LYME DISEASE AND MULTIPLE SCLEROSIS: TRICKY AND SERIOUS MEDICINE
I am not an expert in either disorder. I try to read passionately and study both. Here is my concern. First, the routine labs used to diagnosis Lyme and the common other tick infections Bartonella, Babesia and Ehrlichia are really poor and have been dummied down to meet some pre-determined frequency. Very smart and sincere neurologists and infection physicians are expecting a solid large national lab to be as good with these tests as they are with other types of tests. The fact is they are often exceptional with some types of lab testing, and most are terrible at tick and flea-borne infection testing. I am sorry to find this and I take no pride or joy in reporting this is my finding when I test patients with a certain infections and the blinded lab misses it — sometimes up to 6x.
Lyme disease is very common and it can easily cause antibodies against the myelin sheath or the fat around nerves. Multiple Sclerosis is a real and serious illness.
Finally, it is possible in some patients both are present.
The material below is just meant to increase reflection so that a quick diagnosis does not happen to anyone, and any diagnosis is constantly revisited each year, since the treatments differ profoundly for each illness.
- 1: J Neurol. 2008 May;255(5):732-7. Epub 2008 Mar 17.
Erratum in:- J Neurol. 2008 May;255(5):782.
CSF B--lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis.
Ljżstad U, Mygland A.
Dept. of Neurology, Sżrlandet Sykehus HF, Kristiansand Serviceboks 416, 4604 Kristiansand, Norway. unn.ljostad@sshf.no
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.
Publication Types:
PMID: 18344056 [PubMed - indexed for MEDLINE]
- 2: Med Hypotheses. 2008;70(4):826-30. Epub 2007 Sep 21.
Hypothesized role of galactocerebroside and NKT cells in the etiology of multiple sclerosis.
Blewett MM.
Harvard College, 1129 Harvard Yard Mail Center, Cambridge, United States. mblewett@fas.harvard.edu
According to the molecular mimicry theory, multiple sclerosis (MS) develops when the immune system mistakenly attacks a component of the myelin sheath that is structurally similar to a foreign epitope. The glycolipid galactocerebroside (GalC) is a major component of myelin. As lipids comprise between 70% and 85% of myelin, glycolipids should be investigated as candidate autoantigens in MS. GalC displays broad structural similarities to the Borrelia burgdorferi glycolipid antigen BbGL-2 and to the Sphingomonas antigen GalAGSL. In principle, therefore, these bacteria may induce an autoimmune attack on the myelin sheath. GalC is also structurally similar to natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer). Further studies must be performed to clarify the role of GalC in the activation of NKT cells and the development of MS.
PMID: 17889444 [PubMed - indexed for MEDLINE]
- 3: Med Hypotheses. 2007;69(1):117-9. Epub 2007 Jan 2.
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Lyme borreliosis and multiple sclerosis are associated with primary effusion lymphoma.
Batinac T, Petranovic D, Zamolo G, Petranovic D, Ruzic A.
Department of Dermatovenerology, Rijeka University Hospital, Kresimirova 42, 51000 Rijeka, Croatia.
Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by chronic inflammation and demyelination. Studies suggested that the viral, especially Epstein-Barr virus infection, and bacterial infections, especially Borrelia burgdorferi infection, play a role in etiology of MS. MS prevalence parallels the distribution of the Lyme disease pathogen B. burgdorferi. Criteria used for diagnosis of MS can also be fulfilled in other conditions such as Lyme disease, a multisystem disorder resulting from infection by the tick-borne spirochete, B. burgdorferi. In the late period of Lyme disease demyelinating involvement of central nervous system can develop and MS can be erroneously diagnosed. A Lyme borreliosis can mimick central nervous system lymphoma. Also, B. burgdorferi has been implicated not only in etiology of MS, but also in etiology of lymphoma. Studies suggested that there is an increased risk of non-Hodgkin lymphoma in patients, who had a history of autoimmune diseases such as MS and that both non-Hodgkin's lymphomas and Hodgkin's disease were associated with Epstein-Barr virus infection. A small group of lymphomas called primary effusion lymphomas (PEL) is a recently individualized form of non-Hodgkin's lymphoma (WHO classification) that exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. These lymphomas have also been linked to Epstein-Barr virus and human herpes virus type 8 infections but virus negative cases have been described. Therefore, we propose that MS and neuroborreliosis are linked to central nervous system primary effusion lymphomas. As a first step in confirming or refuting our hypotheses, we suggest a thorough study of CSF in the patients suspected for the diagnosis of MS and Lyme borreliosis.
