In ME, sometimes referred to as me/cfs, the term ‘fatigue’ can often be used in a way that devalues the illness and marginalizes sufferers. ME fatigue is not normal fatigue, a distinction critical for the direction of future research, clinical diagnosis and treatment protocols.
Forget what you think you know about fatigue
Both sets of criteria clarify that while normal fatigue is proportional to the intensity and duration of activity, followed by a quick restoration of energy, ME fatigue is characterized by a pathological low threshold of physical and mental fatigability, exhaustion, pain, and an abnormal exacerbation of symptoms in response to exertion. It is followed by a prolonged recovery period.
It should be noted that fatigue and pain are part of the body’s global protection response and are indispensable bioalarms that alert patients to modify their activities in order to prevent further damage.
PENE is not just fatigue
As defined by the ICC, a cardinal feature of ME is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. The ICC coined a new term “PENE” or Postexertional Neuroimmune Exhaustion to explain the new research findings.
The characteristics of PENE, according to the ICC, are:
- 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.
- Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
- Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
Recovery period is prolonged, usually taking 24h or longer. A relapse can last days, weeks or longer.
- Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
So what’s going on in ME patients?
Researchers are only beginning to scratch the surface with investigations of PENE. What is known now is that there is profound dysfunction of the regulatory control network within and between the nervous systems of ME sufferers.1,2 This interacts with the immune and endocrine systems affecting virtually all body systems, cellular metabolism and ion transport.3
The dysfunctional activity/rest control system and loss of homeostasis result in impaired aerobic energy production and an inability to produce sufficient energy on demand. A test-retest cardiopulmonary exercise study revealed a drop of 22% in peak VO2 and 27% in VO2 at AT on the second day evaluation.4
Both submaximal and self-paced exercise resulted in PENE.5 These impairments and the loss of invigorating effects distinguish ME from depression.
Levels of severity
For a diagnosis of ME, symptom severity must result in a significant reduction of a patient’s premorbid activity level:
- Mild: an approximate 50% reduction in pre-illness activity level
- Moderate: mostly housebound
- Severe: mostly bedridden
- Very Severe: totally bedridden and need help with basic functions
There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects.
Recovery time: e.g. Regardless of a patient’s recovery time from reading for ½ hour, it will take much longer to recover from grocery shopping for ½ hour and even longer if repeated the next day – if able.
Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately.
Impact: e.g. An outstanding athlete could have a 50% reduction in his/her pre-illness activity level and is still more active than a sedentary person.
- Goertzel BN, Pennachin C, de SouzaCoelho L, Gurbaxani B, Maloney EM, Jones JF. Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome. Pharmacogenomics. 2006;7:475–83. [PubMed] ↩
- Underhill JA, Mahalingam M, Peakman M, Wessely S. Lack of association between HLA genotype and chronic fatigue syndrome. Eur J Immunogenet. 2001;28:425–8. [PubMed] ↩
- Sullivan PF, Evengård B, Jacks A, Pedersen NL. Twin analyses of chronic fatigue in a Swedish national sample. Psychol Med. 2005;35:1327–36. [PubMed] ↩
- Landmark-Høyvik H, Reinertsen KV, Loge JH, et al. The genetics and epigenetics of fatigue. PM R. 2010;2:456–65. [PubMed] ↩
- Maher K, Klimas NG, Fletcher MA. Immunology. In: Jason LA, Fennell PA, Taylor RR, editors. Handbook of Chronic Fatigues. Hoboken, New Jersey & Canada: John Wiley & Sons; 2003. pp. 124–51. ↩