Abstract
Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.
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Abbreviations
- CFS:
-
Chronic fatigue syndrome
- TNFα:
-
Tumor necrosis factor
- IL:
-
Interleukin
- NF-ΚB:
-
Nuclear factor-ΚB
- IFN:
-
Interferons
- TLR:
-
Toll-like receptors
- PAMPs:
-
Pathogen-associated molecular patterns
- DAMPs:
-
Damage-associated molecular patterns
- MAPK:
-
Mitogen-activated protein kinase
- ROS:
-
Reactive oxygen species
- RNS:
-
Reactive nitrogen species
- 4-HNE:
-
4-Hydroxynonenal
- MDA:
-
Malondialdehyde
- EBV:
-
Epstein-Barr virus
- CAEBV:
-
Chronic activated Epstein-Barr virus syndrome
- ME:
-
Myalgic encephalomyelitis
- CEBVS:
-
Chronic EBV syndrome
- MS:
-
Multiple sclerosis
- MSRV:
-
MS retrovirus
- HHV:
-
Human herpes virus
- Th2:
-
T helper 2
- DCs:
-
Dendritic cells
- Bcl2:
-
B cell lymphoma 2
- BAX:
-
Bcl-2-associated X protein
- PCR:
-
Polymerase chain reaction
- NS1:
-
Nonstructural protein
- CNS:
-
Central nervous system
- CSF:
-
Cerebrospinal fluid
- TGF-β1:
-
Transforming growth factor β1
- MRI:
-
Magnetic resonance imaging
- HCMV:
-
Human cytomegalovirus
- Nrf2:
-
Nuclear factor erythroid 2 [NF-E2]-related factor 2
- mTOR:
-
Mammalian target of rapamycin protein
- Bf:
-
Borrelia burgdorferi
- PG:
-
Prostaglandin
- ERK:
-
Extracellular signal-regulated kinase
- COX-2:
-
Cyclooxygenase 2
- SC:
-
Stachybotrys chartarum
- NADH:
-
Reduced nicotinamide adenine dinucleotide
- JNK:
-
c-Jun N-terminal kinase
- FoxP3:
-
Forkhead box P3
- DON:
-
Vomitoxin or deoxynivalenol
- STAT3:
-
Signal transducer and activator of transcription 3
- iNOS:
-
Inducible nitric oxide synthase
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Morris, G., Berk, M., Walder, K. et al. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol 53, 2550–2571 (2016). https://doi.org/10.1007/s12035-015-9262-7
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DOI: https://doi.org/10.1007/s12035-015-9262-7