PMID: 17197115 [PubMed - indexed for MEDLINE]
- 4: J Clin Neurophysiol. 2006 Oct;23(5):416-20.
Motion-onset and pattern-reversal visual evoked potentials in diagnostics of neuroborreliosis.
Kubov‡ Z, Szanyi J, Langrov‡ J, Kreml‡cek J, Kuba M, Honegr K.
Department of Pathophysiology, Charles University in Prague, Faculty of Medicine in Hradec Kr‡lovŽ, Czech Republic. kubova@lfhk.cuni.cz
Neuroborreliosis is a form of borreliosis that affects the central and/or peripheral nervous system. Although it can mimic neurologic and ophthalmologic disorders such as multiple sclerosis and optic neuritis, visual evoked potential (VEP) examination is usually not used in neuroborreliosis diagnostics. Combined VEP testing (pattern-reversal VEPs and VEPs produced in response to linear and radial motion) was performed in 81 patients with neuroborreliosis verified by laboratory results (positive polymerase chain reaction or intrathecal antibodies production). Thirty-four patients reported diplopia or blurred vision related to borreliosis. In 33 (40%) patients the VEPs were delayed: motion-onset VEPs were pathologic in 22 (27%) patients, reversal VEPs in 5 (6%) patients, and both VEP types in 6 (7%) patients. The findings suggest that VEP testing (especially the motion-onset VEP testing) can confirm CNS involvement. Much higher sensitivity of motion-onset VEPs in comparison with reversal VEPs can result from rather selective (earlier) involvement of the magnocellular system or the dorsal stream of the visual pathway.
Publication Types:
PMID: 17016151 [PubMed - indexed for MEDLINE]
- 5: 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]
- 6: Adv Nurse Pract. 2005 Sep;13(9):20.
Neuralgia and demyelinating plaques: MS or lyme disease?
Savely G.
South Austin Family Practice Clinic, Austin, Texas, USA.
Publication Types:
PMID: 16152811 [PubMed - indexed for MEDLINE]
- 7: Acta Neurol Scand. 2005 Aug;112(2):97-102.
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Relevance of immunological variables in neuroborreliosis and multiple sclerosis.
Bedn‡rov‡ J, Stourac P, Adam P.
Department of Clinical Microbiology, Faculty Hospital, Masaryk University, Brno, Czech Republic.
OBJECTIVES: The aims were to investigate the frequency of intrathecal synthesis of specific antibodies against measles (M), rubella (R) and varicella zoster (Z) viruses (MRZ reaction) as a diagnostic marker between multiple sclerosis (MS) and neuroborreliosis (NB) groups and to postulate the most typical cerebrospinal fluid (CSF) variables profile of these entities. METHODS: Three cohorts of patients were investigated: MS (n = 42), NB (n = 27) and other neurological diseases (OND) (n = 15). Measles, rubella, varicella zoster and borrelia-specific IgG antibodies were measured by ELISA, Q(alb) (CSF/serum albumin ratio) as a marker of blood-CSF barrier function and specific antibody indices (AI) were calculated according to relevant formulae. IgG oligoclonal bands (OB) were detected by isoelectric focusing and immunoenzymatic staining. RESULTS: Eighty-eight percent of MS patients had positive MRZ reaction and 26.2% had positive anti-borrelia AI. Eighty-nine percent of NB patients had positive anti-borrelia AI and two patients had individually anti-measles and rubella positive AI. MS-CSF variables profile included the presence of IgG OB in 81%, elevated Q(alb) in 31% and normal cell count in 66.7%. Of NB patients IgG OB were positive in 74%, elevated Q(alb) in 81.5% and normal cell count in 7.4%. CONCLUSION: MRZ reaction was proved as statistically significant marker in differential diagnosis between MS and NB. Typical CSF variables profile of these two entities is highly supportive, especially when MRZ is included.
PMID: 16008535 [PubMed - indexed for MEDLINE]
- 8: Brain. 2005 Jul;128(Pt 7):1667-76. Epub 2005 Mar 30.
Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis.
Cepok S, Rosche B, Grummel V, Vogel F, Zhou D, Sayn J, Sommer N, Hartung HP, Hemmer B.
Department of Neurology, Heinrich Heine-University, Duesseldorf, Germany.
