXCL13 is produced by dendritic cells. We then measure the expression of CXCL13 and IgG in tissues and correlated the expression of these host genes with spirochetal load. We also measured expression of dbpA and BBK32, two spirochetal genes important in chronic infection. There was a strong correlation between host immune response gene expression (CXCL13 and IgG) and spirochetal load. Immunohistochemistry of infected nonhuman primates tissue confirmed that CXCL13 is expressed in the nervous system. We conclude that persistent production of CXCL13 and IgG within infected tissue, two characteristics of ectopic germinal centers, are definitive features of LNB.
Publication Types:
PMID: 15929033 [PubMed - indexed for MEDLINE]
Erratum in:- J Neurosurg. 2005 Nov;103(5):938.
Fluorine-18-labeled fluorodeoxyglucose-positron emission tomography studies of acute brainstem Lyme neuroborreliosis [corrected] Case report.
Plotkin M, Hautzel H, Krause BJ, Mohr S, Langen KJ, Mller HW.
Department of Radiology, Nuclear Medicine and Radiooncology, Campus Virchow-Klinikum, University Hospital Charit, Berlin, Germany. michail.plotkin@charite.de
The authors report on a patient suffering from acute Lyme borreliosis who underwent two consecutive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) studies demonstrating the course of the disease. The first FDG-PET study revealed markedly increased glucose metabolism in the brainstem, matching exactly the signal abnormalities exhibited on magnetic resonance images and indicating a brainstem tumor. A second PET scan demonstrated no abnormality in this region, thus reflecting clinical remission following antibiotic therapy. Data in the present case indicate that hypermetabolic findings on FDG-PET studies in the brainstem region should be regarded with caution and that neuroborreliosis must be considered as a possible differential diagnosis.
Publication Types:
PMID: 15926723 [PubMed - indexed for MEDLINE]
[Is neuroborreliosis as a cause of facial paralysis missed?]
[Article in Swedish]
Hagberg L, Strmberg A.
Publication Types:
PMID: 15921117 [PubMed - indexed for MEDLINE]
[Peripheral facial paralysis? Exclude borreliosis, perform LP!]
[Article in Swedish]
Reimer M.
Publication Types:
PMID: 15921115 [PubMed - indexed for MEDLINE]
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Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins.
Ramesh G, Philipp MT.
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Lyme borreliosis, which is prevalent both in the US and in Europe, is an infectious disease that may cause local inflammation in numerous organs. We have hypothesized that, as with some neurodegenerative diseases, the pathogenesis of the neurocognitive deficiencies associated with Lyme neuroborreliosis of the central nervous system also has an inflammatory component. Dysregulated production of pro-inflammatory cytokines such as IL-6 and TNF-alpha can lead to neuronal damage. Mitogen-activated protein kinases (MAPK) play a key role in the regulation of neuronal development, growth, and survival, as well as that of pro-inflammatory cytokine production. As a model, we explored the possibility that MAPK-mediated lipoprotein-induced apoptosis and gliosis of rhesus monkey astrocytes stimulated in vitro. Lipoproteins are the key inflammatory molecule type of Borrelia burgdorferi, the spirochete that causes Lyme disease, and we had previously shown that lipoprotein-induced TNF-alpha production in astrocytes caused astrocyte apoptosis, and IL-6 enhanced proliferation of these cells. Lipoproteins readily activated p38 and Erk1/2 MAPK, thus enlisting these pathways among the kinase pathways that spirochetes may address as they invade the central nervous system. We also investigated whether specific inhibition of p38 and Erk1/2 MAPK would inhibit TNF-alpha and IL-6 production and thus astrocyte apoptosis, and proliferation, respectively. Lipoprotein-stimulated IL-6 production was unaffected by the MAPK inhibitors. In contrast, inhibition of both p38 and Erk1/2 significantly diminished TNF-alpha production, and totally abrogated production of this cytokine when both MAPK pathways were inhibited simultaneously. MAPK inhibition thus may be considered as a strategy to control inflammation and apoptosis in Lyme neuroborreliosis.
Publication Types:
PMID: 15893422 [PubMed - indexed for MEDLINE]
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Increased expression of CXCR3 and CCR5 on memory CD4+ T-cells migrating into the cerebrospinal fluid of patients with neuroborreliosis: the role of CXCL10 and CXCL11.
Lepej SZ, Rode OD, Jeren T, Vince A, Remenar A, Barsi B.
University Hospital for Infectious Diseases, Dr. Fran Mihaljevi, Mirogojska 8, 10000 Zagreb, Croatia. Snjezana.Zidovec.Lepej@bfm.hr
The aim of this study was to evaluate the contribution of chemokine receptor CXCR3 and the corresponding ligands CXCL10 and CXCL11 to the recruitment of peripheral blood (PB) memory CD4+ T-cells into the cerebrospinal fluid (CSF) of patients with acute neuroborreliosis. Percentages of memory CD45RO+CD4+ T-cells expressing CXCR3 and CCR5 were significantly enriched in the CSF compared to the PB. Concentrations of CXCL10 and CXCL11 in the CSF of neuroborreliosis patients were significantly higher compared with the corresponding serum samples. Our results suggest that CXCL10 and CXCL11 create a chemokine gradient between the CSF and serum and recruite CXCR3-expressing memory CD4+ T-cells into the CSF of neuroborreliosis patients and that CCR5 also plays a role in this process.
Publication Types:
PMID: 15885315 [PubMed - indexed for MEDLINE]
Update of:
Lyme disease.
Hayes E, Mead P.
US Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
Publication Types:
PMID: 15865708 [PubMed - indexed for MEDLINE]
Constipation heralding neuroborreliosis: an atypical tale of 2 patients.
Shamim EA, Shamim SA, Liss G, Nylen E, Pincus JH, Yepes M.
Department of Neurology, Georgetown University Medical Center.
This is a report of 2 patients with Lyme disease who initially presented with severe constipation, which progressed to ascending muscular weakness resembling acute idiopathic polyneuritis, with neuropsychiatric symptoms, severe urinary retention, and hyponatremia. These symptoms resolved following proper antibiotic therapy.
Publication Types:
PMID: 15824271 [PubMed - indexed for MEDLINE]
[Role of interleukin-18, interleukin-1beta and its soluble receptor (sIL-1RII) in early and late Lyme borreliosis]
[Article in Polish]
Pietruczuk A, Swierzbinska R, Pietruczuk M, Hermanowska-Szpakowicz T.
Oddzial Internistyczno-Kardiologiczny Samodzielnego Szpitala Miejskiego im. PCK w Bialymstoku.
Although borreliosis was first described as a separate entity more than 20 years ago its pathogenesis still remains unknown. In recent years the role of pro- and antiinflammatory cytokines in the pathogenesis of borreliosis has been discussed. The purpose of the present study was to evaluate the role of IL-1beta, IL-18 and sIL-1RII in the development of early and late stages of borreliosis. The study group consisted of 60 patients divided into 3 groups: patients with erythema migrans, Lyme arthritis and neuroborreliosis. In all groups serum levels of IL-1beta, IL-18 and sIL-1RII were determined and in the patients with neuroborreliosis additionally in cerebrospinal fluid (CSF). The levels of cytokines and sIL-1RII were measured before the start of treatment and after its termination. Before the treatment the levels of IL-1beta, IL-18 and sIL-1RII in serum and CSF were significantly higher in all studied groups compared with the control. After the treatment, despite the regression of the clinical symptoms and significant reduction of initially high levels of the cytokines and sIL-1RII, only the levels of IL-1beta in all patients and the serum level of IL-18 in the patients with neuroborreliosis were comparable with the values in the control group. It could suggest that the inflammatory process was not inhibited completely and confirms the role of IL-1beta, IL-18 and sIL-1RII in the pathogenesis of borreliosis.
Publication Types:
PMID: 15754629 [PubMed - indexed for MEDLINE]
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Bilateral callosities, plantar ulcers and peripheral neuropathy in a 15-year-old nondiabetic boy--think of neuroborreliosis.
Wollina U, Krnert C, Heinig B.
Publication Types:
PMID: 15752310 [PubMed - indexed for MEDLINE]
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CXCL11 is involved in leucocyte recruitment to the central nervous system in neuroborreliosis.
Rupprecht TA, Koedel U, Muhlberger B, Wilske B, Fontana A, Pfister HW.
Dept. of Neurology, Klinikum Grosshadern Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany.
We investigated the role of the CXCR3 chemokine CXCL11 (I-TAC) for leukocyte recruitment to the CSF in neuroborreliosis (NB). CXCL11 levels in the CSF of 17 patients with acute NB were elevated compared with 20 non-inflammatory controls (100.1 vs. 54.1 pg/ml, p = 0.002). Using a modified Boyden chamber chemotaxis-assay, the CSF of patients with acute NB was more chemotactic than the control CSF-samples (p = 0.001). A strong correlation (p < 0.001) between CXCL11 levels, chemotactic activity and CSF-white cell count was detected. Though the chemotactic activity of CSF from NB patients was only partially reduced by a human recombinant CXCL11 antibody, these findings suggest that, among other chemotactic factors, CXCL11 may play a role in the chemotaxis of mononuclear cells in NB.
Publication Types:
PMID: 15750703 [PubMed - indexed for MEDLINE]
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[Concentration of interleukin-18, interleukin-1beta, soluble receptor for interleukin-1 (sIL-1RII) and C-reactive protein in patients with neuroborreliosis]
[Article in Polish]
Pietruczuk A, Swierzbinska R, Pietruczuk M, Kondrusik M, Zajkowska J, Pancewicz S, Hermanowska-Szpakowicz T.
I Oddzial Internistyczno-Kardiologiczny, Samodzielny Szpital Miejski im. PCK w Bialymstoku, ul. H. Sienkiewicza 79, 15-002 Bialystok, Poland. adapietr@yahoo.co.uk
BACKGROUND AND PURPOSE: The aim of the present study was to determine the role of interleukin-18 (IL-18), interleukin-1beta (IL-1beta) and its soluble receptor sIL-1RII in the pathogenesis of neuroborreliosis as well as the usefulness of C-reactive protein (CRP) determination in the diagnosis and monitoring of treatment of Lyme neuroborreliosis. MATERIAL AND METHODS: The study group consisted of 20 patients with Lyme meningitis (age range 16-72 years, mean age 42.6 years). For measurements of IL-18, IL-1beta and sIL-1RII levels in serum and cerebrospinal fluid (CSF) the control group consisted of 10 healthy volunteers and 10 patients with infection of the central nervous system ruled out, respectively. Cytokines and sIL-1RII levels in serum and CSF were measured twice, before and after the 30-day treatment period. Serum and CSF levels of IL-18, IL-1beta and sIL-1RII were measured using ELISA, and CRP serum levels were measured using the immunoturbidimetric method. RESULTS: Before the treatment the concentration of IL-18, IL-1beta and sIL-1RII in serum as well as in CSF was significantly higher as compared to the controls. After the treatment end the level of IL-18, IL-1beta and sIL-1RII was reduced but the serum level of sIL-1RII and CSF level of IL-18 and sIL-1RII remained significantly higher than in the control group. The serum level of CRP was increased only in 15% of patients and after the treatment CRP concentration returned to a basal level (except one patient in whom CRP was slightly higher than in the control group). No correlation between CRP and IL-18, IL-1beta and sIL-1RII was observed. CONCLUSIONS: Our results confirm the involvement of IL-18, IL-1beta and sIL-1RII in the pathogenesis of neuroborreliosis and uselessness of CRP determination in the diagnosis of Lyme meningitis.
Publication Types:
PMID: 15735988 [PubMed - indexed for MEDLINE]
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Delayed resolution of white matter changes following therapy of B burgdorferi encephalitis.
Steinbach JP, Melms A, Skalej M, Dichgans J.
Department of Neurology, Hertie Institute for Clinical Brain Research, University of Tbingen, School of Medicine, Germany. joachim.steinbach@uni-tuebingen.de
Publication Types:
PMID: 15728315 [PubMed - indexed for MEDLINE]
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Severe neuroborreliosis: The benefit of prolonged high-dose combination of antimicrobial agents with steroids--an illustrative case.
Massengo SA, Bonnet F, Braun C, Vital A, Beylot J, Bastard J.
Department of Neurology, Centre Hospitalier de Mont de Marsan, 40000 Mont de Marsan, France. massengoserge@hotmail.com
Neuroborreliosis frequently occurs in endemic areas, whereas encephalomyelitis is uncommon. Treatment consists classically of 2 to 4 weeks of recommended antimicrobial agents with a generally good outcome. A severe case is reported combining an encephalomyelitis with an axonal polyneuropathy. Clinical improvement was observed only with the use of prolonged high dose of 2 antimicrobial agents combined with steroids.
Publication Types:
PMID: 15698718 [PubMed - indexed for MEDLINE]
The Therapy of Lyme Neuroborreliosis.
Pachner AR.
Department of Neurology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. pachner@umdnj.edu.
The challenge for the neurologist in the treatment of Lyme neuroborreliosis is not in the treatment per se, but in the diagnosis. Neurological manifestations of Lyme disease can present in many forms, and diagnostic techniques which detect the spirochete directly; the culture or polymerase chain reaction of the spirochete in cerebrospinal fluid, are of disappointingly low yield. Therefore, the diagnosis is frequently not easy. After the diagnosis is made, antibiotic therapy is straightforward; Lyme neuroborreliosis should be treated with at least 2 weeks of antibiotics. In the United States, intravenous therapy with ceftriaxone or penicillin for 2 weeks is the standard, whereas in Europe oral doxycycline therapy is commonly administered. Either is effective, and my choice of therapy generally depends on the patient. Many patients have symptoms which continue after antibiotic therapy referable to persistent inflammation, and, for those patients, I will commonly prescribe nonsteroidal anti-inflammatory medications.
PMID: 15676120 [PubMed - as supplied by publisher]
Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease.
Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ.
University Institute of Pathology, Division of Neuropathology, University Medical School (CHUV), 1011, Lausanne, Switzerland. judmik@telus.net
The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.
Publication Types:
PMID: 15665404 [PubMed - indexed for MEDLINE]
Research opportunities on human neuroborreliosis.
Gelderblom H, Martin R, Marques AR.
Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
A workshop, sponsored by the National Institutes of Health, was convened in September 2001 to evaluate the current knowledge in neurological Lyme disease. The meeting was centered into discussion of both clinical and basic aspects of the disease. Participants included researchers from the fields of infectious diseases, neurology, rheumatology, autoimmunity and basic immunology, largely but not exclusively focused on Lyme disease. This report summarizes the presentations made at the meeting.
Publication Types:
PMID: 15631071 [PubMed - indexed for MEDLINE]
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[Neurosyphilis and neuroborreliosis. Retrospective evaluation of 22 cases]
[Article in German]
Blatz R, Khn HJ, Hermann W, Rytter M, Rodloff AC.
Institut fr Medizinische Mikrobiologie, Universitt Leipzig. blatzr@medizin.uni-leipzig.de
We present laboratory data from 22 patients suspected of having neurosyphilis. In two cases the suspicion could not be confirmed, and in 20 cases neurosyphilis was detected. The sera from 17 patients were also assayed for Borrelia-specific antibodies. Suspicious immunoglobulin G antibody indices were detected in nine cases and a suspicious immunoglobulin M antibody index in one. In six of these, stored CSF/serum pairs were available to specify the antibodies by immunoblotting. This allowed for the identification of one patient apparently infected by both Borrelia spp. and Treponema pallidum. In all cases of newly suspected neurosyphilis, we recommend considering neuroborreliosis at the same time.
Publication Types:
PMID: 15580469 [PubMed - indexed for MEDLINE]
Update in:
Update of:
Lyme disease.
Hayes E.
US Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
Publication Types:
PMID: 15555127 [PubMed - indexed for MEDLINE]
[Pain and neuroborreliosis]
[Article in German]
Berthele A, Tlle TR.
Neurologische Klinik derTU Mnchen.
Pain is one of the presenting symptoms in acute neuroborreliosis. Classically, acute neuroborreliosis--also known in Europe as Bannwarth's syndrome--is a combination of radicular pain, cranial neuritis and peripheral radiculitis and inflammatory changes of the CSF. The prognosis following antibiotic therapy is favorable. At least in its early stages, however, the diagnosis neuroborreliosis might be missed or mistaken. Thus, targeted assessment of typical signs is needed to expedite examination of the CSF which then permits definitive diagnosis.
Publication Types:
PMID: 15540558 [PubMed - indexed for MEDLINE]
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Acute peripheral facial palsy in Lyme disease -- a distal neuritis at the infection site.
Eiffert H, Karsten A, Schlott T, Ohlenbusch A, Laskawi R, Hoppert M, Christen HJ.
Department of Bacteriology University of Gttingen, Germany.
AIM: Children with acute peripheral facial palsy have often suffered tick bites and/or erythema migrans in the head/neck region on the same side. With respect to the pathogenesis of neuroborreliosis this topographical association was investigated in an animal model. METHODS: A Borrelia garinii strain, isolated from the CSF of a child with acute facial palsy, was injected in 9 rats intracutaneously in the right subauricular region. Infected rats were examined for clinical symptoms of Lyme disease, the spread of the spirochetes was investigated by PCR of necropsies (facial nerves, trigeminus nerves, heart, brain, skin) up to 47 days after infection. The nerve tissues were investigated by histology, immunohistochemistry and electron microscopy. RESULTS: None of the rats developed a facial palsy or other symptoms of Lyme disease. Borrelia DNA was found in the heart after 5 days and in the brain after 7 days of infection up to the end of investigation (47 days), as well as in the ipsilateral peripheral nerves after 7 to 33 days. Borrelia was detected by electron microscopy near endoneural vessels of the facial nerve. Peri-, epi-, and endoneural infiltrations of macrophages, plasma cells and B cells characterized an inflammation of the facial and trigeminus nerves ipsilateral to the infection site. CONCLUSION: An infection with Borrelia garinii in the subauricular region induces an ipsilateral neuritis of peripheral nerves. The particular vulnerability of the human facial nerve may be a result of its long intraosseus course. Thus, an inflammatory edema may injure the nerve in the canalis facialis.
PMID: 15534758 [PubMed - indexed for MEDLINE]
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Acute transverse myelitis as a main manifestation of early stage II neuroborreliosis in two patients.
Meurs L, Labeye D, Declercq I, Piret F, Gille M.
Department of Neurology, Clinique Sainte-Elisabeth, Brussels, Belgium.
Publication Types:
PMID: 15528925 [PubMed - indexed for MEDLINE]
[Rapid development of dementia of an elderly person, diagnosis and successful treatment]
[Article in Finnish]
Andersson C, Nyberg C, Nyman D.
Alands Centralsjukhus Medicinska enheten, Mariehamn.
Publication Types:
PMID: 15508763 [PubMed - indexed for MEDLINE]
Borrelia valaisiana in cerebrospinal fluid.
Diza E, Papa A, Vezyri E, Tsounis S, Milonas I, Antoniadis A.
Publication Types:
PMID: 15503409 [PubMed - indexed for MEDLINE]
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[Evaluation of proinflammatory cytokine (TNF-alpha, IL-1beta, IL-6, IFN-gamma) concentrations in serum and cerebrospinal fluid of patients with neuroborreliosis]
[Article in Polish]
Kondrusik M, Swierzbinska R, Pancewicz S, Zajkowska J, Grygorczuk S, Hermanowska-Szpakowicz T.
Klinika Chorb Zakanych i Neuroinfekcji, Akademia Medyczna w Bialymstoku. mkondrusik@poczta.onet.pl
BACKGROUND AND PURPOSE: Neuroborreliosis is a tick transmitted disease which becomes an increasingly frequent diagnostic and therapeutic problem in physician practice. The purpose of this work was to evaluate the concentration of proinflammatory cytokines: IL-1beta, IL-6, TNF-alpha, IFN-gamma in serum and cerebrospinal fluid of patients with neuroborreliosis. MATERIAL AND METHODS: 20 persons with diagnosed neuroborreliosis and 10 persons as a control group were examined in this study. The examination of serum and cerebrospinal fluid was performed twice, before and after 4-week therapy with antibiotics. The concentration of cytokines was measured by the ELISA method using kits of Bender Medical System and Quantikine RD Systems. RESULTS: The concentration of measured cytokines IL-1beta, IL-6, TNF-alpha and IFN-gamma in serum and cerebrospinal fluid was significantly higher before therapy. After 4-week therapy with antibiotics the concentration of cytokines in cerebrospinal fluid decreased but was still higher than in the control group except for IL-1beta. CONCLUSIONS: The detection of proinflammatory cytokine concentration in serum and cerebrospinal fluid might be helpful as another parameter monitoring the inflammation course and therapy efficacy.
Publication Types:
PMID: 15383953 [PubMed - indexed for MEDLINE]
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Comment on:
MR findings in acute cerebellitis.
Van der Stappen A, De Cauwer H, van den Hauwe L.
Publication Types:
PMID: 15378339 [PubMed - indexed for MEDLINE]
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The VlsE (IR6) peptide ELISA in the serodiagnosis of lyme facial paralysis.
Peltomaa M, McHugh G, Steere AC.
Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. miikka.peltomaa@iki.fi
OBJECTIVE: Facial paralysis is a manifestation of early disseminated Lyme neuroborreliosis. In the current study, we compared the immunoglobulin G (IgG) VlsE (sixth invariant region) peptide enzyme-linked immunosorbent assay (ELISA) with the current two-tier approach of sonicate ELISA and Western blot in the serodiagnosis of Lyme facial paralysis. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Serum samples from 47 Lyme patients with facial paralysis and 86 control subjects were analyzed for IgG antibodies to VlsE peptide of Borrelia burgdorferi and for immunoglobulin M (IgM) and IgG antibodies to sonicate antigens of B. burgdorferi using the two-tier approach. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Serum IgG antibody responses to VlsE (IR6) peptide. RESULTS: All 47 (100%) patients with facial paralysis and 4 (5%) of 86 controls had positive antibody responses to the VlsE peptide. In the two-tier test, 41 (87%) patients had positive IgM, 31 (66%) had positive IgG, and all 47 patients had positive IgM or IgG responses. Of the 86 control subjects, 2 (2%) had positive results with the two-tier test. Thus, the sensitivities of the VlsE and the two-tier tests were 100%; the specificity of the VlsE ELISA was 95% and the specificity of the two-tier test was 98%. CONCLUSIONS: The VlsE peptide ELISA showed a high sensitivity and specificity in the serological diagnosis of Lyme facial paralysis, similar to the two-tier test. The principal advantage of the VlsE peptide ELISA is that it requires only one test rather than four tests. However, the specificity of the VlsE test may not be as high as that of the two-tier test.
Publication Types:
PMID: 15354020 [PubMed - indexed for MEDLINE]
Clinical effects of fluconazole in patients with neuroborreliosis.
Schardt FW.
Betriebsrztliche Untersuchungsstelle, Bayerische Julius-Maximilians-Universitt, Wrzburg, Germany. Fritz.Schardt@mail.uni-wuerzburg.de
Eleven patients with neuro-borreliosis had been treated with 200 mg fluconazole daily for 25 days after an unsuccessful therapy with antibiotics. At the end of treatment eight patients had no borreliosis symptoms and remained free of relapse in a follow-up examination one year later. In the remaining four patients, symptoms were considerably improved. At the end of therapy immune reactivity (IgM+) disappeared in three patients. Since borrelia spp. are almost exclusively localised intracellular, they may depend on certain metabolites of their eucaryotic host cell. Inhibition of P450 and other cytochromes by fluconazole may incapacitate Borrelia upon longterm exposure.
PMID: 15337633 [PubMed - indexed for MEDLINE]
[Isocyanate exposure in first line differential diagnosis. A case report illustrates general practitioners' symptom dilemma]
[Article in Swedish]
Jrhult B.
Oxnehaga vrdcentral, Jnkping. bengt.jarhult@lj.se
Publication Types:
PMID: 15314938 [PubMed - indexed for MEDLINE]
[Lyme borreliosis--the most frequent vector-borne infection in Denmark]
[Article in Danish]
Lebech AM, Hansen K.
H:S Rigshospitalet, Epidemiklinikken og Neurologisk Afdeling. Lebech@dadlnet.dk
PMID: 15283107 [PubMed - indexed for MEDLINE]
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[Clinical courses of acute and chronic neuroborreliosis following treatment with ceftriaxone]
[Article in German]
Kaiser R.
Neurologische Klinik, Stdtisches Klinikum Pforzheim. Kaiser.Neurologische_Klinik@Stadt-Pforzheim.de
Between 1990 and 2000, a total of 101 patients with acute (n=86) or chronic (n=15) neuroborreliosis (proven by clinical data, pleocytosis in the CSF, and elevated Borrelia burgdorferi-specific antibody indices) were treated with 2 g of ceftriaxone per day for either 2 or 3 weeks. The patients were reexamined clinically and serologically after 3, 6, and 12 months. Six (12) months after the antibiotic treatment, about 93% (95%) of the patients with acute neuroborreliosis and 20% (66%) of the patients with chronic neuroborreliosis were cured. One year after treatment, four patients with acute neuroborreliosis still suffered from facial palsy and five with chronic neuroborreliosis still had moderate spastic ataxic gait disturbance. The prognosis of facial palsy in neuroborreliosis is quite similar to that in idiopathic facial palsy, while that in chronic neuroborreliosis largely depends on the time elapsed before diagnosis.
Publication Types:
PMID: 15257378 [PubMed - indexed for MEDLINE]
Heterogeneity of the immunodominant surface protein VlsE among the three genospecies of Borrelia burgdorferi pathogenic for humans.
Gttner G, Schulte-Spechtel U, Wilske B.
Max von Pettenkofer Institute, National Reference Center for Borreliae, Munich, Germany. goettner@m3401.mpk.med.uni-muenchen.de
PMID: 15147003 [PubMed - indexed for MEDLINE]
Significant improvement of the recombinant Borrelia IgG immunoblot for serodiagnosis of early neuroborreliosis.
Schulte-Spechtel U, Lehnert G, Liegl G, Fingerle V, Heimerl C, Johnson B, Wilske B.
Max von Pettenkofer-Institut, National Reference Center for Borreliae, Munich, Germany. Spechtel@m3401.mpk.med.uni-muenchen.de
PMID: 15146999 [PubMed - indexed for MEDLINE]
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Borrelia-specific interferon-gamma and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome.
Widhe M, Jarefors S, Ekerfelt C, Vrethem M, Bergstrom S, Forsberg P, Ernerudh J.
Divisions of Clinical Immunology and Infectious Diseases, Department of Molecular and Clinical Medicine, Linkoping University, Linkoping, Sweden. mona.widhe@imk.liu.se
The Borrelia-specific interferon (IFN)- gamma and interleukin (IL)-4 responses of 113 patients and control subjects were analyzed using the sensitive enzyme-linked immunospot method. Cerebrospinal fluid (CSF) and blood samples were obtained, during the course of disease, from patients with chronic or nonchronic neuroborreliosis (NB) and from control subjects without NB. Blood samples were obtained from patients with Lyme skin manifestations and from healthy blood donors. Early increased secretion of Borrelia-specific IFN- gamma (P<.05) and subsequent up-regulation of IL-4 (P<.05) were detected in the CSF cells of patients with nonchronic NB. In contrast, persistent Borrelia-specific IFN- gamma responses were observed in the CSF cells of patients with chronic NB (P<.05). In patients with erythema migrans, increased IFN- gamma (P<.001) was observed in blood samples obtained early during the course of disease, whereas increased IL-4 (P<.05) was observed after clearance. On the contrary, patients with acrodermatitis chronica atrophicans had Borrelia-specific IFN- gamma (P<.001), but not IL-4, detected in blood samples. The present data suggest that an initial IFN- gamma response, followed by up-regulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN- gamma response may lead to chronic Lyme borreliosis.
Publication Types:
PMID: 15122525 [PubMed - indexed for MEDLINE]
Comment in:
[Clinical spectrum and incidence of neuro-borreliosis in the Netherlands]
[Article in Dutch]
Kuiper H.
Flevoziekenhuis, afd. Neurologie, Hospitaalweg 1, 1315 RA Almere. hkuiper@flevoziekenhuis.nl
OBJECTIVE: To determine the clinical spectrum and incidence of neuroborreliosis in the Netherlands. DESIGN: Retrospective. METHOD: All neurological practices in 106 hospital locations in the Netherlands were asked to look for patients with the codes 'other neurological infections' or 'Borrelia burgdorferi' in their Diagnosis & Treatment Combinations registration or the Neurological Coding System, respectively, concerning the year 2001, then to identify the patients with neuroborreliosis and to send a copy of the correspondence with the family doctor and the laboratory data on these patients, after making them anonymous, for data extraction. Pleocytosis in the cerebrospinal fluid combined with a positive test for IgM or IgG antibodies of B. burgdorferi in the serum or cerebrospinal fluid was used as the criterion for the diagnosis neuroborreliosis. RESULTS: Forty-seven (44%) neurological practices did not respond and twenty-two (21%) either did not use any kind of diagnosis registration system or linkage between the registration and the patient file was impossible. Of the 37 (35%) neurological practices that provided information, 17 had diagnosed neuroborreliosis in 30 patients, 20 of whom met the specified criteria. Fifteen (75%) patients had a radiculopathy, 8 (40%) a peripheral facial palsy and 3 (15%) a myelopathy. CONCLUSION: The clinical spectrum of patients with neuroborreliosis was consistent with that described in Denmark. The incidence of neuroborreliosis found was 3.6 per million inhabitants. The real incidence was probably higher because the registration systems used allowed patients with neuroborreliosis to be booked under other (symptomatic) diagnostic codes, paediatricians were not involved in the study, and relatively few participating neurologists practiced in high-risk areas for tick bites and erythema migrans. The low incidence of neuroborreliosis in combination with a high background level of seropositivity in the population implies a low predictive value of positive Borrelia serology. It is therefore essential that when neuroborreliosis is suspected, the cerebrospinal fluid should always be investigated.
Publication Types:
PMID: 15106319 [PubMed - indexed for MEDLINE]
[Differential diagnosis of Lyme borreliosis]
[Article in German]
Woessner R, Treib J.
Neurologische Klinik, Westpfalz-Klinikum GmbH, Kaiserslautern. r.woessner@gmx.de
In all three stages, Lyme borreliosis offers a wide range of possible differential diagnoses: even the "typical" erythema chronicum migrans may present as erysipelas, erysipeloid, erythema annulare centrifugum or a drug-induced exanthema. In the advanced stages II and III, neuroborreliosis in particular may be mimicked by various other conditions of both infectious and noninfectious etiology. Major examples are CEE (Central European Encephalitis), ehrlichiosis, chlamydial infections and multiple sclerosis. Currently, the biggest diagnostic problem is the non-standardized laboratory diagnostic work-up. For this reason, even in the presence of a positive or borderline IgG antibody result, unclear symptoms should prompt a differential diagnostic investigation.
Publication Types:
PMID: 15104265 [PubMed - indexed for MEDLINE]
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Hypoglycorrhachia in Lyme meningitis.
Dayan NE, Rubin LG, Di John D, Sood SK.
Division of Pediatric Infectious Diseases, Department of Pediatrics, Schneider Children's Hospital of the North Shore-Long Island Jewish Health System, New Hyde Park, NY, USA.
We describe a previously healthy 11-year-old girl with acute neuroborreliosis, who presented with left sixth cranial nerve palsy, elevated intracranial pressure, markedly elevated cerebrospinal fluid leukocyte count and protein concentration and severe hypoglycorrhachia. These laboratory findings are atypical for neuroborreliosis.
Publication Types:
PMID: 15071301 [PubMed - indexed for MEDLINE]
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Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.
Iero I, Elia M, Cosentino FI, Lanuzza B, Spada RS, Toscano G, Tripodi M, Belfiore A, Ferri R.
Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, I-94018 Troina (EN), Italy. ivaniero@oasi.en.it
Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.
Publication Types:
PMID: 15060815 [PubMed - indexed for MEDLINE]
Levels of apolipoprotein A-II in cerebrospinal fluid in patients with neuroborreliosis are associated with lipophagocytosis.
Tborskù L, Adam P, Sobek O, Dostl M, Dvorkov J, Dubsk L.
Department of Clinical Biochemistry, Hospital Homolka, 150 30 Prague, Czechia.
Levels of most of the examined proteins in cerebrospinal fluid (CSF) of 107 patients with neuroborreliosis were associated with cytological findings, the status of hematoencephalic barrier as evaluated by Qalb (cerebrospinal fluid to serum quotient) and the intrathecal synthesis of immunoglobulins. Cytological findings consisted of normal cytology, or both oligocytosis and pleocytosis of monocytes or lymphocytes. The lipophagic elements were present in 20% of samples. Concentrations of apolipoproteins A-I and A-II in the CSF were correlated with the concentration of albumin without regard to the CSF cytology. The levels of apolipoprotein B were increased only in samples with lymphocytic pleocytosis and Qalb > 7.4. The presence of lipophages in the CSF was significantly associated with the CSF concentration of apolipoprotein A-II.
PMID: 15058201 [PubMed - indexed for MEDLINE]
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MR imaging in neuroborreliosis of the cervical spinal cord.
Hattingen E, Weidauer S, Kieslich M, Boda V, Zanella FE.
Institute of Neuroradiology, University of Frankfurt, Schleusenweg 2-16, 60528 Frankfurt, Germany. elkejoerg@web.de
The central nervous system is involved in 10-20% of cases in Lyme disease. The neurological symptoms, time course of the disease and imaging findings are multifaceted. We report two patients with cervical radiculitis. Magnetic resonance imaging revealed strong enhancement of the cervical nerve roots on contrast-enhanced T1-weighted images. These imaging patterns of borrelia-associated radiculitis have not been reported before. Knowledge of these imaging features may help to diagnose neuroborreliosis, which presents with non-specific symptoms.
Publication Types:
PMID: 15048581 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis.
Prasad A, Younger DS.
New York University School of Medicine, New York 10021, USA.
The series on treatable neuromuscular disorders continues with the present article on the peripheral nervous system manifestations of Lyme neuroborreliosis.
PMID: 15010714 [PubMed]
[Borrelia infection with shoulder pain as the primary symptom]
[Article in Danish]
M¿ller TR.
Vejle Sygehus, Neurologisk Afdeling.
Publication Types:
PMID: 15005045 [PubMed - indexed for MEDLINE]
Preferential presence of decorin-binding protein B (BBA25) and BBA50 antibodies in cerebrospinal fluid of patients with neurologic Lyme disease.
Fikrig E, Coyle PK, Schutzer SE, Chen M, Deng Z, Flavell RA.
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. erol.fikrig@yale.edu
Borrelia burgdorferi antibodies preferentially present in cerebrospinal fluid (CSF) were examined by differentially probing a B. burgdorferi expression library with CSF and sera from patients with neurologic Lyme disease. Several phage clones selectively reacted with CSF, and these genes were then expressed in recombinant form and used to detect specific antibody in an enzyme-linked immunosorbent assay. Decorin-binding protein B (BBA25) and BBA50 (hypothetical protein) elicited immunoglobulin G (IgG) or IgM detectable in CSF-but not sera-of patients, demonstrating preferential antibody production during neuroborreliosis.
Publication Types:
PMID: 15004083 [PubMed - indexed for MEDLINE]
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Cranial bacterial infection.
Anslow P.
Department of Neuroradiology, Racliffe Infirmary, Oxford, OX2 6HE, UK. panslow@quista.net
Early diagnosis of cranial sepsis is mandatory if morbidity is to be avoided. In the case of structural integrity of the skull, haematogenous spread or extension from adjacent structures, especially the sinuses, are the most common sources of infection. Infections may be limited to compartments by the meninges or spread diffusely. Focal disease includes brain abscess as well as subdural and extradural empyaema. A history or signs of sinus disease should always be sought. Tuberculosis, lyme disease and listeriosis may present specific pathological findings. A series of cases is presented to illustrate the role of imaging in infective disease and to draw attention to diagnostic and management points of which radiologists should be aware.
Publication Types:
PMID: 14749953 [PubMed - indexed for MEDLINE]
Spinal cord involvement in the nonhuman primate model of Lyme disease.
Bai Y, Narayan K, Dail D, Sondey M, Hodzic E, Barthold SW, Pachner AR, Cadavid D.
Department of Neurology and Neuroscience, and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Lyme borreliosis is a multisystemic disease caused by infection with various genospecies of the spirochete Borrelia burgdorferi. The organs most often affected are the skin, joints, the heart, and the central and peripheral nervous systems. Multiple neurological complications can occur, including aseptic meningitis, encephalopathy, facial nerve palsy, radiculitis, myelitis, and peripheral neuropathy. To investigate spinal cord involvement in the nonhuman primate (NHP) model of Lyme borreliosis, we inoculated 25 adult Macaca mulatta with B. burgdorferi sensu strictu strains N40 by needle (N=9) or by tick (N=4) or 297 by needle (N=2), or with B. burgdorferi genospecies garinii strains Pbi (N=4), 793 (N=2), or Pli (N=4) by needle. Immunosuppression either transiently (TISP) or permanently (IS) was used to facilitate establishment of infection. Tissues and fluids were collected at necropsy 7-24 weeks later. Hematoxylin and eosin staining was used to study inflammation, and immunohistochemistry and digital image analysis to measure inflammation and localize spirochetes. The spirochetal load and C1q expression were measured by TaqMan RT-PCR. The results showed meningoradiculitis developed in only one of the 25 NHP's examined, TISP NHP 321 inoculated with B. garinii strain Pbi. Inflammation was localized to nerve roots, dorsal root ganglia, and leptomeninges but rarely to the spinal cord parenchyma itself. T cells and plasma cells were the predominant inflammatory cells. Significantly increased amounts of IgG, IgM, and C1q were found in inflamed spinal cord. Taqman RT-PCR found spirochetes in the spinal cord only in IS-NHP's, mostly in nerve roots and ganglia rather than in the cord parenchyma. C1q mRNA expression was significantly increased in inflamed spinal cord. This is the first comprehensive study of spinal cord involvement in Lyme borreliosis.
Publication Types:
PMID: 14688796 [PubMed - indexed for MEDLINE]
[Assessment of etiological diagnostics in adults with aseptic encephalomeningitis--own material]
[Article in Polish]
Piekarska A, Zboinska J, Szymczak W.
Klinika Chorb Zakanych Uniwersytetu Medycznego w üodzi.
OBJECTIVE: Epidemiologic, etiologic and clinical assessment of patients with aseptic encephalomeningitis (AE); evaluation of efficacy of diagnostic process. METHODS: From January 1996 to August 2002, in seventy seven patients AE was diagnosed on the basis of lymphocytic predominance in cerebrospinal fluid (CSF) and negative culture of CSF. Analysis comprised: etiology, course of the disease and spectrum of used diagnostic tests. RESULTS: In 48/77 patients (62.3%) etiology was not identified. In 8/77 patients (10.3%) herpes simplex encephalitis was diagnosed, in 7/77 (9.1%) neuroborreliosis, in 6/77 (7.8%) tuberculosis encephalitis, in 3/77 (3.9%) listerial meningitis, in 3/77 (3.9%) mumps meningitis, and in remaining 2/77 (2.6%) tick-borne encephalitis. The incidence of AE was higher in summer (42.9%) than in any other season. In 14/77 patients (18.2%) the episode of unconsciousness occurred in the course of the disease. In 6 of these 14 patient etiology was unknown, in 4 tuberculosis AE, in 2 herpes simplex encephalitis and in 2 neuroborreliosis was diagnosed. In 7 of 77 patients (9.0%) et least one episode of convulsions occurred. CONCLUSIONS: In 62.3% of patients etiology remained unknown due to clinical and economic reasons. Aseptic encephalomeningitis in adults not always mean the viral etiology and mild course of the disease.
