ME/CFS is an acquired, chronic, multi-system disease characterized by significant relapse after physical, cognitive, or emotional exertion of any sort. The disease includes immune, neurological and cognitive impairment, sleep abnormalities, and autonomic dysfunction, resulting in significant functional impairment accompanied by a pathological level of fatigue. The cause of the disease remains unknown, although in many cases symptoms may have been triggered by an infection or other prodromal event.

National Academy of Medicine’s Clinical Diagnostic Criteria (2015)

    1. Impairment of normal function accompanied by fatigue persisting >6 months
    2. Post-exertional malaise (PEM)*
    3. Unrefreshing Sleep*

    Plus at least one of the following:

    1. Cognitive Impairment*
    2. Orthostatic Intolerance (OI)

    *Must be moderate-severe and present >50% of time         

    Other common but more variable features of illness:

    • Pain (headache, muscle and joint aches, hyperalgesia/fibromyalgia)
    • Immune manifestations (allergy, inflammation, sensitivities)
    • Infection (viral or atypical infections)

Diagnostic Criteria

Diagnosis requires that the patient have the following three symptoms:

  • A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest, and
  • Post-exertional malaise,* and
  • Unrefreshing sleep*

At least one of the two following manifestations is also required:

  1. Cognitive impairment*
  2. Orthostatic intolerance

* Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.

Other ME/CFS symptoms include widespread pain; additional forms of sleep disturbance; light, noise, and chemical sensitivity; sore throat; tender lymph nodes; headaches; gastrointestinal problems; and genitourinary issues. The NAM Clinician’s Guide provides further explanation and guidance on how to identify both core symptoms and additional symptoms. (Clinician Coalition Guide)

Syndrome Criteria 

Fatigue & Impairment

There is sufficient evidence that fatigue in ME/CFS is profound, not the result of ongoing excessive exertion, and not substantially alleviated by rest. This fatigue must be accompanied by a substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities and persist for more than 6 months. Fatigue, and particularly the impact of illness on function, should be assessed in making a diagnosis of ME/CFS.


Learn More: 

See Activity Intolerance and Cognitive Impairment Videos under PEM.

Post Exertional Malaise (PEM)

PEM is worsening of a patient’s symptoms and function after exposure to physical or cognitive stressors that were normally tolerated before disease onset. Subjective reports of PEM and prolonged recovery are supported by objective evidence in the scientific literature, including failure to normally reproduce exercise test results (2-day cardiopulmonary exercise test) and impaired cognitive function after exertion. There is sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions.

Learn More: 

  • Add Dr. B’s PPT: 2018 Activity Intolerance & Pacing


The most important primary intervention for ME/CFS is activity management (pacing), which includes management of physical, cognitive, emotional and OI stress.


  • Limiting activity to available energy
  • Short activities spread out through the day
  • Engaging in recovery behaviors between activities
  • Physical and cognitive rest.  Supine position.  Hydration. 
  • Avoidance of  significant DEBT (PEM)
  • An awareness that when debt accrues, it should be “paid off” asap and not allowed to accumulate
  • Being mostly in a preventive, not rescue mode



“Pacing” reduces the frequency and severity of PEM and improves both symptoms and function

  • Ideally, engage in only the amount of activity that doesn’t induce PEM in 24-48 hours
  • The goal in pacing activity is feel “back to baseline” the following morning after sleep
  • If PEM is induced, rest until it resolves
  • Develop a heightened sense of awareness about the threshold of relapse, and the consequences of pushing beyond it


Activity logs, heart rate monitors, smart watches, and the Oura Ring are all helpful tools to give immediate/daily/weekly/monthly feedback on activity and pacing.

Unrefreshing Sleep

Despite the absence of a specific objective alteration in sleep architecture, the data are strong that the complaint of unrefreshing sleep is universal among patients with ME/CFS when questions about sleep specifically address this issue. While polysomnography is not required to diagnose ME/CFS, its use to screen for treatable sleep disorders when indicated is appropriate. Diagnosis of a primary sleep disorder does not rule out a diagnosis of ME/CFS. 

Learn more: 

  • Add Dr. B’s PPT on 2018 CME PP Restorative Sleep


Link to Video: Restorative Sleep


  • Practice sleep hygiene (routine, environment)
  • Rule out primary sleep disorders. If identified, treat. 
  • Minimize sedating medications during the day time
  • Avoid caffeine, alcohol, decongestants, stimulants before bed
  • Avoid brain activating activities before bed
  • Address central sensitives which may be disturbing sleep (ie: restless leg syndrome, pain amplification, central ‘overload’ (PEM).

Cognitive Impairment

Cognitive impairment in ME/CFS includes problems with thinking or executive function exacerbated by exertion, effort, or stress or time pressure. There is sufficient evidence that slowed information processing is common in patients with ME/CFS, and a growing body of evidence shows that it may play a central role in overall neurocognitive impairment associated with the disease (memory impairments, attention deficits, and impaired psychomotor function). Such a deficit may be responsible for disability that results in loss of employment and loss of functional capacity in social environments.