Multiple sclerosis is a chronic inflammatory and demyelinating disorder of the CNS with an unknown aetiology. Although intrathecal immunoglobulin G (IgG) synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of multiple sclerosis patients. We analysed the phenotype and kinetics of different B cell subsets in patients with multiple sclerosis, infectious disease (IND) and non-inflammatory neurological disease (NIND). B cells were detected in the CSF of multiple sclerosis and IND patients, but were largely absent in NIND patients. In the CSF, the majority of B cells had a phenotype of memory B cells and short-lived plasma blasts (PB); plasma cells were absent from the compartment. The proportion of PB was highest in multiple sclerosis patients and patients with acute CNS infection. While PB disappeared rapidly from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in multiple sclerosis patients. CSF PB numbers in multiple sclerosis patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in multiple sclerosis patients.
Publication Types:
PMID: 15800022 [PubMed - indexed for MEDLINE]
- 9: Med Sci Monit. 2005 Apr;11(4):BR121-5. Epub 2005 Mar 24.
Diagnosis of Lyme borreliosis using enzyme immunoanalysis.
Cermakova Z, Ryskova O, Honegr K, Cermakova E, Hanovcova I.
Department of Clinical Microbiology, Faculty of Medicine in Hradec Kr‡lovŽ, Charles University of Prague, Czech Republic. cermakovaz@fnhk.cz
BACKGROUND: Antiborrelia antibodies in Lyme borreliosis (LB) are mostly detected by enzyme immunoassay (EIA), confirmed by immunoblot (the "two-step system"). In indicated cases, direct evidence of Borrelia burgdorferi is obtained with the PCR method, electron microscopy and cultivation. The "one-step system" of testing for IgM and IgG antibodies in LB is economically preferably, but it requires an EIA kit with more than 90% sensitivity and specificity. MATERIAL/METHODS: 90 blood samples were collected, 54 from patients with clinically defined LB and 36 samples from individuals free of LB. IgM and IgG antibodies against Borrelia burgdorferi were detected in parallel with five different EIA kits from various producers. The results were verified clinically in all cases, in disputable cases with additional immunoblot (BAG-Med), and analyzed statistically. RESULTS: Specificity and sensitivity were calculated from the measured values, and diagnostic efficiency was determined for each EIA kit. EIA kits for antiborrelia antibody assay with high specificity have low sensitivity and vice versa. In 9 samples from patients with clinical diagnoses (multiple sclerosis, Parkinson disease, epilepsy, rheumatoid arthritis) we found false positives in EIA and WB tests. CONCLUSIONS: The best results for a "one-step system" of examinations for antiborrelia antibodies were obtained with the Abbot and Euroimmun EIA kits in our set. A "two-step system" of serological examination could be composed from the basic IgM and IgG examination with a high sensitivity EIA kit (Viroimmun, Test-Line) followed with confirmation of positives by specific immunoblot.
PMID: 15795690 [PubMed - indexed for MEDLINE]
- 10: Med Hypotheses. 2005;64(3):438-48.
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Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable?
Fritzsche M.
Clinic for Internal and Geographical Medicine, Soodstrasse 13, 8134 Adliswil, Switzerland. markus.fritzsche@gmx.ch
Apart from its devastating impact on individuals and their families, multiple sclerosis (MS) creates a huge economic burden for society by mainly afflicting young adults in their most productive years. Although effective strategies for symptom management and disease modifying therapies have evolved, there exists no curative treatment yet. Worldwide, MS prevalence parallels the distribution of the Lyme disease pathogen Borrelia (B.) burgdorferi, and in America and Europe, the birth excesses of those individuals who later in life develop MS exactly mirror the seasonal distributions of Borrelia transmitting Ixodes ticks. In addition to known acute infections, no other disease exhibits equally marked epidemiological clusters by season and locality, nurturing the hope that prevention might ultimately be attainable. As minocycline, tinidazole and hydroxychloroquine are reportedly capable of destroying both the spirochaetal and cystic L-form of B. burgdorferi found in MS brains, there emerges also new hope for those already afflicted. The immunomodulating anti-inflammatory potential of minocycline and hydroxychloroquine may furthermore reduce the Jarisch Herxheimer reaction triggered by decaying Borrelia at treatment initiation. Even in those cases unrelated to B. burgdorferi, minocycline is known for its beneficial effect on several factors considered to be detrimental in MS. Patients receiving a combination of these pharmaceuticals are thus expected to be cured or to have a longer period of remission compared to untreated controls. Although the goal of this rational, cost-effective and potentially curative treatment seems simple enough, the importance of a scientifically sound approach cannot be overemphasised. A randomised, prospective, double blinded trial is necessary in patients from B. burgdorferi endemic areas with established MS and/or Borrelia L-forms in their cerebrospinal fluid, and to yield reasonable significance within due time, the groups must be large enough and preferably taken together in a multi-centre study.
