Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases

Garth L. Nicolson, PhD

Disclosures

Lab Med. 2008;39(5):291-299. 

In This Article

Future Directions

This review suggests that various infections could be directly or indirectly involved in the pathogenesis and/or progression of neurodegenerative and neurobehavioral diseases. Although the evidence is far from conclusive for their general involvement,[43] certain cases may eventually be explained by considering infections in the mix of multiple toxic events, such as head trauma, excitotoxicity, nutritional deficiencies, local inflammation, and genetic susceptibilities. These toxic events occur over time and likely participate in pathogenic processes.[2,5,6,7]

An argument can be made that neurodegenerative and neurobehavioral disease progression are affected by various infections. Even if infections are not directly involved in the pathogenesis of neurodegenerative and neurobehavioral diseases, patients with these diseases are at risk for a variety of opportunistic infections that could result in comorbid conditions or promote disease progression. Infections can complicate diagnosis and treatment, and late-stage patients with complex neurological manifestations, meningitis, encephalitis, peripheral neuropathy, psychiatric conditions, or with other signs and symptoms could have infections that are not recognized or treated by their physicians.

Patients with neurodegenerative and neurobehavioral diseases are particularly difficult to treat using single modality approaches. This may be due, in part, to the multifocal nature of their disease and to the fact that often treatments are given to suppress signs and symptoms, rather than treat causes of the disease or its progression. However, even if the causes of neurodegenerative and neurobehavioral diseases are known, by the time therapeutic intervention is undertaken, it may be entirely too late to use this approach. Moreover, if complex, chronic infections are ignored or left untreated, recovery may be difficult to achieve.[139]

Central nervous system infections can stimulate glial responses, and the presence of viral and bacterial infections in nerve cells, in particular, may stimulate autoimmune responses against nerve cell antigens. In the case of MS, some 20 different bacterial and viral infections have been found, but the link between these infections and the pathogenesis of MS is still being debated.[43,70] Perhaps this is the reason that 1 or even a few types of infections cannot be causally linked to MS–there are just too many possibilities. Eventually, certain infections may eventually be linked, at least in a subset of MS patients, to the pathogenesis of this neurodegenerative disease. Further research may shed more light on this important subject.

Does the overall evidence suggest that chronic infections may be involved in the pathogenesis of neurodegenerative and neurobehavioral diseases? At the moment, the evidence is inconclusive. Some individuals can harbor chronic infections without any observable signs or symptoms, although the incidence of infection in such individuals is usually very low, only a few percent (for example[14,15,16,17]). Animal models have provided some additional insight,[117,118,119] but this area will require much more intensive investigation. Some information outside the area exists on the infection of nonhuman primates with neuropathologic microorganisms, such as Mycoplasma fermentans, which results in CNS infection and a fatal disease with neurological signs and symptoms.[166] Animal models that can be reproducibly infected with specific microorganisms to reproduce a similar disease will be an important resource. Future basic and clinical research may ultimately elucidate the involvement of chronic infections in the pathogenesis and progression of neurodegenerative and neurobehavioral diseases.

Finally, one problem that will have to be overcome is the disparity of results from different laboratories.[43] This may be due, in part, to differences in the sources of clinical materials, qualities of reagents, and techniques used. Indeed, in some procedures, such as PCR, there are various problems that must be overcome in the handling of specimens, their stability, presence of interfering substances, contamination, sensitivity and specificity of the tests, and interpretation of the results. Interlaboratory variability will remain a problem unless laboratories work closely together to solve these problems. For example, a multicenter research study on the presence of C. pneumoniae in the CSF of clinically defined, monosymptomatic MS patients was conducted by Sriram and colleagues[167] with good concordance of results. Such studies should eventually alleviate the discrepancies found in the data from different research groups. LM

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