Lyme Disease Causes Encephalopathy—Infection/Inflammation of the Brain

One of the findings noted by many physicians treating Lyme disease that was never treated, or Babesia or Bartonella, is serious personality and neurology troubles. This is no surprise when you realize the emotional centers and relational skills centers of the brain are infected with these infections in some people and this makes them into very sad hateful eccentric people. It is amazing to listen to respected physicians who treat people with tick infections. They seem to typically report the following tick infection personality changes or neurology changes:

Narcissism—they believe they have the answers, despite prolonged and failed treatment. They think they know areas they have no training in such as costs to be educated for NP, PA, DO, ND or MD. They act as if they know the costs to be an MD each year, costs to research or attend conferences, costs for any book, costs to do a blind study, costs to have lawyers, costs for malpractice insurance, costs for staffing, etc.

Entitlement—massive demands for time and huge expectations

Short term memory is decreased—so patients forget instructions

Rage—evidence of huge amounts of time not helping people, but attacking.

Weird posts on the motives of respected clinicians.

Black and White Thinking—past or current healers are the devil or great.

Slowed Learning—they read a book and do not seem to absorb large sections.

Criminal actions, e.g., stealing PDF books which has possible five year jail term, stealing identities, making extreme bizarre accusations, posting home addresses to provoke some attack or _________ on a physician, local politician or insurance staff who is not approving a treatment. I assume the writer or poster also wants harm to come to the family of these individuals.

Hate over fees—they do not appreciate offering treatment for a possibly fatal illness has massive risks. They have no knowledge of expenses just to run an office or lost income just publishing a small journal article. They suffer from a regressed primitive personality that wants the physician to be a mother and offer free unconditional love.

Trivia Complaints—small matters are made into matters worthy of immense time and hateful accusations which are amplified 20x from the brain pathology. Some actually hate some physicians, and instead of moving on and finding a good fit and getting well, they attack someone who is not meeting their perfection standards, which usually include taking insurance, very low rates and mother-like care with free emergency access and free email medicine.

Rape of Physician Boundaries—they want to take five physicians and rip them apart, and take the things they like in each one, to make a perfect MD that meets their standards.

1. Klin Mikrobiol Infekc Lek. 2009 Oct;15(5):160-165.

[Detection of spirochaetal DNA from patients with neuroborreliosis and erythema migrans.]

[Article in Czech]

Moravcová L, Pícha D, Vaňousová D, Hercogová J.

Department of Infectious Diseases, 1st Medical Faculty, Charles University Prague, Czech Republic, Lenka.moravcova@fnb.cz.

Aim: Assessment of PCR procedure for proving of the Borrelia burgdorferi sensu lato DNA in nerve and skin forms of Lyme borreliosis. Methods: DNA from plasma, urine and CSF was isolated by QIAamp DNA mini kit. PCR was deigned as two-step amplification (nested-PCR). Each sample was tested in PCR for five target sequences: two were specific for plasmide genes encoding OspA and OspC proteins and three correlated with genes for 16SrDNA, flagellin and p66 protein. Results: Borrelial DNA was proved in 41 patients suffering from neuroborreliosis out of 56 (77.4 %), among 48 patients with erythema migrans (EM) were found 26 positive (54.2 %). After treatment the specific DNA was detected in 22 patients with neuroborreliosis (41.5 %) and 16 patients with EM (38.1 %). Three months after the treatment 23 patients were positive in both of groups (28.7 %) and next 3 months later the specific DNA was found in 6 (9.5 %). The highest rate of positive results was manifested by 16SrDNA target, lower and comparable results were obtained by OspA, C and flagellin primers, the lowest rate was in p66 system. Conclusion: The tested PCR proved specific DNA in all tested biological fluids in both of the clinical forms of Lyme borreliosis with a relatively high sensitivity. The proving of DNA can not be used for the assessment of the effect of treatment due to the long persistence of PCR positivity after antibiotic treatment. To achieve a sufficient diagnostic sensitivity of PCR it is desirable to use minimally two amplification systems in parallel.

PMID: 19916154 [PubMed - as supplied by publisher]

2. PLoS Pathog. 2009 Nov;5(11):e1000659. Epub 2009 Nov 13.

Microglia are mediators of Borrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells.

Myers TA, Kaushal D, Philipp MT.

Division of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Louisiana, United States of America.

Inflammation has long been implicated as a contributor to pathogenesis in many CNS illnesses, including Lyme neuroborreliosis. Borrelia burgdorferi is the spirochete that causes Lyme disease and it is known to potently induce the production of inflammatory mediators in a variety of cells. In experiments where B. burgdorferi was co-cultured in vitro with primary microglia, we observed robust expression and release of IL-6 and IL-8, CCL2 (MCP-1), CCL3 (MIP-1alpha), CCL4 (MIP-1beta) and CCL5 (RANTES), but we detected no induction of microglial apoptosis. In contrast, SH-SY5Y (SY) neuroblastoma cells co-cultured with B. burgdorferi expressed negligible amounts of inflammatory mediators and also remained resistant to apoptosis. When SY cells were co-cultured with microglia and B. burgdorferi, significant neuronal apoptosis consistently occurred. Confocal microscopy imaging of these cell cultures stained for apoptosis and with cell type-specific markers confirmed that it was predominantly the SY cells that were dying. Microarray analysis demonstrated an intense microglia-mediated inflammatory response to B. burgdorferi including up-regulation in gene transcripts for TLR-2 and NFkappabeta. Surprisingly, a pathway that exhibited profound changes in regard to inflammatory signaling was triggering receptor expressed on myeloid cells-1 (TREM1). Significant transcript alterations in essential p53 pathway genes also occurred in SY cells cultured in the presence of microglia and B. burgdorferi, which indicated a shift from cell survival to preparation for apoptosis when compared to SY cells cultured in the presence of B. burgdorferi alone. Taken together, these findings indicate that B. burgdorferi is not directly toxic to SY cells; rather, these cells become distressed and die in the inflammatory surroundings generated by microglia through a bystander effect. If, as we hypothesized, neuronal apoptosis is the key pathogenic event in Lyme neuroborreliosis, then targeting microglial responses may be a significant therapeutic approach for the treatment of this form of Lyme disease.

PMCID: 2771360 PMID: 19911057 [PubMed - in process]

3. Tidsskr Nor Laegeforen. 2009 Oct 22;129(20):2132-4.

[Laboratory diagnosis of Lyme borreliosis]

[Article in Norwegian]

Kristiansen BE, Grude N, Tveten Y, Emmert A.

Unilabs Telelab, Postboks 1868 Gulset, 3703 Skien, Norway. bjorn.erik.kristiansen@unilabs.com

PMID: 19855455 [PubMed - indexed for MEDLINE]

4. MMW Fortschr Med. 2009 Apr 30;151(18):8.

[New biomarker discovered. Will the diagnosis of neuroborreliosis soon be easier (interview by Maria Weiss)?]

[Article in German]

Rupprecht T.

PMID: 19769063 [PubMed - indexed for MEDLINE]

5. Eur J Paediatr Neurol. 2009 Sep 11. [Epub ahead of print]

Uncommon manifestations of neuroborreliosis in children.

Baumann M, Birnbacher R, Koch J, Strobl R, Rostásy K.

Department of Pediatrics, Division of Pediatric Neurology and Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.

Lyme borreliosis is a tick-borne spirochetal infection which affects the skin, joints, heart and nervous system. Children with a neuroborreliosis usually present with a facial nerve palsy or aseptic meningitis, but the spectrum also includes other rare manifestations. We report four unusual cases of childhood neuroborreliosis and show that seizures with regional leptomeningeal enhancement, acute transverse myelitis, meningoradiculitis with pain and paraesthesia and cranial nerve palsies other than facial nerve palsy can be the leading symptoms of children with neuroborreliosis. All children had serological evidence of an acute infection with Borrelia burgdorferi, a pleocytosis in the cerebrospinal fluid and a complete response to antibiotic treatment. An intrathecal synthesis of IgG antibodies was detected in three children. Thus, diagnostic work up in children with unusual neurological symptoms should include cerebrospinal fluid studies with determination of the white blood cell count and calculation of the antibody index against B. burgdorferi.

PMID: 19748808 [PubMed - as supplied by publisher]

6. J Laryngol Otol. 2009 Sep 10:1-3. [Epub ahead of print]

Recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.

Karosi T, Rácz T, Szekanecz E, Tóth A, Sziklai I.

Department of Otolaryngology Head and Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary.

Objective:We report an extremely rare case of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.Method:Case report presenting a 15-year-old girl referred with hoarseness and soft voice.Results:Right-sided recurrent laryngeal nerve paralysis was observed using videolaryngoscopy. Imaging was used to exclude intracranial, cervical and intrathoracic embryological lesions, vascular malformations and tumours. Laboratory and electrophysiological investigations were used to exclude inflammatory and paraneoplastic processes, endocrinopathy and metabolic disorders. Serological testing was positive for Lyme disease. Parenteral ceftriaxone therapy was commenced. The patient's nerve paralysis showed complete recovery on the seventh day of antibiotic treatment; this was confirmed by videolaryngoscopy.Conclusion:Recurrent laryngeal nerve paralysis is an extremely rare complication of neuroborreliosis associated with Lyme disease. In patients with recurrent laryngeal nerve paralysis in whom the clinical history is uncertain and the usual diagnostic methods give negative results, screening with anti-borrelia immunoglobulin M is suggested.

PMID: 19740453 [PubMed - as supplied by publisher]

7. J Neuroinflammation. 2009 Aug 25;6:23.

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis.

Ramesh G, Borda JT, Gill A, Ribka EP, Morici LA, Mottram P, Martin DS, Jacobs MB, Didier PJ, Philipp MT.

Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA, USA. gramesh@tulane.edu

BACKGROUND: Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. METHODS: We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). RESULTS: ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. CONCLUSION: Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

PMCID: 2748066 PMID: 19706181 [PubMed - indexed for MEDLINE]

8. Acta Clin Belg. 2009 May-Jun;64(3):225-7.

Motor neuron disease features in a patient with neuroborreliosis and a cervical anterior horn lesion.

De Cauwer H, Declerck S, De Smet J, Matthyssen P, Pelzers E, Eykens L, Lagrou K.

Department of Neurology, Klina Regional Hospital, Brasschaat, Belgium. harald.de.cauwer@klina.be

A variety of neurological syndromes has been described in neuroborreliosis: cranial nerve palsies, radiculopathy, axonal neuropathy, stroke, parkinsonism, transverse myelitis, supranuclear palsy, Guillain-Barré syndrome, ... We report a case of neuroborreliosis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper and lower limbs with proximal and distal pareses and atrophies as well as bulbar dysarthria and dysphagia. During the course of the disease the patient developed the clinical picture of a meningoencephalitis. After initiating ceftriaxone treatment the patient showed a complete recovery. In endemic regions for Lyme disease, in all neurological syndromes neuroborreliosis has to be excluded.

PMID: 19670562 [PubMed - indexed for MEDLINE]

9. Eur J Neurol. 2009 Jul 23. [Epub ahead of print]

Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors.

Ljøstad U, Mygland A.

Department of Neurology, Sørlandet Hospital HF, Kristiansand, Norway.

Background and purpose: To chart remaining complaints 1 year after treatment for neuroborreliosis, and to identify risk factors for a non-favorable outcome. Methods: We followed patients treated for neuroborreliosis prospectively, and assessed outcome by a composite clinical score. The impact on outcome of clinical, demographic and laboratory factors were analyzed by univariate analyses and logistic regression. Results: Out of 85 patients 41 (48%) had remaining complaints; 14 had objective findings and 27 subjective symptoms. Remaining complaints were associated with pre-treatment symptom duration >/=6 weeks (OR = 4.062, P = 0.044), high pre-treatment cerebrospinal fluid (CSF) cell count (OR = 1.005, P = 0.001), and female gender (OR = 3.218, P = 0.025). Presence of CSF oligoclonal bands (OCBs) was not analyzed in the logistic regression model due to many missing observations, but was found to be more frequent both pre-treatment (P = 0.004) and after 12 months (P = 0.015) among patients with remaining complaints as compared to patients with complete recovery. Further evaluation showed that objective remaining findings, and not subjective symptoms, were associated with pre-treatment symptom duration >/=6 weeks. No difference in outcome was observed between patients treated with IV ceftriaxone and patients treated with oral doxycycline. Conclusion: Remaining complaints are common after neuroborreliosis. The majority of the complaints are subjective. Pre-treatment symptom duration >/=6 weeks, high pre-treatment CSF cell count, and female gender seem to be risk factors for remaining complaints. Presence of CSF OCBs may also predict a non-favorable outcome, but this should be further studied. Whether subjective and objective complaints are associated with different risk factors is also an issue for future studies.

PMID: 19645771 [PubMed - as supplied by publisher]

10. Neurology. 2009 Jul 28;73(4):326.

Diffuse hyperintense brainstem lesions in neuroborreliosis.

Haene A, Tröger M.

Department of Neurology, Cantonal Hospital Aarau, Tellstrasse, 5001 Aarau, Switzerland. adrian.haene@swissonline.ch

PMID: 19636055 [PubMed - indexed for MEDLINE]

11. Scand J Immunol. 2009 Aug;70(2):141-8.

T-cell epitope mapping of the Borrelia garinii outer surface protein A in lyme neuroborreliosis.

Widhe M, Ekerfelt C, Jarefors S, Skogman BH, Peterson EM, Bergström S, Forsberg P, Ernerudh J.

Division of Clinical Immunology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

PMID: 19630920 [PubMed - indexed for MEDLINE]

12. Radiology. 2009 Oct;253(1):167-73. Epub 2009 Jul 8.

Neuro-lyme disease: MR imaging findings.

Agarwal R, Sze G.

Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.

PURPOSE: To describe the neuroimaging manifestations of Lyme disease at magnetic resonance (MR) imaging of the brain. MATERIALS AND METHODS: Institutional review board approval was obtained and HIPAA compliance was followed. This study retrospectively reviewed the MR imaging findings of all patients seen from 1993 to 2007 in whom neuro-Lyme disease was suspected and who were referred for MR imaging of the brain for the evaluation of neurologic symptoms. RESULTS: Of 392 patients suspected of having neuro-Lyme disease, 66 patients proved to have the disease on the basis of clinical criteria, serologic results, and response to treatment. Seven of these 66 patients showed foci of T2 prolongation in the cerebral white matter, one had an enhancing lesion with edema, and three demonstrated nerve-root or meningeal enhancement. Of the seven patients with foci of T2 prolongation in the white matter, three were an age at which white matter findings due to small-vessel disease are common. CONCLUSION: In cases of nerve-root or meningeal enhancement, Lyme disease should be considered in the differential diagnosis in the proper clinical setting.

PMID: 19587309 [PubMed - indexed for MEDLINE]

13. Curr Opin Infect Dis. 2009 Oct;22(5):450-4.

Lyme borreliosis: a European perspective on diagnosis and clinical management.

Stanek G, Strle F.

Department of Hygiene and Medical Microbiology, Medical University of Vienna, Vienna, Austria. gerold.stanek@meduniwien.ac.at

PURPOSE OF REVIEW: Lyme borreliosis has been widely recognized in Europe, but diagnostic and therapy concepts are still a matter for discussion. False-positive microbiologic results can lead to unnecessary antibiotic treatment, which even in genuine cases is sometimes unnecessarily prolonged. This review addresses new research on diagnosis, treatment, and eco-epidemiology. RECENT FINDINGS: Recent research work in Europe since the last annual review has mostly dealt with diagnostic concepts. Improvement of serology has been achieved by use of multiple recombinant or peptide antigens, or of just the most frequently targeted antigen for detection of specific immunoglobulin G or immunoglobulin M antibodies to Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis. Concerning management of the disease, early work on the efficacy of oral treatment of Lyme neuroborreliosis has been confirmed. Studies on the ecology of the vectors and pathogens have elucidated aspects of epidemiology. SUMMARY: Widespread awareness of Lyme borreliosis in Europe continues to grow due to increasing numbers of medical publications, information on the Internet, and from the media and patient support groups. The emphasis in scientific and medical publications has been on improvements in laboratory diagnostics, confirmation of therapeutic protocols, and the ecology of the vectors and pathogens.

PMID: 19571749 [PubMed - in process]

14. Dtsch Arztebl Int. 2009 Jan;106(5):72-81; quiz 82, I. Epub 2009 Jan 30.

Lyme disease--current state of knowledge.

Nau R, Christen HJ, Eiffert H.

Geriatrisches Zentrum, Evangelisches Krankenhaus Göttingen-Weende, Abteilung für Neurologie, Universitätsklinikum Göttingen, Göttingen, Germany. rnau@gwdg.de

Comment in: Dtsch Arztebl Int. 2009 Jul;106(31-32):524-5; author reply 525. Dtsch Arztebl Int. 2009 Jul;106(31-32):524; author reply 525. Dtsch Arztebl Int. 2009 Jul;106(31-32):524; author reply 525.

BACKGROUND: Lyme disease is the most frequent tick-borne infectious disease in Europe. The discovery of the causative pathogen Borrelia burgdorferi in 1982 opened the way for the firm diagnosis of diseases in several clinical disciplines and for causal antibiotic therapy. At the same time, speculation regarding links between Borrelia infection and a variety of nonspecific symptoms and disorders resulted in overdiagnosis and overtreatment of suspected Lyme disease. METHOD: The authors conducted a selective review of the literature, including various national and international guidelines. RESULTS: The spirochete Borrelia burgdorferi sensu lato is present in approximately 5% to 35% of sheep ticks (Ixodes ricinus) in Germany, depending on the region. In contrast to North America, different genospecies are found in Europe. The most frequent clinical manifestation of Borrelia infection is erythema migrans, followed by neuroborreliosis, arthritis, acrodermatitis chronica atrophicans, and lymphocytosis benigna cutis. Diagnosis is made on the basis of the clinical symptoms, and in stages II and III by detection of Borrelia-specific antibodies. In adults erythema migrans is treated with doxycycline, in children with amoxicillin. The standard treatment of neuroborreliosis is third-generation cephalosporins. CONCLUSIONS: After appropriate antibiotic therapy, the outcome is favorable. In approximately 95% of cases neuroborreliosis is cured without long-term sequelae. When chronic borreliosis is suspected, other potential causes of the clinical syndrome must be painstakingly excluded.

PMCID: 2695290 PMID: 19562015 [PubMed - indexed for MEDLINE]

15. Nervenarzt. 2009 Oct;80(10):1239-51.

[Neuroborreliosis]

[Article in German]

Kaiser R, Fingerle V.

Neurologische Klinik, Klinikum Pforzheim, Kanzlerstrasse 2-6, 75175, Pforzheim, Deutschland. rkaiser@klinikum-pforzheim.de

Neuroborreliosis is easily diagnosed by means of clinical symptoms and laboratory findings. Guiding symptoms are radicular pain and pareses of the extremities and the facial nerve. There is a great number of further less frequently occurring neurological symptoms, which can be attributed to a borrelial infection only by appropriate investigations of the CSF. Radiculitis is cured adequately by oral doxycycline while symptoms of the central nervous system are probably better treated intravenously by ceftriaxone, cefotaxime or penicillin G. Post-Lyme syndrome is a diffuse description of non-specific complaints, which are not the explicit result of a former infection with B. burgdorferi. As further antibiotics do not help and the CSF is unremarkable in most patients, a persistent infection with B. burgdorferi s.l. in all probability can be excluded.

PMID: 19536517 [PubMed - in process]

16. Clin Microbiol Infect. 2009 May;15(5):422-6.

Human brain microvascular endothelial cell traversal by Borrelia burgdorferi requires calcium signaling.

Grab DJ, Nyarko E, Nikolskaia OV, Kim YV, Dumler JS.

Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. dgrab1@jhmi.edu

Neurological manifestations of Lyme disease (or neuroborreliosis) occur variably and while it is clear that Borrelia burgdorferi can invade the nervous system, how it does so is not well understood. Pathogen penetration through the blood brain barrier (BBB) is often influenced by calcium signaling in the endothelial cells triggered by extracellular host-pathogen interactions. We examined the traversal of B. burgdorferi across the human BBB using in vitro model systems constructed of human brain microvascular endothelial cells (HBMEC) grown on Costar Transwell inserts. Pretreatment of the cell monolayers with BAPTA-AM (an intracellular calcium chelator) or phospholipase C (PLC) inhibitor U73122 inhibited B. burgdorferi transmigration. By 5 h, BAPTA-AM significantly inhibited (82-99%; p <0.017) spirochete traversal of HBMEC compared to DMSO controls. Spirochete traversal was almost totally blocked (> or =99%; p <0.017) after pretreatment with the PLC-beta inhibitor U73122 as a result of barrier tightening based on electric cell-substrate impedance sensing (ECIS). The data suggest a role for calcium signaling in CNS spirochete invasion through endothelial cell barriers.

PMID: 19489925 [PubMed - indexed for MEDLINE]

17. Rev Neurol (Paris). 2009 Aug-Sep;165(8-9):694-701. Epub 2009 May 17.

[Epidemiology of Lyme borreliosis and neuroborreliosis in France]

[Article in French]

Blanc F.

