What is myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS)?

What is Myalgic Encephalomyelitis (ME/CFS)?

Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a complex biological illness characterized by profound fatigue lasting at least 6 months with substantial reduction in pre-illness activities, accompanied by postexertional malaise (worsening of symptoms after physical or mental exertion), unrefreshing sleep, and either cognitive impairment or orthostatic intolerance. 1, 2

Core Defining Features

The diagnosis requires all of the following cardinal symptoms:

• Profound fatigue of new or definite onset that is not substantially alleviated by rest and causes significant reduction in occupational, educational, social, or personal activities 1, 2
• Postexertional malaise (PEM) - a worsening of symptoms following physical or cognitive exertion, often delayed by hours or days, which distinguishes ME/CFS from other fatigue conditions 1, 2
• Unrefreshing sleep that does not restore normal energy or function 1
• Cognitive impairment including problems with memory, concentration, and information processing 1
• Orthostatic intolerance with symptoms that worsen upon assuming and maintaining upright posture 1

Duration and Severity

• Symptoms must persist for at least 6 months to meet diagnostic criteria 1, 2
• The illness often follows a viral or bacterial infection in many cases 1
• 25% of patients have severe ME/CFS, meaning they are bed-bound with extreme sensory sensitivity 1
• Prevalence is estimated at 0.5-1.5% in the U.S., with higher rates among females 3

Underlying Pathophysiology

ME/CFS is a biological illness with multiple documented abnormalities, not a psychiatric disorder:

• Immune system dysfunction including diminished natural killer cell function and T cell exhaustion 1
• Mitochondrial dysfunction with impaired energy production and metabolic abnormalities 1, 4
• Neurological abnormalities such as neuroinflammation, reduced cerebral blood flow, and brainstem abnormalities 1
• Vascular and endothelial abnormalities including deformed red blood cells and reduced blood volume 1
• Endocrine dysfunction involving hypothalamus-pituitary-adrenal axis dysfunction and low cortisol levels 1

Critical Diagnostic Pitfalls to Avoid

• Do not misattribute symptoms to simple deconditioning - ME/CFS involves complex pathophysiology beyond lack of fitness 1
• Do not overlook postexertional malaise - this is the hallmark symptom that separates ME/CFS from other fatigue conditions 1
• Do not misdiagnose as a psychiatric disorder - ME/CFS is a biological illness with neurological and immunological components 1
• Do not recommend graded exercise therapy without extreme caution - many patients report severe worsening of symptoms with exercise due to PEM 4, 5

Differential Diagnoses to Consider

Before diagnosing ME/CFS, systematically rule out:

• Anemia, hypothyroidism, and electrolyte disturbances 2
• Depression and anxiety disorders 2
• Sleep disorders 2
• Chronic infections 2
• Postural Orthostatic Tachycardia Syndrome (POTS) - characterized by heart rate increase ≥30 bpm within 10 minutes of standing without hypotension 1
• Long COVID - about half of long COVID patients meet criteria for ME/CFS, with similar pathophysiological mechanisms 1

Economic and Social Impact

• Between 836,000 and 2.5 million Americans have ME/CFS 5
• Annual cost is between $17-24 billion in the U.S. 5
• 29% of patients have unmet healthcare needs and 20% experience food insecurity 5
• Many patients are wheelchair dependent, housebound, or bedbound 6, 5