PMID: 15617845 [PubMed - indexed for MEDLINE]
- 11: Vestn Ross Akad Med Nauk. 2004;(8):3-6.
[Virological and immunological indices in patients with multiple sclerosis]
[Article in Russian]
Agafonov AP, Kameneva SN, Agafonova OA, Neverov AA, Ignat'ev GM.
The level of specific antibodies to viruses of measles, parotitis, type-6 herpes, Epstein-Barr, tick-borne encephalitis and Borrelia burgdorferi as well as presence of genetic samples and antigens of the above infectious antigens were studied in patients with multiple sclerosis (MS). The cytokines Th1 and Th2 parameters were investigated in blood serum of patients at different MS stages. The titer of antibodies to measles virus was noted to be increasing in MS patients with age and disease aggravation. The level of antibodies to any of the studied infectious agents, except for the type-6 herpes virus, was not dynamically changing for as long as 9 months. The viral genetic samples (measles RNA) were detected just once in 2 patients; the detection time coincided in both cases with MS aggravation. The cytokines dynamics failed to correlate with MS aggravation or exacerbation while the total index of all studied cytokines was decreased. A high MMPw 9 content in blood serum correlated with MS exacerbation in 1 patient.
Publication Types:
PMID: 15455682 [PubMed - indexed for MEDLINE]
- 12: Lancet Infect Dis. 2004 Oct;4(10):603-4.
Comment in:
Comment on:
Lyme borreliosis: perspective of a scientist-patient.
Hamlen R.
rhamlen@iximd.com <rhamlen@iximd.com>
Publication Types:
PMID: 15451481 [PubMed - indexed for MEDLINE]
- 13: Neurol Sci. 2004 Apr;25(1):30-3.
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Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.
Iero I, Elia M, Cosentino FI, Lanuzza B, Spada RS, Toscano G, Tripodi M, Belfiore A, Ferri R.
Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, I-94018 Troina (EN), Italy. ivaniero@oasi.en.it
Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.
Publication Types:
PMID: 15060815 [PubMed - indexed for MEDLINE]
- 14: Eur J Neurol. 2003 Nov;10(6):747-8.
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Intrathecal antibody production against Borrelia burgdorferi in a patient with relapsing-remitting multiple sclerosis.
Hartmann M, Pfadenhauer K.
Publication Types:
PMID: 14641530 [PubMed - indexed for MEDLINE]
- 15: Int J Health Geogr. 2002 Dec 20;1(1):5.
Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia.
Fritzsche M.
Clinic for Internal Medicine, Soodstrasse 13, 8134 Adliswil, Switzerland. markus.fritzsche@bluewin.ch
BACKGROUND: Clusters by season and locality reveal a striking epidemiological overlap between sporadic schizophrenia and multiple sclerosis (MS). As the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodid ticks, a meta analysis has been performed between all neuropsychiatric birth excesses including MS and the epidemiology of spirochaetal infectious diseases. RESULTS: The prevalence of MS and schizophrenic birth excesses entirely spares the tropical belt where human treponematoses are endemic, whereas in more temperate climates infection rates of Borrelia garinii in ticks collected from seabirds match the global geographic distribution of MS. If the seasonal fluctuations of Lyme borreliosis in Europe are taken into account, the birth excesses of MS and those of schizophrenia are nine months apart, reflecting the activity of Ixodes ricinus at the time of embryonic implantation and birth. In America, this nine months' shift between MS and schizophrenic births is also reflected by the periodicity of Borrelia burgdorferi transmitting Ixodes pacificus ticks along the West Coast and the periodicity of Ixodes scapularis along the East Coast. With respect to Ixodid tick activity, amongst the neuropsychiatric birth excesses only amyotrophic lateral sclerosis (ALS) shows a similar seasonal trend. CONCLUSION: It cannot be excluded at present that maternal infection by Borrelia burgdorferi poses a risk to the unborn. The seasonal and geographical overlap between schizophrenia, MS and neuroborreliosis rather emphasises a causal relation that derives from exposure to a flagellar virulence factor at conception and delivery. It is hoped that the pathogenic correlation of spirochaetal virulence to temperature and heat shock proteins (HSP) might encourage a new direction of research in molecular epidemiology.
PMID: 12537588 [PubMed - as supplied by publisher]PMCID: PMC149400
- 16: Brain. 2003 Jan;126(Pt 1):20-31.
Comment in:
Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders.
Muraro PA, Wandinger KP, Bielekova B, Gran B, Marques A, Utz U, McFarland HF, Jacobson S, Martin R.
