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CHRONIC OR LATE LYME DISEASE

Posted Oct 14 2012 3:51pm
The Open Neurology Journal

The previous post came from the above link here

Also included are the following with links to the full papers.

Chronic or Late Lyme Neuroborreliosis: Present and Future Judith Miklossy*, Samuel Donta, Kurt Mueller, Oliver Nolte and George Perry Alzheimer Research Center, Prevention Alzheimer International Foundation, 1921 Martigny-Croix, CP 16, Switzerland
This special issue gives a framework of an international effort, to critically and constructively overview the clinical
and pathological aspects of Lyme neuroborreliosis and show directions for future practice and research.
The issue in the diagnosis and treatment of Lyme neuroorreliosis is assessed followed by a comprehensive analysis
of the involvement of connective tissue and associated clinical manifestations. A critical review shows that both the
meningovascular and meningoencephalitic forms, which define chronic or late neurosyphilis also occur in Lyme
neuroborreliosis. Clinical and pathological confir-mation of these tertiary forms and detection of Borrelia burgdorferi in association with tertiary brain lesions were reported by many authors. These observations indicate that similarly to Treponema pallidum, Borrelia burgdorferi infection is directly involved in the late or chronic manifestations of Lyme neuroborreliosis. Chronic or late Lyme neuroborreliosis both refer to tertiary neuroborreliosis, therefore, the use of these terms as different entities is not justified and may lead to
confusion. 

A critical assessment of clinical trials will guide the design of future clinical studies and a detailed analysis of various factors influencing PCR detection of Borrelia specific DNA would be precious to improve the sensitivity of this potentially important diagnostic tool.
*Address correspondence to this author at the International Alzheimer Research Center, Alzheimer Prevention Foundation, 1921 Martigny-Croix, CP
16, Switzerland; Tel: + 41 27 722 0652, +41 79 207 4442;
E-mail: judithmiklossy@bluewin.ch
An update on the virulence determinants of Borrelia burgdorferi and the pathomechanisms involved in Lyme disease is discussed followed by a review showing the importance of co-infections in the diagnosis and treatment of Lyme disease.
Evidence for an infectious origin of various neuropsychiatric symptoms of tick-borne diseases and various psychiatric disorders are also discussed. The involvement of immune system reactions, chronic inflammation, genetic and environmental factors are also considered. Finally an update on the perspectives on Lyme Borreliosis in Canada closes the special issue.
The majority of authors are internationally recognized neurologists and scientists with extensive experience and
complementary expertise in clinical and/or basic research on Lyme disease. The exchange of knowledge at an international level and between experts in various branches of medicine and in basic research is the way to advance faster in this new, promising and important field of medicine. The aim of this special issue is to contribute to this process. This approach motivated the authors at the annual meeting of the German Borreliosis Society (Deutsche Borreliose-Gesellschaft, DBG) in 2011 at Wuppertal, Germany to initiate and realize this special issue.
This issue is dedicated to the memory of Mark A. Smith whose untimely death has left a void for those looking to
novel ideas to solve chronic diseases.


A Reappraisal of the U.S. Clinical Trials of Post-Treatment Lyme Disease Syndrome, 2012; 6: Pp. 79-87
Brian A. Fallon, Eva Petkova, John G. Keilp and Carolyn B. Britton
Published Date: (05 October, 2012)

Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence.

Methods: The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated.

Results: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures.

Conclusions: Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.


The Psychoimmunology of Lyme/Tick-Borne Diseases and its Association with Neuropsychiatric Symptoms, 2012; 6: Pp. 88-93
Robert C. Bransfield
Published Date: (05 October, 2012)

