Possible mechanisms of the formation of chronic fatigue syndrome in the clinical picture of multiple sclerosis

Abstract

A frequent manifestation of multiple sclerosis (MS) is chronic fatigue syndrome, which can be defined as a subjective decrease in the level of physical and/or mental energy. Chronic fatigue syndrome can be divided into asthenia (fatigue at rest), pathological fatigability (fatigue on physical loading), and fatigue on the background of deterioration of other symptoms (exacerbation of MS). There are both central and peripheral mechanisms for the formation of fatigue. The combination of fatigue and affective disturbances, especially depression and sleep disorders (insomnia, restless legs syndrome) is common in MS and may provide evidence that they share common mechanisms--decreases in the activity of the serotoninergic and noradrenergic systems. An important component in the formation of chronic fatigue syndrome consists of endocrine and autoimmune factors, the latter having a greater effect on asthenia than on pathological fatigue. Further studies of the pathogenetic mechanisms of the formation of asthenia and pathological fatigue and clarification of their differential diagnostic signs should allow not only a better understanding of the nature of this syndrome, but also better selection of individual treatment.

Restless Legs Syndrome in Multiple Sclerosis

“…The effectiveness of using psychostimulant agents (e.g. amantadine, pemoline, and modafinil) and antidepressants (fluoxetine, sertraline), whose mechanisms of action are mediated by the monoaminergic systems and lead to declines in the severity of asthenia in 46–68% of cases, is supported by the above-mentioned hypothesis [21]. …”

Sleep disturbances in multiple sclerosis

“…Several etiopathogenic theories have been proposed: central, peripheral, immunological, hormonal, psychosomatic and pharmacological [65][66][67][68][69][70] (see Table 2). Researchers have not reached a consensus on the association of fatigue with clinical or demographic variables, such as age, gender, degree of disability, type of MS, education level and disease duration; nor has it been correlated with either brain atrophy or lesion burden (as measured by MRI) [63].…”

A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis

“…Although the aetiology of CFS has not been established, primary involvement of the central nervous system (CNS) has been suggested . On the basis of consistent post‐mortem findings of midbrain reticular formation lesions in acute poliomyelitis, which has symptoms of severe fatigue, midbrain dysfunction has been postulated as a common mechanism for all post‐viral fatigue .…”