Publication Types:
PMID: 14682162 [PubMed - indexed for MEDLINE]
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Proton MR spectroscopy in neuroborreliosis: a preliminary study.
Ustymowicz A, Tarasw E, Zajkowska J, Walecki J, Hermanowska-Szpakowicz T.
Department of Radiology, Medical Academy, Bialystok, Poland. ambau@yahoo.com
We report results of a magnetic resonance spectroscopy (MRS) study in 12 patients with neuroborreliosis. We used a PRESS sequence, placing an 8 cm3 voxel in normal-appearing white matter of the frontal lobe. Peaks indicating N-acetylaspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mI), lipids (Lip) and lactate (Lac) were identified and ratios of NAA/Cr, Cho/Cr, mI/Cr, Lip/Cr, Lac/Cr calculated. Significant increases in Cho/Cr and Lip/Cr were noted. No abnormality was found in mean NAA/Cr and Lac/Cr, but in four patients there was a decreased NAA peak; mI/Cr ratio was slightly increased. Although the spectroscopic profile in patients with neuroborreliosis seems to be nonspecific, MRS might be useful for assessing tissue damage of the central nervous system.
PMID: 14663542 [PubMed - indexed for MEDLINE]
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Phenotypes indicating cytolytic properties of Borrelia-specific interferon-gamma secreting cells in chronic Lyme neuroborreliosis.
Ekerfelt C, Jarefors S, Tynngrd N, Hedlund M, Sander B, Bergstrm S, Forsberg P, Ernerudh J.
Division of Clinical Immunology, Department of Molecular and Clinical Medicine, University of Linkping, Linkping, Sweden. Christina.Ekerfelt@imk.liu.se
The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-gamma (IFN-gamma), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-gamma. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-gamma-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCRgammadelta, which both have cytolytic properties, were the main phenotypes of IFN-gamma-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.
Publication Types:
PMID: 14644037 [PubMed - indexed for MEDLINE]
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Diagnosis of Lyme neuroborreliosis with antibodies to recombinant proteins DbpA, BBK32, and OspC, and VlsE IR6 peptide.
Panelius J, Lahdenne P, Saxn H, Carlsson SA, Heikkil T, Peltomaa M, Lauhio A, Seppl I.
Haartman Institute, Dept. of Bacteriology and Immunology, University of Helsinki, 21, 00014, Helsinki, Finland. jaana.panelius@helsinki.fi
Three recombinant antigens, decorin binding protein A (DbpA), BBK32, and outer surface protein C (OspC), and IR(6) peptide of borrelial VlsE protein, were evaluated for the diagnosis of neuroborreliosis (NB), using cerebrospinal fluid (CSF) and serum samples from 89 patients. Their performances in enzyme-linked immunosorbent assay (ELISA) were compared with that of commercial flagella antigen. IgG ELISAs were performed with three variants of each recombinant antigen originating from Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii, and with the IR(6) peptide. IgM antibodies were analysed against OspC and flagella. Of the patients whose CSF contained elevated anti-flagella IgG antibodies, 93% were positive for at least three of the new antigens. Of those with negative or borderline CSF anti-flagella antibodies, 51% were positive for three new antigens. Antibodies to BBK32 were detectable mainly in early disease. Antibodies to DbpA and IR(6) were observed in early and late NB. The use of the new antigens at presentation of the disease improved the laboratory diagnosis of NB. In IgG ELISAs, the diagnostic sensitivity of assays with the new antigens was between 75 and 88%, but was only 52% with the flagella antigen. The discriminatory power between patient and control samples appeared better in the CSF than in the serum. We suggest that assessment of CSF antibodies to at least two antigens, using either flagella and one of the new antigens or two of the new antigens, would improve the current diagnostic yield of NB.
Publication Types:
PMID: 14648148 [PubMed - indexed for MEDLINE]
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Neuroborreliosis with vasculitis causing stroke-like manifestations.
Romi F, Krkenes J, Aarli JA, Tysnes OB.
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Publication Types:
PMID: 14639033 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis mimicking primary CNS lymphoma.
Walther EU, Seelos K, Bise K, Mayer M, Straube A.
Department of Neurology, Klinikum Grosshadern, Munich, Germany.
Publication Types:
PMID: 14639029 [PubMed - indexed for MEDLINE]
Comment in:
[Pain, fatigue, depression after borreliosis. Antibiotics used up--what next?]
[Article in German]
Woessner R, Treib J.
Neurologische Klinik, Westpfalz-Klinikum GmbH, Kaiserslautern. rwoessner@westpfalz-klinikum.de
Antibiotic treatment--usually stage-dependent in terms of the active agent, duration and form of application--is the central pillar in the management of Lyme disease. In the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment. In this phase, borreliosis-typical neuropathy and neuralgia, chronic fatigue and neuropsychological deficits predominate. Irrespective of whether renewed antibiotic treatment is indicated or not, symptomatic treatment must be continued.
Publication Types:
PMID: 14603682 [PubMed - indexed for MEDLINE]
Apoptosis in Lyme borreliosis--a preliminary study.
Grygorczuk SS, Pancewicz SA, Kondrusik M, Swierzbinska R, Zajkowska JM, Hermanowska-Szpakowicz T.
Department of Infectious Diseases and Neuroinfections, Medical University of Bialystok, Dluski District Specialized Hospital, ul. Zurawia 14, 15-540 Bialystok, Poland. samgryg@friko6.onet.pl
BACKGROUND: Apoptosis plays an important role in the control of the immune system, and its impairment may be associated with autoimmune responses. Different bacterial and viral pathogens interfere with the regulation of apoptosis. This may take place in Lyme borreliosis, in which pathological autoimmune reactions are likely to occur. MATERIAL/METHODS: A study group consisted of 15 patients with erythema migrans (group I), 15 with Lyme arthritis (group II) and 9 with neuroborreliosis (group III); the control group consisted of 10 healthy subjects. The concentrations of the factors involved in apoptosis regulation--transforming growth factor-beta1 (TGF-beta 1), soluble Fas (sFas), soluble Fas ligand (sFasL) and protein bcl-2--were measured in serum before (examination 1) and after (examination 2) four weeks of antibiotic treatment. RESULTS: The mean concentration of sFas was significantly higher in all study groups compared to controls in examination 1 and 2, and showed a tendency to increase during treatment. The concentration of sFasL was significantly increased in groups II and III in examination 1. The concentration of bcl-2 was elevated significantly in all groups in examination 1 and dropped during treatment, remaining significantly increased in group I. The concentration of TGF-beta 1 was not significantly elevated except for group II in examination 2. CONCLUSIONS: The concentrations of soluble factors involved in the regulation of apoptosis were increased in serum of patients with different forms of Lyme borreliosis. Further studies are necessary to confirm if inappropriate apoptosis of immune cells may contribute to the pathogenesis of Lyme disease.
PMID: 14586269 [PubMed - indexed for MEDLINE]
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[Epidemiology and therapy of Lyme arthritis and other manifestations of Lyme borreliosis in Germany: results of a nation-wide survey]
[Article in German]
Priem S, Munkelt K, Franz JK, Schneider U, Werner T, Burmester GR, Krause A.
Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Universittsklinikum Charit, Berlin.
AIM OF THE STUDY: Only little is known about the epidemiology of Lyme borreliosis in Germany. As an example, it is still unclear if there are regional differences in the incidence of Lyme disease in general or of certain clinical manifestations like Lyme arthritis. Moreover, standardization of diagnostic or therapeutic procedures does not exist. Therefore, a Germany-wide questionnaire-based survey was conducted in order to achieve more epidemiological data and to obtain more information about the diagnostic and therapeutic approaches of general practitioners and specialists. METHODS: A self-designed questionnaire was distributed along with two editions of the journal "Deutsches Arzteblatt" (which is delivered to every physician in Germany) and additionally by a pharmaceutical company. During the collection period from March 1, 1998 to February 28, 1999, patients with Lyme disease were reported and information was given about site of infection, diagnostic procedures, clinical symptoms, treatment, and outcome. RESULTS: Altogether 3935 patients were reported. Their mean age was 43.4 years with the peak incidences around the ages of 10 and 60 years. 37.3% of the questionnaires were sent in by general practitioners, 17.6% by dermatologists, 15.7% by pediatricians, 9.7% by internists, and 2.7% by neurologists. 83% of the patients did not have a special infecion risk. The most frequent clinical Lyme manifestation was erythema migrans (EM), which occurred in 50.9% of the patients. 21.3% suffered from general symptoms. Of special interest, 24.5% of the patients had Lyme arthritis (14.7% mon- or oligoarthritis, 9.8% polyarthritis). Therefore, arthritis was more frequently reported than neuroborreliosis (18.4%). Only 16% of the neuroborreliosis patients and 32% of the arthritis patients remembered having had an EM. 189 patients (4.8%) with lymphadenosis cutis benigna and 100 patients (2.5%) with acrodermatitis chronica atrophicans were reported. In 80.4% of the patients, positive Lyme serology was detected. In a few cases, the diagnosis was established by isolation of borreliae, PCR or histology. 3754 patients were treated by antibiotics. The most frequently used compounds were doxycycline (50.4%), followed by ceftriaxone (22.4%), amoxicillin (13.6%), penicillin (7%), and erythromycin (4.2%) with differences depending on clinical manifestations and specialization of the prescribing physician. In less than 10% of the cases, not evaluated or recommended therapeutic procedures were performed. DISCUSSION: Lyme disease is endemic throughuot Germany. The most frequent manifestations are EM, followed by Lyme arthritis and neuroborreliosis. Less than one third of patients suffering from disseminated or chronic Lyme disease remembered an EM. Most of the physicians taking part in this survey follow treatment recommendations concerning choice of antibiotics and treatment durations.
Publication Types:
PMID: 14579032 [PubMed - indexed for MEDLINE]
[Acute severe leukoencephalitis with posterior lesions due to Borrelia burgdorferi infection]
[Article in French]
Drouet A, Meyer X, Guilloton L, Mullet JP, Dusseau JY, Denoyel GA, Felten D.
Service de neurologie, HIA Desgenettes Lyon (69).
INTRODUCTION: Central nervous system manifestations represent 0.54 to 8% of neurological complication in Lyme disease. OBSERVATION: A 78-year-old woman presented a severe meningo-encephalitis with visual disorders (agnosia, alexia) progressing towards coma. Cranial magnetic resonance imaging revealed large areas of hypersignal T2 in the white matter of the lower, parieto-occipital lobes and left temporal lobe. The cerebrospinal fluid (CSF) contained 16 then 293 white corpuscles/mm3 of lympho-monocytes, increased protein level from 2.67 to 5.83 g/l and an increase in IgG index with oligoclonal distribution of IgG. Serological Elisa analysis for Lyme disease was slightly positive in blood (confirmed by western blot) but clearly in the CSF (IgG and IgM). Treatment with ceftriaxone followed by methylprednisolone provided clinical improvement 3 months later. DISCUSSION: Acute meningo-encephalitis is often benign, protein-like and of good prognosis: the gnosic visual disorders with posterior leukoencephalopathy are unusual. A blood level of specific antibodies slightly positive on Elisa at the early stage of the infection warrants confirmation by Western blot in the blood and by Elisa in the CSF. Additional corticosteroid therapy may be required in the severe forms that evoke acute disseminated encephalomyelitis.
Publication Types:
PMID: 14576583 [PubMed - indexed for MEDLINE]
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Cerebral vasculitis with multiple infarcts caused by lyme disease.
Schmiedel J, Gahn G, von Kummer R, Reichmann H.
Department of Neurology, Carl Gustav Carus University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. Janet.Schmiedel@t-online.de
Publication Types:
PMID: 14534380 [PubMed - indexed for MEDLINE]
[Borreliosis in children - clinical manifestation, diagnosis and treatment]
[Article in Polish]
Duszczyk E, Karney A, Kowalewska-Kantecka B, Gryglicka H.
Klinika Chorob Zakaznych Wieku Dzieciecego, Akademia Medyczna, ul. Wolska 37, Warszawa, Poland.
Lyme Disease (Borreliosis) is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi, transmitted by the bite of ixodes infected ticks. We would like to present our experience with the treatment of borreliosis in collaboration with the Warsaw Medical Academy's Department of Infectious Disease. Fifty-nine children (aged between 14 months to 16 years) were hospitalized or ambulatory treated due to borreliosis during 5 years between 1997 and 2001. Erythema migrans was observed in 50 cases. The main localisations of erythema were: face, neck and chest. One patient showed erythema in several other localisations. Erythema migrans returned in two cases after therapy with Amoxicillin in one case at 6 months, in the other one 12 months later. The incubation period of erythema migrans in children varied from 4 to 30 days. Seven cases from the 59 occurred with central nervous system manifestations. These were children between 6 and 16 years of age. The most frequent (65.5%) clinical manifestations of the central nervous system were meningitis and facial nerve palsy, depression and headaches were observed in 6% of cases. In one case admission to hospital was the result of leucopaenia (2800/mm3), bradycardia, headache and fatigue. The positive serologic test results (Elisa assay) were confirmed in two independent laboratories. We had one patient (5 years old boy) with arthritic manifestations. The diagnosis of Lyme disease was based on clinical manifestations and positive serologic test results (Elisa assay). In the acute stage Elisa assay was positive in 33% only. The erythema migrans cases received treatment with Amoxicillin for two weeks, whilst patients with neuroborreliosis were treated for 4 weeks with Ceftriaxon.
Publication Types:
PMID: 13130169 [PubMed - indexed for MEDLINE]
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Cerebral vasculitis as the only manifestation of Borrelia burgdorferi infection in a 17-year-old patient with basal ganglia infarction.
Heinrich A, Khaw AV, Ahrens N, Kirsch M, Dressel A.
Department of Neurology, University of Greifswald, Greifswald, Germany. alexander.dressel@neurologie.uni-greifswald.de
Publication Types:
PMID: 12944718 [PubMed - indexed for MEDLINE]
Contribution to laboratory diagnostics of neuroborreliosis.
Huckova D, Vozarova L, Ondrkalova M, Traubner P, Streharova A, Predny J.
HPL, Ltd., Microbiological Laboratory, Bratislava, Slovakia. huckova@hpl.sk
BACKGROUND: Neuroborreliosis affects peripheral and central nervous system. OBJECTIVES: Point out on possibilities of laboratory diagnostics of neuroborreliosis. SUBJECTS AND METHODS: During 1997-2001 we tested 666 pair samples of CSF and serum from 661 patients with different neurological diagnosis by ELISA, Westernblot, PCR, completed by biochemical and cytological investigations. RESULTS: We confirmed intrathecal specific IgG antibodies production by AI in 14 cases (2.1%) of total 666 samples tested. From those in 7 cases there were present also IgM antibodies in CSF. We found borderline AI values in 3 cases (0.5%) and isolated intrathecal production, antibodies present only in CSF, in 1 case (0.15%). There were normal AI values found in 25 cases (3.8%). Specific antibody possitivity by WB method was detected only in one case. DNA positivity by PCR was detected in one CSF from 43 samples during 2 years period. CONCLUSIONS: The microbiological test results should not be used in isolation but used in correlation with the biochemical and cytologic tests and also with clinical symptoms and epidemiological data to produce an overall clinical diagnosis. (Tab. 7, Fig. 1, Ref. 21)
PMID: 12940697 [PubMed - indexed for MEDLINE]
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Musical hallucinations in patients with Lyme disease.
Stricker RB, Winger EE.
Department of Medicine, California Pacific Medical Center, 450 Sutter Street, Suite 1504, San Francisco, CA 94108, USA. rstricker@usmamed.com
Musical hallucinations are poorly understood auditory hallucinations that occur in patients with otologic or neurologic diseases. We report the first cases of musical hallucinations in two patients with neurologic Lyme disease. Both subjects were women with clinical and laboratory evidence of chronic Lyme disease, progressive neurologic dysfunction, and abnormal magnetic resonance imaging of the brain. There was no evidence of hearing loss in either case. Musical hallucinations had a sudden onset and took the form of patriotic or operatic music. The auditory hallucinations disappeared with intravenous (i.v.) antibiotic therapy in both patients, but the hallucinations recurred when i.v. antibiotic therapy was discontinued in one case. Response to therapy was accompanied by an increase in the CD57 lymphocyte subset in one patient, whereas recurrent hallucinations were associated with persistently low CD57 levels in the other case. We conclude that musical hallucinations may be associated with neurologic Lyme disease. These auditory hallucinations appear to respond to i.v. antibiotic therapy. Patients with musical hallucinations of unknown cause should be tested for infection with the Lyme disease spirochete.
Publication Types:
PMID: 12940329 [PubMed - indexed for MEDLINE]
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Pathogenesis of Lyme neuroborreliosis: Borrelia burgdorferi lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes.
Ramesh G, Alvarez AL, Roberts ED, Dennis VA, Lasater BL, Alvarez X, Philipp MT.
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433, USA.
Brain invasion by Borrelia burgdorferi, the agent of Lyme disease, results in an inflammatory and neurodegenerative disorder called neuroborreliosis. In humans, neuroborreliosis has been correlated with enhanced concentration of glial fibrillary acidic protein in the cerebrospinal fluid, a sign of astrogliosis. Rhesus monkeys infected by us with B. burgdorferi showed evidence of astrogliosis, namely astrocyte proliferation and apoptosis. We formulated the hypothesis that astrogliosis could be caused by spirochetal lipoproteins. We established primary cultures of rhesus monkey astrocytes and stimulated the cells with recombinant lipidated outer surface protein A (L-OspA), a model B. burgdorferi lipoprotein, and tripalmitoyl-S-glyceryl-Cys-Ser-Lys(4)-OH (Pam(3)Cys), a synthetic lipopeptide that mimics the structure of the lipoprotein lipid moiety. L-OspA elicited not only astrocyte proliferation but also apoptosis, two features observed during astrogliosis. Astrocytes produced both IL-6 and TNF-alpha in response to L-OspA and Pam(3)Cys. Proliferation induced by L-OspA was diminished in the presence of an excess of anti-IL-6 antibody, and apoptosis induced by this lipoprotein was completely suppressed with anti-TNF-alpha antibody. Hence, IL-6 contributes to, and TNF-alpha determines, astrocyte proliferation and apoptosis, respectively, as elicited by lipoproteins. Our results provide proof of the principle that spirochetal lipoproteins could be key virulence factors in Lyme neuroborreliosis, and that astrogliosis might contribute to neuroborreliosis pathogenesis.
Publication Types:
PMID: 12938230 [PubMed - indexed for MEDLINE]
[Electromagnetic fields of extremely high frequency and radon baths in the treatment of Lyme disease with nervous system lesions]
[Article in Russian]
Levitskii EF, Zaitsev AA, Abdulkina NG, Dostovalova OV, Mavliautdinova IM.
Patients with borreliosis caused by exodic tick infestation running with affection of the nervous system were exposed to scanning EHF-therapy (59-63 GHz) on biologically active zones of the upper third of the chest, right brachial joint, biologically active points GI4, E36. Also, they took radon baths. The treatment was planned with consideration of the principles of chronotherapy. This therapeutic approach produced stimulation of general adaptive reactions and reparative processes in the peripheral nervous system.
Publication Types:
PMID: 12924187 [PubMed - indexed for MEDLINE]
[Incidence of tick-borne encephalitis virus and Borrelia burgdorferi infections in farmers of the Lublin province]
[Article in Polish]
Cisak E, Chmielewska-Badora J, Zwolinski J, Dutkiewicz J, Patorska-Mach E.
Zakladu Biologicznych Szkodliwoæci Zawodowych, Instytutu Medycyny Wsi w Lublinie. ewac@galen.imw.lublin.pl
The objective of the study was to evaluate the incidence of tick-borne encephalitis virus and Borrelia burgdorferi infections in farmers of the Lublin province. The study involved sero-epidemiological examinations of 242 farmers (the study group) and 50 healthy urban blood donors (the control group). In both tick-transmitted diseases, the frequency of sero-positive reactions was significantly higher in farmers than in controls. Serological examinations for the detection of tick-borne encephalitis showed 17.3% of positive results among farmers, and only 6.0% (p < 0.05) in the control group. The presence of specific antibodies IgG against Borrelia burgdorferi was observed in 15.3% of the farmers versus 4.0% (p < 0.05) in controls. In the IgM class, 14.0% of farmers showed positive reactions to B. burgdorferi, while in the control group no sero-positive reactions were noted (p < 0.01). The results of the study indicate that farmers are at increased risk of infection with zoonotic tick-transmitted diseases.
Publication Types:
PMID: 12923996 [PubMed - indexed for MEDLINE]
Magnetic resonance imaging of meningoradiculomyelitis in early disseminated Lyme disease.
Tullman MJ, Delman BN, Lublin FD, Weinberger J.
Departments of Neurology and Neuroradiology, Mount Sinai School of Medicine, New York, New York, USA. mark.tullman@mssm.edu
Lyme disease, a multisystem illness caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. There are 3 clinical stages of Lyme disease: early localized, early disseminated, and late persistent disease. Neuroborreliosis, infection of the nervous system by B. burgdorferi, may occur during early disseminated or late persistent disease. Spinal cord involvement in early disseminated disease is extremely rare. In patients with early disseminated neuroborreliosis, treatment with antibiotics often leads to rapid recovery and may prevent further complications of Lyme disease. The authors present the clinical and radiographic findings, both before and after treatment, in a patient with meningoradiculomyelitis due to early disseminated Lyme disease.
Publication Types:
PMID: 12889175 [PubMed - indexed for MEDLINE]
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Central nervous system Lyme disease.
Nachman SA, Pontrelli L.
Stony Brook University, Department of Pediatrics, Stony Brook, NY 11794-8111, USA. Sharon.Nachman@stonybrook.edu
Lyme disease is a disease caused by the spirochete, Borrelia burgdorferi. It is transmitted to humans via a bite from an infected tick. It has several classic stages or categories of illness, including early localized disease, early disseminated disease, and late disease. The focus of this article is on the manifestations, diagnosis, and treatment of Lyme disease of the central nervous system. Copyright 2003 Elsevier Inc. All rights reserved.
Publication Types:
PMID: 12881800 [PubMed - indexed for MEDLINE]
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Lyme disease and the peripheral nervous system.
Halperin JJ.
Department of Neurology, North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030, USA. halperin@nshs.edu
Lyme disease, the multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi, causes a broad variety of peripheral nerve disorders, including single or multiple cranial neuropathies, painful radiculopathies, and diffuse polyneuropathies. Virtually all appear to be varying manifestations of a mononeuropathy multiplex. Diagnosis requires that the patient should have had possible exposure to the only known vectors, Ixodes ticks, and also have either other pathognomonic clinical manifestations or laboratory evidence of exposure. Treatment with antimicrobial regimens is highly effective. The mechanism underlying these neuropathies remains unclear, although interactions between anti-Borrelia antibodies and several peripheral nerve constituent molecules raise intriguing possibilities.
Publication Types:
PMID: 12872317 [PubMed - indexed for MEDLINE]
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Treatment of neuroborreliosis.
Mervine P.
Publication Types:
PMID: 12867845 [PubMed - indexed for MEDLINE]
[Reddish-blue color lower leg with distinct vessel design. "Venous insufficiency" was Lyme borreliosis]
[Article in German]
Jckle R.
PMID: 12866293 [PubMed - indexed for MEDLINE]
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Comment in:
Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.
Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, Dattwyler R, Chandler B.
Department of Neurology, Stony Brook University Medical Center, Stony Brook, NY 11794-8121, USA. lkrupp@notes.cc.sunysb.edu
OBJECTIVE: To determine whether post Lyme syndrome (PLS) is antibiotic responsive. METHODS: The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy. Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo. The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time. The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA). Outcome data were collected at the 6-month visit. RESULTS: Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001). No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection. Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization. CONCLUSIONS: Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.
Publication Types:
PMID: 12821734 [PubMed - indexed for MEDLINE]
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Comment in:
Cognitive function in post-treatment Lyme disease: do additional antibiotics help?
Kaplan RF, Trevino RP, Johnson GM, Levy L, Dornbush R, Hu LT, Evans J, Weinstein A, Schmid CH, Klempner MS.
University of Connecticut School of Medicine, Farmington, USA. kaplan@psychiatry.uchc.edu
BACKGROUND: It is controversial whether additional antibiotic treatment will improve cognitive function in patients with post-treatment chronic Lyme disease (PTCLD). OBJECTIVE: To determine whether antibiotic therapy improves cognitive function in two randomized double-blind placebo-controlled studies of patients with PTCLD. METHODS: A total of 129 patients with a physician-documented history of Lyme disease from three study sites in the northeast United States were studied. Seventy-eight were seropositive for IgG antibodies against Borrelia burgdorferi, and 51 were seronegative. Patients in each group were randomly assigned to receive IV ceftriaxone 2 g daily for 30 days followed by oral doxycycline 200 mg daily for 60 days or matching IV and oral placebos. Assessments were made at 90 and 180 days after treatment. Symptom severity was measured from the cognitive functioning, pain, and role functioning scales of the Medical Outcomes Study (MOS). Memory, attention, and executive functioning were assessed using objective tests. Mood was assessed using the Beck Depression Inventory and Minnesota Multiphasic Personality Inventory. RESULTS: There were no significant baseline differences between seropositive and seronegative groups. Both groups reported a high frequency of MOS symptoms, depression, and somatic complaints but had normal baseline neuropsychological test scores. The combined groups showed significant decreases in MOS symptoms, higher objective test scores, and improved mood between baseline and 90 days. However, there were no significant differences between those receiving antibiotics and placebo. CONCLUSION: Patients with post-treatment chronic Lyme disease who have symptoms but show no evidence of persisting Borrelia infection do not show objective evidence of cognitive impairment. Additional antibiotic therapy was not more beneficial than administering placebo.
Publication Types:
PMID: 12821733 [PubMed - indexed for MEDLINE]
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Comment on:
Treating post Lyme disease: trying to solve one equation with too many unknowns.
Steiner I.
Publication Types:
PMID: 12821728 [PubMed - indexed for MEDLINE]
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Acute facial palsy in children--a 2-year follow-up study with focus on Lyme neuroborreliosis.
Skogman BH, Croner S, Odkvist L.
Division of Pediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University Hospital, SE-581 85, Linkping, Sweden. barbro.hedin-skogman@lio.se
OBJECTIVE: Acute facial palsy in children is believed to be a rather benign neurological condition. Follow-up-studies are sparse, especially including a thorough otoneurological re-examination. The aim of this study was to examine children with a history of facial palsy in order to register the incidence of complete recovery and the severity and nature of sequelae. We also wanted to investigate whether there was a correlation between sequelae and Lyme Borreliosis, treatment or other health problems. METHODS: Twenty-seven children with a history of facial palsy were included. A re-examination was performed by an Ear-Nose-Throat (ENT) specialist 1-2.9 years (median 2) after the acute facial palsy. The otoneurological examination included grading the three branches of the facial nerve with the House-Brackman score, otomicroscopy and investigation with Frenzel glasses. A paediatrician interviewed the families. Medical files were analysed. RESULT: The incidence of complete recovery was 78% at the 2-year follow-up. In six out of 27 children (22%), the facial nerve function was mildly or moderately impaired. Four children reported problems with tear secretion and pronunciation. There was no correlation between sequelae after the facial palsy and gender, age, related symptoms, Lyme neuroborreliosis (NB), treatment, other health problems or performance. CONCLUSION: One fifth of children with an acute facial palsy get a permanent dysfunction of the facial nerve. Other neurological symptoms or health problems do not accompany the sequelae of the facial palsy. Lyme NB or treatment seems to have no correlation to clinical outcome. Factors of importance for complete recovery after an acute facial palsy are still not known.
Publication Types:
PMID: 12745151 [PubMed - indexed for MEDLINE]
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Pain as presenting symptom in Lyme neuroborreliosis.
Dotevall L, Eliasson T, Hagberg L, Mannheimer C.
Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, SE-416 85 Gteborg, Sweden. leif.dotevall@medfak.gu.se
Neurogenic pain with radiculitis is often the starting symptom in adult patients with tick-borne Lyme neuroborreliosis and in some cases the only clinical manifestation. Cranial paresis and other neurologic signs usually occur after the onset of pain. The present paper describes four patients who had severe pain as the main presenting symptom of Lyme neuroborreliosis. Opioids had good short-term effect in two of the cases. Oral doxycycline treatment was used successfully to eliminate the infection.
Publication Types:
PMID: 12725846 [PubMed - indexed for MEDLINE]
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[Heterogeneity of Borrelia burgdorferi: etiopathogenetic relevance and clinical implications]
[Article in German]
Lnemann JD, Krause A.
Universittsklinikum Charit, Medizinische Klinik m.S. Rheumatologie und Klinische Immunologie, 10098 Berlin, Germany.
Of the ten different species of Borrelia (B.) burgdorferi sensu lato which have been characterized to date, only B. burgdorferi sensu stricto, B. garinii and B. afzelii have been identified as pathogenic in humans. It was suggested that different species possess different organotropisms and may preferentially cause distinct clinical manifestations of Lyme disease. Molecular analyses revealed a strong association of B. afzelii with the late cutaneous manifestation acrodermatitis chronica atrophicans, whereas B. garinii was predominantly identified in clinical samples from patients with neuroborreliosis. PCR-based analyses of samples from European patients with Lyme arthritis had given controversial results, but B. burgdorferi sensu stricto appears to be the major pathogen. The identity of the infecting species seems to be a major determinant in the pathogenesis of Lyme arthritis, although its complex immunopathological background and its clinical heterogeneity clearly indicate concomitant factors. Thus, characterization of the infecting organism at the species level on the one hand and linkage of clinical data with pathogenetically relevant immune parameters on the other, shall lead to a more precise understanding of the pathogenesis and the individual clinical course of Lyme borrelioses.
Publication Types:
PMID: 12721702 [PubMed - indexed for MEDLINE]
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[Lyme disease--a reason for sudden sensorineural hearing loss and vestibular neuronitis?]
[Article in German]
Walther LE, Hentschel H, Oehme A, Gudziol H, Beleites E.
Universitts-HNO-Klinik, Friedrich-Schiller-Universitt Jena. Leif.Walther@med.uni-jena.de
BACKGROUND: Lyme disease has been described as one possible cause of sudden sensorineural hearing loss and vestibular neuronitis. The necessity of serological diagnosis and its therapeutic consequences have been discussed controversially. PATIENTS AND METHODS: 344 patients with acute sensorineural hearing loss and 66 patients with vestibular neuronitis were examined in retrospect. By means of ELISA (Enzygnost Borreliosis, Dade Behring Marburg) the specific prevalences of IgG- and IgM-antibodies against borrelia in serum were evaluated. The frequency of seroprevalences for both diseases were compared to those given in the literature. Neurootological findings of the seropositive patients were compared with those of seronegative and analysed statistically. RESULTS: 15.7 % of the patients with sudden sensorineural hearing loss had positive levels of IgG-antibodies. IgM-titers were elevated in 4.7 % of the patients. The seroprevalences for IgM and IgG were above those described by other investigators for the healthy population. Patients with positive IgM-antibodies showed more often low frequency hearing loss than IgG-positive patients. 18.2 % of the patients with neuronitis vestibularis had IgG- and 1.5 % IgM-antibodies against Borrelia. Whereas IgG occurred more often than known for the healthy population, IgM was within the limit for the healthy population. The seropositive group did not show any remarkable neurootological signs compared with the seronegative group. CONCLUSIONS: Because of the elevated seroprevalences Borrelia infections may be one possible but very rare cause of sudden sensorineural hearing loss and vestibular neuronitis. Low frequency hearing loss may be a sign for an infection with Borrelia as an etiological factor especially in combination with seropositive titers. In case of the presence of IgM-antibodies, patients may be treated with oral antibiotics (Doxycyclin, Cefuroxim). In patients with neuronitis vestibularis a neuroborreliosis should be excluded by means of lumbar puncture.
Publication Types:
PMID: 12717599 [PubMed - indexed for MEDLINE]
Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS.
Giunti D, Borsellino G, Benelli R, Marchese M, Capello E, Valle MT, Pedemonte E, Noonan D, Albini A, Bernardi G, Mancardi GL, Battistini L, Uccelli A.
Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy.
The recruitment of lymphocytes across the blood brain barrier (BBB) is mediated by adhesion molecules and chemokines. The expression of activation markers and of chemokine receptors on T cells homing to the nervous system (NS) may help define their functional state. In the cerebrospinal fluid (CSF) of subjects with inflammatory neurological diseases (IND), including multiple sclerosis, we observed an increased number of T cells coexpressing CXCR3 and CCR5 as well as T cells with a CD45RO+ CCR7+ CD27+ memory phenotype. A subset of CCR7+ T cells coexpressed CXCR3 and CCR5. We also detected an increased number of interferon-gamma-producing T cells in the CSF compared with peripheral blood, mostly but not exclusively in the CD45RO+ CCR7- CD27- compartment. T helper 1 (Th1) clones, established from the CSF of individuals with IND and from a healthy subject, similarly migrated to CXCL10, CXCL12, and CCL5. CXCL10, CXCL12, and CCL19 were increased in the CSF of individuals with neuroinflammation. These findings suggest that CSF is enriched in Th1-polarized memory T cells capable of differentiating into effector cells upon antigen encounter. These cells are recruited into the CSF by inducible chemokines. Thus, CSF represents a transitional station for T cells trafficking to and from the NS.
Publication Types:
PMID: 12714572 [PubMed - indexed for MEDLINE]
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[Cranial neuritis with enhancement on post-contrast MRI due to Lyme disease]
[Article in French]
Khalil M, Boncoeur MP, Torny F, Magy L, Couratier P.
Service de Neurologie, CHU Limoges.
We report a case of Lyme disease presenting as an oculomotor nerve palsy and meningitis. T1-weighted postcontrast magnetic resonance images showed marked enhancement of the right third, fifth and sixth nerves. This case illustrates neuroradiological features of cranial nerves during neuroborreliosis.
Publication Types:
PMID: 12703053 [PubMed - indexed for MEDLINE]
[Neuroborreliosis in Vest-Agder]
[Article in Norwegian]
Lj¿stad U, Mygland A, Skarpaas T.
Nevrologisk avdeling, Vest-Agder sykehus 4604 Kristiansand. unn.ljostad@vas.no
PMID: 12683184 [PubMed - indexed for MEDLINE]
[Lyme borreliosis]
[Article in German]
Huppertz HI, Krause A.
Hess-Kinderklinik, Zentralkrankenhaus Bremen. huppertz.bremen@t-online.de
Publication Types:
PMID: 12674737 [PubMed - indexed for MEDLINE]
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Clonal accumulation of activated CD8+ T cells in the central nervous system during the early phase of neuroborreliosis.
Jacobsen M, Zhou D, Cepok S, Nessler S, Happel M, Stei S, Wilske B, Sommer N, Hemmer B.
Department of Neurology, Philipps-University, Marburg, Germany.
Borrelia burgdorferi may cause an acute infection of the central nervous system (CNS) that rarely leads to chronic disease. To characterize host immunity to B. burgdorferi in humans, we performed serial T cell receptor (TCR) variable beta (TCRBV) chain analyses in blood and cerebrospinal fluid (CSF) samples from 10 patients with acute neuroborreliosis. In most patients, we found significant differences in TCRBV expression between CSF and peripheral blood T cells, predominantly involving CD8(+) T cells. T cells that accumulated in the CSF had a memory phenotype and expressed high levels of C-C chemokine receptor 5 and CD69. Serial studies demonstrated that CD8(+) T cell accumulation decreased continuously after resolution of the infection. In 2 patients, serial analysis of the TCR-alpha and -beta chain sequences revealed that overexpression of TCRBV in CSF was caused by extensive clonal expansion of CD8(+) T cells. Our findings support the role of CD8(+) T cells during the early host defense against spirochete infection of the CNS.
Publication Types:
PMID: 12660943 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis revealed as a normal pressure hydrocephalus: a cause of reversible dementia.
Etienne M, Carvalho P, Fauchais AL, Pestel-Caron M, Doucet J, Chassagne P.
Publication Types:
PMID: 12657092 [PubMed - indexed for MEDLINE]
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Clinical data and cerebrospinal fluid findings in Lyme meningitis versus aseptic meningitis.
Tuerlinckx D, Bodart E, Garrino MG, de Bilderling G.
Department of Paediatrics, Cliniques Universitaires de Mont-Godinne, Universit Catholique de Louvain, Mont-Godinne, 5530 Yvoir, Belgium. david.tuerlinckx@pedi.ucl.ac.be
The purpose of this study was to characterise Lyme meningitis (LM) in a Belgian paediatric population and to suggest findings that could allow early distinction from aseptic meningitis (AM). The medical records of patients hospitalised between 1993 and 2000 and with a discharge diagnosis of LM (n=14) or AM (n=16) were retrospectively reviewed. The Kruskal-Wallis test was used to compare data. Of the patients, 16 were identified with AM and 14 with LM, amongst which 7 presented with isolated LM and 7 with associated peripheral facial palsy (PFP). Patients with AM, when compared with LM, complained of more pronounced signs and symptoms of meningitis (fever, headaches, and neck stiffness); they statistically displayed a shorter period of symptoms before admission (1.6 vs 15 days), higher neutrophilic component (mean 56% vs 2.4%), and lower protein levels (mean 0.39 vs 1.12 g/l) on cerebrospinal fluid analysis. In the neuroborreliosis group, the duration of symptoms was shorter and the cerebrospinal protein level was lower in cases of LM associated with PFP compared to isolated LM (mean 1.3 vs 15 days; mean 0.55 g/l vs 1.12 g/l). Conclusions.Our results suggest that some clinical data and laboratory findings may help the physician to diagnose aseptic or Lyme meningitis before completion of serologic testing. LM should be suspected in cases of meningitis with very low CSF neutrophilic counts and high protein levels associated with prolonged duration of symptoms, low grade fever, and absence of pronounced signs of meningitis.
Publication Types:
PMID: 12655417 [PubMed - indexed for MEDLINE]
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Significant improvement of the recombinant Borrelia-specific immunoglobulin G immunoblot test by addition of VlsE and a DbpA homologue derived from Borrelia garinii for diagnosis of early neuroborreliosis.
Schulte-Spechtel U, Lehnert G, Liegl G, Fingerle V, Heimerl C, Johnson BJ, Wilske B.