Disease progression of neuropsychiatric symptoms in Lyme/tick-borne diseases can be better understood by greater attention to psychoimmunology. Although there are multiple contributors that provoke and weaken the immune system, infections and persistent infections are significant causes of pathological immune reactions. Immune mediated effects are a significant contributor to the pathophysiological processes and disease progression. These immune effects include persistent inflammation with cytokine effects and molecular mimicry and both of these mechanisms may be present at the same time in persistent infections. Sickness syndrome associated with interferon treatment and autoimmune limbic encephalopathies are models to understand inflammatory and molecular mimicry effects upon neuropsychiatric symptoms. Progressive inflammatory reactions have been proposed as a model to explain disease progression in depression, psychosis, dementia, epilepsy, autism and other mental illnesses and pathophysiological changes have been associated with oxidative stress, excitotoxicity, changes in homocysteine metabolism and altered tryptophan catabolism. Lyme disease has been associated with the proinflammatory cytokines IL-6, IL-8, IL-12, IL-18 and interferon-gamma, the chemokines CXCL12 and CXCL13 and increased levels proinflammatory lipoproteins. Borrelia burgdorferi surface glycolipids and flagella antibodies appear to elicit anti-neuronal antibodies and anti-neuronal antibodies and Borrelia burgdorferi lipoproteins can disseminate from the periphery to inflame the brain. Autism spectrum disorders associated with Lyme/tick-borne diseases may be mediated by a combination of inflammatory and molecular mimicry mechanisms. Greater interaction is needed between infectious disease specialists, immunologists and psychiatrists to benefit from this awareness and to further understand these mechanisms.


The Lymphocyte Transformation Test for Borrelia Detects Active Lyme Borreliosis and Verifies Effective Antibiotic Treatment, 2012; 6: Pp. 104-112
Volker von Baehr, Cornelia Doebis, Hans-Dieter Volk, Rüdiger von Baehr
Published Date: (05 October, 2012)

Borrelia-specific antibodies are not detectable until several weeks after infection and even if they are present, they are no proof of an active infection. Since the sensitivity of culture and PCR for the diagnosis or exclusion of borreliosis is too low, a method is required that detects an active Borrelia infection as early as possible. For this purpose, a lymphocyte transformation test (LTT) using lysate antigens of Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii and recombinant OspC was developed and validated through investigations of seronegative and seropositive healthy individuals as well as of seropositive patients with clinically manifested borreliosis. The sensitivity of the LTT in clinical borreliosis before antibiotic treatment was determined as 89,4% while the specificity was 98,7%. In 1480 patients with clinically suspected borreliosis, results from serology and LTT were comparable in 79.8% of cases. 18% were serologically positive and LTT-negative. These were mainly patients with borreliosis after antibiotic therapy. 2.2% showed a negative serology and a positive LTT result. Half of them had an early erythema migrans. Following antibiotic treatment, the LTT became negative or borderline in patients with early manifestations of borreliosis, whereas in patients with late symptoms, it showed a regression while still remaining positive. Therefore, we propose the follow-up monitoring of disseminated Borrelia infections as the main indication for the Borrelia-LTT.


Diagnosis of Infectious or Inflammatory Psychosyndromes, 2012; 6: Pp. 113-118
Karl Bechter
Published Date: (05 October, 2012)

Before an outline of the process of diagnosis and differential diagnosis in infectious and/or inflammatory psy-chosyndromes is given, a more general overview onto the approach to organic psychosyndromes seems useful, because in both entities similar principles of causality conclusion are applied. Correlation does not demonstrate causality. Therefore the principles and consensus recommendations, and limitations of causal inference to categorize psychosyndromes as be-ing ‘organic’, is to be discussed in detail.


How do Lyme Borrelia Organisms Cause Disease? The Quest for Virulence Determinants#, 2012; 6: Pp. 119-123
Steven J. Norris
Published Date: (05 October, 2012)

Lyme disease Borrelia are invasive, nontoxigenic, persistent pathogens, and little is known about their mechanisms of pathogenesis. In our laboratory, a signature-tagged mutagenesis (STM) library of over 4,000 Borrelia burgdorferi transposon mutants has been constructed and is being screened for infectivity in mice. In this manner, a global view of the virulence determinants (factors required for full infectivity) is being developed. Additionally, the mechanisms of immune evasion involving the VMP-like system (vls) are under analysis, and cryo-electron microscopy is providing a detailed view of the three-dimensional structure of B. burgdorferi. These approaches will contribute to the improved understanding of how Lyme disease Borrelia cause disease.


All really fascinating articles go to the link above to read in full.

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