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Chronic fatigue is among the manifestations of focal brain lesions. It is most often encountered in multiple sclerosis (MS) and patients with the sequelae of traumatic, inflammatory, and vascular brain damage (encephalopathies). The aim of the present work was to study the mechanisms of formation of this syndrome in 50 patients with focal brain lesions of different origins (in the inactive stage) and to assess the possibility of correcting it using the combined agent Fezam (2 capsules t.i.d. for one month), which contains piracetam and cinarrizine. In patients with encephalopathies, chronic fatigue syndrome was directly associated with the severity of depression. Patients with MS showed changes in the value-sense sphere. Neuropsychological testing showed that the psychological and personality components played a greater role in the origins of chronic fatigue in patients with encephalopathies than in those with MS. Fezam significantly decreased the severity of chronic fatigue, particularly in patients with MS; in the second group (non-MS patients) this was accompanied by a decrease in the severity of depression. Mild side effects (in six patients — 12%) consisted generally of sleep disturbances. These results indicate that Fezam should be used in the treatment of chronic fatigue in patients with focal brain lesions; in encephalopathies it should be combined with psychoactive agents.