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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, Université 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, Sjöwall J, Davidsson L, Forsberg P, Smedby O.
Division of Radiology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, 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 Chorób 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 Chorób 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, Sillanpää H, Seppälä 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 Chorób 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.
Ljøstad U, Skarpaas T, Mygland A.
Department of Neurology, Sørlandet 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.
Universitätsklinik, für Dermatologie, Medizinische Universität 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, Ljøstad U, Søbye M, Mygland A.
Microbiology Unit, Division of Laboratory Medicine, Sørlandet 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, Pitkäranta A, Nyman D, Granlund H, Carlsson SA, Seppälä 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, Universitätskinderklinik, 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 Büdingen HC, Meier M, Harrer MD, Urich E, Becher B, Goebels N.
Clinical Neuroimmunology Unit, Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, CH-8091 Zürich, 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 associé au CNR Borrelia, laboratoire de bactériologie, hôpitaux universitaires de Strasbourg, 3, rue Koeberlé, 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.
Bednárova 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, Geissdörfer 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, université Paris-VI, CHU de la Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 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]
Créange A.
Service de neurologie, centre hospitalier universitaire Henri-Mondor, APHP, université Paris-XII, 94000 Créteil, 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, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 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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