Despite these limitations, however, the committee was able to glean evidence of symptoms, signs, and objective measures for ME/CFS. Issues related to external and internal validity and to reliability frequently have led to inconsistent results across studies, as well as other shortcomings. One of the most significant challenges to achieving a better understanding of ME/CFS results from the methodological limitations of the current research base. The chapter then examines in turn the evidence on fatigue, post-exertional malaise (PEM), sleep-related symptoms, neurocognitive manifestations, and orthostatic intolerance and autonomic dysfunction in ME/CFS. This review of the evidence on major ME/CFS symptoms and manifestations begins with a discussion of the limitations of the research base in this area. Review of the Evidence on Major ME/CFS Symptoms and Manifestations
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