Chronic fatigue syndrome-cfs,Symptoms.
- Background. | 1 | 2 | 3 | 4 | 5 |
- Chronic fatigue is common and is reported in more than 20% of people seen in primary care [1]. However, the neural substrates of chronic fatigue are not well understood. For clinical use, central fatigue is defined as difficulty in the initiation of, or the ability to sustain, voluntary activities [2]. Central fatigue, in contrast with neuromuscular or peripheral fatigue, represents a failure to complete physical and mental tasks that require self-motivation and internal cues, in the absence of demonstrable cognitive failure or motor weakness [3]. Based on this definition, Chaudhuri and Behan [2] proposed a conceptual model for central fatigue. The work output of voluntary activity depends on the applied voluntary effort, which is controlled by motivational input and perceived effort via feedback from motor, sensory and cognitive systems. Hence, any dissociation between the level of internal input (motivational and limbic) and that of the perceived effort from applied voluntary effort results in the sense of fatigue. Assuming that pathological fatigue is an amplified sense of the normal (physiological) fatigue induced by changes in the variables regulating work output, clinical studies of fatigue disorders can provide clues regarding the neural substrates of fatigue. Symptoms of lesions in the pathways of arousal and attention, such as the reticular and limbic systems, and the basal ganglia, generally include pathological fatigue [2]. Fatigue can also be the primary symptom of a disease itself ‐ this is the case in chronic fatigue syndrome (CFS), which might therefore prove to be a good model for studying the mechanisms underlying fatigue sensation.
- CFS is a clinically defined condition characterized by severe disabling fatigue and a combination of symptoms, the prominent features being self-reported impairments in concentration and short-term memory, sleep disturbances and musculoskeletal pain [4]. The diagnosis of CFS can be made only after alternative medical and psychiatric causes of chronic fatigue have been excluded [4]. Recent studies found biochemical and genetic characteristics in CFS patients, such as a decreased concentration of serum acetyl-L-carnitine [5], a serotonin-transporter gene-promoter polymorphism [6], and autoantibodies against the muscarinic cholinergic receptor [7]. Among these, administration of L-carnitine, which is the precursor of acetyl-L-carnitine, is known to improve the clinical status of CFS patients [8]. In the brain, the acetyl moiety of acetyl-L-carnitine is utilized mainly for the biosynthesis of L-glutamate [9]. In CSF patients, a significant decrease in the uptake of acetyl-L-carnitine was found in several regions of the brain, including the prefrontal (Brodmann's area (BA) 9/46d), temporal (BA21 and 41), and anterior cingulate (BA24 and 33) cortices and cerebellum [9]. However, whether such focal cortical hypofunction is due to an anatomical abnormality has not yet been investigated. We hypothesize that there might be regions with explicit anatomical abnormalities that correlate with the severity of fatigue. To measure the reduction in gray-matter volume, we conducted voxel-based morphometry with high-resolution magnetic resonance imaging (MRI) [10,11].
