6.15. LYME DEMENTIA - A LATE OR CHRONIC FORM OF LYME NEUROBORRELIOSIS
A new volume "Dementia" appeared in the prestigious Handbook of Clinical Neurology: Vol 89 (3rd series); Series Editors: Aminoff, Boller and Swaab, Elsevier
Editors: Charles Duyckaerts (Lab de Neuropath R Escourolle, Paris, France) and
Irene Litvan (Raymond Lee Lebby Professor of Parkinson Disease Research, Department of Neurology, University of Louisville School of Medicine, Louisville, KY, USA)
Website order: http://www.ingentaconnect.com/search/article?title=SYPHILIS&title_type=tka&year_from=1998&year_to=2008&database=0&pageSize=20&index=33
In chapters 71 (Ricardo Nitrini: Clinical and therapeutic aspects of dementia in syphilis and Lyme disease) and 72 (Miklossy J. Biology and neuropathology of dementia in syphilis and Lyme disease) the clinical, pathological and biological aspects of syphilis and Lyme disease are discussed. In chapter 72 the neuropathology and biology of late neurosyphilis and late neuroborreliosis are described. Evidences are presented that chronic or late Lyme neuroborreliosis exists. The pathological changes of tertiary Lyme neuroborreliosis (parenchymal Lyme neuroborreliosis) are strikingly similar to those occurring in tertiary neurosyphilis, also called chronic or late neurosyphilis.
Dementia and stroke as a consequence of Treponema pallidum and Borrelia burgdorferi infections also occur in the tertiary or late stages of these spirochetal diseases.
In meningovascular neurosyphilis and neuroborreliosis the leptomeninges and leptomeningeal arteries are involved leading to Heubner's arteritis and arterial thrombosis with secondary cerebral infarct (indirect parenchymal involvement). When Treponema or Borrelia spirochetes invade the nervous tissue (direct parenchymal involvement) there is a meningo-encephalitis or encephalitis. Two different forms are distinguished. In the infiltrative form there is a severe lymphoplasmacytic infiltration and in the atrophic form, a poor or absent lymphoplasmacytic infiltration, however, severe gliosis (astro- and microgliosis), neuronal loss and cortical atrophy are present. The pathology of both, the infiltrative and atrophic forms were clinically and pathologically documented in neurosyphilis and Lyme neuroborreliosis.
The cases with chronic or late Lyme neuroborreliosis, illustrated in the chapter, were published in per reviewed, internationally recognized medical journals. Some of them more than 15 years ago. Chronic or late Lyme neuroborreliosis was confirmed by clinical, pathological and serological examinations and Borrelia spirochetes, their species specific antigens and genes were detected in the tertiary lesions in the brain. Improvement of late or chronic neurosyphilis and neuroborreliosis following antibiotic treatment was repeatedly reported both in syphilis and Lyme disease, however the treatment of late or chronic cases are more difficult. Syphilis was virtually eradicated by the use of Penicillin, indicating that we can also eradicate Lyme disease. Newer approaches to the treatment of Lyme disease should take into account the frequent co-infection with other pathogens and the need of a more prolonged combination therapy, as it is the case in the treatment of tuberculosis. Even in the doubt of tuberculosis the treatment of the patients with "tritherapy" is necessary for 6 months. It should be an example for the future treatment of Lyme disease. Such treatment, as it was the case in tuberculosis and syphilis, will substantially prevent extensive healthcare costs in the future.
http://www.j-alz.com/issues/13/vol13-4.html Press release (IOS Press)
http://www.sciencedaily.com/releases/2008/05/ "Researchers Explore the Emerging Role of Infection in Alzheimer’s Disease
May 22, 2008, Amsterdam – A number of chronic diseases are in fact caused by one or more infectious agents. For example, stomach ulcers are caused by Helicobacter pylori, chronic lung disease in newborns and chronic asthma in adults are both caused by Mycoplasmas and Chlamydia pneumonia, while some other pathogens have been associated with atherosclerosis. The realization that pathogens can produce slowly progressive chronic diseases has opened new lines of research into Alzheimer’s disease.
In a special issue of the Journal of Alzheimer’s Disease published May 2008, guest editors Judith Miklossy, from The University of British Columbia, and Ralph N. Martins, from Edith Cowan University and Hollywood Private Hospital, Perth, Western Australia, and a group of experts explore this exciting topic.
Alzheimer’s disease (AD), the most frequent cause of dementia, is a form of amyloidosis. It has been known for a century that dementia, brain atrophy and amyloidosis can be caused by chronic bacterial infections, namely by Treponema pallidum in the atrophic form of general paresis in syphilis. Bacteria and viruses are powerful stimulators of inflammation. It was suggested by Alois Alzheimer and his colleagues a century ago that microorganisms may be contributors in the generation of senile plaques in AD.
The fact that pathogens may suppress, subvert or evade host defenses and establish chronic or latent infection has received little attention in the past. During infection, active oxygen and nitrogen species generated by inflammatory cells may cause DNA damage, induce apoptosis, and modulate enzyme activities and gene expression. Depending upon the biology of the pathogen and the host defense mechanisms the organism can persist in the infected tissues and cause chronic inflammation and amyloid deposition. The outcome of infection is as much determined by the genetic predisposition of the patient as by the virulence and biology of the infecting agent. Environmental factors and nutrition are critical determinants of disease expression as well.
In this special issue a series of reviews draws attention to both historic and recent observations related to this emerging field of AD research. The first review shows the importance of chronic inflammation in AD, followed by three articles presenting evidence on the involvement of spirochetes, Chlamydia pneumoniae and Herpes simplex virus type 1 in AD. These are followed by a review of amyloid proteins, which occur in many cellular forms in Eukaryotes and Prokaryotes.
The link between several viral and bacterial infections and the most significant genetic factor for AD, APOE ε4, is discussed in the next review. The link between excessive or misplaced iron and a variety of neurodegenerative diseases and infection is reviewed in the final article.
According to Miklossy and Martins, “The historic and new observations reviewed in this special issue clearly show that high priority should be given for further research in this field as it may have major implications for public health, treatment, and prevention as adequate anti-bacterial and anti-viral drugs are available. Treatment of a bacterial infection and associated viral infection may result in regression and, if started early, prevention of disease. The impact on reducing healthcare costs would be substantial.”
Reviews of the special issue of JAD (abstracts)
Claudia Schwab and Patrick L. McGeer
Inflammatory Aspects of Alzheimer Disease and Other Neurodegenerative Disorders
Brian J. Balin, C. Scott Little, Christine J. Hammond, Denah M. Appelt, Judith A. Whittum-Hudson, Hervé C. Gérard, Alan P. Hudson
Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease
Chronic inflammation and amyloidogenesis in Alzheimer's disease – role of spirochètes
Ruth F. Itzhaki and Matthew A. Wozniak
Herpes Simplex Virus Type 1 in Alzheimer’s disease: The Enemy Within
Neal D. Hammer, Xuan Wang, Bryan A. McGuffie, Matthew R. Chapman
Amyloids: Friend or Foe?
Nadezda Urosevic and Ralph N. Martins
Infection and Alzheimer’s disease: The ApoE e4 connection and lipid metabolism
Angela R. Kamer, Ananda Dasanayeke, Ronald G. Craig, Lidia Glodzik-Sobanska, Miroslow Bry, Mony J. de Leon
Alzheimer’s disease and peripheral infections: The possible contribution from periodontal infections, model and hypothesis
Eugene D. Weinberg, Judith Miklossy
Iron withholding: a defense against disease