Learn More

  • Add Dr. B’s PPT: 2018 Cognitive Impairment



  • Address other co-morbid conditions that could be compounding cognitive impairment
  • Pace to prevent symptom escalation
    • Preventative activity management. 
    • Reduce overload (avoid PEM)

Address potential contributors to ‘brain fog.’ (ie: medications, sleep dysfunction, low cellular energy production, OI, etc.)

Orthostatic Intolerance

Orthostatic intolerance is a general term that implies worsening of symptoms upon assuming and maintaining upright posture. Symptoms are improved, although not necessarily abolished, by lying back down or elevating the feet. Sufficient evidence indicates a high prevalence of orthostatic intolerance conditions in ME/CFS as measured by objective heart rate and blood pressure abnormalities and physical findings during standing, bedside orthostatic vital signs, head-up tilt testing, or by patient-reported exacerbation of orthostatic symptoms with standing in day-to-day life. These findings indicate that orthostatic intolerance is a common and clinically important finding in ME/CFS.

Learn more: 

  • Link/embed video: Orthostatic Intolerance 
  • Add Dr. B’s PPT on 2018 CME PP OI Chronic Orthostatic Intolerance Syndromes


Recognize and avoid the common triggers

  • Heat, getting overheated
  • Dehydration
  • Prolonged standing in place
  • Prolonged sitting
  • Prolonged bedrest (confuses the ANS)
  • Muscle atrophy and weakness
  • Abdomen/core, legs
  • Medications that cause/worsen OI

Interventions for OI:

  • External compression
    • Compression socks, pants, sleeves, abdominal binder
    • Key: the more surface area covered, the more compression of blood back to your core
  • Internal constriction (ie: pharmacological interventions)

Increase volume in the vasculature (blood vessels)

    • Consume extra water/fluids to expand blood volume
      • >1 gallon or >2 liters daily as a foundation
    • Increased salt intake helps retain water in the circulation and tissues
      • Must match the fluid intake. 2-5 gms daily (1/2 to 1 tsp)
    • Rapid water ingestion- (16oz) helps reduce OI within 20 minutes (chugging)
  • Pharmacological interventions to increase blood volume Control/cap the rapid heart rate response (if advised)
  • Pharmacological interventions (beta blockers-monitor use!)

Management Resources:

Common Food Items High in Sodium

Oral Rehydration Options

OI Handout 

Compression Socks

NASA Lean Test (for patients)

Important and Frequently Reported Symptoms that Support Diagnosis:

Immune impairment: Acute, infection-like onset; Susceptibility to infection; perpetual flu-like symptoms; sore throat; tender lymph nodes; fever; new or worsened sensitivities to certain substances (e.g. foods, odors, medications, chemicals). Poor NK cell cytotoxicity (NK cell function, not number) correlates with illness severity in patients and could serve as a biomarker for the severity of the disease.

Neurological impairment: Impaired psychomotor function; muscle weakness; twitching; instability; spatial disorientation; ataxia; sensory changes (e.g. sensitivity or intolerance to light, noise and touch).

Pain: Headaches; arthralgia; myalgia; other pain symptoms (all highly variable in presence, nature and severity). 

  • To learn more on amplified pain syndromes, please see our Fibromyalgia page, and the Chronic Fatigue and Pain series located on the medical provider page. 

Other: Gastrointestinal impairments; genitourinary impairment; neuroendocrine manifestations (e.g. cold extremities, weight change, excessive sweating, high/low temperature, chills/shivers, loss of appetite, alcohol intolerance)

Education and Management Resources:


Comorbidity: The occurrence of more than one illness or condition at the same time –Collins English Dictionary


(Content is the property of the U.S. ME/CFS Clinician Coalition) 

In the past, a diagnosis of ME/CFS was made by first excluding all other possible conditions. However, the 2015 National Academy of Medicine report established ME/CFS as a positive diagnosis that can coexist with other conditions, including those in the differential diagnosis. Recognizing co-morbid conditions early and treating them appropriately may improve the patient’s health, function, and quality of life. Commonly comorbid conditions include:  

ME/CFS in Children and Adolescents

According to the Centers for Disease Control and Prevention (CDC), Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling and complex illness. Scientists do not know what causes it, and there is no cure or approved treatment for the illness. ME/CFS is often thought of as a problem in adults, but children (both adolescents and younger children) can also get ME/CFS.

Not as much is known about ME/CFS in children because there have been few studies in this age group. Scientists estimate that up to 2 in 100 children suffer from ME/CFS.ME/CFS is more common in adolescents than in younger children.

Other Helpful Resources

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer -Frontiers in Pediatrics 

Children and Young Adults with ME/CFS – Solve ME/CFS Initiative 

ME/CFS in Adolescents– American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society

Interested in research for/about ME/CFS

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