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Key Clinical Updates in Fatigue & Chronic Fatigue Syndrome

A critical appraisal of the Cochrane reviews addressing exercise and cognitive behavioral therapy as treatments for chronic fatigue syndrome concludes that these treatments are better characterized as "adjunctive therapies."


  • Weight loss; fever.

  • Sleep-disordered breathing.

  • Medications; substance use.


Fatigue, as an isolated symptom, accounts for 1–3% of visits to generalists. The symptom of fatigue is often poorly described and less well defined by patients than symptoms associated with specific dysfunction of organ systems. Fatigue or lassitude and the closely related complaints of weakness, tiredness, and lethargy are often attributed to overexertion, poor physical conditioning, sleep disturbance, obesity, undernutrition, and emotional problems. A history of the patient’s daily living and working habits may obviate the need for extensive and unproductive diagnostic studies.

The diagnosis of chronic fatigue syndrome remains hotly debated because of the lack of a gold standard. Persons with chronic fatigue syndrome meeting specific criteria (such as those from the Centers for Disease Control and Prevention) report a greater frequency of childhood trauma and psychopathology and demonstrate higher levels of emotional instability and self-reported stress than persons who do not have chronic fatigue. Neuropsychological and neuroendocrine studies reveal abnormalities in most patients but no consistent pattern. For example, one study found widespread areas of neuroinflammation in the brain of chronic fatigue syndrome patients that were correlated with the severity of neuropsychological symptoms. A longitudinal MRI study showed no abnormal patterns in rate and extent of brain atrophy, ventricle volume, white matter lesions, cerebral blood flow, or aqueductal cerebrospinal fluid flow. Sleep disorders have been reported in 40–80% of patients with chronic fatigue syndrome, but polysomnographic studies have not shown a greater incidence of primary sleep disorders in those with chronic fatigue syndrome than in controls, suggesting that the sleep disorders are comorbid rather than causative. Veterans of the Gulf War show a tenfold greater incidence of chronic fatigue syndrome compared with nondeployed military personnel. Older patients with chronic fatigue syndrome demonstrate a greater disease impact than younger patients, perhaps secondary to their greater autonomic dysfunction, decreased baroreflex sensitivity, and prolonged left ventricular ejection time. One study found that atopy (especially numerous atopic syndromes) is associated with chronic fatigue syndrome. A retrospective cohort study in Germany found an increased risk of chronic fatigue syndrome after a first-time diagnosis of gastrointestinal infection (hazard ratio, 1.35–1.82). The phenomenon of central sensitization is a potential cause.


A. Fatigue

Clinically relevant fatigue is composed of three major components: generalized weakness (difficulty in initiating activities); easy fatigability (difficulty in completing activities); and mental fatigue (difficulty with concentration and memory). Important diseases that can cause fatigue include hyperthyroidism and hypothyroidism, HF, infections (endocarditis, hepatitis), COPD, sleep apnea, anemia, autoimmune disorders, multiple sclerosis, irritable bowel syndrome, Parkinson disease, cerebral vascular accident, and ...

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