Key words: Multiple sclerosis; modafinil; fatigue; neurotherapeutics; clinical trial.

Introduction and Overview

Fatigue is a disabling symptom in multiple sclerosis (MS), affecting more than 50% of patients with the diagnostic of clinically definite MS. Among patients with fatigue, a high proportion indicates that it represents the most troublesome symptom of the disease (Fisk et al., 1994). As fatigue is a subjective feeling, it usually receives little attention from physicians, patients' family and employers, whereas it has a tremendous impact on the activities of daily life, interfering with work, family life and social activities.

The diagnosis and management of fatigue in MS are complicated by number of issues, including the many forms that the symptom can take. In some cases fatigue may be related to depression, cognitive dysfunction, poor sleeping or motor impairment, defining secondary fatigue. Nevertheless, for many patients, fatigue exists independently of both motor weakness, cognitive or mood disorders: this primary fatigue is felt as an overwhelming sense of tiredness, a lack of energy or a feeling of exhaustion; patients also have the feeling that the effort required to perform action is disproportionately high, and, as a consequence, tend to reduce their physical activity (Comi et al., 2001). This fatigue affects mood and the ability to cope with the disease (Ritvo et al., 1996), and decreases the quality of life (Schwartz et al., 1996).