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, MD 20892-1400, USA. murarop@ninds.nih.gov
T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4(+) and CD8(+) T cell clones through the detection and quantification of T cell receptor (TCR) alpha or beta chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clonotype tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders.
Publication Types:
PMID: 12477694 [PubMed - indexed for MEDLINE]
- 17: Wien Klin Wochenschr. 2002 Jul 31;114(13-14):539-43.
Multiple sclerosis and Lyme borreliosis.
Schmutzhard E.
Department of Neurology, University Hospital, Innsbruck, Austria. erich.schmutzhard@uibk.ac.at
In a deductive approach the two disease entities of multiple sclerosis and chronic progressive neuroborreliosis are discussed. Various clinical features, seroepidemiology, neuroimaging, CSF findings, CSF serology, specific proteins within the CSF and antibodies against neuronal structures as well as the most recent findings of different dendritic cells within the CSF are discussed as a means of differentiating these two disease entities.
Publication Types:
PMID: 12422598 [PubMed - indexed for MEDLINE]
- 18: Lancet. 2002 Aug 3;360(9330):352-3.
Bacterial infection as a cause of multiple sclerosis.
Wolfson C, Talbot P.
Department of Epidemiology and Biostatistics, McGill University, and Centre for Clinical Epidemiology and Community Studies, Lady Davis Institute for Medical Research, Quebec, Montreal, Canada. tinaw@epid.jgh.mcgill.ca
PMID: 12241771 [PubMed - indexed for MEDLINE]
- 19: Nervenarzt. 2002 Feb;73(2):144-8.
[The Multiple Sclerosis Documentation System MSDS. Discussion of a documentation standard for multiple sclerosis]
[Article in German]
Pette M, Eulitz M.
Neurologische UniversitŠtsklinik, Klinikum Carl Gustav Carus, Technische UniversitŠt Dresden, Fetscherstrasse 74, 01307 Dresden.
The MSDS (multiple sclerosis documentation system) has been developed at the Department of Neurology, Technical University of Dresden, Germany, during the last 4 years. The first version of this database application has been in use since October 2000. The MSDS manages information on MS patients, their treating physicians, patient history (symptoms, other diseases, biographical history, family history, habits, medication), clinical signs, results of laboratory examinations (blood chemistry, autoantibodies, borrelia serology, evoked potentials, cranial and spinal cord magnetic resonance imaging), clinical scores relevant for MS, and biosamples. In principle, MSDS allows online data input and semiautomatically generates reports to all general practitioners and neurologists treating the respective patient. Patient information sheets and internal treatment guidelines are part of the system. During a 3-month evaluation, the first version of MSDS was tested at eight university multiple sclerosis ambulatory care units and one general neurology hospital. The overall judgement was favorable. Suggestions for changes and improvements, as well as practical experiences, were considered when developing MSDS 2.0, which will be available by the end of 2001.
Publication Types:
PMID: 11975090 [PubMed - indexed for MEDLINE]
- 20: Nervenarzt. 2001 Oct;72(10):820-3.
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[Multiple sclerosis. Chlamydia hypothesis in debate]
[Article in German]
Derfuss T, Hohlfeld R, Meinl E.
Abteilung fźr Neuroimmunologie, Max-Planck-Institut fźr Neurobiologie, Am Klopferspitz 18A, 82152 Martinsried.
Recently, an association between multiple sclerosis and Chlamydia pneumoniae infection has been suggested. Because standardized PCR protocols are lacking, a series of studies could not clarify whether C. pneumoniae is present in brain tissue and CSF of MS patients. Therefore, other studies focused on the humoral immune response against C. pneumoniae: 24% of MS patients, but only 5% of the control patients showed intrathecally produced antibodies against C. pneumoniae. If an infection with C. pneumoniae was involved in the pathogenesis of MS, one would expect that, in analogy to other infections of the CNS, the oligoclonal bands in the CSF of MS patients would recognize the responsible agent. However, the results we obtained by affinity-mediated immunoblots showed that the oligoclonal bands in the CSF of MS patients are not directed against Chlamydia antigen. In contrast to this, we found that the immunoglobulins in the CSF of neuroborreliosis patients reacted strongly against Borrelia antigen in the affinity-mediated immunoblots. In light of these results we assume that the intrathecal immunoglobulin production against C. pneumoniae is part of a polyspecific immune response. Thus, it is not likely that C. pneumoniae is causally linked to the pathogenesis of multiple sclerosis.
