NEUROBORRELIOOSI

[Bb]

Lähettäjä: Soijuv Lähetetty: 27.9.2005 9:10

Yleensä neuroborrelioosista puhuttaessa mainitaan aivokalvontulehdus tai hermojuurikalvon tulehdus yms. Ruotsalaisen tutkimuksen mukaan borreliabakteeri saattaa aiheuttaa sairauden varhais- ja myöhäisvaiheessa keskushermoston peruskudoksen vaurioita.


Eur J Neurol 1999 Mar;6(2):169-178

Astroglial and neuronal proteins in cerebrospinal fluid as markers of CNS involvement in Lyme neuroborreliosis.

Dotevall L, Hagberg L, Karlsson JE, Rosengren LE
Department of Infectious Diseases, Goteborg University, Goteborg, Sweden.


Is Lyme neuroborreliosis, even in its early phase, a parenchymatous disorder in the central nervous system (CNS), and not merely a meningitic process?

We quantified cerebrospinal fluid (CSF) levels of four nerve and glial cell marker proteins in Lyme neuroborreliosis patients with pretreatment durations of 7-240 days. All 23 patients had meningoradiculitis, and six had objective signs of encephalopathy. Glial fibrillary acidic protein (GFAp) pretreatment levels in CSF, and the light subunit of neurofilament protein (NFL) levels were related to clinical outcome and declined significantly after treatment (P < 0.001 and P < 0.01, respectively). NFL was detectable in 11 out of 22 patients, and pre- and post-treatment NFL levels were associated with the duration of neurological symptoms within 100 days prior to treatment. Neuron-specific enolase (NSE) concentrations also decreased after therapy (P < 0.001), while CSF levels of glial S-100 protein remained unchanged. The pretreatment duration of disease was related to postinfectious sequelae. GFAp, NSE and NFL levels in CSF are unspecific indicators of astroglial and neuronal involvement in CNS disease.

The findings in the present study are in agreement with the hypothesis that early and late stages of Lyme neuroborreliosis damage the CNS parenchyma.

Eur J Neurol 6:169-178 Copyright 1999 Lippincott Williams & Wilkins

PMID: 10053229
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The organism

"....It is still unclear whether most of the neuronal damage is directly caused by the treponemes, or occurs indirectly through immunologic or other mechanisms..'

The Link Between Infections and Psychiatric Diseases
Benedetto Vitiello, MD and Ljubisa Vitkovic, PhD, 1997

http://www.medscape.com/medscape/psychi ... 97/v02.n04 mh30...
tkovic/mh3058.vitkovic.html

Abstract: This article briefly reviews types of psychopathology that have been or can be etiologically related to infectious agents. Particular emphasis is placed on AIDS dementia, schizophrenia, chronic fatigue syndrome, bipolar disorder, and obsessive-compulsive disorder because these diseases are either best understood or intensely investigated with regard to infectious etiology.

Ongoing research efforts aimed at identifying missing links between infections and psychiatric diseases are briefly described, illustrating current
interests and efforts in this area of biomedical research. [Medscape Mental Health 2(4), 1997. © 1997 Medscape, Inc.]

".......Microorganisms other than viruses can cause very complex psychiatric disease, as illustrated by neurosyphilis. Neurosyphilis is a prominent feature of tertiary syphilis (the third and final stage of Treponema pallidum infection). It occurs 1 to 2 decades after the initial treponemal infection and may exhibit a variety of neuropsychiatric symptoms.[71] It has been estimated that 4% to 9% of the cases of untreated syphilis eventually develop symptomatic neurosyphilis.[72]

The combination of effective prevention and penicillin treatment resulted in a dramatic decline in the rate of syphilitic infection after the 1940s.
Reversing this historical trend, the years 1985-1990 have seen a 75% increase in the incidence of syphilis, which is estimated to be approximately 12 cases per 100,000 people per year (or 3 times the rate in 1956).[71] About 50,000 cases of primary or secondary syphilis have been reported in the US between 1985 and 1990.[71] This surge has paralleled the HIV epidemic, thus raising the possibility that immunologic dysfunction related to HIV infection may facilitate treponemal infection.[73]

Although nowadays rare, tertiary syphilis remains the prototype of infection-induced psychopathology. About 10% to 20% of patients with primary syphilis have signs of early involvement of the CNS, with cellular and protein abnormalities in the CSF.[74] These early CSF abnormalities clear quite rapidly, but their occurrence predicts later symptomatic neurosyphilis.[72]

In the first year of infection, there can be a syphilitic meningitis, with headache, neck stiffness, and vomiting. Meningovascular syphilis can occur 4 to 7 years after the infection and display with focal neurologic signs. More than 10 years after the primary infection, the neuropsychiatric symptoms of tertiary syphilis may emerge. They can vary widely and include impaired cognitive performance, memory loss, confabulation, pseudobulbar palsy, mania, depression, and psychosis. If left untreated, it typically progresses toward "general paresis" (ie, chronic progressive dementia); "tabes dorsalis" (ie, peripheral neuropathy, ataxia, autonomic dysfunction); mutism; spasticity; seizures; and eventually death within 3 to 5 years.

Cortical atrophy, especially of the temporal and frontal cortex, is evident on imaging. Histologic examination shows signs of meningoencephalitis, with an inflammatory meningeal reaction, infiltrates of lymphocytes and plasma cells around cortical small vessels, neuronal loss, and astrocytosis. The spirochetes can be identified, especially in cases of dementia. Progressive degeneration of the spinal posterior columns occurs in tabes dorsalis. Both serum and CSF show immunologic reactivity to T pallidum. The CSF of infected individuals contains more white cells and elevated levels of protein and gamma globulin compared with those found in controls. It is still unclear whether most of the neuronal damage is directly caused by the treponemes, or occurs indirectly through immunologic or other mechanisms......"

Conclusions

Many decades after the realization that T pallidum is the etiologic agent of the protean neuropsychiatric manifestations--until then known as general paresis and tabes dorsalis--the role of infections in causing psychiatric diseases remains extremely topical. Infectious pathogenic etiology is clearly established in some psychiatric diseases, such as those associated with AIDS.

In other psychiatric diseases, such as schizophrenia, viral etiology is postulated but not proven (Table II). The exact pathogenic mechanisms linking infections and psychopathology, however, have not been elucidated. It is now apparent that several kinds of microorganisms can damage the CNS parenchyma through an indirect mechanism (ie, not directly by neuronal infection) via complex effects of neurotoxic agents.

Research efforts are now aimed at clarifying these pathogenic mechanisms of CNS damage. Currently, the absence of sensitive and specific markers of CNS infection that can be utilized in vivo severely limits our ability to conduct clinical research in this area. In addition, a precise relationship between changes in the CSF and parenchyma is unknown, thus severely limiting the utility of CSF for diagnostic and therapeutic purposes. Given that CSF is the only compartment of the CNS that can be easily sampled in patients, better understanding of this relationship is urgently needed.

Noninvasive methods of monitoring brain function in humans by imaging are rapidly advancing. Unfortunately, little, if any, research has been directed toward their application to CNS infections. The potential impact of these new methods on diagnosis and treatment of CNS infections and associated psychiatric diseases is enormous.

Finally, it should be pointed out that the development of antiviral agents has not included sufficient attention to their access to and impact on the brain.

Thus, CNS function may deteriorate despite successful treatment in the periphery, and the CNS may become a reservoir of pathogens. More research in this area is clearly needed. Tremendous strides in understanding the links between infections and psychiatric diseases made in the last decade hold great promise for therapeutic advances in the next."