Département de neurologie, CMRR, hôpitaux universitaires de Strasbourg, France. Frederic.Blanc@chru-strasbourg.fr

Lyme borreliosis (LB) is a systemic disease called neuroborreliosis (NB) when neurological symptoms are pre-eminent. LB is a zoonosis caused by Borrelia bacteria transmitted by Ixodes tick-bite. Because of the absence of a national registry, epidemiology of LB in France is not well known. Moreover, diagnosis of NB may be difficult because of the various clinical forms. Acute meningoradiculitis is the most common presentation, but pauci-symptomatic meningitis, encephalitis, myelitis, polyneuropathy, cerebrovascular involvement, and rarely chronic encephalomyelitis are also described. The vector Ixodes ricinus (I. ricinus) is found throughout metropolitan France excepting border areas of the Mediterranean seaside and in regions with an altitude above 1500 meters. In France, the Borrelia infestation rate of Ixodes is 7% with wide disparity between administrative districts. Prospective work in 1999-2000 by 875 general practitioners participating in the "Sentinel" network established the estimated incidence of BL (9.4/100 000) and of NB (0.6/100 000) in France. Incidence is higher in certain regions: in Alsace, prospective work by 419 general practitioners and specialists in cooperation with the national surveillance agency (Institut national de veille sanitaire), estimated BL incidence at 86 to 200/100 000 inhabitants and NB at 10/100 000. Thus, although globally France is a country with a moderate risk for LB, some regions such as Limousin, Auvergne, Lorraine and Alsace, have a high risk of LB, comparable to countries in the northeastern Europe such as Germany and Sweden.

PMID: 19447458 [PubMed - indexed for MEDLINE]

18. Muscle Nerve. 2009 Jun;39(6):851-4.

Perineuritis in acute lyme neuroborreliosis.

Elamin M, Alderazi Y, Mullins G, Farrell MA, O'Connell S, Counihan TJ.

Department of Neurology, University College Hospital, Galway, Ireland.

Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56-year-old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis.

PMID: 19441045 [PubMed - indexed for MEDLINE]

19. Acta Paediatr. 2009 Aug;98(8):1300-6. Epub 2009 May 7.

Differential diagnosis of acute central nervous system infections in children using modern microbiological methods.

Huttunen P, Lappalainen M, Salo E, Lönnqvist T, Jokela P, Hyypiä T, Peltola H.

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, 00029 HUS, Helsinki, Finland. pasihut@iki.fi

AIM: Except bacterial meningitis, the agents causing acute central nervous system (CNS) infections in children are disclosed in only approximately half of the cases, and even less in encephalitis. We studied the potential of modern microbiological assays to improve this poor situation. METHODS: In a prospective study during 3 years, all children attending hospital with suspected CNS infection were examined using a wide collection of microbiological tests using samples from the cerebrospinal fluid, serum, nasal swabs and stool. RESULTS: Among 213 patients, 66 (31%) cases suggested CNS infection and specific aetiology was identified in 56 patients. Of these microbiologically confirmed cases, viral meningitis/encephalitis was diagnosed in 25 (45%), bacterial meningitis in 21 (38%) and neuroborreliosis in 9 (16%) cases while 1 child had fungal infection. In meningitis patients, the causative agent was identified in 85% (35/41) cases and in encephalitis in 75% (12/16). The most common bacteria were Streptococcus agalactiae, Streptococcous pneumonie and Neisseria meningitidis, while the most frequently detected viruses were enteroviruses and varicella zoster virus. CONCLUSION: In 75% to 85% of paediatric CNS infections, specific microbiological diagnosis was obtained with modern laboratory techniques. The results pose a basis for prudent approach to these potentially serious diseases.

PMID: 19432824 [PubMed - indexed for MEDLINE]

20. Clin Microbiol Infect. 2009 Mar 26. [Epub ahead of print]

Concomitant human granulocytic anaplasmosis and Lyme neuroborreliosis.

Lotric-Furlan S, Ruzic-Sabljic E, Strle F.

Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia.

PMID: 19416290 [PubMed - as supplied by publisher]

21. Arch Gen Psychiatry. 2009 May;66(5):554-63.

Regional cerebral blood flow and metabolic rate in persistent Lyme encephalopathy.

Fallon BA, Lipkin RB, Corbera KM, Yu S, Nobler MS, Keilp JG, Petkova E, Lisanby SH, Moeller JR, Slavov I, Van Heertum R, Mensh BD, Sackeim HA.

Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. baf1@columbia.edu

CONTEXT: There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease. OBJECTIVES: To determine whether patients with a history of well-characterized Lyme disease and persistent cognitive deficit show abnormalities in global or topographic distributions of regional cerebral blood flow (rCBF) or cerebral metabolic rate (rCMR). DESIGN: Case-controlled study. SETTING: A university medical center. PARTICIPANTS: A total of 35 patients and 17 healthy volunteers (controls). Patients had well-documented prior Lyme disease, a currently reactive IgG Western blot, prior treatment with at least 3 weeks of intravenous cephalosporin, and objective memory impairment. MAIN OUTCOME MEASURES: Patients with persistent Lyme encephalopathy were compared with age-, sex-, and education-matched controls. Fully quantified assessments of rCBF and rCMR for glucose were obtained while subjects were medication-free using positron emission tomography. The CBF was assessed in 2 resting room air conditions (without snorkel and with snorkel) and 1 challenge condition (room air enhanced with carbon dioxide, ie, hypercapnia). RESULTS: Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (P < .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements. CONCLUSIONS: Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease.

PMID: 19414715 [PubMed - indexed for MEDLINE]

22. Pediatrics. 2009 May;123(5):1408.

Lyme disease: new thoughts and directions.

Nachman S.

Department of Pediatrics, State University of New York at Stony Brook, Stony Brook, New York 11794-8111, USA. sharon.nachman@stonybrook.edu

Comment on: Pediatrics. 2009 May;123(5):e829-34. Pediatrics. 2009 May;123(5):e835-41.

PMID: 19403507 [PubMed - indexed for MEDLINE]

23. Pediatrics. 2009 May;123(5):e829-34.

Prospective validation of a clinical prediction model for Lyme meningitis in children.

Garro AC, Rutman M, Simonsen K, Jaeger JL, Chapin K, Lockhart G.

Rhode Island Hospital, Pediatric Emergency Medicine, Claverick Building, 2nd Floor, Providence, RI 02906, USA. agarro@lifespan.org

Comment in: Pediatrics. 2009 May;123(5):1408.

OBJECTIVE: Lyme meningitis is difficult to differentiate from other causes of aseptic meningitis in Lyme disease-endemic regions. Parenteral antibiotics are indicated for Lyme meningitis but not viral causes of aseptic meningitis. A clinical prediction model was developed to distinguish Lyme meningitis from other causes of aseptic meningitis. Our objective was to prospectively validate this model. METHODS: Children between 2 and 18 years of age presenting to Hasbro Children's Hospital from April through October of 2006 and 2007 were enrolled if a lumbar puncture for meningitis showed a cerebrospinal fluid white blood cell count of >8 cells per microL. Cerebrospinal fluid was sent for Lyme antibody testing. The probability of Lyme meningitis was calculated by using the percentage of cerebrospinal fluid mononuclear cells, duration of headache, and presence of cranial neuropathy by using the prediction model. Definite Lyme meningitis cases were defined as cerebrospinal fluid pleocytosis with (1) positive Lyme serology confirmed by immunoblot or (2) erythema migrans rash. Possible Lyme meningitis cases were defined as cerebrospinal fluid pleocytosis with positive cerebrospinal fluid Lyme antibody. Sensitivity, specificity, and likelihood ratios for definite and possible Lyme meningitis were determined by using 10% increments of calculated probability of Lyme meningitis. RESULTS: Fifty children were enrolled, including 14 children with definite Lyme meningitis, 6 with possible Lyme meningitis, and 30 with aseptic meningitis. A calculated probability of <10% for Lyme meningitis had a negative likelihood ratio of 0.006 for definite and possible Lyme meningitis cases. A calculated probability of >50% for Lyme meningitis had a positive likelihood ratio of 100 using these definitions. CONCLUSIONS: A clinical prediction model using the percentage of cerebrospinal fluid mononuclear cells, headache duration, and presence of cranial neuropathy can differentiate children with Lyme meningitis from children with aseptic meningitis. Our findings suggest categories of low (<10%), indeterminate (10%-50%), and high (>50%) probability of Lyme meningitis.

PMID: 19403476 [PubMed - indexed for MEDLINE]

24. Z Rheumatol. 2009 May;68(3):239-52; quiz 253-4.

[Lyme borreliosis]

[Article in German]

Krause A, Fingerle V.

Rheumakliniken Berlin-Buch und Berlin-Wannsee, Immanuel-Krankenhaus, Königstr. 63, 14109, Berlin, Deutschland. a.krause@immanuel.de

Lyme borreliosis is a multi-system infectious disease that primarily affects the skin, nervous system, heart, and joints. It is caused by the tick-borne spirochete Borrelia burgdorferi sensu lato. Diagnosis is made on the basis of clinical symptoms and supported by a positive serology. Antibiotic therapy should be started immediately after the diagnosis has been established and is administered according to stage and symptoms of the disease. Doxycycline, amoxicillin, and ceftriaxone are the antibiotics of choice. Early Lyme disease is almost always cured by one antibiotic course that also prevents subsequent disease manifestations. After antibiotic therapy of late disease manifestations, symptoms resolve only slowly and remission is usually achieved after weeks or even months. Chronic or therapy-resistant disease courses and residual symptoms after therapy are rare.

PMID: 19387665 [PubMed - indexed for MEDLINE]

25. Diagn Microbiol Infect Dis. 2009 Jul;64(3):347-9. Epub 2009 Apr 18.

The C6 Lyme antibody test has low sensitivity for antibody detection in cerebrospinal fluid.

Vermeersch P, Resseler S, Nackers E, Lagrou K.

University Hospitals Leuven, Belgium.

Our aim was to evaluate the performance of the commercial Immunetics C6 Lyme ELISA assay as a screening assay for anti-Borrelia burgdorferi antibodies in cerebrospinal fluid (CSF). Sensitivity of C6 ELISA was determined in 28 consecutive patients who were diagnosed with neuroborreliosis and had evidence for intrathecal antibody synthesis on immunoblot analysis. The presence of additional bands in CSF or of bands with a stronger intensity in CSF compared with serum was considered evidence of intrathecal synthesis. All 28 patients tested borderline or positive with C6 ELISA on serum. Of the 28 CSF samples, 17 (61%) and 19 (68%) tested positive with C6 ELISA using a threshold of 0.9 and 0.5 (optical density/cutoff). The C6 Lyme ELISA tested has a low sensitivity for antibody detection in cerebrospinal fluid compared with immunoblot analysis.

PMID: 19376674 [PubMed - indexed for MEDLINE]

26. Rev Neurol Dis. 2009 Winter;6(1):4-12.

Nervous system lyme disease: diagnosis and treatment.

Halperin JJ.

Department of Neurosciences, Atlantic Neuroscience Institute, Summit, NJ, USA.

Lyme disease, the multisystem infectious disease caused by the tickborne spirochete Borrelia burgdorferi, frequently affects the peripheral and central nervous systems. The earliest indication of Lyme disease infection is usually erythema migrans. This large, typically macular erythema, often with a target-like pattern of concentric pale and red circles, gradually enlarges day by day, potentially reaching many centimeters in diameter. In a significant proportion of infected individuals, an acute disseminated phase leads to seeding elsewhere in the body. Up to 5% of patients develop cardiac involvement. In about 10% to 15% of patients, the nervous system becomes symptomatically involved. Current serologic diagnostic tools are quite useful, and standard treatment regimens are highly effective. Oral antimicrobials have been shown to be effective in European neuroborreliosis and presumably are equally potent in North American patients. Long-term antibiotic treatment does not provide any additional lasting improvement, but it is frequently associated with significant morbidity.

PMID: 19367218 [PubMed - indexed for MEDLINE]

27. Curr Probl Dermatol. 2009;37:200-6. Epub 2009 Apr 8.

What are the indications for lumbar puncture in patients with Lyme disease?

Rupprecht TA, Pfister HW.

Department of Neurology, Ludwig-Maximilians University, Munich, Germany.

Lyme neuroborreliosis (LNB) is a tick-borne disease of the nervous system, caused by the spirochete Borrelia burgdorferi. Having entered the host at the site of the tick bite, the spirochetes can initially cause a local inflammatory reaction, called erythema migrans. If left untreated, the Borrelia can disseminate in the second stage of the disease and invade the central nervous system, causing LNB. The diagnosis of LNB is based on a compatible clinical picture (meningitis, cranial neuritis or radiculoneuritis), lymphocytic pleocytosis in the cerebrospinal fluid (CSF) and intrathecal Borrelia burgdorferi-specific antibody production. As the clinical picture of LNB may be unspecific, a lumbar puncture to analyze the CSF is usually mandatory for confirmation of the suspected diagnosis. The indications for a lumbar puncture and the limitations of the different diagnostic procedures are the main topics of this review. In addition, a short overview of the epidemiology and the therapeutic principles of LNB is given. Copyright 2009 S. Karger AG, Basel.

PMID: 19367105 [PubMed - indexed for MEDLINE]

28. Curr Probl Dermatol. 2009;37:111-29. Epub 2009 Apr 8.

Treatment and prevention of Lyme disease.

Hansmann Y.

Service des Maladies Infectieuses et Tropicales, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. yves.hansmann@chru-strasbourg.fr

Randomized controlled trials have ascertained the efficiency of antibiotics in treating erythema migrans, the hallmark of early stage Lyme borreliosis. Oral amoxicillin and doxycycline are first-line treatment options, though phenoxymethylpenicillin, cefuroxime axetil and azithromycin are alternative second-line options. Treatments for secondary and tertiary Lyme borreliosis are more poorly documented, and antibiotics are not always effective. This is due to the unique pathophysiology of late Lyme borreliosis, which involves not only bacterial infection, but also immunological response. Since there is no completely reliable method of diagnosis, it is difficult to choose the proper treatment and to evaluate treatment efficacy. However, numerous studies have shown that ceftriaxone and doxycycline are the 2 most efficient antibiotics, particularly in Lyme arthritis and in neuroborreliosis. In late Lyme borreliosis, these antibiotics are less efficient, and different treatment schemes with variations in dosage or duration did not produce convincing results. Copyright 2009 S. Karger AG, Basel.

PMID: 19367098 [PubMed - indexed for MEDLINE]

29. Arch Neurol. 2009 Apr;66(4):534-5.

Bilateral facial palsy in neuroborreliosis.

Hagemann G, Aroyo IM.

Department of Neurology, Friedrich-Schiller-University, Erlanger Alle 101, 07740 Jena, Germany. hagemann@med.uni-jena.de

PMID: 19364942 [PubMed - indexed for MEDLINE]

30. Orv Hetil. 2009 Apr 19;150(16):725-32.

[Lyme borreliosis--experience of the last 25 years in Hungary]

[Article in Hungarian]

Lakos A.

Kullancsbetegségek Ambulanciája, Budapest, Visegrádi u. 14. 1132. alakos@t-online.hu

We recognized the first Hungarian Lyme patients just 25 years ago, in 1984. It was exactly 20 years ago, when we opened the Lyme Disease Outpatient Service at the Central (László) Hospital for Infectious Diseases. 15 years ago we established the financially independent Center for Tick-borne Diseases. The milestones of this work at the Center for Tick-borne Diseases are the description of a new tick-borne rickettsial illness (tick-borne lymphadenopathy), development of a Lyme immunoblot kit and an automated immunoblot reader. We described a simple and reliable method for detection of intrathecal borrelia antibody synthesis which is necessary for the diagnosis of neuroborreliosis. We also developed and routinely apply the comparative immunoblot assay for the evaluation of serological progression and/or regression, which can help the clinicians to decide whether a serological reaction is resulted from a previous healed or an active borrelia infection. We studied the pregnancy outcome of borrelia infected mothers and provided that untreated borrelia infection is associated with higher chance of adverse pregnancy outcome.

PMID: 19362925 [PubMed - indexed for MEDLINE]

31. AJNR Am J Neuroradiol. 2009 Jun;30(6):1079-87. Epub 2009 Apr 3.

Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis.

Hildenbrand P, Craven DE, Jones R, Nemeskal P.

Department of Radiology, Lahey Clinic Medical Center, Burlington, MA 01805, USA. Hildenbrand@lahey.org

Lyme disease has a worldwide distribution and is the most common vector-borne disease in the United States. Incidence, clinical manifestations, and presentations vary by geography, season, and recreational habits. Lyme neuroborreliosis (LNB) is neurologic involvement secondary to systemic infection by the spirochete Borrelia burgdorferi in the United States and by Borrelia garinii or Borrelia afzelii species in Europe. Enhanced awareness of the clinical presentation of Lyme disease allows inclusion of LNB in the imaging differential diagnosis of facial neuritis, multiple enhancing cranial nerves, enhancing noncompressive radiculitis, and pediatric leptomeningitis with white matter hyperintensities on MR imaging. The MR imaging white matter appearance of successfully treated LNB and multiple sclerosis display sufficient similarity to suggest a common autoimmune pathogenesis for both. This review highlights differences in the epidemiology, clinical manifestations, diagnosis, and management of Lyme disease in the United States, Europe, and Asia, with an emphasis on neurologic manifestations and neuroimaging.

PMID: 19346313 [PubMed - indexed for MEDLINE]

32. Clin Immunol. 2009 Jul;132(1):93-102. Epub 2009 Apr 2.

Strong IgG antibody responses to Borrelia burgdorferi glycolipids in patients with Lyme arthritis, a late manifestation of the infection.

Jones KL, Seward RJ, Ben-Menachem G, Glickstein LJ, Costello CE, Steere AC.

Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

In this study, the membrane lipids of B. burgdorferi were separated into 16 fractions; the components in each fraction were identified, and the immunogenicity of each fraction was determined by ELISA using sera from Lyme disease patients. Only the 2 glycolipids, acylated cholesteryl galactoside (ACG, BbGL-I) and monogalactosyl diacylglycerol (MgalD, BbGL-II), were immunogenic. Early in the infection, 24 of 84 patients (29%) who were convalescent from erythema migrans and 19 of the 35 patients (54%) with neuroborreliosis had weak IgG responses to purified MgalD, and a smaller percentage of patients had early responses to synthetic ACG. However, almost all of 75 patients with Lyme arthritis, a late disease manifestation, had strong IgG reactivity with both glycolipids. Thus, almost all patients with Lyme arthritis have strong IgG antibody responses to B. burgdorferi glycolipid antigens.

PMCID: 2752957 PMID: 19342303 [PubMed - indexed for MEDLINE]

33. Eur J Neurol. 2009 May;16(5):639-42. Epub 2009 Mar 20.

Tumefactive demyelinating disease treated with decompressive craniectomy.

Nilsson P, Larsson EM, Kahlon B, Nordström CH, Norrving B.

Department of Neurology, Clinical Sciences Lund, Lund University, Sweden. petra.c.nilsson@skane.se

Comment in: Eur J Neurol. 2009 May;16(5):e102.

BACKGROUND: Tumefactive demyelinating disease (TDD) is a rare primary demyelinating disease with diagnostic and therapeutic challenges. METHODS AND RESULTS: We report a 50-year old woman with TDD successfully treated with decompressive craniectomy and corticosteroids. The patient presented with seizures, subacute progressive hemispheric syndrome, and a tumourlike abnormality on MRI. Demyelinating disease was initially considered unlikely. Due to a rapidly evolving herniation syndrome hemicraniectomy was performed. Outcome was favourable with only very mild neurological deficits 6 weeks later. CONCLUSION: TDD should be considered as a differential diagnosis in tumour-like presentations, and appears to have distinctive neuroimaging features. In the advent of treatement failure from high dose corticosteroids and plasmapheresis and development of severe mass effect, decompressive hemicraniectomy is an important treatment option.

PMID: 19309337 [PubMed - indexed for MEDLINE]

34. Rev Med Chir Soc Med Nat Iasi. 2008 Apr-Jun;112(2):496-501.

[Results of etiologic diagnosis in clinical syndrome consistent with acute and chronic borreliosis]

[Article in Romanian]

Persecă T, Feder A, Molnar GB.

Institutul de Sănătate Publică, Prof. Dr. Iuliu Moldovan" Cluj Napoca.

Borreliosis is a multisystem infection, which in the absence of adequate diagnosis and clinical management, may develop towards various clinical forms of chronic pathology. Due to the heterogeneity of clinical manifestations it is known under more names: erythema migrans, Lyme disease, neuroborreliosis etc. MATERIAL AND METHOD: Taking into account the present interest and the weight in pathology of syndromes consistent with the suspicion of a Borrelia spp. infection, since 2002 we applied in current practice the investigation of this etiology. There have been investigated 481 subjects, clinically suspected of Borrelia spp. infection that had historical risk of tick bite and cases of serous meningitis, after exclusion of usual etiology. Tests were performed on ELISA kits with standardised immunoreagents and recently, for result validation, on Western immunoblot kits (WB). RESULTS: Our results revealed the Borrelia etiology in 32% of cases (27.96-36.29% CI = 95%) at the screening, value expressed by the persistent positivity of the specific immunoglobulins (Ig) IgM (80.5%) and IgM+IgG (19.5%). Historic infection, represented exclusively by IgG positivity, was present in 8.6% (5.87-11.98% CI = 95%) from the cases that were negative for IgM (68%, 63.71-72.04%, CI = 95%). This weight is superposable with the results obtained in investigating a comparable sample of healthy individuals (193 subjects with 6.74% historical IgG, 3.79-10.96%, CI = 95%). Based on these results, it can be considered that ELISA procedure is useful and of reliable prognosis value for screening the Borrelia spp. etiology, the next step, taking into account the higher sensitivity of WB, being WB procedure which is useful for confirmation of ELISA positive cases and for treatment efficiency surveillance. The results prove that Borrelia spp. infections are a public health issue, which due to the diversity of clinical manifestations and diagnosis difficulties need repeated and complex laboratory investigations.

PMID: 19295026 [PubMed - indexed for MEDLINE]

35. Joint Bone Spine. 2009 May;76(3):293-5. Epub 2009 Mar 16.

Atypical forms of syphilis: two cases.

Avenel G, Goëb V, Abboud P, Ait-Abdesselam T, Vittecoq O.