Publication Types:
PMID: 11688186 [PubMed - indexed for MEDLINE]
- 21: Nat Immunol. 2001 Sep;2(9):797-801.
Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry?
Benoist C, Mathis D.
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA, USA. cbdm@joslin.harvard.edu
Autoimmune diseases remain one of the mysteries that perplex immunologists. What makes the immune system, which has evolved to protect an organism from foreign invaders, turn on the organism itself? A popular answer to this question involves the lymphoid network's primordial function: autoimmunity is a by-product of the immune response to microbial infection. For decades there have been tantalizing associations between infectious agents and autoimmunity: beta-hemolytic streptococci and rheumatic fever; B3 Coxsackieviruses and myocarditis; Trypanosoma cruzi and Chagas' disease; diverse viruses and multiple sclerosis; Borrelia burgdorfii and Lyme arthritis; and B4 Coxsackievirus, cytomegalovirus or rubella and type 1 diabetes, to name the most frequently cited examples. In addition, animal models have provided direct evidence that infection with a particular microbe can incite a particular autoimmune disease. Nonetheless, many of the associations appear less than convincing and, even for those that seem to be on solid footing, there is no real understanding of the underlying mechanism(s).
Publication Types:
PMID: 11526389 [PubMed - indexed for MEDLINE]
- 22: J Clin Microbiol. 2001 Sep;39(9):3213-21.
Use of serum immune complexes in a new test that accurately confirms early Lyme disease and active infection with Borrelia burgdorferi.
Brunner M, Sigal LH.
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
The present recommendation for serologic confirmation of Lyme disease (LD) calls for immunoblotting in support of positive or equivocal ELISA. Borrelia burgdorferi releases large quantities of proteins, suggesting that specific antibodies in serum might be trapped in immune complexes (ICs), rendering the antibodies undetectable by standard assays using unmodified serum. Production of ICs requires ongoing antigen production, so persistence of IC might be a marker of ongoing or persisting infection. We developed an immunoglobulin M (IgM) capture assay (EMIBA) measuring IC-derived IgM antibodies and tested it using three well-defined LD populations (from an academic LD referral center, a well-described Centers for Disease Control and Prevention (CDC) serum bank, and a group of erythema migrans patients from whose skin lesions B. burgdorferi was grown) and controls (non-Lyme arthritis inflammatory joint disease, syphilis, multiple sclerosis, and nondisease subjects from a region where LD is endemic, perhaps the most relevant comparison group of all). Previous studies demonstrated that specific antigen-antibody complexes in the sera of patients with LD could be precipitated by polyethylene glycol and could then be disrupted with maintenance of the immunoreactivity of the released antibodies, that specific anti-B. burgdorferi IgM was concentrated in ICs, and that occasionally IgM to specific B. burgdorferi antigens was found in the IC but not in unprocessed serum. EMIBA compared favorably with commercial and CDC flagellin-enhanced enzyme-linked immunosorbent assays and other assays in confirming the diagnosis of LD. EMIBA confirmed early B. burgdorferi infection more accurately than the comparator assays. In addition, EMIBA more accurately differentiated seropositivity in patients with active ongoing infection from seroreactivity persisting long after clinically successful antibiotic therapy; i.e., EMIBA identified seroreactivity indicating a clinical circumstance requiring antibiotic therapy. Thus, EMIBA is a promising new assay for accurate serologic confirmation of early and/or active LD.
Publication Types:
PMID: 11526153 [PubMed - indexed for MEDLINE]PMCID: PMC88321
- 23: Brain. 2001 Jul;124(Pt 7):1325-35.
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Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response.
Derfuss T, Gźrkov R, Then Bergh F, Goebels N, Hartmann M, Barz C, Wilske B, Autenrieth I, Wick M, Hohlfeld R, Meinl E.
