Post-Exertional Malaise

Post-exertional malaise (PEM) is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome — a disproportionate worsening of symptoms following physical, cognitive, or emotional exertion, typically delayed by 12 to 72 hours. PEM is required for diagnosis by the Canadian Consensus Criteria, International Consensus Criteria, and IOM 2015 criteria. Two-day cardiopulmonary exercise testing studies demonstrate reproducible impairment on the second test day, a pattern not seen in deconditioning or other fatiguing conditions. Research into PEM mechanisms explores immune activation, signals suggestive of impaired cellular energy production, autonomic abnormalities, and ion channel findings in immune cells under physiological stress; no single mechanism has been established as causal.