Max von Pettenkofer-Institut fr Medizinische Mikrobiologie und Hygiene der Ludwig-Maximilians-Universitt Mnchen, D-80336 Munich, Germany. Bettina.Wilske@mvp-bak.med.uni-muenchen.de
We investigated whether the recombinant Borrelia Western blot test previously described (B. Wilske, C. Habermann, V. Fingerle, B. Hillenbrand, S. Jauris-Heipke, G. Lehnert, I. Pradel, D. Rssler, and U. Schulte-Spechtel, Med. Microbiol. Immunol. 188:139-144, 1999) can be improved by the addition of VlsE and additional DbpA and OspC homologues. By using a panel of sera from 36 neuroborreliosis patients and 67 control patients, the diagnostic sensitivity of the recombinant immunoblot test was significantly increased (86.1% versus 52.7%) without loss of specificity and was higher (86.1% versus 63.8%) than that of the conventional whole-cell lysate immunoblot test (U. Hauser, G. Lehnert, R. Lobentanzer, and B. Wilske, J. Clin. Microbiol. 35:1433-1444, 1997). Improvement was mainly due to the presence of VlsE and DbpA.
Publication Types:
PMID: 12624072 [PubMed - indexed for MEDLINE]
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[Lyme borreliosis]
[Article in French]
Tranchant C, Warter JM.
Service des maladies du Systme Nerveux et du Muscle, Hpitaux Universitaires, Strasbourg.
Lyme disease is a multisystemic disease caused by a spirochete, Borrelia Burgdorferi that is transmitted by ticks. A clinical diagnosis is easy when a tick bite is followed 3 weeks later by erythema migrans, than by involvement of nervous system, joints or heart. In case of neuroborreliosis, serological tests, performed in blood and cerebro-spinal fluid, support the diagnosis and patients recover rapidly with antibacterial treatments. However an accurate diagnosis remains sometimes problematic, especially distinction between a coincidental positive serologic test and a nervous system Lyme borreliosis which require antibiotics. Furthermore, the role of autoimmunity in the pathophysiology of late Lyme disease, antibiotic choice in early disease, duration of treatment, and utility of vaccination are discussed.
Publication Types:
PMID: 12618650 [PubMed - indexed for MEDLINE]
Bone marrow manifestation of Lyme disease (Lyme Borreliosis).
Kvasnicka HM, Thiele J, Ahmadi T.
Institute of Pathology, University of Cologne, Cologne, Germany. hm.kvasnicka@uni-koeln.de
Publication Types:
PMID: 12614200 [PubMed - indexed for MEDLINE]
[Evaluation of oxidoreductive potential of patients with neuroborreliosis]
[Article in Polish]
Pancewicz SA, Skrzydlewska E, Hermanowska-Szpakowicz T, Stankiewicz A, Kondrusik M.
Klinika Chorb Zakanych i Neuroinfekcji AM w Bialymstoku.
AIM: The purpose of the study was to evaluate parameters of oxidoreductive system in serum and cerebrospinal fluid (CSF) of patients with neuroborreliosis. MATERIAL AND METHODS: The cases were 25 patients aged 21 to 64 (x = 42.3) hospitalized with diagnosis of neuroborreliosis. Activity of superoxide dismutase (Cu, Zn-SOD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px) and concentration of sulphydryl groups (-SH) and malondialdehyde (MDA) in serum and CSF were tested. The control group consisted of 10 patients with diagnosis of discopathy. An examination was performed twice: before and after treatment. RESULTS: Results of the study showed lack of stability in an oxidoreductive system during neuroborreliosis both in serum and in CSF. In CSF activity of SOD was increased while activity of GSH-Px and GSSG-R were decreased. Also concentration of -SH and lipid peroxidation products measured as MDA were increased. The increase of SOD, GSH-Px, GSSG-R activity and concentration of -SH and MDA in serum were detected. CONCLUSIONS: Disorders of an oxidoreductive system in CSF and serum during neuroborreliosis were observed. These changes persisted despite treatment and normalization of inflammatory CSF markers.
Publication Types:
PMID: 12608092 [PubMed - indexed for MEDLINE]
Update in:
Update of:
Lyme disease.
Hayes E.
US Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
Publication Types:
PMID: 12603910 [PubMed - indexed for MEDLINE]
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Simultaneous involvement of third and sixth cranial nerve in a patient with Lyme disease.
Lell M, Schmid A, Stemper B, Maihfner C, Heckmann JG, Tomandl BF.
Division of Neuroradiology, Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, Germany.
We report a 57-year-old woman with neuroborreliosis presenting with headache, shoulder muscle pain and double vision. MRI demonstrated enhancement of the right third and sixth cranial nerves. A 3D MP-RAGE sequence was used to perform multiplanar reformations to show this more graphically. The patient was free of symptoms 1 month after completion of therapy, when thickening and contrast enhancement of the nerves were less pronounced.
Publication Types:
PMID: 12592489 [PubMed - indexed for MEDLINE]
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Sudden deafness and Lyme disease.
Lorenzi MC, Bittar RS, Pedalini ME, Zerati F, Yoshinari NH, Bento RF.
Department of Otorhinolaryngology, Hospital das Clnicas and Faculdade de Medicina da Universidade de So Paulo, So Paulo, Brazil.
OBJECTIVES/HYPOTHESIS: Otolaryngological manifestations are common in Lyme disease, affecting up to 75% of patients. One of these symptoms is sudden deafness. Hearing loss has been frequently described in Lyme disease; on the other hand, titers seropositive for, the causal agent of this disease, have been found in almost 20% of cases of sudden deafness. No consensual information exists on the outcome of Borrelia-seropositive patients or on the importance of determining Borrelia antibody titers. The present study aimed to determine the prevalence of seropositivity for Borrelia in sudden deafness, describing clinical characteristics and outcomes. STUDY DESIGN: This was a prospective observational study. METHODS: Forty-seven consecutive patients with sudden deafness were enrolled in the study. Demographic data, the presence of tinnitus and vertigo, and low- and high-frequency pure-tone averages were recorded. The percentage of hearing recovery was determined. Data obtained from Borrelia-seropositive patients were described and compared with those from the seronegative group. RESULTS: Titers positive for antibodies were present in 21.3% of the cases. Seropositive and seronegative groups of patients were homogeneous concerning age, sex distribution, the presence of tinnitus and vertigo, and high- and low-frequency hearing thresholds. Hearing outcome was not significantly different between the groups of patients. CONCLUSIONS: No distinctive clinical characteristic was found between seropositive and seronegative subjects. The hearing outcome of treated Borrelia-seropositive patients was similar to that of the seronegative group.
PMID: 12567088 [PubMed - indexed for MEDLINE]
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Intracerebral haemorrhage as a manifestation of Lyme neuroborreliosis?
Scheid R, Hund-Georgiadis M, von Cramon DY.
Day Clinic of Cognitive Neurology, University of Leipzig, Germany. scheid@cns.mpg.de
Lyme Neuroborreliosis (LNB) has repeatedly been reported to cause cerebral vasculitis. However, there is no reliable information about the incidence of cerebral vessel affection. The majority of reports deal with ischaemic consequences, and there are a few reports of subarachnoid haemorrhage (SAH). We report a case of otherwise unexplained intracerebral haemorrhage (ICH) where clinical and laboratory tests have shown LNB. Late stage LNB might not only cause ischaemic, but haemorrhagic stroke as well.
Publication Types:
PMID: 12535004 [PubMed - indexed for MEDLINE]
Acute myelitis in early Borrelia burgdorferi infection.
Lesca G, Deschamps R, Lubetzki C, Levy R, Assous M.
Publication Types:
PMID: 12532941 [PubMed - indexed for MEDLINE]
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Successful treatment of neuroborreliosis with ten day regimens.
Thorstrand C, Belfrage E, Bennet R, Malmborg P, Eriksson M.
Sachsska Children's Hospital, Stockholm, Sweden.
BACKGROUND: There have been few large reports of the treatment and outcome of neuroborreliosis in children. METHODS: All 203 children with symptoms, cerebrospinal fluid and serologic findings compatible with neuroborreliosis and treated at one of the four pediatric hospitals in Stockholm from 1994 through 1996 were included. Children were treated with intravenous beta-lactam antibiotics or oral doxycycline for 10 days and followed until the resolution of symptoms. RESULTS: At the end of treatment 58% and after 2 months 92% of the children had no symptoms. Cerebrospinal fluid findings had no statistically significant influence on the outcome. Facial paralysis persisted longer than other symptoms. CONCLUSIONS: The prognosis of neuroborreliosis in children 2 months after treatment seems to be excellent with 10-day treatment regimens.
Publication Types:
PMID: 12488665 [PubMed - indexed for MEDLINE]
Pertussis toxin-induced reversible encephalopathy dependent on monocyte chemoattractant protein-1 overexpression in mice.
Huang D, Tani M, Wang J, Han Y, He TT, Weaver J, Charo IF, Tuohy VK, Rollins BJ, Ransohoff RM.
Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
In this report we describe pertussis toxin-induced reversible encephalopathy dependent on monocyte chemoattractant protein-1 (MCP-1) overexpression (PREMO), a novel animal model that exhibits features of human encephalopathic complications of inflammatory disorders such as viral meningoencephalitis and Lyme neuroborreliosis as well as the mild toxic encephalopathy that commonly precedes relapses of multiple sclerosis (MS). Overexpression of the mouse MCP-1 gene product (classically termed JE) in astrocytes, the major physiological CNS cellular source of MCP-1, failed to induce neurological impairment. Unexpectedly, transgenic (tg) mice overexpressing MCP-1 at a high level (MCP-1(hi)) manifested transient, severe encephalopathy with high mortality after injections of pertussis toxin (PTx) plus complete Freund's adjuvant (CFA). Surviving mice showed markedly improved function and did not relapse during a prolonged period of observation. Tg mice that expressed lower levels of MCP-1 were affected minimally after CFA/PTx injections, and tg expression of other chemokines failed to elicit this disorder. The disorder was significantly milder in mice lacking T-cells, which therefore play a deleterious role in this encephalopathic process. Disruption of CC chemokine receptor 2 (CCR2) abolished both CNS inflammation and encephalopathy, identifying CCR2 as a relevant receptor for this disorder. Proinflammatory and type 1 cytokines including TNF-alpha, IL-1beta, IFN-gamma, IL-2, RANTES, and IP-10 were elevated in CNS tissues from mice with PREMO. These studies characterize a novel model of reversible inflammatory encephalopathy that is dependent on both genetic and environmental factors.
Publication Types:
PMID: 12486156 [PubMed - indexed for MEDLINE]
Comment in:
Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders.
Muraro PA, Wandinger KP, Bielekova B, Gran B, Marques A, Utz U, McFarland HF, Jacobson S, Martin R.
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, MD 20892-1400, USA. murarop@ninds.nih.gov
T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4(+) and CD8(+) T cell clones through the detection and quantification of T cell receptor (TCR) alpha or beta chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders.
Publication Types:
PMID: 12477694 [PubMed - indexed for MEDLINE]
A case of Bannwarth syndrome.
Farrugia ME.
Weatherall Institute of Molecular Medicine, Neurosciences Group, John Radcliffe Hospital, Oxford OX3 9DS.
Publication Types:
PMID: 12474619 [PubMed - indexed for MEDLINE]
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Phrenic nerve paralysis secondary to Lyme neuroborreliosis.
Ishaq S, Quinet R, Saba J.
Department of Internal Medicine, Section on Rheumatology, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Publication Types:
PMID: 12473782 [PubMed - indexed for MEDLINE]
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Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis.
Grusell M, Widhe M, Ekerfelt C.
Division of Clinical Immunology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, University Hospital, Linkping, Sweden.
Lyme neuroborreliosis is a complex disease with different clinical outcomes and where immunopathological mechanisms are probably involved. In this study, sera and cerebrospinal fluid (CSF) from 21 neuroborreliosis patients and 26 control patients were analyzed for the Th1-inducing cytokines, interleukin (IL)-12 and IL-18, and the Th2 associated, soluble CD30 (sCD30) by ELISA. The results showed an increased number of neuroborreliosis patients expressing IL-12 (p<0.05) and IL-18 (p<0.05) in the CSF when compared with the controls, but no indication of increased levels in the sera. Nor were there any differences regarding levels of sCD30 in the sera or the CSF, indicating a local Th1-generating milieu in the target organ of neuroborreliosis.
Publication Types:
PMID: 12458049 [PubMed - indexed for MEDLINE]
Double infection with tick borne encephalitis virus and Borrelia burgdorferi sensu lato.
Cimperman J, Maraspin V, Lotric-Furlan S, Ruzi-Sablji E, Avsic-Zupanc T, Strle F.
University Medical Centre, Ljubljana, Slovenia.
The limited information on co-infection with Borrelia burgdorferi sensu lato and tick-borne encephalitis (TBE) virus was a stimulus for presentation of two patients with well-defined double infection of the central nervous system. TBE virus and B. burgdorferi sensu lato infections are searched for in all patients with lymphocytic meningitis and/or meningoencephalitis admitted to our department. During the last ten years we identified two patients who had ELISA IgM and IgG antibodies to TBE virus in serum and a positive PCR result for TBE virus in cerebrospinal fluid as well as B. burgdorferi sensu lato isolated from cerebrospinal fluid. Intrathecal production of borrelial antibodies was not proven in either of the two patients. These findings show that in patients with acute lymphocytic meningitis originating in regions endemic for Lyme borreliosis and TBE, the possibility of concomitant infection should be considered.
Publication Types:
PMID: 12422613 [PubMed - indexed for MEDLINE]
Limitation of serological testing for Lyme borreliosis: evaluation of ELISA and western blot in comparison with PCR and culture methods.
Tylewska-Wierzbanowska S, Chmielewski T.
Department of Bacteriology, National Institute of Hygiene, Warsaw, Poland. stylewska@pzh.gov.pl
The aim of the study was to evaluate a one-step procedure using an ELISA test of high specificity and a two-step procedure using immunoblot as a confirmation test, and to compare the results of serological testing with detection of bacterial DNA and living spirochetes. Sera, synovial (SF) and cerebro-spinal fluids (CSF) were obtained from 90 patients with clinical symptoms of Lyme borreliosis. Serum samples were tested with recombinant ELISA and Western blot assay. Citrated blood, cerebrospinal and synovial fluids samples were cultured in cell line and tested by PCR to detect spirochetes. No correlation was found between levels of specific B. burgdorferi antibodies detected with a recombinant antigen ELISA and the number of protein fractions developed with these antibodies by immunoblot. Moreover, Lyme borreliosis patients who have live spirochetes in body fluids have low or negative levels of borrelial antibodies in their sera. This indicates that an efficient diagnosis of Lyme borreliosis has to be based on a combination of various techniques such as serology, PCR and culture, not solely on serology.
Publication Types:
PMID: 12422608 [PubMed - indexed for MEDLINE]
Characterization of Borrelia burgdorferi sensu lato strains isolated from human material in Slovenia.
Ruzi-Sablji E, Maraspin V, Lotric-Furlan S, Jurca T, Logar M, Pikelj-Pecnik A, Strle F.
Institute of Microbiology and Immunology, Medical Faculty, Ljubljana, Slovenia. eva.ruzic-sabljic@mf.uni-lj.si
The aim of the study was to assess genotypic and phenotypic diversity among a large number of clinical isolates of Borrelia burgdorferi sensu lato obtained from patients in Slovenia. Plasmid profiles and species identification were determined by PFGE, protein profiles by SDS-PAGE. Of 706 B. burgdorferi sensu lato human isolates 599 (85%) were found to be B. afzelii, 101 (14%) B. garinii and six (1%) B. burgdorferi sensu stricto. The vast majority of strains (605; 86%) were isolated from skin, 58 (8%) from blood, and 43 (6%) from CSF. When analysed by RFLP, B. afzelii strains were unique, while heterogeneity was found within B. garinii and B. burgdorferi sensu stricto species. An unusual plasmid content was found in 52/706 (7%) isolated strains, more often in B. garinii than in B. afzelii strains. A plasmid dimer was found in B. afzelii and B. garinii strains, whereas multiple copies of the large plasmid were associated nearly exclusively with B. garinii strains. Analysis of protein profiles revealed that OspA and OspB are expressed more often by B. afzelii strains, and OspC by B. garinii strains. Heterogeneity of Borrelia strains may play a significant role in the virulence and pathogenesis of the infection. Differences in antigenic components have an important impact on serological testing and vaccine development.
PMID: 12422599 [PubMed - indexed for MEDLINE]
Multiple sclerosis and Lyme borreliosis.
Schmutzhard E.
Department of Neurology, University Hospital, Innsbruck, Austria. erich.schmutzhard@uibk.ac.at
In a deductive approach the two disease entities of multiple sclerosis and chronic progressive neuroborreliosis are discussed. Various clinical features, seroepidemiology, neuroimaging, CSF findings, CSF serology, specific proteins within the CSF and antibodies against neuronal structures as well as the most recent findings of different dendritic cells within the CSF are discussed as a means of differentiating these two disease entities.
Publication Types:
PMID: 12422598 [PubMed - indexed for MEDLINE]
Cerebrospinal fluid findings in patients with symptoms suggesting chronic Lyme borreliosis.
Ogrinc K, Lotric-Furlan S, Maraspin V, Cimperman J, Ruzi-Sablji E, Strle F.
Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia. katarina.orgrinc1@guest.arnes.si
BACKGROUND: Patients with non-specific long-lasting symptoms such as headache, concentration disturbances, and vertigo and who have positive serum borrelial antibody titres are often assumed to have chronic Lyme borreliosis. Because of the possibility that they may have central nervous system involvement they are frequently treated with courses of i.v. ceftriaxone. We assessed central nervous system involvement by examining cerebrospinal fluid samples in a group of such patients. PATIENTS AND METHODS: Adult patients who qualified for the study had non-specific symptoms suggesting central nervous system involvement for longer than six months (but without overt clinical signs of such involvement) and positive serum borrelial antibody titres and/or erythema migrans prior to the onset of symptoms. Cerebrospinal fluid was examined in all patients. RESULTS: None of the 77 patients included in the study (median duration of symptoms 18 months) had pleocytosis and there was no isolation of Borrelia burgdorferi sensu lato from cerebrospinal fluid. Mildly elevated protein concentration and intrathecal borrelial IgG antibody synthesis were demonstrated in 16 (21%) and 7 (9.1%) patients, respectively. CONCLUSIONS: In patients with non-specific long-lasting symptoms attributed to Lyme borreliosis but with the absence of overt clinical signs suggesting central nervous system involvement, the findings of cerebrospinal fluid examination are usually in the normal range. Routine treatment of such patients with i.v. ceftriaxone is not to be encouraged.
PMID: 12422597 [PubMed - indexed for MEDLINE]
Procalcitonin levels in patients with Lyme borreliosis.
Lotric-Furlan S, Maraspin-Carman V, Cimperman J, Ogrinc K, Stopar T, Strle F.
Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia. stanka.lotric-furlan@mf.uni-lj.si
BACKGROUND: Serum and cerebrospinal fluid (CSF) procalcitonin levels were assessed and compared for different groups of patients with Lyme borreliosis. PATIENTS AND METHODS: 50 adult patients with Lyme borreliosis, referred to our department from March to June 2001, were included in this prospective study. Patients were divided into three groups. The first group consisted of 20 consecutive patients with typical solitary erythema migrans, representing early localised Lyme borreliosis, the second group comprised 20 patients with early disseminated Lyme borreliosis (10 with multiple erythema migrans and 10 with neuroborreliosis), and 10 patients with acrodermatitis chronica athrophicans represented the group with chronic Lyme borreliosis. Blood specimens were taken from all patients included in the study, but CSF samples were restricted to those with disseminated and chronic Lyme borreliosis. The serum and CSF procalcitonin levels were determined utilizing the LUMI PCT (an immunoluminometric assay using two antigen-specific monoclonal antibodies). RESULTS: Serum and CSF procalcitonin levels were in normal range in the large majority of patients. The levels of serum procalcitonin did not differ in the three groups of patients with Lyme borreliosis (p = 0.5006). The corresponding values for patients with solitary erythema migrans (early localised Lyme borreliosis), early disseminated Lyme borreliosis, and chronic Lyme borreliosis were 0.26 (0.11-0.43), 0.22 (0.10-0.67), and 0.28 (0.13-0.66) microgram/ml, respectively. Moreover, procalcitonin levels in CSF were also low and comparable for patients with multiple erythema migrans (median 0.38, range 0.24-0.54 microgram/ml), neuroborreliosis (median 0.16, range 0.10-0.47 microgram/ml), and acrodermatitis chronica athrophicans (median 0.30, range 0.15-0.45 microgram/ml). The differences were not statistically significant (p = 0.7579). CONCLUSIONS: In the large majority of patients with Lyme borreliosis procalcitonin values are within normal range. Serum and CSF procalcitonin levels are of no value for differentiation between early localised, early disseminated and chronic Lyme borreliosis.
PMID: 12422595 [PubMed - indexed for MEDLINE]
Children with multiple erythema migrans: are there any pre-treatment symptoms and/or signs suggestive for central nervous system involvement?
Arnez M, Pleterski-Rigler D, Luznik-Bufon T, Ruzi-Sablji E, Strle F.
Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia. maja.arnez@kclj.si
OBJECTIVE: To establish eventual signs and symptoms suggestive for central nervous system involvement in children with multiple erythema migrans. METHODS: Patients younger than 15 years with multiple erythema migrans, diagnosed at our department from 1996 to 2000, were included in this prospective study. Demographic, clinical and laboratory findings were obtained and compared for a group of patients with pleocytosis (interpreted as a sign of central nervous system involvement) and a group of children with normal cerebrospinal fluid findings. RESULTS: Cerebrospinal fluid pleocytosis (cell counts > or = 5 x 10(6)/l) was detected in 55/214 (25.7%) children; it was lymphocytic in 94.5% of patients and ranged from 5 to 320 (median, 10 x 10(6)/l). Compared with the group with normal cerebrospinal fluid findings, patients with pleocytosis more often reported having had Lyme borreliosis in the past (8/55 versus 3/159; p = 0.0011), had longer incubation periods (25.5 versus 14 days; p = 0.0269), larger diameter of the largest erythema migrans at the time of first examination (10 versus 5.5 cm; p = 0.0055), higher frequency of associated systemic symptoms (45.5% versus 21.4%; p = 0.0011), positive meningeal signs (10.9% versus 1.9%; p = 0.0100), borrelial IgG antibodies in cerebrospinal fluid (3/49 versus 0/150; p = 0.0142) and B. burgdorferi s.l. isolated from cerebrospinal fluid (7/52 versus 1/147; p = 0.0004), but less often had mild initial disease (67.3% versus 88.7%; p = 0.0006). CONCLUSIONS: Cerebrospinal fluid pleocytosis was detected in 25.7% of children with multiple erythema migrans. Although several clinical and laboratory abnormalities were present significantly more often in patients with elevated cell counts than with normal cerebrospinal fluid findings, discriminatory significance for the majority of these abnormalities was low, particularly because of low negative predictive values. In more than 2/3 of patients with pleocytosis the initial disease was mild, fewer than 1/2 reported systemic symptoms, and meningeal signs were expressed in only 11%.
PMID: 12422594 [PubMed - indexed for MEDLINE]
Internuclear ophthalmoplegia as the first sign of neuroborreliosis.
Hardon WJ, Bernsen HJ, van Nouhuys-Leenders J, Mulder B.
Publication Types:
PMID: 12420716 [PubMed - indexed for MEDLINE]
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Geniculate neuralgia as a manifestation of neuroborreliosis.
Frese A, Lttmann RJ, Husstedt IW, Ringelstein EB, Evers S.
Department of Neurology, University of Mnster, Germany.
Publication Types:
PMID: 12390649 [PubMed - indexed for MEDLINE]
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Lymphocyte subset numbers in cerebrospinal fluid: comparison of tick-borne encephalitis and neuroborreliosis.
Holub M, Kluckov Z, Beran O, Aster V, Lobovsk A.
Charles University, Prague, First Faculty of Medicine, 3rd Department of Infectious and Tropical Diseases, Czech Republic. holub@wadsworth.org
OBJECTIVE: The aim of this study was to analyze lymphocyte subset numbers in cerebrospinal fluid (CSF) from patients with tick-borne encephalitis (TBE) and acute neuroborreliosis. METHODS: CSF lymphocyte subsets were enumerated in 42 TBE and nine neuroborreliosis patients using flow cytometry. RESULTS: The CSF numbers of CD4+, CD8+, HLA-DR+ and total-T lymphocytes, B lymphocytes, and NK cells were all greater in neuroborreliosis patients than in TBE patients. Neuroborreliosis patients showed positive correlation of CSF protein levels with the numbers of CD4+, HLA-DR+ and total-T lymphocytes. Also, the numbers of CSF B lymphocytes correlated positively with intrathecal Borrelia burgdorferi-specific IgG antibodies. Conversely, TBE patients demonstrated intrathecal protein levels that correlated positively with all investigated CSF lymphocyte subsets. CONCLUSION: These results suggest an intensive recruitment of lymphocyte subsets into the central nervous system (CNS) during acute neuroborreliosis, whereas TBE is characterized by a lower accumulation of lymphocyte subsets in the CSF.
Publication Types:
PMID: 12371925 [PubMed - indexed for MEDLINE]
Update in:
Lyme disease.
Hayes E.
US Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
Publication Types:
PMID: 12230693 [PubMed - indexed for MEDLINE]
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Intracranial hypertension in neuroborreliosis.
Hrtel C, Schilling S, Neppert B, Tiemer B, Sperner J.
Department of Paediatrics, University of Lbeck Medical School, Germany. haertel@paedia.ukl.mu-luebeck.de
Neuroborreliosis is an infection of the nervous system caused by the spirochete Borrelia burgdorferi, from which patients most commonly develop lymphocytic meningitis, radiculoneuritis, or cranial neuropathy. In this report a 9-year-old male with an unusual neurological complication of neuroborreliosis--benign intracranial hypertension (BIH)--is described. Clinical symptoms of BIH, which consist of increased CSF pressure in the absence of an intracranial mass or obstruction to the circulation of CSF, resolved completely after antibiotic therapy with ceftriaxone.
Publication Types:
PMID: 12227619 [PubMed - indexed for MEDLINE]
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Borrelia burgdorferi induces inflammatory mediator production by murine microglia.
Rasley A, Anguita J, Marriott I.
Department of Biology, 9201 University City Boulevard, University of North Carolina at Charlotte, 28223, Charlotte, NC, USA.
Lyme disease has been associated with damaging inflammation within the central nervous system. In the present study, we demonstrate that Borrelia burgdorferi is a significant stimulus for the production of IL-6, TNF-alpha, and PGE(2) by microglia. This effect is associated with induction of NF-kappaB, and increased expression of Toll-like receptor 2 and CD14, receptors known to underlie spirochete activation of other immune cell types. These studies identify microglia as a previously unappreciated source of inflammatory mediator production following challenge with B. burgdorferi. Such production may play an important role during the development of Lyme neuroborreliosis.
Publication Types:
PMID: 12225885 [PubMed - indexed for MEDLINE]
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Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-alpha and transforming growth factor-beta1 responses are associated with chronic neuroborreliosis.
Widhe M, Grusell M, Ekerfelt C, Vrethem M, Forsberg P, Ernerudh J.
Division of Clinical Immunology, Faculty of Health Sciences, University of Linkping, Sweden. mona.widhe@imk.liu.se
The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-alpha were found in non-chronic patients than in chronic patients (P<0.05). Moreover, TGF-beta1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0.01). Elevated serum levels of TGF-beta1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0.05). The high TNF-alpha levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-beta1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.
Publication Types:
PMID: 12225362 [PubMed - indexed for MEDLINE]
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Chronic symptoms are common in patients with neuroborreliosis -- a questionnaire follow-up study.
Vrethem M, Hellblom L, Widlund M, Ahl M, Danielsson O, Ernerudh J, Forsberg P.
Division of Neurology, University Hospital, Linkping, Sweden, Division of Neurophysiology, University Hospital, Linkping, Sweden. magnus.vrethem@lio.se
OBJECTIVES: The existence of chronic neuroborreliosis is controversial. The aim of our study was to investigate the existence and kind of persistent symptoms in patients previously treated because of neurological symptoms as a result of neuroborreliosis. MATERIALS AND METHODS: A total of 106 patients with neuroborreliosis, according to established criteria, and a control group of 123 patients with Borrelia induced erythema migrans diagnosed in a general practitioner office were studied. A questionnaire was sent to patients and controls concerning their health situation. Time from onset of neurological symptoms to the questionnaire send out was 32 months (mean) for the patients with neuroborreliosis and 33 months (mean) for the controls. RESULTS: Fifty per cent of the individuals in the patient group compared with 16% of the individuals in the control group showed persistent complaints after their Borrelia infection (P < 0.0001). The most significant differences between the groups were the presence of neuropsychiatric symptoms such as headache, attention problems, memory difficulties and depression. Paresthesia, pain and persistent facial palsy was also significantly more common in patients treated because of neuroborreliosis. CONCLUSION: Our study shows that persisting neurological symptoms are common after a neuroborreliosis infection. The pathological mechanisms that lay behind the development of chronic symptoms, however, are still uncertain.
Publication Types:
PMID: 12225315 [PubMed - indexed for MEDLINE]
[Mental disorders in the course of lyme borreliosis and tick borne encephalitis]
[Article in Polish]
Juchnowicz D, Rudnik I, Czernikiewicz A, Zajkowska J, Pancewicz SA.
Klinika Psychiatrii AM w Bialymstoku.
BACKGROUND: Lyme borreliosis is a chronic, multisystem disease, of prolong course with three consecutive stages, caused by a tick-transmitted spirochete Borrelia burgdorferi. Tick Borne Encephalitis (TBE) is neuroinfection caused by Tick Borne Encephalitis Virus (TBEV). OBJECTIVE: We evaluated the occurrence of psychiatric manifestations in the early phase of borreliosis-erythema migrans and neuroboreliosis as well as in its late phase--in arthritis and in the Tick-Born Encephalitis. The aim of the study was to single out the most frequent psychiatric symptoms and psychopathological syndroms and to determine their dynamics. METHODS: The study was carried out between 1999 and 2000 and comprised 174 patients of the Department of Psychiatry and Department of Infectious and Neuroinfectious Diseases of Medical Academy in Bialystok. Seventy seven patients diagnosed with arthritis, 20 with neuroborreliosis, 26 with skin manifestation-erythrema migrans and 51 with KZM participated. All subjects underwent psychiatric evaluation twice--during hospitalization and six month after discharge. Mental status examinations included general psychiatric examination and battery of scales and tests: Mini Mental State Examination, Beck Depression Inventory, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Reitan's Trail Making Test, Choynowsky Memory Scale, Symptoms Inventory and neuropsychological testing. RESULTS: Both in the course of TBE and Lyme borreliosis the majority of patients experienced psychiatric problems in the acute phase of disease as well as in the late phase--3, 6 months after the onset of the disease. The most common psychiatric manifestations were depressive disorders--episodes of depression or organic mood disorders, and cognitive deficits which manifest themselves as mild cognitive disorder or dementia. CONCLUSION: Psychiatric assessment is important in early stage of kzm and borreliosis but first of all after termination of acute symptomatology.
Publication Types:
PMID: 12194228 [PubMed - indexed for MEDLINE]
[Neuroborreliosis]
[Article in Finnish]
Lahdenne P, Seppl IJ, Peltomaa M.
HYKS:n lasten ja nuorten sairaala PL 281, 00029 HUS. pekka.lahdenne@hus.fi
Publication Types:
PMID: 12181951 [PubMed - indexed for MEDLINE]
5-y Follow-up study of patients with neuroborreliosis.
Berglund J, Stjernberg L, Ornstein K, Tykesson-Joelsson K, Walter H.
Department of Community Medicine, Lund University, Malm, Sweden. johan.berglund@ltblekinge.se
The objective of this follow-up study was to determine the long-term outcome of strictly classified cases of neuroborreliosis treated with antibiotics. A 1-y prospective population-based survey of Lyme borreliosis was conducted in southern Sweden between 1992 and 1993. A total of 349 identified cases with suspected neuroborreliosis were followed up 5 y later. Medical records were reviewed and all participants filled in a questionnaire. Of those patients classified with definite neuroborreliosis, 114/130 completed the follow-up, of whom 111 had completed the initial antibiotic treatment. Of the 114 patients followed up, 86 (75%) had recovered completely and 70 (61%) had recovered within 6 months. Residual neurological symptoms, such as facial palsy, concentration disorder, paresthesia and/or neuropathy, were reported by 28/114 patients. No significant differences between different antibiotic treatments were observed in terms of the occurrence of sequelae. To conclude, we found that 25% (95% confidence interval 17-33%) of the patients suffered from residual neurological symptoms 5 y post-treatment. However, the clinical outcome of treated neuroborreliosis is favorable as only 14/114 (12%) patients had sequelae that influenced their daily activities post-treatment. Early diagnosis and treatment would seem to be of great importance in order to avoid such sequelae.
Publication Types:
PMID: 12160168 [PubMed - indexed for MEDLINE]
[The onset of chronic Lyme-borreliosis after the cure of tick-borne rickettsia infection in simultaneous infection]
[Article in Russian]
Mediannikov OIu, Sidel'nikov IuN.
A case of a male patient with chronic Lyme borreliosis running with marked neurological symptoms (Garin-Bujardoux-Bannwarth syndrome) is reported. Two years before the disease manifestation the patient was infected by the tick with both borrelia and Rickettsia sibirica. The latter infection provoked an acute fever in tick-borne rickettsiosis immediately after the tick's bite. This masked development of Lyme borreliosis which manifested only 5 months later as a neurological disease. It is thought necessary to propose a rational scheme of antibiotic treatment of patients with tick-transmissible diseases.
Publication Types:
PMID: 12138808 [PubMed - indexed for MEDLINE]
[Diagnosis and therapy of neuroborreliosis. On the hunt for the "great imitator"]
[Article in German]
Kursawe HK.
Neurologische Abteilung, St. Josefs-Krankenhaus Potsdam. H.Kursawe@Alexius.de
Neurological manifestations are characteristic of stage 2 and stage 3 borreliosis. In stage 2, some 15% of the patients have neurological symptoms expressed as a triad of aseptic meningitis, cranial neuritis and radiculitis. Stage 3--chronic neuroborreliosis affects some 5% of untreated patients. The condition has its onset at the earliest 6 months after the infection, and is characterized by encephalopathic symptoms, such as fatigue, sleep and memory disturbances, and depressive states. Further manifestations of this stage may be Lyme polyneuropathy, in rare cases also progressive borrelia encephalomyelitis and cerebrovascular neuroborreliosis. The treatment of choice is intravenous administration of cephalosporins over 2-4 weeks. The success of treatment should be assessed on the basis of the clinical course rather than on laboratory results. Patience is required in the treatment of the post-Lyme syndrome, characterized by residual symptoms, recurrences or a relapsing course.
Publication Types:
PMID: 12116569 [PubMed - indexed for MEDLINE]
Three major Lyme Borrelia genospecies (Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii) identified by PCR in cerebrospinal fluid from patients with neuroborreliosis in Sweden.
Ornstein K, Berglund J, Bergstrm S, Norrby R, Barbour AG.
Department of Medical Microbiology, Dermatology and Infectious Diseases, Lund University, Sweden. katharina.ornstein@infek.lu.se
The Lyme Borrelia genospecies Borrelia afzelii and B. garinii have previously been isolated using a culture method in Swedish patients with Lyme borreliosis (LB). There are reports suggesting that the genospecies distribution in human tissue specimens as determined by molecular methods is different from that obtained by culture. In the present study, we developed a nested PCR for detection of Lyme Borrelia-specific DNA in cerebrospinal fluid from Swedish patients with LB. The genospecies were subsequently identified by sequence analysis in a total of 7 PCR-positive patients. Two sequences were identified as B. burgdorferi sensu stricto (s. s.), 1 as B. afzelii and 4 as B. garinii. These are the first reported cases in which B. burgdorferi s. s. has been shown to be the causative agent of human LB in Sweden. The results of our study confirm that the use of direct molecular analytical methods for Borrelia genospecies identification in clinical specimens can provide epidemiological information additional to that obtained by culture.
Publication Types:
PMID: 12069016 [PubMed - indexed for MEDLINE]
Retrobulbar neuritis associated with Borrelia afzelii infection.
Strmen P, Broskova D, Stanislavova M, Kmety E, Mateicka F.
Department of Ophthalmology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
PURPOSE: To report retrobulbar neuritis caused by Borrelia afzelii culturally proved from cerebrospinal fluid (CSF). METHODS: A 23 year old female underwent ophthalmologic, laboratory and other auxilliary examinations. RESULTS: CSF cultures grew spirochetal microorganisms, serotyped by monoclonal antibodies as Borrelia afzelii. Following the serological and cultural results, treatment with doxycycline 200 mg daily was started and kept for three weeks. Gradual improvement of the visual acuity of the right eye was observed with full recovery to 20/20. CONCLUSIONS: Borrelia infection should be considered in the differential diagnosis of retrobulbar neuritis. CSF should be examined also culturally. (Ref. 5.)
Publication Types:
PMID: 12061028 [PubMed - indexed for MEDLINE]
Oral concerns in Lyme disease.
Rhodus NL, Falace DA.
University of Minnesota School of Dentistry, Minneapolis, Minnesota 55455, USA.
PMID: 11989326 [PubMed - indexed for MEDLINE]
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Covert vision sign.
Brzdil M, Kuba R, Daniel P, Sochórkov D, Dobsk M, Rektor I.
Publication Types:
PMID: 11985645 [PubMed - indexed for MEDLINE]
Polymerase chain reaction in diagnosis of Borrelia burgdorferi infections and studies on taxonomic classification.
Lebech AM.
Department of Clinical Biochemistry, Statens Seruminstitut, Copenhagen, Denmark.