Service de Rhumatologie, CHU-Hôpitaux de Rouen, & Inserm, U905, IFRMP23, Institut de Biologie Clinique, Rouen, France. avenel_gilles@hotmail.fr

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. A chancre usually develops initially. Organ involvement and neurological complications may occur, sometimes several years after the initial exposure. We managed two patients with syphilis responsible for joint or neurological manifestations, diagnosed in 2008. One patient presented with oligoarthritis involving the knees and right elbow, coinciding with a maculopapular and pustular eruption. In the other patient, meningoradiculitis involving the T8, T9, and T10 metameres prompted a test for Lyme disease, which was weakly positive, leading to evaluation for false-positivity due to a cross-reaction. Neither patient was infected with the HIV.

PMID: 19289298 [PubMed - indexed for MEDLINE]

36. Scand J Infect Dis. 2009;41(5):355-62.

Laboratory data in children with Lyme neuroborreliosis, relation to clinical presentation and duration of symptoms.

Tveitnes D, Øymar K, Natås O.

Departments of Paediatrics, University of Bergen, Norway.

The occurrence of IgM and IgG antibodies against Borrelia burgdoferi in serum and cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies (antibody index) were studied in relation to clinical presentation and the duration of symptoms before diagnosis in 146 children diagnosed with neuroborreliosis. Lymphocytic meningitis was demonstrated in 141 of these children. Levels of white blood cells (WBC) and protein in CSF correlated significantly to numbers of d with symptoms. Children were divided into 3 clinical groups: A (n = 37): only cranial neuropathy; B (n = 68): both cranial neuropathy and other neurological symptoms; C (n = 41): neurological symptoms without cranial neuropathy. Levels of WBC and protein in CSF as well as the proportion of children with antibodies in serum and CSF were generally lowest in group A, intermediate in group B and highest in group C. The proportion of children with antibodies in serum and CSF and a positive antibody index was also related to duration of symptoms; the antibody index was present in 51% of children with symptoms < or = 7 d, and in 80% of children with symptoms > 7 d (p<0.01). The clinical presentation and duration of symptoms must be considered when interpreting laboratory data in children with suspected neuroborreliosis.

PMID: 19253089 [PubMed - indexed for MEDLINE]

37. Wien Med Wochenschr. 2009;159(1-2):58-61.

Normal pressure hydrocephalus or neuroborreliosis?

Aboul-Enein F, Kristoferitsch W.

Department of Neurology, Sozialmedizinisches Zentrum Ost, Donauspital, Vienna, Austria. fahmy.aboul-enein@chello.at

BACKGROUND: An 80-year-old woman presented with progressive cognitive decline and with a 6-month history of gait ataxia. Brain MRI depicted enlarged ventricles and periventricular lesions. Clinical improvement after CSF spinal tap test suggested a normal pressure hydrocephalus syndrome. But CSF pleocytosis with activated lymphocytes and plasma cells and intrathecal Borrelia burgdorferi specific antibody production led to the diagnosis of active Lyme neuroborreliosis. Clinical symptoms of NPH resolved after a course of ceftriaxone. METHODS: Neurological examination, MMSE, brain MRI, lumbar puncture, spinal tap test. RESULTS: Dementia due Borrelia burgdorferi infection with chronic meningitis was reversible after treatment with iv.2 g ceftriaxone per day for 4 weeks. CONCLUSIONS: Rare but treatable dementias must be diagnosed promptly to slow down or even reverse cognitive decline.

PMID: 19225737 [PubMed - indexed for MEDLINE]

38. Przegl Epidemiol. 2008;62(4):793-800.

[Evaluation of cerebrospinal fluid serotonin (5-HT) concentration in patients with post-Lyme disease syndrome--preliminary study]

[Article in Polish]

Kepa L, Oczko-Grzesik B, Badura-Glombik T.

Oddział Chorób Zakaźnych Slaskiego Uniwersytetu Medycznego w Bytomiu.

The aim of the study was evaluation of usefulness of cerebrospinal fluid (CSF) serotonin level examination in diagnostics of post-Lyme disease syndrome. The study was performed in 16 subjects. In all individuals CSF serotonin concentration was estimated on the 1st day of hospitalization. In patients with depressive and cognitive impairments, proved in neuropsychological tests, - group I--mean CSF serotonin concentration was 1,26 ng/ml, whereas in subjects without abnormalities in tests--group II--respectively--3,87 ng/ml. The difference of mean CSF serotonin levels was statistically significant (p<0,01). The obtained results indicate usefulness of this CSF parameter, besides neuropsychological tests, in objective evaluation of clinical state in patients with post-Lyme disease syndrome.

PMID: 19209742 [PubMed - indexed for MEDLINE]

39. Przegl Lek. 2008;65(11):810-2.

[Neuroboreliosis with motoric disturbations in the developmental age]

[Article in Polish]

Skowronek-Bała B, Wesołowska E, Gergont A, Kaciński M.

Klinika Neurologii Dzieciecej, Uniwersytet Jagielloński Collegium Medicum, Kraków. neupedkr@cm-uj.krakow.pl

BACKGROUND: Neurological symptoms develop in 10-20% of children suffered borreliosis (LD). AIM OF THE STUDY: It was a presentation of motoric disturbances of neuroboreliosis in children. MATERIAL AND METHODS: Children with neuroborreliosis and other neurological diseases were admitted to the University hospital during 2005-2007. Of these 13 patients, there were 9 males and 4 females, ranging in age between 3-17 years. Neurological diagnostic was performed using ELISA Biomedica kit and western blot bands. A 2-6 week sequential treatment with either iv ceftazidime or amoxicillin and oral doxycycline or amoxicillin was provided. Children were monitored regularly during the next 4-36 months. RESULTS: The 13 children with neuroborreliosis constitute 0.5% of the pediatric neurology department's patients. The clinical manifestation of LD were usual and unusual from patient to patient. They included four cases of facial nerve paralysis (with bilateral paralysis in one case), in three cases transverse myelitis and in a single case, hemiparesis, and oculomotor nerve paresis. In 9/13 children motoric disturbances of neuroboreliosis was diagnosed indeed. The antibiotic treatment was successful in 6 patients and only partially effective in 3 children with facial nerve paralysis. CONCLUSION: The most common symptoms of neuroborreliosis in children was motoric dysfunction.

PMID: 19205367 [PubMed - indexed for MEDLINE]

40. Neurology. 2009 Jan 27;72(4):385-6; discussion 386.

Re: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Prolonged Lyme disease treatment: enough is enough.

Szantyr BM.

Comment on: Neurology. 2009 Jan 27;72(4):384-5; author reply 385.

PMID: 19180683 [PubMed - indexed for MEDLINE]

41. Neurology. 2009 Jan 27;72(4):384-5; author reply 385.

Re: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Prolonged Lyme disease treatment: enough is enough.

Maloney EL.

Comment in: Neurology. 2009 Jan 27;72(4):385-6; discussion 386.

Comment on: Neurology. 2008 Mar 25;70(13):986-7. Neurology. 2008 Mar 25;70(13):992-1003.

PMID: 19180682 [PubMed - indexed for MEDLINE]

42. Neurology. 2009 Jan 27;72(4):383-4; author reply 384.

Re: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Prolonged Lyme disease treatment: enough is enough.

Marques A, Shaw P, Schmid CH, Steere A, Kaplan RF, Hassett A, Shapiro E, Wormser GP.

Comment on: Neurology. 2008 Mar 25;70(13):992-1003.

PMID: 19171842 [PubMed - indexed for MEDLINE]

43. Neurology. 2009 Jan 20;72(3):291.

Ocular flutter as the first manifestation of Lyme disease.

Gyllenborg J, Milea D.

Department of Neurology, Glostrup Hospital, University of Copenhagen, 57, Nordre Ringvej, DK-2600 Glostrup, Denmark. jesper@gyllenborg.dk

PMID: 19153379 [PubMed - indexed for MEDLINE]

44. Joint Bone Spine. 2009 Mar;76(2):202-4. Epub 2009 Jan 14.

Parsonage-Turner syndrome revealing Lyme borreliosis.

Wendling D, Sevrin P, Bouchaud-Chabot A, Chabroux A, Toussirot E, Bardin T, Michel F.

Service de Rhumatologie, CHU Jean Minjoz, et EA 3186 Agents Pathogènes et Inflammation Université de Franche-Comté, Boulevard Fleming, 25030 Besançon, France. dwendling@chu-besancon.fr

Parsonage-Turner syndrome, also known as acute brachial neuritis or neuralgic amyotrophy, can be caused by various infectious agents. We report on four patients who experienced Parsonage-Turner syndrome as the first manifestation of Lyme disease. The clinical picture was typical, with acute shoulder pain followed rapidly by weakness and wasting of the shoulder girdle muscles. Electrophysiological testing showed denervation. A single patient reported erythema chronicum migrans after a tick bite. Examination of the cerebrospinal fluid showed lymphocytosis and protein elevation in 3 patients. Serological tests for Lyme disease were positive in the serum in all 4 patients and in the cerebrospinal fluid in 2 patients. Antibiotic therapy ensured a favorable outcome in all 4 cases. Two patients achieved a full recovery within 6 months. Parsonage-Turner syndrome should be added to the list of manifestations of neuroborreliosis. Serological tests for Lyme disease should be performed routinely in patients with Parsonage-Turner syndrome.

PMID: 19147387 [PubMed - indexed for MEDLINE]

45. Acta Neurol Belg. 2008 Sep;108(3):103-6.

Acute ischaemic pontine stroke revealing lyme neuroborreliosis in a young adult.

Van Snick S, Duprez TP, Kabamba B, Van De Wyngaert FA, Sindic CJ.

Service de Neurologie, Université catholique de Louvain, Brussels, Belgium.

We report the case of a 23-year-old male patient who suddenly developed right hemiparesis, cerebellar ataxia, dysarthria, and bilateral dysmetria. Brain magnetic resonance (MR) examination demonstrated hyperacute ischaemic lesions within the pons. CSF analysis revealed a high protein content, lymphocytic pleocytosis, and oligoclonal IgG bands not present in the serum. Elevated IgM and IgG anti-Borrelia burgdorferi antibodies were shown in both serum and CSF samples, associated with an intrathecal synthesis of these antibodies. Ischaemic CNS lesions have been rarely observed as the first manifestation of Lyme neuroborreliosis. The putative mechanism for parenchymal ischaemia is the local extension of inflammatory changes from meninges to the wall of penetrating arterioles.

PMID: 19115674 [PubMed - indexed for MEDLINE]

46. Lakartidningen. 2008 Nov 19-25;105(47):3455.

[Bell palsy: Exclude neuroborreliosis prior to cortisone administration]

[Article in Swedish]

Strömberg A.

Comment on: Lakartidningen. 2008 Oct 15-21;105(42):2942.

PMID: 19112978 [PubMed - indexed for MEDLINE]

47. Pol Merkur Lekarski. 2008 Sep;25(147):254-6.

[Re-infection with Borrelia burgdorferi s.l in a patient with a history of neuroborreliosis--case report]

[Article in Polish]

Grygorczuk S, Pancewicz S, Zajkowska J, Kondrusik M, Swierzbińska R, Moniuszko A, Pawlak-Zalewska W.

Uniwersytet Medyczny w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji. neuroin@amb.edu.pl

Reinfection with Borrelia burgdorferi s.l., which is likely in highly exposed persons, has not been described in Poland so far. Symptoms of Lyme arthritis, preceded by typical skin lesion (erythema migrans) appeared in 46 years old women 5 years after successful treatment of borrelial meningitis. Re-appearance of symptoms of Lyme borreliosis following localized skin lesion, after a long asymptomatic period, as well as accompanying increase in specific antibodies, point to reinfection with Borrelia burgdorferi sensu lato. Different localization of systemic symptoms during two episodes of Lyme disease suggests infection with distinct genospecies of B. burgdorferi s.l. This case confirms risk of recurrent infections with different B. burgdorferi s.l. genospecies in inhabitants of highly endemic areas in the north-east of Poland, which may pose necessity of repeated antibiotic treatment.

PMID: 19112843 [PubMed - indexed for MEDLINE]

48. Am J Emerg Med. 2008 Nov;26(9):1069.e5-6.

Acute ataxia in a 4-year-old boy: a case of Lyme disease neuroborreliosis.

Lopez MD, Wise C.

Departments of Emergency Medicine and Pediatrics Medical College of Georgia, Augusta, CA 30912, USA. mlopez@mcg.edu

We present a case of a 4-year-old who presented to the emergency department with an unsteady gait for 2 days. Ataxia is a rare but known manifestation of cerebellar involvement in Lyme disease. A 4-year-old (17 kg) boy with no significant medical history presented to the emergency department (ED) with history of nonbloody emesis for 2 weeks and an unsteady gait for 2 days. Over the past 2 days, his gait had gotten progressively worse until he was unable to walk without assistance. The vomiting would usually occur 1 hour after eating meals. He had also complained of a single headache, which occurred approximately 10 days before admission. The headache did not occur in the early morning hours or wake him up from his sleep. His appetite for the weeks before admission had progressively decreased, and he had also become more irritable, especially when stimulated. He had increased fatigue for the week before presentation. His parents denied any fever, rhinorrhea, cough, diarrhea, rash, bruising, bleeding, or hematuria. The patient denied any abdominal pain or headache while in the ED.

PMID: 19091290 [PubMed - indexed for MEDLINE]

49. Parasitol Res. 2008 Dec;103 Suppl 1:S117-20. Epub 2008 Nov 23.

Epidemiological situation of Lyme borreliosis in germany: surveillance data from six Eastern German States, 2002 to 2006.

Fülöp B, Poggensee G.

Department of Infectious Disease Epidemiology, Robert-Koch Institute, Berlin, Germany.

Lyme borreliosis is the most frequent vector-borne disease in Germany; however, in only six states in the eastern part of Germany (Berlin, Brandenburg, Mecklenburg Western Pomerania, Saxony, Saxony-Anhalt and Thuringia) is early Lyme disease (erythema migrans and early neuroborreliosis) a notifiable disease. Between 2002 and 2006, the incidence increased constantly; in 2002, the incidence per 100,000 inhabitants was 17.8 and rose by 110% to 37.3 in 2006. The incidence among the states varies greatly with Brandenburg accounting for the highest incidence (77.6 per 100,000 inhabitants) and Berlin for the lowest incidence (5.7 per 100,00 inhabitants). The age distribution is bimodal with incidence peaks in childhood between the ages 5 to 9 and in adulthood in the age group 65 to 69 years. In general, females are more frequently affected than males (55% versus 45%). Erythema migrans and early neuroborreliosis affected 20,787 patients (90%) and 799 patients (3%), respectively. Around 70% of all cases occurred between June and September. Further studies are needed to answer the question to which extent the annual increase can be related to a changing epidemiological situation or to other factors such as growing awareness, better diagnostic tools and changing recreational habits.

PMID: 19030893 [PubMed - indexed for MEDLINE]

50. Scand J Infect Dis. 2009;41(2):88-94.

Clinical characteristics of childhood Lyme neuroborreliosis in an endemic area of northern Europe.

Øymar K, Tveitnes D.

Department of Paediatrics, Stavanger University Hospital, Stavanger, Norway. oykn@sus.no

Neuroborreliosis may be caused by different species of Borrelia burgdorferi (BB) and the clinical presentation of neuroborreliosis in children may differ between geographical areas due to occurrence of different BB genospecies. The aim of this study was to evaluate the clinical characteristics in children with neuroborreliosis in an endemic area of Scandinavia. During 1996-2006, children with suspected neuroborreliosis referred to Stavanger University Hospital were investigated by a standard procedure including a lumbar puncture. A total of 143 children were diagnosed with neuroborreliosis, and all cases were diagnosed from April to December. The most common clinical presentations were symptoms of mild meningitis (75%) and/or facial nerve palsy (69%). Radicular pain was present in only 10 children. In all but 5 children, laboratory signs of meningitis were present. Erythema migrans preceded the neurological symptoms in only 27% of the children. In conclusion, we have found that in an endemic area of northern Europe, meningitis is present in the majority of children with neuroborreliosis, and that symptoms of a mild meningitis or facial nerve palsy are the most common presentations.

PMID: 19065451 [PubMed - indexed for MEDLINE]

51. Pediatr Infect Dis J. 2008 Dec;27(12):1089-94.

Lyme neuroborreliosis in children: a prospective study of clinical features, prognosis, and outcome.

Skogman BH, Croner S, Nordwall M, Eknefelt M, Ernerudh J, Forsberg P.

Pediatric Clinic at the University Hospital, Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. hedinskogman@ltdalarna.se

BACKGROUND: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery. MATERIAL/METHODS: Children being evaluated for NB (n = 177) in southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but no Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid. Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174). RESULTS: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified. CONCLUSIONS: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.

PMID: 19008771 [PubMed - indexed for MEDLINE]

52. J Vis Exp. 2007;(10):527. Epub 2007 Dec 4.

Isolation of mononuclear cells from the central nervous system of rats with EAE.

Beeton C, Chandy KG.

Department of Physiology and Biophysics, University of California, Irvine, USA. cbeeton@uci.edu

Whether studying an autoimmune disease directed to the central nervous system (CNS), such as experimental autoimmune encephalomyelitis (EAE, 1), or the immune response to an infection of the CNS, such as poliomyelitis, Lyme neuroborreliosis, or neurosyphilis, it is often necessary to isolate the CNS-infiltrating immune cells.In this video-protocol we demonstrate how to isolate mononuclear cells (MNCs) from the CNS of a rat with EAE. The first step of this procedure requires a cardiac perfusion of the rodent with a saline solution to ensure that no blood remains in the blood vessels irrigating the CNS. Any blood contamination will artificially increase the number of apparent CNS-infiltrating MNCs and may alter the apparent composition of the immune infiltrate. We then demonstrate how to remove the brain and spinal cord of the rat for subsequent dilaceration to prepare a single-cell suspension. This suspension is separated on a two-layer Percoll gradient to isolate the MNCs. After washing, these cells are then ready to undergo any required procedure. Mononuclear cells isolated using this procedure are viable and can be used for electrophysiology, flow cytometry (FACS), or biochemistry. If the technique is performed under sterile conditions (using sterile instruments in a tissue culture hood) the cells can also be grown in tissue culture medium. A given cell population can be further purified using either magnetic separation procedures or a FACS.

PMCID: 2557079 PMID: 18989401 [PubMed - indexed for MEDLINE]

53. Int J Dermatol. 2008 Oct;47(10):1004-10.

Examination of specific DNA by PCR in patients with different forms of Lyme borreliosis.

Pícha D, Moravcová L, Holecková D, Zd'árský E, Valesová M, Maresová V, Hercogová J, Vanousová D.

Charles University, 2nd Medical School, 1st Clinic for Infectious Diseases, Teaching Hospital Bulovka, Prague, Czech Republic. dusan.picha@fnb.cz

BACKGROUND: Borrelial specific DNA was examined in a group of 62 patients with different forms of Lyme borreliosis (LB) (32 patients suffered from neuroborreliosis, 19 manifested erythema migrans, and 11 joint involvement). METHODS: Nested-PCR system with five newly derived primers was used in parallel. The study was organized prospectively, the presence of DNA was tested for plasma, CSF, joint fluid and urine before treatment, and plasma, joint fluid and urine were examined after treatment. RESULTS: Before therapy, 36 patients (58.1%) were DNA positive on the whole; 21 positive patients (65.6%) were found in the group of neuroborreliosis, 8 (42.1%) showed signs of skin involvement, and 7 (63.6%) were positive in arthritis. After treatment, 11 patients (36.7%) were positive in neuroborreliosis, 3 (17.6%) in skin form, and 6 (54.5%) in joint form of LB. Among 97 positive amplifications the most frequent target was found in primer corresponding with 16S rDNA (50 samples, 51.5%). Lower but very similar results were obtained with primers for OspA (18 positive amplifications; 18.6%), OspC (13 positive amplifications; 13.4%), and flagellin (13 positive amplifications; 13.4%). There were 11 patients in whom only DNA and no specific antibodies were found. CONCLUSIONS: Specific DNA was found in all clinical groups of LB with similar sensitivity. Examination of the borrelial DNA in urine displayed the same sensitivity as in CSF and had a two times higher sensitivity than in plasma.

PMID: 18986344 [PubMed - indexed for MEDLINE]

54. MMW Fortschr Med. 2008 Sep 18;150(38):35.

[Facial nerve paresis]

[Article in German]

Glocker FX.

MediClin Seidel-Klinik Bad Bellingen, Zentrum für Rheumatologie, Wirbelsäulenleiden und Neuromuskuläre Erkrankungen, Hebelweg 4, D-79415 Bad Bellingen, franz.glocker@uniklinik-freiburg.de

PMID: 18983050 [PubMed - indexed for MEDLINE]

55. Ugeskr Laeger. 2008 Oct 20;170(43):3420-4.

[Neuroborreliosis in North Jutland]

[Article in Danish]

Krabbe NV, Jensen TE, Nielsen HI.

Infektionsmedicinsk Afdeling, Aalborg Sygehus, DK-9000 Aalborg. henrik.nielsen@rn.dk

INTRODUCTION: Infection with Borrelia sp. is common in Denmark, and dissemination to the central nervous system (neuroborreliosis) may develop in a minority of cases with varying symptoms. We here present a population-based review of neuroborreliosis in Northern Denmark. MATERIAL AND METHODS: We identified 84 patients with neuroborreliosis from North Jutland County in the period 1998-2006 based on the demonstration of intrathecal antibody production to B. burgdorferi, and we reviewed the medical records for symptoms, diagnosis, treatment and outcome. RESULTS: Paresis of the facialis nerve and fever were more common among children than among adults, whereas radiculitis and sensory symptoms were more frequent among adults than among children. Eight of 84 patients (10%) reported only nonneurological symptoms. All patients were treated with antibiotics for at least ten days. Information on outcome was available for 76 patients (90%) of whom 16 (19%) had persistent sequelae after six months. Patients with persistent sequelae had a lower cell count in the cerebrospinal fluid than patients without sequelae. Patients with a diagnostic delay of less than 28 days had less sequelae than patients with a delay longer than 28 days. CONCLUSION: Symptoms in neuroborreliosis are heterogeneous, although some symptoms are common in children while others are predominant in adults. Early diagnosis of neuroborreliosis potentially improves the outcome.