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Chronic intrathecal immunoglobulin (Ig) production is a hallmark of multiple sclerosis characterized by the presence of oligoclonal IgGs and, in addition, polyspecific recognition of different pathogens such as measles, rubella and herpes zoster virus. While the antigen specificity of the oligoclonal IgGs in multiple sclerosis is largely unknown, the oligoclonal IgGs arising during CNS infectious diseases are reactive against the specific pathogen. Recently, a link between Chlamydia pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple sclerosis, we analysed (i) whether there is intrathecal IgG production against C. pneumoniae in multiple sclerosis and (ii) if the oligoclonal IgGs in the CSF of multiple sclerosis patients recognize C. pneumoniae. By studying paired serum-CSF samples from 120 subjects (definite multiple sclerosis, 46; probable multiple sclerosis, 12; other inflammatory neurological diseases, 35; other neurological diseases, 27) by enzyme-linked immunosorbent assay, we found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases, produced IgGs specific for C. pneumoniae intrathecally (definite multiple sclerosis versus other inflammatory neurological diseases: P = 0.027). The presence of intrathecal IgGs to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG bands from multiple sclerosis patients with an intrathecal Ig production to C. pneumoniae did not react towards purified elementary bodies and reticulate bodies of C. pneumoniae on affinity-mediated immunoblot following isoelectric focusing (IEF-western blots). In contrast, the IgGs in the CSF of control patients with neuroborreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi, by IEF-western blot analysis. Concomitant analysis of the CSF of 23 patients with a nested polymerase chain reaction for C. pneumoniae was negative in all cases. Together, our findings strongly suggest that the immune response to C. pneumoniae is part of a polyspecific intrathecal Ig production, as is commonly observed with other pathogens. This argues against a specific role for C. pneumoniae in multiple sclerosis.
Publication Types:
PMID: 11408328 [PubMed - indexed for MEDLINE]
- 24: Ann Agric Environ Med. 2000;7(2):141-3.
Lyme borreliosis and multiple sclerosis: any connection? A seroepidemic study.
Chmielewska-Badora J, Cisak E, Dutkiewicz J.
Department of Occupational Biohazards, Institute of Agricultural Medicine, Jaczewskiego 2, 20-090 Lublin, Poland.
A total of 769 adult neurological patients hospitalised in clinics and hospitals situated in the Lublin region (eastern Poland) were examined during the years 1997-2000 with ELISA test for the presence of anti-Borrelia burgdorferi sensu lato antibodies. A statististically significant (p=0.0422) relationship was found between the clinically confirmed diagnosis of multiple sclerosis and the positive serologic reaction with Borrelia antigen. Ten out 26 patients with multiple sclerosis (38.5%) showed positive serologic reaction to Borrelia, whereas among the total number of examined neurological patients the frequency of positive findings was twice as low (19.4%). The result suggests that multiple sclerosis may be often associated with Borrelia infection
Publication Types:
PMID: 11153045 [PubMed - indexed for MEDLINE]
- 25: Neurology. 2000 Dec 12;55(11):1704-14.
Mechanisms of immunomodulation by glatiramer acetate.
Gran B, Tranquill LR, Chen M, Bielekova B, Zhou W, Dhib-Jalbut S, Martin R.
Cellular Immunology Section, Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892, USA.
OBJECTIVE: To define the mechanism of action of glatiramer acetate (GA; formerly known as copolymer-1) as an immunomodulatory treatment for MS. BACKGROUND: The proposed mechanisms of action of GA include 1) functional inhibition of myelin-reactive T cells by human leukocyte antigen (HLA) blocking, 2) T-cell receptor (TCR) antagonism, and 3) induction of T helper 2 (Th2) immunomodulatory cells. In this report, the authors examined the effects of GA on the functional activation of human T-cell clones (TCC) specific for myelin basic protein (MBP) and for foreign antigens. Several questions were addressed: Is the inhibitory effect of GA specific for autoantigens? Is it mediated by blocking the interaction between peptide and HLA molecule? Is GA a partial agonist or TCR antagonist, or does it induce anergy? Does it induce Th2 modulatory T cells? METHODS: The effects of GA on antigen-induced activation of human TCC specific for MBP, influenza virus hemagglutinin, and Borrelia burgdorferi were studied by proliferation and cytokine measurements, TCR downmodulation, and anergy assays. GA-specific TCC were generated in vitro from the peripheral blood of patients and healthy controls by limiting dilution. RESULTS: GA more strongly inhibited the proliferation of MBP, as compared with foreign antigen-specific TCC; in some MBP-specific TCC, the production of Th1-type cytokines was preferentially inhibited. In addition to HLA competition, the induction of anergy, but not direct TCR antagonism, was observed. Numerous GA-specific TCC were generated from the peripheral blood of both MS patients and normal controls, and a fraction of these showed a Th2 phenotype. CONCLUSIONS: This study confirms a preferential inhibitory effect of GA on autoreactive TCC. With respect to cellular mechanisms, although HLA competition appears to play the most important role in functional inhibition in vitro, a direct effect on the TCR may be involved at least in some autoreactive T cells as shown by anergy induction. Although not confirmed at the clonal level, it is demonstrated further that GA induces T cells that crossreact with myelin proteins. GA-specific, Th2-modulatory cells may play an important role in mediating the effect of the drug in vivo.
