PENE: An explanation of the ICC term
PEM was once the abbreviation for the cardinal feature of ME, which is a
global exacerbation of symptoms following minimal amounts of cognitive
or physical activity.
"exhaustion unrelated to an excessively demanding schedule that would
induce fatigue in an otherwise healthy adult."
(PEM according to Reeves et al. 2003)
Several groups including the CDC however have manipulated the term and
there are now several versions in use which can be used in conjunction
with other well known criterias.
The latest is from the International Consensus Criteria (ICC) for ME and
is abbreviated to PENE.
"A. Postexertional neuroimmune exhaustion (PENEpen'-e):Compulsory
This cardinal feature is a pathological inability to produce sufficient
energy on demand with prominent symptoms primarily in theneuroimmune
Characteristics are as follows:
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. Postexertional symptom exacerbation: e.g.acute flu-like symptoms,
pain and worsening of other symptoms.
3. Postexertional exhaustion may occur immediately after activity or be
delayed by hours or days.
4. Recovery period is prolonged, usually taking 24h 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."
(International Consensus Criteria for ME, 2011)
To meet thefull ICC for ME, the authors of the criteria have said that a
person must have PENE. So it is important that thisfeature be accurate
to the disease ME when used for research purposes orclinical diagnoses.
Specificallyit is not the meaning of the letters PENE that is important,
but the actualdescription where we discover the truth about this term.
PICKING THROUGH THE CRITERIA FOR PENE
"This cardinal feature is a pathological inability to produce
sufficient energy on demand"
Firstly PENEis said to be an inability to produce enough energy when
needed. This is commonin people who are deconditioned or depressed.
Therefore this is not unique toME patients and would not separate them
from those people.
Next the authors list several characteristics of PENE, but none are said
to be required for PENE, and as we will explain they are also not
actually the landmark feature that ME patients experience.
"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
Number 1 is a quick fatigability after activity. This is the same as
the initial description and again applies to deconditioned or depressed
"2. Postexertional symptom exacerbation: e.g.acute flu-like symptoms,
pain and worsening of other symptoms."
Number 2 is exacerbation of symptoms. This is not however a global
exacerbation ofsymptoms, but allows for any symptom exacerbation. So
for instance, pain would increase for anyone who is deconditionedor
depressed, due to his or her fitness levels.
"3. Postexertional exhaustion may occur immediately after activity or be
delayed by hours or days."
Number 3 ispost activity tiredness. This is not strictly said to be
delayed, but can beimmediate, and again can be applied to deconditioned
or depressed people.
"4. Recovery period is prolonged, usually taking24 hor longer. A relapse
can last days, weeks or longer."
Number 4 isrecovery delay. This too could be applied to deconditioned or
"5. Low threshold of physical and mental fatigability (lack of stamina)
results in a substantial reduction in pre-illness activity level."
Number 5 is like number 1 and is lack of stamina, and again applies to
deconditioned or depressed people.
So how canPENE be the landmark feature of ME when it can also be applied
to deconditionedand depressed people? And when it is not a global
exacerbation of symptoms following even trivial increases incognitive or
PENE, MELANCHOLIC DEPRESSION & THE CANADIAN CRITERIA
PENE is not in actual fact a new description. It is exactly the same as
the description of PEM used in the Canadian criteria,which also allows
people without the cardinal feature of ME to be entered into a study.
Only the words have been rearranged
"Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss
of physical and mental stamina, rapid muscular and cognitive
fatigability,post exertional malaise and/or fatigue and/or pain and a
tendency for other associated symptoms within the patient's cluster
ofsymptoms to worsen. There is a pathologically slow recovery
period.usually 24 hours or longer."
(Canadian consensus criteria, 2003)
What is really portrayed by both PENE in the ICC and PEM in the Canadian
criteria is therefore a mixture of reactions by people with different
conditions in response to activity, none of which are strictly the
cardinal feature of ME.
This however will not come as a surprise to clinicians working the
field, for Leonard Jason and others (2001) have already shown that PEM
(AKA PENE) also occurs in people with melancholic depression and those
with no fatigue.
WHERE TO GO NOW?
A new term,PAR (post activity relapse), has been proposed by Morris and
Maes (2012) as a moreaccurate description of the feature ME patients
describe, and is not so easilysubstituted for the commonly found fatigue
after exertion. It also leaves little room for assumptionon the part of
clinicians who are yet to catch up with scientific develops inME
"This section will propose an immuno-inflammatory explanation for the
hallmark symptoms of the disease,including fatigue, malaise,
neurocognitive symptoms and a range of abnormal responses to exertion
that may be delayed by 24 or even 48 h, which is often labeled as post
exertional malaise. The term refers to abnormal responses to even a
trivial increase in normal levels of physical or neurocognitive
activity.Post activity relapse may therefore be a better term. This
phenomenon is often reported by ME patients to be similar to the acute
phase of influenza, with symptoms indicating infection/inflammation,
e.g. sore throat, lymph tenderness or swelling, malaise, hyperalgesia
and brain fog. Insignificant increases in physical activity or minor
cognitive tasks may exacerbate immune dysfunction,inflammation and O&NS
thereby producing further signs of the disease. The effect may be
delayed, but is predictable and accumulative, varying in duration
dependant on disease severity and accumulative activity levels. "
(Morris and Maes, 2012)
We believe it would be to the advantage of other patients if they now
began to use this term to communicate with doctors, their family and
friends, until the biology of this feature is defined by an objective