Post exertional malaise, a starting point to investigate and understand myalgic encephalomyelitis/chronic fatigue syndrome.

Exercise is an important contributor to general health and is considered a
potential remedy for chronic diseases. This is in strong contrast with the
observation that in most ME/CFS patients exercise aggravates their symptoms.
Recently, post-exertional malaise (PEM) is defined as the key symptom of
ME/CFS. The etiology and pathophysiological mechanisms underlying ME/CFS are
still unknown and objective diagnostic criteria are not available. Various
hypotheses are postulated including disorders of several organ systems but the
heterogenous presentation of symptoms in patients, and the multisystem deficits
complicate reaching an all-encompassing hypothesis. It seems therefore
reasonable to focus on the key symptom, i.e., PEM. PEM can be induced by minor
cognitive or physical exertion and can be assessed with questionnaires. Acute
physical activity triggers complex cardiovascular, metabolic, and molecular
responses and for ME/CFS, it is important to understand the relation between
these acute processes and the prolonged presentation of aggravated symptoms. We
therefore want to measure metabolites, cardiovascular responses, cognitive
performance, muscle force and fatigability in 50 controls matched on group
level for sex, age, and activity. To follow changes in these parameters over we
perform time-series analysis, before, during and after recovery of task
performance. Besides understanding these interactions, it is also essential to
understand how these acute and prolonged responses affect behaviour and
perception. To obtain objective and subjective measures of perception we
include advanced brain activation analysis (measures of brain activity and
network analysis), together with effort and PEM-related questionnaires.

To explore the pathophysiology of post-exertional malaise (PEM). Investigate
the changes occurring in cardiovascular parameters, cognitive capacity,
physical capacities, brain activation and perfusion, and metabolites in
patients with ME/CFS compared with sex, age, and activity matched controls
before and after physical and cognitive fatiguing tasks on two consecutive
days. Secondary objectives are to investigate the differences in sleep
patterns, activity levels and heart rate variability in ME/CFS patients and
their matched controls as well as to find associations between patient report
outcomes and changes in the response of organ systems.

A single centre, cross-sectional, experimental study in which effects of
cognitive and physical tasks are followed.

Participants will be asked to perform physical and cognitive fatiguing tasks
while measuring cardiovascular parameters as well as brain activation and
perfusion and various blood samples will be taken. Regarding the experimental
protocol it is anticipated that after performing our protocol ME/CFS patients
will perceive a temporary worsening of their symptoms (e.g. fatigue, muscular
and joint pain, headaches, brain fog), but no serious adverse events are
expected. The importance of investigating worsening of symptoms in detail and
on so many different levels, allows us to identify and better understand the
parameters involved in the mechanisms of the disease. Possible additional
burdens that all our participants may experience during our study are the
following:

Collection of 8 blood samples over three days

Determination of voluntary muscle activation with the superimposed twitch
technique may feel a bit painful but for less than one second.

Standardized vascular occlusion test of the thigh muscle can feel uncomfortable

Time investment: 5 times 2.5 hours of measurements as well as the filling in of
the questionnaires at home (90 min* + 4*3 min), total= ca. 14.5 hours.