Lyme borreliosis caused by the spirochete Borrelia burgdorferi is now the most common vectorborne disease in North America, Europe and Asia. It is a multisystemic infection which may cause skin, neurological, cardiac or rheumatologic disorders. The aims of the present thesis were: (i) to develop a PCR assay for direct detection of B. burgdorferi DNA and to evaluate the diagnostic utility of PCR in clinical specimens from patients with Lyme borreliosis and (ii) to study the taxonomic classification of B. burgdorferi isolates and its implications for epidemiology and clinical presentation. Laboratory diagnosis of Lyme borreliosis by direct demonstration of B. burgdorferi in clinical specimens would compared to current serology allow (i) optimal specificity, (ii) increased sensitivity during the first weeks of infection, when the antibody response is not yet detectable and (iii) discrimination between ongoing and past infection. Due to the extreme paucity of spirochetes in clinical specimens neither in vitro culture nor antigen detection had yielded a sufficient diagnostic sensitivity. Thus the recently introduced highly sensitive PCR methodology could be a solution and was thus studied. Assays for PCR amplification and subsequent identification of B. burgdorferi specific sequences were established and used. For all assays the analytical sensitivity was a few genome copies using purified DNA as template. The efficacy of PCR was initially evaluated using tissue samples from experimentally infected gerbils in order to start with biological samples a priori known to contain B. burgdorferi. B. burgdorferi DNA was detectable in 88% of the specimens. Thus the diagnostic sensitivity of PCR was comparable to and even higher than in vitro culture. PCR was significantly more sensitive than a histological B. burgdorferi specific immunophosphatase-staining method. The utility of the PCR was then tested for identification of B. burgdorferi DNA in skin biopsies from 31 patients with erythema migrans. The sensitivity of PCR was 71%, which was superior to culture and serology. Based on own and otherwise published results there is clear evidence for PCR being the most sensitive and specific test for detection of B. burgdorferi in skin biopsies from patients with both early and late dermatoborreliosis. However, since the clinical diagnosis of dermatoborreliosis in most instances is easy, an invasive procedure as a skin biopsy, will only be justified in patients with an atypical clinical presentation. The most frequent and serious manifestation of disseminated Lyme borreliosis is neuroborreliosis. PCR was applied to 190 patients with untreated and confirmed neuroborreliosis. B. burgdorferi DNA was detectable in 17-21% of CSF samples from patients with neuroborreliosis. In patients with very early neuroborreliosis (< 2 weeks), still being negative for specific intrathecal antibody synthesis, a positive PCR was more frequent than in patients with longer disease duration. PCR can be used as a diagnostic aid in these patients. However, in general the measurement of specific intrathecal antibody production in patients with neuroborreliosis was superior to PCR. In urine samples from patients with Lyme borreliosis the diagnostic sensitivity varied, generally showing a low reproducibility. Urine is thus not regarded as a suitable sample source for B. burgdorferi PCR. The reason may be the variable presence of Taq polymerase inhibitors. Based on a semi-quantitative detection system for amplicons, reflecting the input amount of specific DNA and thus the density of spirochetes in the clinical samples high amounts of DNA were found in skin biopsies whereas especially in urine the amount of DNA was low. When the present study was initiated there was no accepted classification of B. burgdorferi. A heterogeneity among B. burgdorferi strains might have important implications for understanding the epidemiology and different clinical presentations (dermatoborreliosis versus neuroborreliosis) and courses (self-limiting versus chronic disease). Furthermore, strain differences were of importance for selection of suitable antigens for diagnostic assays and for vaccine development. Since then, B. burgdorferi isolates have been studied by phenotypic and genotypic traits and have been shown to be highly heterogeneous. Our first approach was to genotype a panel of human B. burgdorferi isolates by restriction fragment length polymorphism (RFLP) of three genes. Thereafter, sequencing and dideoxy fingerprinting of ospA was applied. By RFLP the strains could be differentiated into two to five groups. The RFLP classification was compared with four different phenotypic and genotypic methods including the rRNA typing. Results obtained with the different methods correlated highly and confirmed the meanwhile accepted taxonomic classification by Baranton et al., According to this the term B. burgdorferi sensu lato comprises three different human pathogenic genospecies B. burgdorferi sensu stricto, B. garinii and B. afzelii. All three genospecies have been isolated among Danish patients with Lyme borreliosis and are thus prevalent in Denmark. Since isolation of B. burgdorferi from patients with Lyme borreliosis is laborious and often unsuccessful molecular typing methods based on PCR are recommended obviating the need for isolation by prior culture. Of special interest was to study a possible association of neuroborreliosis to certain B. burgdorferi genospecies, indicating species depended organotropism. By RFLP all six CSF isolates tested belonged to B. garinii and that 6 out of 7 isolates from patients with acrodermatitis chronica atrophicans belonged to B. afzelii. Due to the low culture yield of B. burgdorferi from CSF, the association of B. garinii and neuroborreliosis was further studied by sequence analysis and dideoxyfingerprinting analysis of ospA PCR amplicons obtained from CSF samples from patients with neuroborreliosis. Phylogenetic analysis showed that in 11 out of 13 patients B. garinii DNA was found in CSF. These data strongly supports the hypothesis that B. garinii is the principal agent of Lyme neuroborreliosis in Europe. Similarly it was shown that B. afzelii is associated with acrodermatitis chronica atrophicans and thus dermatoborreliosis. Due to a strain dependent different selection pressure in culture only PCR based methods can be used to answer whether mixed infection in patients specimens occur. Our data indicate that mixed infections in humans if ever are rare.
Publication Types:
PMID: 11985118 [PubMed - indexed for MEDLINE]
Neurologic aspects of Lyme disease.
Coyle PK, Schutzer SE.
Department of Neurology, School of Medicine, State University of New York, Stony Brook, Stony Brook, New York, USA. pcoyle@notes.cc.sunysb.edu
Lyme disease has emerged as a major infection with frequent neurologic manifestations. These manifestations probably reflect several predominantly indirect pathogenetic mechanisms and involve host, vector, and organism factors. With early diagnosis and appropriate antibiotic treatment, patients do well. Because culture is not reliable, diagnosis has relied on positive serology to document exposure. Serology should improve as second-generation assays become available. Although there is a preventive vaccine based on the lipoprotein OspA, newer vaccines in development may prove more desirable. Lyme disease provides a valuable model to study how infectious pathogens cause neurologic disease.
Publication Types:
PMID: 11982301 [PubMed - indexed for MEDLINE]
[A patient with neuroborreliosis presenting gadolinium-enhanced MRI lesions in bilateral facial nerves]
[Article in Japanese]
Tokunaga H, Ohyagi Y, Furuya H, Araki T, Yamada T, Isogai E, Kira J.
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University.
We report a 33-year-old man with bilateral facial paralysis due to neuroborreliosis. About three weeks after rhinorrhea and fever lasting four days, he noticed fatigue in the legs and paresthesia in all four extremities. Another week later, he developed paresthesia in his tongue and bilateral facial muscle weakness, and was admitted to our hospital. On admission, neurological examination revealed moderate bilateral facial muscle weakness, mild paresthesia in the tongue and four extremities, and decreased Achilles tendon reflex bilaterally. Mild pleocytosis and increased protein were found in the cerebrospinal fluid (CSF). IgM antibodies that reacted with the antigens of Borrelia garinii and Borrelia afzelii were found in his serum. Clinically and serologically, he was thus diagnosed as having neuroborreliosis. Brain MRI revealed gadolinium-enhanced lesions of the bilateral facial nerves in the facial nerve canal portion. After three weeks of treatment with 100 mg/day doxycycline and 2 g/day ceftriaxone sodium, his symptoms and CSF abnormalities were rapidly improved. Although facial nerve paralysis is a major symptom of neuroborreliosis, the present report is the first to detect the inflammatory lesions of the facial nerves in the facial nerve canal portion by MRI.
Publication Types:
PMID: 11968752 [PubMed - indexed for MEDLINE]
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Large cerebral vessel occlusive disease in Lyme neuroborreliosis.
Klingebiel R, Benndorf G, Schmitt M, von Moers A, Lehmann R.
Neuroradiology Section, Department of Radiology, Charit Campus Mitte, Humboldt University Berlin, Germany. Randolf.Klingebiel@charite.de
We report on a 12-year-old, previously healthy girl with an acute hemiparesis as the predominant clinical manifestation of Lyme neuroborreliosis (LNB). The diagnosis of LNB was based on cerebrospinal fluid (CSF) studies, laboratory findings and the clinical course whereas the patient's history and the lack of characteristic skin lesions obscured the diagnosis in the beginning. After four weeks of antibiotic and physiotherapeutic treatment, the hemiparetic symptoms had completely resolved. Although evidence of vasculitic and perivascular inflammation in LNB has been described in the literature, large cerebral vessel occlusive disease represents a rare finding. Appropriate treatment strategies can lead to good clinical rehabilitation, as shown in this case, making the timely diagnosis a crucial issue. We conclude that LNB should be considered in every stroke-like episode of unknown origin in children, even in the absence of a history of a tick bite or typical skin lesions.
Publication Types:
PMID: 11930275 [PubMed - indexed for MEDLINE]
[Estimation of platelet counts and their morphological parameters in patients infected by borrelia burgdorferi]
[Article in Polish]
Zajkowska JM, Hermanowska-Szpakowicz T, Wysocka J, Pancewicz S, Lipska A, Kasprzycka E.
Kliniki Chorb Zakanych i Neuroinfekcji, Bialymstoku. zajkowsk@kki.net.pl
Platelet counts and their morphologic parameters in patients with Lyme borreliosis before and after antibiotic therapy (4 weeks of treatment) were estimated. 30 patients aged 17-60, x = 41 were evaluated: 7 with Erythema migrans, 3 patients with neuroborreliosis in the from Lymphocytic meningitis and 20 ones with Lyme arthritis. Control group consisted of 19 healthy persons aged 34-52, x = 43. Hematologic analyser Coulter MAXM was used for testing PLT, MPV, PCT and PDW. The results indicated that patients with Lyme boreliosis have decreasing platelet count with simultaneously increasing their volume in comparison with healthy control. It may result from the involement of platelets in defense mechanisms of infected host. The decrease of platelet count after the antibiotic treatment in comparison with the control group may be the reflection of influence of antibiotic treatment on thrombopoesis.
Publication Types:
PMID: 11928555 [PubMed - indexed for MEDLINE]
[Borrelia burgdorferi infection in children]
[Article in Polish]
Duszczyk E, Kowalik-Mikolajewska B.
Klinika Chorb Zakanych Wieku Dzieciecego Instytutu Chorb Zakanych i Pasozytniczych Akademii Medycznej w Warszawie.
OBJECTIVE: The aim of our analysis of causes of borreliosis in children hospitalized or ambulatory treated in the Clinic of Infectious Disease in Childhood of Medical University in Warsaw. METHODS AND MAIN OBSERVATIONS: We observed 113 children from 6 month to 15 years old. Erythema migrans was diagnosed in 97 cases and in 3 cases was multiple erytheme migrans. RESULTS AND CONCLUSIONS: Neuroborreliosis was diagnosed in 11 children. In the treatment neuroboreliosis the ceftriaxon and cristalline penicillin was administrated.
Publication Types:
PMID: 11921739 [PubMed - indexed for MEDLINE]
[Against Lyme borreliosis vaccination also, soon. Until then: antibiotics as early as possible!]
[Article in German]
Bischoff A.
Publication Types:
PMID: 11921651 [PubMed - indexed for MEDLINE]
Psychiatric presentations of non-HIV infectious diseases. Neurocysticercosis, Lyme disease, and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection.
Schneider RK, Robinson MJ, Levenson JL.
Departments of Psychiatry and Internal Medicine, Division of Consultation-Liaison Psychiatry, Medical College of Virginia, Campus of Virginia Commonwealth University, Richmond, Virginia, USA. rkschnei@hsc.vcu.edu
Infectious diseases can cause an array of symptoms, including psychiatric symptoms. Psychiatrists serving the medically ill need to be aware not only of classic infectious diseases (e.g., neurosyphilis and HIV), but also of less commonly discussed infectious diseases (e.g., NCC, PANDAS, and Lyme disease). These examples represent an internationally endemic disease (e.g., NCC), a probable immunogenetic disease (e.g., PANDAS), and a frequently overdiagnosed and overtreated disease (Lyme disease).
Publication Types:
PMID: 11912935 [PubMed - indexed for MEDLINE]
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[Multiple mononeuropathy and inflammatory syndrome manifested in Lyme disease]
[Article in French]
Jalladeau E, Pradat PF, Maisonobe T, Lger JM.
Fdration de Neurologie Mazarin, Groupe Hospitalier Piti-Salptrire, Paris.
Meningo-radiculitis is the most common peripheral nerve system involvement of Lyme disease. We report the observation of a 73 year-old woman presenting a subacute multiple mononeuropathy and a severe inflammatory syndrome. Diagnosis of Lyme disease was confirmed by a lymphocytic meningitis with positive serologic results in the cerebrospinal fluid. Nerve biopsy showed inflammatory cells spreading along the endoneurium. This case report emphasizes that Lyme disease may present as a multiple mononeuropathy mimicking a vasculitic neuropathy.
Publication Types:
PMID: 11885524 [PubMed - indexed for MEDLINE]
[Lyme neuroborreliosis in More and Romsdal]
[Article in Norwegian]
Eld¿en G, Vik IS, Vik E, Midgard R.
Nevrologisk avdeling, Fylkessjukehuset i Molde 6407 Molde. matsern@online.no
BACKGROUND: The broad variations in the clinical manifestation in Lyme borreliosis underline the importance of laboratory investigations in serum and cerebrospinal fluid. MATERIAL AND METHODS: We have studied patients with neurological signs compatible with Lyme neuroborreliosis, pleocytosis in cerebrospinal fluid and positive Borrelia serology in serum/cerebrospinal fluid analysed by ELISA. We have evaluated clinical characteristics, laboratory parameters, treatment effects, and incidence variations. RESULTS: We included 25 patients in the study. Isolated facial palsy was often seen, but clinical manifestations showed huge variation. Fourteen of 25 (56%) patients had positive Borrelia burgdorferi-IgM and IgG titres in cerebrospinal fluid despite negative tests in serum. The mean annual incidence rate in the county judged by notified cases to the Norwegian Surveillance System for Communicable Diseases (MSIS) was 4.4/100,000 in the period 1989-99 as compared to the national rate of 4.3/100,000 in the same period. In 1998, however, the annual incidence rate in the county was 8.8/100,000 as compared to the national rate of 4.1/100,000. INTERPRETATION: The diversity of symptoms and signs suggests a liberal attitude towards serological testing including CSF analyses. M¿re and Romsdal is a high incidence region for Lyme borreliosis in Norway. The annual variation in incidence might reflect a changing prevalence of the tick vector along the Norwegian coastline.
Publication Types:
PMID: 11875896 [PubMed - indexed for MEDLINE]
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Species-specific serodiagnosis of Lyme arthritis and neuroborreliosis due to Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii by using decorin binding protein A.
Heikkil T, Seppl I, Saxen H, Panelius J, Yrjninen H, Lahdenne P.
Hospital for Children and Adolescents, University of Helsinki, Finland. tero.heikkila@helsinki.fi
The antigenic potential of decorin binding protein A (DbpA) was evaluated in serodiagnosis of human Lyme borreliosis (LB). The dbpA was cloned and sequenced from the three pathogenic Borrelia species common in Europe. Sequence analysis revealed high interspecies heterogeneity. The identity of the predicted amino acid sequences was 43 to 62% among Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii. The respective recombinant DbpAs (rDbpAs) were produced and tested as antigens by Western blotting and enzyme-linked immunosorbent assay (ELISA). One hundred percent of patients with neuroborreliosis (NB) and 93% of patients with Lyme arthritis (LA) reacted positively. Sera from the majority of patients reacted with one rDbpA only and had no or low cross-reactivity to other two variant proteins. In patients with culture-positive erythema migrans (EM), the sensitivity of rDbpA immunoglobulin G (IgG) or IgM ELISA was low. The DbpA seems to be a sensitive and specific antigen for the serodiagnosis of LA or NB, but not of EM, provided that variants from all three pathogenic borrelial species are included in the combined set of antigens.
Publication Types:
PMID: 11825956 [PubMed - indexed for MEDLINE]
[Isolated posterior cord syndrome in Lyme s disease: a clinico neurophysiological study]
[Article in Spanish]
Gutirrez MA, de Pablos C, Oterino A, Garca Monc JC.
Servicio de Neurofisiologa Clnica; Hospital Universitario Marqus de Valdecilla, Santander, 39008, Espaa. mariaantonia1@navegalia.com
INTRODUCTION: Lyme disease, caused by spirochete Borrelia burgdorferi, is a multisystemic infectious disorder with prominent neurologic involvement, affecting both the peripheral and the central nervous system. Meningitis, cranial neuritis and radiculoneuritis are the usual manifestations in the acute phase, and peripheral neuropathy in the chronic phase. Other less common manifestations have been also described. Here we report one case of Lyme disease confirmed by PCR, with a previously undescribed neurological manifestation, and the neurophysiological studies performed before and after treatment. CLINICAL CASE: Our patient showed a chronic and progressive clinical picture consisting of instability on walking and distal paresthesia of lower limbs, suggestive of posterior column disfunction. The neurophysiological exam performed prior to treatment with ceftriaxone revealed bilateral absence of lower limbs somatosensory evoked potentials (SEPs), without alterations in the distal nervous conduction or in upper limbs SEPs. The exam performed after treatment revealed a partial recovery of lower limb SEP with presence of an evoked response in SEP of left lower limb, coincident with a transitory clinical improvement of paresthesia in the same extremity. CONCLUSIONS: Our findings reveal that posterior column disfunction can be a neurological manifestation of Lyme disease. Furthermore the neurophysiological study shows that this manifestation is partially reversible following treatment. Our study emphasize the importance of the neurophysiological tests for the diagnosis and follow up of neurological manifestations of Lyme disease.
Publication Types:
PMID: 11785008 [PubMed - indexed for MEDLINE]
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Erratum in:- Immunol Rev. 2002 Sep;187:139.
The rhesus model of Lyme neuroborreliosis.
Pachner AR, Gelderblom H, Cadavid D.
Neurosciences, UMDNJ - New Jersey Medical School, Newark, NJ, USA.
Similarity of pathology and disease progression make the non-human primate (NHP) model of Lyme neuroborreliosis appropriate and valuable. In the NHP model of Lyme neuroborreliosis, spirochetal density in the nervous system and other tissues has been measured by polymerase chain reaction and correlated to anti-Borrelia burgdorferi antibody in the serum and cerebrospinal fluid and to inflammation in tissues. Despite the demonstrable presence of Borrelia burgdorferi, the causative agent of Lyme borreliosis, only minor inflammation of the central nervous system occurs, though inflammation can be demonstrated in other tissues. Infected animals also develop anti-Borrelia burgdorferi antibody in the serum, although increased amplitude of antibody is not predictive of higher levels of infection. The NHP model continues to provide important insight into the disease process in humans.
Publication Types:
PMID: 11782257 [PubMed - indexed for MEDLINE]
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Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections.
Pashenkov M, Teleshova N, Kouwenhoven M, Smirnova T, Jin YP, Kostulas V, Huang YM, Pinegin B, Boiko A, Link H.
Division of Neurology, Karolinska Institute, Huddinge University Hospital R54, SE-14186, Stockholm, Sweden. Mikhail.Pashenkov@neurotec.ki.se
Dendritic cells (DC) accumulate in the CNS during inflammation and may contribute to local immune responses. Two DC subsets present in human cerebrospinal fluid (CSF) are probably recruited from myeloid (CD11c(+)CD123(dim)) and plasmacytoid (CD11c(-)CD123(high)) blood DC. In bacterial meningitis and especially in Lyme meningoencephalitis, numbers of myeloid and plasmacytoid DC in CSF were increased, compared to non-inflammatory neurological diseases, and correlated with chemotactic activity of CSF for immature monocyte-derived DC (moDC). Multiple DC chemoattractants, including macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-1, MCP-3, RANTES and stromal cell-derived factor (SDF)-1alpha were elevated in CSF in these two neuroinfections. Chemotaxis of immature moDC induced by these CSFs could be partially inhibited by mAbs against CXCR4, the receptor for SDF-1alpha, and CD88, the receptor for C5a. SDF-1alpha present in CSF also chemoattracted mature moDC, which in vivo could correspond to a diminished migration of antigen-bearing DC from the CSF to secondary lymphoid organs. Regulation of DC trafficking to and from the CSF may represent a mechanism of controlling the CNS inflammation.
Publication Types:
PMID: 11777549 [PubMed - indexed for MEDLINE]
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Abdominal wall weakness and lumboabdominal pain revealing neuroborreliosis: a report of three cases.
Mormont E, Esselinckx W, De Ronde T, Hanson P, Deltombe T, Laloux P.
Cliniques Universitaires UCL de Mont-Godinne, Universit Catholique de Louvain, Yvoir, Belgium.
The authors report three cases of thoracic radiculoneuropathy disclosing neuroborreliosis. All three patients had low back and abdominal pain and two had marked abdominal wall paresis. EMG confirmed a motor involvement of the lower thoracic roots and CSF analysis revealed a lymphocytic meningitis in all three cases. Antibodies against Borrelia burgdorferi were present in both the serum and the CSF. A favourable outcome was obtained in all three patients with appropriate antibiotherapy. The differential diagnosis of this misleading presentation is discussed.
Publication Types:
PMID: 11771534 [PubMed - indexed for MEDLINE]
Avidity determination of Borrelia burgdorferi-specific IgG antibodies in Lyme disease.
Rauer S, Beitlich P, Neubert U, Rasiah C, Kaiser R.
Department of Neurology, Albert Ludwig University, Freiburg, Germany. rauer@nz11.ukl.uni-freiburg.de
The avidity indices of Borrelia burgdorferi-specific IgG antibodies were estimated using ELISA in sera from patients with different stages of Lyme disease. In addition, sera from healthy students with proof of borrelial-specific IgG antibodies from standard serology were tested. Low avidity indices were detected predominantly in sera from patients with early-stage Lyme disease [erythema migrans (EM); n = 25]. High avidity indices were found in healthy students (n = 72) and in most of the patients with neuroborreliosis (NB; n = 44) and chronic late-stage Lyme disease [acrodermatitis chronica atrophicans (ACA); n = 36]. In conclusion, early-stage Lyme disease (EM) could be differentiated from advanced and chronic stages (NB, ACA) and from "seropositive" healthy persons using avidity determination in the majority of patients in this study.
Publication Types:
PMID: 11760158 [PubMed - indexed for MEDLINE]
A controlled study of cognitive deficits in children with chronic Lyme disease.
Tager FA, Fallon BA, Keilp J, Rissenberg M, Jones CR, Liebowitz MR.
Columbia University Department of Psychiatry, Division of Behavioral Medicine, New York, New York 10032, USA. ft49@columbia.edu
Although neurologic Lyme disease is known to cause cognitive dysfunction in adults, little is known about its long-term sequelae in children. Twenty children with a history of new-onset cognitive complaints after Lyme disease were compared with 20 matched healthy control subjects. Each child was assessed with measures of cognition and psychopathology. Children with Lyme disease had significantly more cognitive and psychiatric disturbances. Cognitive deficits were still found after controlling for anxiety, depression, and fatigue. Lyme disease in children may be accompanied by long-term neuropsychiatric disturbances, resulting in psychosocial and academic impairments. Areas for further study are discussed.
Publication Types:
PMID: 11748319 [PubMed - indexed for MEDLINE]
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FLAIR and magnetization transfer imaging of patients with post-treatment Lyme disease syndrome.
Morgen K, Martin R, Stone RD, Grafman J, Kadom N, McFarland HF, Marques A.
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1400, USA.
OBJECTIVE: To determine patterns of abnormalities on cerebral MRI that may characterize subgroups of patients with post-treatment Lyme disease syndrome (PTLDS) and to help identify pathomechanisms of disease. METHODS: The authors analyzed the distribution of cerebral lesions in a cohort of 27 patients with PTLDS. A subgroup of eight patients with PTLDS was further studied using whole-brain magnetization transfer ratio measures to identify abnormalities not seen on T2-weighted images. RESULTS: Four patients had focal neurologic deficits, relapsing-remitting disease, and lesions in a distribution typical of MS. Twenty-three patients presented with nonfocal symptoms such as fatigue, subjective memory deficits, and mood disturbance. Twelve of these patients had normal MRI, including the more sensitive fluid-attenuated inversion recovery sequence, 10 had primarily punctate and subcortical lesions, and one patient had multiple periventricular lesions. CONCLUSIONS: In a portion of patients with post-treatment Lyme disease syndrome, white-matter hyperintensities tend to occur in subcortical arteriolar watershed areas and are not specific. Magnetization transfer ratio analysis did not provide evidence for structural abnormalities of the brain parenchyma in patients with nonfocal disease.
PMID: 11739813 [PubMed - indexed for MEDLINE]
Serum and cerebrospinal fluid pathology in patients with sudden sensorineural hearing loss.
Finizia C, Jnsson R, Hanner P.
Department of Otorhinolaryngology, Sahlgrenska University Hospital, Mlndal, Sweden.
The serum and cerebrospinal fluid (CSF) pathology of patients with sudden sensorineural hearing loss (SHL), both seropositive and seronegative to Borrelia burgdorferi (Bb), was prospectively studied. Nineteen consecutive patients were included and trends between the degree of hearing recovery and serum/CSF pathology and given therapy were examined. The pilot study showed a high prevalence (68%) of pathology in serum and CSF in patients with SHL. In 54% of the patients, elevated levels of CSF proteins and/or pathological CSF cell counts were present without positive antibodies to Bb. Positive levels of antibodies against Bb or pathological proteins in CSF were associated with better hearing recovery (means of 47.2 and 51.7%, respectively). The audiometric configuration "high frequency sloping" hearing impairment was associated with the lowest degree of hearing recovery. Patients with SHL and positive serology to Bb who received antibiotic treatment (oral tetracycline), with or without steroids, had the best hearing recovery in this study (61.7 and 48.4%, respectively). In conclusion, we found a high prevalence of serum and CSF pathology in a consecutive group of patients with SHL. Early appropriate antibiotic treatment may prevent the development of major late complications of Lyme disease/borreliosis. We also find it justified to perform more general serological analyses, including CSF analysis, in patients with SHL. A more liberal approach to testing and development of test protocols for SHL patients will increase our knowledge in this field.
Publication Types:
PMID: 11718246 [PubMed - indexed for MEDLINE]
Comment on:
[Facial paresis in children; consider Lyme disease]
[Article in Dutch]
Meinardi H.
Publication Types:
PMID: 11605320 [PubMed - indexed for MEDLINE]
Cerebrospinal fluid.
Adam P, Tborskù L, Sobek O, Hildebrand T, Kelbich P, Prócha M, Hynek J.
Laboratory of Reference for CSF and Neuroimmunology, Homolka Hospital Prague, Czech Republic.
Publication Types:
PMID: 11605255 [PubMed - indexed for MEDLINE]
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Protection against tick-transmitted Lyme disease in dogs vaccinated with a multiantigenic vaccine.
Straubinger RK, Dharma Rao T, Davidson E, Summers BA, Jacobson RH, Frey AB.
Universitt Leipzig, Veterinrmedizinische Fakultt, Institut fr Immunologie, An den Tierkliniken 11, 04103, Leipzig, Germany. straubinger@vetmed.uni-leipzig.de
In an effort to develop a safe and effective vaccine for the prevention of Lyme borreliosis that addresses concerns raised over currently available vaccines, dogs were vaccinated twice with a multiantigenic preparation of Borrelia burgdorferi, strain N40, on days 0 and 20 of the experiment. About 70 and 154 days after the first immunization, dogs were challenged by exposing them to field-collected Ixodes scapularis ticks harboring B. burgdorferi. Vaccinated dogs were completely protected from infection by all criteria utilized to assess infection, developed high-titer anti-B. burgdorferi serum antibodies and growth inhibitory activity which persisted for over 200 days, and did not demonstrate any untoward consequence of vaccination. Serum absorption experiments revealed that borreliacidal and most likely protective antibodies in dogs receiving the multiantigenic preparation were not only elicited against the OspA antigen, but were also produced against additional yet to be determined targets on B. burgdorferi organisms. These data demonstrate that a multiantigenic vaccine is effective in preventing Lyme disease transmitted via the natural vector.
Publication Types:
PMID: 11567763 [PubMed - indexed for MEDLINE]
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Comment in:
Concurrent infection of the central nervous system by Borrelia burgdorferi and Bartonella henselae: evidence for a novel tick-borne disease complex.
Eskow E, Rao RV, Mordechai E.
Hunterdon Medical Center, Flemington, NJ, USA.
OBJECTIVES: To investigate Bartonella henselae as a potential human tick-borne pathogen and to evaluate its role as a coinfecting agent of the central nervous system in the presence of neuroborreliosis. DESIGN: Case report study. SETTING: A primary health care center in Flemington, NJ, and the Department of Research and Development at Medical Diagnostic Laboratories LLC in Mt Laurel, NJ. SUBJECTS: Two male patients (aged 14 and 36 years) and 2 female patients (aged 15 and 30 years, respectively) with a history of tick bites and Lyme disease. MAIN OUTCOME MEASURES: Laboratory and diagnostic findings before and after antimicrobial therapy. RESULTS: Patients residing in a Lyme-endemic area of New Jersey with ongoing symptoms attributed to chronic Lyme disease were evaluated for possible coinfection with Bartonella species. Elevated levels of B henselae-specific antibodies were found in these patients using the immunofluorescent assay. Bartonella henselae-specific DNA was detected in their blood. None of these patients exhibited the clinical characteristics of cat-scratch disease. Findings of cerebrospinal fluid analysis revealed the presence of both B henselae- and Borrelia burgdorferi-specific DNA. Bartonella henselae-specific DNA was also detected in live deer ticks obtained from the households of 2 of these patients. CONCLUSIONS: Our data implicate B henselae as a potential human tick-borne pathogen. Patients with a history of neuroborreliosis who have incomplete resolution of symptoms should be evaluated for B henselae infection.
Publication Types:
PMID: 11559306 [PubMed - indexed for MEDLINE]
Central and peripheral nervous system infection, immunity, and inflammation in the NHP model of Lyme borreliosis.
Pachner AR, Cadavid D, Shu G, Dail D, Pachner S, Hodzic E, Barthold SW.
Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark 07103, USA. pachner@umdnj.edu
The relationship between chronic infection, antispirochetal immunity, and inflammation is unknown in Lyme neuroborreliosis. In the nonhuman primate model of Lyme neuroborreliosis, we measured spirochetal density in the nervous system and other tissues by polymerase chain reaction and correlated these values to anti-Borrelia burgdorferi antibody in the serum and cerebrospinal fluid, and to inflammation in tissues. Despite substantial presence of Borrelia burgdorferi, the causative agent of Lyme borreliosis, in the central nervous system, only minor inflammation was present there, though skeletal and cardiac muscle, which contained similar levels of spirochete, were highly inflamed. Anti-Borrelia burgdoferi antibody was present in the cerebrospinal fluid but was not selectively concentrated. All infected animals developed anti-Borrelia burgdorferi antibody in the serum, but increased amplitude of antibody was not predictive of higher levels of infection. These data demonstrate that Lyme neuroborreliosis is a persistent infection, that spirochetal presence is a necessary but not sufficient condition for inflammation, and that antibody measured in serum may not predict the severity of infection.
Publication Types:
PMID: 11558789 [PubMed - indexed for MEDLINE]
[Antibacterial therapy in tick borreliosis (Lyme disease)]
[Article in Russian]
Ushkalova EA.
Peoples' Friendship University of Russia, Moscow.
Publication Types:
PMID: 11544751 [PubMed - indexed for MEDLINE]
Comment in:
Comment on:
[Facial paresis in children; consider Lyme disease]
[Article in Dutch]
Dekker CJ.
Publication Types:
PMID: 11503319 [PubMed - indexed for MEDLINE]
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Tick bite induced respiratory failure. Diaphragm palsy in Lyme disease.
Winterholler M, Erbguth FJ.
Publication Types:
PMID: 11497145 [PubMed - indexed for MEDLINE]
[What is your diagnosis? Bannwarth syndrome (acute Lyme neuroborreliosis)]
[Article in German]
Pfister HW.
Neurologische Universittsklinik Grosshadern Marchioninistrasse 15 D-81377 Mnchen.
Publication Types:
PMID: 11458772 [PubMed - indexed for MEDLINE]
Optic nerve lesion following neuroborreliosis: a case report.
Burkhard C, Gleichmann M, Wilhelm H.
Ahaus Eye Hospital, Germany. carsten@dr-burkhard.de
PURPOSE: Neuroborreliosis may cause various neuro-ophthalmological complications. We describe a case with a bilateral optic neuropathy. CASE REPORT: A 58-year-old female developed facial paresis six weeks after an insect bite. One week later she developed bilateral optic disc swelling with haemorrhages and nerve fibre bundle defects in the lower visual field of the left eye. In CSF and serum, raised IgM and IgG titres to Borrelia burgdorferi were found. Systemic antibiotic treatment led to improvement of the vision and facial paresis, but not all visual field defects resolved, probably due to ischemic lesions of the optic disc. DISCUSSION/CONCLUSIONS: In optic nerve lesions due to neuroborreliosis it is difficult to distinguish between inflammatory and ischemic lesions. This patient demonstrated features of an ischemic optic nerve lesion.
Publication Types:
PMID: 11456029 [PubMed - indexed for MEDLINE]
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Dysarthria as the isolated clinical symptom of borreliosis--a case report.
Gustaw K, Mirecka U.
Outpatients Neurological Department, Institute of Agricultural Medicine, Jaczewskiego 2, P.O. Box 185, 20-950 Lublin, Poland. gustaw@galen.imw.lublin.pl
This report presents a case of dysarthria due to hypoglossal nerve mono-neuropathy as the only consequence of neuroborreliosis. The 65-year-old man with a seven-months history of articulation disturbances was examined. The speech of the patient was slow and laboured. A slight weakness of the muscles of the tongue (left-side) was observed. The patient suffered from meningitis due to Borrelia burgdorferi infection in 1999 and initially underwent a successful antibiotic treatment. Detailed radiological investigation and psychological tests were performed and co-existing neurological diseases were excluded. To describe profile of speech abnormalities the dysarthria scale was designed based on S. J. Robertson Dysarthria Profile. There were a few disturbances found in self-assessment of speech, intelligibility, articulation, and prosody but especially in the morphology of the articulation muscles, diadochokinesis, the reflexes (in the mouth, larynx and pharynx). Needle EMG examination confirmed the diagnosis of mono-neuropathy of left hypoglossal nerve. The study confirms the fact that neuroborreliosis may evoke chronic consequences.
Publication Types:
PMID: 11426931 [PubMed - indexed for MEDLINE]
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Neurological and psychological symptoms after the severe acute neuroborreliosis.
Gustaw K, Beltowska K, Studzinska MM.
Outpatients Neurological Department, Institute of Agricultural Medicine, Jaczewskiego 2, P.O. Box 185, 20-950 Lublin, Poland. gustaw@galen.imw.lublin.pl
The purpose of this study was to delineate distant neurological and neuropsychological effects of severe neuroborreliosis. A group of 33 patients (12 men and 21 women) were selected for the study. Every patient had suffered from severe meningitis, meningoencephalitis or meningopolyradiculoneuritis due to neuroborreliosis in the chronic form of the illness. Standardised medical interview, physical examination and a series of neuropsychological tests (WAIS-R, BDI, BENTON-BENDER, DUM) were performed. In the clinical history, 36.4% of the patients complained of headache, 27.3% of subjective memory distortions; 33.3% of the patients suffered from sleeplessness. The neurological examination showed that 36.4% of the patients experienced such cerebellum integrity disturbances as abnormalities in gait and coordination or even mild ataxia. 21.2% of the patients experienced dysfunction in the proprioceptive pathways, 9% asymmetry in deep tendon reflexes (DTR's), 27.3% disturbances in the sensory responses. The examination showed, however, no muscular strength abnormalities. Half of the patients had slight depression. Psychological tests indicated that 21.2% of the patients had problems in thinking process and experienced memory impairment. 36.4% of the patients had significant organic damage in the central nervous system. The results of this study suggest the existence of long-lasting consequences of acute neuroborreliosis, which can significantly influence the quality of life of patients.
PMID: 11426930 [PubMed - indexed for MEDLINE]
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Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response.
Derfuss T, Grkov R, Then Bergh F, Goebels N, Hartmann M, Barz C, Wilske B, Autenrieth I, Wick M, Hohlfeld R, Meinl E.
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Chronic intrathecal immunoglobulin (Ig) production is a hallmark of multiple sclerosis characterized by the presence of oligoclonal IgGs and, in addition, polyspecific recognition of different pathogens such as measles, rubella and herpes zoster virus. While the antigen specificity of the oligoclonal IgGs in multiple sclerosis is largely unknown, the oligoclonal IgGs arising during CNS infectious diseases are reactive against the specific pathogen. Recently, a link between Chlamydia pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple sclerosis, we analysed (i) whether there is intrathecal IgG production against C. pneumoniae in multiple sclerosis and (ii) if the oligoclonal IgGs in the CSF of multiple sclerosis patients recognize C. pneumoniae. By studying paired serum-CSF samples from 120 subjects (definite multiple sclerosis, 46; probable multiple sclerosis, 12; other inflammatory neurological diseases, 35; other neurological diseases, 27) by enzyme-linked immunosorbent assay, we found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases, produced IgGs specific for C. pneumoniae intrathecally (definite multiple sclerosis versus other inflammatory neurological diseases: P = 0.027). The presence of intrathecal IgGs to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG bands from multiple sclerosis patients with an intrathecal Ig production to C. pneumoniae did not react towards purified elementary bodies and reticulate bodies of C. pneumoniae on affinity-mediated immunoblot following isoelectric focusing (IEF-western blots). In contrast, the IgGs in the CSF of control patients with neuroborreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi, by IEF-western blot analysis. Concomitant analysis of the CSF of 23 patients with a nested polymerase chain reaction for C. pneumoniae was negative in all cases. Together, our findings strongly suggest that the immune response to C. pneumoniae is part of a polyspecific intrathecal Ig production, as is commonly observed with other pathogens. This argues against a specific role for C. pneumoniae in multiple sclerosis.
Publication Types:
PMID: 11408328 [PubMed - indexed for MEDLINE]
Comment in:
[Facial paresis in children; consider Lyme disease]
[Article in Dutch]
Dorresteijn EM, Kouwenberg JM.
Leids Universitair Medisch Centrum, afd. Kindergeneeskunde, Leiden.
Three girls, aged 3, 7 and 13 years, developed acute peripheral facial palsy. The first patient was initially diagnosed as having Bell's palsy. The third patient had negative serology at first assessment, on the basis of which the diagnosis of Lyme disease was temporarily rejected. Ultimately, all three appeared to have neuroborreliosis. They were treated with intravenous ceftriaxone and recovered well. Facial palsy in childhood is frequently caused by Lyme borreliosis and infection with Borrelia burgdorferi should therefore be investigated, even if there are no signs of a tick bite or erythema migrans. Diagnosis is made by serology, followed by immunoblotting to confirm a positive result. In case of strong suspicion based on the patient's history or physical examination or a positive serology, lumbar puncture should be carried out. Antibiotic treatment facilitates recovery and prevents complications.
Publication Types:
PMID: 11407277 [PubMed - indexed for MEDLINE]
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Competitive inhibition ELISA for the detection of Borrelia burgdorferi antigens--failure to detect antigen in the cerebrospinal fluid from patients with neuroborreliosis.
Rauer S, Conrad A.
Publication Types:
PMID: 11393297 [PubMed - indexed for MEDLINE]
Follow-up of patients treated with oral doxycycline for Lyme neuroborreliosis.
Karkkonen K, Stiernstedt SH, Karlsson M.
Department of Infectious Diseases, Karolinska Institutet, Huddinge, Sweden.
The clinical outcome for 69 patients treated with oral doxycycline for Lyme neuroborreliosis was studied retrospectively. The clinical follow-up time was 14 d to 2 y (median 7 months). All patients improved during and after treatment. A complete recovery was seen in 56 patients by 14 d to 9 months (median 6 weeks) after therapy, while 13 patients (19%) still had persistent sequelae 1 y after antibiotic treatment. Six patients were retreated because of new or persistent symptoms, but in no patient was a treatment failure proven. A questionnaire was sent to each patient, asking for time to recovery, sequelae and relapse of symptoms. No patient had experienced relapse of symptoms associated with Lyme neuroborreliosis when answering the questionnaire 2-9 y after treatment. Oral doxycycline seems to be an effective, convenient and inexpensive alternative for the treatment of Lyme neuroborreliosis.
