Fatigue : better understanding, better therapy?

Fatigue affects 75-95% of all multiple sclerosis (MS) patients. It belongs to one of the most disabling symptoms in multiple sclerosis causing social and occupational problems and affecting quality of life in a markedly negative way. Fatigue can be present at all stages of the disease including disease onset and often persists throughout the disease course. The pathophysiology is still unknown although several reasonable suggestions have been made. In this context peripheral and central abnormalities as well as neuroendocrine alterations were discussed as causal factors for fatigue. Even though these factors might contribute in part to the pathology they are not able to explain the entire complexity of the symptom. The current understanding of fatigue as a multicausal symptom complicates a reliable assessment. At present, methods to assess fatigue in an objective way are still missing. The knowledge about the pathology itself therefore mostly depends on subjective measures such as self-reports from patients. Without quantitative measures, however, it is difficult to define fatigue and to differentiate it from non-pathological tiredness. By developing different fatigue scales one has aimed at least at standardising the fatigue symptom and quantifying its dimension. However, these scales often suffer from insufficient discriminatory power between patients and controls, they often do not differentiate between cognitive and motor fatigue, and they were not validated according to methodological standards. At present, therefore, no reliable self-report instrument is available to diagnose patients' fatigue in clinical routine. Objective measures as might be provided by electrophysiological methods are employed even considerably less frequently but might be an interesting methodological approach for the future. The definition of fatigue being difficult and the pathophysiology still unknown, the development of specific therapeutic standards consequently is problematic as well. Various drugs that are supposed to raise the level of neuronal activity have been investigated for the management of MS fatigue. Significant benefits were described for some of the drugs in some subgroups of patients while in others adverse reactions were observed before a benefit could be noticed. It is recommended to combine non-pharmacological treatments and pharmacological approaches in treating MS fatigue. However, one has to be aware that a specific fatigue treatment is still lacking and that the options available today cannot be regarded as a standard treatment for fatigue. The present article will introduce the complexity of MS fatigue by discussing the major issues, assessment and treatment options.