If fatigue is suspected, a thorough history is the first step of the diagnostic workup. Begin with an open-ended question that specifically addresses the patient’s energy level or the presence of tiredness. Patients should be allowed to use their own descriptors. If a classic description of fatigue (exhaustion, tiredness, low energy, lack of stamina) cannot be elucidated, then the patient may be speaking of another symptom, which will necessitate ruling out alternative or concomitant conditions.
If the patient’s symptoms suggest sleepiness or hypersomnolence, the use of validated instruments to characterize the symptom further may be useful. The Epworth Sleepiness Scale is a validated 8-item questionnaire used in the outpatient setting to evaluate subjective sleepiness. It uses a 4-point Likert scale to quantify the patient’s likelihood of falling asleep (dozing) in 8 sedentary circumstances (Johns 1991). A score of 10 or higher indicates sleepiness. Another useful instrument used to quantify sleep quality is the Pittsburgh Sleep Quality Index (PSQI), which is a 19-item instrument that measures sleep quality and disturbances over the preceding month (Buysse et al 1989). Prior studies have shown that measurement of perceived sleep quality using the PSQI may correlate with fatigue in persons with multiple sclerosis (Kaynak et al 2006). The presence of sleepiness, poor sleep quality, or the use of sleep as a recovery mechanism for fatigue necessitates screening for potential sleep disorders, including obstructive sleep apnea, insomnia, narcolepsy, periodic leg movement disorder, and restless legs syndrome. Although restless legs syndrome and insomnia are clinical diagnoses, overnight polysomnography is recommended for symptoms suggestive of obstructive sleep apnea or periodic leg movement disorder. Symptoms suggestive of narcolepsy warrant a nocturnal polysomnogram followed by a daytime multiple sleep latency test. Referral to a sleep specialist for assistance with diagnosis or treatment may be useful.
Symptoms of depressed mood, anhedonia, or psychomotor retardation should alert the clinician to screen for depression. A positive screen warrants prompt treatment or referral to a mental health specialist. Reassessments should be conducted frequently to assess treatment responsiveness. Associated sleep disturbances that may accompany depression, such as insomnia, should be treated separately if they persist following treatment.
Anemia, infection, vitamin deficiencies, and thyroid abnormalities should be ruled out with appropriate laboratory testing when appropriate. Medications with known side effects of hypersomnolence should be identified and minimized, if possible.
If fatigue persists after ruling out/addressing other treatable conditions, quantification of its severity may be useful to track treatment progress. Many instruments for quantification are available, including scales designed specifically for persons with multiple sclerosis. Two of the most widely used scales include Krupp’s Fatigue Severity Scale (FSS) (Krupp et al 1989) and the Modified Fatigue Impact Scale (MFIS), which was derived from the Fatigue Impact Scale (Fisk et al 1994). Both scales correlate well with each other, have shown acceptable consistency and reliability, and can be easily administered in the clinic. The FSS consists of 9 items based on a Likert scale (range 1 to 7). A score of 36 or more suggests fatigue. The MFIS contains 21 items on a Likert scale (range 0 to 4) that cover the physical, cognitive, and psychosocial aspects of fatigue; a general score is obtained by totaling these items. A score of 38 or more suggests fatigue.