PMID: 11345216 [PubMed - indexed for MEDLINE]
[Psychologic disorders in acute and persistent neuroborreliosis]
[Article in Polish]
Poplawska R, Konarzewska B, Gudel-Trochimowicz I, Szulc A.
Klinika Chorb Psychicznych AM w Bialymstoku.
In the risk group, inhabiting endemic areas, even non-specific symptoms should alert the physician to the possibility of infection caused by the spirochete. The invasion of central nervous system (neuroborreliosis) may be the cause for persisting, irreversible intellectual impairment and memory deficits. Brain lesions are the result of misdiagnosis and delayed antibiotic treatment. This paper describes a case of neuroborreliosis with atypical beginning and diagnostic difficulties.
Publication Types:
PMID: 11320549 [PubMed - indexed for MEDLINE]
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Characterization of Lyme borreliosis isolates from patients with erythema migrans and neuroborreliosis in southern Sweden.
Ornstein K, Berglund J, Nilsson I, Norrby R, Bergstrm S.
Department of Infectious Diseases and Medical Microbiology, Lund University, Lund, Sweden.
Southern Sweden is an area of Lyme borreliosis (LB) endemicity, with an incidence of 69 cases per 100,000 inhabitants. The most frequent clinical manifestations are erythema migrans (77%) and neuroborreliosis (16%). There was no record of human Borrelia strains being isolated from patients in this region before the prospective study reported here. Borrelia spirochetes were isolated from skin and cerebrospinal fluid (CSF) from LB patients living in the region. A total of 39 strains were characterized by OspA serotype analysis, species-specific PCR, and signature nucleotide analysis of the 16S rRNA gene. Of 33 skin isolates, 31 (93.9%) were Borrelia afzelii strains and 2 (6.1%) were Borrelia garinii strains. Of six CSF isolates, five (83.3%) were B. garinii and one (16.7%) was B. afzelii. Neither Borrelia burgdorferi sensu stricto strains nor multiple infections were observed. The B. afzelii isolates were of OspA serotype 2. Three B. garinii strains were of OspA serotype 5, and the remaining four strains were of OspA serotype 6. All of the B. garinii strains belonged to the same 16S ribosomal DNA ribotype class. Our findings agree with earlier findings from other geographic regions in Europe where B. afzelii and B. garinii have been recovered predominantly from skin and CSF cultures, respectively. To further study the possible presence in Sweden of the genotype B. burgdorferi sensu stricto, which is known to be present in Europe and to occur predominantly in patients with Lyme arthritis, molecular detection of Borrelia-specific DNA in synovial samples from Lyme arthritis patients should be performed.
Publication Types:
PMID: 11283044 [PubMed - indexed for MEDLINE]
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[Autochthonous cases of tick-borne encephalitis in Rhineland-Palatinate]
[Article in German]
Woessner R, Mhl A, von Arnim WH, Treib J.
Neurologische Klinik, Westpfalz-Klinikum GmbH, Kaiserslautern.
Tick-borne encephalitis (TBE) is a neurotrophic viral disease which is endemic to certain regions. Such areas in Germany include Bavaria, Baden-Wrttemberg, and the Odenwald region in Hessen. So far, it has not been endemic to Rhineland-Palatinate. There, only two single cases of TBE occurred in the years 1992 and 1997, near the town of Idar-Oberstein. We report two new cases of TBE which appeared in 1999 and two current cases from the Idar-Oberstein region which have been verified clinically and serologically. At admission, the patients suffered from headache, muscle pains, and high fever, in one case meningitis was suspected. In all four patients, serology for borrelia was negative in serum and CSF. The described cases indicate that it is possible to acquire TBE in Rhineland-Palatinate, although only two cases have been reported in this area over the previous 10 years. Particularly in regions with a low incidence of TBE, the disease should be taken into consideration as a differential diagnosis. Studies of tick populations in regions with a low incidence can help in evaluating the benefit of possible vaccine recommendations by local public health authorities.
Publication Types:
PMID: 11256150 [PubMed - indexed for MEDLINE]
[Neuroborreliosis]
[Article in French]
Machurot PY, Fumal A, Sadzot B.
Les Cliniques St-Joseph ASBL, Lige.
Lyme disease, or borreliosis, is an endemic affection in Belgium. It is transmitted by a spirochete, Borrelia burgdorferi. The particularity of the infecting genomic group, Borrelia garinii, implies that half of the reported cases of Lyme disease in our country have neurologic manifestations. Due to the marked clinical heterogeneity and the difficult serologic diagnosis, neuroborreliosis is often part of the differential diagnosis in neurology. The antibiotic treatment is necessary because it decreases the risk of more advanced stages of the disease. We hope that a vaccination will soon be available in Belgium.
Publication Types:
PMID: 11256131 [PubMed - indexed for MEDLINE]
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Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs.
Reiber H, Peter JB.
Neurochemistry Laboratory, University Gttingen, Robert-Koch-Strasse 40, D-37075 Gttingen, Germany. hreiber@med.uni-goettingen.de
Cerebrospinal fluid (CSF) analysis is a basic tool for diagnosis of neurological diseases. Knowledge regarding blood-CSF barrier function (molecular flux/CSF flow theory) and neuroimmunology is reviewed to aid understanding and evaluation of CSF data. Disease-related immunoglobulin patterns (IgG, IgA, IgM with reference to albumin) are described in CSF/serum quotient diagrams with the hyperbolic reference range for blood-derived protein fractions in CSF. Clinical relevance of complementary analyses (cytology, PCR, oligoclonal IgG, antibody detection and brain-derived proteins) is briefly discussed. Integrated CSF data reports are shown with numerical and graphical data representation, reference range-related interpretation and diagnosis-related comments. The principles and rationale of general CSF analysis reported in this review should enable the reader to accurately interpret CSF data profiles, and to plan a proper evaluation of new brain- or blood-derived analytes in CSF.
Publication Types:
PMID: 11239944 [PubMed - indexed for MEDLINE]
Lyme borreliosis in rhesus macaques: effects of corticosteroids on spirochetal load and isotype switching of anti-borrelia burgdorferi antibody.
Pachner AR, Amemiya K, Bartlett M, Schaefer H, Reddy K, Zhang WF.
Department of Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 S. Orange St., Newark, NJ 07103, USA. pachner@umdnj.edu
Experimental Borrelia burgdorferi infection of rhesus monkeys is an excellent model of Lyme disease and closely parallels the infection in humans. Little is known about the interaction of host immunity with the spirochete in patients with chronic infection. We hypothesized that rapid development of anti-B. burgdorferi antibody in immunocompetent nonhuman primates (NHPs) is the major determinant of the reduction of the spirochetal load in Lyme borreliosis. This hypothesis was tested by measurement of the spirochetal load by PCR in association with characterization of the anti-B. burgdorferi humoral immune response in immunocompetent NHPs versus that in corticosteroid-treated NHPs. Although anti-B. burgdorferi immunoglobulin G (IgG) antibody was effectively inhibited in dexamethasone (Dex)-treated NHPs, anti-B. burgdorferi IgM antibody levels continued to rise after the first month and reached levels in excess of IgM levels in immunocompetent NHPs. This vigorous production of anti-B. burgdorferi IgM antibodies was also studied in vitro by measurement of antibody produced by B. burgdorferi-stimulated peripheral blood mononuclear cells. Despite these high IgM antispirochetal antibodies in Dex-treated NHPs, spirochetal loads were much higher in these animals. These data indicate that Dex treatment results in interference with isotype switching in this model and provide evidence that anti-B. burgdorferi IgG antibody is much more effective than IgM antibody in decreasing the spirochetal load in infected animals.
PMID: 11238200 [PubMed - indexed for MEDLINE]
Spontaneous brain hemorrhage associated with Lyme neuroborreliosis.
Seijo Martnez M, Grandes Ibez J, Snchez Herrero J, Garca-Monc JC.
Servicio de Neurologa, Complexo Hospitalario de Pontevedra, Lureiro Crespo, s/n 36001 Pontevedra. mseijom@meditex.es
We present the case of a patient with late neuroborreliosis and a spontaneous temporal lobe hemorrhage. Although ischemic stroke and subarachnoid hemorrhage have been reported in association with Lyme disease, intraparenchymal brain hemorrhage has not been previously described in the course of this disease. The patient is a 48-year old male with a progressive spastic paraparesis of months' duration who presented acute headache, confusion, severe left hemiparesis with sensory deficit and homonymous hemianopsia. A cranial computed tomography scan showed an extensive right temporal lobe hemorrhage with subarachnoid invasion. Brain angiographic and angio-magnetic resonance imaging studies excluded hemorrhage-predisposing vascular abnormalities. Cerebrospinal fluid (CSF) studies disclosed mononuclear pleocytosis with elevated protein levels. Both serum and CSF anti-Borrelia titers were significantly increased, and serum Western Blot showed bands to protein 34 (ops B), 57, 59 and 62. The patient was treated with ceftriaxone for 4 weeks, with a favorable outcome. It is suspected that cause of the hemorrhage was parenchymatous Lyme-associated vascular damage and/or microaneurysmatic rupture.
Publication Types:
PMID: 11234662 [PubMed - indexed for MEDLINE]
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Two subsets of dendritic cells are present in human cerebrospinal fluid.
Pashenkov M, Huang YM, Kostulas V, Haglund M, Sderstrm M, Link H.
Division of Neurology, Karolinska Institutet, Huddinge University Hospital, R54, SE-14186 Huddinge, Sweden. Mikhail.Pashenkov@neurotec.ki.se
Little is known about the presence of dendritic cells in the human CNS. To investigate the occurrence of dendritic cells in the CSF, paired blood/CSF samples from patients with multiple sclerosis, acute optic neuritis, Lyme neuroborreliosis, other inflammatory neurological diseases and non-inflammatory neurological diseases were examined using flow cytometry. Almost all CSF samples contained myeloid (lin-CD11c+HLA-DR++CD123(dim)) and plasmacytoid (lin-CD11c-HLA-DR+CD123(high)) dendritic cells. In non-inflammatory neurological diseases, dendritic cells of either subset only constituted up to 1% of CSF mononuclear cells. Myeloid CSF dendritic cells were elevated in optic neuritis, neuroborreliosis and other inflammatory neurological disorders, while plasmacytoid dendritic cells were elevated in all neuroinflammatory conditions studied, with especially high numbers in neuroborreliosis. Numbers of CSF dendritic cells correlated with the common parameters of CNS inflammation. The myeloid dendritic cells in CSF expressed higher levels of HLA-DR, CD86, CD80 and CD40 than those in blood, whereas expression of these molecules by plasmacytoid dendritic cells was equal in blood and CSF. Both CSF and blood dendritic cells expressed the chemokine receptor CCR5. This is the first demonstration that dendritic cells are present in human CSF and that plasmacytoid dendritic cells are present in a non-lymphoid compartment. Myeloid and plasmacytoid dendritic cells in CSF may contribute to orchestration of the local immune responses.
Publication Types:
PMID: 11222448 [PubMed - indexed for MEDLINE]
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Lyme borreliosis mimicking central nervous system malignancy: the diagnostic pitfall of cerebrospinal fluid cytology.
Kieslich M, Fiedler A, Driever PH, Weis R, Schwabe D, Jacobi G.
Department of Pediatric Neurology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany. mkieslich@zki.uni-frankfurt.de
We report two children with acute loss of neurological functions and signs of an increased intracranial pressure. Imaging techniques ruled out space occupying lesions, whereas CSF cytology indicated CNS involvement of a non-Hodgkin lymphoma in the form of abnormal lymphocytic pleocytosis with malignancy criteria fulfilling lymphoid cells. CSF protein electrophoresis and Borrelia burgdorferi serology revealed neuroborreliosis which was successfully treated with antibiotic therapy. The malignancy mimicking cytology is based on a blastoid transformation of B- and T-lymphocytes due to the antigenic stimulus of B. burgdorferi infection. Lymphoid cells in the CSF of a patient with acute or chronic neurological symptoms raise the differential diagnosis of inflammatory etiology versus CNS lymphoma. Monomorphism and higher quantity of the lymphoid cells point to CNS lymphoma. A lower quantity and polyclonal pattern of lymphoid cells associated with an elevated protein fraction caused by intrathecal immunoglobulin synthesis suggest an inflammatory etiology.
Publication Types:
PMID: 11185583 [PubMed - indexed for MEDLINE]
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Clinical comparison of immunoblot and antibody index for detection of intrathecal synthesis of specific antibodies in Lyme neuroborreliosis.
Pcha D, Moravcov L, Zdrskù E, Benes J.
1st Clinic for Infectious Diseases, Faculty Hospital Bulovka, Prague, Czech Republic.
Publication Types:
PMID: 11117651 [PubMed - indexed for MEDLINE]
[Neurologic syndromes in Lyme disease]
[Article in Polish]
Zajkowska JM, Hermanowska-Szpakowicz T, Kondrusik M, Pancewicz SA.
Kliniki Chorb Pasozytniczych i Neuroinfekcji AM w Bialymstoku.
Lyme borreliosis, multisystem disease, when involve neurologic system is named neuroborrelosis. Symptomatology of neuroborreliosis is rich and various. Difficulties in recognition are connected usually with long period from tick bite to late neurological signs. Any headache and psychiatric disorder in the course of Lyme disease could be an early manifestation of invasion of the CNS by the spirochaetes. Each part of neurologic system could be involved. The most common clinical picture of neuroborreliosis is meningitis with cranial or peripheral neuropathies connected with radiculalgia, less common are encephalitis and myelitis, neuropathies and polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Vasculitis and autoimmunology processes are present. Encephalopathy is due to neuroimmunomodulators, like lymphokines and by toxico-metabolic effect could be connected with each form of systemic borreliosis. Spheroplast L-form of borrelia could be responsible for difficulties with their eradication. Diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in subarachnoid space, detection of activated lymphocytes, other antigens detection in CSF (also after dissociation of complexes) or borrelial DNA sequences.
Publication Types:
PMID: 11081332 [PubMed - indexed for MEDLINE]
Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis.
Lebech AM, Hansen K, Brandrup F, Clemmensen O, Halkier-S¿rensen L.
Borrelia Laboratory, Department of Clinical Biochemistry, Statens Seruminstitut, Copenhagen. lebech@dadlnet.dk
BACKGROUND: The aim of the study is to evaluate the diagnostic sensitivity of a 16S ribosomal RNA-based PCR on clinical specimens from patients with erythema migrans (EM) and neuroborreliosis and to compare the sensitivities with those obtained by in vitro culture and serological testing. A semiquantitative detection system, representing the input amount of specific DNA and thus the density of spirochetes in clinical specimens, indicated the preferred clinical sample to obtain for PCR testing. METHODS AND RESULTS: Skin biopsy and urine samples from 31 patients with EM and cerebrospinal fluid (CSF) and urine samples from 30 patients with neuroborreliosis were investigated. Borrelia burgdorferi DNA was detected in 71% of the skin biopsy specimens and 13% of the urine samples from patients with EM. Forty-one percent of the patients with EM were found to have B burgdorferi-specific antibodies in serum, and B burgdorferi was cultured in 29% of the EM specimens. For patients with neuroborreliosis, the diagnostic sensitivities in CSF and urine samples were 17% and 7%, respectively. Specific intrathecal antibody production was found in 90% of the patients, and 87% showed elevated B burgdorferi antibodies in serum. In general, PCR of skin biopsy samples yielded very high amounts of amplicons versus low amounts for CSF and urine samples. CONCLUSIONS: PCR of skin biopsy specimens is currently the most sensitive and specific test for the diagnosis of patients with EM, superior to culture and serological testing. For B burgdorferi-specific CSF disgnosis in patients with neuroborreliosis, the measurement of specific intrathecal antibody synthesis is superior to PCR. However, in patients with a short duration of disease (<14 days), PCR may be a useful diagnostic supplement. PCR of urine samples cannot be recommended at the present time for routine diagnosis of patients with EM or neuroborreliosis.
Publication Types:
PMID: 11066015 [PubMed - indexed for MEDLINE]
Spatial risk assessment for Lyme borreliosis in Denmark.
Jensen PM, Hansen H, Frandsen F.
Department of Ecology, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.
A study of nymphal and adult Ixodes ricinus density was performed in well-defined spruce and beech forest habitats with different levels of roe deer abundance and soil water capacity. In 35 habitats, a total of 489 larvae, 1,611 nymphs and 193 adult I. ricinus ticks were collected. Tick density was found to be influenced by roe deer abundance and soil water capacity. Based on this evaluation, a model predicting increasing number of ticks with increasing roe deer abundance and soil water capacity was suggested. A total of 1,045 nymphs and 106 adult ticks were tested for infection with Borrelia burgdorferi sensu lato Of these, 53 nymphs and 6 adults were found to be infected, leading to an general infection rate of 5% and 6% for nymphs and adults, respectively. Prevalences of Borrelia burgdorferi sensu lato in nymphal I. ricinus were found to be independent of roe deer abundance and soil water capacity. The correlation between human neuroborreliosis incidence and the estimated number of I. ricinus based on roe deer abundance and soil water capacity was examined. Differences in human neuroborreliosis incidence were found to correspond with the expected spatial differences in tick density in 12 counties in Denmark.
Publication Types:
PMID: 11055662 [PubMed - indexed for MEDLINE]
Temporal risk assessment for Lyme borreliosis in Denmark.
Jensen PM, Frandsen F.
Department of Ecology, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.
The prevalence of Borrelia burgdorferi sensu lato in Ixodes ricinus nymphs in Denmark was found to be approximately 5%. The mean abundance of infected nymphs varied from 0.3 to 4.4 per 100 m2 according to site. The seasonal occurrence of infected nymphs in a beech forest coincided with seasonal distribution of neuroborreliosis cases. In order to establish a working hypothesis, it was assumed that the availability of habitats and human habitat preferences is one of the factors leading to low number of neuroborreliosis cases in the spring. In addition, this paper gives a description of the neuroborreliosis cases in Denmark in the period 1985-97 and offers a possible explanation for the variation in cases. The explanation is based on an assessment of tick density, which by comparison with the number of neuroborreliosis cases provides information on the infectivity of ticks. The model suggests that high temperatures and low precipitation in the autumn is essential for the transmission of B. burgdorferi sensu lato to reservoir hosts or development of B. burgdorferi sensu lato within ticks, which secures high tick infectivity in the following season.
Publication Types:
PMID: 11055661 [PubMed - indexed for MEDLINE]
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Matrix metalloproteinase-9 (MMP-9) in human cerebrospinal fluid (CSF): elevated levels are primarily related to CSF cell count.
Yushchenko M, Weber F, Mder M, Schll U, Maliszewska M, Tumani H, Felgenhauer K, Beuche W.
Department of Neurology, Georg-August-University, Robert-Koch-Str. 40, D-37075, Gttingen, Germany.
Matrix metalloproteinase-9 (MMP-9) was investigated by enzyme-linked immunosorbent assay (ELISA) and zymography in 111 paired CSF and serum samples from patients with various neurological disorders. In 20 patients with blood-brain barrier (BBB) impairment but normal CSF cell count, elevated levels of MMP-9 were not observed by ELISA measurement. Another 11 patients characterized in the same way, exhibited only slightly increased MMP-9 levels. In contrast, in 12 patients with intact BBB but elevated CSF cell count, MMP-9 was increased too. It was shown by the more sensitive zymography that MMP-9 increased if CSF cell count exceeded five cells per microl. Spearman rank statistics revealed that MMP-9 concentration in CSF correlated with CSF cell count (r=0.755; P<0.0001), but not with CSF/serum albumin ratio (Q(Alb)) (r=0.212; P=0.057), a measure for BBB impairment. Moreover, the CSF/serum MMP-9 ratio (Q(MMP-9)) did not correlate with Q(Alb)(r=0.192; P=0.100). By use of a Boyden chamber, in which granulocytes migrated through a reconstituted basement membrane, it was demonstrated that the MMP-9 concentration in the lower chamber correlated very significantly with the number of accumulated cells (r(2)=0.7692; P<0.0001). The meaning of the increase of MMP-9 in CSF is critically discussed.
Publication Types:
PMID: 11024556 [PubMed - indexed for MEDLINE]
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False-negative serology in patients with neuroborreliosis and the value of employing of different borrelial strains in serological assays.
Kaiser R.
Neurologische Klinik und Poliklinik der Albert-Ludwigs-Universitt Freiburg, Germany.
The risk of obtaining false-negative results in serological assays in serum and CSF specimens with only one strain of Borrelia burgdorferi sensu lato as antigen was investigated in 79 patients with neuroborreliosis with specimens obtained at initial presentation. Serum antibodies were assessed by immunoblotting; the criteria of Hauser et al. were used to evaluate the test. The intrathecal synthesis of borrelial-specific IgM and IgG antibodies was examined by enzyme immunoassay (EIA). Strains of B. burgdorferi sensu stricto (BbZ160), B. garinii (Bbii50) and B. afzelii (PKO) served as sources of antigen in both assays. All patients produced either a positive IgM or IgG test in serum with at least one strain of B. burgdorferi sensu lato. Reactivity of IgM or IgG antibodies, or both, with antigens of all three strains was demonstrated in 67 (85%) of 79 sera. The correlation of results of immunoblotting with different strains was significantly better for IgG (85%) than for IgM antibodies (54%). The variability of positive IgM reactions in 18 specimens was mainly due to the fact that the antibodies were directed to the relevant variable outer-surface protein C (p23). Intrathecal synthesis of IgG antibodies was demonstrated in 58 patients (81%) of 72 and of IgM antibodies in 25 of 58 patients. No patient had isolated intrathecal synthesis of IgM antibodies. The majority of CSF samples (56 of 58) were assessed as IgG antibody-positive, independent of the borrelial strain used as antigen in EIA, whereas only 10 of 25 IgM antibody-positive CSF specimens reacted with all three strains. All patients in the study had intrathecal antibody synthesis demonstrable at 6-week follow-up. From this study it is concluded that there is a small, but real, risk of false-negative serological findings at the time of initial clinical presentation in patients with typical symptoms of neuroborreliosis. In these patients a negative serological result with one strain should prompt the repetition of the test with other strains of B. burgdorferi sensu lato.
Publication Types:
PMID: 11023188 [PubMed - indexed for MEDLINE]
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Comment on:
Possibility of the use of oral long-acting tetracyclines in the treatment of Lyme neuroborreliosis.
De Maria A, Primavera A.
Publication Types:
PMID: 11017854 [PubMed - indexed for MEDLINE]
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Lyme borreliosis, an etiological factor in sensorineural hearing loss?
Peltomaa M, Pyykk I, Sappl I, Viitanen L, Viljanen M.
Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland. miikka.peltomaa@iki.fi
The incidence of Lyme borreliosis was studied prospectively in 165 patients with acute idiopathic sensorineural hearing loss. The prevalence of positive levels of antibodies against Borrelia burgdorferi was sixfold higher in patients with sensorineural hearing loss than in the general population in Finland. Four patients fulfilled the criteria for Lyme borreliosis. No specific risk factors were found with which to predict the occurrence of Lyme borreliosis among patients with hearing loss. In logistic regression modeling the poor outcome of hearing loss was best explained by advanced age, high-frequency or flat-type hearing loss, and absence of positive levels of antibodies against B. burgdorferi. Although the causal relationship between Lyme borreliosis and sensorineural hearing loss is difficult to verify, we suggest that Lyme borreliosis is a rare but potentially treatable cause of sudden deafness. We propose that in endemic areas antibodies against Lyme borreliosis should be determined in patients with idiopathic sensorineural hearing loss.
Publication Types:
PMID: 10993551 [PubMed - indexed for MEDLINE]
Loss of the sense of humor.
Ramanan SV.
Publication Types:
PMID: 10979069 [PubMed - indexed for MEDLINE]
[Borreliosis associated with Lofgren's syndrome]
[Article in Danish]
Klint H, Siboni AH.
Medicinsk Afdeling, Centralsygehuset i Esbjerg.
A man with positive Borrelia-titres, joint pain, erythema nodosum and fever was treated with penicillin. After finding hilar adenitis Lfgren's syndrome was thought to be more likely and penicillin was discontinued. Later the patient developed symptoms of neuroborreliosis and S-Borrelia IgG was 10 units. After treatment with doxycycline symptoms disappeared and IgG levels fell.
Publication Types:
PMID: 10962918 [PubMed - indexed for MEDLINE]
Chorea as a symptom of neuroborreliosis: a case study.
Piccolo I, Thiella G, Sterzi R, Colombo N, Defanti CA.
Division of Neurology, Hospital Niguarda Ca' Granda, Milan, Italy.
Borrelia burgdorferi (Bb) can cause a large number of neurological symptoms. Although extrapyramidal disturbances are rare (representing less than 2% of all neurological complications), diffuse choreic dyskinesias have been described during the course of mild encephalitis. The data published in the literature suggest that there are clinical and neurological analogies between neuroborreliosis and multiple sclerosis (MS). The presence of specific anti-Bb antibodies in cerebrospinal fluid is a discriminating factor that allows a diagnosis of neuroborreliosis to be made. We describe the case of a patient with Lyme disease, characterised by widespread chorea and behavioural disturbances. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating a diagnosis, and the uncertainties concerning the pathophysiology and clinical/neuroradiological correlations of the disease.
Publication Types:
PMID: 10933464 [PubMed - indexed for MEDLINE]
Chronic neuroborreliosis in infancy.
Zamponi N, Cardinali C, Tavoni MA, Porfiri L, Rossi R, Manca A.
Department of Neurology, G. Salesi Children's Hospital, Ancona, Italy.
Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%-50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
Publication Types:
PMID: 10933439 [PubMed - indexed for MEDLINE]
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Lyme disease.
Evans J.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA. janine.evans@yale.edu
Lyme disease (LD) is the most common tick-borne disease in the US. The overall trend has been an average annual increase in cases since surveillance was initiated by the Centers for Disease Control and Prevention in 1982. To date, 10 different Borrelia species have been described within the Borrelia burgdorferi sensu lato complex, although only Borrelia burgdorferi sensu strico, Borrelia garinii, and Borrelia afzelii have been associated with human disease. Ixodes ticks often carry more than one potential pathogen, and co-infection with B. burgdorferi and other organisms have been reported. Recent findings suggested that maintenance cycles of other tick-borne pathogens may be different than those for B. burgdorferi. A better understanding of the pathogenesis of Lyme arthritis has provided clues about the mechanisms responsible for variation in clinical expression of the disease. Results of therapeutic trials in Lyme neuroborreliosis are likely to have an impact upon treatment recommendations. A long term follow-up study of children treated for LD indicated that the prognosis is excellent in most cases. A safe vaccine for the prevention of LD has been approved in adults. Preliminary data suggested that the vaccine is safe and immunogenic in children.
Publication Types:
PMID: 10910185 [PubMed - indexed for MEDLINE]
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Primarily chronic and cerebrovascular course of Lyme neuroborreliosis: case reports and literature review.
Wilke M, Eiffert H, Christen HJ, Hanefeld F.
Kinderklinik der Georg-August- Universitat, Abteilung Kinderheilkunde, Schwerpunkt Neuropadiatrie, Robert-Koch-Strabetae 40, 37075 Gottingen, Germany.
As part of an ongoing study aiming to define the clinical spectrum of neuroborreliosis in childhood, we have identified four patients with unusual clinical manifestations. Two patients suffered from a primarily chronic form of neuroborreliosis and displayed only non-specific symptoms. An 11 year old boy presented with long standing symptoms of severe weight loss and chronic headache, while the other patient had pre-existing mental and motor retardation and developed seizures and failure to thrive. Two further children who presented with acute hemiparesis as a result of cerebral ischaemic infarction had a cerebrovascular course of neuroborreliosis. One was a 15 year old girl; the other, a 5 year old boy, is to our knowledge the youngest patient described with this course of illness. Following adequate antibiotic treatment, all patients showed substantial improvement of their respective symptoms. Laboratory and magnetic resonance imaging findings as well as clinical course are discussed and the relevant literature is reviewed.
Publication Types:
PMID: 10869004 [PubMed - indexed for MEDLINE]
Opsoclonus-myoclonus syndrome in a child with neuroborreliosis.
Vukelic D, Bozinovic D, Morovic M, Tesovic G, Ruzic Sabljic E, Barisic N, Knezovic I.
University Hospital for Infectious Diseases, dr F. Mihaljevi, Zagreb, Croatia.
Opsoclonus-myoclonus is a rare neurological syndrome affecting children and adults. In children it occurs as a parainfectious process or a paraneoplastic syndrome in association with neuroblastoma. Here we report it presenting as an unusual neurological manifestation of Lyme borreliosis. To our knowledge, this is the first report which describes recovery from this syndrome in a child.
Publication Types:
PMID: 10841099 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis mimics stroke: a case report.
Zhang Y, Lafontant G, Bonner FJ Jr.
Department of Physical Medicine and Rehabilitation, Graduate Hospital, Philadelphia, PA, USA.
Lyme neuroborreliosis is diagnostically challenging because of its diverse manifestations. The well-documented neurologic spectrum includes lymphocytic meningitis, cranial neuropathy, and radiculoneuritis in the early disseminated stage; and peripheral neuropathy, chronic encephalomyelitis, and mild encephalopathy in the late persistent stage. This case report describes a 74-year-old man who developed progressive left hemiparesis and facial palsy. The patient was hospitalized to rule out a cerebral vascular accident. The diagnosis of Lyme borreliosis was established with serologic studies. The patient was treated with intravenous ceftriaxone and responded with rapid clinical and functional recovery. Lyme neuroborreliosis presenting as hemiparesis has rarely been reported. Prompt diagnosis and treatment appear to facilitate symptomatic relief and prevent persistent neurologic deficits.
Publication Types:
PMID: 10768546 [PubMed - indexed for MEDLINE]
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Epitope mapping of the immunodominant invariable region of Borrelia burgdorferi VlsE in three host species.
Liang FT, Philipp MT.
Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433, USA.
VlsE, the variable surface antigen of Borrelia burgdorferi, contains a 26-amino-acid-long immunodominant invariable region, IR(6). In the present study, three overlapping 14-mer peptides reproducing the sequence of IR(6) were used as peptide-based enzyme-linked immunosorbent assay antigens to map this invariable region in infected monkeys, mice, and human Lyme disease patients. Antibodies of the two primate species appeared to recognize IR(6) as a single antigenic determinant, while mouse antibodies recognized multiple epitopes within this region.
Publication Types:
PMID: 10722641 [PubMed - indexed for MEDLINE]
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An indirect hemagglutination antibody test to detect antibodies to Borrelia burgdorferi in patients with Lyme disease.
Pavia CS, Wormser GP, Bittker S, Cooper D.
NYCOM Microbiology Laboratory of NYIT, Old Westbury, NY 11568, USA. cpavia@iris.nyit.edu
An indirect hemagglutination antibody (IHA) test was evaluated for its ability to detect borrelial antibodies in serum samples from patients with Lyme disease. The key test reagent developed for this antibody detection system was tannic acid-treated and glutaraldehyde-fixed sheep red blood cells (SRBC) containing Borrelia burgdorferi (Bb) antigens attached to the outer surface of the SRBC. In order to establish suitable cut-off titers, initial specificity and sensitivity measurements were made using sera from 100 anonymous healthy volunteers and 30 additional pre-determined samples known to be non-reactive or reactive for Lyme disease or syphilis. These results were compared with those obtained using a commercially available ELISA. At titers >/=64, the IHA test had a combined 98% specificity and 100% sensitivity for these 130 serum samples, 30 of which were known positives or negatives, whereas the ELISA was less specific (93%) and much less sensitive (80%). Subsequent testing was performed on sera from 65 patients with the erythema migrans (EM) rash and 20 patients with early disseminated (cardiac/neurologic) symptoms or with Lyme arthritis. At initial presentation, 46-48% of the EM patients had IHA reactivity, with titers >/=128, while 42% were positive in the ELISA. Follow-up testing performed on these EM patients, 8-12 days after receiving antibiotic treatment, revealed that Bb antibodies were detected best by the IHA test (83-86% reactive) relative to the ELISA (81% reactive). Bb antibodies were readily detectable on all of the serum samples from the early disseminated and late stage Lyme disease cases in both assay systems. Based on these results and because of its technical and interpretive simplicity, the IHA test should be considered as a useful and convenient alternative for the serological analysis of Bb infections.
Publication Types:
PMID: 10699672 [PubMed - indexed for MEDLINE]
[The coexistence of an intracranial tumor and a positive epidemiologic history of Lyme borreliosis as the reason for diagnostic problems--case report]
[Article in Polish]
Biesiada G, Kalinowska-Nowak A.
Katedry i Kliniki Chorb Zakanych Collegium Medicum Uniwersytetu Jagiellonskiego w Krakowie.
The authors present the case of a patient treated in the Department of Infectious Diseases at CMUJ in Cracow. The patient's full clinical picture suggested the possibility of the development of neuroborreliosis and disguised the symptoms of a developing intracranial tumor. Neuroborreliosis was suspected due to epidemiologic history (a tick bite, erythema migrans), general symptoms (fatigue, hypersomnia, apathy, dysmnesia, concentration disorders) and neurological symptoms, seropositive tests for Borrelia burgdorferi in serum and cerebrospinal fluid (IgG), increased protein concentration in cerebrospinal fluid. Owing to the fact that the serologic criteria of neuroborreliosis were not fulfilled, and other symptoms (loss of consciousness) appeared, CT was done. The CT showed the presence of a tumor in the longitudinal fissure of the brain, which, after intraoperative and histopathological examination, was defined as meningioma.
Publication Types:
PMID: 10695387 [PubMed - indexed for MEDLINE]
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Upregulation of matrix metalloproteinase-9 in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis.
Kirchner A, Koedel U, Fingerle V, Paul R, Wilske B, Pfister HW.
Department of Neurology, Klinikum Grobetahadern, Ludwig-Maximilians- University, Munich, Germany.
It was investigated (1) whether metalloproteinase-9 (MMP-9), MMP-3, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, the natural tissue inhibitor of MMP-9) are increased in the CSF of patients with Lyme neuroborreliosis and (2) whether macrophages can express MMP-9 when stimulated with Borrelia burgdorferi. Zymography showed MMP-9 activity in 26 of 31 (84%) CSF samples from patients with acute stage 2 Lyme neuroborreliosis, but not in 20 controls with non-inflammatory neurological disorders. Activity of MMP-2 was detected in all CSF samples in both patients with neuroborreliosis and controls, suggesting a constitutive release of MMP-2. Using enzyme linked immunosorbent assay (ELISA) MMP-3 (which can activate MMP-9) was detected in low concentrations in the CSF of 13 of 29 patients with neuroborreliosis, but not in controls. TIMP-1 was increased twofold in CSF samples from patients with neuroborreliosis in comparison with the controls. MMP-9 activity was induced in vitro in a mouse macrophage cell line (RAW 264.7) when stimulated with two different genospecies of B burgdorferi (B garinii, B afzelii ). This MMP-9 activity was reduced in a dose dependent manner when macrophages stimulated with B burgdorferi were coincubated with NF-kappaB SN50, a cell permeable peptide which inhibits the translocation of NF-kappaB into the nucleus of stimulated cells. The data show that (1) MMP-9 activity is present in the CSF of patients with neuroborreliosis, (2) macrophages stimulated with B burgdorferi are a possible source of MMP-9 increase, and (3) activation of NF-kappaB may play a part in the upregulation of MMP-9 by B burgdorferi.
Publication Types:
PMID: 10675223 [PubMed - indexed for MEDLINE]
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Intrathecal release of sICAM-1 into CSF in neuroborreliosis--increased brain-derived fraction.
Lewczuk P, Reiber H, Korenke GC, Bollensen E, Dorta-Contreras AJ.
Neurochemistry Laboratory, University of Goettingen, Germany. lewczuk@exmax1.mpiem.gwdg.de
In the present study, we report sICAM-1 concentration in the cerebrospinal fluid (CSF) and serum of patients with neuroborreliosis (NB, n = 11), compared to the data from a control group of patients with corresponding blood/CSF barrier dysfunction but without inflammation in the central nervous system (disc prolaps, DP, n = 11). In NB, the sICAM-1 concentration in CSF was increased up to six-fold (ranges: 6.6-42.8 ng/ml and 2.2-9.8 ng/ml for NB and DP respectively) with no change in serum sICAM-1. The corresponding sICAM-1 CSF/serum concentration quotients (Q(ICAM)) were in the ranges: 22.5-171.3 X 10(-3), and 8.8-27.8 X 10(-3) for NB and DP respectively. This finding can be explained by increase of the brain-derived fraction of sICAM-1 in NB. In one case we observed increased Q(ICAM) on 6th day after admission to the hospital (171.3 X 10(-3) at the time of the first lumbar puncture slightly increasing to 243.6 x 10(-3) five days later), followed by normalization, in two remaining repunctured patients we observed decreasing QICAM with normalizing Q(Alb).
PMID: 10674994 [PubMed - indexed for MEDLINE]
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Comment in:
Comment on:
Adverse effects of minocycline versus doxycycline in the treatment of Lyme neuroborreliosis.
Dotevall L, Hagberg L.
Publication Types:
PMID: 10671363 [PubMed - indexed for MEDLINE]
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[Ischemic stroke caused by neuroborreliosis]
[Article in French]
Laroche C, Lienhardt A, Boulesteix J.
Service de pdiatrie II, CHU Dupuytren, Limoges, France.
Ischemic stroke in children is rare and its etiology is frequently unknown. CASE REPORT: We report the case of a nine-year-old boy who presented a right ischemic lenticular stroke due to neuroborreliosis, with a good outcome after antibiotic treatment. CONCLUSION: We suggest that it is important to search for neuroborreliosis in case of an ischemic stroke in children; the study of cerebral spinal fluid is a good diagnostic marker.
Publication Types:
PMID: 10627902 [PubMed - indexed for MEDLINE]
Overdiagnosis and overtreatment of Lyme neuroborreliosis are preventable.
Prasad A, Sankar D.
Department of Neurology, New York University Medical Center, NY 10016, USA.
The problems of diagnosis and treatment of Lyme neuroborreliosis can be minimised by strictly following the clinical diagnostic criteria, and understanding the pitfalls of laboratory tests. The diagnosis is based solely on objective clinical findings, with serologic test results used only to confirm the diagnosis. It must be underscored that serologic testing, when ordered without regard for clinical presentation (i.e., used as a screen), may be misleading due to its extremely low positive predictive value. Enzyme-linked immunosorbent assay should always be confirmed by Western blot. The cerebrospinal fluid Borrelia burgdorferi antibody index is more meaningful than simple titres of specific antibody. Polymerase chain reaction is still a research tool and should not be utilised without clinical correlation. All serologic tests and polymerase chain reaction may remain positive long after successful treatment. Overdiagnosis and overtreatment can be minimised by following these guidelines.
Publication Types:
PMID: 10621874 [PubMed - indexed for MEDLINE]
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Comment in:
Comment on:
Minocycline versus doxycycline in the treatment of Lyme neuroborreliosis.
Cunha BA.
