PEM, a Starting Point to Investigate ME/CFS

Heart rate (bpm) and blood pressure (mmHg) are measured with a continuous non-invasive monitoring system (Finapres Midi). The BP sensor is positioned around the middle finger on the second phalanx of the left hand and subjects must hold their arm at breast level. The recorded values during T1 and T2 will be compared between tasks, as well as between groups and sessions.

Short isometric maximal voluntary contractions (MVC) of the right index finger abductor (FDI). The maximal index finger abduction force (newton) is measured with a force transducer which is held by the participant. The measurement is repeated 3 times per hand and the highest value is taken. On the second and third repetition, a superimposed twitch stimulation (SIT) will be induced to assess the voluntary activation during maximal contraction.

The participant is asked to produce force at different submaximal force targets (20%, 40%, 60%). The targets are presented on a monitor and subjects get online feedback of the target force and their produced force.

The participant performs a maximal contraction for 2 minutes. During the 2 minutes contraction 7 SIT stimulation are given to the subject to assess voluntary muscle activation during a fatiguing task.

This test assesses the ability to inhibit cognitive interference, which occurs when the processing of a stimulus feature affects the simultaneous processing of another attribute of the same stimulus. Participants see a word describing a colour on a screen, the word is written in the same or different colour than the word they will read. They are asked to press a yes or no button to indicate whether the colour of the word and the meaning of the word matches (yes) or not (no). The number of correct answers and the reaction time will be assessed.

Blood oxygenation level dependent (BOLD): changes both in oxy- and deoxyhemoglobin concentration. Brain activation in different tasks will be compared between groups and sessions.

Is a non-invasive fMRI technique that uses arterial water as an endogenous tracer to measure cerebral blood flow. ASL provides reliable absolute quantification of cerebral blood flow with high spatial and temporal resolution. Perfusion data are used to identify patients suffering from impaired autoregulation of cerebral blood flow and to obtain associations with cardiovascular responses and muscle fatigue.

Oxy- and deoxyhemoglobine concentrations are measured at the prefrontal cortex and leg muscle with a non-invasive near infrared spectroscopy device (NIRS), where small sensors are positioned on the forehead and the quadriceps muscle. For this measurement a standardized vascular occlusion test will be performed on the quadriceps muscle to assess the local tissue oxygen consumption and the microvascular reperfusion and reactivity. This measurement will be used as calibration to normalize per subject the oxy- and deoxyhemoglobin concentrations allowing for comparisons between subjects. The oxygenated and deoxygenated values for the prefrontal cortex and leg muscle will be compared across tasks, groups and sessions.

This test assesses functional lower extremity strength. Subjects sit on a chair and stand up repeatedly for 30 s. Arms of the subject are crossed and held against the chest. The number of cycles of standing up from sitting are counted.

MVC of the handgrip is measured with a hydraulic hand dynamometer (JAMAR Hand Dynamometer). The measurement is repeated 3 times.

To measure routine activities in daily life, participants will be asked to wear an activity device (Actigraph) on their dominant hip as well as a heart rate device (polar H10) around their chest. During the 7 days of wearing the devices participant will be asked to fill out an activity diary.

The difference in activity level and heart rate variables will be compared across the groups.

The blood samples are used to analyse the short-lasting changes in metabolites before and after the performance of physical and cognitive tasks and long-lasting changes on the next day

Maximal voluntary force (MVC) of the knee extensors is measured with a custom-built dynamometer. Subjects are seated in a chair with the knee and hip in 90° of flexion with their non-dominant lower leg strapped to the chair's lever arm (~ 10 cm up to lateral malleolus). Subjects are instructed to contract their knee extensors as rapidly and forcefully as possible and to maintain force generation for 5 s. MVC is determined as the peak force.

Is a questionnaire used to measure the severity of tiredness in fatiguing illnesses. Scores per question range from 0 to 3. The higher the score the more fatigue experienced.

It is a multipurpose, short-form health survey with 36 questions. It yields an eight-scale profile of scores as well as physical and mental health summary measures. It is useful in comparing general and specific populations and comparing the relative burden of diseases. Higher scores indicate a better health status.

DSQ-2 is a questionnaire that assesses the key symptoms of ME/CFS. At each item, participants have to rate the frequency and severity of the symptom on a scale from 0 to 4. The higher the scores the worse the symptoms.

Bell scale is a scale that describes the levels of physical and mental activity health. The scores range from 0 to 100, the higher the score the better the health.

Is a questionnaire assessing sleep quality and disturbances. The higher the score the worse the sleep quality.

Is a questionnaire to determine levels of anxiety and depression that a person is experiencing. Higher scores reflect a stronger impact.

Is a questionnaire of 31 questions that assesses the autonomic nervous system symptoms. Higher score indicates greater autonomic symptom severity.

Is a questionnaire related to sense of fatigue. The questionnaire consists of 21 questions providing assessment of the effect of fatigue in terms of physical, cognitive, and psychosocial function. Higher scores reflect a higher impact of fatigue.

Is a questionnaire that assesses the onset, triggers and recovery of PEM.

Is a questionnaire that measures an individual's health status. It has five dimensions on mobility, usual activities, self-care, pain and discomfort and anxiety and depression. The higher the score the higher the impact on the quality of life.

Is a questionnaire that assesses the severity of 12 main symptoms from o to 10, with 10 being the most severe.