The central feature of ME under this definition is post-exertional neuroimmune exhaustion (PENE). To meet the criteria, an individual must have PENE, described in the following manner: “This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions.

“Characteristics are:

1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.

2. Post-exertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.

3. Post-exertional exhaustion may occur immediately after activity or be delayed by hours or days.

4. Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.

5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.”

The individual must demonstrate neurological impairment by meeting a total of at least three symptoms from three of these four categories:

1. Neurocognitive impairment:
   1. Difficulty processing information: slowed thought, impaired concentration
   2. Short-term memory loss
2. Pain:
   1. Headaches
   2. Significant pain can be experienced in muscles, muscle-tendon junctions, joints, abdomen or chest. It is non-inflammatory in nature and often migrates.
3. Sleep disturbance:
4. Neurosensory, perceptual and motor disturbances:
   1. Neurosensory and perceptual
   2. Motor

The individual must demonstrate immunological impairment by meeting a total of at least three symptoms from three of these five categories:

1.  Flu-like symptoms may be recurrent or chronic and typically activate or worsen with exertion.
2.  Susceptibility to viral infections with prolonged recovery periods.
3. Gastointestinal tract.
4. Genitoruinary.
5.  Sensitivities to food, medications, odours or chemicals

The individual must have one of the following symptoms that demonstrate energy production/transport impairment:
1. Cardiovascular
2. Respiratory
3. Loss of thermostatic stability
4. Intolerance of extremes of temperature.

For more details on these symptoms clusters and additional directives for applying these lists in clinical settings vs. research settings see the full paper (click here).