Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters

Objectives: Fatigue is one of the most common, yet poorly defined, disabling symptoms in patients with multiple sclerosis (MS). To delineate more clearly the frequency and type of fatigue, we first compared four widely used fatigue scales in consecutive MS patients. Secondly, to further clarify the nature of fatigue, we investigated its relation to physical disability, course of the disease, immunotherapy, and depression. Patients and Methods: Between February and September 2000, 151 consecutive MS patients entering our outpatient clinic (94 relapsing-remitting, 50 secondary progressive, and 7 primary progressive patients; mean age 29.0-7.3 years, mean disease duration 9.9-6.7 years, median EDSS 3.5) filled in a standardized questionnaire including four fatigue scales - Fatigue Severity Scale (FSS), MS-specific FSS (MFSS), Modified Fatigue Impact Scale (MFIS), and Visual Analogue Scale (VAS). Patients were included in the ‘MS-related fatigue group’ (MS-F) when they stated in the questionnaire that fatigue: 1) is one of their three most disabling symptoms; 2) occurs daily or on most of the days; and 3) limits their activities at home or at work. Patients fulfilling none of these criteria were classified as ‘MS-related nonfatigue group’ (MS-NF). Depression was measured by Beck’s Depression Inventory (BDI). Results: Although all scales showed significant differences between MS-F and MS-NF, correlation between these scales was, at best, moderate (correlation coefficients ranging from 0.06 to 0.56). The most discriminative scales were FSS and MFIS, showing no overlap of the 10th and 90th percentiles for the MS-F and MS-NF groups, with cut-off values of 4.6 and 38, respectively. Depression (BDI≥18) was present in 24 of 148 patients who filled in the BDI (16%). FSS was significantly correlated with physical disability (r =0.33, p <0.0001) and BDI (r =0.41, p<0.0001), but not with age, disease duration, clinical activity, and treatment with interferon-b. In multivariate analysis, however, only BDI independently predicted fatigue. Conclusions: The association of fatigue and depression suggests that there might be either common underlying mechanisms or interdependence by a cause-and-effect relationship that requires further investigation. The weak correlation within various fatigue scales is best explained by the fact that fatigue is a multidimensional symptom and, therefore, the available tests measure and weight different aspects of fatigue. Our findings underline the necessity for a more exact definition of fatigue and the development of more valid tools if these are to be used to evaluate treatments.