Publication Types:
PMID: 11113226 [PubMed - indexed for MEDLINE]
- 26: Ital J Neurol Sci. 1998 Aug;19(4):235-9.
Chorea as a symptom of neuroborreliosis: a case study.
Piccolo I, Thiella G, Sterzi R, Colombo N, Defanti CA.
Division of Neurology, Hospital Niguarda Ca' Granda, Milan, Italy.
Borrelia burgdorferi (Bb) can cause a large number of neurological symptoms. Although extrapyramidal disturbances are rare (representing less than 2% of all neurological complications), diffuse choreic dyskinesias have been described during the course of mild encephalitis. The data published in the literature suggest that there are clinical and neurological analogies between neuroborreliosis and multiple sclerosis (MS). The presence of specific anti-Bb antibodies in cerebrospinal fluid is a discriminating factor that allows a diagnosis of neuroborreliosis to be made. We describe the case of a patient with Lyme disease, characterised by widespread chorea and behavioural disturbances. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating a diagnosis, and the uncertainties concerning the pathophysiology and clinical/neuroradiological correlations of the disease.
Publication Types:
PMID: 10933464 [PubMed - indexed for MEDLINE]
- 27: J Neurosci Res. 1999 Dec 15;58(6):779-90.
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Borrelia burgdorferi induces matrix metalloproteinases by neural cultures.
Perides G, Tanner-Brown LM, Eskildsen MA, Klempner MS.
Tupper Research Institute, Department of Medicine, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts. gperides@caregroup.harvard.edu
Matrix metalloproteinases (MMPs) are associated with chronic neurologic diseases such as multiple sclerosis and senile dementia. Lyme disease is a multisystemic infection involving the nervous system, skin, joints, and heart. Neurologic manifestations of chronic Lyme disease include encephalopathy and cranial and peripheral neuropathy. Borrelia burgdorferi, the spirochaete causing Lyme disease, has been cultured from the cerebrospinal fluid (CSF), and B. burgdorferi DNA is frequently detected in the CSF of patients with Lyme neuroborreliosis. We used cerebral and cerebellar primary cultures to determine whether B. burgdorferi induces the production of MMPs by primary neural cultures. B. burgdorferi in a dose- and time-dependent manner induced the expression of MMP-9 by primary neural cultures but had no effect on the expression of MMP-2. Human and rat type I astrocytes expressed MMP-9 when incubated with B. burgdorferi in the same manner as primary neural cultures. This response may play a role in the symptomatology and the pathogenesis of Lyme neuroborreliosis. Copyright 1999 Wiley-Liss, Inc.
Publication Types:
PMID: 10583909 [PubMed - indexed for MEDLINE]
- 28: Klin Monatsbl Augenheilkd. 1999 Oct;215(4):258-62.
[Eye involvement in circumscript scleroderma--manifestation of borreliosis?]
[Article in German]
Framme C, Dietrich J, Lohmann CP, Sachs HG.
Augenklinik und Poliklinik, Klinikum, UniversitŠt Regensburg.
BACKGROUND: The circumscript cutaneous sclerosis is an inflammato-edematous erythema of the skin, usually leading to a plaque-like sclerosis and cutaneous atrophy. The etiology of this disease remains unknown, but some authors presume a systemic infection with Borrelia burgdorferi as the underlying pathological condition. PATIENT: We present a case of a 66-year-old male patient who suffered from episcleritis of his left eye. Funduscopy showed an unilateral papillary edema. Visual acuity was 1.0. The patient had multiple erythemata of the skin of the body-trunk and the arms. On histological examination the lesions were compatible with circumscript sclerosis. Neurological examination was normal. Brain imaging (MRI), CSF examination and serology showed no pathological findings, although the patient presented with raised antibodies against Borrelia burgdorferi (IgG positive, IGM negative). Intravenous antibiotic treatment and topical steroids for three weeks resulted in a complete recovery of the scleritis, but had no effect on the papillary edema. CONCLUSION: Inflammatory pathological findings of the eye can be associated with circumscript sclerosis, a disease, that is normally limited to the skin. The pathological mechanism remains unclear. The presumption of an underlying borreliosis could not be confirmed in this case.
Publication Types:
PMID: 10572891 [PubMed - indexed for MEDLINE]
- 29: Cell Immunol. 1999 May 25;194(1):118-23.
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Cross-reactivity of Borrelia burgdorferi and myelin basic protein-specific T cells is not observed in borrelial encephalomyelitis.
Pohl-Koppe A, Logigian EL, Steere AC, Hafler DA.
C