PMID: 18976599 [PubMed - indexed for MEDLINE]

56. Pediatrics. 2008 Nov;122(5):e1080-5. Epub 2008 Oct 17.

Clinical predictors of Lyme disease among children with a peripheral facial palsy at an emergency department in a Lyme disease-endemic area.

Nigrovic LE, Thompson AD, Fine AM, Kimia A.

Division of Emergency Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA. lise.nigrovic@childrens.harvard.edu

INTRODUCTION: Although Lyme disease can cause peripheral facial palsy in Lyme disease-endemic areas, diagnostic predictors in children have not been described. OBJECTIVE: Our goal was to determine clinical predictors of Lyme disease as the etiology of peripheral facial palsy in children presenting to an emergency department in a Lyme disease-endemic area. METHODS: We reviewed all available electronic medical charts of children

PMID: 18931349 [PubMed - indexed for MEDLINE]

57. Can Fam Physician. 2008 Oct;54(10):1381-4.

Lyme disease: a zoonotic disease of increasing importance to Canadians.

Ogden NH, Artsob H, Lindsay LR, Sockett PN.

Centre for Foodborne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada. Nicholas_Ogden@phac-aspc.gc.ca

PMCID: 2567255 PMID: 18854461 [PubMed - indexed for MEDLINE]

58. Tidsskr Nor Laegeforen. 2008 Sep 25;128(18):2060-1.

[Increase in childhood neuroborreliosis]

[Article in Norwegian]

Øymar K, Tveitnes D.

Kvinne-Barneklinikken, Stavanger universitetssjukehus, 4068 Stavanger. oykn@sus.no

BACKGROUND: Data from the Norwegian Institute of Public Health suggest that the incidence of neuroborreliosis has increased in Norway during recent years. However, this may also be due to a change in diagnostic procedures and increased awareness of the disease. MATERIAL AND METHODS: At the pediatric department in Stavanger University Hospital we have systematically diagnosed and registered data on all children with neuroborreliosis in a database since 1996. RESULTS: The number of children diagnosed with neuroborreliosis increased in the entire period from 1996 to 2007 (p < 0.001). The median number of children diagnosed per year increased from 10.5 to 18.5 from the first to the second 6 year-period (p = 0.004). INTERPRETATION: There has been a real increase in childhood neuroborreliosis during the last 12 years.

PMID: 18846121 [PubMed - indexed for MEDLINE]

59. Am J Pathol. 2008 Nov;173(5):1415-27. Epub 2008 Oct 2.

Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis.

Ramesh G, Borda JT, Dufour J, Kaushal D, Ramamoorthy R, Lackner AA, Philipp MT.

Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferi induces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivo model that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferi to penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P = 0.005) for the cytokine tumor necrosis factor-alpha and 2.31-fold (P = 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1beta, COX-2, and CXCL13 were visualized in glial cells in situ by immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivo intraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferi produces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis.

PMCID: 2570132 PMID: 18832582 [PubMed - indexed for MEDLINE]

60. Int J Immunopathol Pharmacol. 2008 Jul-Sep;21(3):553-66.

Antibodies as predictors of complex autoimmune diseases and cancer.

Vojdani A.

Immunosciences Lab., Inc., Beverly Hills, CA, USA. immunsci@ix.netcom.com

Erratum in: Int J Immunopathol Pharmacol. 2008 Oct-Dec;21(4):following 1051.

The pathologic role of autoantibodies in many autoimmune diseases is widely accepted. An enzyme immunoassay was used for measurement of antibodies against disease-specific antigens and etiologic agents for cross-reactive antigens associated with them. This antibody assay was applied to a panel of antigens for the detection of different neuroautoimmune diseases that included multiple sclerosis, motor peripheral neuropathies, multifocal motor neuropathy, amyotrophic lateral sclerosis, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection. We studied women with pregnancies complicated by neural tube defect, neuroborreliosis, autism and patients with possible somatic hypermutation. Antibodies were also measured against antigens and etiologic agents associated with primary biliary cirrhosis and chronic obstructive pulmonary disease. And, finally, antibodies were measured against several tumor antigens or peptides which are expressed in prostatic, breast and colon tissues. This panel of different autoantibodies was applied to 290 patients with neuroautoimmune disorders, cancer, and possible somatic hypermutation. The levels of these antibodies against different tissue-specific antigens and etiologic agents associated with them were significantly elevated in patients versus controls. We hope that this novel 96 antigen-specific ELISA will be used in additional studies that will prove its clinical efficacy, not only for the early diagnosis of many neuroautoimmune, liver and lung autoimmune disorders, but also for prognosis and the implementation of preventive steps for many complex diseases.

PMID: 18831922 [PubMed - indexed for MEDLINE]

61. J Neuroinflammation. 2008 Sep 25;5:40.

Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis.

Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL.

Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada. judithmiklossy@bluewin.ch

BACKGROUND: The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis. METHOD: Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes. RESULTS: Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex. CONCLUSION: The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form.

PMCID: 2564911 PMID: 18817547 [PubMed - indexed for MEDLINE]

62. Cerebrovasc Dis. 2008;26(5):455-61. Epub 2008 Sep 23.

Cerebral vasculitis and stroke in Lyme neuroborreliosis. Two case reports and review of current knowledge.

Topakian R, Stieglbauer K, Nussbaumer K, Aichner FT.

Department of Neurology, Academic Teaching Hospital Wagner-Jauregg, Linz, Austria. raffi.topakian@hotmail.com

We report on 2 patients with cerebral vasculitis and stroke due to Lyme neuroborreliosis (LNB). Both patients had a prodromal stage involving headaches, and showed meningeal enhancement in addition to ischemic infarctions on brain magnetic resonance imaging and diffuse vasculitis on vascular imaging. Serological and cerebrospinal (CSF) fluid studies confirmed the diagnosis of active LNB. Ceftriaxone for 3 weeks led to an excellent recovery and improvements in the CSF examination findings. Stroke physicians should be aware of this rare presentation of LNB. A review of the current knowledge on cerebral vasculitis due to LNB is provided. 2008 S. Karger AG, Basel.

PMID: 18810231 [PubMed - indexed for MEDLINE]

63. Infection. 2008 Oct;36(5):463-6. Epub 2008 Sep 13.

Borrelia antibodies in children evaluated for Lyme neuroborreliosis.

Bennet R, Lindgren V, Zweygberg Wirgart B.

Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. rutger.bennet@karolinska.se

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

PMID: 18791841 [PubMed - indexed for MEDLINE]

64. J Ky Med Assoc. 2008 Jul;106(7):317-9.

Coma falsely attributed to Lyme disease.

Manalai P, Bhalavat RM, Dobbs MR, Lippmann S.

University of Louisville School of Medicine, Department of Psychiatry and Behavioral Science, KY 40202, USA.

Neuroborreliosis has very low prevalence in Kentucky and coma due to Lyme disease is uncommon in North America. A patient diagnosed with Lyme disease in Kentucky, based on coma, typical inflammatory changes on brain imaging, and a positive ELISA resulted in an erroneous clinical impression. Diagnosis should have been confirmed by a positive result on Western Blot, polymerase chain reaction (PCR), or real-time polymerase chain reaction (RT-PCR) testing. Physicians must apply careful consideration before diagnosing a rare disease in areas where that condition is uncommon without first eliminating other differential options. Neuroborreliosis clinicalfindings are nonspecific and often require confirmatory testing, especially in nonclassical case presentations.

PMID: 18777697 [PubMed - indexed for MEDLINE]

65. Rev Neurol (Paris). 2009 Mar;165(3):273-7. Epub 2008 Aug 28.

[Recurrent ischemic strokes revealing Lyme meningovascularitis]

[Article in French]

Sparsa L, Blanc F, Lauer V, Cretin B, Marescaux C, Wolff V.

Département de neurologie, hôpital Civil, hôpitaux universitaires, 1, place de l'Hôpital, 6700 Strasbourg, France.

INTRODUCTION: Infectious vascularitis is an unusual cause of ischemic stroke (IS). We report a case of Lyme meningovascularitis complicated with multiple IS. CASE REPORT: A 64-year-old man, without any cardiovascular risk factor, was admitted for a right hemiparesia with a left thalamic hypodensity on the initial cerebral CT scan. No cause for this presumed IS could be identified. Later, the patient developed cognitive impairment and a bilateral cerebellar syndrome. Multiple infarcts and multiple intracranial stenosis were seen on cerebral MRI with magnetic resonance angiography (MRA). Cerebrospinal fluid tests showed meningitis and positive Lyme serology with an intrathecal specific anti-Borrelia antibody index. Antibiotic treatment was followed by good biological and partial clinicoradiological outcome. CONCLUSION: The diagnosis of Lyme neuroborreliosis should be entertained as a possible cause of IS in highly endemic zones.

PMID: 18760428 [PubMed - indexed for MEDLINE]

66. Med Mal Infect. 2008 Oct;38(10):543-8.

[Results of a prospective standardized study of 30 patients with chronic neurological and cognitive disorders after tick bites]

[Article in French]

Roche Lanquetot MO, Ader F, Durand MC, Carlier R, Defferriere H, Dinh A, Herrmann JL, Guillemot D, Perronne C, Salomon J.

Unité de Maladies Infectieuses, Inserm U657, CHU Raymond-Poincaré, Assistance publique-Hôpitaux de Paris, Université de Versailles Saint-Quentin-en-Yvelines, 104, boulevard Raymond-Poincaré, 92380 Garches, France

OBJECTIVE: Patients with chronic neurological disorders and cognitive impairment after tick bites are difficult to manage despite standard antibiotic therapy for Lyme disease. We wanted to correctly assess the disorders. METHODS: Thirty patients were hospitalized for a standardized evaluation of their disorders: clinical examination, biological and serological studies, cerebral MRI, CSF study, neurophysiological exams, and neuropsychological evaluation of cognitive functions. RESULTS: Clinical and biological results were non informative. We observed significant CSF abnormalities (64%), MRI Flair pictures (41%), neurophysiological exams (47%), and cognitive evaluation (100%). CONCLUSIONS: A large and standardized evaluation should be made for each patient to improve the management and probably the treatment of these complex chronic symptoms observed after tick bites.

PMID: 18722064 [PubMed - indexed for MEDLINE]

67. Scand J Infect Dis. 2008;40(11-12):985-7.

Neuroborreliosis recurrence: reinfection or relapse?

Krabbe NV, Ejlertsen T, Nielsen H.

Department of Infectious Diseases, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.

We report the case of a 47-y-old female with documented neuroborreliosis, who had a complete recovery after 10 d of intravenous high-dose penicillin followed after 9 months by a new episode of documented neuroborreliosis. The case probably represents a rare case of true reinfection rather than relapse.

PMID: 18720254 [PubMed - indexed for MEDLINE]

68. J Clin Microbiol. 2008 Oct;46(10):3375-9. Epub 2008 Aug 20.

Validation of cultivation and PCR methods for diagnosis of Lyme neuroborreliosis.

Cerar T, Ogrinc K, Cimperman J, Lotric-Furlan S, Strle F, Ruzić-Sabljić E.

University of Ljubljana, Faculty of Medicine, Institute of Microbiology and Immunology, Zaloska 4, 1105 Ljubljana, Slovenia. tjasa.cerar@mf.uni-lj.si

Borrelial infection may manifest with a wide range of clinical signs, and in many cases, microbiological findings are essential for a proper diagnosis. This study included 48 patients with a working clinical diagnosis of Lyme neuroborreliosis, 45 patients with a working clinical diagnosis of suspected Lyme neuroborreliosis, and a control group comprising 42 patients with tick-borne encephalitis and 21 neurosurgical patients. The aim of the study was to analyze and compare findings of two PCR methods and Borrelia burgdorferi sensu lato culture results by examination of prospectively collected cerebrospinal fluid (CSF) and blood specimens from patients with clinical features of Lyme neuroborreliosis. Borrelial DNA was detected with at least one of the PCR approaches in 16/135 (11.9%) blood samples and 24/156 (15.4%) CSF samples. Using MseI restriction of PCR products of the amplified rrf-rrl region, we identified the majority of strains as Borrelia afzelii. Borreliae were isolated from 1/135 (0.7%) blood samples and from 5/156 (3.2%) CSF specimens. Using MluI restriction for characterization of isolated strains, Borrelia garinii was identified in all CSF isolates. Our study revealed that different approaches for direct demonstration of borrelial infection give distinct results, that there is an urgent need for standardization of the methods for direct detection of borrelial infection, and that the design of studies evaluating the validation of such methods should include appropriate control group(s) to enable assessment of both sensitivity and specificity.

PMCID: 2566093 PMID: 18716226 [PubMed - indexed for MEDLINE]

69. Infect Immun. 2008 Oct;76(10):4385-95. Epub 2008 Aug 11.

Toll-like receptors: insights into their possible role in the pathogenesis of lyme neuroborreliosis.

Bernardino AL, Myers TA, Alvarez X, Hasegawa A, Philipp MT.

Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana 70433, USA.

Lyme neuroborreliosis is likely caused by inflammatory effects of the tick-borne spirochete Borrelia burgdorferi on the nervous system. Microglia, the resident macrophage cells within the central nervous system (CNS), are important in initiating an immune response to microbial products. In addition, astrocytes, the major CNS glial cell type, also can contribute to brain inflammation. TLRs (Toll-like receptors) are used by glial cells to recognize pathogen-associated molecular patterns (PAMPs), mediate innate responses, and initiate an acquired immune response. Here we hypothesize that because of their PAMP specificities, TLR1, -2, -5, and -9 may be involved in the pathogenesis of Lyme neuroborreliosis. Previous reports have shown that the rhesus monkey is the only animal model to exhibit signs of Lyme neuroborreliosis. Therefore, we used primary cultures of rhesus astrocytes and microglia to determine the role of TLRs in mediating proinflammatory responses to B. burgdorferi. The results indicate that microglia and astrocytes respond to B. burgdorferi through TLR1/2 and TLR5. In addition, we observed that phagocytosis of B. burgdorferi by microglia enhances not only the expression of TLR1, -2, and -5, but also that of TLR4. Taken together, our data provide proof of the concept that astrocyte and microglial TLR1, -2, and -5 are involved in the in vivo response of primate glial cells to B. burgdorferi. The proinflammatory molecules elicited by these TLR-mediated responses could be a significant factor in the pathogenesis of Lyme neuroborreliosis.

PMCID: 2546821 PMID: 18694963 [PubMed - indexed for MEDLINE]

70. Schmerz. 2008 Oct;22(5):615-23.

[Pain and neuroborreliosis: significance, diagnosis and treatment]

[Article in German]

Rupprecht TA, Birnbaum T, Pfister HW.

Neurologische Klinik, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377 München, Deutschland.

Lyme neuroborreliosis is a tick-borne infection of the central nervous system caused by the spirochete Borrelia burgdorferi. The most frequent manifestation of neuroborreliosis in Europe is meningoradiculitis or Bannwarth's syndrome. One of its hallmarks is intense, lancinating, radicular pain, especially at night. Its characteristics are rather different to other forms of neuropathic pain in respect to the dynamics, localisation and therapeutic responses. This review therefore summarises not only the general symptoms, diagnostic procedures and therapy of Lyme neuroborreliosis, but also revises the characteristics and therapeutic options of painful meningoradiculitis in Bannwarth's syndrome.

PMID: 18688658 [PubMed - indexed for MEDLINE]

71. Med Arh. 2008;62(2):107-10.

[Lyme borreliosis in Bosnia and Herzegovina--clinical, laboratory and epidemiological research]

[Article in Bosnian]

Dautović-Krkić S, Cavaljuga S, Ferhatović M, Mostarac N, Gojak R, Hadzović M, Hadzić A.

Klinika za infektivne bolesti, Klinicki centar Univerziteta u Sarajevu.

Lyme borreliosis is multisistemic zoonosis that is transmitted from animals to humans by ticks of the Ixodes ricinus complex, which presents vectors for causative organism. Lyme borreliosis is caused by Borelia burgdorferi sensu lato, which has four different species. Objective of this research was to investigate frequency of borreliosis on our material, to determine seasonal yearly distribution of disease and to investigate variability of clinical forms of disease. MATERIALS AND METHODS: Retrospective analysis of medical records and discharge notes of treated patients with borreliosis in period 01 January 1996-31 December 2006 was conducted at the Clinic for Infectious Diseases in Sarajevo. Diagnosis of disease was confirmed serologically using Indirect Immunofluorescency method (IF), ELISA and Western-blot methods. RESULTS: During the investigated period at Clinic for Infectious Diseases, 51 patient with borreliosis was treated. Most affected was work-capable population. Since year 2000 number of treated patients is increasing. Disease is registered from May to September with peak in June. Most frequent symptoms were fever, fatigue, myalgias, and arthralgias. Disease was mainly diagnosed as Erythema migrans (39), than neuroborreliosis (7), borelial arthritis (4) and rarely eye infections-endophtalmitis and episcleritis. CONCLUSION: based on conducted 11-year period research of borreliosis we can conclude following: disease is mainly diagnosed as Erythema migrans, followed by neuroborreliosis. Women were more affected than men. Work-capable population is exposed to higher risk of getting disease. Highest peak of disease was in June. Due to various clinical forms and severity of late complications (II and III stage) it would be useful to conduct borreliosis testing with every etiologically unexplained neurological, cardiac and bone-joint manifestation.

PMID: 18669233 [PubMed - indexed for MEDLINE]

72. Rev Med Liege. 2008 May-Jun;63(5-6):349-53.

[Neuroborreliosis]

[Article in French]

Cuvelier ML, Léonard P, Rikir E, Huynen R, Sadzot B.

Service de Neurologie, CHU Sart Tilman, Liège, Belgique.

Borrelia burgdorferi infection is a frequent disease in our country. The neurological complications of this infection are found essentially in the early dissemination stage and in the late stage of the disease. Neuroborreliosis symptoms are most often characterized by radiculalgia resisting to treatment, sometimes associated to a cranial neuropathy, predominantly facial. The evolution is satisfactory under adapted antibiotherapy. This antiobiotherapy remains necessary despite the fact that most neuroborreliosis complications resolve spontaneously. Treatment permits to avoid the appearance of late complications or of possible extraneurological symptoms.

PMID: 18669203 [PubMed - indexed for MEDLINE]

73. Pract Neurol. 2008 Aug;8(4):256-9.

An exotic cause for confusion in the garden.

Williams F, Ginsberg L, Brenner R, Cohen A.

Department of Neurology, Royal Free Hospital, London, UK.

PMID: 18644913 [PubMed - indexed for MEDLINE]

74. Arch Dis Child Educ Pract Ed. 2008 Aug;93(4):132-4.

Should Lyme disease affecting the nervous system be treated with oral or intravenous antibiotics?

Selby G, Bridges SJ, Hanington L.

Musgrove Park Hospital, Taunton & Somerset NHS Trust, Taunton, UK. georginaselby@hotmail.com

PMID: 18644904 [PubMed - indexed for MEDLINE]

75. Pol Merkur Lekarski. 2008 May;24(143):453-7.

[Neuroborreliosis--some aspects of pathogenesis, diagnosis and treatment]

[Article in Polish]

Zajkowska JM, Pancewicz SA, Grygorczuk S, Kondrusik M, Moniuszko A, Lakwa K.

Medical University of Białystok, Department of Infectious Diseases and Neuroinfections, Poland.

Chosen pathophysiological aspects of Lyme borreliosis influencing on neurological symptoms, difficulties in diagnosis of neuroborreliosis and current opinions about effectivness of treatment. European recomendations--results of EUCALB expert group, AAN-American Academy Neurology supported some important studies connected with duration of therapy are described.

PMID: 18634395 [PubMed - indexed for MEDLINE]

76. J Shoulder Elbow Surg. 2008 Nov-Dec;17(6):e24-7. Epub 2008 Jul 15.

Operative treatment of a winged scapula due to peripheral nerve palsy in Lyme disease: a case report and review of the literature.

Bischel OE, Hempfing A, Rickert M, Loew M.

Department of Shoulder and Elbow Surgery, Stiftung Orthopädische Universitätsklinik, Heidelberg, Germany. Oliver.Bischel@ok.uni-heidelberg.de

PMID: 18632291 [PubMed - indexed for MEDLINE]

77. Pol Arch Med Wewn. 2008 May;118(5):314-7.

Neuroborreliosis with extrapyramidal symptoms: a case report.

Biesiada G, Czapiel J, Sobczyk-Krupiarz I, Garlicki A, Mach T.

Department of Infectious Diseases, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jagiellonian University School of Medicine, Kraków, Poland. gbiesiada@op.pl

The disease of Lyme is a tick-borne infection. It involves skin, the nervous system, joints and the heart. Spirochaeta Borrelia burgdorferi is the etiologic agent of the disease. In the majority of cases, clinical symptoms, like migrating erythema, occur from 3 to 30 days, sometimes to 3 months after a bite from a tick. The early disseminated infection involves multiple migrating erythema, neuroborreliosis, arthritis, myocarditis and other organ-related symptoms. The late stage of chronic infection involves chronic atrophic leg dermatitis, neurological and rheumatological symptoms, and other organ-related symptoms which persist for above 12 months. The diagnosis of the disease of Lyme is based upon specific clinical symptoms confirmed by serologic tests. The two-step diagnostic protocol including the ELISA method, confirmed by the Western-blot test, is optimal. The present article describes a case of a 59-year-old man, a computer specialist, who often spends his free time walking in woods for recreation, and who was bitten by a tick 3 years before hospitalization. The bite resulted in migrating erythema that subsided without antimicrobial treatment. In spite of this, the man had not changed his hobby exposing himself to bites from ticks. One year later, multiple migrating erythema and extrapyramidalis symptoms appeared without any other organ malfunctions. In the current year, the patient was admitted to the Infectious Diseases Hospital, and received antibiotics (ceftriaxon) with following neurological improvement. Several months later, extrapyramidal symptoms increased. On the day of admission to the hospital, the neurologic examination showed abnormalities of upper and lower limbs movements (propulsive walking and the right lower leg traction), the right hand tremor, pouts of the face, and sleepiness.

