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Fatigue in multiple sclerosis: is the picture getting simpler or more complex?

F ATIGUE IS ONE OF THE MOST COMMON AND disabling symptoms of multiple sclerosis (MS). Not only does fatigue affect up to 87% of patients with MS but as many as 40% of patients with MS regard fatigue to be their most disabling symptom. Although several therapies have shown some promise in the treatment of fatigue in patients with MS, the lack of a truly effective treatment for this symptom may be due to the underlying pathophysiology for MS fatigue still being debated. Many factors can contribute to fatigue experienced by patients with MS. In addition to the underlying disease process, factors such as depression, deconditioning, hypothyroidism, anemia, and medications can all contribute to fatigue in patients with MS, making the study of this phenomenon quite complex. Although fatigue in patients with MS can be worsened owing to depression and poor sleep habits, there are several clinical clues to suggest that MS fatigue is related to the underlying pathophysiology of the disease. First, similar to the Uthoff phenomenon, MS fatigue is strongly temperature dependent. It often occurs as an episode, similar to other MS exacerbations, and may even precede typical MS relapses. While most neurologists experienced in the management of patients with MS recognize fatigue as a major component of the disease, many other physicians often dismiss complaints of fatigue. Many psychological symptoms as well as physiological complaints are often described by the patient in terms of fatigue. Because complaints of fatigue are often difficult to define and many patients with MS describe a lack of physical energy, it has been difficult to deal with MS fatigue in terms of its underlying cause.