From Molecular Neurobiology, 20 January 2014 [Epub ahead of print].
The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.
Morris G(1), Berk M, Galecki P, Walder K, Maes M.
1) Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, UK.
Abstract
Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue.
The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders.
This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump.
Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.
From the European Journal of Applied Physiology, September 2014.
Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome.
Neu D, Mairesse O, Montana X, Gilson M, Corazza F, Lefevre N, Linkowski P, Le Bon O, Verbanck P.
Sleep Laboratory and Unit for Chronobiology U78, Department of Psychiatry, Brugmann University Hospital, Université Libre de Bruxelles (U.L.B), Arthur Van Gehuchten Square, 1020, Brussels, Belgium, daniel.neu@chu-brugmann.be.
Abstract
OBJECTIVES
To investigate associated dimensions of fatigue regarding cognitive impairment, psychomotor performances, muscular effort power and circulating cytokine levels and their relations to symptom intensity in a sample of pure chronic fatigue syndrome (CFS) patients without overlapping objective sleepiness or sleep disorders.
METHODS
16 CFS patients were compared to 14 matched controls. We assessed structured symptom-scales, polysomnography, multiple sleep latency tests, attention (Zazzo-Cancellation ZCT, digit-symbol-substitution DSST), psychomotor vigilance and speed (PVT, finger tapping test, FTT), dynamometer handgrip force (tonic and phasic trials) and circulating cytokines (IFN-γ, IL-1b, IL-6, IL-8, IL-10, TNF-α).
RESULTS
In addition to fatigue, CFS patients presented with higher affective symptom intensity and worse perceived sleep quality. Polysomnography showed more slow-wave sleep and microarousals in CFS but similar sleep time, efficiency and light-sleep durations than controls. Patients presented with impaired attention (DSST, ZCT), slower reaction times (PVT) but not with lower hit rates (FTT). Notwithstanding lower grip strength during tonic and phasic trials, CFS also presented with higher fatigability during phasic trials. Cytokine levels were increased for IL-1b, IL-8, IL-10 and TNF-α and fatigue intensity was correlated to grip strength and IL-8.
CONCLUSIONS
In contrast to sleepiness, chronic fatigue is a more complex phenomenon that cannot be reduced to one single measured dimension (i.e., sleep propensity). Showing its relations to different measurements, our study reflects this multidimensionality, in a psychosomatic disorder such as CFS. To obtain objective information, routine assessments of fatigue should rule out sleepiness, combine aspects of mental and physical fatigue and focus on fatigability.
I just dropped the researchers in Belgium (the second study) a very polite email note to point out that the World Health Organization classified CFS/ME as a neurological condition not a psychosomatic condition.