PMID: 18619183 [PubMed - indexed for MEDLINE]

78. Neurology. 2008 Jul 8;71(2):151; author reply 151-2.

Relevance of the antibody index to diagnose lyme neuroborreliosis among seropositive patients.

Ljøstad U, Mygland A.

PMID: 18606973 [PubMed - indexed for MEDLINE]

79. Neurology. 2008 Jul 8;71(2):150; author reply 150-1.

Relevance of the antibody index to diagnose lyme neuroborreliosis among seropositive patients.

Lanska DJ.

Comment on: Neurology. 2007 Sep 4;69(10):953-8.

PMID: 18606972 [PubMed - indexed for MEDLINE]

80. Trans Am Clin Climatol Assoc. 2008;119:39-51; discussion 51-2.

Zoonoses-with friends like this, who needs enemies?

Baum SG.

Albert Einstein College of Medicine, Bronx, New York 10461, USA. sbaum@aecom.yu.edu

Zoonoses are infections that are spread from animals to humans. Most often, humans are "dead-end" hosts, meaning that there is no subsequent human-to-human transmission. If one considers most of the emerging infections that were recognized at the end of the last century and the beginning of this century, they would fall into the category of zoonoses. One of the most important common traits exhibited by infections that have been or can be eliminated from the face of the earth (e.g. smallpox, measles, polio) is the absence of any host other than humans. Therefore, zoonses represent infections that can never be eliminated and must be considered as permanent and recurrent factors to be dealt with in protecting human health.

PMCID: 2394705 PMID: 18596867 [PubMed - indexed for MEDLINE]

81. Scand J Infect Dis. 2008;40(6-7):587-8.

Neuroborreliosis manifested as persistent vomiting in three children.

Baehr A, Gerecke A, Liese C, Berner R.

Centre for Paediatrics and Adolescent Medicine, University Medical Centre, Freiburg, Germany.

Neuroborreliosis usually presents with facial palsy and meningitis, but unspecific symptoms may also occur and can result in delayed diagnosis. We report on 3 children in whom persistent vomiting was the key clinical finding of neuroborreliosis.

PMID: 18584555 [PubMed - indexed for MEDLINE]

82. Lancet Neurol. 2008 Aug;7(8):665-6. Epub 2008 Jun 21.

Oral doxycycline for neuroborreliosis.

Wormser GP, Halperin JJ.

Comment on: Lancet Neurol. 2008 Aug;7(8):690-5.

PMID: 18567540 [PubMed - indexed for MEDLINE]

83. Lancet Neurol. 2008 Aug;7(8):690-5. Epub 2008 Jun 21.

Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial.

Ljøstad U, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, Mygland A.

Department of Neurology, Sørlandet Hospital HF, Kristiansand, Norway. unn.ljostad@sshf.no

Erratum in: Lancet Neurol. 2008 Aug;7(8):675.

Comment in: Lancet Neurol. 2008 Aug;7(8):665-6.

BACKGROUND: Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis. METHODS: From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801. FINDINGS: Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events. INTERPRETATION: Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.

PMID: 18567539 [PubMed - indexed for MEDLINE]

84. Acta Neurol Scand Suppl. 2008;188:22-8.

Management of neuroborreliosis in European adult patients.

Ljøstad U, Henriksen TH.

Department of Neurology, Sørlandet Sykehus HF, Kristiansand, Norway. unn.ljostad@sshf.no

OBJECTIVES: To survey present knowledge and controversies in European neuroborreliosis. Material and METHODS: The article is based on available literature, own experience, and a speech held by the authors. together on the Norwegian annual neurological meeting. RESULTS: Diagnosis of neuroborreliosis is based on clinical neurological findings, laboratory support of borrelia infection, and indications of causality between neurological findings and borreliosis. In the absence of means to identify B. burgdorferi, antibody tests are used for laboratory diagnosis. Two to three weeks courses of IV penicillin or ceftriaxone are highly effective in neuroborreliosis. Oral doxycyclin is probably equally effective. Remaining symptoms five years after treatment for neuroborreliosis are reported in 25-50% of patients. CONCLUSIONS: We suggest two levels of diagnostic accuracy; definite and possible neuroborreliosis. These case definitions are proposed to make the basis for treatment decisions. The prognosis of neuroborreliosis and pathophysiology of post-treatment conditions need further studies. Extensive treatments with antibiotics are not recommended.

PMID: 18439217 [PubMed - indexed for MEDLINE]

85. Pediatr Infect Dis J. 2008 Jul;27(7):605-12.

Improved laboratory diagnostics of Lyme neuroborreliosis in children by detection of antibodies to new antigens in cerebrospinal fluid.

Skogman BH, Croner S, Forsberg P, Ernerudh J, Lahdenne P, Sillanpää H, Seppälä I.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköoping University, Sweden. barbro.hedinskogman@ltdalarna.se

BACKGROUND: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens. METHODS: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16). RESULTS: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated. CONCLUSIONS: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.

PMID: 18536620 [PubMed - indexed for MEDLINE]

86. Clin Infect Dis. 2008 Jul 15;47(2):188-95.

Prospective study of serologic tests for lyme disease.

Steere AC, McHugh G, Damle N, Sikand VK.

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. asteere@partners.org

Comment in: Clin Infect Dis. 2008 Jul 15;47(2):196-7. Clin Infect Dis. 2008 Oct 15;47(8):1111-2; author reply 1112-3.

BACKGROUND: Tests to determine serum antibody levels-the 2-tier sonicate immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and Western blot method or the IgG of the variable major protein-like sequence-expressed (VlsE) sixth invariant region (C6) peptide ELISA method-are the major tests available for support of the diagnosis of Lyme disease. However, these tests have not been assessed prospectively. METHODS: We used these tests prospectively to determine serologic responses in 134 patients with various manifestations of Lyme disease, 89 patients with other illnesses (with or without a history of Lyme disease), and 136 healthy subjects from areas of endemicity and areas in which the infection was not endemic. RESULTS: With 2-tier tests and the C6 peptide ELISA, only approximately one-third of 76 patients with erythema migrans had results that were positive for IgM or IgG seroreactivity with Borrelia burgdorferi in acute-phase samples. During convalescence, 3-4 weeks later, almost two-thirds of patients had seroreactivity with the spirochete B. burgdorferi. The frequencies of seroreactivity were significantly greater among patients with spirochetal dissemination than they were among those who lacked evidence of disseminated disease. Of the 44 patients with Lyme disease who had neurologic, heart, or joint involvement, all had positive C6 peptide ELISA results, 42 had IgG responses with 2-tier tests, and 2 patients with facial palsy had only IgM responses. However, among the control groups, the IgG Western blot was slightly more specific than the C6 peptide ELISA. The differences between the 2 test systems (2-tier testing and C6 peptide ELISA) with respect to sensitivity and specificity were not statistically significant. CONCLUSIONS: Except in patients with erythema migrans, both test systems were sensitive for support of the diagnosis of Lyme disease. However, with current methods, 2-tier testing was associated with slightly better specificity.

PMID: 18532885 [PubMed - indexed for MEDLINE]

87. J Alzheimers Dis. 2008 May;13(4):381-91.

Chronic inflammation and amyloidogenesis in Alzheimer's disease — role of Spirochetes.

Miklossy J.

University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada. judithmiklossy@bluewin.ch

Alzheimer's disease (AD) is associated with dementia, brain atrophy and the aggregation and accumulation of a cortical amyloid-beta peptide (Abeta). Chronic bacterial infections are frequently associated with amyloid deposition. It had been known from a century that the spirochete Treponema pallidum can cause dementia in the atrophic form of general paresis. It is noteworthy that the pathological hallmarks of this atrophic form are similar to those of AD. Recent observations showed that bacteria, including spirochetes contain amyloidogenic proteins and also that Abeta deposition and tau phosphorylation can be induced in or in vivo following exposure to bacteria or LPS. Bacteria or their poorly degradable debris are powerful inflammatory cytokine inducers, activate complement, affect vascular permeability, generate nitric oxide and free radicals, induce apoptosis and are amyloidogenic. All these processes are involved in the pathogenesis of AD. Old and new observations, reviewed here, indicate that to consider the possibility that bacteria, including several types of spirochetes highly prevalent in the population at large or their persisting debris may initiate cascade of events leading to chronic inflammation and amyloid deposition in AD is important, as appropriate antibacterial and antiinflammatory therapy would be available to prevent dementia.

PMID: 18487847 [PubMed - indexed for MEDLINE]

88. Neurol Sci. 2008 Apr;29(2):109-12. Epub 2008 May 16.

Multiple cranial nerve involvement in Bannwarth's syndrome.

Vianello M, Marchiori G, Giometto B.

O.U. Neurology, Ca' Foncello Hospital, Piazza Ospedale 1, 31100, Treviso, Italy.

Bannwarth's syndrome is a tick-transmitted neurological disease caused by spirochetes of the Borrelia burgdorferi group. Neurological manifestations of the disease occur after skin erythema and include: neuritic pain, lymphocytic pleocytosis without headache and sometimes cranial neuritis. We present the case of a man who complained of a neurological syndrome without evidence of tick bite and concurrent manifestation of the infection, for whom serological analysis only revealed the infection after testing repetitive specimens. We discuss the need to start early therapy when clinical manifestations are suggestive of the disease in endemic areas.

PMID: 18483708 [PubMed - indexed for MEDLINE]

89. Tidsskr Nor Laegeforen. 2008 May 15;128(10):1175-8.

[Lyme borreliosis in adults]

[Article in Norwegian]

Ljøstad U, Mygland A.

Nevrologisk avdeling, Sørlandet Sykehus Kristiansand, Serviceboks 416, 4604 Kristiansand. unn.ljostad@sshf.no

Comment in: Tidsskr Nor Laegeforen. 2008 Aug 14;128(15):1681; author reply 1681.

BACKGROUND: Lyme borreliosis is a MULTISYSTEM: tick-borne infection caused by the spirochete Borrelia burgdorferi. We present a survey of clinical stages, diagnosis, treatment and prognosis of Lyme borreliosis in adults. MATERIAL AND METHODS: The article is based on literature retrieved through database searches and own experience. RESULTS AND INTERPRETATION: In Norway, Lyme borreliosis is most prevalent in coastal areas from the south and up to Trøndelag. Lyme disease can be classified into three stages; localised stage, and early and late disseminated stages. A laboratory gold standard does not exist, so the diagnosis is based on a combination of clinical manifestations and indirect detection of the bacteria, most often specific antibodies. Antibody results must be interpreted with caution. No medication is needed after a tick bite, but all manifestations of Lyme borreliosis should be treated with antibiotics according to guidelines. The prognosis is generally good. Post Lyme disease with persistent symptoms after borreliosis is a controversial condition. No studies have demonstrated persistent infection with borrelia bacteria in patients with chronic complaints after adequate antibiotic treatment, and additional antibiotic treatment does not improve quality of life in these patients.

PMID: 18480867 [PubMed - indexed for MEDLINE]

90. Infect Dis Clin North Am. 2008 Jun;22(2):327-39, vii.

Lyme disease: European perspective.

Stanek G, Strle F.

Medical University of Vienna, Clinical Institute of Hygiene and Medical Microbiology, Vienna, Austria. gerold.stanek@meduniwien.ac.at

The main clinical features of Lyme borreliosis seem to be the same in Europe and North America; however, the course of erythema migrans is distinct, with multiple erythema migrans and hematogeneous dissemination in early Lyme borreliosis less frequently observed in Europe. Moreover, the skin manifestations borrelial lymphocytoma and acrodermatitis chronica atrophicans are apparently European phenomena. Meningoradiculoneuritis in Lyme neuroborreliosis, with its severe radicular pain, is more prominent in Europe. Similar difficulties exist on both sides of the Atlantic with the serologic diagnosis of Lyme borreliosis.

PMID: 18452805 [PubMed - indexed for MEDLINE]

91. Infect Dis Clin North Am. 2008 Jun;22(2):315-26, vii.

Lyme disease in children.

Feder HM Jr.

University of Connecticut Health Center, Farmington, CT 06030, USA. feder@nso2.uchc.edu

This article reviews pediatric Lyme disease in the United States. The agent of Lyme disease includes three pathogenic species (Borrelia burgdorferi, B afzelii, and B garinii), but only B. burgdorferi strains are found in the United States. The article's discussion is limited to the single species B burgdorferi.

PMID: 18452804 [PubMed - indexed for MEDLINE]

92. Infect Dis Clin North Am. 2008 Jun;22(2):261-74, vi.

Nervous system Lyme disease.

Halperin JJ.

Department of Neurosciences, Atlantic Neuroscience Institute & Overlook Hospital, Summit, NJ 07902, USA. john.halperin@atlantichealth.org

Lyme disease affects the nervous system in about 10% to 15% of infected individuals, most commonly causing lymphocytic meningitis. Cranial neuropathies, particularly facial nerve palsy, also occur frequently. Figuring prominently in the European literature, but less emphasized in the United States, is painful radiculitis, radicular pain involving a limb or trunk dermatome. Treatment of neuroborreliosis is usually straightforward; oral antibiotics may suffice in many patients. In severe cases, 2 to 4 weeks of parenteral therapy is necessary. All available evidence indicates that treatment of more than 4 weeks' duration carries substantial risk but minimal if any additional benefit.

PMID: 18452800 [PubMed - indexed for MEDLINE]

93. Mayo Clin Proc. 2008 May;83(5):566-71.

Diagnosis and treatment of Lyme disease.

Bratton RL, Whiteside JW, Hovan MJ, Engle RL, Edwards FD.

Department of Family Medicine, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA.

Lyme disease is the most common tick-borne disease in the United States. This review details the risk factors, clinical presentation, treatment, and prophylaxis for the disease. Information was obtained from a search of the PubMed and MEDLINE databases (keyword: Lyme disease) for articles published from August 31, 1997, through September 1, 2007. Approximately 20,000 cases of Lyme disease are reported annually. Residents of the coastal Northeast, northwest California, and the Great Lakes region are at highest risk. Children and those spending extended time outdoors in wooded areas are also at increased risk. The disease is transmitted to humans through the bite of the Ixodes tick (Ixodes scapularis and Ixodes pacificus). Typically, the tick must feed for at least 36 hours for transmission of the causative bacterium, Borrelia burgdorferi, to occur. Each of the 3 stages of the disease is associated with specific clinical features: early localized infection, with erythema migrans, fever, malaise, fatigue, headache, myalgias, and arthralgias; early disseminated infection (occurring days to weeks later), with neurologic, musculoskeletal, or cardiovascular symptoms and multiple erythema migrans lesions; and late disseminated infection, with intermittent swelling and pain of 1 or more joints (especially knees). Neurologic manifestations (neuropathy or encephalopathy) may occur. Diagnosis is usually made clinically. Treatment is accomplished with doxycycline or amoxicillin; cefuroxime axetil or erythromycin can be used as an alternative. Late or severe disease requires intravenous ceftriaxone or penicillin G. Single-dose doxycycline (200 mg orally) can be used as prophylaxis in selected patients. Preventive measures should be emphasized to patients to help reduce risk.

PMID: 18452688 [PubMed - indexed for MEDLINE]

94. APMIS. 2008 May;116(5):393-9.

C6-peptide serology as diagnostic tool in neuroborreliosis.

Tjernberg I, Schön T, Ernerudh J, Wistedt AC, Forsberg P, Eliasson I.

Department of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden. ivart@ltkalmar.se

The aim of this study was to evaluate the usefulness of borrelia serology (Quick ELISA C6 Borrelia assay kit) as a diagnostic tool in cases of suspected neuroborreliosis. A retrospective patient material consisting of 124 paired serum and cerebrospinal fluid samples with a positive anti-borrelia antibody index (AI) using the IDEIA Lyme Neuroborreliosis test was compared with 124 AI-negative matched control subjects. The patients were divided into four groups based on presence of pleocytosis and age above or below 12 years. The presence of positive C6 serology in AI-positive patients with pleocytosis was 89% (83/93), significantly different (p<0.01) from in patients without pleocytosis (58%, 18/31). In AI-positive patients aged > or =12 years with pleocytosis, 94% (51/54) had a positive C6 serology. Of AI-positive patients with a symptom duration of more than 30 days, 93% (27/29) were positive by the C6 test. We conclude that the C6 serum test, together with clinical evaluation, is a powerful diagnostic tool in adult (> or =12 years) European patients with suspected neuroborreliosis with a symptom duration of more than 30 days. Patients with suspected neuroborreliosis and positive C6 results should be further investigated by lumbar puncture for definite diagnosis.

PMID: 18452429 [PubMed - indexed for MEDLINE]

95. Przegl Lek. 2007;64 Suppl 3:38-40.

CNS Lyme disease manifestation in children.

Kaciński M, Zajac A, Skowronek-Bała B, Kroczka S, Gergont A, Kubik A.

Department of Pediatric Neurology, Jagiellonian University, Krakow, Poland. neupedkr@cm-uj.krakow.pl

BACKGROUND: Neurological symptoms develop in 10-20% of children with borreliosis. AIM OF THE STUDY: It was a presentation of clinical manifestation of neuroborreliosis in children. MATERIAL AND METHODS: Children with neuroborreliosis and other neurological diseases were admitted to the University Hospital during 2005-2006 without any selection. Of these 9 patients, there were seven males and two females, ranging in age between 3-17 years. Neurological diagnostic was performed using ELISA Biomedica kit and western blot bands. A 2-6 week sequential treatment with either i.v. ceftazidime or amoxicillin and oral doxycycline or amoxicillin was provided. Children were monitored regularly during the next 4-24 months. RESULTS: The 9 children with borreliosis constitute 0.53% of the pediatric neurology department's patients. The clinical manifestation of LD were usual and unusual from patient to patient. They included three cases of facial nerve paralysis (with bilateral paralysis in one case). In two cases, they included transverse myelitis and in a single case, hemiparesis, meningitis and acute ataxia. Typically, other patients with early stage borreliosis first manifest focal seizures, raising the suspicion that borreliosis could be responsible for triggering seizures. The antibiotic treatment was successful in 7 patients and only partially effective in 2 children with facial nerve paralysis. CONCLUSIONS: The most common symptom of neuroborreliosis in children is motor dysfunction. Acute ataxia may be a clinical presentation of neuroborreliosis. It is probable that borreliosis_triggers seizures in children with EEG abnormalities.

PMID: 18431910 [PubMed - indexed for MEDLINE]

96. Rev Med Interne. 2008 Nov;29(11):932-5. Epub 2008 Apr 10.

[Sciatica with motor loss revealing meningoradiculitis due to varicella-zoster virus]

[Article in French]

Abourazzak F, Couchouron T, Meadeb J, Perdriger A, Tattevin P, Moutel A, Le Goff B, Hajjaj-Hassouni N, Chalès G.

Service de rhumatologie, CHU de Rabat-Salé, hôpital El-Ayachi, Maroc. abourazakf@yahoo.fr

Herpes zoster is a disease which occurs secondary to the reactivation of varicella-zoster virus. Motor involvement in acute herpes zoster is rare. We report a case of sciatica L5 due to herpes zoster infection with motor loss. Typical skin lesions occurred one week before the sciatica. Radiological finding did not explain the paresis. The diagnosis of zoster sciatica with motor involvement was suspected. Serological tests and cerebrospinal fluid examination established the diagnosis. The antiviral and physical treatment was conducted in order to improve functional outcome.

PMID: 18406019 [PubMed - indexed for MEDLINE]

97. Neurol Sci. 2008 Feb;29(1):11-4. Epub 2008 Apr 1.

Viliuisk encephalomyelitis in Northeastern Siberia is not caused by Borrelia burgdorferi infection.

Storch A, Vladimirtsev VA, Tumani H, Wellinghausen N, Haas A, Krivoshapkin VG, Ludolph AC.

Department of Neurology, Technical University of Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. alexander.storch@neuro.med.tu-dresden.de

Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeastern Siberia and generally believed to be a chronic encephalomyelitis of unknown origin. We investigated 17 patients with a clinical diagnosis of VE within the Viliuiski region of Sakha (Yakutian) Republic to explore the core clinical syndrome of chronic VE and subsequently whether VE is caused by Borrelia burgdorferi infection. We found a chronic myelopathy as the core of the syndrome, often following an acute phase with a meningo-radiculo-neuropathy, suggestive of chronic neuroborreliosis. A search for inflammatory parameters in a larger cohort in blood (39 VE patients and 41 controls) and CSF samples (10 VE patients and 7 controls) excluded an ongoing chronic infection, but revealed evidence for an immunological scar or a chronic inflammatory ("autoimmune") response in the CSF. In addition, we detected signs of a previous exposure to Borrelia burgdorferi antigens in a subset of chronic VE patients with positive serological results using ELISA/immunoblot in 54/10% and 22/0% of VE patients and controls, respectively (p values of 0.003/0.034; Fisher's exact test). However, CSF analyses did not show a link between exposure or at least immunological reaction against Borrelia and the risk of suffering from VE. Our data provide the first evidence of the presence of Borrelia burgdorferi or similar pathogens in Northeastern Siberia, but do not support a causative role of these pathogens in the aetiopathogenesis of VE.

PMID: 18379734 [PubMed - indexed for MEDLINE]

98. J Neurol. 2008 May;255(5):732-7. Epub 2008 Mar 17.

CSF B--lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis.

Ljøstad U, Mygland A.

Dept. of Neurology, Sørlandet Sykehus HF, Kristiansand Serviceboks 416, 4604 Kristiansand, Norway. unn.ljostad@sshf.no

Erratum in: J Neurol. 2008 May;255(5):782.