Publication Types:
PMID: 10619782 [PubMed - indexed for MEDLINE]
[Diagnosis and therapy of Lyme neuroborreliosis]
[Article in German]
Pfister HW.
Neurologische Klinik, Klinikum Grosshadern, Ludwig Maximilians Universitt Mnchen.
Lyme-Borreliosis which in Europe is transmitted by Ixodes ricinus presents in three stages with 1st a localised infection (erythema chronicum migrans), 2nd a disseminated infection (e.g., meningoradiculitis), and 3rd a persistent chronic infection (e.g., encephalomyelitis, cerebral vasculitis), whereby not all stages invariably become clinically apparent. The diagnosis is based on the typical clinical presentation, the lumbar puncture (lymphocytic pleocytosis), and serological test from the blood as well as from the CSF (intrathecal antibody production!). The frequency of positive serological results depends on the duration and the type of the disease. In stage 1 20-50% of the patients show increased IgM-antibodies, in stage 2 70-90% show increased IgM- and or IgG-antibodies, and in stage 3 almost 100% of the patients have positive IgG-antibodies. The Lyme-Neuroborreliosis usually is treated with Ceftriaxon 2 g/d intravenously over 14 (Stage 2) or 21 (Stage 3) days.
Publication Types:
PMID: 10596280 [PubMed - indexed for MEDLINE]
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Borrelia burgdorferi induces matrix metalloproteinases by neural cultures.
Perides G, Tanner-Brown LM, Eskildsen MA, Klempner MS.
Tupper Research Institute, Department of Medicine, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts. gperides@caregroup.harvard.edu
Matrix metalloproteinases (MMPs) are associated with chronic neurologic diseases such as multiple sclerosis and senile dementia. Lyme disease is a multisystemic infection involving the nervous system, skin, joints, and heart. Neurologic manifestations of chronic Lyme disease include encephalopathy and cranial and peripheral neuropathy. Borrelia burgdorferi, the spirochaete causing Lyme disease, has been cultured from the cerebrospinal fluid (CSF), and B. burgdorferi DNA is frequently detected in the CSF of patients with Lyme neuroborreliosis. We used cerebral and cerebellar primary cultures to determine whether B. burgdorferi induces the production of MMPs by primary neural cultures. B. burgdorferi in a dose- and time-dependent manner induced the expression of MMP-9 by primary neural cultures but had no effect on the expression of MMP-2. Human and rat type I astrocytes expressed MMP-9 when incubated with B. burgdorferi in the same manner as primary neural cultures. This response may play a role in the symptomatology and the pathogenesis of Lyme neuroborreliosis. Copyright 1999 Wiley-Liss, Inc.
Publication Types:
PMID: 10583909 [PubMed - indexed for MEDLINE]
Comment in:
Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease.
Hemmer B, Gran B, Zhao Y, Marques A, Pascal J, Tzou A, Kondo T, Cortese I, Bielekova B, Straus SE, McFarland HF, Houghten R, Simon R, Pinilla C, Martin R.
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5B-16, 10 Center DR MSC 1400, Bethesda, Maryland 20892-1400, USA.
Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases.
Publication Types:
PMID: 10581079 [PubMed - indexed for MEDLINE]
Increased IgA rheumatoid factor and V(H)1 associated cross reactive idiotype expression in patients with Lyme arthritis and neuroborreliosis.
Axford JS, Rees DH, Mageed RA, Wordsworth P, Alavi A, Steere AC.
Academic Unit for Musculoskeletal Disease, St George's Hospital Medical School, London.
OBJECTIVE: To investigate whether autoreactive mechanisms occur in Lyme disease (LD) by determining IgA, IgG and IgM rheumatoid factor (RF) concentrations and RF associated cross reactive idiotype (CRI) expression in the serum of LD patients, with comparison to patients with rheumatoid arthritis (RA). METHODS: The RF isotype profiles were determined in 59 patients with LD; erythema migrans (EM) (n=19), neuroborreliosis (NB) (n=20) and Lyme arthritis (LA) (n=20). Mouse monoclonal antibodies (mAbs) G6 and G8 (V(H)1 gene associated), D12 (V(H)3 gene associated) and C7 (V(kappa)III gene associated) were then used to determine the RF associated CRI expression on IgM antibodies in 16 of these LD patients (eight seropositive for RF); (EM (n=3), NB (n=6), LA (n=7)). RESULTS: Seven (18%) patients with either NB or LA had increased concentrations of IgA RF compared with none with EM. Significant differences in the number of patients with raised concentrations of IgG RF or IgM RF were not found between the LD patient groups. Five (3NB, 1LA and 1 EM) (31%) and three (2NB and 1LA) (19%) of LD patients had raised concentrations of the CRIs recognised by mAbs G6 and G8, respectively. These CRIs were detected in LD sera both with and without raised concentrations of RF and were not demonstrated on anti-Borrelia burgdorferi antibodies using ELISA. No LD sera tested had raised concentrations of the determinants recognised by mAbs C7 or D12. CONCLUSION: Significantly raised concentrations of IgA RF and increased use of V(H)1 germline gene associated CRIs are found on IgM antibodies in the serum of LD patients. These data indicate the recruitment of autoreactive B lymphocytes in some patients with the later stages of LD.
Publication Types:
PMID: 10577962 [PubMed - indexed for MEDLINE]
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Scored antibody reactivity determined by immunoblotting shows an association between clinical manifestations and presence of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. Valaisiana in humans.
Ryffel K, Pter O, Rutti B, Suard A, Dayer E.
Maladies Infectieuses et Immunologie, Institut Central des Hpitaux Valaisans, 1950 Sion-CH, Switzerland.
An immunoglobulin G immunoblot was developed with antigenic extracts of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. valaisiana genospecies and was reacted with sera from patients with neuroborreliosis, acrodermatitis, and Lyme arthritis. A detailed analysis of the reactivities of the protein bands was performed, and a two-step scoring procedure was selected to determine the preferential reactivity of sera to one particular genospecies. The discriminative potential of 5 proteins (12-kDa, 16-kDa, 18-kDa, OspA, and 66-kDa proteins) was used as a rapid first-step scoring method, followed by scoring of 14 additional protein bands if necessary. The advantage of this procedure is the low percentage of serum samples with inconclusive results for one of the four species (10% for patients with neuroborreliosis, 6% for patients with acrodermatitis chronica atrophicans, and 6% for patients with Lyme arthritis). Among 31 serum samples from patients with neuroborreliosis, 16 were more reactive to B. garinii, 7 were more reactive to B. afzelii, 3 were more reactive to B. valaisiana, and 2 were more reactive to B. burgdorferi sensu stricto. Of 31 serum samples from patients with acrodermatitis, 26 showed a higher level of reactivity to B. afzelii. Of 34 serum samples from patients with Lyme arthritis, 21 were more reactive to B. burgdorferi sensu stricto, 10 were more reactive to B. afzelii, and 1 was more reactive to B. valaisiana. Our results suggest an organotropism of Borrelia species and provide some evidence of a pathogenic potential of B. valaisiana in humans.
Publication Types:
PMID: 10565936 [PubMed - indexed for MEDLINE]
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Genetic analysis of Borrelia garinii OspA serotype 4 strains associated with neuroborreliosis: evidence for extensive genetic homogeneity.
Marconi RT, Hohenberger S, Jauris-Heipke S, Schulte-Spechtel U, LaVoie CP, Rssler D, Wilske B.
Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0678, USA.
Infection with Borrelia garinii outer surface protein (Osp) A serotype 4 strains has been correlated with the development of neuroborreliosis in Lyme borreliosis patients in Europe. OspA serotype 4 isolates have been recovered primarily from human cerebrospinal fluid, suggesting a tropism for this environment. Previous studies with monoclonal antibodies directed against OspA and OspC demonstrated that OspA serotype 4 strains are antigenically closely related. In view of the pronounced antigenic and genetic variability that has been noted in the Osps of other Borrelia isolates, we sought to determine if OspA serotype 4 strains represent a recently emerged clonal lineage of B. garinii. Toward this goal, a representative group of OspA serotype 4 strains was analyzed for traits that typically exhibit hypervariability among isolates that cause Lyme borreliosis. The following criteria were assessed: (i) ospC sequences, (ii) plasmid composition, (iii) genomic restriction fragment length polymorphism (RFLP) patterns, and (iv) the RFLP patterns of the upstream homology box (UHB) element which flanks members of the UHB gene family at their 5' end. Collectively, these analyses demonstrate genetic homogeneity, suggesting that OspA serotype 4 strains are a recently emerged clonal lineage with an apparent tropism for the central nervous system.
Publication Types:
PMID: 10565915 [PubMed - indexed for MEDLINE]
Spirochetal infection of the nervous system.
Estanislao LB, Pachner AR.
Department of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA.
Neurologic infection is a characteristic feature of spirochetes. The neurologic manifestations of spirochetal infection are a source of continuing public concern: Lyme neuroborreliosis in endemic areas, neurosyphilis in HIV infected patients, and neuroborreliosis during outbreaks of relapsing fever. These are reviewed in this article. The techniques for diagnosis and recommendations in the management of these infections are also discussed.
Publication Types:
PMID: 10517928 [PubMed - indexed for MEDLINE]
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[Secondary normal pressure hydrocephalus. A complication of chronic neuroborreliosis]
[Article in German]
Druschky K, Stefan H, Grehl H, Neundrfer B.
Neurologische Klinik, Friedrich-Alexander-Universitt Erlangen-Nrnberg.
We report about a 57-year-old patient suffering from the typical symptoms of normal-pressure hydrocephalus (NPH) including gait disturbance, urinary incontinence, and mental deterioration. CSF analysis established the diagnosis of chronic active Lyme neuroborreliosis with lymphocytic pleocytosis and intrathecal Borrelia burgdorferi antibody production. After several weeks of i.v. antibiotic treatment we observed normalization of CSF parameters as well as a clear improvement of clinical symptoms so that surgical shunting was no longer indicated. Interference with subarachnoid CSF flow may be a possible cause of the observed symptomatic NPH in a patient with chronic Lyme neuroborreliosis.
Publication Types:
PMID: 10412702 [PubMed - indexed for MEDLINE]
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Protection from Lyme neuroborreliosis in nonhuman primates with a multiantigenic vaccine.
Pachner AR, Delaney E, Zhang WF, O'Neill T, Major E, Frey AB, Davidson E.
Georgetown University School of Medicine, Washington, DC, USA.
In an effort to develop an effective and safe vaccine for lyme disease, rhesus macaques were injected with a multiantigenic preparation of Borrelia burgdorferi, strain N40. One month later animals were boosted before intradermal challenge with infectious B. burgdorferi. Challenges were performed at 1 and again at 5 months after the booster vaccination. Vaccinated and control nonvaccinated animals were monitored for development of systemic infection by measurement of serum anti-spirochetal antibodies by ELISA and Western blotting, and neurological involvement was monitored by testing of cerebrospinal fluid (CSF) and PCR analysis of central nervous system (CNS) tissue obtained at necropsy. Two control nonhuman primates (NHPs), given saline injections instead of vaccine and then challenged with B. burgdorferi, developed CSF pleocytosis, PCR positivity of the brain, and high levels of specific anti-B. burgdorferi antibody in the serum and CSF. Necropsy studies revealed widespread invasion of the CNS of one of these animals by the spirochete. In contrast, none of the four vaccinated animals developed evidence of invasion of the CNS after either of two challenge inoculations with infectious B. burgdorferi. In addition to resisting infection, no vaccinated animal demonstrated any untoward consequence of vaccination. These data demonstrate that a multiantigenic vaccine is effective in preventing systemic infection and lyme neuroboreliosis in NHPs and suggest that a successful vaccine could be developed in humans which would prevent lyme disease.
PMID: 10370376 [PubMed - indexed for MEDLINE]
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Characterization of Lyme meningitis and comparison with viral meningitis in children.
Eppes SC, Nelson DK, Lewis LL, Klein JD.
Division of Infectious Diseases, Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA. seppes@nemours.org
OBJECTIVES: The objectives of this study were to characterize Lyme meningitis (LM) in the pediatric population; to compare LM with viral meningitis (VM) with respect to epidemiology, history and physical examination, and laboratory data; and to provide means of early distinction of Lyme neuroborreliosis from other forms of aseptic meningitis. METHODS: This retrospective analysis involved children admitted to Alfred I. duPont Hospital for Children between 1990 and 1996 whose discharge diagnoses indicated viral or aseptic meningitis or Lyme disease. LM was defined as the presence of cerebrospinal fluid (CSF) pleocytosis with positive Lyme serology and/or erythema migrans. Patients were considered to have VM if they exhibited CSF pleocytosis and had a positive viral culture. Demographic, clinical, and laboratory data were collected for each patient, and patients with LM were compared with age-matched patients with VM. RESULTS: Of 179 patient records, 12 patients with LM and 10 patients with VM (all, >2 years old) were identified by using the above criteria. In comparing LM patients with VM patients, we noted no differences among demographic variables. Children with LM had significantly lower temperatures at the time of presentation. The presence of headache, neck pain, and malaise was similar for the two groups, but the duration of these symptoms was significantly longer among LM patients. Five children with LM had cranial neuropathies. All but 1 LM patient exhibited either papilledema, erythema migrans, or cranial neuropathy. These three findings were absent in the VM group. On CSF analysis, LM patients had fewer white blood cells (mean, 80/mm3 versus 301/mm3) and a significantly greater percentage of mononuclear cells than the VM patients. CONCLUSIONS: In this study, in a Lyme-endemic area, LM was about as common as VM in older children who were hospitalized with aseptic meningitis. Attention to pertinent epidemiologic and historical data, along with physical and CSF findings, allows early differentiation of LM from VM.
Publication Types:
PMID: 10224172 [PubMed - indexed for MEDLINE]
Comment in:
Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis.
Dotevall L, Hagberg L.
Department of Infectious Diseases, Institute of Internal Medicine, Gteborg University, Sweden. leif.dotevall@medfak.gu.se
Twenty-nine patients, aged 11-79 years (mean, 50 years), with Lyme neuroborreliosis, facial nerve palsy, and meningitis were treated with oral doxycycline (daily dose, 200-400 mg) for 9-17 days in a prospective, nonrandomized study. Facial paresis was bilateral in eight (28%) of the 29 patients. Twenty-six patients (90%) recovered without sequelae within 6 months, while three of the patients with bilateral facial palsy at admission had remaining paresis at follow-up. In five patients, contralateral facial paresis developed 1-12 days after initiation of therapy, and two patients were retreated with antibiotics. Posttreatment examinations of cerebrospinal fluid showed a marked decrease of inflammatory cells and protein concentrations compared with pretreatment levels in all followed up patients. The favorable clinical outcome agrees with findings of other reports on intravenous antibiotic therapy for Lyme disease-associated meningitis with facial palsy. Our conclusion is that oral doxycycline is an effective and convenient therapy for Lyme disease-associated facial palsy.
Publication Types:
PMID: 10194080 [PubMed - indexed for MEDLINE]
Diagnostic Detection and Direct Genotyping of Borrelia burgdor feri Regular by Polymerase Chain Reaction in Cerebrospinal Fluid in Lyme Neuroborreliosis.
Lebechdouble dagger AM , Hansendouble dagger K , Rutledge section sign BJ , Kolbert section sign CP , Rys section sign PN , Persing section sign DH .
Borrelia Laboratory, Department of Clinical Bio - chemistry Statens Seruminstitut, Copenhagen, Denmark
Background: A DNA target imbalance in favor of the plasmid-borne outer surface protein A (OspA) versus chromosomal genes has been thought to explain the relatively high diagnostic sensitivity of an OspA-based polymerase chain reaction (PCR) on joint fluid from patients with Lyme arthritis. The aim of this study was to evaluate the diagnostic sensitivity of the OspA-based PCR on cerebrospinal fluid (CSF) samples from patients with Lyme neuroborreliosis and to perform DNA sequence analysis on the amplicon to determine the genospecies of Borrelia present in the CSF. Methods and Results: CSF from 150 consecutively diagnosed European patients with untreated active neuroborreliosis was investigated. Borrelia burgdorferi DNA was detected in 31 of 150 patients with Lyme neuroborreliosis (20.6%). Genotyping of the amplicons was possible in 13 of the CSF samples and revealed that 11 of the 13 patients had been infected with Borrelia garinii, 1 with Borrelia afzelii, and 1 specimen showed evidence of a mixture of B. garinii and B. afzelii sequences. Conclusions: The diagnostic sensitivity of the OspA-based PCR for detection of B. burgdorferi DNA in CSF was comparable to that found previously using PCR assays based on genomic targets. The predominance of B. garinii DNA (92%) found in CSF substantially supports the current hypothesis that B. garinii is the principal agent of Lyme neuroborreliosis in Europe. Mixed infections, comprising different genospecies of B. burgdorferi sensu lato, seem to be the exception.
PMID: 10089270 [PubMed - as supplied by publisher]
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Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis.
Dotevall L, Hagberg L, Karlsson JE, Rosengren LE.
Department of Infectious Diseases, Goteborg University, Goteborg, Sweden. leif.dotevall@medfak.gu.se
Is Lyme neuroborreliosis, even in its early phase, a parenchymatous disorder in the central nervous system (CNS), and not merely a meningitic process? We quantified cerebrospinal fluid (CSF) levels of four nerve and glial cell marker proteins in Lyme neuroborreliosis patients with pretreatment durations of 7-240 days. All 23 patients had meningoradiculitis, and six had objective signs of encephalopathy. Glial fibrillary acidic protein (GFAp) pretreatment levels in CSF, and the light subunit of neurofilament protein (NFL) levels were related to clinical outcome and declined significantly after treatment (P < 0.001 and P < 0.01, respectively). NFL was detectable in 11 out of 22 patients, and pre- and post-treatment NFL levels were associated with the duration of neurological symptoms within 100 days prior to treatment. Neuron-specific enolase (NSE) concentrations also decreased after therapy (P < 0.001), while CSF levels of glial S-100 protein remained unchanged. The pretreatment duration of disease was related to postinfectious sequelae. GFAp, NSE and NFL levels in CSF are unspecific indicators of astroglial and neuronal involvement in CNS disease. The findings in the present study are in agreement with the hypothesis that early and late stages of Lyme neuroborreliosis damage the CNS parenchyma. Copyright 1999 Lippincott Williams & Wilkins.
Publication Types:
PMID: 10053229 [PubMed - indexed for MEDLINE]
Pathogenesis of neuroborreliosis--lessons from a monkey model.
Pachner AR, Schaefer H, Amemiya K, Cadavid D, Zhang WF, Reddy K, O'Neill T.
Department of Neurology, Georgetown University Hospital, Washington, D.C., USA.
The diagnosis of human LNB can be difficult, because its major clinical manifestations--meningitis, facial palsy, radiculitis, and neuritis--are non-specific and the characteristic skin lesion is usually absent at the time of neurological involvement. Thus, CSF assays are often used in diagnosis. Culture of CSF is rarely performed because it has a low yield and requires special culture medium. PCR of the CSF identified spirochetal DNA in clinical specimens with greater sensitivity, but it suffers from a number of disadvantages. Measurement of specific antibody in the CSF also has its limitations. The role of available assays for LNB has not been studied carefully in a comparative investigation. The recent development of the nonhumane primate (NHP) model of LNB allows us to address this need in a faithful model of human LNB. We compared PCR and culture in their ability to detect spirochetal presence in the CSF and brain tissue of infected NHPs, and related these measures of infection to the development of anti-B. burgdorferi antibody. We also tested a bioassay, the mouse infectivity test (MIT), in this model. Using these four assays (PCR, culture, MIT, and CSF Ab) at least one assay for spirochetal presence in CSFs from NHPs was positive in 87% of CSFs tested during early infection in the CNS. Detection of spirochetal presence by PCR, MIT, and culture in the CSF was inversely related to the concomitant presence of anti-B. burgdorferi antibody intrathecally. The performance of any particular test was associated with the strength of the host immune response. In early CNS infection, when anti-B. burgdorferi antibody had not yet appeared, or in immunocompromised hosts, the MIT compared favorably to culture and PCR in infected NHPs; antibody in the CSF was the most useful assay in immunocompetent NHPs. This is the first study demonstrating that a bioassay using inoculation of mice, the mouse infectivity test (MIT), has potential as a useful adjunct in the diagnosis of LNB. The MIT for LNB was modeled after the rabbit infectivity test or RIT, which is considered the "gold standard" for the diagnosis of the related CNS infection, neurosyphilis, and felt to be very sensitive and specific. The presence of specific anti-B. burgdorferi antibody in the CSF is the most widely used assay for Lyme neuroborreliosis. In the immunocompetent NHPs in our study it was a very successful assay for detection of CNS invasion. However, it is frequently false-negative, especially early in the course of the infection, or if there is transient immunosuppression. Transient suppression of the anti-B. burgdorferi immune response in the human could occur in instances of co-infection, i.e. simultaneous transmission via the tick of another pathogen other than B. burgdorferi. Thus, mild immunosuppression as accomplished in our NHPs with corticosteroids was designed to mimic conditions in the human host which allow B. burgdorferi in the natural state to gain a firm foothold in the central nervous system in the 10-15% of B. burgdorferi-infected patients who develop clinically symptomatic nervous system disease. This study is the first to compare utility of available diagnostic techniques in LNB in which necropsy proved presence of infection in the CNS. None of the assays was ideal for all conditions, and the utility of the assay was associated with the host immune status. The differences in the responses of immunocompromised and immunocompetent NHPs in this study were striking. In immunocompetent NHPs the window of opportunity for CNS invasion prior to the development of CSF antibody was brief, and the chance of detection of spirochete low by any of the three techniques used (i.e. culture, PCR, or MIT); in this group, measurement of CSF antibody was generally diagnostic. In immunocompromised NHPs, intrathecal antibody production was delayed, and this helpful diagnostic assay was false-negative; diagnosis required more labor-intensive assays such as PCR, culture, an
Publication Types:
PMID: 10048168 [PubMed - indexed for MEDLINE]
[Diagnosis of Lyme neuroborreliosis]
[Article in Serbian]
Pavlovi DM.
Institute of Neurology, Clinical Centre of Serbia, Belgrade.
Lyme neuroborreliosis is a disease of the central and/or peripheral nervous system caused by spirochete Borrelia burgdorferi. The diagnosis of Lyme neuroborreliosis is based on the clinical picture, differential diagnosis, serological tests with two-step approach and confirmation of positive results, monitoring of antibody titers and effects of adequate therapy. In failure revision of diagnosis is necessary, and if the diagnosis of Lyme neuroborreliosis is correct the effects of the therapy should patiently be expected. Relapse or reinfection are confirmed by new raise in titer of specific antibodies, new symptomatology and new antigens.
Publication Types:
PMID: 9863367 [PubMed - indexed for MEDLINE]
10 questions about Lyme neuroborreliosis.
Prasad A, Hanson R.
Department of Neurology, New York University Medical Center, New York 10016, USA.
The diagnosis of Lyme neuroborreliosis requires a high index of suspicion and chronological correlation of the clinical findings and laboratory data. The limitations of serologic tests must be understood. Cerebrospinal fluid anti-Borrelia burgdorferi antibody index is currently the best indicator of Lyme neuroborreliosis.
PMID: 9784947 [PubMed - indexed for MEDLINE]
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Detection of active infection in nonhuman primates with Lyme neuroborreliosis: comparison of PCR, culture, and a bioassay.
Pachner AR, Zhang WF, Schaefer H, Schaefer S, O'Neill T.
Department of Neurology, Georgetown University School of Medicine, Washington, D.C., USA. apachn01Wgumedlib.georgetown.edu
Ideally a diagnosis of infection of the central nervous system (CNS) is made by culture of the etiologic pathogen, but Borrelia burgdorferi, the causative agent of Lyme neuroborreliosis (LNB), is rarely cultured from the cerebrospinal fluid (CSF). PCR and measurement of specific antibody in the CSF also have their limitations. The role of available assays for LNB has not been studied carefully in a comparative investigation. There is a need to assess the reliability of assays and to increase the ability to document active infection in the CNS. The recent development of the nonhuman primate (NHP) model of LNB allowed us to address this need in a faithful model of human LNB. In this study we compared the abilities of PCR and culture to detect the presence of spirochetes in the CSF and brain tissue of infected NHPs and related these measures of infection to the development of anti-B. burgdorferi antibody. We also tested a bioassay, the mouse infectivity test (MIT), in this model. Fourteen of 16 CSFs from four NHPs were positive by at least one of these techniques. Detection of spirochetes in the CSF by PCR, the MIT, and culture was inversely related to the concomitant presence of anti-B. burgdorferi antibody intrathecally. The performance of any particular test was associated with the strength of the host immune response. In early CNS infection, when anti-B. burgdorferi antibody had not yet appeared, or in immunocompromised hosts, the MIT compared favorably to culture and PCR for infected NHPs; antibody in the CSF was the most useful assay for immunocompetent NHPs.
Publication Types:
PMID: 9774573 [PubMed - indexed for MEDLINE]
Immunoserologic evidence of Human Granulocytic Ehrlichiosis in Danish patients with Lyme neuroborreliosis.
Lebech AM, Hansen K, Pancholi P, Sloan LM, Magera JM, Persing DH.
Department of Clinical Biochemistry, Statens Seruminstitut, University Hospital Hvidovre, Copenhagen, Denmark.
Human Granulocytic Ehrlichiosis (HGE) is a recently described human illness in the US which manifests as fever, myalgia and headache combined with pancytopenia and elevated concentrations of hepatic transaminases. Genetic analyses indicate that the agent of HGE appears to be an Ehrlichia species that is closely related to E. equi and E. phagocytophila. Ixodes dammini and I. scapularis were identified as potential vectors of HGE. Ixodes ticks are also the vector of Borrelia burgdorferi, the agent of Lyme borreliosis. The presence of antibodies against Ehrlichia in 132 sera from Danish patients with definite Lyme neuroborreliosis were examined in order to provide immunoserologic evidence of this infection in Denmark. Patients with Lyme neuroborreliosis were chosen as a test cohort, as these patients had been infested by a tick sufficient for transmission of B. burgdorferi. All had cerebrospinal fluid lymphocytic pleocytosis. As controls, serum samples from 50 healthy Danish blood donors were included. Of the 132 patients with Lyme neuroborreliosis, 5 (3.8%) reacted with the E. equi antigen substrate at titres 1:128. None of the blood donors were found seropositive for E. equi. At least 2 of the patients found seropositive for HGE constituted probable cases of HGE with E. equi antibody titres of at least 80 combined with fever, headache and myalgias. However, in no cases were we able to detect the presence of the HGE agent in the serum by PCR. We conclude that human exposure to granulocytic Ehrlichiae species may also occur in Europe, although further studies will be necessary to document active infection with these potential pathogens.
Publication Types:
PMID: 9730306 [PubMed - indexed for MEDLINE]
Pathogenesis of Lyme neuroborreliosis in the rhesus monkey: the early disseminated and chronic phases of disease in the peripheral nervous system.
Roberts ED, Bohm RP Jr, Lowrie RC Jr, Habicht G, Katona L, Piesman J, Philipp MT.
Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433, USA.
The histopathologic and immunohistochemical features of early and late neuroborreliosis of the peripheral nervous system were investigated in rhesus macaques infected with the JD1 strain of Borrelia burgdorferi. Infection was proven by culture or polymerase chain reaction analysis of skin biopsies and indirectly by Western blot analysis. Three months after infection, neuritis involving multiple nerves was the most consistent neurologic manifestation. Both macrophages and B lymphocytes but not T lymphocytes were present in the cellular infiltrates. Axonal structures surrounding infiltrates had changes consisting of demyelination and axonal phagocytosis. Some of the Schwann cells in lesions stained with anti-nitrotyrosine and anti-tumor necrosis factor-alpha antibodies. B. burgdorferi, or antigens thereof, were visualized immunohistochemically within macrophages. Forty-six months after infection, the most common changes were regenerative, whereas neuritis was infrequent. Aberrant axonal regeneration, irregularly sized myelinated fibers, and fibrosis were frequently observed. Possible mechanisms to explain the appearance and subsidence of Lyme neuritis are discussed.
Publication Types:
PMID: 9728541 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis.
Haass A.
Neurological Department, University of the Saarland, Homburg/Saar, Germany. 0684167360-0001@t-online.de
A broad variability in the clinical manifestations is observed in the European and North American borrelioses. This is dependent on bacterial strain differences in virulence and organotropism, and on different immune responses to Borrelia burgdorferi of the host in these areas. Experimental neuroborreliosis has given insights into mediators and molecular mechanisms of inflammation induced by B. burgdorferi. Histopathological investigations have described the different patterns of injury in the peripheral and central nervous systems. The classic symptoms of neuroborreliosis have been supplemented by new clinical syndromes and neuropsychological investigations. In clinical trials, the efficacy and cost effectiveness of recommended oral and intravenous antibiotic therapies have been compared in early Lyme disease, arthritis and acute disseminated Lyme disease.
Publication Types:
PMID: 9642545 [PubMed - indexed for MEDLINE]
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[Thoraco-abdominal manifestation of stage II Lyme neuroborreliosis]
[Article in German]
Pfadenhauer K, Schnsteiner T, Sthr M.
Neurologische Klinik mit klinischer Neurophysiologie, Zentralklinikum Augsburg.
In the past little attention was paid to the thoracoabdominal manifestation of Lyme radiculoneuritis, because paralysis of the abdominal wall muscles was considered to be a very uncommon clinical manifestation of Lyme neuroborreliosis. In a group of 90 patients suffering from early stage Lyme neuroborreliosis we found abdominal wall weakness in 11 cases. In the majority of patients thoracoabdominal radiculoneuritis was located in the lower thoracic segments (Th 7-12) and involved more than 3 segments (62%) mostly bilaterally (69%). Abdominal wall paralysis was mostly bilateral (91%) and involved always the lower half of the abdominal wall. It was very severe in 18%. Electromyographic studies were done in the paraspinal and abdominal wall muscles showing fibrillation potentials and positive sharp waves in 86% and 50%, respectively. Diagnosis of thoracoabdominal radiculoneuritis in Lyme neuroborreliosis may be difficult and diagnostic errors may occur. Therefore we recommend to look carefully for paralysis of the abdominal wall, which can easily be overlooked on routine neurological examination. In patients from an area with a high incidence of Lyme disease it is recommended to exclude neuroborreliosis even in patients with known diabetes mellitus in order to avoid the misdiagnosis of diabetic thoracoabdominal radiculopathy. This has occured in 2 of our patients.
Publication Types:
PMID: 9606679 [PubMed - indexed for MEDLINE]
Erratum in:- Funct Neurol 1998 Apr-Jun;13(2):104.
Neuroborreliosis in county Baranya, Hungary.
Pl E, Barta Z, Nagy F, Wgner M, Vcsei L.
Department of Neurology, University Medical School of Pcs, Hungary.
The incidence and clinical characteristics of Lyme neuroborreliosis (NB) in a region of high prevalence of tick-bite in Hungary is described. In the county Baranya 66 patients were recorded in a five-year period (1989-93). Fifty-six patients (85%) were in "early", and 10 patients (15%) in "late stage" of NB. The sex distribution was equal. The incidence of NB was 2.9-100,000/year in this region. The incidence of radiculitis/neuritis, meningitis, encephalitis and myelitis in the sample was 56.1%, 19.7%, 18.2% and 6%, respectively. The EEG and evoked potentials showed both central and peripheral neural involvement, EMG and ENG abnormalities were related to the peripheral clinical signs. Non-specific white matter lesions could be found by MRI in 5 patients with central involvement. Cerebrospinal fluid changes were not obligatory but a better indicator of inflammatory process in cases with meningitis and/or encephalitis forms (positivity 75%) than in cases with myelitis and radiculitis (positivity 49%).
Publication Types:
PMID: 9584873 [PubMed - indexed for MEDLINE]
Matrix metalloproteinases in the cerebrospinal fluid of patients with Lyme neuroborreliosis.
Perides G, Charness ME, Tanner LM, Pter O, Satz N, Steere AC, Klempner MS.
Tupper Research Institute, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA. george.perides@es.nemc.org
Neurologic manifestations of Lyme disease include meningitis, encephalopathy, and cranial and peripheral neuropathy. There are no sensitive markers for neuroborreliosis, and diagnosis is often based on clinical presentation and cerebrospinal fluid (CSF) abnormalities, including intrathecal antibody production. Matrix metalloproteinase (MMP) activity in CSF was compared in patients with neuroborreliosis, patients with diverse neurologic disorders, and healthy controls. The CSF of 17 of 18 healthy subjects and 33 of 37 patients with neurologic symptoms and normal CSF and imaging studies contained only MMP2. The CSF of several patients with neurologic disorders contained MMP2, MMP9, and gelatinolytic activity at 130 and 250 kDa. The 130-kDa MMP was found without the 92-kDa MMP9 in the CSF of 11 (79%) of 14 patients with neuroborreliosis and only 7 (6%) of 118 control patients (P < .001). This pattern of CSF gelatinase activity may be a useful marker for neuroborreliosis.
Publication Types:
PMID: 9466528 [PubMed - indexed for MEDLINE]
Enzyme-linked immunosorbent assays with recombinant internal flagellin fragments derived from different species of Borrelia burgdorferi sensu lato for the serodiagnosis of Lyme neuroborreliosis.
Hauser U, Wilske B.
Max von Pettenkofer-Institut fr Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universitt Mnchen, Germany. hauser@m3401.mpk.med.uni-muenchen.de
The serodiagnosis of early Lyme neuroborreliosis is hampered by false negative results and one of the reasons could be the heterogeneity of strains of Borrelia burgdorferi sensu lato. For this study IgG enzyme-linked immunosorbent assays (ELISAs) with recombinant internal flagellin fragments (p41/i; amino acids 129-251) derived from strains PKo (B. afzelii), B31 (B. burgdorferi sensu stricto), and PBi (B. garinii) and ELISAs with whole-cell detergent extracts of strains PKo, PKa2 (B. burgdorferi sensu stricto), and PBi were compared. Cut off absorbance values were defined by the 94th and 92th percentiles of 200 sera from blood donors. Sera from patients with clinically defined neuroborreliosis [n = 88; 41 culture proven and 47 intentionally selected by the criteria specific IgG cerebrospinal fluid/serum index > or = 2 and a serum IgG immunofluorescence assay value of < 1:64] were tested. The sensitivities of the three whole-cell detergent-extract ELISAs were similar (46.6-49.2%), whereas those of the recombinant ELISAs were highest with p41/i:PBi (57.1%) and lowest with p41/i:PKo (21.5%). A combination of the p41/i:PBi and the p41/i:B31 test was most sensitive (59.8%). The correlation of absorbance values of different assays was very high for the three whole-cell detergent-extract ELISAs, whereas the absorbance values obtained with the three recombinant tests differed considerably. The greatest differences were observed between p41/i:PKo and any of the other two recombinant antigens. The differences in immune reactivity of patients sera (due to strain heterogeneity?) seems to have more influence on the results of an assay based on a single antigen than on a whole-cell-based test.
Publication Types:
PMID: 9403843 [PubMed - indexed for MEDLINE]
Borrelia burgdorferi-seropositive chronic encephalomyelopathy: Lyme neuroborreliosis? An autopsied report.
Kobayashi K, Mizukoshi C, Aoki T, Muramori F, Hayashi M, Miyazu K, Koshino Y, Ohta M, Nakanishi I, Yamaguchi N.
Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
A 36-year-old Japanese woman presented with progressive cerebellar signs and mental deterioration of subacute course after her return from the USA. Her serum antibody to spirochete Borrelia burgdorferi was significantly elevated. A necropsy 4 years after her initial neurological signs revealed multifocal inflammatory change in the cerebral cortex, thalamus, superior colliculus, dentate nucleus, inferior olivary nucleus and spinal cord. The lesions showed spongiform change, neuronal cell loss, astrocytosis and proliferation of activated microglial cells. The internal capsule was partially vacuolated and the spinal cord, notably at the thoracic level, was demyelinated and cavitated in the lateral funiculus. Microglial cells aggregated within and around the spongiform lesions and microglial nodules were present in the medulla oblongata. Use of Warthin-Starry stain demonstrated silver-impregnated organisms strongly suggesting B. burgdorferi in the central nervous tissues. The dentate nucleus and inferior olivary nucleus showed the most advanced lesions with profound fibrillary gliosis. Occlusive vascular change was relatively mild, and fibrous thickening of the leptomeninges with lymphocyte infiltrates was localized in the basal midbrain. The ataxic symptoms were due to the dentate and olivary nucleus lesions and mental deterioration was attributable to the cortical and thalamic lesions. Spongiform change, neuronal cell loss, and microglial activation are characteristic pathological features in the present case. The cerebellar ataxia and subsequent mental deterioration are unusual clinical features of Lyme neuroborreliosis. Spirochete B. burgdorferi can cause focal inflammatory parenchymal change in the central nervous tissues and the present case may be an encephalitic form of Lyme neuroborreliosis.
Publication Types:
PMID: 9370092 [PubMed - indexed for MEDLINE]
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Detection of Borrelia burgdorferi DNA and complement membrane attack complex deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary Lyme disease.
Maimone D, Villanova M, Stanta G, Bonin S, Malandrini A, Guazzi GC, Annunziata P.
Institute of Neurological Sciences, University of Siena, Italy.
We report a patient who developed a chronic sensory-motor polyneuropathy and a progressive myelopathy 4 years after a tick bite. An increased serum antibody titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis, although a concomitant cervical spondylosis probably contributed to spinal cord damage. Treatment with ceftriaxone resulted in a marked improvement of neuropathic symptoms, providing indirect evidence of spirochetal infection. Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural nerve confirmed the diagnosis, demonstrating that the spirochete localized in the peripheral nervous system. The presence of complement membrane attack complex deposits and macrophage infiltrates around epineurial vessels and within the endoneurium suggests that the neuropathy in our patient was immune-mediated.
Publication Types:
PMID: 9236787 [PubMed - indexed for MEDLINE]
Brain perfusion SPECT in Lyme neuroborreliosis.
Sumiya H, Kobayashi K, Mizukoshi C, Aoki T, Koshino Y, Taki J, Tonami N.
Department of Nuclear Medicine, Kanazawa University School of Medicine, Japan.
SPECT imaging brain perfusion using 99mTc-HMPAO was performed on a 38-yr-old women with Lyme neuroborreliosis confirmed by autopsy. The patient had been suspected of spinocerebellar degeneration. Cerebral blood flow was diffusely decreased throughout cerebral cortices but cerebellar blood flow was not impaired, which indicated that the diagnosis was unlikely spinocerebellar degeneration. These findings suggested that brain perfusion SPECT provides useful information in diagnosing the patients with Lyme neuroborreliosis, especially when spinocerebellar degeneration is included in the differential diagnosis.
Publication Types:
PMID: 9225802 [PubMed - indexed for MEDLINE]
Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis.
Pachner AR, Amemiya K, Delaney E, O'Neill T, Hughes CA, Zhang WF.
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007, USA.
