Overview

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 myalgic encephalomyelitis (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, hence it is important to understand the relation between these acute processes and the prolonged presentation of aggravated symptoms (PEM). We therefore want to measure metabolites, cardiovascular responses, cognitive performance, muscle force and fatigability in 50 patients and 50 controls matched on group level for sex, age, and activity. To follow changes in these parameters we perform time-series analysis, including data obtained before, during and after task performance. Besides understanding these interactions, it is also essential to understand how these acute and prolonged responses affect behaviour and perception.

Eligibility

Inclusion Criteria:

• Willing and be able to complete all study procedures
• Able to provide informed consent

Additional inclusion criteria for ME/CFS patients

• ME/CFS patients have to meet the criteria of the ICC OR CCC.
• A self-reported illness narrative of the development of persistent fatigue and post-exertional malaise according to the DSQ-2. The persistent fatigue may have an acute onset or become progressively worse over 6 months.

Exclusion Criteria:

• Use of immune-modulating drugs in the past 3 months.
• A serious medical condition that may explain symptoms similar to ME/CFS, such as cancer, coronary artery disease, uncontrolled diabetes, chronic infection (hepatitis B and C, tuberculosis, HIV), inflammatory diseases, autoimmune diseases (e.g. such as rheumatoid arthritis, lupus or polymyositis), severe COPD or other severe persistent respiratory disease, severe anemia, renal failure, Addison's or Cushing's disease or severe neurological disease (such as Parkinson's disease).
• History of head injury with loss of consciousness or amnesia lasting greater than a few seconds within last five years or lasting greater than 5 minutes at any point during their lifetime. Persons with medical record evidence of post-concussive symptoms lasting more than six months are also excluded.
• Suspected, probable, or confirmed Lyme disease
• Current or substance use disorder within last 5 years
• A mood disorder or other psychiatric diagnosis prior to a diagnosis of ME/CFS.
• Pregnant, actively seeking to become or breastfeeding in the past 12 months.
• BMI \>35.
• having cognitive or communication problems which reduces the capacity to understand instructions.
• planned a change in medication during the testing period.
• Use of medication that affects the blood pressure (e.g. Beta-blockers, fludrocortisone, vasoconstrictors).
• Participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
• Claustrophobia
• Current (within 1 week) use of prescription or over-the-counter medications, herbal supplements, or nutraceuticals that may influence brain excitability that the potential participant is either unwilling or clinically unable to safely wean off for the duration of the period of the visits. The possibility for a potential participant to be weaned off medication will be cooperatively determined by both the clinical investigative team and personal physicians. Examples of medications that influence brain excitability include tricyclic antidepressants, hypnotic, antiepileptic, antipsychotic medication, stimulants, antihistamines, muscle relaxants, dopaminergic medications, and sleep medications.
• Use of B12 high dosage injections
• Being colorblind

Additional exclusion criteria for control subjects:

• performing high intensity or moderate intensity activities more than 30 minutes per week
• substantial fatigue as determined using MFIS fatigue questionnaire \>30