Recent studies have suggested a diagnostic role of the B-lymphocyte attracting chemokine (CXCL13) in the cerebrospinal fluid (CSF) in Lyme neuroborreliosis (LNB). Our aim was to evaluate diagnostic accuracy of CSF CXCL13 in a cohort of 59 consecutive patients referred to hospital for suspected LNB. Thirty-seven patients were classified as definite LNB and used as the reference standard. Seven were classified as probable, and seven as possible LNB. Eight patients did not fulfil case definitions and were used as controls. At presentation, CSF CXCL13 was elevated in all patients with definite LNB, as compared to a positive CSF B. burgdorferi (Bb) antibody index (AI) in 33 of 37. Pre-treatment sensitivity of elevated CSF [corrected] Bb Al [corrected] was 100 % (95 % CI = 91-100) and 89 % [corrected] (95 % CI = 75-96) respectively (p = 0.053). Among the eight control patients, CSF CXCL13 was normal in five and only slightly elevated in three, and Bb AI was negative in five. Specificity of CSF CXCL13 and Bb AI was similar 63 % (95 % CI = 31-86) (p = 1.0).CSF CXCL13 was elevated in 6/7 patients with probable LNB and 3/7 patients with possible LNB. Bb AI was negative in all these 14 patients. An additional control group consisted of 31 patients with multiple sclerosis (MS), 11 with non-inflammatory neurological diseases, and ten with verified non-Lyme meningitis and high CSF cell count. CSF CXCL13 was slightly elevated in 15 MS patients, and in nine meningitis patients. Mean CSF CXCL13 was higher in definite LNB (3524 ng/g CSF protein) than in MS (27 ng/g) and non-Lyme meningitis (23 ng/g) (p < 0.001). Four months post-treatment CSF CXCL13 was normalized in 82 % of patients with definite LNB, as compared to a negative Bb AI in 10 % (p < 0.001).CSF CXCL13 may be a useful supplement in early diagnosis of acute LNB.

PMID: 18344056 [PubMed - indexed for MEDLINE]

99. Epidemiol Infect. 2008 Dec;136(12):1707-11. Epub 2008 Mar 6.

Neuroborreliosis in the South West of England.

Lovett JK, Evans PH, O'Connell S, Gutowski NJ.

Southampton General Hospital, Southampton, UK. Joanna@jlovett.fsworld.co.uk

Although Lyme borreliosis is increasingly diagnosed in the United Kingdom, few systematic studies have been performed there. UK data suggest that the commonest complications are neurological, but inadequate information exists about their nature and the incidence of late neuroborreliosis. Local data are necessary because clinical presentations may show geographical variation. This study aimed to provide data on clinical manifestations in an area of South West England and to estimate treatment delay. We reviewed clinical records of 88 patients in the Royal Devon and Exeter Hospital catchment area who had positive Borrelia antibody tests during a 5-year period. Fifty-six (64%) reported tick bites. The commonest presentations were erythema migrans (65%) and arthralgia/myalgia (27%). However, 22 patients (25%) had neurological symptoms other than headache alone. Fourteen had facial palsy, eight had confusion/drowsiness, four had meningism, five had radiculopathy, two had sixth nerve palsies, and two had peripheral neuropathies. No late, progressive or atypical neurological syndromes were found. Neurological manifestations were generally predictable and usually included either (or all) of meningoencephalitis, facial palsy or radiculopathy.

PMID: 18325130 [PubMed - indexed for MEDLINE]

100. Folia Microbiol (Praha). 2007;52(5):529-34.

Analysis of cerebrospinal fluid cell populations with monoclonal antibodies.

Adam P, Sobeka O, Scott CS.

Laboratory of Reference for Cerebrospinal Fluid and Neuroimmunology, Homolka Hospital, 150 30 Prague, Czechia. pavel.adam@homolka.cz

Sixty-five samples of cerebrospinal fluid (CSF) were evaluated using an automated cytoflow method with the CD-Sapphire hematology analyzer in order to investigate possible relationships between cell population patterns and diagnostic groups and better understand the biology of neurological disease. A basic panel of CD markers, including CD3/4/8/19/138/HLA-DR, was used to analyze CSF samples from clinical and laboratory confirmed cases of multiple sclerosis, neuroborreliosis, viral and bacterial neuroinfective diseases, malignant infiltrations of meninges and scavenger macrophagic reactions of the central nervous system. The principles of immune response and the contribution of cytological 'disease-related patterns' for these nosological entities are described. The distinct patterns of lymphocyte subpopulations in neuroborreliosis appear to be characteristic and could possibly serve as diagnostic indicators. Further verification and research will be necessary to clarify the significance and nature of CD4+ CD8+ positive subset in cerebrospinal fluid.

PMID: 18298052 [PubMed - indexed for MEDLINE]

101. Med Pr. 2007;58(5):439-47.

[Diagnostics of Lyme disease]

[Article in Polish]

Gasiorowski J, Witecka-Knysz E, Knysz B, Gerber H, Gładysz A.

Katedra i Klinika Chorób Zakaźnych, Chorób Watroby i Nabytych Niedoborów Odpornościowych Akademia Medyczna, Wrocław. jacekgasiorowski@yahoo.co.uk

Although many years have passed since Borrelia burgdorferi was first identified, advances in understanding biology and clinical course of infection made and new diagnostic procedures developed, Lyme disease is still difficult to diagnose. Therefore, it is often wrongly diagnosed and unnecessarily treated. In this paper we analyzed the latest data on Lyme disease diagnostic methods, paying much attention to their limitations and correct interpretation of results. In routine diagnosis of this diseases, indirect tests, based on the detection of specific IgM and IgG antibodies, are most useful. The Lyme disease diagnosis should begin with screening tests, which are highly sensitive but not specific enough and sometimes yield false positive results, then all positive results should be verified by confirmation tests, which allow to distinguish between true positive results and healthy individuals with false positive ones.

PMID: 18274096 [PubMed - indexed for MEDLINE]

102. Eur J Paediatr Neurol. 2008 Nov;12(6):501-4. Epub 2008 Feb 11.

Lyme disease with lymphocytic meningitis, trigeminal palsy and silent thalamic lesion.

Köchling J, Freitag HJ, Bollinger T, Herz A, Sperner J.

Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. koechling@paedia.ukl.mu-luebeck.de

We describe a follow-up in a 15-year-old boy with neuroborreliosis diagnosed by clinical symptoms, CSF and serum analysis. MRI revealed a thalamic lesion and an enhancement of the right trigeminal nerve clinically associated with mild hypasthesia in the right maxillary region. Both, clinical symptoms and radiological findings disappeared within 2 months after treatment. Borrelia burgdorferi specific IgM and IgG in CSF and IgG in serum became negative between 6 and 12 months after diagnosis. We show that neuroborreliosis at an early stage may present only with moderate neurological deficits and that at this stage MRI reveals distinct cerebral lesions which might even precede clinical manifestation. Thus, early diagnosis and treatment of neuroborreliosis may prevent persistent neurologic lesions.

PMID: 18262812 [PubMed - indexed for MEDLINE]

103. Microbes Infect. 2008 Feb;10(2):135-42. Epub 2007 Nov 5.

Outer surface protein E antibody response and its effect on complement factor H binding to OspE in Lyme borreliosis.

Panelius J, Meri T, Seppälä I, Eholuoto M, Alitalo A, Meri S.

Haartman Institute, Department of Bacteriology and Immunology, P.O. Box 21, University of Helsinki, Helsinki FIN-00014, Finland. jaana.panelius@helsinki.fi

Borrelia burgdorferi sensu stricto and B. afzelii, but not B. garinii, are able to escape complement attack by binding factor H via OspE proteins. Recent finding of ospE genes also in B. garinii isolates has raised the question whether, under in vivo-conditions, B. garinii also expresses OspE proteins and consequently induces an antibody response. We set up an IgG ELISA by using recombinant OspE as an antigen. Sixty percent of acute and 64% of convalescent 25 erythema migrans patient samples were positive for anti-OspE antibodies. Anti-OspE antibodies were also found in the sera (83.6%) and cerebrospinal fluids (36%) of patients with neuroborreliosis. Since B. garinii is the major causative agent of neuroborreliosis, the result suggests that OspE is expressed by B. garinii in vivo. Of the 10 acrodermatitis chronica atrophicans patients, 80% had anti-OspE antibodies. Anti-OspE antibody positive sera inhibited factor H binding to Borrelia more efficiently than normal control sera (65% vs. 33.7%). Our results indicate that Borrelia spirochetes, including B. garinii, can induce the production of anti-OspE antibodies. This implies that OspE protein is produced in vivo by B. garinii possibly enabling it to escape complement and cause a CNS infection.

PMID: 18248762 [PubMed - indexed for MEDLINE]

104. Adv Med Sci. 2007;52:174-8.

Concentration of TGF-beta1 in the supernatant of peripheral blood mononuclear cells cultures from patients with early disseminated and chronic lyme borreliosis.

Grygorczuk S, Chmielewski T, Zajkowska J, Swierzbińska R, Pancewicz S, Kondrusik M, Tylewska-Wierzbanowska S, Hermanowska-Szpakowicz T.

Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, ul. Zurawia 14, 15-540 Białystok, Poland. neuroin@amb.edu.pl

PURPOSE: The aberrant inflammatory response is probably involved in the pathogenesis of chronic Lyme borreliosis, including chronic Lyme arthritis and neuroborreliosis. Transforming growth factor-beta 1 (TGF-beta1) is an important anti-inflammatory and immunomodulatory cytokine and its deficient synthesis is linked to exaggerated inflammation and immune response. MATERIAL AND METHODS: Peripheral blood mononuclear cells (PBMC) from 25 patients with Lyme borreliosis and 6 controls were incubated for 7 days with suspension of Borrelia afzeli, B. garinii and B. burgdorferi sensu stricto spirochetes. TGF-beta1 concentration in culture supernatants was measured with ELISA. Results were analyzed according to disease duration (group I--chronic borreliosis, n=20; group II--early borreliosis, n=5) and clinical form (LA--arthritis, NB--neuroborreliosis). RESULTS: TGF-beta1 concentration was increased in supernatants of PBMC cultures of patients with early neuroborreliosis, in comparison with chronic borreliosis and controls. In chronic, but not in early borreliosis, there was a tendency for decrease of TGF-beta1 synthesis under stimulation with B. burgdorferi spirochetes. CONCLUSIONS: Impaired synthesis of TGF-beta1 by mononuclear cells seems to be present in patients with chronic forms of Lyme borreliosis when compared to those with early stage of the disease. It may be a factor contributing to the persistence of inadequate inflammatory response in patients in whom chronic form of the disease develops.

PMID: 18217413 [PubMed - indexed for MEDLINE]

105. Eur J Paediatr Neurol. 2008 Sep;12(5):366-70. Epub 2008 Feb 21.

Canalicular magnetic stimulation lacks specificity to differentiate idiopathic facial palsy from borreliosis in children.

Hufschmidt A, Müller-Felber W, Tzitiridou M, Fietzek UM, Haberl C, Heinen F.

Department of Neurology, Verbundkrankenhaus Bernkastel-Wittlich, Koblenzer Street 91, Wittlich, Germany. a.hufschmidt@kh-wittlich.de

OBJECTIVE: To investigate the role of transcranial magnetic stimulation (TMS) to differentiate between idiopathic facial nerve palsy (iFNP) and facial nerve palsy due to borreliosis (bFNP). PATIENTS AND METHODS: Transcranial and intracanalicular magnetic and peripheral electrical stimulation of the facial nerve together with clinical grading according to the House and Brackmann scale were performed in 14 children and adolescents with facial palsy (median age 11.5 yr, range 4.6-16.5 yr). Serum and cerebrospinal fluid (CSF) were evaluated for antibodies against Borrelia burgdorferi and CSF cell count, glucose and protein content were screened with methods of routine laboratory testing. Data of patients were compared with normal values established in 10 healthy subjects (median age 10.2 yr, range 5.1-15.3 yr). RESULTS: Patients with iFNP showed a significant decrease in MEP amplitude to canalicular magnetic stimulation compared with healthy controls (p=0.03). However, MEP amplitude did not discriminate sufficiently between the two groups, because the ranges of dispersion of MEP amplitudes overlapped. Patients with bFNP had normal MEP amplitudes to canalicular magnetic stimulation compared with normal subjects. CONCLUSION: Diagnostic assessment by TMS failed to provide a reliable diagnostic criterion for distinguishing between iFNP and bFNP in children and adolescents.

PMID: 18206409 [PubMed - indexed for MEDLINE]

106. Lakartidningen. 2007 Nov 28-Dec 4;104(48):3621-2.

[Neuroborreliosis with bad reputation. This is no mystical, difficult-to-treat infection!]

[Article in Swedish]

Hagberg L, Dotevall L.

Sahlgrenska Universitetssjukhuset/Ostra, Göteborg. lars.hagberg@medfak.gu.se

PMID: 18193671 [PubMed - indexed for MEDLINE]

107. Arch Pediatr. 2008 Jan;15(1):41-4. Epub 2007 Dec 26.

[Acute hemiparesis revealing a neuroborreliosis in a child]

[Article in French]

Rénard C, Marignier S, Gillet Y, Roure-Sobas C, Guibaud L, Des Portes V, Lion-François L.

Service de neurologie, hôpital Debrousse, 29, rue des Soeurs Bouvier, 69322 Lyon cedex 05, France.

We report on a 11-year-old boy who had 2 acute hemiparesis episodes over a period of 1 month. He suffered from headache and fatigue since 1 year. He could not remember neither a tick bite nor a local erythematous skin lesion. The diagnosis of neuroborreliosis was based on intrathecal production of specifics antibodies. Furthermore, the CSF/blood glucose ratio was decreased (0.14), which was rarely described. Cranial MRI showed left capsulothalamic inflammation and a vasculitis. The patient was successfully treated by ceftriaxone. Neuroborreliosis should be considered in all children with stroke-like episode, even in the absence of a history of a tick bite.

PMID: 18155890 [PubMed - indexed for MEDLINE]

108. Mol Med. 2008 Mar-Apr;14(3-4):205-12.

The pathogenesis of lyme neuroborreliosis: from infection to inflammation.

Rupprecht TA, Koedel U, Fingerle V, Pfister HW.

Department of Neurology, Ludwig-Maximilians University, Munich, Germany.

This review describes the current knowledge of the pathogenesis of acute Lyme neuroborreliosis (LNB), from invasion to inflammation of the central nervous system. Borrelia burgdorferi (B.b.) enters the host through a tick bite on the skin and may disseminate from there to secondary organs, including the central nervous system. To achieve this, B.b. first has to evade the hostile immune system. In a second step, the borrelia have to reach the central nervous system and cross the blood-brain barrier. Once in the cerebrospinal fluid (CSF), the spirochetes elicit an inflammatory response. We describe current knowledge about the infiltration of leukocytes into the CSF in LNB. In the final section, we discuss the mechanisms by which the spirochetal infection leads to the observed neural dysfunction. To conclude, we construct a stringent concept of the pathogenesis of LNB.

PMCID: 2148032 PMID: 18097481 [PubMed - indexed for MEDLINE]

109. Lancet Neurol. 2008 Jan;7(1):25; author reply 25.

Lyme neuroborreliosis in Great Britain.

Tweedie A.

Comment on: Lancet Neurol. 2007 Jun;6(6):544-52.

PMID: 18093557 [PubMed - indexed for MEDLINE]

110. Pol Merkur Lekarski. 2007 Sep;23(135):174-8.

[Concentration of soluble forms of selectins in serum and in cerebrospinal fluid in group of patients with neuroborreliosis--a preliminary study]

[Article in Polish]

Moniuszko AM, Pancewicz SA, Kondrusik M, Zajkowska J, Grygorczuk S, Swierzbińska R.

Akademia Medyczna w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji.

The results of the research already done, suggest an important role of selectins in inflammatory process of various etiology. Lack of selectins or their ligands causes severe complications, such as chronic inflammatory processes. The aim of this study was to analyze the role of selectins sL, sE and sP in the development and course of neuroborreliosis in the form of meningitis. We have also analyzed the influence of treatment on changes of selectins' concentration in serum and cerebrospinal fluid. MATERIAL AND METHODS: We have analyzed 17 patients with neuroborreliosis presenting as meningitis, in whom we measured by immunoenzymatic method concentration of selectins sL, sP and sE in blood and cerebrospinal fluid before and after 4-week therapy with cefotaxim. We used Human sL-selectin, Human sE-selectin and Human sP-selectin kits produced by Bender Med. Systems, Austria. Control group for measurement of concentration of selectins in serum consisted of 8 healthy patients. Control group for measurement of concentration of selectins in cerebrospinal fluid consisted of 8 patients, in whom lumbar puncture excluded inflammatory disease of the central nervous system. RESULTS: In serum concentration of selectins sL and sP was significantly higher comparing to control group. After treatment concentration of these selectins decreased, but still was significantly higher than in control group. Only concentration of selectin sE was significantly lower than in control group and after treatment decreased further remaining lower comparing to control group. In cerebrospinal fluid concentration of selectin sL was significantly higher comparing to control group and increased after treatment. Concentration of selectins sE and sP increased before treatment and decreased after treatment, but still remained elevated comparing to control group. CONCLUSIONS: Persistence of increased concentration of selectins sP and sL in serum and also of selectin sE in cerebrospinal fluid in patients with neuroborreliosis after completed antibiotic therapy and regression of clinical symptoms can suggest permanence of chronic inflammatory state in consequence of survival of B. burgdorferi spirochetes in affected tissues.

PMID: 18080689 [PubMed - indexed for MEDLINE]

111. New Microbiol. 2007 Oct;30(4):399-410.

Evaluation of a genotyping method based on the ospA gene to detect Borrelia burgdorferi sensu lato in multiple samples of lyme borreliosis patients.

Floris R, Menardi G, Bressan R, Trevisan G, Ortenzio S, Rorai E, Cinco M.

Spirochete Laboratory, Dipartimento di Scienze Biomediche, Università di Trieste, Italy.

In this study we have developed a new Restriction-Fragment-Length-Polymorphism (RFLP) genotyping method for rapid detection and identification of Borrelia genospecies present as unique species or as co-infection in multiple specimens obtained simultaneously from 29 individual patients affected by early or late Lyme borreliosis (LB). The target of the RFLP-genotyping was the heterogeneous plasmid located ospA gene, thus we developed a method able to detect and differentiate between six clinically relevant Borrelia genospecies circulating in Europe, B. burgdorferi sensu stricto, B. garinii, B. afzelii, B. valaisiana, B. bissettii and B. spielmanii. In this study Borrelia DNA could be detected by PCR in at least one specimen of each patient, except in one case of neuroborreliosis (NB); blood samples gave the highest sensitivity in all patient groups. The genotyping indicated that B. afzelii was present in 8 patients with skin involvement, B. garinii in 2 cases of NB and 4 cases with skin involvement, B. burgdorferi sensu stricto was detected in one patient with skin involvement and another with Lyme arthritis. Different Borrelia species in distinct specimens were identified in one patient with EM. The RFLP analysis of 11 patients revealed mixed patterns, which suggested pluri-infection with different Borrelia species.

PMID: 18080675 [PubMed - indexed for MEDLINE]

112. Nervenarzt. 2008 Apr;79(4):462-4.

[Isolated neuritis of the oculomotor nerve in infectious mononucleosis]

[Article in German]

Erben Y, Gonzalez Hofmann C, Steinmetz H, Ziemann U.

Klinik für Neurologie, Johann-Wolfgang-Goethe-Universität, Schleusenweg 2-16, 60528, Franfurt am Main, Deutschland.

A 19-year-old immune-competent patient developed right-sided headache and, subsequently, subacute diplopia. On clinical examination he had incomplete right oculomotor palsy. Cranial MRI showed pathologic contrast enhancement of the right oculomotor nerve at its exit point from the mesencephalon, and the CSF displayed slight pleocytosis. The following relevant differential diagnoses were not supported by additional examinations: neurosarcoidosis, Lyme neuroborreliosis, neurosyphilis, tuberculous meningitis, viral meningitis (HIV, VZV, CMV), CNS lymphoma, vasculitis associated with rheumatic disease, Tolosa-Hunt syndrome, and diabetic neuropathy. However, on the basis of blood lymphocytosis, positive heterophile antibody test (Paul-Bunnell test), the presence of IgM antibodies against Epstein-Barr virus capsid antigen, and elevated transaminases, infectious mononucleosis was diagnosed. Isolated neuritis of the oculomotor nerve is a rare parainfectious manifestation of infectious mononucleosis.

PMID: 18058080 [PubMed - indexed for MEDLINE]

113. Tidsskr Nor Laegeforen. 2007 Nov 29;127(23):3061-3.

[Borreliosis as the cause of disability pensions in Norway]

[Article in Norwegian]

Reiso H, Brage S.

Helse-nettverket, Arendal kommune, Serviceboks 650, 4809 Arendal. harald.reiso@medisin.uio.no

BACKGROUND: Borreliosis is a bacterial infection transferred by tick-bites. Neuroborreliosis is the most frequent disseminated form of the disorder in Norway. Registers exist in Norway on all reported communicable diseases (The Norwegian Surveillance System for Communicable Diseases [MSIS]) and disability pension diagnoses (The Norwegian Directorate of Labour and Welfare). MATERIAL AND METHODS: Geographic distributions of borreliosis and changes over time are presented. Disability pensions (coded by International Classification of Diseases [ICD]) in the period 1998-2005, in which borreliosis was used as the primary or secondary diagnosis (ICD-10), were compared with MSIS-data for borreliosis on municipal and county levels. RESULTS: Borreliosis was the cause of disability pensions in 55 cases. The Vestfold and Agder counties had the highest number of cases. Larvik municipality had 9 cases, Arendal had four and Kristiansand had nine cases. The annual rates of new disability pensions caused by borreliosis were low but increasing in the period 1998-2005. The disability pension rates tended to reflect changes in the number of MSIS-reported cases, with pensions changing 1-2 years after MSIS-changes. Most MSIS-reported cases are in the Agder and Telemark counties. INTERPRETATION: Disability pension are rarely caused by borreliosis. The annual incidence of disability pensions seems to reflect the number of MSIS-reported cases of borreliosis. The Agder and Vestfold counties have the highest incidence.