In patients with Lyme neuroborreliosis, inflammation and symptoms of fatigue and malaise occur out of proportion to the relatively low number of spirochetes present. Previous studies have identified interleukin-6 (IL-6) as a candidate molecule for amplification of CNS inflammation in this disease. We pursued this possibility by measuring cytokine gene expression by reverse-transcriptase polymerase chain reaction (RT-PCR) in the brain of rhesus macaques actively infected with Borrelia burgdorferi. Samples of brain tissue were screened for IL-6 and interferon gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and capture and ELISA readout of hybridization product. The number of copies in positive samples was then quantitated using qRT-PCR-ELISA, in which wild-type cytokine cDNA competes with recombinant competitor DNA in the PCR. Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines. These data support the hypothesis that cytokines such as IL-6 are important amplification molecules for CNS inflammation in Lyme neuroborreliosis.
Publication Types:
PMID: 9222183 [PubMed - indexed for MEDLINE]
Detection of a 130-kD matrix metalloproteinase in cerebrospinal fluid from a patient with Lyme neuroborreliosis.
Hu LT, Perides G, Tanner LM, Klempner MS.
Tupper Research Institute, New England Medical Center, Boston, Massachusetts, USA.
Publication Types:
PMID: 9195108 [PubMed - indexed for MEDLINE]
Immunologic mechanisms in Lyme neuroborreliosis: the potential role of autoimmunity and molecular mimicry.
Sigal LH.
Department of Medicine and Disease Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.
Most of the clinical manifestations of Lyme disease are due to the local presence of the causative agent, Borrelia burgdorferi, in the affected tissues. However, the precise means of tissue damage are not well understood and there is no proof that the organism, live or dead, is always present. An understanding of the complex interaction between the organism, the immune response elicited by the organism, and the host can explain manifestations of the disease and persistence of symptoms and signs after the antibiotic-induced death of the organism. It is possible that dead spirochetes, or fragments thereof may persist and act as a focus of ongoing inflammation. Different immunogenetic types may predispose to different immunologic responses, with distinct clinical outcomes. Vascular changes induced by the infection, either by local infection or the effects of cytokines on the vessel wall, may underlie tissue pathology. Finally, the immune response to B. burgdorferi may elicit the production of antibodies capable of recognizing and damaging or modifying normal host tissues. Only by establishing the mechanisms causing tissue damage in Lyme disease can rational therapeutic strategies be developed. Only by understanding these mechanisms can physicians and patients interpret clinical responses to therapy and accurately appreciate the clinical prognosis.
Publication Types:
PMID: 9166962 [PubMed - indexed for MEDLINE]
Mechanisms of injury in Lyme neuroborreliosis.
Garcia-Monco JC, Benach JL.
Department of Neurology, Hospital de Galdacano, Vizcaya, Spain.
Neurologic injury in infection with Borrelia burgdorferi can be due to the direct action of the spirochetes and spirochetal products on neural cells. There is in vitro evidence for the adherence of this organism to neurons, to glia, and to Schwann cells. Adhesion was found to be associated with galactocerebroside, a glycolipid component of myelin, and could act as a receptor for B. burgdorferi in oligodendroglia and in Schwann cells. Another pathway for neurologic injury could be through amplification of the inflammatory response by newly invading organisms (acute) and persisting (chronic) organisms. There is experimental evidence for production of IL-6, TNF-alpha, and nitric oxide by neural cells exposed to B. burgdorferi. Similar findings have been obtained from neuroborreliosis patients. Although less likely, there is the possibility that autoreactive mechanisms could have a role in the development of some manifestations of neuroborreliosis.
Publication Types:
PMID: 9166961 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis in the rhesus monkey.
England JD, Bohm RP Jr, Roberts ED, Philipp MT.
Department of Neurology, Louisiana State University School of Medicine, New Orleans, USA.
Although there are several animal models of Lyme disease, only the rhesus monkey model exhibits all of the key manifestations of the disease. After infection with Borrelia burgdorferi, rhesus monkeys develop signs of early localized, early disseminated, and chronic Lyme disease. Specific features include erythema migrans, uveitis, myocarditis, arthritis, and disease of the peripheral and central nervous system. One of the unique features of the rhesus monkey model is the development of Lyme neuroborreliosis. Peripheral nervous system (PNS) involvement is usually in the form of a mononeuropathy multiplex with primarily axonal-loss features. Evidence of central nervous system (CNS) disease has included CSF pleocytosis, meningeal inflammation, spinal cord lesions, and polymerase chain reaction (PCR) data consistent with chronic CNS infection. The pathogenesis of Lyme neuroborreliosis is not well understood, but it is likely to involve complex interactions between B. burgdorferi and host immune mechanisms.
Publication Types:
PMID: 9166960 [PubMed - indexed for MEDLINE]
Peripheral nervous system Lyme borreliosis.
Logigian EL.
Harvard Medical School, Clinical Neurophysiology Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
There are acute and chronic Lyme neuropathies. The seasonal acute syndromes of cranial neuritis or radiculoneuritis are generally quite distinctive, but may cause diagnostic difficulty when one syndrome occurs without the other, when erythema migrans is absent or missed, and when meningeal signs are minimal or absent. The chronic Lyme radiculoneuropathies are less severe, and less distinctive. Their recognition depends on eliciting a history of earlier classical manifestations of Lyme disease and by laboratory testing. In both acute and chronic Lyme radiculoneuropathy, electrophysiologic testing often proves the presence of a sensorimotor, axon loss polyradiculoneuropathy. Both acute and chronic Lyme radiculoneuropathy have similar pathologic features and can be classified as a nonvasculitic mononeuritis multiplex. The pathogenesis is uncertain; both direct infection as well as parainfectious mechanisms may play a role. The treatment with which we have the most experience is intravenous ceftriaxone 2 g/day for 2 to 4 weeks. Improvement occurs rapidly over days to weeks in early Lyme neuroborreliosis, but slowly over many months in chronic neuroborreliosis.
Publication Types:
PMID: 9166956 [PubMed - indexed for MEDLINE]
[Lyme neuroborreliosis with acute meningitis as the presenting manifestation: report of a case]
[Article in Chinese]
Sheng R, Wang A, Liu X.
Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing.
To enhance the understanding of Lyme disease, a case of Lyme neuroborreliosis with acute meningitis as the presenting manifestation was reported. The diagnosis was confirmed by elevated serum antibody response to B. burgdorferi using both ELISA and Western blotting, excluding other causes of neurological abnormalities and the typical response of our patient to antibiotics. This case indicates the existence of Lyme disease in Beijing area. If the etiology of a meningitis with lymphocytic pleocytosis is not known, it is important that Lyme neuroborreliosis should be considered as one of the differential diagnoses and detection of antibody to B. burgdorferi in serum and cerebrospinal fluid performed in time. A brief review of the literature including epidemiology, clinical menifestations, diagnosis and treatment of Lyme disease was made.
Publication Types:
PMID: 9812556 [PubMed - indexed for MEDLINE]
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Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature.
Oksi J, Kalimo H, Marttila RJ, Marjamki M, Sonninen P, Nikoskelainen J, Viljanen MK.
Department of Internal Medicine, Turku University Central Hospital, Finland.
Despite a rapid increase in the number of patients with Lyme neuroborreliosis (LNB), its neuropathological aspects are poorly understood. The objective of this study was evaluation of neuropathological, microbiological, and magnetic resonance imaging (MRI) findings in three patients with the Borrelia burgdorferi infection and neurological disease from whom brain tissue specimens were available. Perivascular or vasculitic lymphocytic inflammation was detected in all specimens. Large areas of demyelination in periventricular white matter were detected histologically and by MRI in one patient. The disease had a fatal outcome in this patient. Brain MRI suggested malignancies in two patients before histopathological studies were carried out. One of these two patients was a child with sudden hemiparesis. Another was a 40-year-old man presenting with epileptic seizures and MRI-detected multifocal lesions, which disappeared after repeated courses of antibiotics. We conclude that cerebral lymphocytic vasculitis and multifocal encephalitis may be associated with B. burgdorferi infection. The presence of B. burgdorferi DNA in tissue samples from areas with inflammatory changes indicates that direct invasion of B. burgdorferi may be the pathogenetic mechanism for focal encephalitis in LNB.
Publication Types:
PMID: 9010017 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis masquerading as a brainstem tumor in a 15-year-old.
Curless RG, Schatz NJ, Bowen BC, Rodriguez Z, Ruiz A.
Department of Neurology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Florida, USA.
A 15-year-old boy had onset of unilateral facial weakness. A few days later, he experienced mild vertigo, double vision, and headache. Examination confirmed a peripheral right seventh nerve weakness in addition to an internuclear ophthalmoplegia. The neurologic features suggested a pontine glioma. A T2-weighted MRI scan revealed demyelinating lesions in the pons and in several areas of the cerebrum, including the periventricular region. Subsequent history revealed that he had been diagnosed with Lyme arthritis 7 years earlier while living in Connecticut. The radiographic studies favored a diagnosis of multiple sclerosis. However, studies of blood and cerebrospinal fluid established a diagnosis of Lyme neuroborreliosis.
Publication Types:
PMID: 8916168 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis presenting with propriospinal myoclonus.
de la Sayette V, Schaeffer S, Queruel C, Bertran F, Defer G, Hazera P, Gallet E.
Publication Types:
PMID: 8890788 [PubMed - indexed for MEDLINE]
Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis.
Nocton JJ, Bloom BJ, Rutledge BJ, Persing DH, Logigian EL, Schmid CH, Steere AC.
Division of Rheumatology/Immunology, New England Medical Center, Boston, Massachusetts02111, USA.
A polymerase chain reaction (PCR) assay that detects Borrelia burgdorferi DNA in cerebrospinal fluid (CSF) was evaluated as a diagnostic test for acute or chronic Lyme neuroborreliosis. In one laboratory, 102 samples were tested blindly, and 40 samples were retested in a second laboratory. In the first laboratory, B. burgdorferi DNA was detected in CSF samples in 6 (38%) of 16 patients with acute neuroborreliosis, 11 (25%) of 44 with chronic neuroborreliosis, and none of 42 samples from patients with other illnesses. There was a significant correlation between PCR results and the duration of previous intravenous antibiotic therapy. The overall frequency of positive results was similar in the second laboratory, but concordance between the laboratories and among primer-probe sets was limited because many samples were positive with only one primer-probe set. Thus, PCR testing can sometimes detect B. burgdorferi DNA in CSF in patients with acute or chronic neuroborreliosis, but with current methods, the sensitivity of the test is limited.
Publication Types:
PMID: 8769624 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis in children.
Christen HJ.
Department of Pediatrics, University Hospital, Goettingen, Germany.
Children are more likely than adults to be bitten by ticks and thus more likely to be infected by Borrelia burgdorferi. In a serosurvey the infection rate measured by immunoglobulin G (IgG) antibodies was 2.6%. In a prospective hospital-based multicentre study 169 children with Lyme neuroborreliosis were examined; the infection was diagnosed by detection of specific immunoglobulin M (IgM) antibodies in the cerebrospinal fluid (CSF) using an IgM capture ELISA. The yearly incidence of Lyme neuroborreliosis was 5.8 cases per 100,000 children aged 1-13. Facial palsy and lymphocytic meningitis account for nearly 90% of all cases with neuroborreliosis indicating striking differences in the clinical spectrum between children and adults. Lyme borreliosis proves to be the most frequently verifiable cause of acute peripheral facial palsy in children, causing every second case of this disorder in the summer and autumn. In cases of facial palsy, nearly all patients with a positive history of tick bite or erythema migrans in the head and neck region show ipsilateral subsequent facial nerve palsy, suggesting a direct invasion via the affected nerve by Borrelia burgdorferi. Lyme borreliosis is the third most frequent cause of lymphocytic meningitis in childhood. Inflammatory changes of the cerebrospinal fluid along with the presence of specific antibodies are mandatory for the diagnosis of Lyme neuroborreliosis. High-dose intravenous penicillin G as well as third-generation cephalosporins prove to be effective in paediatric Lyme neuroborreliosis.
Publication Types:
PMID: 8811167 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis disguised as normal pressure hydrocephalus.
Danek A, Uttner I, Yoursry T, Pfister HW.
Department of Neurology, Ludwig-Maximilians-Universitt, Klinikum Grosshadern, Munich, Germany.
A 74-year-old woman presented with gait impairment, urinary incontinence, and dementia. She showed lymphocytic CSF pleocytosis and pronounced intrathecal Borrelia burgdorferi antibody production, indicating active Lyme neuroborreliosis. The syndrome of normal-pressure hydrocephalus (NPH) fully remitted after ceftriaxone treatment. Lyme neuroborreliosis may cause NPH by interfering with subarachnoid CSF flow.
Publication Types:
PMID: 8649583 [PubMed - indexed for MEDLINE]
Three species of Borrelia burgdorferi sensu lato (B. burgdorferi sensu stricto, B afzelii, and B. garinii) identified from cerebrospinal fluid isolates by pulsed-field gel electrophoresis and PCR.
Busch U, Hizo-Teufel C, Boehmer R, Fingerle V, Nitschko H, Wilske B, Preac-Mursic V.
Max von Pettenkofer-Institut fr Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians Universitt, Munich, Germany.
A total of 36 European Borrelia burgdorferi sensu lato cerebrospinal fluid isolates (mainly from southern Germany) were analyzed by pulsed-field gel electrophoresis (PFGE) for large restriction fragment pattern (LRFP) and linear plasmid profiles. Analyzing this large panel of isolates, we detected all three species of B. burgdorferi sensu lato pathogenic for humans in cerebrospinal fluid from patients with Lyme neuroborreliosis by PFGE typing after MluI digestion: 21 B. garinii (58%), 10 B. afzelii (28%), and 4 B. burgdorferi sensu stricto (11%) strains as well as 1 isolate with bands characteristic of both B. afzelii and B. garinii. Species classification by PFGE typing was confirmed by 16S rRNA-specific PCR. Eighteen isolates (11 B. garinii, 6 B. afzelii, and 1 B. burgdorferi sensu stricto isolate) were further characterized by LRFP with four different restriction enzymes (ApaI, KspI, SmaI, and XhoI). All B. afzelii isolates showed identical patterns for each restriction enzyme group. Considerable heterogeneity was demonstrated within the B. garinii group. Subsequent analysis of plasmid profiles revealed only marginal differences for B. afzelii strains but different patterns for B. garinii isolates. In one B. afzelii strain we found a linear plasmid of about 110 kbp not described before. LRFP analysis by PFGE is a suitable tool for the molecular characterization of B. burgdorferi sensu lato strains and allows determination not only of the species but also of the subtypes within B. garinii.
PMID: 8727878 [PubMed - indexed for MEDLINE]
Value of clinical symptoms, intrathecal specific antibody production and PCR in CSF in the diagnosis of childhood Lyme neuroborreliosis.
Issakainen J, Gnehm HE, Lucchini GM, Zbinden R.
Children's Hospital, Kantonsspital Aarau.
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.
PMID: 8676596 [PubMed - indexed for MEDLINE]
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Trigeminal neuralgia as a clinical manifestation of Lyme neuroborreliosis.
Fritz C, Rsler A, Heyden B, Braune HJ.
Publication Types:
PMID: 8965114 [PubMed - indexed for MEDLINE]
Increased cerebrospinal fluid levels of glial fibrillary acidic protein (GFAp) in Lyme neuroborreliosis.
Dotevall L, Rosengren LE, Hagberg L.
Dept. of Infectious Diseases, Ostra University Hospital, Gteborg University, Sweden.
Glial fibrillary acidic protein (GFAp), the main protein constituent of the intermediate filaments of astrocytes, was analysed in the cerebrospinal fluid (CSF) of 20 patients with Lyme neuroborreliosis as a marker of the astroglial reaction. The mean GFAp level before antibiotic treatment in the study group was significantly elevated (592 pg/ml +/- 596 [SD]) compared to that in 24 healthy controls (121 +/- 87 [SD]) (p < 0.01). The highest CSF-GFAp levels were seen in the patients with the most severe disease, but the levels were also increased in patients with peripheral paresis, such as facial palsy with no or only minor encephalitic symptoms. This implies that the infection was not limited to radix dorsalis or the meningeal tissues, but affected the central nervous system as well. Furthermore, the astroglial reaction seemed to occur early in Lyme neuroborreliosis since CSF-GFAp levels were elevated also in patients with recent (< 3 weeks) onset of disease. After antibiotic treatment, the GFAp levels decreased. It is suggested the CSF-GFAp concentrations might be useful for monitoring CNS involvement in Lyme neuroborreliosis.
Publication Types:
PMID: 8740104 [PubMed - indexed for MEDLINE]
[Chronic neuroborreliosis in Lyme disease]
[Article in Russian]
Logigian EL.
Acute and chronic syndromes of Lyme neuroborreliosis are recognized. Acute syndromes are clinically pronounced and comprise meningitis, neuritis of the cranial nerve, radiculoneuritis. Chronic syndromes are less evident. These are moderate encephalopathy and radiculoneuropathy. The diagnosis of the chronic syndrome is based on the presence of early classic signs of BL. CSF must be tested for routine procedure and in pair with serum in the test for selective accumulation of antibodies to Bb in the CSF. Neurophysiological studies help detect memory defects. Electrophysiological tests verify radiculoneuropathy. NMR investigation of the brain and SPECT-scanning may demonstrate damage to the white brain matter. We have much experience with i.v. administration of ceftriaxone (2 g/day for 4 weeks) which relieved neurological syndromes several months later.
Publication Types:
PMID: 9082597 [PubMed - indexed for MEDLINE]
The immune response to infectious diseases of the central nervous system: a tenuous balance.
Pachner AR.
Department of Neurology, Georgetown University Medical Center, Washington DC 20007-2197, USA.
The outcome of CNS infection is dependent on both the organism and host. Acute infections are usually cleared with minimal residua. However, chronic infections of the CNS, such as HIV, PML, HSV, polio, Lyme neuroborreliosis, and neurosyphilis, are becoming increasingly recognized as a cause of severe neurological morbidity, and are poorly understood. We will need to learn more about the CNS as an immune compartment to increase our knowledge of these infections.
Publication Types:
PMID: 8984677 [PubMed - indexed for MEDLINE]
[Lyme neuroborreliosis of mental manifestation. Apropos of a case]
[Article in French]
Gueglio B, Raffi F, Marjolet M.
Publication Types:
PMID: 8881389 [PubMed - indexed for MEDLINE]
Ceftriaxone in the treatment of Lyme neuroborreliosis.
Rohcov H, Hancil J, Hulinsk D, Mailer H, Havlk J.
Hospital of Infectious Diseases, Charles University, Prague, Czech Republic.
In an open non-comparative clinical trial with the aim of evaluating the clinical efficacy and safety of a 14 day course of 2 g ceftriaxone once daily, 46 patients with neuroborreliosis were entered at the Infectious Diseases Teaching Hospital in Prague 8. In 39 patients the diagnosis was early Lyme neuroborreliosis. Seven patients suffered from late stage disease. Clinical results were 30% of patients cured at the end of treatment and 85% after 9 months in early stage disease. In late stage disease two patients out of seven were cured and four had improved after 12 months. One patient died because of cardiac infarction. In no patient had treatment to be discontinued because of adverse reactions to antibiotics.
Publication Types:
PMID: 8852479 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia burgdorferi-reactive cells secreting interferon-gamma.
Wang WZ, Fredrikson S, Sun JB, Link H.
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi-reactive T cells secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and influences the pathogenesis of LN remains to be studied.
Publication Types:
PMID: 8552994 [PubMed - indexed for MEDLINE]
Lyme disease presenting as isolated acute urinary retention caused by transverse myelitis: an electrophysiological and urodynamical study.
Olivares JP, Pallas F, Ceccaldi M, Viton JM, Raoult D, Planche D, Delarque A.
Department of Rehabilitation, Timone Hospital, Marseille, France.
Several neurological manifestations of Lyme disease, both central and peripheral, have been described. Reported here is a case of acute transverse myelitis related to a Lyme neuroborreliosis that presented with isolated acute urinary retention and no lower-extremity impairment. This case, documented by urodynamic and electrophysiological investigations, partially resolved after 6 weeks of intravenous ceftriaxone, affording the removal of the indwelling catheter. Alpha blocker therapy was needed for 3 months, until the complete normalisation of urodynamic and electrophysiological records. This case study indicates that whenever urinary retention is encountered associated with acute transverse myelitis or alone, the patient should be investigated for Lyme disease.
Publication Types:
PMID: 8540796 [PubMed - indexed for MEDLINE]
Comment in:
Neuroborreliosis in the nonhuman primate: Borrelia burgdorferi persists in the central nervous system.
Pachner AR, Delaney E, O'Neill T.
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Neurological involvement in Lyme disease is common, and is frequently difficult to diagnose and treat. Little is known about the fate of the causative spirochete Borrelia burgdorferi in the central nervous system (CNS). To determine the frequency of parenchymal infection and to determine localization of the organism, polymerase chain reaction/hybridization assays were performed in a newly described model of Lyme neuroborreliosis in nonhuman primates infected with B. burgdorferi. Polymerase chain reaction/hybridization of CNS tissues from 5 infected nonhuman primates was performed. Substantial amounts of B. burgdorferi DNA were detected in the CNS in all infected animals, with a predilection toward subtentorial structures. These data suggest that Lyme neuroborreliosis represents persistent infection with B. burgdorferi.
PMID: 7574465 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis.
Garcia-Monco JC, Benach JL.
Department of Neurology, Hospital de Galdacano, Vizcaya, Spain.
Neuroborreliosis, an infection of the nervous system caused by spirochetes of the genus Borrelia, has achieved worldwide attention in the last decade as part of the clinical spectrum of Lyme disease. This disorder, caused by Borrelia burgdorferi, has increased in incidence to become the most frequent arthropod-borne infection in North America and Europe. As a result of this rapid rise in incidence and of its protean neurological manifestations, this disease has created an important challenge to modern neurology. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. This review takes a chronological approach to clinical neuroborreliosis to summarize its most important aspects. The limitations as well as the benefits of laboratory diagnosis are also considered, with the aim of providing assistance in this area. Recent advances in neuroimmunology regarding the pathogenesis of neuroborreliosis that may elucidate its protean clinical spectrum are summarized.
Publication Types:
PMID: 7778842 [PubMed - indexed for MEDLINE]
Neuroborreliosis.
Halperin JJ.
Department of Neurology, North Shore University Hospital, Manhasset, New York 11030, USA.
Lyme disease is a multisystem infectious disease with frequent nervous system involvement. It affects peripheral nerves, the meningeal lining of the central nervous system (CNS), and the CNS parenchyma, but the underlying pathophysiology remains unclear. Considerable data suggest that dividing Lyme neuroborreliosis into early and late disease stages, as has been done with syphilis--the other well-known spirochetosis that affects the nervous system--lacks pathophysiologic validity. Early CNS seeding has been demonstrated, however, and lymphocytic meningitis and facial paralysis tend to occur relatively early in infection, although radiculoneuropathy and cranial neuropathies may also occur later. Less fulminant forms of peripheral nerve or CNS involvement may present later in the disease course. Encephalomyelitis may occur early or late but is rare; encephalopathy is far more common and tends to occur in patients with evidence of systemic (but not necessarily CNS) Lyme disease. Diagnosis of CNS infection has been difficult, and most studies have relied on indirect methods. Demonstration of intrathecal production of anti-Borrelia burgdorferi antibodies provides the strongest evidence, but correction for the amount of peripheral blood immunoreactivity to B. burgdorferi that crosses the blood-brain barrier is essential. Newer technologies have been applied in an effort to improve detection of B. burgdorferi itself--polymerase chain reaction may provide a sensitive tool for organism detection to complement immunologic techniques. The optimal treatment regimen for Lyme disease has not been defined, but a course of ceftriaxone (2 g/day) or cefotaxime (6 g/day) for 3-4 weeks is commonly prescribed. Intravenous penicillin and oral doxycycline (200 mg/day) for 2 weeks have been used successfully to treat Lyme meningitis, but these results require confirmation.
Publication Types:
PMID: 7726192 [PubMed - indexed for MEDLINE]
[Unusual case of bilateral optic neuritis in Lyme neuroborreliosis]
[Article in French]
Bouat C, Meyer F, Rosier S, Boitte JP, Lawani R, Bregigeon M.
Service d'Ophtalmologie, l'Hpital d'Instruction des Armes Laveran, Marseille, France.
The most common manifestations of Lyme disease are neurologic and rheumatologic, but ophthalmologic lesions can also occur and may even be dominant. The authors describe a case of bilateral optic neuropathy associated with Lyme borreliosis that quickly led to near-total blindness. In addition to a loss in visual acuity and field bilateral papillary edema was documented by angiofluorography. A spectacular improvement was obtained under combined antimicrobial therapy using doxycycline and corticosteroid therapy. The patient rapidly recovered full vision. These observations are discussed within the context of Lyme disease with a review of other relevant ophthalmologic complications. The importance of careful interpretation of serology is emphasized.
Publication Types:
PMID: 10906986 [PubMed - indexed for MEDLINE]
Inoculation of nonhuman primates with the N40 strain of Borrelia burgdorferi leads to a model of Lyme neuroborreliosis faithful to the human disease.
Pachner AR, Delaney E, O'Neill T, Major E.
Department of Neurology, Georgetown University Medical Center, Washington, DC.
We injected rhesus macaques with a highly infective strain of Borrelia burgdorferi to assess whether experimentally inoculated nonhuman primates (NHPs) could serve as models of human Lyme neuroborreliosis (LNB). The animals developed biopsy-confirmed erythema migrans in the area of the inoculations. ELISA testing of sera revealed strong antibody reactivity to B burgdorferi antigens, and Western blotting showed that 16-, 22-, 31-, 34-, and 41-kd proteins of the spirochete were major antigens recognized by antibody. Culture and polymerase chain reaction (PCR) testing of serial CSF specimens revealed that chronic infection of the CNS occurred in all NHPs injected. CSF pleocytosis occurred concurrently with CNS infection. Brain MRI revealed intense meningeal inflammation in one NHP as manifested by gadolinium uptake by the dura at the base of the temporal lobes. All animals had measurable antibody in the CSF after invasion. These studies are the first to demonstrate that experimental LNB in NHPs is a reliable model faithful to the human disease, with spirochetal invasion of the subarachnoid space. This also is the first report of CSF samples positive by culture in experimental LNB. Inflammation in the CNS as manifested by CSF pleocytosis and MRI findings was also correlated with the presence of spirochetal DNA detected by PCR. These data support the hypothesis that the pathogenesis of LNB is associated with direct spirochetal invasion, and provide evidence that CNS involvement is more common than heretofore thought.
PMID: 7824109 [PubMed - indexed for MEDLINE]
[Inflammatory demyelinating neuropathy in neuroborreliosis]
[Article in German]
Zifko U, Wondrusch E, Machacek E, Grisold W.
Neurologischen Abteilung, Kaiser-Franz-Josef-Spitals, Wien.
A patient with acute onset of radicular pain developed an asymmetric neuropathy within a few weeks. Neurophysiology and nerve biopsy findings revealed a demyelinating neuropathy. Cerebrospinal fluid showed mild pleocytosis, increased protein levels and elevated antibody titers against Borrelia burgdorferi suggesting Lyme neuroborreliosis. Although peripheral nervous system complications of Lyme borreliosis are common, the association with chronic demyelinating neuropathy has not been described before.
Publication Types:
PMID: 7610671 [PubMed - indexed for MEDLINE]
[Pathomechanisms of neuroborreliosis]
[Article in German]
Garcia-Monco JC.
Abteilung fr Neurologie des Hospital de Galdakao, Bizkaia, Spanien.
Lyme neuroborreliosis has a protean clinical spectrum and a complex and still obscure pathogenesis. Central and peripheral nervous system involvement may occur, with several different mechanisms acting together or separately. Invasion of the nervous system by Borrelia burgdorferi occurs early in the course of the infection. Direct interaction of the spirochete with neural cells may result in neurological damage, as may the immune response elicited against the organism. Both T- and B-cell autoreactivity against endogenous neural structures is present and there seems to be a crossreaction between neural antigens and the flagellin of Borrelia burgdorferi. Meningitis is probably due, at least in part, to inflammatory mechanisms elicited by the presence of spirochetes in the CSF. Inflammatory and angiopathic peripheral nerve changes may lead to axonal damage resulting in peripheral neuropathy. The elaboration of proinflammatory mediators provides another possible pathway for nerve cell injury. There is still a lack of a suitable animal model to recreate the neurological manifestations paralleling human disease. However, rat and mouse models and, more recently, nonhuman primates have so far provided important information on the pathogenesis of this infection and hopefully will provide the opportunity to elucidate many still unclear mechanisms.
Publication Types:
PMID: 7610667 [PubMed - indexed for MEDLINE]
Variable CSF findings in early and late Lyme neuroborreliosis: a follow-up study in 47 patients.
Kaiser R.
Department of Neurology, University of Freiburg, Germany.
The cerebrospinal fluid (CSF) of 37 patients with early Lyme neuroborreliosis (ELN) and of 10 patients with late Lyme neuroborreliosis (LLN, duration of symptoms > or = 7 months) was investigated for typical features differentiating between acute and chronic courses of disease. Individual patients were studied after 2 and 4 weeks, and 3, 6, and 12 months. Patients with ELN presented predominantly with symptoms of the peripheral nervous system, while patients with LLN generally suffered from symptoms of the central nervous system. At the first lumbar puncture, patients with ELN revealed a more intense pleocytosis in the CSF (P < 0.02) and a higher intrathecal synthesis of total IgM (P < 0.0003) and of Borrelia burgdorferi-specific IgM antibodies (P < 0.01). At the same time, in patients with LLN, the blood-CSF barrier was more severely impaired (P = 0.03), and local production of total IgG (P = 0.0001), of B. burgdorferi-specific IgG antibodies (P = 0.03) and of total IgA (P = 0.001) was more markedly increased. The quantity of intrathecally produced B. burgdorferi-specific IgA antibodies did not differ between the two study groups. Clinical recovery was usually accompanied by a considerable improvement of the blood-CSF barrier function and pleocytosis. After 6 months, the intrathecal synthesis of total IgG had significantly decreased in patients with ELN but not in those with LLN. At the same time, the CSF of most patients in both study groups still contained intrathecally produced B. burgdorferi-specific IgG antibodies. In the absence of clinical illness or symptoms of inflammation 6 and 12 months after treatment, B. burgdorferi-specific IgG antibodies in the CSF might simply indicate an anamnestic reaction to a previous infection of the central nervous system. Six months after antibiotic treatment, patients with ELN still revealed evidence of intrathecal synthesis of total IgM, whereas those with LLN did not. These antibodies, however, were not related to B. burgdorferi.
Publication Types:
PMID: 7897449 [PubMed - indexed for MEDLINE]
Multiple sclerosis and positive Lyme serology.
Lana-Peixoto MA.
Faculdade de Medicina da Universidade Federal de Minas Gerais, Brasil.
As Lyme neuroborreliosis (LNB) may clinically mimic multiple sclerosis (MS) the presence of antibodies to Borrelia burgdorferi in serum of patients with a MS-like disease in non-endemic areas for Lyme disease may be troublesome. We report the case of a 45-year-old white female with the diagnosis of relapsing/remitting form of MS due to a 15-year history of optic neuritis and recurrent episodes of motor and sensation disturbance in the upper right limb and in both lower extremities associated with bladder dysfunction. A magnetic resonance imaging of the brain revealed multiple high intensity periventricular white matter lesions. The patient had been exposed to ticks but did not recall the presence of erythema migrans. ELISA for Lyme disease was positive in two different laboratories and the positive serology was confirmed by Western blotting. No convincing response followed treatment with ceftriaxone. Although it is clear that the patient had been infect by Borrelia burgdorferi the relationship of this spirochetal infection with the neurological disease could not be ascertained.
Publication Types:
PMID: 7611954 [PubMed - indexed for MEDLINE]
A rabbit model of Lyme neuroborreliosis: characterization by PCR, serology, and sequencing of the OspA gene from the brain.
Pachner AR, Braswell ST, Delaney E, Amemiya K, Major E.
Department of Neurology, Georgetown University Medical Center, Washington, DC.
To test whether rabbits can serve as a model for Lyme neuroborreliosis (LNB), we injected New Zealand white rabbits with Borrelia burgdorferi. We obtained samples of blood and CSF for culture, polymerase chain reaction/hybridization (PCR/H), serology, and Western blot. We then sacrificed the rabbits 2 to 3 months after infection and removed organs for culture and PCR/H analysis. The rabbits developed an antibody response, characterized by ELISA and Western blot analysis, consistent with a systemic infection. PCR/H and blood cultures were negative, but PCR/H analysis of CSF in one rabbit was positive. Positive PCR/H analysis of organs from the rabbits was consistent with widespread dissemination of the organism. The most consistently infected organ was the CNS. To determine whether antigenic variation occurred at the genetic level, we compared the sequences of the OspA gene of both the infecting strain and the brain PCR product. The differences between the two were minimal, indicating that variation in the OspA gene did not occur during in vivo infection in the rabbit. Thus, rabbits, after intradermal inoculation with B burgdorferi, develop a chronic systemic infection in which the CNS is a consistent target. These data indicate that rabbits may be an excellent model of LNB.
Publication Types:
PMID: 7936251 [PubMed - indexed for MEDLINE]
Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy.
Gasse T, Murr C, Meyersbach P, Schmutzhard E, Wachter H, Fuchs D.
Klinik fr Neurologie, Universitt Innsbruck, Austria.
Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism. Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection. Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan. Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients. The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis.
Publication Types:
PMID: 7865624 [PubMed - indexed for MEDLINE]
Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis.
Karlsson M, Hammers-Berggren S, Lindquist L, Stiernstedt G, Svenungsson B.
Karolinska Institute, Stockholm, Sweden.
To compare the efficacy of oral doxycycline and IV penicillin G for the treatment of neuroborreliosis, we randomized consecutive patients with Lyme neuroborreliosis to receive either IV penicillin G (3 g q 6 h) or oral deoxycycline (200 mg q 24 h) for 14 days. All patients had antibodies against Borrelia burgdorferi in serum, CSF, or both, or had a positive CSF culture. Twenty-three patients randomized to penicillin G and 31 patients to doxycycline were included in the study. All patients improved during treatment, and there were no significant differences between the two treatment groups in patient scoring, CSF analysis, or serologic and clinical follow-up during 1 year. There were no treatment failures, although one patient in each treatment group was re-treated because of residual symptoms. In conclusion, oral doxycycline is an adequate and cost-effective alternative to IV penicillin for the treatment of Lyme neuroborreliosis.
Publication Types:
PMID: 8035916 [PubMed - indexed for MEDLINE]
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Comparison of two methods for detecting intrathecal synthesis of Borrelia burgdorferi-specific antibodies and PCR for diagnosis of Lyme neuroborreliosis.
Zbinden R, Goldenberger D, Lucchini GM, Altwegg M.
Institute of Microbiology, Kantonsspital, Aarau, Switzerland.
An indirect immunofluorescence assay (IFA), a commercial capture enzyme-linked immunosorbent assay (ELISA), and PCR were compared for the diagnosis of Lyme neuroborreliosis in 16 individuals. Borrelia burgdorferi-specific intrathecal immunoglobulin G was found in 10 of 16 patients by IFA and in 8 of 12 patients by capture ELISA. PCRs performed on cerebrospinal fluid samples stored at -70 degrees C were positive for one of eight children and one of four adults with intrathecal antibody production and negative for all four adults without intrathecal antibody production. For two children with facial palsy following erythema chronicum migrans, neither IFA nor capture ELISA detected specific intrathecal antibodies and PCR was also negative. We conclude that both clinical manifestations and laboratory parameters are important for the diagnosis of Lyme neuroborreliosis.
Publication Types:
PMID: 7929776 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis: improvements of the laboratory diagnosis and a survey of epidemiological and clinical features in Denmark 1985-1990.
Hansen K.
Department of Infection-Immunology, Statens Seruminstitut, Copenhagen, Denmark.
Lyme neuroborreliosis (LNB) has within the last few years become one of the most frequent neuroinfections. This thesis is based on 7 publications which have two main topics: (i) to improve and develop laboratory methods for routine diagnosis of LNB, (ii) to generate epidemiological data for LNB and to achieve a descriptive clinical delimitation of this disease. Laboratory diagnosis in Lyme borreliosis is based on detection of a Borrelia burgdorferi (Bb) specific immune response. Up till now serological assays have not achieved a sufficient diagnostic specificity and sensitivity. This is partly due to the use of test antigens consisting of all proteins of the spirochete including broadly cross-reacting antigens. In order to improve diagnostic antibody detection we isolated an immunodominant structural protein of Bb, the motility organelle the flagellum. The use of native, morphologically intact flagella as test antigen in ELISA led to a significantly increased diagnostic specificity, and, especially in early disease, to an improved diagnostic sensitivity. Reservations regarding the use of only one out of the over 100 proteins of Bb as a diagnostic antigen probe are groundless. The early as well as the late immune response to Bb always includes antibodies to the flagellum. The Bb flagellum is as a test antigen not completely Bb specific. Compared with all other antigen preparations however, the flagellum is at present the best compromise, if a sensitive and specific routine serology is requested. The diagnostic performance of specific IgM detection was improved with a mu-capture ELISA, which used biotin labelled Bb flagella. Compared to conventional indirect ELISA this technique avoids false positive results due to IgM rheumatoid factor interference and false low or false negative results due to IgG competition for the test antigen. The antibody response in Bb infection develops slowly. Patients with LNB can be antibody negative in blood up to 6-8 weeks after onset of neurological symptoms. Longstanding but seronegative disease in untreated patients is unlikely to occur. Expectations of further improvement of Lyme borreliosis serology focuses presently on the performance of the outer surface protein (Osp) C as a test antigen and on the genus specific domain of the Bb flagellin. Theoretically this region constitutes the best candidate for a better test antigen either as a recombinant or a synthetic peptide. In LNB a prominent Bb specific intrathecal antibody response develops.(ABSTRACT TRUNCATED AT 400 WORDS)
Publication Types:
PMID: 8165888 [PubMed - indexed for MEDLINE]
[Demonstration of intrathecal antibody formation against Borrelia burgdorferi in Lyme neuroborreliosis]
[Article in German]
Zbinden R, Stech J, Brgi W, Meier T.
Mikrobiologisches Institut, Kantonsspitals Aarau.
Neurologic complications are common in Lyme borreliosis. In adults in particular, detection of intrathecally formed antibodies to B. burgdorferi is a decisive diagnostic criterion. As in neurosyphilis diagnosis, the specific antibody titer against B. burgdorferi in the CSF is compared with the serum titer by calculating the specific antibody indices, taking into account the disturbed blood/CSF barrier. Deriving from these specific indices, we adapt by dilution the serum IgG level to that in the CSF of the same day, thus allowing for passive diffusion of antibody through the blood/CSF barrier. Determination of the specific antibody titer by indirect immunofluorescence demonstrates intrathecal synthesis of specific antibodies against B. burgdorferi if the CSF titer is higher than in the diluted serum tested in parallel. The individual methods are presented in a group of patients.
Publication Types:
PMID: 8272804 [PubMed - indexed for MEDLINE]
Acute Lyme neuropathy presenting with polyradicular pain, abdominal protrusion, and cranial neuropathy.
