Fatigue: from a symptom to a web of diseases. A medical and cultural vision

Fatigue is a common symptom due to a plethora of causes that include those secondary to general disorders and to neurological diseases. In recent years fatigue has reached greater protagonism as a consequence of post-COVID-19 syndrome, which is frequent and the most common cause of chronic fatigue. This is part of a group of disorders mainly characterized by asthenia (lack of strength) that is persistent and disabling. Marshall Marinker profiled them as those with high “illness” and low “sickness”, meaning a dominant feeling of inner suffering that contrasts with a low external and social consideration. Such a setting will produce mismatches in the laboral, familial and social arena that in the end may be responsible for associated stigmatization. This proves the role of social factors in diseases lacking biological markers. Their relevance has fluctuated all along the history, from the ancient neurasthenia to the present syndromes of chronic fatigue that, shyly, begin to be recognized. We are facing a group of diseases that obey to different origins and distinct mechanisms, such as microbiota dysfunction or alteration of the the gut-brain axis. These are barely known and opened to research and new therapeutical proposals that so far lack enough evidence as to be implemented. It is also remarkable the presence of dysfunction of brain activity. Its main features are mismatches of the integration between primary motor and motor integration areas and also hyperactivation of areas usually nonactive during muscle contraction. These facts are opening new ways to promising research. Primary fatigue syndromes are distinct to secondary forms, which are linked to different organ diseases and to neurological disorders. The last ones can be generated at central level (multiple sclerosis, post-stroke or post-epileptic, tumoral, degenerative dementias, Parkinson disease, amyotrophic lateral sclerosis, dysautonomia, sleep disorders) or at peripheral level (muscle, nerve, neuromuscular junction). Their clinical characteristics are distinctive in both groups and among the different disorders; they are useful as a guide for diagnosis and are disclosed here.