PMID: 18049495 [PubMed - indexed for MEDLINE]

114. Pol Merkur Lekarski. 2007 Aug;23(134):103-6.

[Clinical forms of neuroborreliosis among hospitalized patients in the years 2000-2005]

[Article in Polish]

Czupryna P, Kuśmierczyk J, Zajkowska JM, Ciemerych M, Kondrusik M, Ciemerych A, Pancewicz SA.

Akademia Medyczna w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji. avalon-5@wp.pl

THE AIM OF THE STUDY: To evaluate the frequency of clinical forms as well as laboratory and neuroimaging results of patients with diagnosed neuroborreliosis in the years 2000-2005 due to neuroborreliosis. MATERIAL AND METHODS: The records of 125 patients at the age of 21-83 (mean 49 years) treated in the years 2000-2005 in the Department of Infectious Diseases and Neuroinfections, Medical University, Bialystok were subject to retrospective analysis. Diagnosis was based on case history along with a clinical picture and presence of antibodies against Borrelia burgdorferi, using ELISA test (Borrelia IgM and Borrelia IgG recombinant Biomedica). The subject of the detailed analysis was demographic data, clinical symptoms as well as subjective complaints, results of neurological examinations, the results of cerebrospinal fluid (CSF) parameters and results of serologic tests. RESULTS: The most frequent clinical symptoms observed were: headaches 71%, vertigo 44%, meningeal symptoms 22% and neurological paresis 27% (including facial palsy--23%). Inflammatory changes in CSF in the form of increased proteins concentration and pleocytosis were present among 34% of patients. In all cases the antibodies against B. burgdorferi were present in CSF in diagnostically significant titer. Serum presence of antibodies antiborrelia IgM was found with 55% of patients and anibodies antiborrelia IgG with 76% of patients. 17% of patients suffering from neuroborreliosis were also coinfected with tick-borne encephalitis virus. Along with the neurological symptoms, which were crucial to diagnosis, general symptoms coexisted, such as: weakness 35%, arthralgia 54% and nausea 17%. In the analyzed period of time neuroborreliosis was diagnosed in a 13% of hospitalized patient suffering from borreliosis. CONCLUSIONS: Absence of erythema migrans does not exclude existence of neuroborreliosis. Symptoms that may suggest presence of neuroborreliosis are not only neurological symptoms such as facial palsy, but also memory and concentration disorders and general symptoms.

PMID: 18044338 [PubMed - indexed for MEDLINE]

115. Rev Neurol (Paris). 2007 Nov;163(11):1039-47.

[Acute myelitis and Lyme disease]

[Article in French]

Blanc F, Froelich S, Vuillemet F, Carré S, Baldauf E, de Martino S, Jaulhac B, Maitrot D, Tranchant C, de Seze J.

Département de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg. Frederic.Blanc@chru-strasbourg.fr

INTRODUCTION: Acute myelitis accounts for 4 to 5 percent of all cases of neuroborreliosis. In the literature, simultaneous spinal MRI and cerebrospinal fluid (CSF) investigations are presented for only 8 cases. We describe here 3 cases of acute Lyme myelitis. METHOD: In a cohort of 45 patients with neuroborreliosis, diagnosed between January 1998 and January 2005, 3 had acute myelitis. Clinical, biological and radiological data were studied. CASE REPORTS: The three patients had motor, sensorial and sphincter involvement. Extra-spinal involvement, such as fever and headache for one, facial nerve palsy for the second and subarachnoid hemorrhage for the third, was also noted. Pleocytosis varied from 10 to 520 white cells per mm3. Lyme serology was positive in CSF for all. Intrathecal anti-Borrelia antibody index was positive or intermediate for all three patients. Spinal cord MRI revealed a large hyperintense zone involving more than 3 vertebral segments. Myelitis was central, posterior or transverse in the axial plane. The clinical course was favorable after a three-week course of appropriate antibiotics. CONCLUSION: These 3 cases and the others from the literature show the diversity of the clinical and radiological features of acute myelitis: transverse, central or posterior myelitis. Thus, Lyme serology in CSF in indicated for patients presenting acute myelitis, particularly in endemic areas.

PMID: 18033042 [PubMed - indexed for MEDLINE]

116. Eur J Neurol. 2007 Dec;14(12):e1-2.

Opsoclonus myoclonus syndrome in two cases with neuroborreliosis.

Skeie GO, Eldøen G, Skeie BS, Midgard R, Kristoffersen EK, Bindoff LA.

PMID: 18028183 [PubMed - indexed for MEDLINE]

117. Onkologie. 2007 Nov;30(11):564-6. Epub 2007 Oct 16.

Lyme disease in a patient with chronic lymphocytic leukemia mimics leukemic meningeosis.

Schweighofer CD, Fätkenheuer G, Staib P, Hallek M, Reiser M.

Department of Internal Medicine I, University of Cologne, Germany. carmen.schweighofer@uk-koeln.de

BACKGROUND: Involvement of the central nervous system (CNS) is a rare complication of chronic lymphocytic leukemia (CLL) and seems to be more frequent in patients with Richter's syndrome or prolymphocytic transformation. Cases with leptomeningeal involvement reported in the literature mostly do not discuss the definition of CLL-associated meningeosis and the exclusion of neuroborreliosis. PATIENT AND METHODS: We present the case of a 75-year-old male patient who was admitted to a rural hospital with ataxia, disorientation, and signs of progressive CLL disease. He was diagnosed of suspicious meningeosis leukemica, and treatment was started with dexamethasone for leukemic CNS involvement. RESULTS: When referred to our center, careful immunophenotyping of the CNS lymphocytes as well as assessment for infectious causes of lymphocytic meningitis led to the diagnosis of Lyme disease/neuroborreliosis. An antibiotic regimen with ceftriaxone for 3 weeks resulted in complete remission of all symptoms. There was no need for CLL treatment. CONCLUSION: In conclusion, this case report should alert clinicians that lymphocytic meningeal involvement in CLL patients accounts for the rare leukemic meningeosis only if cerebrospinal fluid cells show a predominating immunophenotype of typical BCLL cells, i.e. by flow cytometry, and if any infectious cause including Lyme disease has been ruled out.

PMID: 17992027 [PubMed - indexed for MEDLINE]

118. Neurology. 2008 Mar 25;70(13):992-1003. Epub 2007 Oct 10.

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.

Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, Slavov I, Cheng J, Dobkin J, Nelson DR, Sackeim HA.

Columbia University, 1051 Riverside Drive, Unit 69, New York, NY 10032, USA. baf1@columbia.edu

Comment in: Neurology. 2008 Mar 25;70(13):986-7. Neurology. 2009 Jan 27;72(4):383-4; author reply 384. Neurology. 2009 Jan 27;72(4):384-5; author reply 385.

BACKGROUND: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. METHODS: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. RESULTS: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. CONCLUSION: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.

PMID: 17928580 [PubMed - indexed for MEDLINE]

119. Neurology. 2008 Mar 25;70(13):986-7. Epub 2007 Oct 10.

Prolonged Lyme disease treatment: enough is enough.

Halperin JJ.

Comment in: Neurology. 2008 Oct 21;71(17):1379-80; author reply 1380-1. Neurology. 2008 Oct 21;71(17):1380; author reply 1380-1. Neurology. 2009 Jan 27;72(4):384-5; author reply 385.

Comment on: Neurology. 2008 Mar 25;70(13):992-1003.

PMID: 17928578 [PubMed - indexed for MEDLINE]

120. Diagn Microbiol Infect Dis. 2007 Dec;59(4):355-63. Epub 2007 Sep 20.

Antigen biochips verify and extend the scope of antibody detection in Lyme borreliosis.

Du W, Ma X, Nyman D, Povlsen K, Akguen N, Schneider EM.

Section Experimental Anesthesiology, University Clinic Ulm, D-89075 Ulm, Germany. weidong.du@uni-ulm.de

The antibody response of serum IgM and IgG of patients with neuroborreliosis and erythema migrans of Lyme borreliosis (LB) was examined against a 41-kDa flagellar antigen and an 8-mer synthetic OspC8 peptide (VAESPKKP) derived from the C-terminus of outer surface protein C (OspC) from Borrelia garinii. We developed a streptavidin-modified biochip-based immunodiagnosis and compared it with conventional methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). The diagnostic sensitivity of the coated biochips was demonstrated to be identical, and the results of conventional assays such as ELISA and WB were confirmed. Flagellar antigens lead to better diagnosis because of a higher discriminative value. By contrast, OspC8, a peptide derived from the outer surface antigen, is less sensitive to identify immunity in LB. The inferior antigenicity of OspC8 may be due to epitope masking. Overall, this system is open to simultaneously analyze a larger family of peptides differing in length. Thus, an array approach is generally more advantageous to extend the pattern of antigens to be tested for antigenicity in LB. Serial analysis during ongoing disease may be valuable to learn more about the course of the disease and intermittent reactivation of infection. Protein biochip as a potential substitution of ELISA and WB method offers the opportunity to study serum immunity in a multiplicity of patients simultaneously.

PMID: 17888607 [PubMed - indexed for MEDLINE]

121. J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1160-1.

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.

PMID: 17878200 [PubMed - indexed for MEDLINE]

122. Neurology. 2007 Sep 4;69(10):953-8.

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

Comment in: Neurology. 2007 Sep 4;69(10):949-50. Neurology. 2008 Jul 8;71(2):150; author reply 150-1.

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]

123. Hautarzt. 2007 Jun;58(6):541-50, quiz 551-2.

[Lyme borreliosis in children. Epidemiology, diagnosis, clinical treatment, and therapy]

[Article in German]

Fingerle V, Huppertz HI.

Nationales Referenzzentrum für Borrelien, Max-von-Pettenkofer-Institut, Ludwig-Maxmillians-Universität München. fingerle@m3401.mpk.med.uni-muenchen.de

In Europe, Lyme borreliosis is the most common disease communicated by ticks and especially affects the skin, nervous system, joints, and heart. It is caused by at least four species of the spirochete Borrelia burgdorferi. The various pathologies are classified as early forms (erythema migrans, borrelia lymphocytom, early neuroborreliosis, carditis) or late forms (arthritis, acrodermatitis chronica atrophicans, chronic neuroborreliosis). The accuracy of serodiagnosis is 20-50% with erythema migrans, 70-90% with early neuroborreliosis, and nearly 100% with Lyme arthritis. Following special indications, the agent is confirmed by skin biopsy or spinal or joint puncture. Oral therapy is performed with amoxicillin, doxycycline, and cefuroxime, and intravenous therapy uses ceftriaxone, cefotaxime, or penicillin G. All in all, the prognosis of treated Lyme borreliosis is good. In childhood permanent defects are extremely rare, even following long-term manifestation at an early age.

PMID: 17729432 [PubMed - indexed for MEDLINE]

124. Acta Radiol. 2007 Sep;48(7):755-62.

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]

125. Wiad Lek. 2007;60(3-4):167-70.

[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.

PMID: 17726871 [PubMed - indexed for MEDLINE]

126. Med Mal Infect. 2007 Jul-Aug;37(7-8):368-80. Epub 2007 Aug 17.

[Treatment and follow up of disseminated and late Lyme disease]

[Article in French]

Mohseni Zadeh M.

Service de médecine interne et de maladies infectieuses et tropicales, hôpital civil, 1, place de l'Hôpital, BP 426, 67091 Strasbourg cedex, France. m.mohseni@caramail.com

The aim of this review was to analyze the current strategies of treatment and follow-up of disseminated and late Lyme borreliosis. A comprehensive search was performed using the Medline database. Only relevant reviews, expert guidelines and randomized controlled clinical trials were selected and, if necessary, open trials. Major drugs used in these studies were amoxicillin, doxycycline, penicillin G, and ceftriaxone. Oral administration of antibiotics was preferred in Lyme arthritis whereas parenteral drugs were mostly used in neuroborreliosis. The treatment duration usually ranged from 14 to 30 days. Prolonged antibiotic courses recommended by some authors in post-Lyme syndromes were not validated by several randomized placebo controlled studies. Follow up patterns were analyzed in order to determine possible prognosis parameters allowing to distinguih active Borrelia burgdorferi infection from a sequel of infection.

PMID: 17707605 [PubMed - indexed for MEDLINE]

127. Lancet Neurol. 2007 Sep;6(9):756-7; author reply 757.

Unexplained cerebral vasculitis and stroke: keep Lyme neuroborreliosis in mind.

Topakian R, Stieglbauer K, Aichner FT.

Comment on: Lancet Neurol. 2007 Jun;6(6):544-52.

PMID: 17706557 [PubMed - indexed for MEDLINE]

128. Przegl Epidemiol. 2007;61(1):73-8.

[Diagnostic difficulties in neuroborreliosis in children]

[Article in Polish]

Talarek E, Duszczyk E, Zarnowska H.

Klinika Chorób Zakaźnych 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).

PMID: 17702442 [PubMed - indexed for MEDLINE]

129. Przegl Epidemiol. 2007;61(1):59-65.

[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, Kuśmierczyk J, Ciemerych A, Ciemerych M, Kondrusik M, Pancewicz S, Grygorczuk S, Hermanowska-Szpakowicz T.

Klinika Chorób Zakaźnvch i Neuroinfekcii AM w Białvmstoku.

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.

PMID: 17702440 [PubMed - indexed for MEDLINE]

130. Scand J Infect Dis. 2007;39(9):775-80.

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.

PMID: 17701715 [PubMed - indexed for MEDLINE]

131. Pol Merkur Lekarski. 2007 Apr;22(130):275-9.

[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 Białymstoku, 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.

PMID: 17684925 [PubMed - indexed for MEDLINE]

132. Eur J Neurol. 2007 Aug;14(8):873-6.

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.

PMID: 17662007 [PubMed - indexed for MEDLINE]

133. Acta Neurol Scand. 2007 Aug;116(2):133-6.

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.

PMID: 17661801 [PubMed - indexed for MEDLINE]

134. Eur J Clin Microbiol Infect Dis. 2007 Oct;26(10):685-93.

Lyme meningoradiculitis: prospective evaluation of biological diagnosis methods.

Roux F, Boyer E, Jaulhac B, Dernis E, Closs-Prophette F, Puéchal X.

Service de Rhumatologie, Centre Hospitalier du Mans, 194 avenue Rubillard, 72000, Le Mans, France.

The symptoms of Lyme meningoradiculitis and the value of biological examinations in an endemic area were determined in a prospective study in which data were collected on all patients consecutively hospitalised for Lyme meningoradiculitis at our institution during an 18-month period. Specific antibody titres in the serum and cerebrospinal fluid (CSF) were determined by Vidas enzyme-linked-immunosorbent-assay (IgG + IgM), Dade-Behring enzyme immunoassay (EIA) (IgM; IgG) and Western blot analysis (IgG). We also searched for Borrelia burgdorferi in the CSF by PCR analysis and following culture on a specific medium. A control group was recruited, consisting of 16 consecutive patients who had been referred during the same period with suspected but not confirmed Lyme meningoradiculitis. Eleven patients were included. Borrelia EIA of the serum revealed that 40% of the patients had both elevated specific IgM titres and intrathecal synthesis of specific IgG; 40% of the patients was negative for IgM but had isolated intrathecal synthesis of IgG; 20% of the patients had elevated specific IgM titres without intrathecal synthesis of IgG. PCR analysis and the CSF culture were positive in one case only (B. garinii). The results of this study highlight the importance of systematic serological testing for B. burgdorferi in the CSF in the case of early neuroborreliosis suspicion, even in the absence of IgM serum antibodies, which was the case in 40% of the patients in the present study. Nevertheless, intrathecal anti-B. burgdorferi IgG synthesis, which remains the "gold standard" for the diagnosis of neuroborreliosis, was not detectable in 20% of the patients for whom diagnosis was subsequently confirmed by demonstration of specific serum IgM.

PMID: 17629757 [PubMed - indexed for MEDLINE]

135. MMW Fortschr Med. 2006 Nov 9;148(45):8.

[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.

PMID: 17615738 [PubMed - indexed for MEDLINE]

136. Eur J Clin Microbiol Infect Dis. 2007 Sep;26(9):675-7.

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.

PMID: 17605055 [PubMed - indexed for MEDLINE]

137. Eur J Clin Microbiol Infect Dis. 2007 Aug;26(8):571-81.

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.

PMID: 17587070 [PubMed - indexed for MEDLINE]

138. Praxis (Bern 1994). 2007 May 16;96(20):815-7.

[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.

PMID: 17566418 [PubMed - indexed for MEDLINE]

139. Infect Immun. 2007 Sep;75(9):4351-6. Epub 2007 Jun 11.

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.

PMCID: 1951179 PMID: 17562761 [PubMed - indexed for MEDLINE]

140. Neurology. 2007 Jul 3;69(1):91-102. Epub 2007 May 23.

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.

Erratum in: Neurology. 2008 Apr 1;70(14):1223.

Comment in: Neurology. 2008 May 6;70(19):1719; author reply 1719-20. South Med J. 2008 Jul;101(7):672.

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).

PMID: 17522387 [PubMed - indexed for MEDLINE]

141. Infect Immun. 2007 Aug;75(8):3842-7. Epub 2007 May 21.

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."

PMCID: 1951992 PMID: 17517881 [PubMed - indexed for MEDLINE]

142. Med Mal Infect. 2007 Jul-Aug;37(7-8):496-506. Epub 2007 May 23.

[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.

PMID: 17512148 [PubMed - indexed for MEDLINE]

143. Lancet Neurol. 2007 Jun;6(6):544-52.

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

Comment in: Lancet Neurol. 2007 Sep;6(9):756-7; author reply 757. Lancet Neurol. 2008 Jan;7(1):25; author reply 25.

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.

PMID: 17509489 [PubMed - indexed for MEDLINE]

144. Int J Hematol. 2007 May;85(4):323-5.

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.

PMID: 17483076 [PubMed - indexed for MEDLINE]

145. Folia Microbiol (Praha). 2006;51(6):599-603.

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]

146. N Engl J Med. 2007 Apr 12;356(15):1561-70.

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.

Comment in: N Engl J Med. 2007 Jul 12;357(2):197; author reply 197. N Engl J Med. 2007 Jul 12;357(2):197; author reply 197.

PMID: 17429088 [PubMed - indexed for MEDLINE]

147. Neurology. 2007 Apr 10;68(15):1232-3.

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

PMID: 17420411 [PubMed - indexed for MEDLINE]

148. Med Mal Infect. 2007 Jul-Aug;37(7-8):487-95. Epub 2007 Apr 3.

[Laboratory methods for the diagnosis of clinical forms of Lyme borreliosis]

[Article in French]

Assous MV.

Microbiologie, faculté de médecine René-Descartes, université de Paris-V, Paris, France. mvassous@gmail.com

Methods used to diagnose Lyme borreliosis (LB) vary according to clinical presentations. A very good basis to clarify this nosological and clinical entity is the study published by the "European Concerted Action on Lyme Borreliosis" (EUCALB). In fact, only few studies were performed on cohorts of patients including all clinical forms of LB. For Erythema migrans, serology sensitivity is low (20% to 50%), while the sensitivity of culture or PCR reaches 50%. In early-complicated forms, serology is more sensitive (70 to 90%) with the presence of concomitant IgG and IgM. Screening for antibodies in CSF is very useful for the diagnosis of neuroborreliosis. For this clinical form, culture or PCR sensitivity is disappointing (10 to 30%). In arthritis and acrodermatitis chronica atrophicans (ACA), IgG serology is 100% positive with very high titers; however IgM serology is only positive in 5 to 10% of the cases. In ACA, culture sensitivity ranges from 20 to 60% and PCR sensitivity from 60 to 90%. Specificity of antibodies, natural exposure to the etiologic agent, and cross-reactivity are critical for the final interpretation of serological assessment. Only the use of "serological profiles" allows the exploitation of detailed results (isotypes, intensity). In this approach, IgG avidity could be constructive. The western-blot is intended to confirm the specificity of antibodies found in screening methods (Elisa).

PMID: 17408896 [PubMed - indexed for MEDLINE]

149. MedGenMed. 2006 Sep 19;8(3):71.

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.

PMCID: 1781324 PMID: 17406193 [PubMed - indexed for MEDLINE]

150. Infection. 2007 Apr;35(2):110-3.

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.

PMID: 17401717 [PubMed - indexed for MEDLINE]

151. Med Mal Infect. 2007 Jul-Aug;37(7-8):518-22. Epub 2007 Mar 21.

[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.

PMID: 17376626 [PubMed - indexed for MEDLINE]

152. Med Mal Infect. 2007 Jul-Aug;37(7-8):532-9. Epub 2007 Mar 26.

[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.

PMID: 17368785 [PubMed - indexed for MEDLINE]

153. Med Mal Infect. 2007 Jul-Aug;37(7-8):479-86. Epub 2007 Mar 23.

[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.

PMID: 17367972 [PubMed - indexed for MEDLINE]

154. Scand J Infect Dis. 2007;39(2):187-90.

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.

PMID: 17366045 [PubMed - indexed for MEDLINE]

155. Med Mal Infect. 2007 Jul-Aug;37(7-8):435-45. Epub 2007 Mar 9.

[Neurologic and psychiatric manifestations of Lyme disease]

[Article in French]

Blanc F; GEBLY.