Krishnamurthy KB, Liu GT, Logigian EL.
Division of Neurology, Brigham and Women's Hospital, Boston, MA 02115.
A 53-year-old man developed multifocal radicular pain. The diagnosis of Lyme neuroborreliosis was delayed until bifacial paresis and right lower abdominal wall weakness developed, prompting further evaluation. Cerebrospinal fluid (CSF) examination showed aseptic meningitis. Antibodies directed against Borrelia burgdorferi were present in the serum; higher titers were present in the CSF, indicating local antibody production. Electrophysiologic studies showed both an axonal polyradiculopathy as well as demyelinative facial palsy. Ceftriaxone therapy led to marked improvement in pain and facial palsies.
Publication Types:
PMID: 8413380 [PubMed - indexed for MEDLINE]
Cerebrospinal fluid neopterin concentrations in central nervous system infection.
Hagberg L, Dotevall L, Norkrans G, Larsson M, Wachter H, Fuchs D.
Dept. of Infectious Diseases, University of Gteborg, Sweden.
Cerebrospinal fluid (CSF) neopterin levels were determined by RIA in individuals with central nervous system (CNS) or human immunodeficiency virus (HIV) infections and in healthy controls. The mean CSF neopterin concentrations were 63.0 nmol/L in 15 patients with acute bacterial meningitis, 54.9 nmol/L in 15 patients with Lyme neuroborreliosis, 32.5 nmol/L in 10 patients with viral meningitis, 130.9 nmol/L in 8 patients with viral encephalitis, 13.9 nmol/L in 15 patients with asymptomatic HIV infection, 26.0 nmol/L in 11 patients with AIDS without dementia, 65.4 nmol/L in 4 patients with AIDS dementia, and 4.2 nmol/L in 24 healthy controls. Although patients with viral encephalitis had higher mean neopterin levels than any other patient category studied, the CSF neopterin concentrations cannot be used to discriminate between viral and bacterial infections. Analysis of CSF levels of neopterin may be useful as guidance in following clinical course and effect of treatment and can provide information of value in addition to CSF cell count as a measurement of CNS immune stimulation.
Publication Types:
PMID: 8228365 [PubMed - indexed for MEDLINE]
Intrathecal antibody synthesis in Lyme neuroborreliosis: use of recombinant p41 and a 14-kDa flagellin fragment in ELISA.
Kaiser R, Rasiah C, Gassmann G, Vogt A, Lcking CH.
Neurologische Klinik und Poliklinik, Universitt Freiburg, Germany.
The intrathecal synthesis of IgM and IgG antibodies to Borrelia burgdorferi sonicate, to recombinant flagellin (41 kDa) and to a tryptic peptide of the flagellin (14-kDa fragment) was determined by ELISA in paired cerebrospinal fluid (CSF) and serum samples from 35 patients with Lyme neuroborreliosis (LNB) and in 10 patients with neurosyphilis. The antibody index (AI = QBb/QIg) was calculated from the ratio between CSF/serum quotients for specific antibodies (QBb) and total immunoglobulins (QIg). For the examination of IgG antibodies, the sonicate ELISA was performed with and without pre-absorption with Treponema phagedenis. Of 35 patients with LNB, 31 had intrathecal IgG response to B. burgdorferi demonstrated by sonicate ELISA (24 after absorption of cross-reactive antibodies), 29 had a response demonstrated by flagellin ELISA and 21 of 35 by 14-kDa ELISA. In patients with neurosyphilis the AI (IgG) was elevated in the sonicate ELISA in 7 of 10 samples (none of 10 after absorption of cross-reactive antibodies), in the flagellin ELISA in 5 of 10 samples and in the 14-kDa ELISA in none of 10 samples. Intrathecal synthesis of IgM antibodies to B. burgdorferi was demonstrated in patients with neuroborreliosis by sonicate ELISA in 20 of 35 samples, by flagellin ELISA in 16 of 35 samples and by 14-kDa ELISA in 9 of 35 samples. No intrathecal synthesis of B. burgdorferi-specific IgM could be detected by any assay in patients with neurosyphilis.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Types:
PMID: 8411090 [PubMed - indexed for MEDLINE]
The polymerase chain reaction in the diagnosis of Lyme neuroborreliosis.
Pachner AR, Delaney E.
Department of Neurology, Georgetown University School of Medicine, Washington, DC.
The polymerase chain reaction is sensitive and specific in the detection of defined DNA sequences and holds promise for diagnosing the presence of fastidious microorganisms in human infectious diseases. We developed a methodology for nested polymerase chain reaction and hybridization analysis of the cerebrospinal fluid using primers from a genomic Borrelia burgdorferi sequence and applied it to the cerebrospinal fluid (CSF) of patients suspected of having Lyme neuroborreliosis and other diseases. Polymerase chain reaction and hybridization demonstrated extremely high sensitivity for spirochetal DNA, and was highly specific, with a false-positivity rate of less than 3%. However, the results were negative or indeterminate in 54% of CSF samples from patients with definite or probable disease, indicating an absence, or extremely low level, of spirochetes or spirochetal DNA in a significant percentage of patients with Lyme neuroborreliosis. Polymerase chain reaction and hybridization of the CSF can thus be considered a useful adjunct in diagnosis, but its negativity does not rule out Lyme neuroborreliosis.
Publication Types:
PMID: 8215242 [PubMed - indexed for MEDLINE]
Screening for neuroborreliosis in patients with stroke.
Hammers-Berggren S, Grndahl A, Karlsson M, von Arbin M, Carlsson A, Stiernstedt G.
Department of Infectious Diseases, Danderyd Hospital, Sweden.
BACKGROUND AND PURPOSE: Borrelia burgdorferi, the etiologic agent of Lyme disease, can cause different neurological manifestations. We studied the prevalence of Lyme neuroborreliosis in patients with stroke. METHODS: During a 1-year period, sera from patients with cerebral thrombosis or transient ischemic attack without cardioembolism were investigated for antibodies against B burgdorferi. RESULTS: One of 281 patients had a positive serum immunoglobulin M titer and 23 of 281 (8%) had positive serum immunoglobulin G titers against B burgdorferi. One of the 24 seropositive patients, with a diagnosis of transient ischemic attack due to dysphasia, had a lymphocytic pleocytosis and intrathecal antibody production against B burgdorferi. The medical history revealed a 9-month period of general and neurological symptoms compatible with Lyme neuroborreliosis before the strokelike incidents. CONCLUSIONS: We conclude that Lyme neuroborreliosis may imitate stroke, but screening for antibodies against B burgdorferi seems to be of little value and may be replaced by a careful medical history.
Publication Types:
PMID: 8362437 [PubMed - indexed for MEDLINE]
Bacterial meningitis and Lyme neuroborreliosis in childhood.
Christen HJ.
Department of Pediatrics and Pediatric Neurology, University of Goettingen, Germany.
Neurologic infections represent a major problem in child neurology. Recent research on this issue has had important implications for diagnosis and pathophysiology of infectious diseases of the child's brain, resulting in new therapeutic approaches. A better understanding of the molecular pathophysiology of bacterial meningitis has developed, and therapeutic interventions focus on the host's inflammatory response. Therapeutic trials with dexamethasone in addition to antibiotic treatment have yielded promising results in reducing morbidity and long-term neurologic sequelae in bacterial meningitis. The detection of Lyme borreliosis in 1977 substantially influenced the differential diagnosis of inflammatory central nervous system diseases. Lyme neuroborreliosis proved a main cause of acute peripheral facial palsy and aseptic meningitis in children. An effective antibiotic treatment has become available for a large number of patients with these illnesses.
Publication Types:
PMID: 8507911 [PubMed - indexed for MEDLINE]
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Headache resembling tension-type headache as the single manifestation of Lyme neuroborreliosis.
Brinck T, Hansen K, Olesen J.
Department of Neurology, Gentofte Hospital, University of Copenhagen, Denmark.
We present two patients with monosymptomatic headache resembling chronic tension-type headache as the first manifestation of Lyme neuroborreliosis. The headache developed over a few days in both cases and lasted for three months in the first case and for two and a half years in the second case before the diagnosis of Lyme neuroborreliosis was made. Neuroimaging and many laboratory investigations did not lead to the diagnosis, which was only established after lumbar puncture. The CSF in both cases showed high protein, lymphocytic pleocytosis and Borrelia burgdorferi-specific intrathecal antibody synthesis. The headache disappeared completely after treatment with penicillin G. In patients suffering from daily headaches which have developed subacutely, Lyme neuroborreliosis should be considered even in the absence of signs of meningeal irritation. A lumbar puncture should be performed more often than is presently customary and the CSF should be examined for pleocytosis as well as Borrelia burgdorferi-specific intrathecal antibody synthesis.
Publication Types:
PMID: 8358780 [PubMed - indexed for MEDLINE]
Polymerase chain reaction with the 30-kb circular plasmid of Borrelia burgdorferi B31 as a target for detection of the Lyme borreliosis agents in cerebrospinal fluid.
Amouriaux P, Assous M, Margarita D, Baranton G, Saint Girons I.
Unit de Bactriologie molculaire et mdicale, Institut Pasteur, Paris.
The polymerase chain reaction (PCR) was developed for use in the detection of Borrelia burgdorferi sensu lato, the Lyme disease agent. A 333-bp fragment of the 30-kbp circular plasmid from Borrelia burgdorferi B31 was amplified and PCR products were analysed by DNA-DNA hybridization. Sensitivity was enhanced by addition of a carrier to the samples before treatment and enabled detection of as few as 1 to 10 bacteria. Specific products were obtained only with the Lyme disease agents, but not with other spirochetes or unrelated bacteria. B. burgdorferi sensu lato was detected in cerebrospinal fluid (CSF) from 11 out of 45 patients with confirmed Lyme neuroborreliosis. In a prospective study, 20 out of 315 CSF samples from potential patients were PCR-positive. Forty uninfected patients were PCR-negative.
Publication Types:
PMID: 8210678 [PubMed - indexed for MEDLINE]
Epidemiology and clinical manifestations of Lyme borreliosis in childhood. A prospective multicentre study with special regard to neuroborreliosis.
Christen HJ, Hanefeld F, Eiffert H, Thomssen R.
Department of Pediatrics, University Hospital, Gttingen, Germany.
Lyme borreliosis is a tick-borne infection caused by the spirochete Borrelia burgdorferi, whose discovery in 1982 solved an aetiological mystery involving a variety of dermatological and neurological disorders and explained their association with Lyme disease. Lyme borreliosis occurs frequently and is readily treatable with antibiotics. Along with its discovery, however, came the realization that it is difficult to diagnose accurately, especially antibody diagnosis. False-positive antibody results in particular led to gradual widening of the clinical spectrum, and differential diagnosis became increasingly difficult. This prospective, multicentre study presents a systematic description of Lyme borreliosis in childhood, emphasizing epidemiological and clinical issues. Because, predominantly, inpatients were examined, Lyme neuroborreliosis was the focus of the study, with the chief concern being to minimize false-positive results. To this end, we chose to narrow the diagnostic criteria, using the presence of specific antibodies in the cerebrospinal fluid as the determining factor. The epidemiological investigation was focused on the incidence of Lyme neuroborreliosis in childhood in southern Lower Saxony as well as on the prevalence of Lyme neuroborreliosis among acute-inflammatory neurological illnesses in children. The clinical part of the study aimed at establishing criteria for differential diagnosis in addition to the detection of specific antibodies. The detection of specific IgM antibodies using an IgM capture ELISA confirmed the presence of acute Lyme borreliosis. The study examined 208 children with Lyme borreliosis, of whom 169 had Lyme neuroborreliosis, from mid-1986 until the end of 1989. The yearly incidence of Lyme neuroborreliosis in Lower Saxony was 5.8 cases/100,000 children aged 1 to 13. The manifestation index was 0.16, or one case of Lyme neuroborreliosis per 620 infected children, compared with the presence of specific antibodies against B. burgdorferi for children in the same age group and region. Both the seasonal distribution of Lyme borreliosis, which peaked in summer and autumn, as well as the information about when the tick bites took place point to an incubation period of a few weeks. The most frequent manifestation of Lyme neuroborreliosis in childhood was acute peripheral facial palsy, found in 55% of all cases (n = 93). Lyme borreliosis proved to be the most frequently verifiable cause of acute peripheral facial palsy in children, causing every second case of this disorder in summer and autumn.(ABSTRACT TRUNCATED AT 400 WORDS)
Publication Types:
PMID: 8443440 [PubMed - indexed for MEDLINE]
Western blotting in evaluating Lyme seropositivity and the utility of a gel densitometric approach.
Pachner AR, Ricalton NS.
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007.
The antibody response to Borrelia burgdorferi is widely used in the diagnosis of Lyme neuroborreliosis and other manifestations of Lyme disease. However, a problem with immunoassays has been a significant number of false positives. The Western blotting technique is a useful adjunct in the serodiagnosis of other infections, but its use in Lyme borreliosis has been limited because of a lack of definition of what constitutes a positive assay. Using a gel densitometric analysis, we devised quantitative criteria for positivity and tested our criteria by matching blot results with clinical characteristics in a retrospectively studied group of 20 patients with Lyme disease, 23 healthy controls, and 18 patients with other neurologic and rheumatologic diseases. We then evaluated these criteria prospectively in serum from 35 ELISA-positive patients, and found that the serum from the majority of patients with positive serologies by ELISA were negative by Western blot. The Western blot-negative seropositive patients usually had other inflammatory or infectious diseases. We conclude that quantitative Western blotting is a helpful test in the serodiagnosis of Lyme neuroborreliosis and other manifestations of Lyme disease.
PMID: 1436533 [PubMed - indexed for MEDLINE]
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Detection of Borrelia burgdorferi DNA in urine samples and cerebrospinal fluid samples from patients with early and late Lyme neuroborreliosis by polymerase chain reaction.
Lebech AM, Hansen K.
Department of Infection-Immunology, Statens Seruminstitut, Copenhagen, Denmark.
A polymerase chain reaction (PCR) was developed for use in the identification of a 248-bp fragment of the Borrelia burgdorferi flagellin gene in urine and cerebrospinal fluid (CSF) from patients with Lyme neuroborreliosis. The specificities of the PCR products were confirmed by DNA-DNA hybridization with an internal probe. The assay had a detection limit of 10 in vitro-cultivated B. burgdorferi. The PCR assay seemed to be species wide as well as species specific, since DNA from all 21 B. burgdorferi isolates from humans tested but not from Borrelia hermsii or Treponema pallidum could be amplified. We tested 10 consecutively diagnosed patients with untreated neuroborreliosis. There was lymphocytic pleocytosis and intrathecal B. burgdorferi-specific antibody synthesis in the CSF of all patients. Urine and CSF samples were investigated by PCR before, during, and up to 8.5 months after therapy. B. burgdorferi DNA was detected in urine samples from nine patients; five patients, including two patients with chronic neuroborreliosis, were PCR positive prior to treatment, whereas urine samples from the remaining four patients obtained 3 to 6 days after the onset of therapy became PCR positive. All urine samples obtained greater than 4 weeks after therapy were negative by PCR. PCR of CSF was less sensitive, and samples from only four patients, including one with chronic neuroborreliosis, were positive. We conclude that urine is a more suitable sample source than CSF for use in B. burgdorferi DNA detection by PCR. Normalization of inflammatory CSF changes and the negative PCR results during follow-up even in patients with chronic neuroborreliosis do not point to a persistent infection. The future role of PCR as a diagnostic tool for Lyme neuroborreliosis is still uncertain.
Publication Types:
PMID: 1629318 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis manifesting as an intracranial mass lesion.
Murray R, Morawetz R, Kepes J, el Gammal T, LeDoux M.
Department of Surgery, University of Alabama, School of Medicine, Birmingham.
Lyme neuroborreliosis is one of the chronic manifestations of Lyme disease and is caused by the neurotropic spirochete, Borrelia burgdorferi. Two of the three stages of Lyme disease potentially involve the central nervous system: a second stage that may manifest as meningitis, cranial neuritis, or radiculoneuritis; and a third stage, or chronic neuroborreliosis, with parenchymal involvement. The tertiary stage may mimic many conditions, including multiple sclerosis, polyneuropathy, viral encephalitis, brain tumor, vasculitis, encephalopathy, psychiatric illness, and myelopathy. We report a 10-year-old child with signs, symptoms, and radiological manifestations of intracranial mass lesions, without previously recognized manifestations of Lyme disease. This proved to be Lyme neuroborreliosis, documented by histological and serological examination, which responded well to antibiotic therapy. The need to establish a tissue diagnosis of intracranial mass lesions is emphasized, and the utility of a computed tomographic-guided stereotactic system for this purpose is discussed.
Publication Types:
PMID: 1584393 [PubMed - indexed for MEDLINE]
The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985-1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production.
Hansen K, Lebech AM.
Department of Infection-Immunology, Statens Seruminstitut, Copenhagen, Denmark.
This prospective study reports the clinical and epidemiological features of 187 consecutive patients with neuroborreliosis recognized in Denmark over the 6-yr period, 1985-1990. Only patients with intrathecal Borrelia burgdorferi specific antibody synthesis were included. In 1990 regional incidences varied between 5.7 and 24.1 per million. Ninety-four percent of the patients had early (second stage) neuroborreliosis. The most common manifestation was a painful lymphocytic meningoradiculitis (Bannwarth's syndrome) either with paresis (61%) or as a radicular pain syndrome only (25%). Central nervous system (CNS) involvement in early neuroborreliosis was rare; 4% had signs of myelitis and only one patient had acute encephalitis. Children showed a different course of the disease. Six percent of the patients suffered a chronic course with a disease duration between 6 mths and 6 yrs either as chronic lymphocytic meningitis (1.6%) or as third stage chronic encephalomyelitis (4.3%). Meningeal signs were rare despite pronounced inflammatory cerebrospinal fluid (CSF) changes (median cell count 160/microliters; median protein concentration 1.13 g/l). High dose i.v. penicillin G was administered to 91% of the patients. Based on the clinical outcome and normalization of CSF no treatment failures were recognized. The final morbidity after a median follow-up of 33 mths was low; disabling sequelae were reported in nine patients, mainly those with previous CNS involvement. We conclude that neuroborreliosis is a common and characteristic neurological disorder. The diagnosis should be based on the demonstration of inflammatory CSF changes and B. burgdorferi specific intrathecal antibody production.
Publication Types:
PMID: 1606475 [PubMed - indexed for MEDLINE]
Comment in:
PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients.
Keller TL, Halperin JJ, Whitman M.
Division of Cell and Molecular Biology, Dana Farber Cancer Institute, Boston, MA.
We used the polymerase chain reaction (PCR), a method useful in the detection of Borrelia burgdorferi in vitro, to evaluate CSF in patients thought to have neuroborreliosis. Nested pairs of oligonucleotide primers were designed to recognize the C-terminal region of B burgdorferi OspA. CSF samples were obtained from (1) patients with immunologic evidence of systemic B burgdorferi infection and clinical manifestations suggestive of CNS dysfunction, (2) seronegative patients with clinical disorders consistent with Lyme borreliosis, and (3) patient and contamination controls; all were analyzed in a blinded fashion. PCR detected B burgdorferi OspA DNA in CSF of (1) 10 of 11 patients with Lyme encephalopathy, (2) 28 of 37 patients with inflammatory CNS disease, (3) seven of seven seronegative patients with Lyme-compatible disorders, and (4) zero of 23 patient controls. Zero of 83 additional contamination controls were PCR-positive. In eight patients from whom we obtained CSF before and after parenteral antimicrobial therapy, PCR results invariably predicted clinical outcome accurately.
Publication Types:
PMID: 1734321 [PubMed - indexed for MEDLINE]
Central nervous system abnormalities in Lyme neuroborreliosis.
Halperin JJ, Volkman DJ, Wu P.
Department of Neurology, State University of New York, Stony Brook 11794.
Intrathecal production of anti-Borrelia burgdorferi antibody occurs frequently in CNS Lyme, yet reliable diagnosis of neuroborreliosis is still considered difficult and controversial. Therefore, we assessed the utility of this measurement in 103 Lyme patients. Among 15 patients with Lyme meningoradiculitis and 41 controls, diagnostic specificity was 93% and sensitivity 87%. Application of this method permits the identification of a rare B burgdorferi-associated multifocal encephalitis (brain infection) and its differentiation from a milder encephalopathy, or confusional state; the latter may not require CNS bacterial invasion. The encephalitis involves white matter more often than gray; severity varies widely. Of six patients with this antibiotic-responsive encephalitis, five were positive for HLA DQw3(DQw7). We conclude that (1) measurement of intrathecal antibody production is a reliable indicator of CNS infection, (2) North American neuroborreliosis includes the same spectrum of neurologic dysfunction as described in Europe, and (3) HLA typing may be useful in furthering our understanding of severe CNS involvement.
Publication Types:
PMID: 1922798 [PubMed - indexed for MEDLINE]
Antibody response against autologous and heterologous isolates of Borrelia burgdorferi in four patients with Lyme neuroborreliosis.
Karlsson M.
Department of Infectious Diseases, Danderyd Hospital, Sweden.
Serum and cerebrospinal fluid (CSF) samples from four patients with Lyme neuroborreliosis were analyzed for IgM and IgG antibodies by an indirect enzyme immunoassay with the four patients' own CSF isolate of Borrelia burgdorferi and two tick isolates, strains STG152 and B31, as antigens. No major differences in the antibody response were found comparing autologous and heterologous strains as sonicate antigens, although a tendency towards a stronger response to the autologous isolates was noted in samples from two patients.
Publication Types:
PMID: 1810726 [PubMed - indexed for MEDLINE]
[Subacute organic psychosyndrome as a clinical manifestation of infection with stage II Borrelia burgdorferi without further neurologic manifestations]
[Article in German]
Reess J, Mauch E, Kornhuber HH.
Fachklinik fr Neurologie Dietenbronn, Schwendi.
A 60-year old man developed a subacute psychoorganic syndrome over four weeks. CCT was normal, except a slight atrophy of the cerebellar superior vermiform process. In the CSF we found 1696/3 cells, suggesting a lesion of the hemato-encephalic barrier, an autochthonous IgG production and an increased specific antibody-titre (10.3) for Borrelia burgdorferi. Based on these data a Lyme-Neuroborreliosis being diagnosed. Treatment with Cefotaxim and Gentamycin was successful, a complete remission of the psychopathological symptoms had been obtained. This case is an uncommon manifestation of a Borrelia-burgdorferi-infection of the CNS with psychopathological symptoms but no neurological deficit. We conclude that an affection of the CNS with Borrelia burgdorferi must always be taken into consideration in patients presenting a subacute psychoorganic syndrome of unknown etiology.
Publication Types:
PMID: 1944717 [PubMed - indexed for MEDLINE]
Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi--specific immunoglobulin G, A, and M.
Hansen K, Lebech AM.
Borrelia Laboratory, Department of Infection-Immunology, Statens Seruminstitut, Copenhagen, Denmark.
An antibody capture enzyme-linked immunosorbent assay was developed to measure directly intrathecal immunoglobulin (Ig) G, A, and M synthesis specific for Borrelia burgdorferi. Purified, biotin-avidin-peroxidase-labeled B. burgdorferi flagella was used as test antigen. Paired cerebrospinal fluid and serum specimens from 100 patients with clinically definite neuroborreliosis and 35 control subjects with neurological diseases were examined. Significant B. burgdorferi-specific intrathecal IgG, A, and M production was found in 89%, 65% and 67% of patients with neuroborreliosis. Local synthesis of specific IgA was only seen in patients with significant local IgG synthesis. Antibody production in cerebrospinal fluid began by 2 weeks after onset of neurological symptoms. At the end of the second week specific IgM, IgG, or both, was detected in 88% of the patients. Specific IgG synthesis was present in all patients by 6 weeks after onset. Specific local IgM synthesis usually disappeared by 3 to 6 months after therapy, whereas specific IgG synthesis persisted after recovery. Even in patients with a severely altered blood-brain barrier, the assay discriminated between intrathecal antibody synthesis and antibody leakage from serum. The assay makes diagnostic measurement of B. burgdorferi-specific intrathecal antibody synthesis reliable, rapid, and accessible as a routine serological test.
Publication Types:
PMID: 1897911 [PubMed - indexed for MEDLINE]
[Diagnosis of Lyme neuroborreliosis. Detection of intrathecal antibody formation]
[Article in German]
Wilske B, Bader L, Pfister HW, Preac-Mursic V.
Max-von-Pettenkofer-Institut fr Hygiene und Medizinische Mikrobiologie, Universitt Mnchen.
The most common neurological manifestation of Lyme disease is lymphocytic meningoradiculitis (Banwarth's syndrome, stage II). In rare cases, chronic progressive encephalomyelitis (stage III) with symptoms similar to multiple sclerosis is observed. Antibodies against Borrelia burgdorferi are detectable in 70-90% of stage II cases, with IgM-antibodies predominating in the first two weeks, and IgG-antibodies thereafter. Detection of specific intrathecal antibodies is the best serodiagnostic parameter for diagnosing neuroborreliosis. With the aid of a CSF/serum index determination (on the basis of a comparison of IgG-antibody ELISA titers in CSF and serum with identical IgG concentrations) involvement of the nervous system was shown in 64% and 77%, respectively, of 76 stage II cases (diagnostic significance 98% and 100%, respectively). In particular when tertiary forms of the disease are suspected immunoblot techniques (Western blot, IEF-affinity blot) are recommended confirmatory tests.
Publication Types:
PMID: 1937323 [PubMed - indexed for MEDLINE]
Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis.
Baig S, Olsson T, Hjeberg B, Link H.
Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
An autoimmune response to myelin basic protein (MBP) has been proposed to participate in the development of the chronic neurologic manifestations that may accompany Borrelia burgdorferi-induced Lyme disease. Using an immunospot assay, we counted cells secreting antibodies to MBP. Anti-MBP IgG antibody-secreting cells were detected in CSF from eight of 13 consecutive patients with Lyme neuroborreliosis irrespective of stage of disease. The numbers were between 1/370 and 1/5,000 CSF cells (mean, 1/1,250 in the 13 patients). The highest numbers were encountered in two patients with severe signs of CNS involvement. The numbers decreased in parallel with clinical improvement after treatment. Anti-MBP IgG antibody-secreting cells were also observed in the CSF from patients with a variety of other inflammatory diseases of the nervous system, and their role in the development of tissue damage remains unsettled. Anti-MBP IgG antibody-secreting cells were not detected in the patients' blood, reflecting accumulation of this autoantibody response to CSF.
Publication Types:
PMID: 1707148 [PubMed - indexed for MEDLINE]
Anti-Borrelia burgdorferi antibody response over the course of Lyme neuroborreliosis.
Baig S, Olsson T, Hansen K, Link H.
Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Characteristic findings on examination of cerebrospinal fluid (CSF) in Lyme neuroborreliosis include mononuclear pleocytosis, oligoclonal immunoglobulin G (IgG) bands, and evidence for local production of specific antibodies. We utilized an immunospot assay to detect cells secreting anti-Borrelia burgdorferi antibodies of different isotypes over the course of disease. Such cells were detected in CSF from 13 consecutive patients with neuroborreliosis examined before treatment. IgG antibody-secreting cells were present in high numbers (mean, 32 cells per 10(4) CSF cells), whereas IgA and IgM antibody-secreting cells were found less frequently and at lower numbers (mean, 5 and 6 cells per 10(4) CSF cells, respectively). Clinical improvement after penicillin treatment was paralleled by a rapid decline of antibody-secreting cells in CSF, but they were still detected, although at lower numbers, in 5 of 10 patients examined more than 6 months after treatment. This specific B-cell response persisted despite clinical improvement. Whether it reflects persistence of antigen is unsettled.
PMID: 1997408 [PubMed - indexed for MEDLINE]
Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis.
Pfister HW, Preac-Mursic V, Wilske B, Schielke E, Srgel F, Einhupl KM.
Neurological Department, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16). Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime. However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.
Publication Types:
PMID: 1988514 [PubMed - indexed for MEDLINE]
North American Lyme neuroborreliosis.
Halperin JJ.
Department of Neurology, State University of New York, Stony Brook 11794.
Clinical, neurophysiologic and laboratory findings obtained in American patients with nervous system Lyme borreliosis were compared to published observations in European neuroborreliosis patients. In both populations, Borrelia burgdorferi infection is commonly associated with neurologic abnormalities. European reports have emphasized dramatic clinical phenomena, such as painful radiculitis (Garin-Bujadoux-Bannwarth syndrome) and chronic progressive spastic paraparesis. North American patients seem to develop milder forms of nervous system involvement. Peripheral nervous system manifestations take a variety of forms, ranging from mild, intermittent sensory symptoms, to typical painful radiculitis. Despite the range of clinical presentations, neurophysiologic and morphologic analyses indicate these all represent different manifestations of the same pathophysiologic process, which, in turn, is similar to what has been described in Garin-Bujadoux-Bannwarth syndrome. Similarly, central nervous system (CNS) symptoms vary widely, ranging from a mild confusional state to a severe encephalitis. The encephalitis is probably due to direct CNS infection. In some instances the confusional state may also be due to CNS infection but it is likely that in many patients it is not. As in European patients, the most reliable indicator of CNS infection appears to be the intrathecal production of anti-B burgdorferi antibodies. Although North American Lyme borreliosis patients may often develop milder forms of nervous system involvement that their European counterparts, there is considerable overlap, and the underlying pathophysiologic mechanisms are probably identical.
Publication Types:
PMID: 1658921 [PubMed - indexed for MEDLINE]
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Lyme neuroborreliosis. Peripheral nervous system manifestations.
Halperin J, Luft BJ, Volkman DJ, Dattwyler RJ.
Department of Neurology, State University of New York, Stony Brook 11794.
An ever increasing number of apparently unrelated peripheral nervous system (PNS) disorders has been associated with Lyme borreliosis. To ascertain their relative frequency and significance, we studied prospectively 74 consecutive patients with late Lyme disease, with and without PNS symptoms: 53% had intermittent limb paraesthesiae, 25% the carpal tunnel syndrome, 8% painful radiculopathy, and 3% Bell's palsy; 39% had disseminated neurophysiological abnormalities. To assess the interrelationships among these syndromes, we reviewed the neurophysiological findings in all 163 such patients that we have studied to date. Reversible abnormalities of distal conduction were the most common finding. Demyelinating neuropathy was extremely rare. The pattern of abnormality was similar in all patient groups, regardless of whether the symptoms suggested radiculopathy, Bell's palsy, or neuropathy. We conclude that (1) reversible PNS abnormalities occur in one-third of our patients with late Lyme borreliosis, and (2) the pattern of electrophysiological abnormalities is the same in all and is indicative of widespread axonal damage, suggesting that these different presentations reflect varying manifestations of the same pathological process.
Publication Types:
PMID: 2168778 [PubMed - indexed for MEDLINE]
Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis.
Dotevall L, Fuchs D, Reibnegger G, Wachter H, Hagberg L.
Department of Infectious Diseases, University of Gteborg, Sweden.
Elevated (greater than 3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis.
Publication Types:
PMID: 2210852 [PubMed - indexed for MEDLINE]
Evaluation of the intrathecal antibody response to Borrelia burgdorferi as a diagnostic test for Lyme neuroborreliosis.
Steere AC, Berardi VP, Weeks KE, Logigian EL, Ackermann R.
Division of Rheumatology/Immunology, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111.
The intrathecal antibody response to Borrelia burgdorferi was evaluated in American and West German patients with Lyme neuroborreliosis. By an antibody capture enzyme immunoassay, 12 (92%) of 13 patients from the USA with Lyme meningitis were found to have intrathecal antibody production to B. burgdorferi, usually of multiple isotypes, most commonly IgA. Of 12 patients with putative late central nervous system manifestations of Lyme disease, 5 (42%) had local production of IgG or IgA spirochetal antibody, but cerebrospinal fluid (CSF) abnormalities could not be demonstrated in 6 patients with late peripheral nervous system manifestations of the disorder. Compared with American patients, 30 European patients with neuroborreliosis had significantly higher CSF:serum ratios of specific antibody both early and late in the illness. Intrathecal antibody determinations are the most specific diagnostic test currently available for Lyme neuroborreliosis, but local antibody production in CSF is an inconsistent finding in American patients with late neurologic manifestations of the disorder.
Publication Types:
PMID: 2345301 [PubMed - indexed for MEDLINE]
Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis.
Hansen K, Cruz M, Link H.
Borrelia Laboratory, Department of Treponematoses, Statens Seruminstitut, Copenhagen, Denmark.
Cerebrospinal fluid (CSF) and serum from 45 patients with lymphocytic meningoradiculitis were examined by isoelectric focusing combined with immunoblotting to detect Borrelia burgdorferi-specific oligoclonal immunoglobulin G (IgG) bands. In pretreatment samples, 35 patients (78%) showed B. burgdorferi-specific oligoclonal IgG in CSF indicative of intrathecal antibody production. At 2, 3-6, and 6 weeks after onset, respectively, such bands were present in 5 (42%) of 12, 21 (88%) of 24, and in all of 9 patients (100%). Up to 1 year after therapy, specific oligoclonal bands in CSF tended to remain unchanged despite clinical recovery. B. burgdorferi-specific oligoclonal bands in serum were found in 7 patients. These bands had identical migration patterns as in CSF, but were fewer in number and in some patients showed a temporal evolution different from their CSF counterpart. Not all oligoclonal IgG in CSF reacted with B. burgdorferi. The 41-kDa flagellar antigen was shown to be a major antigen in the intrathecal immune response. The demonstration of B. burgdorferi-specific oligoclonal IgG in CSF is a sensitive and reliable indicator of Lyme neuroborreliosis.
Publication Types:
PMID: 2345300 [PubMed - indexed for MEDLINE]
Meningovascular form of neuroborreliosis: similarities between neuropathological findings in a case of Lyme disease and those occurring in tertiary neurosyphilis.
Miklossy J, Kuntzer T, Bogousslavsky J, Regli F, Janzer RC.
University Institute of Pathology, Division of Neuropathology, Lausanne, Switzerland.
Recent observations have delineated the neurological manifestations of Lyme disease, but, to our knowledge, no detailed neuropathological study from autopsy cases has been reported. In this report we describe the neuropathological findings in a case of Lyme neuroborreliosis. The chronic meningitis, the occlusive meningovascular and secondary parenchymal changes that we found are similar to those occurring in the meningovascular form of neurosyphilis. Thus, we suggest that the case described here represents the meningovascular form of tertiary Lyme neuroborreliosis.
Publication Types:
PMID: 2251916 [PubMed - indexed for MEDLINE]
Cefotaxime vs penicillin G for acute neurologic manifestations in Lyme borreliosis. A prospective randomized study.
Pfister HW, Preac-Mursic V, Wilske B, Einhupl KM.
Neurologische Klinik der Universitt, Klinikum Grosshadern, Mnchen, West Germany.
We randomly assigned 21 patients with painful Lyme neuroborreliosis radiculitis (Bannwarth's syndrome) and neuroborreliosis meningitis to a 10-day treatment with either penicillin G. 4 x 5 million U/d (n = 10) or cefotaxime sodium, 3 x 2 g/d (n = 11), intravenously. We were not able to demonstrate clinical differences between groups, either during the 10-day treatment period or at follow-up examination a mean of 7.7 months after antibiotic therapy. Cerebrospinal fluid cefotaxime concentrations reached the minimum inhibitory concentration at the 90% level for Borrelia burgdorferi in all patients, while none of the patients treated with penicillin G had cerebrospinal fluid concentrations above the minimum inhibitory concentration at the 90% value. We conclude that patients with acute neurologic manifestations of Lyme borreliosis may benefit from a 10-day treatment with cefotaxime or penicillin G. Cerebrospinal fluid antibiotic concentrations above the minimum inhibitory concentration at the 90% value, as observed in all patients treated with cefotaxime, offer the most hope for long-term prognosis.
Publication Types:
PMID: 2684107 [PubMed - indexed for MEDLINE]
Latent Lyme neuroborreliosis: presence of Borrelia burgdorferi in the cerebrospinal fluid without concurrent inflammatory signs.
Pfister HW, Preac-Mursic V, Wilske B, Einhupl KM, Weinberger K.
Neurologische Klinik, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, was isolated from the CSF of a patient with elevated serum IgG antibody titers against B burgdorferi and a history of multiple tick bites. The absence of concurrent inflammatory signs of CSF as well as intrathecal antibody production indicates a phase of latent Lyme neuroborreliosis in which no tissue infection or reaction has yet occurred. Bilateral tinnitus was the only clinical symptom in this patient. The persistence of the bilateral tinnitus after antibiotic therapy did not support a causal relationship between this symptom and the borrelial infection.
Publication Types:
PMID: 2668788 [PubMed - indexed for MEDLINE]
Penetration of doxycycline into cerebrospinal fluid in patients treated for suspected Lyme neuroborreliosis.
Dotevall L, Hagberg L.
Department of Infectious Diseases, University of Gteborg, Sweden.
Twelve patients were treated orally with 100 mg of doxycycline twice a day (b.i.d.) and 10 patients were treated with 200 mg b.i.d. for suspected tick-borne neuroborreliosis (Lyme borreliosis). At 5 to 8 days after the start of therapy, the mean concentrations in serum were 4.7 micrograms/ml for the doxycycline dose of 100 mg b.i.d. and 7.5 micrograms/ml for 200 mg b.i.d., 2 to 3 h after the last drug administration. The corresponding levels for cerebrospinal fluid were 0.6 and 1.1 micrograms/ml. Since a doxycycline concentration in cerebrospinal fluid above the estimated MIC for Borrelia burgdorferi (0.6 to 0.7 microgram/ml) is wanted in patients treated for severe neuroborreliosis, the higher dose is preferable.
PMID: 2782858 [PubMed - indexed for MEDLINE]
Comment in:
Lyme neuroborreliosis: central nervous system manifestations.
Halperin JJ, Luft BJ, Anand AK, Roque CT, Alvarez O, Volkman DJ, Dattwyler RJ.
Department of Neurology, State University of New York, Stony Brook.
We evaluated 85 patients with serologic evidence of Borrelia burgdorferi infection. Manifestations included encephalopathy (41), neuropathy (27), meningitis (2), multiple sclerosis (MS) (6), and psychiatric disorders (3). We performed lumbar punctures in 53, brain MRI in 33, and evoked potentials (EPs) in 33. Only patients with an MS-like illness had abnormal EPs, elevated IgG index, and oligoclonal bands in the cerebrospinal fluid. Twelve of 18 patients with encephalopathy, meningitis, or focal CNS disease had evidence of intrathecal synthesis of anti-B burgdorferi antibody, compared with no patients with either MS-like or psychiatric illnesses, and only 2/24 patients with neuropathy. MRIs were abnormal in 7/17 patients with encephalopathy, 5/6 patients with an MS-like illness, and no others. We conclude that (1) intrathecal concentration of specific antibody is a useful marker of CNS B burgdorferi infection; (2) Lyme disease causes an encephalopathy, probably due to infection of the CNS; (3) MS patients with serum immunoreactivity against B burgdorferi lack evidence of CNS infection with this organism.
Publication Types:
PMID: 2542840 [PubMed - indexed for MEDLINE]
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