Département de neurologie, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg, France. frederic.blanc@chru-strasbourg.fr

The neurological and psychiatric manifestations of Borrelia burgdorferi sensu lato are so numerous that Borrelia is also called the "new great imitator". Thus knowing about the multiple clinical aspects of neuroborreliosis is necessary for the clinician. We reviewed literature for "classical" neuroborreliosis such as acute meningoradiculitis or chronicle encephalomyelitis, but also for encephalitis, myelitis, polyneuritis, radiculitis and more controversial disorders such as chronic neurological disorders, ischemic and hemorrhagic stroke, and motor neuron disease. We specified every time on which basis each disorder was attributed to Lyme disease, particularly if European or American criteria were met. Every part of the nervous system can be involved: from central to peripheral nervous system, and even muscles. In endemic areas, Lyme serology must be assessed in case of unexplained neurological or psychiatric disorder. In case of positive serology, CSF assessment with intrathecal anti-Borrelia antibody index will be more efficient to prove the diagnosis.

PMID: 17350199 [PubMed - indexed for MEDLINE]

156. Intensive Care Med. 2007 Mar;33(3):542-4. Epub 2007 Feb 14.

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

PMCID: 1915615 PMID: 17325838 [PubMed - indexed for MEDLINE]

157. Curr Treat Options Neurol. 2007 Mar;9(2):93-100.

Diagnosis and treatment of the neuromuscular manifestations of lyme disease.

Halperin JJ.

John J. Halperin, MD Atlantic Neuroscience Institute and New York University School of Medicine, Overlook Hospital, 99 Beauvoir Avenue, Summit, NJ 07902, USA. john.halperin@atlantichealth.org.

Although estimates vary, the nervous system appears to be involved in 10% to 15% of patients infected with Borrelia burgdorferi. The resulting disorders, known collectively as neuroborreliosis or nervous system Lyme disease, generally respond well to antimicrobial therapy. Definitive treatment of nervous system infection typically consists of 2 to 4 weeks of parenteral ceftriaxone, cefotaxime, or high-dose penicillin (Class III). However, numerous European studies have shown that oral doxycycline is equally effective in patients with Lyme meningitis and cranial neuritis (Class II and III). This may be equally valid in patients infected with the strains prevalent in the United States, but this remains to be established.

PMID: 17298770 [PubMed - in process]

158. Presse Med. 2007 Jan;36(1 Pt 1):61-3. Epub 2006 Dec 11.

[Back pain without radiculitis as an initial manifestation of Lyme disease: two cases]

[Article in French]

Chanier S, Lauxerois M, Rieu V.

Service de Médecine, Centre Hospitalier, Thiers. sevchanier@voila.fr

INTRODUCTION: The most frequent neurological expression of Lyme disease (borreliosis) during its secondary phase is meningoradiculitis, but atypical presentations occur. Lyme disease must be considered especially in endemic areas and during the summer (May-October). CASES: We report cases of two patients with unusual clinical presentations of neuroborreliosis. Both had acute inflammatory back pain, resistant to the usual analgesic treatment. Both patients responded negatively to questions about tick bites and erythema migrans. Laboratory tests revealed an inflammatory process in only one patient. Lyme disease was confirmed by lymphocytic meningitis and serological tests positive for Borrelia in blood (both cases) and cerebrospinal fluid (one case). Antibiotic treatment led to the disappearance of pain and the normalization of laboratory tests. DISCUSSION: Inflammatory back pain, even without radiculitis, may be related to Lyme disease in endemic areas.

PMID: 17261450 [PubMed - indexed for MEDLINE]

159. Pediatrics. 2007 Jan;119(1):219-20.

Predictive model for Lyme meningitis: a reply.

Avery RA, Frank G, Eppes SC.

Comment on: Pediatrics. 2006 Jul;118(1):438-9.

PMID: 17200294 [PubMed - indexed for MEDLINE]

160. Med Hypotheses. 2007;69(1):117-9. Epub 2007 Jan 2.

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]

161. Clin Exp Immunol. 2007 Jan;147(1):18-27.

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 Linköping, 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.

PMCID: 1810439 PMID: 17177959 [PubMed - indexed for MEDLINE]

162. Wien Klin Wochenschr. 2006 Nov;118(21-22):686-90.

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.

PMID: 17160608 [PubMed - indexed for MEDLINE]

163. Wien Klin Wochenschr. 2006 Nov;118(21-22):638-42.

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.

PMID: 17160601 [PubMed - indexed for MEDLINE]

164. J Neuroimmunol. 2007 Feb;183(1-2):200-7. Epub 2006 Dec 8.

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, Jönköping, and Division of Clinical Immunology, Department of Molecular and Clinical Medicine, Linköping 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.

PMID: 17157926 [PubMed - indexed for MEDLINE]

165. Euro Surveill. 2006;11(10):257-60.

Laboratory diagnosis of Lyme borreliosis at the Portuguese National Institute of Health (1990-2004).

Lopes de Carvalho I, Núncio MS.

Centre for Vectors and Infectious Diseases Research, Instituto Nacional de Saude Dr. Ricardo Jorge (National Institute of Health), Aguas de Moura, Portugal.

Lyme borreliosis is considered to be an emerging infection in some regions of the world, including Portugal. The first Portuguese human case of Lyme borreliosis was identified in 1989. Since 1999, this disease is considered a notifiable disease (DDO) in Portugal, but only a few cases are reported each year, which does not allow consistent analysis of risk factors and the impact on public health. In this study the authors analyse the data available at the Centre for Vectors and Infectious Diseases Research (CEVDI) laboratory, at the Instituto Nacional de Saude Dr. Ricardo Jorge (National Institute of Health, INSA) during the past 15 years (1990-2004) and evaluate them against the registry of national reported cases (1999-2004). Serological tests were the basis for laboratory diagnosis. Data on year of diagnosis, sex, age, geographical origin and clinical signs are available for 628 well documented Portuguese positive cases. The number of cases per year varied between 2 and 78, with the highest number of cases reported in 1997. Of the positive cases, 53.5% were female and the age group most affected was 35-44 years old. Neuroborreliosis was the most common clinical manifestation (37.3%). Human cases were detected in 17 of the 20 regions of Portugal, and the highest number of laboratory confirmed cases were from the Lisbon district. The comparison of the number of notified cases and the number of positive cases confirmed by our laboratory show that Lyme borreliosis is clearly an underreported disease. Due to the scattered distribution of the positive cases and the low prevalence of the tick species Ixodes ricinus, the most effective prevention measure for Lyme borreliosis in Portugal is education of the risk groups on how to prevent tick bites.

PMID: 17130658 [PubMed - indexed for MEDLINE]

166. Rev Med Suisse. 2006 Sep 20;2(79):2122-4, 2126-32.

[Trigeminal neuralgia, neuroborreliosis, and herpes: finding the intruder]

[Article in French]

Abetel G, Danthe C, Hungerbühler P, Lavanchy JD, Nicollier A, Russ D.

PMID: 17073180 [PubMed - indexed for MEDLINE]

167. Infect Immun. 2007 Jan;75(1):243-51. Epub 2006 Oct 23.

Cerebrospinal fluid-infiltrating CD4+ T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early lyme encephalitis.

Lünemann 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.

PMCID: 1828376 PMID: 17060473 [PubMed - indexed for MEDLINE]

168. Microbes Infect. 2006 Nov-Dec;8(14-15):2832-40. Epub 2006 Sep 22.

Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi.

Livengood JA, Gilmore RD Jr.

Centers for Disease Control and Prevention, Division of Vector-borne Infectious Diseases, 3150 Rampart Road, CSU Foothills Campus, Fort Collins, CO 80522, USA.

Human infection by Borrelia burgdorferi, the etiological agent for Lyme disease, can result in serious acute and late-term disorders including neuroborreliosis, a degenerative condition of the peripheral and central nervous systems. To examine the mechanisms involved in the cellular pathogenesis of neuroborreliosis, we investigated the ability of B. burgdorferi to attach to and/or invade a panel of human neuroglial and cortical neuronal cells. In all neural cells tested, we observed B. burgdorferi in association with the cell by confocal microscopy. Further analysis by differential immunofluorescent staining of external and internal organisms, and a gentamicin protection assay demonstrated an intracellular localization of B. burgdorferi. A non-infectious strain of B. burgdorferi was attenuated in its ability to associate with these neural cells, suggesting that a specific borrelial factor related to cellular infectivity was responsible for the association. Cytopathic effects were not observed following infection of these cell lines with B. burgdorferi, and internalized spirochetes were found to be viable. Invasion of neural cells by B. burgdorferi provides a putative mechanism for the organism to avoid the host's immune response while potentially causing functional damage to neural cells during infection of the CNS.

PMID: 17045505 [PubMed - indexed for MEDLINE]

169. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1293-4.

Reinfection with Lyme borreliosis presenting as a painful polyradiculopathy: Bannwarth's, Beevor's and Borrelia.

Miller RF, O'Connell S, Manji H.

PMCID: 2077394 PMID: 17043300 [PubMed - indexed for MEDLINE]

170. J Med Microbiol. 2006 Nov;55(Pt 11):1597-9.

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 Würzburg, D-97080 Würzburg, 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.

PMID: 17030923 [PubMed - indexed for MEDLINE]

171. J Clin Neurophysiol. 2006 Oct;23(5):416-20.

Motion-onset and pattern-reversal visual evoked potentials in diagnostics of neuroborreliosis.

Kubová Z, Szanyi J, Langrová J, Kremlácek J, Kuba M, Honegr K.

Department of Pathophysiology, Charles University in Prague, Faculty of Medicine in Hradec Králové, 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.

PMID: 17016151 [PubMed - indexed for MEDLINE]

172. Ugeskr Laeger. 2006 Aug 21;168(34):2805-7.

[Laboratory diagnosis of infection caused by Borrelia burgdorferi]

[Article in Danish]

Dessau RB, Bangsborg JM, Jensen TP, Hansen K, Lebech AM, Andersen CØ.

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.

PMID: 16942701 [PubMed - indexed for MEDLINE]

173. Infect Immun. 2006 Nov;74(11):6408-18. Epub 2006 Aug 28.

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.

PMCID: 1695479 PMID: 16940140 [PubMed - indexed for MEDLINE]

174. Clin Infect Dis. 2006 Sep 15;43(6):704-10. Epub 2006 Aug 8.

Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid.

Strle F, Ruzić-Sabljić 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.

PMID: 16912943 [PubMed - indexed for MEDLINE]

175. Przegl Epidemiol. 2006;60 Suppl 1:177-85.

[Western-blot with VLSE protein and "in vivo" antigens in Lyme borreliosis diagnosis]

[Article in Polish]

Zajkowska J, Kondrusik M, Pancewicz S, Grygorczuk S, Swierzbińska R, Hermanowska-Szpakowicz T, Czeczuga A, Sienkiewicz I.

Klinika Chorób Zakainych i Neuroinfekcji AM w Białymstoku.

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.

PMID: 16909799 [PubMed - indexed for MEDLINE]

176. Przegl Epidemiol. 2006;60 Suppl 1:167-70.

[New aspects of pathogenesis of Lyme borreliosis]

[Article in Polish]

Zajkowska J, Grygorczuk S, Kondrusik M, Pancewicz S, Hermanowska-Szpakowicz T.

Klinika Chorób Zakaźnych i Neuroinfekcji AM w Białymstoku.

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.

PMID: 16909797 [PubMed - indexed for MEDLINE]

177. Przegl Epidemiol. 2006;60 Suppl 1:109-17.

[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, Swierzbińska R, Hermanowska-Szpakowicz T.

Oddział Internistyczno-Kardiologiczny SP ZOZ w Sokółce.

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.

PMID: 16909787 [PubMed - indexed for MEDLINE]

178. Przegl Epidemiol. 2006;60 Suppl 1:60-1.

[Preliminary studies on presence of antineuronal antibodies in serum of patients with Lyme borreliosis]

[Article in Polish]

Klimczak M, Hermanowska-Szpakowicz T, Zabek J, Zajkowska J, Pancewicz S, Kondrusik M, Grygorczuk S.

Katedra i Klinika Chorób Zakaźnych Akademii Medycznej we Wrocławiu.

Wide spectrum of autoantibodies reactive against neuronal antigens was detected in sera of 32 of 50 studied patients with Lyme borreliosis. This may be potentially of importance in the pathogenesis of neuroborreliosis.

PMID: 16909778 [PubMed - indexed for MEDLINE]

179. Przegl Epidemiol. 2006;60 Suppl 1:39-45.

[Multifocal central nervous system lesions --multiple sclerosis or neuroborreliosis?]

[Article in Polish]

Drozdowski W.

Klinika Neurologii AM w Białymstoku.

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.

PMID: 16909774 [PubMed - indexed for MEDLINE]

180. Przegl Epidemiol. 2006;60 Suppl 1:16-22.

[Specific features of Borrelia burgdorferi infection in children]

[Article in Polish]

Andrzejewski A, Woźniakowska-Gésicka T, Wiśniewska-Ligier M.

III Klinika Pediatrii, Instytut "Centrum Zdrowia Matki Polki" w Lodzi.

Clinical picture of Borrelia burgdorferi infection has been presented in 89 children from Lodz region. The analysis showed significant domination of cases with non specific symptoms (41.6%) as: fever or headache and cases with affected central and peripheral nervous system (30.3%). Peripheral cranial nerves paralysis and symptoms of cerebrospinal meningitis dominated among children with neuroborreliosis. Unlike descriptions concerning adults, majority of the observed symptoms were changes characteristic for I stage of the disease. Dermatosis was found only in (19%) child and symptoms of arthritis in (9%) of them. Contact with tick was stated in 56.8% of the analysed children. Incidence of the disease occurred throughout the whole year, more frequently in summer and autumn months.

PMID: 16909770 [PubMed - indexed for MEDLINE]

181. Clin Microbiol Infect. 2006 Sep;12(9):894-900.

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.

PMID: 16882295 [PubMed - indexed for MEDLINE]

182. Arch Dis Child. 2006 Aug;91(8):660.

Nonparalytic poliomyelitis in Lyme borreliosis.

van Baalen A, Muhle H, Straube T, Jansen O, Stephani U.

University Medical Center Schleswig-Holstein, Christian-Albrechts-Universität zu Kiel, Germany. van.baalen@pedneuro.uni-kiel.de

PMCID: 2083043 PMID: 16861483 [PubMed - indexed for MEDLINE]

183. MMW Fortschr Med. 2006 Jun 22;148(25):39-41.

[Stage-oriented treatment of Lyme borreliosis]

[Article in German]

Fingerle V, Wilske B.

Nationales Referenzzentrum für Borrelien, Max v. Pettenkofer Institut, LMU München. 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.

PMID: 16859159 [PubMed - indexed for MEDLINE]

184. Scand J Infect Dis. 2006;38(8):747-8.

Symptoms of post-Lyme syndrome in long-term outcome of patients with neuroborreliosis.

Pícha D, Moravcova L, Lasikova S, Holeckova D, Maresova V.

PMID: 16857637 [PubMed - indexed for MEDLINE]

185. Pediatrics. 2006 Jul;118(1):438-9.

Predictive model for Lyme meningitis.

Porwancher R.

Comment in: Pediatrics. 2007 Jan;119(1):219-20.

Comment on: Pediatrics. 2006 Jan;117(1):e1-7.

PMID: 16818599 [PubMed - indexed for MEDLINE]

186. Neurocrit Care. 2006;4(3):260-6.

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.

PMID: 16757836 [PubMed - indexed for MEDLINE]

187. Lakartidningen. 2006 May 3-9;103(18):1454; author reply 1455.

[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.

Comment on: Lakartidningen. 2006 Mar 1-7;103(9):668.

PMID: 16729462 [PubMed - indexed for MEDLINE]

188. Eur J Neurol. 2006 May;13(5):536-8.

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.

PMID: 16722982 [PubMed - indexed for MEDLINE]

189. Infection. 2006 Apr;34(2):100-2.

Neuroborreliosis in an HIV-1 positive patient.

Cerný R, Machala L, Bojar M, Rozsypal H, Pícha D.

Department of Neurology, Charles University in Prague, 2nd Faculty of Medicine, V Uvalu 84, 15006 Praha 5, Czech Republic. rudolf.cerny@lfmotol.cuni.cz

Simultaneous co-infections of Borrelia burgdorferi sensu lato and HIV-1 are rare events, with only six published cases. A case of acute neuroborreliosis with facial palsy, meningoradiculitis (Bannwarth's syndrome) in an HIV-1 positive individual is described. Diagnosis was confirmed by Western immunoblot analysis of serum and CSF and by proof of intrathecal production of antibodies against B. garinii. The patient was successfully treated with cefotaxime. In all published HIV+ cases, the course of borreliosis did not differ from that of the HIV negative population and the prognosis in properly treated patients was good.

PMID: 16703302 [PubMed - indexed for MEDLINE]

190. Wiad Lek. 2006;59(1-2):23-6.

[Borreliosis--increasing clinical problem]

[Article in Polish]

Dybowska D.

Katedry i Kliniki Chorób Zakaźnych Akademii Medycznej im. L. Rydygiera w Bydgoszczy.

Lyme disease (LD) is due to infection with Borrelia burgdorferi (B. burgdorferi). We analysed some aspects of epidemiology and clinical manifestation of borreliosis. We tried to estimate the efficiency of diagnostic methods and treatment. We analyzed medical documentation of 300 patients with LD treated in our department between 1993-2001. The diagnosis was made according to Lyme Disease Foundation's criteria. Patients suffering from LD were divided into 3 groups according to stages of the disease. The most frequent manifestation of LD was erythema migrans (EM). The number of LD cases had increased during the observation time. The exposition to tick-bites was greater during summer and early autumn. The great number of patients with EM was observed at the same time. Cases of Lyme arthritis (LA), disseminated EM, Lyme carditis (LC) and neuroborreliosis represented the group number 2. LA, uveitis and acrodermatitis chronica atrophicans (ACA) were diagnosed in the third group of patients. Serological markers of B. burgdorferi infection were found in about 50% of cases of EM and in each patient in group 2 and 3. Complete recovery after antibiotic therapy was observed in every case in early LD and partial one in the late stage.

PMID: 16646287 [PubMed - indexed for MEDLINE]

191. Rev Neurol. 2006 Apr 10;42 Suppl 3:S91-6.

Neuroborreliosis and the pediatric population: a review.

López-Alberola RF.

Section of Child Neurology, University of Miami School of Medicine, Miami, Florida 33136, USA. rlopez@med.miami.edu

AIMS: To review the medical literature on neuroborreliosis, in particular its clinical features in both adults and children, and highlight the differences between the two groups, with an emphasis on the pediatric population. DEVELOPMENT: The neurologic manifestations of the disease variably affect different areas of the neuroaxis, central or peripheral, and can present with early or late symptomatology, depending on the age group. Although the literature includes a wide range of neurologic abnormalities, the most frequent symptom reported in the pediatric population is headache, and the most common sign being facial palsy. An immunologic process with cross-reacting antibodies and antibodies directed against neuronal proteins may exist as the causative factor. Because of characteristic cerebrospinal fluid (CSF) findings, CSF examination and serologic testing for Borrelia burgdorferi, the causative agent, should be performed in patients, particularly if a child, having been in an endemic area, presenting with an acute neurologic disorder of unexplained etiology. Treatment with antibiotics, if initiated early-on, is curative, especially in children. CONCLUSIONS: The pediatric population carries the highest risk for Lyme disease relative to other age groups. Younger patients tend to be more acutely affected, with involvement primarily of the central nervous system, exhibiting an inflammatory response in the CSF and signs/symptoms of aseptic meningitis and facial nerve palsy, whereas older patients present with features of peripheral nervous system pathology, tipically with a radiculopathy. Despite having a greater incidence of neuroborreliosis, the clinical course in most children is milder and shorter than that reported for adults.

PMID: 16642458 [PubMed - indexed for MEDLINE]

192. AJNR Am J Neuroradiol. 2006 Apr;27(4):892-4.

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]

193. Zh Nevrol Psikhiatr Im S S Korsakova. 2006;106(3):48-51.

[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.

PMID: 16608111 [PubMed - indexed for MEDLINE]

194. J Neuroimmunol. 2006 Jun;175(1-2):5-11. Epub 2006 Mar 6.

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.

PMID: 16603253 [PubMed - indexed for MEDLINE]

195. Lakartidningen. 2006 Mar 1-7;103(9):668.

[Penicillin V treatment in erythema migrans can give a false security]

[Article in Swedish]

Wahlberg P, Nyman D.

Comment in: Lakartidningen. 2006 May 3-9;103(18):1454; author reply 1455.

PMID: 16583549 [PubMed - indexed for MEDLINE]

196. Neuroradiology. 2006 Jul;48(7):506; author reply 507. Epub 2006 Mar 28.

Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis.

Scheid R.

Comment on: Neuroradiology. 2005 Sep;47(9):664-7.

PMID: 16568298 [PubMed - indexed for MEDLINE]

197. Acta Neurol Scand. 2006 Apr;113(4):248-55.

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]

198. Curr Microbiol. 2006 Apr;52(4):330-2. Epub 2006 Mar 9.

Lyme disease associated with Alzheimer's disease.

Meer-Scherrer L, Chang Loa C, Adelson ME, Mordechai E, Lobrinus JA, Fallon BA, Tilton RC.

Laurence Meer-Scherrer, 37 Flammat, Aumatt, Switzerland.

This case report discusses a patient with co-occurring neuroborreliosis and Alzheimer's disease (AD). Although no claim is made for causality nor is there objective evidence that spirochetes are involved in AD, co-infection may exacerbate the symptoms of either neuroborreliosis or AD. Much is to be learned about the role of spirochetes in degenerative central nervous system disease.

PMID: 16528463 [PubMed - indexed for MEDLINE]

199. Int J Med Microbiol. 2006 May;296 Suppl 40:11-6. Epub 2006 Mar 9.

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.

PMID: 16524775 [PubMed - indexed for MEDLINE]

200. Lakartidningen. 2006 Jan 25-31;103(4):217-8.

[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 för vetenskapshistoria, Stockholm. erling@kva.se

PMID: 16491554 [PubMed - indexed for MEDLINE]